key: cord- - zlqny m authors: azadmanjir, zahra; jazayeri, seyed behzad; habibi arejan, roya; ghodsi, zahra; sharif-alhoseini, mahdi; kheiri, ghazaleh; zendehdel, kazem; safdarian, mahdi; sadeghian, farideh; khazaeipour, zahra; naghdi, khatereh; arab kheradmand, jalil; saadat, soheil; pirnejad, habibollah; fazel, mohammad reza; fakharian, esmail; mohammadzadeh, mahdi; sadeghi-naini, mohsen; saberi, houshang; derakhshan, pegah; sabour, hadis; benzel, edward c.; oreilly, gerard; noonan, vanessa; vaccaro, alexander r.; emami-razavi, seyed hassan; rahimi-movaghar, vafa title: the data set development for the national spinal cord injury registry of iran (nscir-ir): progress toward improving the quality of care date: - - journal: spinal cord ser cases doi: . /s - - -x sha: doc_id: cord_uid: zlqny m study design: descriptive study. objectives: the aim of this manuscript is to describe the development process of the data set for the national spinal cord injury registry of iran (nscir-ir). setting: sci community in iran. methods: the nscir-ir data set was developed in months, from march to october . an expert panel of members was formed. after a review of data sets of similar registries in developed countries, the selection and modification of the basic framework were performed over meetings, based on the objectives and feasibility of the registry. results: the final version of the data set was composed of data elements including sociodemographic, hospital admission, injury incidence, prehospital procedures, emergency department visit, medical history, vertebral injury, spinal cord injury details, interventions, complications, and discharge data. it also includes components of the international standards for the neurologic classification of spinal cord injury (isncsci) and data elements related to quality of life, pressure ulcers, pain, and spasticity. conclusion: the nscir-ir data set was developed in order to meet the quality improvement objectives of the registry. the process was centered around choosing the data elements assessing care provided to individuals in the acute and chronic phases of sci in hospital settings. the international spinal cord injury data set was selected as a basic framework, helped by comparison with data from other countries. expert panel modifications facilitated the implementation of the registry process with the current clinical workflow in hospitals. different incidences of traumatic spine fractures (tsf) with or without spinal cord injury (sci) have been reported in different geographic regions [ ] [ ] [ ] [ ] [ ] . the incidence of traumatic sci (tsci) varies between . and . per one million around the world; in developing countries, an incidence of . sci per million has been reported [ , ] . in iran, heidari et al. reported tsf in . % ( out of , ) of trauma admissions between and using the national trauma registry (ntr) data [ ] ; . % ( out of ) of people with tsf admitted to a hospital had an associated sci. in another study, the incidence of tsf in tehran was estimated to be about . per , and less than half of these patients had a simultaneous sci [ ] . the incidence of tsci in iran was estimated as per , persons by another study [ ] . when the spinal cord is damaged, long-term disability often ensues [ ] . tsci is a condition with multiple comorbidities and considerable health, social, and economic impacts. the burden of these impacts can be managed by improving quality of care. the lack of a reliable source of information about spine trauma with or without sci is a significant barrier in evaluation and planning of systems of prevention, control, and care [ ] . until now, there was no spine-specific trauma database or registry system in iran. the national sci registry of iran (nscir-ir) is a project supported by the ministry of health and medical education to collect and provide tsf and sci data to evaluate and improve the quality of care of persons with sci [ ] . the development of a data set is an essential phase of designing a registry system [ ] . according to kowal et al., a data set is a common set of data elements used to collect and report data in the registry [ ] . many studies have emphasized the importance of a data set to create national databases and support information sharing on diseases, injuries, and other health-related problems [ ] [ ] [ ] . one of the most important and effective tasks for the success or failure of a registry system is the selection of appropriate data items [ ] . data set development is a critical step for nonepidemiologic registries on traumatic conditions that can lead to long-term disabilities such as tsf/sci. the objectives for a sci registry are focused on care and outcome measurements, requiring various data inputs from different independent and distinct resources. this study focuses on the development process of the data set for the nscir-ir and delineates our experiences, which might be useful for future registries, specifically in developing countries with limited budgets, resources, and information technology infrastructures. the development of nscir-ir has been one of the main priorities of the national iranian sci research network since . the data set of nscir-ir was developed between march and october . an expert panel with three neurosurgeons, one physiatrist, one general practitioner, one nurse, one community medicine physician, one emergency physician, two epidemiologists, and one health information management specialist was formed. we followed a stepwise approach in the development of the data set. the steps included (i) review of the data sets in similar sci registries, (ii) selection of a data set as the base framework of the nscir-ir data set by the expert panel, and (iii) modification of the basic framework according to data needs, registry objectives, and feasibility of data collection. first, a simple review was performed on the data sets of three sci registries of australia (australian spinal cord register), canada (rick hansen sci registry (rhscir)), and europe (european multicenter study about sci). later, the rhscir data set was selected as our basic framework to develop an initial draft data set. the selections were made based on the similarity of rhscir to our registry in registry type (spinal column and sci (tsf/sci)) inclusion criteria. sixteen sessions of the expert panel were held between march and october . we translated the rhscir data set dictionary into farsi and then our expert panel independently reviewed the translation. the accessibility of the data elements of the rhscir was examined by experts who were aware of the clinical documentation status and the general content of medical records in hospitals of iran. it was noted that several variables are not recorded in patients' hospital charts; therefore, patient medical records were considered as the secondary data source of the registry. comparability of our registry data with other countries was another issue that was discussed by the expert panel. international data standards are recommended by the world health organization (who), therefore, the international sci data sets (iscids) were also reviewed. at the third step, the expert panel made changes to iranian data set of nscir-ir in order to accommodate our major data elements and concerns of quality of care. for example, our data set registers different time points from injury time to the time of arrival of ambulance to the trauma scene, time of arrival to hospital, or to a referral center, and time of the surgical stabilization with or without spinal cord decompression. with this design, it will be possible to identify major time delay points in our care providing system. table compares the rhscir data set with the two other registries [ , ] . the rhscir data set includes more than variables that cover quality of care [ , ] . the rhscir data set has two types of minimal and extended data elements in which the minimal data set includes mandatory data elements that must be recorded for all patients including those who do not consent to be part of the registry. these minimal data set includes name, family name, age, time, place and mechanism of injury, and questions which are essential for patients' treatment by care providers. the extended data elements ( elements) are recorded only for patients who consent to be part of the registry [ ] . our expert panel reviewed the rhscir data elements. some of the rhscir data elements were not accessible through primary data sources of the registry e.g., patient-reported or clinician-reported data, observation and measurement by the registry members. medical records were considered as the secondary data source of the registry, however, several variables in the rhscir data set were also not recorded in the patient medical records. table shows the data items and variables, which we did not include in our registry ( table ) . according to the review of who and iscids [ ] [ ] [ ] , our strategic committee had considerations regarding comparability of the designed data set with international data. who recommends the use of standardized coding systems such as the international classification of diseases (icd), international standards for neurological classification of sci and iscids for data collection to facilitate comparison between different patients, centers, and countries [ ] . the rhscir data set and other data sets (appendix ) were different from the iscids. therefore, the expert panel decided was not convinced to use the rhscir data set due to concerns of accessibility and comparability of data in our registry with the rhscir data set. the expert panel concluded to use iscids as the basic framework of nscir-ir data set. iscids includes a core data set and several specialized data sets. the core data set includes variables that are the minimal data required for collection for all people with sci in acute inpatient settings [ ] . there are more data sets which are focused on different aspects of sci and sci consequences [ ] . according to the registry objectives and registration process, the expert panel selected data items from iscids. data selections were based on accessibility of data and usefulness in quality of care assessment in the acute settings. selected data items were organized into five sections based on the logical sequence in the process of care (table ) . after translation of data items into farsi, case report forms were designed. panel members evaluated designed forms and applied the required methods. major and minor modifications were made to overcome the mentioned challenges in box ( table ). the final version of the nscir-ir data set was developed with data elements. it includes one data set for acute and one data set for chronic phase of injury (rehospitalization data). our data items are two of types: mandatory and conditional. conditional data items are data items that are considered as mandatory based on the clinical situation of the patient. if a data item is not applicable for a patient, it is not necessary to be completed for that patient. for example, if the accident was not a traffic accident, then it is not necessary to record the accident data. table shows the components of the final version of nscir-ir data set. the items were organized into seven case report forms for acute phase and four case report forms for the chronic phase. all were used in the pilot phase of registry implementation (table ). after months of implementation of the pilot phase in three trauma hospitals, changes were made to the data set that are (i) details on the types of respiratory, cardiovascular, and other comorbidities were added into admission form, (ii) procedures in the first hospital in cases with inter-hospital patient transfer were added into admission form, (iii) injury type of atlas and axis cervical vertebra (c -c ), were separated from the other vertebrae and were added as a question into the injury form, (iv) one item was added into the intervention form for the vertebra or vertebrae on which surgery was performed, and (v) one item was added into the discharge form for the type of external fixation device, which patient uses at the time of hospital discharge. our study presents an overview of the data set development process for the nscir-ir. our evidence-based approach along with interdisciplinary expert panel review helped us to develop a comprehensive, yet applicable, data set. some groups have used review of current evidence and formation of working groups to select the registry data elements [ , ] . others have conducted either a survey or delphi method on an initial version of the data set [ ] [ ] [ ] . svensson-ranallo et al. [ ] performed a comprehensive review for methodologies of data set development in health table the data items and variables which we did not include in national spinal cord injury registry of iran (nscir-ir). socio-demographic income (personal and household income), paid and unpaid work status, living condition and setting, weight, height and body mass index. social history drinking and smoking, neurological status before the injury. status at injury time neurological status and delirium and injury severity score (iss), details of procedures such as ventilator assistance and patient respiratory evaluation, intraoperative imaging, estimated blood loss, intraoperative adverse events, rehabilitation consultation. assistant equipment and devices mobility, transfer and vehicle aids, mobility and walking and balance assessment measures, rehabilitation services pre-and post-discharge. care. the results of this review showed that there are different methods such as survey, systematic review, chart review, and delphi technique. the most common methods are the use of experts and stakeholders, but the authors suggested a combined approach with literature review, chart review, expert committee, and organized data for developing the minimum data set [ ] . in our study, we used the literature review and expert committee to form the data sets. it is important to choose the right data elements for a registry. tee et al. stated that correct data selection items of a registry lead to a balance between comprehensiveness and practicality of the registry [ ] . although, at first, we wanted to have a comprehensive and detailed data set, which meets all present and future data requirements for research and care evaluation, the unavailability of most data items and the necessity of an international framework for comparability of our registry led us toward using the iscids. compliance evaluation of determined data elements with routine clinical practice was effective to reduce registration workload. imposition of required uncommon practice in current clinical practice increases the cost. tee et al. emphasized the number of data elements collected that should be practical based on routine process [ ] . for example, when we chose the rhscir data set as our framework, we found that some of the data were not accessible at all through primary data sources of the registry. for example, we found the hesitancy of our patients in providing data related to their income, work status, drinking, and some other measures as a big barrier for data collection. in other words, assessing income is very difficult in iran especially in people who are self-employed. most selfemployed iranians do not express their real income for cultural reasons. usually, government employees have specific income data. in addition, assessments and interventions for patients in clinical practice differ between iran and canada. for instance, height and weight of patients are not taken on arrival to the hospital. also, some clinical assessments such as mobility or pain assessment with specialized tools (e.g., berg balance scale, leeds assessment of neuropathic symptoms and signs, douleur neuropathique ) are not part of the routine assessments in iran. also, rehabilitation and assistive devices are not provided in a specialized manner to the patients in the acute phase. instead, rehabilitation and support services are available at the level of long-term care. although, there is connection between the acute care system and long-term care system; there is a lack of communication and information sharing between care providers working in the two levels of iran health care system. patients normally work as messengers, carrying information between the two levels. in contrast, canada has a robust information technology infrastructure. there are multiple database and reporting systems at all of the health care services levels. these include the hospital morbidity database and discharge abstract database for ambulatory and hospital care, national rehabilitation reporting system for rehabilitation care, ntr for trauma care, continuing care reporting system, and home care reporting system for continuing and long-term care [ ] [ ] [ ] [ ] [ ] [ ] . using primary data sources is not practical in iran due to limited human resources for registration and funds allocated according to the large scale of data that led to a time-consuming and tedious registration process. therefore, it was predicted that using the canadian sci registry as the backbone of data set in nscir-ir is impractical. the nscir-ir data set contains spine trauma data such as the injury morphology and injury type according to the aospine injury classification system. the classification is used only in the rhscir and not used by other tsf/sci registries. therefore, it is a strong point of the nscir-ir data set. in relation to patient outcome, the data set includes the glasgow outcome scale that is a physician-reported outcome; however, it does not include any patient-reported outcome data, specifically about patient functional independence. other sci registries use standard measures for patient-reported outcome such as the short form or health survey, the spinal cord independence measure, or the functional independence measure [ , , ] . this is a weak point of the nscir-ir data set. the challenges of sci registry system . lack of specific data in medical records such as sexual status, fecal and urinary incontinence, height, and weight. . specialized tests and assessments are not part of the routine clinical practice in the acute phase of spinal trauma care and are performed when clinically indicated. these tests include endocrine tests, musculoskeletal function tests, and pulmonary function tests. . restrictions on adding to the workload of the clinical team for documenting data other than the data in medical records. . the need of data gathering by dedicated, trained staff to accurately register specialized data. . the need to perform a time-consuming and tedious interview with patients to gather data with low-relevancy to the registry objectives; regarding the limited time and human resource that it would lead to a decrease in data accuracy and increase per case registry costs. . the need near to real-time data gathering for improving data accuracy of some data such as pain assessment scale. . the necessity for data gathering of more details about the incident resulting in trauma, patient condition in prehospital and providing care according to registry objectives. for example, use of safety equipment in traffic accidents such as airbags, seat belts, immobilization, the state of consciousness, the patient outcome of acute care, and quality of care assessment. . the necessity of using more clinical standards for reporting some conditions in order to improve comparability. for example, fracture type, patient outcome, etc. table lists of major and minor modifications on initial national spinal cord injury registry of iran (nscir-ir) data set. modifications reason for the modification removing the musculoskeletal assessment data elements. they are not common in clinical paractice in iranian hospitals. removing some data items from groups of metabolic and endocrine function tests, urinary and bowel function tests, entire groups of endocrine system and fasting serum lipid profile. they are not the part of routine clinical practice in acute phase of spine trauma care. adding some required data elements which were not included in international spinal cord injury data set (e.g., more information for contact with patient, the entity of associated injuries, mode of transport to hospital, prehospital procedures, and glasgow coma scale (gcs)). they were considered essential to assess the quality of care. adding aospine injury classification system as clinical standards. it is beneficial for reporting of spine fracture types and researches on them. adding the full data elements of international standards for neurological classification of spinal cord injury (asia). it is important to assess the severity of the injury. replacing of the validated persian version of world health organization quality of life measure (whoqol-bref) [ ] instead of the three items of the quality of life basic data set. who quality of life-bref scale (whoqol-bref) provides better understanding on patient outcome according to registry objectives. transferring detailed pain assessment from data set of acute care phase to the conditional data items of chronic phase. the most common pain in the acute phase of injury is fracture pain and injury site. assessment of pain due to trauma to other areas of the body was not an objective for our registry in the acute phase. adding the data items including the modified ashworth scale. it was necessary for our registry in rehospitalization of patient due to spasticity as conditional data items of chronic phase. changing the data element titles. for better understanding. regrouping some data in designed forms according to logical and time sequence of care process. to integrate with the clinical workflow of hospitals. using the iscids as the basic framework of the nscir-ir data set facilitates international comparisons on the quality of provided care to tsf/sci patients. one of the limitations of our study was that we chose variables based on the expert's opinion on the availability of data in current medical records. however, due to lack of electronic health records and national or regional standards in medical records documentations, expert opinion was the best resource that we could rely on. in summary, the nscir-ir data set was developed to meet the quality objectives of the registry. it focuses on data representing quality of care provided to patients with tsci in the acute and chronic phases of their injury. the selected basic framework of the data set for the iscids can help to compare national data with data from other countries. expert panel modifications facilitate the integration of the registration process with the current clinical workflow within the hospitals. anonymous data of nscir-ir may be accessible for research use, upon written request and approval from the steering committee. funding nscir-ir has been financially supported by deputy of research and technology, ministry of health and medical education (mohme) of iran. author contributions za wrote the draft of the paper, designed and implemented the nscir-ir project from idea to deployment, and also has a major role in data set and case report forms development. za made major revisions to the paper and its appendix. vr-m designed and implemented the nscir-ir project from idea to deployment including data set development and also made major revisions to the paper. sbj contributed to the design of nscir-ir project and also made major revisions to the paper. rha, go, vn, arv, ecb, ms, ms-a, hp, ef, and zg contributed to revision of the manuscript. kn contributed to the nscir-ir project as registrar. gk prepared the appendix. zk, hs, kz, jak, ss, and fs were members of the expert panel and contributed to the paper's revision. rha refined the paper according to final comments and modifications. conflict of interest the authors declare that they have no conflict of interest. ethical approval this study was approved by research ethics committee of tehran university of medical sciences as a part of national spinal cord injury registry study. publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. global prevalence and incidence of traumatic spinal cord injury a -year follow-up of the incidence of traumatic spinal cord injuries in western norway the epidemiology of traumatic spinal cord injury in british columbia incidence of traumatic spinal cord injury in thessaloniki incidence trends of traumatic spinal cord 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development, and use of trauma registries and trauma data sources in decision making in injury the rick hansen spinal cord injury registry (rhscir): a national patient-registry spinal cord injury registry dataset. version . . canada: rick hansen inistitiue protocol: rick hansen spinal cord injury registry (rhscir). canada: rick hansen inistitiue international perspectives on spinal cord injury. geneva: world health organization international spinal cord injury data sets international spinal cord injury core data set designing a minimum data set for breast cancer: a starting point for breast cancer registration in iran development of an international prostate cancer outcomes registry minimum data set for cystic fibrosis registry: a case study in iran development a minimum data set of the information management system for burns developing a minimum data set of the information management system for orthopedic injuries in iran a framework and standardized methodology for developing minimum clinical datasets dedicated spine trauma clinical quality registries: a systematic review discharge abstract database (dad) metadata: canadian institute for health information hospital mental health database (hmhdb) metadata: canadian institute for health information home care reporting system (hcrs) metadata: canadian institute for health information continuing care reporting system (ccrs) metadata: canadian institute for health information version . . adelaide: australian institute of health and welfare's (aihw) national injury surveillance unit (nisu) development and utilisation of the australian spinal cord injury register scoping study to enhance spinal cord injury data connectivity within australia and internationally the international spinal cord injury pain basic data set (version . ) international spinal cord injury spinal column injury basic data set international spinal cord injury: spinal interventions and surgical procedures basic data set biering-sørensen f. international spinal cord injury cardiovascular function basic data set international spinal cord injury pulmonary function basic data set international spinal cord injury endocrine and metabolic basic data set (version . ) biering-sørensen f. international bowel function basic spinal cord injury data set international lower urinary tract function basic spinal cord injury data set international spinal cord injury quality of life basic data set international spinal cord injury musculoskeletal basic data set international spinal cord injury upper extremity basic data set international spinal cord injury skin and thermoregulation function basic data set the world health organization quality of life (whoqol-bref) questionnaire: translation and validation study of the iranian version kheiri , • kazem zendehdel • mahdi safdarian • farideh sadeghian , • zahra khazaeipour • khatereh naghdi • jalil arab kheradmand • soheil saadat • habibollah pirnejad • mohammad reza fazel • esmail fakharian • mahdi mohammadzadeh • mohsen sadeghi-naini , • houshang saberi , • pegah derakhshan • hadis acknowledgements we would like to thank the deputy of research and technology, ministry of health and medical education of iran for supporting the nscir-ir. also, we thank the office of university and industry communication in tehran university of medical sciences, and all experts who provided insight and expertize that greatly assisted the research. key: cord- -yac kzaf authors: eden, john-sebastian; rockett, rebecca; carter, ian; rahman, hossinur; de ligt, joep; hadfield, james; storey, matthew; ren, xiaoyun; tulloch, rachel; basile, kerri; wells, jessica; byun, roy; gilroy, nicky; o’sullivan, matthew v; sintchenko, vitali; chen, sharon c; maddocks, susan; sorrell, tania c; holmes, edward c; dwyer, dominic e; kok, jen title: an emergent clade of sars-cov- linked to returned travellers from iran date: - - journal: virus evol doi: . /ve/veaa sha: doc_id: cord_uid: yac kzaf the sars-cov- epidemic has rapidly spread outside china with major outbreaks occurring in italy, south korea, and iran. phylogenetic analyses of whole-genome sequencing data identified a distinct sars-cov- clade linked to travellers returning from iran to australia and new zealand. this study highlights potential viral diversity driving the epidemic in iran, and underscores the power of rapid genome sequencing and public data sharing to improve the detection and management of emerging infectious diseases. from a public health perspective, the real-time whole-genome sequencing (wgs) of emerging viruses enables the informed development and design of molecular diagnostic assays, and tracing patterns of spread across multiple epidemiological scales (i.e. genomic epidemiology). however, wgs capacities and data sharing policies vary in different countries and jurisdictions, leading to potential sampling bias due to delayed or underrepresented sequencing data from some areas with substantial sars-cov- activity. herein, we show that the genomic analyses of sars-cov- strains from australian returned travellers with covid- disease may provide important insights into viral diversity present in regions currently lacking genomic data. in late december , a cluster of cases of pneumonia of unknown aetiology in wuhan city, hubei province, china was reported by health authorities (wuhan municipal health commission ). a novel betacoronavirus, designated sars-cov- , was identified as the causative agent (wu et al. ) of the disease now known as covid- , with substantial humanto-human transmission (lu et al. ) . to contain a growing epidemic, chinese authorities implemented strict quarantine measures in wuhan and surrounding areas in hubei province. significant delays in the global spread of the virus were achieved, but despite these measures, cases were exported to other countries. as of march , these numbered more than countries, on all continents except antarctica; the total number of confirmed infections exceeded , and there were nearly , deaths (dong, du, and gardner ) . although the majority of cases have occurred in china, major outbreaks have also been reported in italy, south korea, and iran (world health organisation a). importantly, there is widespread local transmission in multiple countries outside china following independent importations of infection from visitors and returned travellers. viral extracts were prepared from respiratory tract samples where sars-cov- was detected by reverse-transcription polymerase chain reaction (rt-pcr) using world health organisation ( b) recommended primers and probes targeting the e and rdrp genes. in new south wales (nsw), australia, wgs for sars-cov- was developed based on an existing amplicon-based illumina sequencing approach (di giallonardo et al. ). viral extracts were reverse transcribed with ssiv vilo cdna master mix and then used as input for multiple overlapping pcr reactions ( . kb each) spanning the viral genome using platinum superfi master mix (primers provided in supplementary table s ). amplicons were pooled equally, purified, and quantified. nextera xt libraries were prepared and sequencing was performed with multiplexing on an illumina iseq ( cycle flow cell). in new zealand, the artic network protocol was used for wgs (quick ) . in short, -bp tiling amplicons designed with primal scheme (grubaugh et al. a ) were used to amplify viral cdna prepared with superscript iii. a sequence library was then constructed using the oxford nanopore ligation sequencing kit and sequenced on a r . . minion flow cell. near-complete viral genomes were then assembled de novo in geneious prime . . or through reference mapping with rampart v . . (hadfield ) using the artic network ncov- novel coronavirus bioinformatics protocol (loman and rambaut ) . in total, sars-cov- genomes were sequenced from cases in nsw diagnosed between january and march , as well as a single genome from the first patient in auckland, new zealand sampled on february (table ) . australian and new zealand sequences were aligned to global reference strains sourced from gisaid with mafft (katoh ) and then compared phylogenetically using a maximumlikelihood approach-phyml v . . (guindon and gascuel ) . the australian strains of sars-cov- were dispersed across the global sars-cov- phylogeny (fig. a) . the first four cases of covid- disease in nsw occurred between and january , and these were closely related with - single nucleotide polymorphisms (snps) difference to the dominant variant circulating in wuhan at the time (prototype strain mn /sars-cov- /wuhan-hu- ). as the four patients identified in this period had recently returned from china, this region was the likely source of infection. from february , travel to australia from mainland china was restricted to returning australian residents and their children, who were placed in home quarantine for days. despite the intensive testing of such returning travellers, no further cases of covid- were detected in nsw until february , when sars-cov- was detected in an individual returning from iran (nsw ). a close contact of this individual also tested positive (nsw ) providing the first evidence of local transmission within nsw. this was followed by further iran travel-linked cases in nsw (nsw , nsw , nsw , and nsw ) and new zealand (nz ). of note, the genomes of all patients with a history of travel to iran were part of a monophyletic group defined by three nucleotide substitutions (g a, t c, and g t) in the sars-cov- genome relative to the wuhan prototype strain (fig. b) . g a and t c both occur in coding regions with g a producing a non-synonymous change (v i) in the orf ab-encoded non-structural protein region. g t occurs in the -utr. in addition to the australian and new zealand strains, this clade also included a traveller who had returned to canada from iran (bc_ _ - ), providing further evidence of its likely link to the iranian epidemic. indeed, a search of all currently available gisaid sequences and metadata revealed no other complete genome sequences from patients with documented history of travel to or residence in iran (as of march ). a search of partial sequences identified two sars-cov- sequences which originated in iran ( /irn/ tehran aw/ - - and /irn/tehran be/ - - ) spanning a nt region of the viral nucleoprotein (n). although short in length, these two sequences covered one of the informative snps defining this clade-t c, and both iranian strains matched the sequences from patients with travel histories to iran and grouped by phylogenetic analysis (supplementary figs. s and s ). technological advancements and the widespread adoption of wgs in pathogen genomics have transformed public health and infectious disease outbreak responses (popovich and snitkin ) . previously, disease investigations often relied on the targeted sequencing of a small locus to identify genotypes and infer patterns of spread along with epidemiological data (dudas and bedford ) . as seen with the recent west african ebola (dudas et al. ) and zika virus epidemics (grubaugh et al. ) , rapid wgs significantly increases resolution of diagnosis and surveillance thereby strengthening links between genomic, clinical, and epidemiological data (grenfell ) , and potentially uncovering outbreaks in unsampled locations (grubaugh et al. b ). this advance improves our understanding of pathogen origins and spread that ultimately lead to stronger and more timely intervention and control measures (grubaugh et al. c) . following the first release of the sars-cov- genome (wu et al. ) , public health and research laboratories worldwide have rapidly shared sequences on public data repositories such as gisaid (shu and mccauley ) (n ¼ genomes as of march ) that have been used to provide near real-time snapshots of global diversity through public analytic and visualization tools (hadfield et al. ) . although all known cases linked to iran are contained in this clade, it is important to note the presence of two chinese strains sampled during mid-january from hubei and shandong provinces. it is expected that further chinese strains will be identified that fall in this clade, and across the entire phylogenetic diversity of sars-cov- as this is where the outbreak started, including likely for the outbreak in iran itself. however, while we cannot completely discount that the cases in australia and new zealand came from other sources including china, our phylogenetic analyses, as well as epidemiological (recent travel to iran) and clinical data (date of symptom onset), provide evidence that this clade of sars-cov- is directly linked to the iranian epidemic, from where genomic data are currently lacking. importantly, the seemingly multiple importations of very closely related viruses from iran into australia suggest that this diversity reflects the early stages of sars-cov- transmission within iran. supplementary data are available at virus evolution online. evolution of human respiratory syncytial virus (rsv) over multiple seasons in new south wales an interactive web-based dashboard to track covid- in real time the ability of single genes vs full genomes to resolve time and space in outbreak analysis virus genomes reveal factors that spread and sustained the ebola epidemic unifying the epidemiological and evolutionary dynamics of pathogens an amplicon-based sequencing framework for accurately measuring intrahost virus diversity using primalseq and ivar a simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood nextstrain: real-time tracking of pathogen evolution mafft: a novel method for rapid multiple sequence alignment based on fast fourier transform genomic characterisation and epidemiology of novel coronavirus: implications for virus origins and receptor binding whole genome sequencing-implications for infection prevention and outbreak investigations gisaid: global initiative on sharing all influenza data-from vision to reality b) coronavirus disease (covid- ) technical guidance: laboratory testing for a new coronavirus associated with human respiratory disease in china briefing on the current pneumonia epidemic situation in our city the members of the ncov- study group also include linda donovan, shanil kumar, tyna tran, danny ko, christine ngo, tharshini sivaruban, verlaine timms, connie lam, mailie gall, karen-ann gray, rosemarie sadsad, and alicia arnott. the authors acknowledge the sydney informatics hub and the use of the university of sydney's high-performance computing cluster, artemis, and all the laboratories that have referred sars-cov- samples to the centre for infectious diseases and microbiology laboratory services, nsw health pathology -institute of clinical pathology and medical research, westmead hospital. we would finally like to thank all the authors who have kindly shared genome data on gisaid, and we have included a table (supplementary table s ) outlining the authors and institutes involved. data including the sequences in this study are available for download from https:// www.gisaid.org/. this study was supported by the prevention research support programme funded by the new south wales ministry of health and the nhmrc centre of research excellence in emerging infectious diseases (gnt ).conflict of interest: none declared. key: cord- -w ao ic authors: bahrami, somayeh; alborzi, ali reza title: prevalence of subclinical coccidiosis in river buffalo calves of southwest of iran date: - - journal: acta parasitol doi: . /s - - - sha: doc_id: cord_uid: w ao ic despite the importance of buffalo farming in iran, little is known in this country about the abundance and distribution of eimeria spp. in the animal species. the present study was designed to investigate the prevalence and species characterization of eimeria oocysts in river buffalo calves of khuzestan province, southwest of iran. of the total fecal samples examined for eimeria, ( %) were found infected with species of the parasite. among the identified species of eimeria, e. bovis was found to be the predominant etiological agent ( . %), followed in order by e. canadensis ( . %), e. zuernii ( . %), e. ellipsoidalis ( . %), e. subspherica ( . %), e. brasiliensis ( . %), e. auburnensis ( . %), e. alabamensis ( . %), e. pellita ( . %), e. illinoisensis ( . %) and e. bukidnonensis ( . %). in most calves multiple infections with three species were present. while, . % of calves showed heavy infection, . and . % of calves showed weak and moderate infection, respectively. there was no significant difference in the opg values between the calves of different localities. there was also no significant difference between the prevalence rate of infection in males and females. a total of . % of all faecal samples were found to be diarrheic. a highly significant relationship could be identified between the occurrence of diarrhea and the level of e. bovis and e. zuernii oocysts excretion. considering the pervasive occurrence and negative effects of the infection on the health condition and the growth performance of buffalo calves, infections should receive increased attention by both farmers and veterinarians. eimeria spp. is a protozoan genus that causes the world wide distributed parasitic disease known as coccidiosis. infection by this protozoan causes economic losses due to reduced weight gain and deaths of young animals. more than twelve different species of eimeria in cattle and buffalo have been documented until now. most species are considered to have a low pathogenicity, whereas infection with e. bovis or e. zuernii may cause severe disease in calves (daugschies and najdrowski ) . high infection pressure, lack of preventive and therapeutic measures when clinical disease manifests, can lead to outbreaks and high mortality among calves (fox ) . coccidiosis in calves commonly occurs as subclinical, without typical signs of the disease but may though causes great economic losses due to damage in intestine lining, resulting in malabsorption. infected calves are also more susceptible to secondary diseases, such as pneumonia, bacterial enteritis and viral infections (fox ) . nevertheless, over-reliance on these drugs is an economic burden. additionally parasite resistance may reduce our ability to successfully control this disease (harper and makatouni ) . recent studies have shown that eimeria spp. are widespread in ruminants, but these parasites appear to be of low priority when questioning the farmers and observing statistics of veterinary diagnostics. this situation has triggered efforts towards the investigation on this parasite. according to the latest available statistics, there are about thousand head of buffaloes in iran which is ranked th among countries in the world. there is a considerable population (> , head) of river buffalo (bubalus bubalis) in khuzestan province southwest region of iran which play a significant role in rural life by producing milk and meat while tolerating the impact of harsh environmental conditions (taheri dezfuli et al. ) . in iran, there is no published data available on eimeria infection in river buffalo. since, the highest prevalence of oocyst shedding and dis-*corresponding author: s.bahrami@scu.ac.ir somayeh bahrami and ali reza alborzi ease incidence occurs in calves less than a year of age, the objective of this study was to obtain information about the prevalence of coccidiosis amongst the river buffalo calves in farms of the region and to determine which eimeria spp. are involved in natural infections. the study was conducted in khuzestan, southwest province of iran from december to july . it has a border of about km², between degree and minutes to degree and min of eastern longitude from prime meridian and degree and min to degree and min of northern latitude from equator (statistical book of khuzestan province, ) . the province has hot and wet summers, mild spring and cold winters. the buffalo population mainly comprises local domestic species, which are well adapted to the climate of the area. a total of fecal samples ( females and males) were collected from calves (birth to months of age). samples were taken from four geographical localities of khuzestan province where the most population of buffalo herds are raised. samples were taken from northeast of the province ( samples), south of the province ( samples), east of the province ( samples) and southwest of the province ( samples). the farms participating in this study had been selected randomly. most of the buffalo herds in this province have small size (less than fifty animals). up to farms in each locality were visited once during the observation period. on average, % of the total numbers of animals in the farms were sampled. therefore, on each farm, individual samples were collected from three to five randomly selected calves. the age of the animals was documented according to the owner records. fecal samples were collected directly from rectum or immediately after defecation in a wide-mouth plastic bottle. all the samples were classified on collection according to their consistency, as normal or diarrheic feces (liquid or semi-liquid feces). until tested for eimeria spp. oocysts in the laboratory, the fecal samples were stored under refrigerated conditions. each fecal sample was examined for coccidian oocysts using modified mcmaster technique with sheather's sugar flotation solution and light microscope (ernst and benz ) and expressed as oocysts per gram of faeces (opg). after counting the eimeria oocysts in the feces of each animal, the numbers of opg were graded as follows: , opg ( +, weak); , to , opg ( +, moderate); and > , opg ( +, heavy). to reduce variation, all counts and identification of oocysts were done by one individual throughout the study. three g of the feces were mixed thoroughly with ml potassium dichromate . % (w/v) solution. the mixture was strained through thick gauze to remove coarse plant matter, poured in thin layers into petri dishes and left to sporulate for - days at room temperature. after sporulation, the potassium dichro-mate fecal solution was centrifuged in a test tube at , rpm for min. the supernatant was decanted and sediment put into a faecalyser tube. a % sugar solution was poured in to the faecalyser tube until a meniscus formed. a coverslip was placed on the tube, then carefully removed and placed on a microscope slide. at least sporulated oocysts from each sample were measured using a research microscope with × magnification. differentiation of eimeria spp. oocysts was made by measurement and based on morphological criteria according to levine ( ) , eckert et al. ( ) and soulsby ( ) . results were analysed using the one-way anova and independent-samples t test (spss ). the significance levels are expressed at a % confidence level (p ≤ . ) throughout. coccidiosis is a serious economic problem in sub-clinically infected animals because they appear normal outwardly, but developmental stages damage the absorptive surface of the intestine and weaken the immune system, leading to reduced feed consumption, poor feed conversion, slow weight gain and increased susceptibility to other infections (fitzgerald , daugschies and najdrowski ) . in khuzestan province of iran no attention has yet been paid to this parasitic infection because of the lack of detailed information on the presence of different eimeria spp. of local buffalo herds. in the present study % of calves were infected with eimeria oocysts. the high proportion of infected calves, supports our hypothesis that probably all farms in khuzestan province are infected with these ubiquitous parasites. the susceptibility of hosts to eimerian parasites depends on their age, genetic predisposition, innate or adaptive immunity, stress level, handling, location of the parasite in the intestinal epithelium, number and location of endogenous stages, as well as climatic and other factors (hayat et al. ) . the hot and humid climate of khuzestan province is advantageous to both the expansion of river buffalo herds and the high prevalence of parasites in these animals. these environmental conditions may have con- subclinical coccidiosis in river buffalo calves tributed optimal conditions for oocyst sporulation and thus, for buffalo infection. other factors like poor nutrition, poor sanitation, and overcrowding increased the level of infection and incidence of the disease due to stress-induced immunosuppression. some studies showed that a strong association was observed between housing system and risk of eimeria infection (rehman et al. ) . in this study animals were reared in closed houses with the non-cemented floor type and they were fed on the ground. feeding of calves on the ground increase the chances of contamination of the feed with eimeria oocysts and non-cemented floor is difficult to clean. abebe et al. ( ) and rehman et al. ( ) believed that grounds fed animals are at higher risk to eimeria infection than trough fed calves. in this study sex has no significant effect on the prevalence or intensity of infection (p > . ). these results were in accordance with findings of ahmed and soad ( ) , but this data is in contrast with the results obtained by rehman et al. ( ) and priti et al. ( ) . they showed that eimeria infection was found to be more prevalent in female calves. based on our results . % of infected calves were infected with only one eimeria spp. mixed infections were generally present. in most calves ( . %) multiple infections with three species were present. the species detected and their prevalence rates are given in table i . e. bovis was found to be the most prevalent species. it occurred in . % of the samples. e. canadensis was the second frequent species ( . %), followed by e. zuernii ( . %) and e. ellipsoidalis ( . %). it was found that most infections were weak ( . %) whereas . % and . % of samples contained moderate and large numbers of oocysts, respectively. there was no significant difference in the opg values between calves of different localities. among the six identified species of eimeria in rehman et al. study ( ) , e. bovis was found to be the highest prevalent species. after sporulation of positive samples in koutny et al. ( ) experiment, eimeria species were found. ten different species of eimeria were identified from the fecal samples of local domestic beef cattle collected from the five localities of afyon province of turkey (cicek et al. ) . in hungary eimeria oocysts were found in % of calve and seven species were identified. among the identified species of eimeria, e. auburnensis was found to be the highest prevalent species (farkas et al. ). in our study . % of fecal samples were found to be diarrheic. a highly significant relationship could be identified between the occurrence of diarrhea and the level of oocyst excretion of e. bovis and e. zuernii. two bovine species (e. bovis and e. zuernii) are known pathogens causing morbidity and mortality (niilo ; friend and stockdale ) . on the other hand, although e. bovis was the most prevalent species in calves, but clinical coccidiosis was not observed. many authors believe that the presence of a pathogenic eimeria species (e. bovis and e. zuernii) does not necessarily indicate clinical disease (parker and jones , waruiru et al. ) . in this study, species of the animals were found to be harbouring pathogenic species of coccidia and yet no clinical symptoms were being exhibited. this indicates that other factors, the number of oocysts ingested, the presence of a concurrent microbial infection (hoblet et al. ) , weather conditions including ambient temperatures and moisture (munyua and ngotho ), the production system and management practices used by the farmer and general conditions of animal husbandry (niilo ) , the functional level of protective immunity and enzootic stability (parker and jones ) , may be decisive in whether clinical disease is precipitated or not. most of animals examined during the present study had low opg, suggesting that the infections were usually sub-clinical. however, the economic consequences of the sub-clinical infections are of importance. most animals can act as asymptomatic carriers and shed large numbers of oocysts into the environment and remain a main source of infection. based on these preliminary results, it can be concluded that eimeria spp. are widely distributed in iranian river buffalo farms. to minimize the impact of coccidiosis, proper hygiene measures and ensuring unfavorable conditions for oocyst survival in the environment should be of utmost importance. if necessary and possible, application of anti-coccidial compound should be also considered. epidemiology of eimeria infections in calves in addis ababa and debrezeit dairy farms applied studies on coccidiosis in growing buffalo calves with special reference to oxidant/antioxidant status world prevalence of coccidia in beef cattle in western turkey infectious disease and veterinary public health morphological characteristics of oocysts coccidiosis studies on coccidiosis of calves in hungarian dairy farms the economic impact of coccidiosis in domestic animals coccidiosis in cattle experimental eimeria bovis infection in calves. a histopathological study prevalence of coccidiosis in cattle and buffaloes with emphasis on age, breed, sex, season and management consumer perception of organic food production and farm animal welfare concurrent experimentally induced infection with eimeria bovis and coronavirus unweaned dairy calves bovine eimeria species in austria veterinary protozoology prevalence of eimeria species in cattle in kenya bovine coccidiosis in canada the development of eimerian infections during the first eight months of life in unweaned beef calves in adry tropical region of australia. veterinary parasitology prevalence of bovine coccidiosis at patna epidemiology and economic benefits of treating goat coccidiosis helminth, arthropods and protozoa of domesticated animals economic weights of milk production traits for buffalo herds in the southwest of iran using profit equation the prevalence and intensity of helminth and coccidial infections in dairy cattle in central kenya acknowledgment.this study was supported by the research grant provided by shahid chamran university of ahvaz. key: cord- -xc vv x authors: eslahi, aida vafae; badri, milad; khorshidi, ali; majidiani, hamidreza; hooshmand, elham; hosseini, hamid; taghipour, ali; foroutan, masoud; pestehchian, nader; firoozeh, farzaneh; riahi, seyed mohammad; zibaei, mohammad title: prevalence of toxocara and toxascaris infection among human and animals in iran with meta-analysis approach date: - - journal: bmc infect dis doi: . /s - - - sha: doc_id: cord_uid: xc vv x background: toxocariasis is a worldwide zoonotic parasitic disease caused by species of toxocara and toxascaris, common in dogs and cats. herein, a meta-analysis was contrived to assess the prevalence of toxocara/toxascaris in carnivore and human hosts in different regions of iran from april to june . methods: the available online articles of english (pubmed, science direct, scopus, and ovid) and persian (sid, iran medex, magiran, and iran doc) databases and also the articles that presented in held parasitology congresses of iran were involved. results: the weighted prevalence of toxocara/toxascaris in dogs (canis familiaris) and cats (felis catus) was . % ( % ci: . – . %) and . % ( % ci: . – . %), respectively. also, pooled prevalence in jackal (canis aureus) and red fox (vulpes vulpes) was . % ( % ci: . – . %) and . % ( % ci: . – . %), correspondingly. weighted mean prevalence of human cases with overall records was . % ( % ci: . – . %). the weighted prevalence of toxocara canis, toxocara cati, and toxascaris leonina was represented as . % ( % ci: . – . %), . % ( % ci: – . %) and . % ( % ci: . – . %), respectively. conclusion: our meta-analysis results illustrate a considerable prevalence rate of toxocara/toxascaris, particularly in cats and dogs of northern parts of iran. the presence of suitable animal hosts, optimum climate and close contact of humans and animals would have been the reason for higher seroprevalence rates of human cases in our region. given the significance clinical outcomes of human toxocara/toxascaris, necessary measures should be taken. zoonoses are those complications which are transmissible between human and animal populations [ ] . in this regard dogs and cats are considered as a public health concern, as they may harbor various pathogens such as zoonotic helminths including toxocara species [ ] . toxocariasis is a worldwide parasitic infection, primarily rendered by t. canis in dogs, t. cati in cats and foxes and t. leonina in a wide range of carnivores [ ] . mature worms lay eggs in the intestinal lumen of their host, which are excreted into the environment via defecation and pass their developmental stages in optimum soil and climate conditions. upon ingestion of embryonated eggs by another host, the larvae would emerge and invade the intestinal mucosa, then migrate through viscera such as lungs, liver, and kidneys. in addition, transplacental and transmammary transmission to puppies and kittens are important routes of infection. in an epidemiological perspective, animal hosts parasitized by adult worms in their gut can disseminate infection by shedding parasite eggs into environment [ ] . in an epidemiological perspective, animal hosts parasitized by adult worms in their gut, can shed parasite eggs, hence considered as a source for dissemination of the infection [ ] . human infection occurs by accidental ingestion of eggs, and, to a lesser extent, via pica and devouring on the paratenic hosts, including chicken, cattle, lamb, pig, and earthworms [ , ] . consequently, developmentally-arrested larvae migrate through body organs, but don't develop into mature worms; hence, they provoke an array of syndromes enclosing vlm, nlm, and olm as well as covert infection and asymptomatic toxocariasis [ ] [ ] [ ] . although rare, cardiac-associated toxocariasis is a serious, life-threatening complication due to vlm which has recently been emphasized [ ] . most of the infected individuals manifest nonspecific symptoms such as a cough, rhonchus, dyspnea and pyrexia along with hepatomegaly and eosinophilic granuloma, which implicates diagnosis of the infection using more sensitive approaches such as immunological assays i.e., elisa for screening and western blot for confirmation, rather than histological or parasitological methods [ , ] . toxocariasis cause by t. cati and t. canis frequently impacts young cats and dogs from birth to year old, entailing respiratory signs (coughing due to pulmonary larval migration), general failure to thrive (retarded growth, emaciation, debilitated body coat and arthralgia) and intestinal disorders (alternating diarrhea and constipation, pot-belly and vomiting). no remarkable trait is seen following toxascaris infection in dogs and/or cats and it is usually well-tolerated [ ] [ ] [ ] . one of the characteristic of helminthic parasites is the stimulation of the immune system that leads to increased th response and high production of il- , il- , il- , il- , il- , eosinophils, and ige. toxocara larvae can causes severe hyper eosinophilia and allergic involvements with effect on ige and il- . consequently, the production of specific antibodies provides the most complete evidence for toxocara infection, which is the base of diagnostic tests such as elisa and western blot for reactivity to larval tes antigen [ ] [ ] [ ] . iran, a middle eastern country, possesses several climatological areas with particular characteristics in each region; this would have a significant bias on the epidemiology of toxocara/toxascaris species. in the previous studies the infection of dogs and cats with toxocara species in different parts of iran has been shown [ ] . despite the prevalence of toxocara canis in the most areas, molecular studies on cat nematodes in shiraz, in south-central iran showed that, the most prevalent one is t. cati [ ] . toxocara vitulorum is frequently found in ruminants. its main hosts are cattle and buffalo in tropical and sub-tropical regions [ ] . it has been reported that % ( % ci: - %; out of samples) of soil samples gathered from public parks of the iran were positive for toxocara spp. eggs [ ] . on the other hand, due to increasing body of work on toxocara prevalence in various human/animal hosts in iran, a comprehensive review would be exceedingly beneficial for appraising progresses about this zoonosis. therefore, this meta-analysis attempts to fill the current gaps and provides insights into parasite prevalence with respect to host type, toxocara and toxascaris species, and geographical region in the country. iran has a population of approximately million (as of ), and is located between ° and ° n and ° and ° e, which covers a wide territory in the middle east area ( , , km ) . the country borders afghanistan and pakistan to the east, iraq and turkey to the west, the persian gulf and oman sea to the south, and azerbaijan, armenia, and turkmenistan to the north. the iranian plateau climate is generally hot and dry, however the caspian sea coast in northern parts, comprising golestan, mazandaran and guilan provinces, is mediterranean-like, demonstrating heavy rainfalls, vegetation-enriched, surrounded by dense forests and a diverse range of carnivorous animals these geo-ecological features would provide a well-established setting for most parasites, e.g. soil-transmitted helminthiases, to localize in the area and parasitize many canid species. also, the country is a mountainous region with several mountain ranges, mostly located at the western and northern parts such as zagros mountain ranges with colder winters and heavy snowfalls. the annual precipitation is mm in the eastern part of the plain and more than mm in the western parts [ ] [ ] [ ] [ ] . the prisma protocol (preferred reporting items for systematic reviews and meta-analysis) was employed to conduct this meta-analysis [ ] . in order to assess the prevalence of t. canis, t. cati and t. leonina in humans and carnivores of different parts of iran, we investigated the available online articles of both persian (sid, iran medex, magiran, iran doc) and english (pubmed, science direct, scopus, ovid) databases. the search include between april and june . also, the articles that presented in held parasitology congresses of iran were involved. a combination of the following search terms were employed in our literature searches as follows: ("toxocariasis" or "toxocara infection" or "toxocara canis" or "toxocara cati" or "toxascaris leonina") and ("carnivora" or "human") and ("prevalence" or "epidemiology") and ("iran"). after hand searching in bibliographic list of obtained full-text records for any related literature as well as removing duplicates, two independent reviewers screened the titles and abstracts for initial inclusion. a third reviewer was also involved for consensus in the case of any disagreements. finally, those records that met the following inclusion criteria were eligible to enter our meta-analysis: (a) peer-reviewed originally-published papers both in english or persian; (b) being available online between april till june ; (c) crosssectional investigations that assessed the prevalence of toxocara spp. in various carnivores and human populations in iran; (d) studies that detected toxocara infection using at least one of the parasitological, serological and molecular methods; (e) exact total sample size, positive samples and the respective prevalence rates were available. empirical studies and any kind of review papers were excluded and failed for further analysis. a detailed variable of each of articles, including: province, year of publication, study design, sample size, detection method, and prevalence rates, in addition to animal species and sampling method for animal-based investigations were gathered. in this study, the jbi critical appraisal checklist for prevalence studies was employed [ ] . the jbi checklist was used for quality assessment of the included articles. this checklist contains eight questions with four options including, yes, no, unclear, and not applicable (additional file : figure s ). briefly, a study can be awarded a maximum of one star for each numbered item. the papers with a total score of ≤ and ≥ points were specified as the moderate and high quality, respectively. based on the obtained score, the authors have decided to include and exclude the papers [ ] . briefly, meta-analysis was yielded as a forest plot representing the prevalence estimates and related confidence intervals of each study along with summary measures. also, the heterogeneity was analyzed using stata statistical software (version . ) to calculate cochran's q and i statistics. i values of , , and % were considered as low, moderate and high heterogeneity, respectively [ ] . furthermore, the funnel plot based on egger's regression test illustrates publication bias and small study effects. in the current study, i was substantial; therefore, we used a random effects model at a % ci, to give a more conservative estimate of the toxocara infection prevalence. following systematic search of eight databases, totally records human studies and animal investigations were found eligible regarding toxocara/toxascaris (fig. ) . during a -years period, , human individuals were examined and the calculated weighted prevalence was . % ( % ci: . - . %) (tables and ). the trend line of human toxocara/toxascaris infection demonstrated that the prevalence has declined in spite of increased bulk of work on human population (additional file : figure s ). most records ( studies) were conducted in both rural and urban circumstances, however seroprevalence was mostly predominant in urban regions with % ( % ci: . - . %) (no showed data). people under years old were mostly examined by serodiagnosis approach, indicating . % ( % ci: . - . %) seroprevalence rate (additional file : figure s ). a number of entries contributed to prevalence of toxocara/toxascaris in dogs (canis familiaris), showing a prevalence of . % ( % ci: . - . %). the weighted prevalence of toxocara/toxascaris was higher in investigations which examined cats (felis catus) [ . % ( % ci: . - . %)] (tables and ) . interestingly, one study also used serodiagnosis in cats indicating a . % ( % ci: . - . %) seroprevalence (additional file : figure s ). four studies (all necropsy-based) dedicated to prevalence of toxocara/toxascaris in jackal (canis aureus), representing a . % ( % ci: . - . %) frequency. a and ). according to the detection method, the highest total prevalence of t. canis in feces was related to the formalin-ether method [ . % ( % ci: . - . %)] (additional file : figure s ). also the most total prevalence of t. cati in feces was related to the formalin-ether method [ . % ( % ci: . - . %)] (additional file : figure s ). among toxocara/toxascaris species examined through included studies in iran, t. cati possessed the highest prevalence rate with . % ( % ci: . - . %) ( (figs. , and ) . there was no statistically significant association between the estimated pooled prevalence of toxocara/toxascaris infection in human population and mean temperature (p = . ), humidity (p = . ), longitude (p = . ), and latitude (p = . ). among three parasite species, only humidity (p = . ) and latitude (p = . ) for t. canis were statistically significant, while others were not remarkably involved (fig. ). the current systematic review and meta-analysis was aimed to elucidate the prevalence of toxocara spp. infection in animal and human hosts in iran. the human infection was highly concentrated in two northern provinces (mazandaran and east azerbaijan) (fig. ) , highlighting optimum geo-ecological milieu in those parts of the country because of high percentage humidity due to vicinity to the caspian sea as well as considerable rainfall during the year; notwithstanding, we didn't found any statistically significant correlation between human toxocara/toxascaris seroprevalence studies and fig. the total prevalence of t. cati infection in carnivores of iran geographical parameters comprising mean temperature, humidity, longitude and latitude (fig. ) . despite of equal records of toxocara/toxascaris infection from rural and urban areas, seroprevalence was partly elevated in urban regions rather than rural territories, resulting from the likely heterogeneity among studies and/or lack of sufficient records; care must be taken in interpreting such result as rural areas are naturally considered as higher risk areas than urban [ , , , ] . toxocariasis due to several species of toxocara and/or toxascaris roundworms is still a seriously notifiable public health issue, particularly due to its intricate transmission routes [ ] . in human this infection is caused by t. canis, in particular, and t. cati renders several issues comprising vlm, olm, nlm and covert disease, each of which is represented by manifestations of the involved organ [ , ] . toxocara/toxascaris infection in human populations is considered as a chronic parasite in nature which is distributed worldwide, particularly in tropical underdeveloped countries [ ] . several risk factors are supposed to play a major role in toxocara/toxascaris distribution among the human population, consisting of habitation in rustic areas, soil contact, consuming the undercooked meat of the infected paratenic host, insufficient and unhygienic water repositories, poor housing and low education as well [ ] [ ] [ ] [ ] . furthermore, owing to the adventurous nature of children, such as tasting any objects, eating soil and/or earthworms and being in the vicinity of dogs and cats, they are considered as a substantial risk group regarding toxocariasis [ , ] . hence, public places in which children may walk around such as parks, playgrounds, beaches and sandboxes are crucial territories for the acquisition of the infection [ , ] . since most individuals do not manifest any pathognomonic symptoms, the actual prevalence rate of the infection remains to be elucidated, even in industrialized nations [ , ] . considering that toxocara parasites do not develop into adult stage in humans, coproscopy is unnecessary; thus, biopsy and direct parasite observation are the gold standard methods [ ] . however, such examination is invasive and relies on the larval load and the infection phase [ ] . therefore, routine diagnosis of infection and/or exposure in human cases can be done by elisa to detect specific antibody against tes antigens, which should be further validated by immunoblotting [ , ] . as previously mentioned, tes-based elisa tests are mostly used for human seroprevalence studies. despite having proper immunogenicity, native tes antigens may cross-react with antibodies elicited against other helminths specifically ascaris lumbricoides which decreases test specificity [ ] . therefore, the results may be regarded as suspicious, particularly when no immunoblotting confirmation is done, specifically in endemic regions where there exists the possibility of helminth co-infections. alternative detection methods in paratenic or accidental hosts are including pathological inspection, larvae morphometry as well as pcr-based experiments [ ] . a great deal of effort has been devoted to revealing the seroprevalence of human toxocara/toxascaris infection worldwide. in africa, elevated seroprevalence rates of infection were detected, encompassing % in egypt to % in gabon and % in réunion island [ , ] . additionally, the seroprevalence ranges in asia and south america included - . % and . - %, respectively [ ] [ ] [ ] . comparable to other territories, rates of seropositive human cases were relatively low in european and north american countries [ ] , implicating improved hygiene practices and public awareness in industrialized nations. in total, seroprevalence data integration in epidemiological investigations is not reasonable for several reasons, comprising sampling disparities, antigen preparation, and quality, different cutoff levels, cross-reactivity especially in the tropics were polyparasitism exist and inability to explicitly distinguish the infection by various toxocara spp. therefore, expanding our evidence based on human toxocara infection would be corroborated by a better understanding of parasite biology, in particular, the immune evasion mechanism of larvae, and utilization of advanced, species-specific diagnostic tools [ ] . the calculated total prevalence of infection in cats (felis catus) was higher [ . % ( % ci: . - . %)] than in dogs (canis familiaris) [ . % ( % ci: - %)] in the country (table ). similar to human seropositive cases, carnivores in northern iran were the most frequent hosts being parasitized by toxocara spp., whereas minimum animals were infected in central parts [ % ( % ci: - %)]. among wild canine species in iran, only jackal (canis aureus) and red fox (vulpes vulpes) were diagnosed with toxocara/toxascaris infection, with . % ( % ci: . - . %) and . % ( % ci: . - . %), respectively (table ) . moreover, it was deduced that the weighted prevalence of t. canis, t. cati, and t. leonina in iran were . % ( % ci: . - . %), . % ( % ci: . - . %), and . % ( % ci: . - . %), respectively. given fig. the total prevalence of t. canis infection in carnivores of iran geographical characteristics, only humidity (p = . ) and latitude (p = . ) were significantly linked to t. canis infection. increasing latitude would likely result in decreased mean temperature and more temperate climates than the equator area. water vaporization and condensation in northern parts of the country due to the vicinity to the caspian sea and high mountain ranges and humid weather substantially implicate in toxocara/ toxascaris larval development, as proved in the laboratory [ , ] . the survey of the infection in carnivores is usually made via traditional parasitological methods (e.g. floatation technique) to detect eggs as well as intestinal necropsy of dead carcasses [ , ] . nevertheless, each detection method may provide a prevalence rate different from other modalities, which this issue would implicate potential biases in reporting and/or interpreting data. as we stated in the results section, necropsy has been shown as a better and efficient detection tool than fecal examination. for instance, more than -fold prevalence of toxocara/toxascaris spp. in dogs was obtained using necropsy [ [ ] [ ] [ ] [ ] . in dogs dwelling in the americas, t. canis infection prevalence varied from . % in canadian provinces to % in cuba. also, t. cati was mostly prevailed in argentina and brazil with and %, respectively [ ] [ ] [ ] [ ] . the highest t. canis and t. cati infection rates in asia were dedicated to russia and china with and . %, respectively [ , ] . additionally, mild toxocara species infections were identified in african domestic carnivores [ ] [ ] [ ] [ ] . globally, the highest t. leonina prevalence (up to %) was observed in domestic dogs from russia [ ] . wildlife probably plays a critical role in the epidemiology of toxocara species, as they may be considered as potent reservoir for these enigmatic roundworms [ ] . patent t. canis infections are generally higher in young foxes (under months of age); although, a relatively high prevalence rate have also been among adult foxes in endemic territories, representing weak immune status against intestinal [ ] . the prevalence of t. canis in european foxes varies between . % (in italy) and . % (in denmark), as well as . and . % prevalence in canada and japan, respectively [ ] . the lowest and highest t. leonina prevalence in red fox was reported from kirghizstan ( . %) and the slovak republic ( . %), respectively [ ] . regarding golden jackal (canis aureus) moderate prevalence rates of toxascaris leonina have been reported around the world, such as in azerbaijan ( . %), bulgaria ( %) and russia ( . %). the prevalence of t. canis in this wildlife species ranges - % in asia and - . % in european countries, whereas t. cati was only detected in jackals dwelling in russia ( - %) [ , ] . considering that there are only golden jackal studies and red fox (vulpes vulpes) studies, there exist paucity of data on toxocara/toxascaris prevalence in wild canine and feline fauna of iran, which highlights more subtle investigations. approximately, since the middle of previous century a periurban rise in european foxes population carrying toxocara/toxascaris worm burdens have posed a great environmental risk of contamination with parasite ova. on the other hand, they act a critical role in maintaining t. canis wildlife cycle with implications in constant transmission to human populations and pet dogs [ ] . the findings of the present study indicated a mild seroprevalence in human population; also, infection in cats was higher than dogs, however unbalanced sampling may have influenced these findings. most of the infected cases were from north of iran, which possess a favorable ecological milieu for appropriate animal hosts and toxocara egg development (i.e., - °c in laboratory-based conditions, during - weeks [ ] . despite the improved hygiene and health surveillance systems as well as a wide-range public awareness in developed countries, still toxocara/toxascaris infection remains a public health concern in those areas and the rest of the world as well. during the time, there have been established a close companionship between dogs and cats with humans, and during past decades it has been even strengthened. however, these associations, particularly in underdeveloped nations, have been accompanied with poor veterinary infrastructures. this, along with free-roaming or community-owned dogs and cats pose a serious threat for zoonoses transmission to human societies [ ] . with respect to the constant infection cycle in carnivores and the life-threatening traits of human toxocariasis, revisiting the epidemiological strategies in companion animals enclosing anti-helminthic medication and screening plans such as the routine fecal examination is of utmost importance. in addition, it is highly emphasized that future human investigations focus on using recombinant tes antigens with high sensitivity and specificity and less cross-reactivity. also, it is better to identify anti-toxocara igg coupled with tes rather than total igg and employ western blot as a complementary diagnostic technique [ ] . moreover, it is recommended to educate laboratory technicians for accurate parasite detection, regularly deworm puppies and kittens to decrease the worm burden, perform proactive chemoprophylaxis approach and cultivate knowledge among the public as well as physicians regarding the clinical consequences of the disease. the interwoven collaboration among blood banks, veterinary diagnostic laboratories and municipalities (control stray dog/cat populations in urban areas) would provide a more completed picture of disease seroprevalence and distribution in people and animals, giving us the opportunity for targeted intervention strategies and better management of this zoonotic enigma. in parallel to above-mentioned recommendations the wsava has recently found a one health committee to highlight the transmission potential of zoonotic infectious agents from dog/cat to human. besides the oie has recently extended the surveillance of wildlife diseases through wahid in the world. all of these expanded fields of epidemilogical data would assist the global community towards better understanding of human-domestic animal-wildlife interplay and control of human zoonotic diseases [ ] . it is noteworthy to mention that some limitations constrained our findings en route performing current systematic review and meta-analysis, including ) lack of risk factor appraisal, ) absence of a standard, easy-touse diagnostic tool in case of human studies to particularly discern the involved toxocara spp., ) lack of investigations considering different aspects of human toxocara-induced complications such as vlm, olm, and covert infection. certainly, with these in hands, we could achieve the more complete picture of the current in conclusion, this study revealed that toxocara and toxascaris infection in iran among people is mild while in dogs and cats are high. exclusive studies including human, animal and environmental health data should be conducted in different geographical regions of the country. the outcome of such studies will allow the government and non-government organization to set proprieties and design strategies, combining accurate surveillance and prevention of these zoonotic diseases. the use of animals as a surveillance tool for monitoring environmental health hazards, human health hazards and bioterrorism toxocara seroprevalence and associated risk factors in the united states toxocariasis in north america: a systematic review the 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jackal parasites reveals high diversity of species changes in the distribution of red foxes (vulpes vulpes) in urban areas in great britain: findings and limitations of a media-driven nationwide survey lehrbuch der parasitologie für die tiermedizin [textbook of parasitology for veterinary medicine surveillance of zoonotic infectious disease transmitted by small companion animals publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations the authors would like to thank all staff of the department of parasitology of tarbiat modares university and alborz university of medical sciences, iran. supplementary information accompanies this paper at https://doi.org/ . /s - - - .additional file : figure s . the quality assessment of included studies of human population additional file : figure s . the weighted prevalence of human toxocara/toxascaris by the year in iran additional file : figure s . the weighted prevalence of human toxocara/toxascarisby the age in iran additional file : figure s . the weighted prevalence of toxocara/ toxascaris in iran dogs by study method additional file : figure s . the total prevalence of t. canis in feces of animals according to the different parasitology methodsin carnivore population in iran. mb, ff, and mz extracted the data and wrote the study manuscript. ak and smr contributed to data analysis and interpretation the manuscript. all authors read the manuscript and participated in the preparation of the final version of the manuscript. all authors read and approved the final manuscript. there was no any funding or sponsoring organization for this review. the datasets used and analyzed during the current study are available from the corresponding author on reasonable request. the study design including its ethical aspects was reviewed and approved by the ethics committee of alborz university of medical sciences. not applicable. the authors declare that they have no competing interests.author details key: cord- - k vkgf authors: fan, jingchun; liu, xiaodong; shao, guojun; qi, junpin; li, yi; pan, weimin; hambly, brett d.; bao, shisan title: the epidemiology of reverse transmission of covid- in gansu province, china date: - - journal: travel med infect dis doi: . /j.tmaid. . sha: doc_id: cord_uid: k vkgf background: the transmission of covid- is about to come under control within china, however, an emerging challenge to the chinese authorities is reverse transmission due to covid- patients/carriers evacuating from overseas to china. methods: we analysed the epidemiological characteristics of chinese citizens evacuated from iran. all confirmed covid- cases amongst the returnees were displayed by the spatial distribution pattern of the extent of covid- infection. results: characteristics that differed significantly amongst these returnees compared to the original infected cohorts in gansu were mean age, occupation and sex. differences observed between infected patients and non-patients amongst returnees were age, sex, race, occupation, the use of facemasks, and residential situation in iran. the clinical features that were significantly related to infection were chill, shortness of breath, chest pain and nausea. spatial distribution pattern analysis indicated that infected returnees had resided within iranian provinces that had experienced high levels of covid- . the spatial distribution of the original homes of these returnees before departure for iran demonstrated that returnees will largely return to northwest china, to regions that have only experienced low levels of infection within china. conclusion: blocking the reverse transmission of covid- is critical in preventing a secondary outbreak of covid- . quarantine of the people's republic of china, now requires that a mandatory days quarantine is to be applied to anyone entering china from abroad from countries that have had covid- patients till further notice [ ] . on nd march , there were confirmed covid- cases and new cases in iran with the mortality rate of . % [ ] . to provide support to chinese citizens who are currently overseas in significant covid- outbreak regions, to minimize their risk of covid- infection, the chinese government has sent charter planes to evacuate chinese citizens from a number of covid- -affected countries, particularly italy [ ] and iran [ ] to designated provinces. a total of overseas chinese citizens were returned from iran, arriving at lanzhou, the capital of gansu province on and march , to escape this international epicenter of covid- , and also to provide covid- -affected patients with better medical care [ ] . thus, the most urgent task/challenge for the chinese quarantine authority (cdc equivalent) has been to identify possible/actual covid- infected patients and/or people highly suspected of developing a covid- infection, to enable quarantine of these high risk individuals, to minimise possible reverse transmission of covid- from overseas to the chinese population. we report here the epidemiological characteristics and the clinical features of chinese people evacuated from iran to the quarantine centre of gansu province. we aim to provide critical and objective information to help control the spread of covid- to other provinces and countries. there were a total of chinese overseas citizens evacuated from iran. all of these returnees had resided in provinces within iran that had experienced high levels of local covid- disease. none of the returnees had been tested or clinically screened for covid- prior to their return to china. these returnees were quarantined in lanzhou, gansu province upon arrival. on arrival at lanzhou airport in gansu province, the returnees were isolated in a designated hotel and screened using clinical tools i.e. thermometer, and questions concerning any symptoms, any history of close contact with any known infected people or any persons with symptoms suggestive of covid- . all of the returnees were tested using a swab of the oral/nasopharynx for pcr testing for the the statistical analysis included demographic characteristics, exposure history, clinical symptoms, and pre-existing illness. median (iqr) was used to describe the ages of the returnees and case-patients due to the data being not normally distributed. for categorical variables, if expected cell sizes were < , the fisher exact test was used to compare the frequency between or among groups; otherwise, the χ test was used. a two-sided α of less than . was considered statistically significant. statistical analyses were performed using the sas software, version . , unless otherwise indicated. this study has been approved by the ethics committee of the affiliated hospital of gansu university of chinese medicine (no. ). . results there was a total of overseas chinese evacuated from iran to gansu province, china, arriving on - march ( figure ). most of these returnees were students ( %, / ). their demographics were: male vs female vs , age range months to years, median age was years (iqr: , ). the ethnicity of the majority of these returnees ( %, / ) is from the hui race whose religious background is islamic. there were covid- laboratory confirmed cases ( %, / ) among the returnees until march (first - days after arrival in gansu) and no more new cases up to date. most of the cohort were between - years old, because most are students studying in iran, with the exception of children, who were months to years old, and people who were > years old. of the positive cases, there were only or persons who believed that they had no close contact with either covid- symptomatic persons or covid- patients, respectively. among a total of returnees, there was a significant positive correlation between the incidence of covid- infection and male sex (χ = . , p= . ), younger age ( - y) (p= . ), hui/other races (p= . ), or residing in a dormitory (χ = . , p= . ) ( table ) . paradoxically, we also observed that wearing a facemask while in iran increased the risk for covid- infection (χ = . , p= . ) ( table ) . among the confirmed covid- patients, the age ranged from to years, median years (iqr: , ). there were cases that developed into a critical condition ( %, / covid- cases) in the period till march . we further analysed differences in clinical symptoms and pre-existing illnesses as a function of covid- status between the infected patients and non-infected returnees. the clinical presentations included fever, chill, cough, stuffy nose, running nose, sore throat, headache, fatigue, dizziness, muscle pain, joint pain, shortness of breath, dyspnoea, chest stress, chest pain, conjunctivitis, nausea, vomiting, diarrhoea, and stomach ache. significant differences were observed for the following symptoms: chill (p= . ), shortness of breath (p= . ), chest pain (p= . ) and nausea (p= . ), comparing the infected patients and non-infected returnees (table ). pre-existing diseases amongst all the returnees included hypertension, diabetes mellitus, cardiovascular diseases, asthma, chronic obstructive pulmonary disease, lung cancer, chronic renal and liver diseases, and immunodeficiency diseases. however, there was no difference in the presence of pre-existing disease between the infected patients and non-infected returnees. the original places of residence of these returnees were from provinces or municipalities in china, mainly within the north west of china, e.g. ningxia hui autonomous region ( , %), gansu province ( , %) and henan province ( , %) ( figure ). prior to their evacuation from iran, the majority of these returnees had been living in qom province ( , %), tehran province our data are consistent with the reports above, demonstrating that most of these returnees from iran were young adult international students, who would be expected to have strong immune systems and few co-morbidities. however, in the current study, the infection rate was extraordinarily high among the returnees, being % ( / ), compared to the rates in the general population in gansu of . per , or < . % ( / , , ). the % infection rate amongst the returnees was also much higher than that of a symptomatic secondary attack rate of . % ( % acknowledge that the explanation for the higher infection rate among these returnees may be mainly due to two possible reasons: firstly, the relative lack of self-protection or, secondly, lack of sanitisation during the early stages of spread during their stay in iran. additionally, it is likely that the iran government has experienced difficulties scaling up its response to combating the epidemic due to the economic loss and supply issues caused by the after an apparently asymptomatic infection [ ] . thus, a substantial threat could occur in the community if such covid- case(s) are misdiagnosed and these returnees are allowed to eventually proceed to their final destination(s) after days quarantine. although the infection rate was high ( %), there was a relatively low severe/critical attack rate among these returnees from iran with only ( %), which was far below the results from jiangxi province ( %) [ ] and gansu province ( . %) within china [ ] . however, this rate is close to the age-based rate published recently by imperial college london of approximately . % of patients requiring hospitalisation in the age range - years [ ] . our explanation for such a difference might be due to most of the returnees were male students, which may be mainly due to the universities preference for religious study in iran [ ] . interestingly, the attack rate of covid- amongst females was rather less than male ( : . ) in our current study, which is very different from the reports in the general population there was % rate of covid- cases amongst international students, which is substantially paradoxically, our data show that the covid- infection rate was greater amongst those who wore masks while in iran ( % infection rate) compared to those who did not wear masks ( % infection rate). we speculate that this observation may be related to several factors: firstly, returnees who chose to wear masks may have been involved in activities that placed them at greater risk of exposure, for example, living in dormitories, attending university classes and mosques. all three of these activities were identified in this study as increasing the risk of infection. by comparison, those returnees who chose not to wear masks may have been largely involved in low risk activities, for example, house-bound spouses engaged in domestic duties and childcare. secondly, those who wore masks may have over-estimated the effectiveness of the masks in preventing infection, and thus may have neglected other measures to avoid infection, such as social distancing and scrupulous hygiene. thirdly, the masks may not have met p /n standards for use against viral infections and/or the technique for using the masks may have been inadequate, for example, touching the outside of the mask after use or multiple uses of the same mask. we note that recommendations concerning the mass wearing of masks remains controversial [ ], and we urge caution in the application of our data in relation to this issue. apparently, prior to and during the evacuation, many of these returnees were not fully aware who was/were covid- patients, particularly since a number of them ( , %) were asymptomatic prior to their return, with their clinical presentations occurring during the current study. therefore, considerable caution should be exercised in screening for covid- infection based only on clinical presentation. our data further confirm that among the reverse transmission covid- returnees, the clinical presentations, including chill, shortness of breath, chest pain and nausea were still the typical manifestations for covid- , in comparison with presentations of covid- within the local chinese population. furthermore, the transmission routes is/are likely to still be similar to the local routes, i.e. the droplet inhalation and faecal-oral routes [ ] . currently, the quarantine approach used at the airport and/or on the airplane is primarily based on the measurement of body temperature only, which is unlikely to be sufficient; alternative more sensitive and specific screening approaches are urgently needed. however, we acknowledge that there does not seem to be another more appropriate screening measurement that is more sensitive and similar in cost available at this stage. world health organization. coronavirus disease (covid- ) situation report - world health organization. coronavirus disease (covid- ) situation report - water supply and drainage design of wind environment simulation of wuhan huoshenshan hospital and response of planning analysis to epidemic prevention work the experience of wuhan cabin mobile hospital national health commission of the people's republic of china introduction for gansu 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made mandatory in wuhan ministry of education, the people's republic of china. moe party leadership group issues notice for covid- control and educational reforms center for disease control and prevent. steps to prevent illness wearing face masks in the community during the covid- pandemic: altruism and solidarity transmission routes of -ncov and controls in dental practice address for correspondence: shisan bao, discipline of pathology key: cord- -tnw hbm authors: einian, majid; tabarraei, hamid reza title: modeling of covid- pandemic and scenarios for containment date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: tnw hbm the impact of covid- pandemic on the global health and world's economy have been profound and unseen since the spanish flu of - . as of now, many countries have been severely affected, partly because of slow responses to the crisis, ill-preparedness of their health system, and the fragile health infrastructure and the shortage of protective equipment. this note evaluates various scenarios, based on an estimation of number of identified and unidentified infected cases, and examines the effectiveness of different policy responses to contain this pandemic. our result, based on an estimation of the model for iran, show that in many instances the number of unidentified cases, including asymptomatic individuals, could be much bigger than the reported numbers. the results confirm that in such circumstances, social distancing alone cannot be an effective policy unless a large portion of the population confine themselves for an extended period of time, which is not only difficult to implement, but it could also prove extremely costly and damaging to the economy. an alternative policy, this note argues, is to couple effective social distancing with extensive testing, even to those who are asymptomatic, and isolate the identified cases actively. otherwise, many lives will be lost, and the health system will collapse, adding to the ongoing economic troubles that many countries have started to encounter. as the impacts of the coronavirus-covid- -rattle the world on its path to more than countries and territories (as of march ), countries show astonishingly similar behavior, at least in the first phase, of this pandemic. similar to some deadly diseases that affect individuals, it seems that the society and/or the governing authorities of many countries, go through the similar stages as individuals, namely denial, anger, blame, depression, and acceptance. we understand form scientists, that the sooner a patient accepts her sickness, the sooner she can receive treatment and care. a prolonged process to reach acceptance, makes it more difficult to effectively tackle the disease, and in many instances, if left untreated with unfortunate deadly outcomes. for instance, iran is a prime example of a country that has prolonged the denial phase, and in doing so, has created a situation that might lead to a catastrophic outcome and could result in a human tragedy. the authorities in iran broke the news by announcing the death of two covid- victims on february , , just a day before nationwide parliamentary elections. although it is almost impossible to know the exact date and the number of infected people prior to the official announcement, the number of new cases suddenly jumped from zero on february to around cases a week later. iran initially refused to quarantine the holy city of qom, the source city of covid- in iran, and let the virus spread all over the country, and in a matter of a few weeks, all cities reported new cases of infected patients. today, the pattern of pandemic in iran indicates that, even after one month, the country is still grappling with the early stages of this terrible diseases and is unable to move on to the stage which it accepts the reality and takes extra-ordinary but necessary measures to confront the spread of the virus. the data pattern in iran shows a high death rate at the beginning of the pandemic, which then declined and reached the global average after a couple of weeks. similarly, the pattern of identified cases has been very different across countries. for instance, while the crisis started sooner in iran than many other countries, infected cases rose quickly in europe and the us, and surpassed those of iran. this is in despite of complete shutdown in many european countries and many states in the us. similar to many other countries, this might have been due to the lack of resources for testing and identifying infected individuals. this is why this note tries to account for identified as well as unidentified cases and simulate a model-based number of infected population. we use a modified susceptible, exposed, infected, and recovered (seir) model to simulate the spread of covid- . although the model is fairly sophisticated, it is easily understood and it is estimated with available public data. the results for iran show that active cases might be significantly higher than officially reported by to times in an optimistic scenario of shelter-inplace policy of percent of the population. in a scenario where half of the individuals confine themselves, still around three million individuals get infected of which thousand will die. therefore, the under-reporting of infected cases, although unintentional, not only undermines the integrity of responses, but ultimately puts more people at risk as they go unrecognized and untreated and continue to spread the virus with no end in sight. the note examines multiple policy scenarios and their effectiveness. although the model is estimated for iran, many countries are in similar stages of the pandemic or soon will be in the same stage and therefore, based on the results, extreme measures need to be adopted to save lives and stop further spread of the virus. social distancing alone cannot stop this disease except if more than percent of the population confine themselves for quite an extended period of time. however, if the number of testing increases massively, and countries' authorities successfully isolate infected individuals, the pandemic can be controlled before the summertime, even with a less degree of confinement. while the paper simulates various scenarios of containment, it does not address the economic cost of each scenario. in line with recent findings, the note argues that a fast and aggressive multi-layer intervention is needed to have a substantial dent of the transmission. what the paper calls for is a clear and transparent strategy by governments to implement social distancing and aggressive testing. the testing, should be targeted to geographic locations that the virus is wide spread, to airports and cruise ships, to road travellers, and anyone who has been in areas that are hot spot or has been in any contact with someone in affected locations over the past two weeks. the strategy should not "just" focus on those that show symptoms but should include "all" who might have been exposed. in this exceptional environment, governments can use temporarily a combination of location data and credit card information to track covid- in their countries and use surveillance tools to monitor quarantined individuals. deterministic compartmental models are simple yet powerful models in describing this kind of epidemic outbreaks. we developed a variant of the seir model for the epidemic dynamic and control of covid- , using seven state variables and a minimal number of parameters to avoid over-fitting. the model is estimated for iran, but it can be estimated for other country examples. it is different from a standard seir model by distinguishing hidden and identified infected cases. indeed, standard seir models are estimated assuming that all infected people are reported. such an assumption for the novel coronavirus pandemic is largely unreasonable, as many infected people show no or mild symptoms and as the testing procedure is not available in mass, many remain undetected. thus, we divide infected compartment into infected but not reported (i) and infected, detected and reported (q) groups. we assume that identified cases are less infectious by taking self-precautionary measures and/or due to hospitalization. while unidentified cases can largely continue to infect the rest of the population. the model, therefore, . cc-by . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . distinguishes between the confirmed infected individuals, which are observable in data, and the total infected individuals. in reality, the number of confirmed cases is a function of medical tests and the preparedness of the healthcare system. covid- has an infection capability during the incubation (pre-symptomatic) period. in addition, based on the detection method, there exists a delay between the time that an individual is infected and the time this person is detected. state variables and parameters of the model in equations ( . )-( . ) capture these characteristics. figure shows the schematic diagrams illustrating these states (compartments). we denote the share of susceptible individuals with no resistance to the disease in the population by s t . e t is the share of people who are exposed to the virus but are not yet infected nor infectious. i t is the infected population share who are undetected and hence un-quarantined. these individuals can be either symptomatic or pre-symptomatic. a share of these individuals, q, are detected and move to somewhat quarantined population q t . among both infected populations, r t = r i t + r q t recover and for some time become resistant to new infections. finally, we assume those who are detected are the individuals who need medical assistance and those that their general health condition might have deteriorated quickly. a share of these individuals, δ, pass away (d t ). finally, due to the high pace of the current outbreak, the model is a closed model in the sense that there are no new birth and death, except for the disease itself. in a simple sier model, people are removed (hence the letter r in seir) from the analyzed population due to either immunity/ resistance to the disease or death. dividing the recovered into "recovered from i" and "recovered from q" groups, and keeping in mind that we only have data on recovered from q and number of deaths (d), we can fit the model compartments to these series. the values of β i and β q depend on the contact rate between individuals and the probability of transmission in an encounter. /σ is the mean latent period and /γ i and /γ q are the mean infectious periods for each group of patients. finally, γ i and γ q are the recovery rates and δ is the death rate among the q group. the model is simulated by solving a deterministic ordinary differential equations (ode), given the parameters (β , β , σ, γ i , q, γ q , δ) and the initial conditions to obtain a realistic simulation of the baseline model and possible scenarios, we needed to estimate or calibrate these parameters and initial conditions. since we are at the beginning of the epidemic cycle and the full distribution is not yet revealed, the model cannot be properly fit to a probability distribution function. as a result, the model is estimated by minimizing the differences between actual and predicted share of cases for observable data series which are q, r q , and d based on an extension of drake ( ) . the model is estimated using iran's official data for the number of confirmed, recovered and death cases . as there are limited observable state variables, we fix or restrict a few parameters based on the reports in the literature to avoid over-fitting. first, based on the genomic studies on the phylogeny of sars-cov- , two genetic mutations of the virus has happened in iran (the nextstrain team, ) , first between january th and january th , and the second between january th and january th . thus, the virus was present in iran before january th , long before the first official record of the disease in iran (february th ), but not before january st as the parent mutation has occurred in hubei, china between january st and january th . so, the starting time of the simulations should be between january st and january th . initial values for observable states are obviously zero. second, we pin down the relationship between β i and γ i , and between β q and γ q , such that β q γ q = . , i.e., the minimum basic reproduction value and β i γ i to be equal to maximum basic reproduction number of . , based on various reported values . third, the relationship between γ q and δ is fixed at . percent to match the case fatality rate with the one estimated by baud et al. ( ) . without these restrictions, the parameters and initial states can be estimated, but the issue of over-fitting resides and leads to misspecification. based on the optimization, the epidemic started on jan th with infected and exposed people. in the absence of any control measures and/or changes in individual behaviors, we would expect a peak of infection (some of identified and unidentified patients) to occur around may , (figure ). as discussed in the previous section, we fix r i = . and r q = . in this scenario for the whole epidemic period. under this assumption, percent of the population will be infected by around may th . as the epidemic progresses, at the peak, around million identified individuals will be sick and will need medical assistance. in total, in an uncontrolled epidemic, around thousand iranians will die from this disease, not accounting for all other patients who will not get proper medical assistance during this period due to an overwhelmed medical system being. in a cabinet meeting, iran's minister of health mentioned that the maximum capacity of intensive care of all hospitals in iran stands around , beds. under the baseline scenario and without any control measures, at a percent hospitalization rate of identified cases, all icu beds in iran will be filled by april and even all hospital beds will be filled on may (figure ). some , individuals will die per day around mid-june (figure ). . cc-by . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. . cc-by . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint although iran initially refused to fully quarantine the holy city of qom and later the other cities, the government started to react to the epidemic by cancelling all cultural, religious and sportive events, and closing of universities and schools in several cities. the authorities refused to quarantine areas affected by the outbreak and instead asked people to remain inside their houses on a voluntary basis, without any enforcing measures. some religious sites remained open until mid-march. unlike every year in late march (persian new year) the authorities urged the public to avoid travelling for the two-weeks holidays. however, according the official statistics, roads were still busy, and millions of people travelled, making the self-quarantine policy ineffective. in the absence of firm suppression policies , we simulate the model based on the changes in the behaviors of the public by comparing i) the baseline or uncontrolled scenario, ii) with complete isolation of identified infected cases, iii) case isolation and self-quarantine, iv) intensive testing, identification of cases and quarantine, v) a combination of previous scenarios, vi) abandoning shelter-in-place policy one month after the peak of the epidemic under scenario v. scenario (ii) is implemented by assuming β q = , meaning that as soon as an individual is reported as infected, all necessary measures are taken to stop contagion from this person to other people. china forced hospitalization of all "confirmed cases" and not just those who required hospital care, to reduce onward transmission in the household and potentially in other social settings. results show that this scenario is not effective and the epidemic progress almost at the same rate with and without complete isolation of identified cases. scenario (iii) is implemented by choosing smaller values for β i of the base scenario, as it depends on the contact rate between individuals, in addition to β q = . adding social distancing saves many lives (figure ), but at this stage of the epidemic at least to percent of the population should practice shelter-in-place. sadly, if only one quarter of the population continue regular contacts with each other, the number of death cases can easily surpass a quarter of a million, and clearly, this policy will not be enough to overrun hospitals' maximum capacity (figure ). we implement scenario (iv) by assuming that the health authorities will increase number of testing by folds. this helps isolate infected cases, provides patients with necessary medical assistance and decelerates spread of the disease to the rest of population. this policy would shift individuals from i group to q group, enforcing better implementation of precautionary measures and control of contagion. the results are shown in figure . even in this case, more than percent of the population will contract the disease and the death toll will remain very heavy. only by combining this scenario with previous scenarios, one can be hopeful to control the epidemic and save lives. figure : total death count in case isolation and partial self-quarantine in different levels. . cc-by . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . https: //doi.org/ . //doi.org/ . / scenario (v) shows the result for the combined policies, assuming that only percent of the population respect the shelter-in-place policy, while testing and identification process intensify by folds. figure shows the results for the combined policy. if implemented immediately, the total number of deaths by end-june will remain below thousand individuals. the maximum number of infected cases (i + q) will reach its maximum at , on may th and the majority of the population will not contract the virus. finally, in the last scenario, we assume that last set of policies were effective enough to reach the peak of the epidemic on may and the shelter-in-place policy continues by an additional -days period. as a result, businesses and government will open on june , while the intensive testing continues. we assume that as the shelter-in-place policy ends, all individuals remain vigilant and take hygiene measures. under this scenario, social interaction reduces by percent compared to normal times. as a result, the number of patients in need of intensive care surpasses the total icu beds capacity before the end of june, while it remains below the total number of hospital beds in the country until the end of year. . cc-by . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint figure : ending the shelter-in-place policy -days after the peak of scenario (v), assuming that intensive testing continues and social interaction diminishes by percent. table reports the number of death and recoveries at end- . obviously, the combined set of policies, described in scenario v yields the best outcome with the lowest fatality and infected cases. comparing scenario iii and iv, we conclude that a combined intensive testing, identifying infected individuals, and quarantine is a more effective policy than just a shelter-in-place policy. as discussed, scenario vi is the same as scenario v, assuming that the authorities end the shelterin-place policy -days after the peak of the pandemic. unfortunately, under such scenario the death toll can be still multiplied by times compared to the scenario where social interactions are just reduced and kept low by percent. if the social interaction is increased to normal times, the death toll can be times larger than in the scenario v. many governments are impatient to open their countries businesses. they are rightly worried about the economic cost of a prolonged shutdown of economic activity. there are already outcry across countries by those who have lost their jobs. many in low income and developing countries cannot afford to stay in home for long, since there are not enough safety nets to protect the most vulnerable. on the other hand, even in advanced economies, the ripple effect of a lengthy and uncertain shutdown of the economy is too painful. this is the reason that countries' authorities have to start implementing a broad range of decisive actions. such policies should be put in place to save lives of thousands of people, alleviate pressures on the health system, and provide an opportunity for the people to go back to a normal living setting. these comprehensive set of measures include isolation of infected cases, shelter-inplace, and intensive and extensive testing. good examples are germany, south korea and not surprisingly china, where it not only hospitalized all cases, but also enforced a population-wide . cc-by . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . https://doi.org/ . / scenario d r i ii iii iv v vi table : end of results social distancing to curb the contagion. unlike the current approach in some countries, where only the symptomatic cases are tested, the authorities should provide intensive and extensive testing and try to identify almost-all infected cases. this process would identify asymptomatic but infected cases and stop them of spreading the virus. this is key for a successful containment policy. given the geographic distribution of the pandemic, the testing should focus on the most affected locations first and then expand to those people who have visited the hot spots or have been in contact with anyone in those areas, while everyone practice social distancing. a combination policy, as discussed above, not only reduces the number of infected, and ultimately the death toll, but it shorten the shelter-in-place period and consequently lowers the economic cost. correspondence real estimates of mortality following covid- infection. the lancet infectious diseases fitting epidemics in r how scientists quantify the intensity of an outbreak like covid- impact of non-pharmaceutical interventions (npis) to reduce covid- mortality and healthcare demand substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (sars-cov ) time-varying transmission dynamics of novel coronavirus pneumonia in china novel coronavirus -ncov: early estimation of epidemiological parameters and epidemic predictions pattern of early human-to-human transmission of wuhan the novel coronavirus, -ncov, is highly contagious and more infectious than initially estimated genomic epidemiology of novel coronavirus estimating clinical severity of covid- from the transmission dynamics in wuhan, china key: cord- - b h xog authors: rezaei, fatemeh; maracy, mohammad r; yarmohammadian, mohammad h; ardalan, ali; keyvanara, mahmood title: preparedness of community-based organisations in biohazard: reliability and validity of an assessment tool date: - - journal: fam med community health doi: . /fmch- - sha: doc_id: cord_uid: b h xog the purpose of this study was to develop a tool for community-based health organisations (cbhos) to evaluate the preparedness in biohazards concerning epidemics or bioterrorism. we searched concepts on partnerships of cbhos with health systems in guidelines of the centers for disease control and prevention and literature. then, we validated the researcher-made tool by face validity, content validity, exploratory factor analysis (efa), confirmatory factor analysis (cfa) and criterion validity. data were collected by sending the tool to cbhos serving under supervision of iran’s ministry of health. opinions of health professionals and stakeholders in cbhos were used to assess face and content validity. factor loads in efa were based on three-factor structure that verified by cfa. we used spss v. and mplus software for statistical analysis. about health-based cbhos participated. after conducting face validity and calculating content validity ratio and content validity index, we reached items in the field of planning, training and infrastructure. we conducted construct validity using cbhos. three items exchanged between the fields according to factor loads in efa, and cfa verified the model fit as comparative fit index, tucker-lewis index and root mean square error of approximation were . , and . , respectively. the cronbach’s of the whole tool was . . spearman correlation coefficient confirmed criterion validity as coefficient was . . planning, training and infrastructure fields are the most important aspects of preparedness in health-based cbhos. applying the new assessment tool in future studies will show the weaknesses and capabilities of health-based cbhos in biohazard and clear necessary intervention actions for health authorities. community-based organisations (cbos) are indispensable partners in health systems. in disasters and management of epidemics, some governments cannot provide an adequate response with limited resources. these organisations have the necessary knowledge about community culture, structure and resources, and facilitate access to deprived and marginalised communities in times of need. besides, federal emergency management agency and centers for disease control and prevention (cdc) have encouraged coordination with volunteer organisations whose goal is to support and coordinate with government agencies in disasters. contrary to these requirements, there is limited evidence regarding the readiness of these organisations for bioterrorism or epidemic/pandemic. for instance, in order to prevent the spread of zika virus, organisations are expected to have very high communication skills to warn high-risk groups. in a study by zhi et al; they emphasised the need to educate the staff of faith-based organisations especially in exercises and drills. eventually, clawson et al examined the community health centres' preparedness in the case of bioterrorism. they demonstrated that less than half of the centres possessed bioterrorism preparedness in their plan and only one-third among them included bioterrorism preparedness in their written policies. frequent religious mass gatherings and food serving in customs gathering exposure iran in the various potentiality of outbreaks and bioterrorism. [ ] [ ] [ ] besides, limited access to resources in epidemic seasons in developing countries like iran would worsen the situation. although iran has an extensive community-based primary healthcare (phc) network that raise community awareness of local risk profiles and aid community, a population-based study revealed that overall community awareness and preparedness for even routine disasters is low. [ ] [ ] [ ] iran's phc network has taken some advocacy and training programmes focusing on community partnership. cbos can equip public health officials with information about vulnerable groups and how to meet their particular needs. however, iran still lacks an assessment tool evaluating the preparedness of cbos in biohazards. according to the above evidence, the necessity of formulating specific criteria in open access the context of preparedness for cbos is obvious. therefore, this study aimed to develop a comprehensive tool to evaluate the level of cbhos' preparedness in times of epidemics or bioterrorism thereby identifying the prerequisites of cbhos' participation for government decision makers. participants and sampling method the study population was cbhos in the country. based on cochrane's formula, approximately samples should be included in the study. receiving a compiled list of cbos from vice-chancellery for social affairs, the tool was disseminated in cbhos' social networks. additionally, we sent the participation appeal through contact channels five times for each cbhos. these are organisations that, according to experts from the centers for disease control at deputy of health, possess the eligibility and capabilities necessary to work with the health system as an assisting or cooperating agencies during biohazards. inclusion criteria were: cbhos that served more than clients and provide services to clients at the time of the study with a registered office to carry out their duties. the identity of the person filling the questionnaire and their organisation remained disclosed in the data collection forms; instead, a code was assigned at the time of data entry. face validity, content validity, exploratory factor analysis (efa), confirmatory factor analysis (cfa) and criterion validity were used to validate this researcher-made tool. assessing the face validity, health professionals in disasters/emergencies and some stakeholders from cbhos read questions of the instrument to examine the level of difficulty, the degree of mismatches and to check the ambiguity of phrases and meanings of words, thereby making appropriate changes in persian based on their comments. the qualitative content validity determined by the grammar, the proper use of words, the importance of questions, the ordering of questions and the time required to complete the toolkit were all taken into consideration. for quantitative content validity, content validity ratio (cvr) was used to ensure that the most important content was chosen (necessity of question), and the content validity index (cvi) was used to ensure using the best way to measure content. cvr is used to ensure that the most relevant and correct content is selected. in quantitative content validity, after collecting expert opinions, if the cvr based on lawshe's table was more than % and the cvi based on the davis study was over %, the necessity, relevance, transparency and simplicity of the questions were acceptable. we used efa to determine the factors loads based on three factors extracted as the assumption of this study. cfa, also, was used to verify the factor structure and the hypothesis that a relationship between observed variables and their underlying latent constructs exists. in order to assess the concurrent criterion validity, the 'organisational preparedness checklist for a major earthquake or other large-scale disaster events' questionnaire developed by austin et al was applied. the questionnaire consists of phrases in four periods that include 'last year', 'between year to years', 'over the past years' and 'never'. the researcher-made tool was designed to determine the preparedness level of cbhos in biohazards. after studying the guidelines of office of the assistant secretary for preparedness and response (aspr) [ ] [ ] [ ] along with other information sources, the research team eliminated duplicates/repetition of initial items pool. the researchers extracted all concepts promoting the partnership and cooperation of cbos with the health system under the first set of capabilities named 'community preparedness' in the public health preparedness capabilities guideline. then, fundamental concepts of the tools that are available from the literature were integrated into the primary tool to evaluate cbhos' preparedness. we evaluated the construct validity with efa in spss v. software and cfa in mplus software (muthén and muthén, los angeles, california, usa). fitting indexes included comparative fit index (cfi), tucker-lewis index comparative fit index (tli), root mean square error of approximation (rmsea) and weighted root mean square residual. cronbach's α was used to measure the internal consistency. at first, we obtained items. there were items in the planning field, items in the field of education and items under infrastructure. for each item, a range of four options was considered, including 'not done', 'due to review', 'planned but not implemented' and 'completely implemented'. in face validity, four items in the planning field, one item in the field of training and two items in the infrastructure field were omitted. after reviewing the questions, healthcare professionals who specialised in the field of disasters and emergencies inspected the qualitative content validity. following this, based on the comments, certain corrections were made regarding the wording and language used in the questionnaire. in quantitative content validity, based on the cvr and cvi indicators, items in the planning field, items in the field of training and items in the infrastructure field were open access deleted. finally, items remained for entry into the construct validity stage. efa and cfa about cbhos volunteered to participate in the study. the kaiser-meyer-olkin test for sampling adequacy was . . next, to determine if the correlation matrix had a significant difference with zero and factor analysis was justifiable or not, the bartlett test of sphericity was performed, which turned out to be χ and p< . . these values indicated that the factor analysis is justifiable based on the correlation matrix, and the items can be used for factor analysis. in this study, limiting the extracting factors by referring to the 'community preparedness' principle of the cdc guideline in the field of public health emergencies and applying varimax rotation, efa with three factors were performed. we considered an inflection point of . as the minimum factor load needed to maintain the items. thus, items without deletion were entered into the cfa stage. two questions of the planning field and one question of the infrastructure field were exchanged based on the rotation matrix and the loadings factor, which were conceptually meaningful. the questions in the table and and in table were those exchanged questions. all items in the training field remained in the factor structure according to factor loads (table ) . the three-factor model confirmed by deleting item in the substructure field based on cfa findings (table ) . table shows cfa fitting indexes. the cronbach's α in the planning, training and infrastructure field were . , . and . , respectively. the cronbach's α of the whole tool was . . scores showed that the reliability of the tool is acceptable. thirty-four cbhos completed the austin questionnaire, and the spearman correlation coefficient was . that mean the criterion validity of the tool is acceptable. in this study, a tool was developed to assess the preparedness of cbhos during biohazards. the researcher-made tool consisted of planning, training and infrastructure fields based on previous studies. after achieving face and content validity, cfa was used for the threefactor model fit. efa was also used to compare the items replaced in the proposed model. some studies noted that items with a factor load above . and even . were acceptable. therefore, in the cfa, a single item with factor load less than . was deleted. table shows that the rmsea value of the model is . . according to previous studies, if the rmsea is between . and . , the model is acceptable. the index of cfi and tli is more than . , which shows that the three-factor model is acceptable. hence, in this study, we used cfa to compare the model fit of our tool with the proposed structure of the hhs office of the aspr. the office has divided the functions of community preparedness into three categories as planning, training and skills, equipment and technology. however, in this research, the research team consented to use the term 'infrastructure' instead of 'equipment and technology'. according to a cross-sectional study, the most challenging aspect in implementing the capabilities of the cdc's guideline is training and planning, and % of failing is related to infrastructure field. evidence from a qualitative study shows that planning and training fields are the most significant challenges faced by health workers in response to hurricane sandy. another study showed '"community preparedness"' as the common standard in both the accreditation standards developed by public health accreditation board (phab) and the capabilities of cdc's guideline. therefore, strengthening all organisations in community-based preparedness can improve both accreditation standards and follow cdc guideline. also, the fields of training, planning and infrastructure are common in both the guideline and the accreditation standards. in this regard, the categorisation of cbhos' preparation activities in the three areas in our research is consistent with the study. importance of community partnerships in disasters has motivated researchers to develop various assessment tools for evaluating cbhos' preparedness. glik et al and clawson et al developed tools as an instrument monitoring collaboration between local health departments and cbos. however, they focused more on the duties of health departments in engaging cbos. austin et al showed that cbos' preparedness in earthquake needs seven clusters of assessment including internal training, external response, response capabilities, information collection and distribution to staff, preparation, building protection and supplies. moreover, baezconde et al assessed preparedness of non-governmental organisations (ngos) considering social and structural needs. socially, ngos have high 'social will' but little 'community readiness' to participate in emergencies. structurally, ngos' linkage to voluntary organisations and public health departments lack enough coordination. an assessment tool with biohazard approach for cbo' preparedness is rare in literature, and we have tried to fill this gap. the cbhos in iran conduct weekly meetings at the health departments of medical universities wherein their fields of cooperation are identified. the representatives of cbhos participate at these meetings, and health authorities discuss fields that health systems lack an adequate budget or cannot intervene due to legislation. thus, cbhos depending on their capabilities would offer their cooperation with the health system. the aforementioned meetings will be held more actively in times of disasters. the evaluation of these cbhos in iran in terms of their capacities, capabilities, strengths and weaknesses in the field of planning, training and infrastructure can be achieved using this assessment tool. therefore, the government departments that licensed cbhos could plan out the relevant training needed before biohazards and be aware of their capacities to use them in times of disasters or empower capacities for future actions. moreover, biological hazard is a threatening disaster in iran owing to the various cultural and religious mass gathering posing a high risk of occurrence, namely, the epidemic of influenza, hepatitis b and d, various types of haemorrhagic fevers and brucellosis. in response to these epidemics, iran has used many strategies to cope with them. these include recruiting a surveillance system with mandatory reports of particular disease according to the guidelines of the ministry of health, training health personnel to prevent transmission of the disease in the community especially the high-risk group, using mass media to persuade community involvement in preventing transmission, controlling the vectors by using pesticides, educating people with high-risk job due to exposure to the disease source, preventing high-risk people in participating in hajj (pilgrimage), mandatory vaccination if participating in certain religious occasions and educating hygiene habits like washing hands and using a mask in very crowded places. cbhos participate in these actives to serve their covered population. [ ] [ ] [ ] [ ] [ ] this tool can help them to assess their preparedness in biohazard and recognise the need of enhancing their capacity. limitations it was not possible to check the reliability through testretest due to the low participation of cbhos in the research. we will use some qualitative or mixed method studies to verify this tool in future. in comparison with the aspr guidelines, our findings might reflect some potential item limitations regarding to ambiguous translation and wording sentences that would make difficult to answer for participants. we collected data on cbhos through the ministry of health. we used creditable mathematic calculation based on mature model and revised by experts' opinion. besides, this tool is used to measure the preparedness of cbhos and their ability to participate in biohazard and identify their weaknesses. the tool could aid better understanding of the training and skills required for cbhos to participate during hazards. furthermore, cbos can use this tool to participate in drills and practices. finally, the preparedness tool can help cbos improve their planning, training and infrastructure. the authors will verify credibility and extend its usability to improve its quality continuously. facilitating partnerships with community-and faith-based organizations for disaster preparedness and response: results of a national survey of public health departments agility and discipline: critical success factors for disaster response public health systems: a social networks perspective crisis and emergency risk communication in a pandemic: a model for building capacity and resilience of minority communities planing to be prepared: an empirical examination of the role of voluntary organizations in county government emergency planning assessing city preparedness for a biological attack mass-fatality incident preparedness among faith-based organizations are community health centers prepared for bioterrorism? pandemic influenza a (h n ) infection among hajj pilgrims from southern iran: a real-time rt-pcr-based study a food poisoning outbreak by shigella boydii in kerman-iran prevention of pneumococcal infections during mass gathering titering of pandemic h n influenza virus hemagglutinin inhibition antibody in nonvaccinated pregnant women in shiraz, southern iran effectiveness of a primary health care program on urban and rural community disaster preparedness, islamic republic of iran: a community intervention trial iranian health houses open the door to primary care effectiveness of community participation in earthquake preparedness: a communitybased participatory intervention study of tehran assessing the effectiveness and feasibility of implementing mitigation measures for an influenza pandemic in remote and isolated first nations communities: a qualitative community-based participatory research approach sampling techniques principles of questionnaire design in medical science studies content validity and its estimation the content validity index: are you sure you know what's being reported? critique and recommendations validity and reliability of the instruments and types of measurments in health applied researches objectifying content validity: conducting a content validity study in social work research designing and determining psychometric properties of the domestic elder abuse questionnaire critical values for lawshe's content validity ratio: revisiting the original methods of calculation exploratory or confirmatory factor analysis? surviving the next disaster: assessing the preparedness of community-based organizations public health preparedness capabilities: national standards for state and local planning. in: services usdohah centers for disease control and prevention - health care preparedness and response capabilities in: (hhs) dohahs u.s.: office of the assistant secretary for preparedness and response healthcare preparedness capabilities: national guidance for healthcare system preparedness community health agency administrators' access to public health data for program planning, evaluation, and grant preparation reliability and validity of the assessment for disaster engagement with partners tool (adept) for local health departments structural equation modeling and regression: guidelines for research practice using multivariate statistics. th edn evaluating the use of exploratory factor analysis in psychological research comparative fit indexes in structural models progress in public health emergency preparedness-united states community assessment for public health emergency response (casper): an innovative emergency management tool in the united states new york state public health system response to hurricane sandy: lessons from the field. disaster med. public health prep accreditation and emergency preparedness: linkages and opportunities for leveraging the connections reliability and validity of the assessment for disaster engagement with partners tool (adept) for local health departments maximizing participation of hispanic community-based/non-governmental organizations (ngos) in emergency preparedness comparing the model of government support programs for specific patients in iran enhancing community based health programs in iran: a multi-objective location-allocation model molecular epidemiology of crimean-congo hemorrhagic fever virus genome isolated from ticks of hamadan province of iran prevalence of human influenza virus in iran: evidence from a systematic review and meta-analysis histological and serological epidemiology of hepatitis delta virus coinfection among patients with chronic active hepatitis b virus in razavi khorasan province, northeastern iran the epidemiology and trend of hepatitis c infection in hamadan province: west of iran epidemiology of q fever in iran: a systematic review and meta-analysis for estimating serological and molecular prevalence acknowledgements the authors would like to thank the members of the departments of health in disasters and emergencies in the medical university of isfahan and tehran for contributing helpful comments on developing a validated assessment tool. key: cord- -i v lyd authors: madraki, golshan; grasso, isabella; otala, jacqueline; liu, yu; matthews, jeanna title: characterizing and comparing covid- misinformation across languages, countries and platforms date: - - journal: nan doi: nan sha: doc_id: cord_uid: i v lyd misinformation/disinformation about covid- has been rampant on social media around the world. in this study, we investigate covid- misinformation/ disinformation on social media in multiple languages - farsi (persian), chinese, and english, about multiple countries - iran, china, and the united states (us), and on multiple platforms such as twitter, facebook, instagram, weibo, and whatsapp. misinformation, especially about a global pandemic, is a global problem yet it is common for studies of covid- misinformation on social media to focus on a single language, like english, a single country, like the us, or a single platform, like twitter. we utilized opportunistic sampling to compile specific items of viral and yet debunked misinformation across these languages, countries and platforms emerged between january and august . we then categorized this collection based both on the topics of the misinformation and the underlying roots of that misinformation. our multi-cultural and multilingual team observed that the nature of covid- misinformation on social media varied in substantial ways across different languages/countries depending on the cultures, beliefs/religions, popularity of social media, types of platforms, freedom of speech and the power of people versus governments. we observe that politics is at the root of most of the collected misinformation across all three languages in this dataset. we further observe the different impact of government restrictions on platforms and platform restrictions on content in iran, china, and the us and their impact on a key question of our age: how do we control misinformation without silencing the voices we need to hold governments accountable? along with the covid- pandemic crisis, an infodemic (world health organization, ) crisis has affected all aspects of human lives from elections to public health response around the world. social media has played a critical role in this infodemic crisis. first, social media offers a free and easy-access platform for users to share content (both true and false) in the form of posts, videos, pictures, and memes, all with a wide range of audiences (weinberger, ) . second, the covid- outbreak has forced people around the world to be quarantined and consequently interactions have shifted away from face-toface interactions and even more towards online/social media interactions. this means that more people are exposed to unreliable content circulating on social media and many users struggle with distinguishing between facts and lies/fictions about covid- . since the beginning of the pandemic, some official efforts have been implemented to debunk these lies and inaccurate information circulating on social media, despite substantial disagreement about which corrective measures for fact checking are practical and appropriate for massive social media platforms. still, these efforts seem not enough and there is a widespread consensus that an integrated sustainable global effort is warranted across different languages and through different platforms as are targeted in our study (dizikes, ; pennycook et al., a) . in the literature, the problematic information has been categorized into misinformation, disinformation, and malinformation, with some debate about definitions (karduni, ; wardle, ) . in this paper, we consider the following definitions: misinformation is incorrect information created without the intention of causing harm (e.g. encouraging people to wear a face shield without realizing how ineffective it could be). disinformation is incorrect information and intentionally created to hurt an individual, a group, or a country (e.g. a drug company spreading out a false rumor that its new medicine can cure covid- with an intent to increase profit.) mal-information is correct information (based on reality), but used to cause harm to an individual, a group, or a country (e.g. justifying the high rate of confirmed cases by claiming that it is because of increasing the rate of testing.) (infodemic toolkit, ; kujawski, ; wardle, ) . distinguishing between these three categories, particularly misinformation and disinformation, can be difficult or even impossible in some cases as can require assessing the intent of the creator. thus, more broadly, here in this paper, we will use the general term 'misinformation' to refer to all three categories. according to a study from oxford university, misinformation is also often true information reconfigured or recontextualize and less commonly fabricated (brennen et al., ) . this reconfigured information can circulate even faster than fully fabricated stories, taking in % of the interactions in one study (brennen et al., ) . in this paper, covid- misinformation, broadly defined to include disinformation and mal-information as well, will be investigated within multiple languages (chinese, english, and farsi) about multiple countries (china, iran, and the usa) on different social media platforms. the covid- pandemic broke out first in wuhan, china in december . then, iran became a hotspot in february . the usa has been a clear hotspot as well with % of confirmed world-wide covid cases despite only . % of the world population (dong et al., ) . we chose these three countries as a lens through which to consider major differences between covid- misinformation around the world. we show how examining social media misinformation from the perspective of one country, one language, or one platform, misses important and more holistic aspects of the pandemic. through this research, we build a more comprehensive picture of how misinformation has exacerbated the covid- crisis around the world. our research team includes native speakers of chinese, english, and farsi who were born and raised in china, iran, and the usa. to the best of our knowledge, we are the first to examine the multilingual social media landscape by using the opportunistic sampling method to collect a dataset of verified and viral covid- misinformation across languages: chinese, english, and farsi. our multicultural and multilingual team observed that the nature of covid- misinformation on social media varies in substantial ways across different languages/countries depending on the cultures, beliefs, religions, popularity of social media, types of platforms, freedom of speech, the power of people versus governments, etc. based on these observations, we proposed a novel and comprehensive categorization of the covid- misinformation based on their topics and roots such that these categories are all relevant and extendable in all three languages. it is worth noting the difference in government policies for controlling misinformation in iran, china, and the usa. china has strict government control over which platforms can be used and enforces these controls. approved platforms aggressively remove misinformation of some kinds, but not all. iran also has laws restricting which platforms can be used, but does much less to actually enforce these laws. it makes some platforms more inconvenient to use, but does less to actually prevent it. the usa has some new laws restricting the use of social media platforms, specifically chinese social media platforms. whether these laws will stand remains to be seen. there are some attempts to control the flow of some types of misinformation on platforms like twitter and facebook based on self-regulation by the platform and not government regulation. throughout our study, we examine the impact of these different approaches on the types of misinformation spreading. misinformation is not a new phenomenon, it has been around for centuries in the forms of rumors, gossip conspiracy theories, etc. (burston et al., ) . however, the emergence of the publishing industry in the th century provided an official modern platform for misinformation. the st century has been characterized by the explosion of information through the internet. the technology, particularly social media, has amplified the spread of misinformation and its adverse impacts by providing a fast and free channel to share any information whether true or false (lazer et al., ) . since the beginning of the pandemic, catastrophic and lifethreatening impacts of tremendous amounts of misinformation circulating on social media have appeared (donovan, ) . for instance, due to fake news, some individuals used toxic home remedies resulting in injury and death (vigdor, a ). misinformation has provoked many people to hoard some vital necessary products (e.g., n mask, sanitizers, toilet papers, etc.) causing a shortage of supplies for essential workers (vigdor, b the closest related work to this research is the misinfodemic report developed by meedan and written by alimardini et al (alimardani & elswah, ) . this qualitative report considers a more global response to misinformation, showcasing seven countries compared to several united states-only studies. meedan divides their report into the crumbling of public trust, informal leaders of information, and impact of the infodemic on governance. their coverage of countries is extensive, but our research adds a balance of qualitative and quantitative analysis comparing countries, languages and platforms within our sample. purely quantitative research that involves misinformation globally has been done by pew research. they surveyed social media users within several countries about how often they encounter obviously fake content (silver, ) . this study tries to point researchers toward countries that seem to be encountering misinformation more frequently. this type of quantitative research does not dive as deeply into the content, topics and root of misinformation present within each country surveyed. twitter, facebook, instagram, whatsapp, weibo, wechat and tiktok are the most popular social media platforms in china, iran, and the usa. however, due to the censorship and political reasons, some strict restrictions have been imposed on these platforms in some cases (rachman, ) . whatsapp is a cross-platform encrypted messaging application acquired by facebook, and its monthly active users have reached billion as of march (clement, b) . it has . million users just in the usa as of (andjelic, ) . whatsapp is completely banned in china. whatsapp is legally allowed to be used in iran and has become even more popular in iran after the iranian government blocked telegram in which used to be the most popular messaging application in iran. the government claimed that telegram had endangered national security (erdbrink, ) . whatsapp has become a makeshift social media platform in iran as group chats have begun including thousands of members forwarding and sharing information. although the government has blocked many social media platforms officially, many iranians still use vpn and proxy anti-filter apps/tools to access blocked social media. however, this access is more limited and requires some technical tools and skills. this has helped to drive usage towards whatsapp which is a private end-to-end encrypted messaging platform without tracing capabilities. partly as a result, whatsapp has become a major source of misinformation in iran and many other countries (alimardani & elswah, ) . whatsapp recently limited the number of times users can forward a message to only five times, in an attempt to fight against misinformation (kastrenakes, ). tiktok was developed by bytedance (字节跳动), a chinese company in beijing. tiktok has a version used only in china called douyin (抖音) to separate the domestic users from international users. due to the concern of cyber security, tiktok operation in the usa will be transferred to a new company named tiktok global and will cooperate with oracle and walmart to ensure the data safety (lin, l., ). tiktok is allowed to be used in iran. keywords and hashtags are the major methods to search on social media and we use both to collect our data set. all platforms named in this study supports both keywords and hashtag search. hashtags on whatsapp might not be as popular as other platforms however this function makes the search process very easy even through a private message chain (patkar, ) . unlike hashtags on american platforms, a hashtag on weibo is owned by a host. also, each hashtag has its own unique webpage, which is called 超级话题 (i.e., topic or super topic). since january , many super topics have appeared around covid- on weibo. figure shows a sample of super topic webpage on weibo. the topic host and the largest contributor to this topic is a state media. although english hashtags are allowed on weibo, almost all hashtags are in simplified chinese. weibo needs the symbol "#" before and after a term to function as hashtags, unlike twitter which only needs "#" before. wechat channels is a popular feature of wechat and contain public feeds of content. hashtag and keywords search can be used in wechat channels. selecting an appropriate sampling methodology is a major challenge when it comes to social media studies. nonbiased sampling from social media is often difficult because the dataset is so highly dynamic, massive in size, and difficult to filter. the sheer volume of data--facebook has over million users and twitter has a rate of , tweets per minute--makes the gold standard of data acquisition, true random sampling, challenging. this can be even more complicated when sampling for misinformation since our underlying population is not all posts, but those posts that contain misinformation that has been refuted or debunked by recognized fact-checking organizations. hashtag and keyword filters do not necessarily guarantee to find misinformation, and even if a suspected post is found, we are reliant on the efficiency of journalists in fact-checking posts and content which is also biased by the particular needs and intentions of journalists and respective media outlets (pingree et al., ) . in this study, we utilized an opportunistic sampling strategy, meaning that our sampling was determined by the population, or presence of misinformation on social media, that was available and officially debunked at the time, and our abilities to find them. we used chinese, english, and farsi hashtag and keyword filters to collect specific items of debunked misinformation that spread virally between january and august . when we encountered a particular item in one of our languages, first we used fact checking organizations to see if that claim had been debunked using fact-checking sources such as international fact checking network (ifcn), platform based factchecking tools in twitter, facebook and google, and organizations using claim review (poynter, n.d.; schema, ) . the item is logged only if we could find a verified debunking source; otherwise, it is discarded. we estimate that number of logs could be doubled if we did not have the debunking constraint. then we watched for posts with the same claim in our other languages and on other platforms. we also sought out independent media reports beyond our own direct experience that the referenced claim was spreading virally. thus, each of these items of misinformation in our study represents thousands of posts repeating the same debunked claim, often across multiple languages and platforms. out of these collected pieces of misinformation, are in chinese, in english, in farsi. we admit that our data set may be unintentionally biased considering the biased nature of social media and the fact that all authors are currently in the usa, so we might be more exposed to english misinformation. furthermore, due to the lack of copyright laws enforcements in iran, a single piece of misinformation might have been repeatedly debunked by too many sources which prolongs and complicates the search process for new pieces. figure represents a clearer breakdown of our collected data and the overlaps in misinformation across languages. strict filtering and censorship policies for chinese social media is a major factor in the notably lower totals. this can be considered as a benefit of the aggressive censoring of some types of misinformation in china. however, this could come at the expense of silencing voices that are needed to counter other kinds of misinformation. this is a key question being explored in this paper. there are , , pieces of misinformation found exclusively in chinese, english, and farsi only, respectively. out of overall pieces of misinformation, occurred in only farsi and english ( %) which is the largest overlap among possible pairs of languages while farsi and chinese have the least overlap (less than %). of the collected pieces of misinformation, % have been found in all three languages. given the complicated nature of tracking misinformation across multiple languages' social media landscapes, a comprehensive categorization over the topics of covid- misinformation was critical to analyze the catastrophic infodemic occurring during this global pandemic. we identified top level categories for the topics of covid- misinformation. we found that these proposed categories were inclusive enough to cover the chinese, english, and farsi misinformation in our collection. these categories are also extendable to also cover the possible future misinformation. the description of these categories are as follows: includes rumors, actions, and false claims to manipulate the official statistics of death and confirmed cases including exaggerating or downplaying the numbers. includes conspiracy theories and rumors spread out about other countries' roles related to the new virus. . virus transmission: includes topics related to misleading, superstitious, or fake, methods by which the virus can transmit, asymptomatic period, basic reproduction number (r ). . others: includes topics such as contact tracing (pros and cons of contact tracing, and rumors about the amount of personal information needed to be collected for the contact tracing purposes); recovery (the length of recovery periods, antibody level after the recovery, immunity of recovered patients, etc.); prediction of the pandemic; compensations, and more topics; etc. the topics for each of our collected samples were inductively examined to be specific to covid- misinformation and accordingly classified within the proposed categories. figure represents the proportion of each topic within our overall collection across languages. about a quarter of the total collected misinformation in our sample fell under the topic of prevention-individual. also, the top three topics of the collected misinformation mostly concern the individual behavior. in a few cases, the same claim has been reported in more than one category, e.g., "drinking bleach" has been circulating on social media as both a cure and prevention method. in fact, this high proportion of misinformation within the context of individual behavior verifies the vulnerability of users to misinformation to cope with uncertainty and uncontrollability of pandemic circumstances. an interesting observation on the topics of misinformation in these three languages is that the percentage of categories in english and farsi are comparable. furthermore, the top two categories for both farsi and english are "prevention-individual" and "virus transmission". this suggests that the iranian laws coupled with weak enforcement still allows misinformation of a similar kind to flow in iran as in the usa with fewer laws and restrictions. the greatest difference in english and farsi belongs to the category of misinformation related to "other countries". meanwhile, chinese and farsi misinformation within this category have similar records. since most of the chinese and farsi rumors about other countries have political roots and considering the controlling governments in iran and china, such similarity is not surprising. it is interesting that despite tight control of other kinds of misinformation in china, this category is still specifically allowed to flow. the top category of the chinese sample belongs to the topic of "origin" of the virus which is actually still a question mark for the world. we also observed a larger variety of topics in english which explains the relatively higher percentage of english misinformation categorized as "others". for instance, misinformation related to contact tracing could only be found in the usa. one of the reasons could be the fact that some laws and rules vary from one state to another in the usa (e.g., misinformation about federal and state compensation and financial support from businesses and individuals) and this confusing landscape of varying laws opens up space for misinformation to flow. in this section, we delve beyond a classification of misinformation by topic to the roots of misinformation. for example, jang et al. reported that most misinformation stems from a false statement quoted by a public figure; or is deliberate misinformation used for a particular purpose (jang et al, ) . we found that covid- misinformation also followed this same pattern. we identified the following six categories for the roots of the misinformation. it should be noted that we use the term "root", but we could have instead used terms such as "reason" for or "source" of misinformation. . political-related roots: a false statement quoted by a political figure; or related to governments and the relationship between countries; or used for political purposes, e.g., elections. . medical/science-related roots: a false statement quoted by someone claiming to be a medical expert, e.g., doctors, nurses, etc.; or a false perception related to medical research outcomes. statement quoted by a celebrity, influencer, or popular/public figure in the media field; or, a misleading/false content such as a video, photo or an article gets viral through media, e.g., tv, press, etc. . religious-related roots: a false statement quoted by a religious figure; related to religious and/or traditional and superstitious beliefs. . criminal-related roots: a false statement which has been claimed by a scammer or hackers for criminal purposes such as fraud, access to personal information. . others: any other false statements that cannot be substantiated to be related to the mentioned categories including hoaxes, jokes and other undesignated misinformation. for each of our pieces of misinformation, we attempted to track the source that led to this content going viral. the roots of misinformation collected in our sample are verified by reliable references and categorized in one of these six categories by human annotators. if a false statement has been quoted by multiple sources, then the source which made the statement goes viral will be considered as the root of the statement. as figure represents, more than one third ( . %) of the misinformation has been related to political roots which is alarming and shows the critical role of governments and political figures in the infomedic. for example, researchers analyzing -million english-language articles about the pandemic found that usa president trump was the largest driver of the infodemic over that sample (evanega et al., ) . we could not verify the roots of % of our sample, indicating the breadth and diversity of covid- misinformation; these have been categorized as "others". the three countries selected in this paper have their own unique characteristics and cultural structures and here we further discuss the roots of misinformation, particularly the religious and political roots, separately in iran, china, and the usa in the following subsections as well as a discussion of commonalities across these countries. the covid- misinformation circulating on chinese social media landscape reflects significant differences in political systems between china and the western world. for such reasons, misinformation from the western world is translated, filtered, and reflected in chinese social media. a primary root of misinformation circulation in china is the presence of fake science-based claims. when considering chinese social media, it is important to consider the systems of aggressive censorship in china that results in a strict politically filtered internet. global misinformation which has been translated and reflected in chinese social media environment can be considered politically biased since the vast majority of social media in china is tightly controlled by the state. an interesting trend observed in chinese social media is that some already debunked misinformation from the rest of the world, especially the usa, has been translated and widely shared in chinese platforms to criticize the western world's attempts to fight covid- . this pattern of disclosing the debunked misinformation is a politically manipulated misinformation per se. thus, we can only call this type of message pseudo "misinformation" (e.g. reports of president trump suggested injecting bleach to treat . in this case, it appears that the reason this misinformation is allowed to flow is more of a criticism of the usa and the susceptibility of its citizens to misinformation that appears clearly ridiculous to the average chinese citizen. through translating and sharing this message, people in china have been shocked to see such clear misinformation from the usa president and will further believe in more similar information regarding the unsuccessful control of covid- in the usa. much of the true misinformation in china are fake-science misinformation based on some assumption without sufficient evidence and scientific work to support it. though a post may point to scientific sources to back up the claim, it is difficult for most people to verify the source due to the language barrier. specifically, most people do not have the capacity of reading research publications in english or even of translating the name of the journal. this style of post can be used to give the impression of a scientific evidence that may not exist. in our chinese samples, the largest category of roots of misinformation belongs to politics ( %) which is aligned with our analysis for english and farsi samples (figure -a) . due to tight controls and censoring in china, collecting samples of covid- misinformation in chinese has been relatively harder than english and farsi. also, identifying the roots of the collected covid- misinformation is complicated. the roots of % of the chinese misinformation remain undesignated and categorized as "others". surprisingly, a large proportion of covid- misinformation in chinese has been started by celebrities and/or pop culture ( %) which is larger than the english and farsi corresponding category. unlike the iran and usa, most chinese are irreligious and atheist (huff post & briggs, ; noack, ) . however traditional chinese beliefs have been identified among covid- misinformation in chinese (only %) and categorized as having religious roots. we could not identify any misinformation in chinese associated with the criminal roots ( %). this is a strong result and could be considered one benefit of tight government control over social media in china. confronted with the impact of misinformation on western democracies (e.g. advice to drink bleach), chinese citizens could be convinced that the aggressive censorship policies help keep their society safer for criminal elements and viral misinformation. misinformation in the usa is commonly in the form of counter-expertise, the rejection of mainstream academic expertise, which dates back to the th century (douglas, ) . this form of misinformation began with christian fundamentalists rejecting evolution as it contradicted the bible (douglas, ) . since then, counter-expertise looks to distrust mainstream scientific media by promoting alternative thoughts through alternative media. this alternative media happens to be far more susceptible to misinformation (douglas, ) . such alternative media has released misinformation throughout the pandemic, with fox news ("fox's dr. marc siegel", ) stating "the virus should be compared to the flu because at worst case scenario it could be the flu". across the usa, churches have successfully resisted complying with government-led preventive measures and health orders. a recent study shows that % of protestant/evangelical ministers held in-person worship as of july , (vondracek, ) . the persistence to stay open and hold in-person worship has led to churches becoming hot spots for positive cases (conger et al., ) . father joseph illo, leader of the star of the sea church, sent out misinformation to churchgoers stating that "the news reports about covid are largely unreal" (bisacky, ) . however, not all churches within the usa are rejecting mainstream media or health orders. the current politically polarized atmosphere in the usa is also a major driver of misinformation. misinformation related to politics is often fabricated to create confirmation bias among readers, subsequently leading to heightened ingroup/party identification and polarization (douglas, ) (e.g. "the political party i identify with fought for the right thing, as opposed to the other party"). covid- misinformation spread by political figures in the usa may be a symptom of deflection and scapegoating due to inadequate administrative response. usa government sources have suggested a conspiracy theory that covid- was created in a chinese laboratory (aljazeera news, ). deflection is apparent as the usa president donald trump suggested "quick fixes" and "cures", such as hydroxychloroquine, azithromycin, and convalescent plasma (caplan, ) , that have limited testing and results as potential cures or "game changers in the history of medicine". it is necessary to acknowledge the severity and seriousness of the spread of misinformation from the usa public officials. in our collection of misinformation samples from the usa about one third ( %) have political roots ( figure -b) . while the spread of information from public officials to win elections is not new, the role of the mass media as a corrective measure on this behavior has changed. the media is now competing with social media for advertisements, which has resulted in pressure to cater content to users, further perpetuating political polarization (scheufele & krause, ) . from drastically downplaying the seriousness of the virus to stating that "one day it's like a miracle, it will disappear" (the white house, ), the usa government has contributed heavily to covid- misinformation on all media platforms. the role of celebrities in driving american culture (clemmons, ) and the power of american public figures' words should not be underestimated. in our sample, % of the collected misinformation in the usa has been directly traced back to a celebrity, influencers or popular figure. for example, on july , instagram removed madonna's post "for making false claims about cures and prevention methods for covid- " (solis, ) . false statements by self-claimed medical related crew or wrong and manipulated interpretation from medical facts are another major root of misinformation in the usa ( % of our sample represented in figure -b). covid- misinformation has hit iran harshly. two major reasons have been identified for creating and spreading misinformation: first, discourse about covid- is politically manipulated by the government (alimardani & elswah, ); second, official religious figures have interfered with covid- related issues and religion has been a barrier for ordinary hardliners to be unbiased. in general, social media reflects that people do not trust the covid information released by either government or religious officials. when the official channels of communication of information fail, people start clinging to their own unofficial channels of information gathering without monitoring the validity of the information which eventually intensifies the spread of misinformation. iran has a controlling and conservative government which micro-manages all aspects of people' lives. this characteristic of the government politicizes every subject including the pandemic. thus, it is not surprising that much of the covid- misinformation found in farsi has political roots. an ironic piece of misinformation with political roots in iran is that the government believes the covid- misinformation present in iran has been started mainly by "enemies", referring to the usa government ("bbc news persian", ). another example of political misinformation is that the iran government promoted a fake testing technology called "coronavirus remote detectors" which can detect infected individuals from a distance of yards. the unveiling ceremony on april th went viral all-over the iranian press and social media. religion has also played a critical role in spreading covid- misinformation in iran. for instance, some official religious hardliners falsely believe that sacred protection from religious shrines would prevent infection (malekian, ) . in iran, some shiite muslim religious figures often use people's faith to oppose "westernized" facts, sometimes including scientific facts. for example, on february , , a religious figure, ayatollah abbas tabrizian, advised people to rub their anuses with violet oil to prevent and cure covid- . this post on his official telegram channel (with more than , followers) has been viral on all farsi social media. users reshared this post with mixed reactions that included both adherence and ridicule (the new arab, ). as it was expected, in our collected farsi sample, the top category of roots of misinformation belongs to politics ( %) (figure -c). the next largest proportion of the misinformation has medical/science roots including both western misinformation and local and traditional persian remedies. about % of our sampled misinformation has religious roots. considering the bold role of religion in iran, this rate seems relatively low. however, the virality of this misinformation has been substantial, such that some of the misinformation is still circulating on social media, even after it officially got debunked. some however have been transformed into sarcasm to be used as a form of protest against hard-core religious figures. a b c figure : proportion of the chinese (n= ), english (n= ), and farsi (n= ) collected data across the proposed categories for roots of covid- misinformation. a recent study showed that there is an intersection between fake news and religion in societies with religious background (douglas, ) . our observation on this matter in iran is aligned with this study given the islamic background of iran ( %). however, our sample could not confirm the same result in the usa and china. given the impact of the christian community in the usa (bailey, ), % religious roots for the english misinformation was surprisingly lower than our initial expectation. when politics and government play a significant role in the destiny of a society (which is the case in iran, china, and the usa), a political polarization phenomenon will emerge (facing history and ourselves, ). political polarization has been known as an important factor to spread misinformation in a society and the meaningful relationship between misinformation and political polarization has been profoundly investigated in the literature ( the absence of misinformation with criminal roots in chinese social media is notable. this is an example of a key difference in how government strategy directly influences the types of misinformation to which the public is exposed. as a result, some societies are more vulnerable to criminal misinformation. given that politics was the largest root of misinformation across all three languages in this dataset, all societies are extremely vulnerable to government misinformation. however, some have more potential to counter government misinformation with information from private sources. in many ways, this is perhaps the key question for countries and societies around the world going forward in deciding how they want to control misinformation and infodemic. for liberal democracies, a key challenge is determining how to control misinformation without silencing the voices needed to hold government misinformation accountable. our major goal is to analyze the covid- misinformation on different social media platforms across different languages to gain a more holistic, global understanding of the misinformation's landscape. this effort is an initial step to diminish the current infodemic happening along with the pandemic. by increasing public knowledge of the adverse impacts of misinformation on public health during the pandemic, many lives could be saved. to achieve our goal, the opportunistic sampling approach was utilized to compile pieces of verified misinformation posted virally in chinese, english, and farsi across twitter, facebook, weibo, wechat, whatsapp, instagram, and tiktok between january and august . each of these pieces represented thousands of posts across platforms and often across languages. then, a classification approach was proposed to categorize the collected misinformation based on both their topics and roots. we identified high level topics being inclusive and relevant in all three languages. we also identified major categories for the roots of misinformation. our study yielded the following important results: • politics was the largest root of misinformation across all three languages in this dataset. • overall, the english and farsi samples have more in common in terms of the topic of misinformation than chinese specifically regarding individual prevention methods. • the absence of misinformation with criminal roots and fewer categories of misinformation overall in chinese social media is notable and points out a critically important tradeoff in the control of misinformation. we note important differences in how government controls on social media platforms drive usage onto some platforms and away from others, with different infrastructure for tracking and controlling misinformation. understanding how different countries utilize social media and their restrictions gives better insight as to how to regulate disruptive behavior. a key challenge going forward for all societies and countries will be in determining how to control misinformation without silencing the voices needed to hold governments accountable. overall, it is clear how focusing beyond english, beyond the usa, and beyond the usa-based social media platforms are essential to providing a clear understanding of the effects of misinformation and the effectiveness of misinformation control strategies around the world. muslims 'immune to coronavirus' some imams in somalia say, putting public at risk trust, religion, and politics: coronavirus misinformation in iran whatsapp statistics: revenue, usage, and history. fortunly christianity is declining at a rapid pace, but americans still hold positive views about religion's role in society rouhani: the conspiracy of our enemies to shut down the country for fear of the corona concerns raised after san francisco church shares misinformation on covid- types, sources, and claims of reuters institute for the study of journalism a brief history of fake news trump opened the floodgates for convalescent plasma too soon stop the spread of rumors coping with stress coronavirus: video of an undertrial in mumbai falsely viral as nizamuddin markaz attendee spitting at cop statistics: weibo monthly active users (mau) & dau. china internet watch wechat statistical highlights ; miniprogram dau> m number of monthly active facebook users worldwide as of nd quarter (in millions) number of monthly active whatsapp users worldwide from the psychology of secular saints: americans worship celebrities for better or worse churches were eager to reopen. now they are confronting coronavirus cases most popular social media sites in china the catch to putting warning labels on fake news social-media companies must flatten the curve of misinformation an interactive web-based dashboard to track covid- in real time religion and fake news: faith-based alternative information ecosystems in the the psychology of conspiracy theories coronavirus misinformation: quantifying sources and themes in the covid- 'infodemic'. the cornell alliance for science iran, like russia before it, tries to block telegram app explainer: political polarization in the united states the coronavirus doesn't discriminate, but u.s. health care showing familiar biases iran ranked world's th instagram user. financial tribune marc siegel says "worse case scenario study: rising religious tide in china overwhelms atheist doctrine an empirical investigation of network polarization a computational approach for examining the roots and spreading patterns of fake news: evolution tree analysis which countries block twitter & which no longer ban twitter? hidemyass human-misinformation interaction: understanding the interdisciplinary approach needed to computationally combat false information whatsapp limits message forwarding in fight against misinformation. the verge melanin doesn't protect against coronavirus coronavirus goes viral: quantifying the covid- misinformation epidemic on twitter combating fake news: an agenda for research and action mass polarization: manifestations and measurements tiktok owner puts deal with oracle twitter statistics every marketer should know in could covid- inspire the faithful? scholars predict spirituality surge in our future iranian hardliners accused of breaking into shrines closed to prevent coronavirus spread twitter is banned in china, so how does it have million users there? tech times taking stock with teens® − piper sandler completes th semi-annual generation z survey of map: these are the world's least religious countries the u.s. national pandemic emotional impact report secret ways to use hashtags you've never tried before. make use of the implied truth effect: attaching warnings to a subset of fake news headlines increases perceived accuracy of headlines without warnings fighting misinformation on social media using crowdsourced judgments of news source quality it was already dangerous to be muslim in india. then came the coronavirus checking facts and fighting back: why journalists should defend their profession verified signatories of the ifcn code of principles. ifcn code of principles chinese censorship is spreading beyond its borders american teens use tiktok. statista many black, asian americans say they have experienced discrimination amid coronavirus claimreview -schema.org type science audiences, misinformation, and fake news misinformation and fears about its impact are pervasive in emerging economies these celebrities have been flagged on social media for spreading coronavirus risk for asians, africans, caucasians− revealed japanese and chinese at highest risk for coronavirus applying essential oil to anus 'cures coronavirus is the new crown virus a laboratory biochemical weapon? only infect asians? why are conspiracy theories soaring? scholar analysis: the government deliberately nurturing and condoning remarks by president trump in meeting with african american leaders. the white house man fatally poisons himself while self-medicating for coronavirus, doctor says a hoarder's huge stockpile of masks and gloves will now go to doctors and nurses % of churches meeting for in-person worship, study finds. washington times information disorder: toward an interdisciplinary framework for research and policy making understanding information disorder too big to know: rethinking knowledge now that the facts aren't the facts, experts are everywhere, and the smartest person in the room is the room st who infodemiology conference. who the authors would like to kindly acknowledge assistance from gillian kurtic and yan chen for contributions to the paper including help reviewing, organizing, and formatting. we also thank dr. ricardo baeza-yates for his detailed feedback, wise advice and thought-provoking questions. we gratefully acknowledge funding from clarkson university epidemic and virus-related research innovation fund. key: cord- -i hfj ca authors: hufbauer, gary clyde; jung, euijin title: what's new in economic sanctions? date: - - journal: eur econ rev doi: . /j.euroecorev. . sha: doc_id: cord_uid: i hfj ca nan exceptions and monetary rewards. also, cyber warfare and private litigation are illustrated as unconventional measures. the emergence of new weapons and the growing preference of sender countries to use them creates fresh concerns, which are discussed at the end of this section. financial tools. very early in the post second world war era, the united states and its european allies used the international monetary fund, the world bank, and regional development banksinstitutions they controlled --as on-off spigots to block or limit funding to target countries. this was supplemented by outright denial or slow-walking bilateral grants and loans (military and economic) to persuade recalcitrant foreign leaders. the soviet union did much the same to coerce wayward satellites during these decades. prior to south african sanctions in the late s and early s, private banks headquartered in western countries were rarely instructed or even cautioned by their home governments to restrict loans or financial services to target countries (such services as correspondent relations or floating sovereign debt). partly this reflected the operations of private banks in that era: they did relatively little business in countries that were prime candidates for economic sanctions. but also, it reflected hesitation by western governments to "meddle" in the affairs of private banks. all this changed with the presidency of barack obama, and the wide-ranging sanctions against middle east targets. private banks based in the west were instructed not to do business with iraq or iran, and heavy fines were imposed on european banks (such as société générale and hsbc) that sought to evade the strictures. equally important, when sanctions against iran gathered force in , most iranian banks were cut off from the world's financial centers. this was achieved both by proscriptions against doing business with iranian banks and by denial of their wire transfers through swift or fedwire. these novel techniques threw sand into the creaky domain of iranian finance, hobbling an economy that was already suffering from severe mismanagement. why was president obama so eager to enlist financial institutions in the conflict with iran? saddled with flagging military ventures in iraq and afghanistan, obama wanted to avoid, at all costs, a third military front with iran. like multiple leaders before him, obama searched for "silver bullet" sanctions that would force iran to the bargaining table. finance seemed to fit the bill, and indeed financial pressure was a critical element in creating the joint comprehensive program of action (jcpoa) which seemed to end the conflict over nuclear weapons in . not so quick. president trump dismissed the jcpoa as ineffective. yet he resurrected and reinforced the financial techniques applied by his predecessors, though european cooperation became more reluctant than during the obama years. many european foreign ministers believe that the jcpoa was as good a deal as iran would ever sign and, unlike trump, hesitated to blow it up. however, iran's threat, publicized on june , , to enrich more uranium than permitted in the jcpoa agreement unless european sanctions are lifted, could eventually alter european views. offers hard to refuse. prior to the st century, alliances of willing sender country were formed under un auspices, often with blessings from the security council, the organization of american states, or ad hoc groups. in earlier decades, the united states enacted statutes (e.g., the helms-burton law in ) and issued regulations designed to force foreign subsidiaries of us firms, and even foreign firms, not to do business with targets such as cuba and china. these laws and regulations sparked nationalist backlashes in canada, france and other us allies because us measures were perceived to intrude on sovereign powers abroad. in recent decades, the united states has devised a more direct technique --offer banks and industrial firms in europe, japan, korea and elsewhere a choice: do business in the target country, or do business in the united states, but not both. this was obama's way of implementing broad sanctions against iran, and trump is doing the same. this new approach of making offers bank-by-bank, and firm-by-firm achieves results with far less backlash. moreover, the surveillance techniques of the national security agency (nsa) and central intelligence agency (cia) provide powerful deterrence against "cheating". very likely the offer technique will be applied widely in the future. as beijing flexes its economic muscle, china may well adopt the same technique. as a harbinger, china has extended belt-and-road loans to nearly every country in latin america except paraguaywhich committed the offense of granting diplomatic recognition to taiwan. humanitarian exceptions. seldom acknowledged but hard to deny, broad economic sanctions are akin to area bombing, also known as carpet bombing, a technique favored by sir arthur "bomber" harris during the second world war and embraced by winston churchill. carpet bombing inevitably kills innocent children and other civilians; broad sanctions inevitably inflict privation and disease on the poorer strata of society, often the young and old. one answer to the moral dilemma is to make exceptions for exports of food, medicines and other arguably humanitarian products. this answer, intended to pacify critical western journalists as well as help the vulnerable, came into vogue in the s and is now a regular component of nearly every episode. even president trump's renewed sanctions against cuba and north korea have humanitarian exceptions. critics of trump's sanctions against venezuelacutting off us oil purchases and diverting citgo earningshave been quick to cite the humanitarian harm to ordinary venezuelans. nevertheless, the overwhelming trend in the past two decades is away from comprehensive sanctions to "smart" or "targeted" sanctions. in the scores of cases unknown to the general public, limited sanctions are the preferred toolsanctions aimed at specific individuals, companies or transactions, without causing humanitarian harm to the public. however, in high profile casesthe ones average readers remember, such as iran, cuba, north korea and venezuelathe flavor is comprehensive sanctions. so, humanitarian exceptions remain as key component of sanctions policy. diplomatic exceptions. in pre- st century episodes, sender countries were nominally "all in" the sanctions regime. however, cheating was widespread among senders, even for declared adherents to a un security council resolution. less than faithful observance was an informal means of avoiding burdens. as well, token compensation was sometimes extended to states neighboring the target, to mitigate their hardship from diminished trade. the serbian and iraq episodes are examples. to recruit countries into the "sheriff's posse", tailored exceptions were woven into the iranian sanction regime spearheaded by president obama. countries heavily dependent on iranian oil could maintain traditional, or modestly scaled back, import levels. such exceptions enlisted turkey, india, china and a few others into the regime. president trump's renewed sanctions against iran contained similar exceptions, but with flexible time limits that eventually ran out. the new approach anticipates the reality of unenthusiastic posse members by negotiating diplomatic exceptions in the launch plan. whether diplomatic exceptions and humanitarian carve outs make a difference in assembling a "coalition of the willing", or the ultimate success of sanctions, remains to be explored. weaponized tariffs. president trump has inaugurated an almost novel technique to the realm of economic sanctionsnot an easy feat after more than two centuries of practice since the napoleonic wars. trump has weaponized the us tariff regime, raising selective rates well above maximum ("bound") levels committed both in the wto and regional and bilateral free trade agreements. during the great depression of the s, many countries raised their tariffs as a retaliatory tool in response to the smoot-hawley act. but in that era international commitments did not bind national tariff levels. trump's justification for weaponization is simple: "when a country [usa] is losing many billions of dollars on trade with virtually every country it does business with, trade wars are good, and easy to win." once trump settled in the white house, his campaign promises were put in action through tariffs on merchandise imports from china and mexico. contending that chinese practices of forcing technology transfers and stealing intellectual property are threats to the us economy and national security, trump imposed percent and percent tariffs on $ billion imports from china. in response, china retaliated by imposing tariffs on some $ billion imports from the united states, and lowering tariffs to imports from other countries. trump threatened to impose tariffs on the rest of chinese imports (about $ billion), but the threat was shelved at the g summit held in osaka, japan on june - , . in september , however, trump raised us tariffs on some imports and more tariffs were threatened. but in january , the us and china negotiated a "phase one" deal committing china to step up its purchases of us goods and services (a huge increase over two years of $ billion compared with ), and the additional tariffs were put on ice. if the us is dissatisfied with chinese performance on any of the phase one commitments, the tariffs can be reinstated. that could well happen in the runup to the us presidential election in november , as one means for trump to advertise that he is tougher on china than his rival, former vice president joe biden. a much smaller version of the same strategy was applied to mexico, to resolve the issue of central american refugees passing through mexico to the united states. trump announced that a percent tariff would be imposed on all products imported from mexico, starting june , , unless mexico reduced the flow of illegal migrants. moreover, he threatened to increase the tariff in percent stages, up to percent, to be reached on october , . mexico caved, and agreed to deploy up to , national guard troops to its southern border and take additional measures to slow the refugee flow. in turn, trump suspended the imposition of tariffs. in , the percentage of us trade affected by sanctions was under percent. several conflicts later, but before trump entered the white house, still only percent of us trade was similarly affected. just adding trump's tariffs on $ billion imports from china and chinese retaliation against $ billions of us exports, that percentage has now reached percent, a magnitude of macroeconomic significance. one unintended result is to erode business confidence worldwide and diminish cross-border investment. with his weaponized approach, trump has significantly eroded the distinction between routine commercial tactics in search of markets abroad, on the one hand, and economic sanctions in pursuit of foreign policy goals, on the other. the erosion is particularly evident with respect to china, where trump's trade war presages a new cold war (explored later, and likely to be pursued, with fresh vigor, if a democrat captures the white house in ). since the founding of the general agreement on tariffs and trade (the gatt) in , the united states and other members have imposed penalty duties on top of bound tariffs in retaliation against specific foreign practicesnotably countervailing duties against subsidized imports and anti-dumping duties against imports sold below average cost or prevailing prices abroad. but these and other penalty duties are targeted on narrow product categories in response to individual offenses. trump's tariffs are aimed at a wide range of products (all autos, all steel, everything chinese) in pursuit of broad goals that mix commerce and foreign policy (e.g., slash bilateral trade deficits, restore us preeminence as a manufacturing power, or limit technology exports that could strengthen china's military). in kindred spirit, the trump administration is pushing a bill titled the "reciprocal trade act" that would enhance presidential powers to raise us tariffs against specific imports from countries that impose higher tariffs than existing us rates. it is hard to classify the draft bill as commercial policy or sanctions policy, since it conflates the two. moreover, trump's tariff agenda is buttressed by fresh limitations on foreign investment in the united states, via regulations issued under the new foreign investment risk review modernization act (firrma). the regulations create a pilot program that will reviewin a secret star chamber process under the auspices of the committee on foreign investment in the united states (cfius) --virtually every foreign acquisition, even of minority interests, in any us company with a technology flavor. again, the distinction is blurred almost beyond recognition between commercial objectives and foreign policy goals. likewise, new regulations issued under the export control reform act of (ecra) subject a broad range of technology exports to government oversight, another conflation of commercial and foreign policy. new databases have yet to catch up with the weaponization of import tariffs, investment policy, and export controls. for the moment, case-by-case studies will be needed to appraise the success of trump's approach. the imposition of steel and aluminum tariffs, and the threat of auto tariffs, on canada and mexico appear to have wrested concessions from the two neighbors in the renegotiation of the north american free trade agreement (nafta)negotiations that led to the us-mexico-canada agreement (usmca). further, mexico clamped down on central american refugees bound for the united states, in response to trump's threat of escalating tariffs. in january , the phase one agreement promised a massive increase in chinese purchases of us exports, along with many market-opening measures. whether beijing can or will carry out these promises remains to be seen, especially in the wake of the coronavirus epidemic and heightened technology tensions with washington. whatever the outcome of these episodes, the conflation of commercial policy with sanctions policy has dramatically and adversely changed the face of world trade and finance. since the second world war, the united states has espoused market principles for trade and financea world economy where government sets the rules, but private firms determine purchases and prices. the new flavor, in the trump era, is managed trade and financegovernment both sets rules and determines outcomes. as other countries emulate trump, it's hard to believe the us will benefit. the research task for scholars is to evaluate not only the outcome of individual episodes, but also how the new flavor affects the global system. if the conflation becomes a customary staple of sanctions and commercial policy, past the trump administration, our prognosis is gloomy. monetary rewards. every sanctions episode contains the seeds of relief, simply from the potential removal of barriers to trade, investment and finance. ever since the marshall plan was launched to thwart soviet expansion, the united states has conditioned military or economic aid on the behavior of recipient countries. in the th century, south korea, pakistan, chile, egypt and others have been targets of such positive measures. the new twist, in the realm of positive measures, is the twinning of negative threats with positive incentives. this was done by europe to slow the arrival of syrian and other refugees via turkey. the negative threat was to harden the border between turkey and its european neighbors; the positive measure was money. eu promised to pay about $ . billion to turkey to contain refugees at the eu-turkish border in . in a similar spirit, president trump has tabled vague offers of loans and grants, coupled with the threat of stiffer sanctions, to entice north korea and iran to curtail and even eliminate their nuclear arsenals. following the celebrated meeting of presidents trump and kim jung un at the end of june , more positive measures seemed to be on the negotiating table, but a subsequent chill seems to have ended the nascent détente. far more massive, china launched its "belt and road" initiative, offering huge loans, possibly with a grant element, for infrastructure projects in adjacent and distant friendly countries. how much will be expended to improve sea, rail and road ties with china remains to be determined, but the amounts are likely to run into hundreds of billions if not trillions of dollars. indeed, a new study suggests the belt and road initiative could eventually invest as much as $ trillion in infrastructure projects. anything approaching this magnitude will give china enormous leverage to influence recipient countries, both by offering finance and by withdrawing finance. the realm of "positive sanctions", as they have been called, is potentially broad and ambiguous. we prefer to confine the term to situations where the promise of monetary rewards is twinned with the imposition or threat of negative sanctions in a quid pro quo fashion. for example, beltand-road loans are clearly conditioned on the target country not recognizing taiwan and establishing friendly trade and investment relations with china. us offers to north korea and iran hinge on their abandonment of nuclear weapons. cyber warfare. cyber-attacks clearly rate as a st century innovation. through nsa wizardry, the united states has possessed the capability, for at least a quarter century, to descend chaos on the banking, telecommunications, and power systems of adversaries. other countries, not only china and russia, but also north korea and india, and allies like germany, france, britain and israel possess similar if not quite equal capabilities. moreover, the united states is highly vulnerable, still struggling to create a cyber command capable of mounting defensive measures. during obama's tenure, the pentagon and the national security advisor eschewed offensive use of cyber capabilities, arguing that cyber warfare was akin to kinetic warfare. in a classified executive order, president trump has reversed that policy, opening the possibility of offensive cyber-attacks in future economic sanctions episodes. media reports indicate that cyber measures have already been deployed against russia (its electrical grid) and iran (its financial system). russia made its mark with extensive disinformation and hacking activities during the us presidential election. but influencing foreign elections is nothing new in the sanctions world; the united states often deployed media campaigns during the cold war to shift election results in europe and latin america. what's new is posting fake opinions and news on social media and hacking private email accounts. future episodes seem all but certain, starting with the november us presidential election. private litigation. in a bygone era, sovereign states were shielded from foreign private litigation by the doctrine of sovereign immunity. while the doctrine has been gradually eroded, we define private litigation, when launched in the courts of a hostile country, as a new weapon in the sanctions armory. thus, in april , the trump administration withdrew the executive order, issued by its predecessors, which barred private litigation against cuban and foreign entities for "trafficking" in cuban property expropriated from american firms and citizens. such suits were authorized by the helms-burton law of but suspended by the clinton administration to settle a case brought against the united states in the wto by the european union. the trump administration's action could unleash multiple private cases, with claims aggregating billions of dollars. once the cases are filed, it will be beyond the administration's powers to shut them down. hence, they will not be useful as bargaining chips with the cuban government, but they will inflict punishment on cuban and foreign firms (principally european and canadian corporations). blocking statutes and bruised relations between washington and its allies seem likely. as another example, using the amended foreign sovereign immunities act (fsia) that allows us victims of terrorism to sue designated state sponsors of terrorism for their terrorist acts, the us federal courts over the last two decades issued some judgments finding iran liable for terrorist action that claimed american victims, resulting in over $ billion in damages against iranian government entities and officials. for example, us courts found iran --acting through hezbollah --liable for americans killed in the bombing of the us marine corps barracks in beirut and other attacks. recently the us supreme court ruled that $ billion in frozen iranian assets can be turned over to the survivors of the bombing. trump's policies with respect to cuba may set a precedent for other sanctions cases. private litigation could become more common if the congress amends the foreign sovereign immunities act of to broaden existing exceptions to the immunities doctrine to include "trafficking" and other offenses that sanctioned countries and their commercial partners are likely to commit (for example, canceling contracts or imposing tariffs on us exports). from the standpoint of us foreign policy, private litigation may serve as deterrent and retribution, but not as a tool of international negotiation. use. an overriding reason for the us preference is the record of murky outcomes and outright failures in military actions against somalia, iraq and afghanistanall reminiscent of vietnam. economic sanctions rarely lead to american deaths, unlike military operations. whether sanctions succeed in achieving their goals seems far less important to the public than the outcome of military conflicts. moreover, when it comes to challenging russia or china, sanctions are the only tool: us military measures would threaten nuclear war. parallel concerns can be found in the preference of other great powers for economic weapons. the chinese market, like its us counterpart, is big enough that shutting access commands the attention of an adversary. south korea is the exemplary case, with implications for vietnam, malaysia and thailand. china cannot threaten military strikes against south korea, taiwan or japan without triggering a us military response, but china can easily close its market to exports from offending neighbors. russia faces the same dilemma with respect to nato members, but it has enjoyed a relatively free military hand in georgia, ukraine and syriacorrectly calculating that the united states would not respond in those theaters. for other theaters, social media and cyber campaigns are far cheaper than overt or covert russian military actions. the european union lacks a joint military force and has no prospect of acquiring one. apart from moral suasion, economic sanctions are the eu's sole enforcement tool with bearable economic and political cost. in sum, the growing use of economic sanctions carries adverse implications for the stability and survival of nato and wto. for nato, frictions between the united states and its security allies weaken the effectiveness of sanctions on iran and other targets and foster dissent between senior officials. the misalignment in iran sanction policy became worse when the european union blocked the us attempt to reimpose un sanctions on iran. meanwhile, trump's cuban policy irritates business firms abroad and seems pointless to canadian and european military leaders. trump's broad national security justification for section tariffs under the trade act, and his tariff reprisals under section of the trade act, directly threaten the rules-based multilateral trading system overseen by the wto. on their face, us trade measures conflict with wto rules, but since collateral us actions have dismantled the wto's appellate body, aggrieved foreign countries have no meaningful forum for settling disputes. accordingly, they have resorted to retaliatory measures which are equally inconsistent with wto rules. underlying the largest frictions is the new cold war and it's not at all clear that the wto system can house both the united states and china. given the global trade and investment reach of both antagonists, a split of the wto into two domains will inflict substantial costs on the other member countries. in practice, if not in name, the world trade organization may not survive. through the turn of century, the united states was the dominant sender country, participating in about percent of cases, often with a posse of allies, followed by the erstwhile soviet union, the united kingdom and the european union. after the end of the cold war in , the united states sometimes secured un security council resolutions that enlisted nominally committed sender countries. during that era, us targets dotted the globe, while russian targets were concentrated in neighboring countries, and uk and eu targets were concentrated in africa (but the uk often joined far-flung us-led episodes). in recent years, new actors and new targets are changing the traditional landscape of sanctions, reflecting technological advances and the rise of social media. to this day, the united states remains the dominant sender, but starting in the late s and early s the european union became much more active, allied with the united nations, regional partners or the united states. eu targets were concentrated in africa, usually countries ridden with strife, ruled by despots, or victims of military coups. the european union sometimes achieved a modest degree of success in stabilizing these countries or displacing their political leaders. for example, the european union introduced restrictive measures against zimbabwe in in relation to the escalating domestic repression against political opponents, and the violation of human rights including freedom of speech. the eu sanctions included arms embargo, travel restrictions and asset freeze. after the constitutional referendum in zimbabwe was held, most sanctions have been suspended, but several congolese individuals are still subject to asset freeze and travel bans. entering the s, the european union built a policy framework for more effective use of targeted sanctions. to this end, the eu updated its guidelines for member states, calling for timely implementation and evaluation. eu sanctions aim to deter terrorism (e.g. iran), delay nuclear proliferation (e.g. iran and north korea), reduce human rights violations (e.g., nicaragua), reverse annexation of foreign territory (e.g. russia), and destabilize foreign leaders (e.g., ivory coast). between and , the european union introduced more than different sanctions against states. for example, in , eu members agreed to impose travel bans and asset freezes on nicaraguan individuals and entities responsible for human rights violations. all designated individuals and entities are listed in the official eu sanctions database. one eu concern is coping with us "extraterritorial" sanctions. when trump revoked us participation in the iranian nuclear agreement and imposed secondary sanctions against firms doing business with iran (mainly energy deals), third countries became subject to us sanctions. some argued that european foreign policy autonomy was at risk because the eu could be seen as coerced into following us foreign policy. to bypass this perception, france, germany and britain created the "instrument for supporting trade exchanges" (instex) as a special vehicle to help eu firms do business with iran and facilitate non-us dollar transactions. despite trump's criticism of instex, the eu successfully made its first transaction with iran using this financial mechanism in march . however, this divergence weakened the overall impact of sanctions and lessened the already small likelihood that iran would abandon its nuclear goals. when trump re-imposed nuclear sanctions, iran became less compliant with the jcpoa. in iran has exceeded a threshold on uranium enrichment agreed to in the deal, but continues to work with iaea inspectors in verification and monitoring of sites related to the deal with limiting their access to certain sites. russia. shorn of direct control over its erstwhile satellites, russia turned to active diplomacy towards the "near abroad". economic sanctions accompanied the diplomatic mix, leading to episodes aimed at discouraging ties with the west, seizing disputed territory, or protecting russian-speaking minorities. for instance, russia imposed economic sanctions on estonia and latvia in response to alleged discrimination against russian minorities ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) . restrictions on oil and gas exports and access to russian markets are customary tools. entering the s, russia often imposed sanctions as a retaliatory instrument to counteract western measures against russia's own provocative actions, such as the invasion of ukraine, the nerve agent attack on a former russian spy, and the cyberattack on us elections. responding to us and eu sanctions for the invasion of ukraine in , russia imposed travel bans and food embargos on the two senders. following annual renewals, these will remain in effect until the end of . counter sanctions also apply to ukraine in response to ukraine's decision to expand its own list of prohibited imports from russia. trade in energy and food products between russia and ukraine has essentially stopped. xi jinping, apparently leader for life, has changed the music. ten sanction cases can be identified between and , which is triple the number of cases between and . china's growing economic power and its integration with the world markets enables china to influence the foreign policies of neighboring countries and even distant nations. president xi's belt-and-road initiative is by far the largest "positive sanction" since the marshall plan. as they embrace belt-and-road projects, many countries in asia and latin america adopt a friendly approach to china in the united nations and other international fora. alongside, china deploys negative measures such as trade and investment restrictions, popular boycotts, limits on chinese tourism, and informal pressure on business entities. unilateral sanctions are typically imposed when china perceives specific threats to its national security and sovereignty. for example, china cut off diplomatic and trade talks, and curtailed imports of norwegian salmon, when norway awarded the nobel peace prize to chinese dissident liu xiaobo. in a similar vein, after south korea installed its defensive missile system of us design in - , china restricted tourism and imports of cultural products and used regulatory measures to close almost south korean owned retail stores in china. these sanctions did not reverse norwegian or south korean policies, but they did send diplomatic signals to other countries that might consider crossing chinese "red lines" (harrell et al, ) . all three countries have different reasons for employing sanctions-related policies. the european union prioritizes its own liberal principles, even as it disagrees with us positions on iran and other targets. russia's approach to dominate its neighbors hasn't changed much, but in addition russia has frequently imposed retaliatory sanctions when russia itself became a target country. as a newcomer to the offensive use of sanctions, china has specialized in coercive measures that boldly announce the "red lines" in its relations with foreign powers. non-state actors. in the united states and europe, civil society has actively pushed government to impose sanctions for bad behavior abroad, particularly in the realm of human rights. the first big campaign took place in the late s when ad hoc groups persuaded us states and private firms to sever ties with south africa. more recently, the kimberly process, aimed at limiting the global market for "conflict diamonds", was embraced by de beers and other dominant firms. the magnitsky act --retaliation against human rights abuses and death suffered by the russian lawyer magnitskystemmed from the lobbying efforts of his erstwhile employer to blacklist the responsible russian officials. finally, a group of ngos impelled us sanctions against senior burmese military leaders responsible for severe violations of human rights during episodes of killing rohingya people. gathering steam today are efforts to punish china for its harsh treatment of the uighur population and hong kong protestors andover a longer time framenew sanctions against purveyors of coal and other fossil fuels. civil society has increased its influence on sanction process as its network spreads to the globe via social networks and helps raise public awareness of concerning issues. "specially designated" targets. fairly recent is the imposition of sanctions against "specially designated" persons or firms. terrorists, drug dealers and money launderers were early targets, but an innovation is black-listing political and business leaders and select firms. thanks to advanced technology in communication and data processing, national intelligence agencies such as nsa and cia can identify assets, travel patterns, families and commercial contacts of designated firms and individuals. since january , significant sanctions were launched against designated entities. the european union imposed its first sanctions in response to a chemical attack, targeting four russian military intelligence agents for poisoning a former russian double agent living in britain. meanwhile, the us sanctioned a state-owned oil company, petroleos de venezuela, s.a. (pdvsa), restricting us firms from buying venezuelan crude. the us complaint against pdvsa was its financial support of the maduro regime. in august , the trump administration imposed financial sanctions on individuals who implemented china's national security law in hong kong, including chief executive carry lam. in turn, china retaliated with similar measures against us politicians who were prominent critics. deterrence. while certainly not a new goal, deterrence has played a large role in recent cases. no analyst could expect sanctions to diminish putin's support of pro-russian forces in eastern ukraine, much less dislodge russian occupation of crimea. but intelligence officers and foreign ministers could reasonably expect that stiff sanctions in response to russian adventures would deter further russian military expansioninto moldova, the baltics, or central asia. at this writing, putin has not followed hitler's playbook, beyond the takeover of crimea in march and the subsequent support of pro-russian forces in eastern ukraine. perhaps deterrence worked. turning to another theater, us and allied sanctions against iran, even with renewed force starting in , were unlikely to force the supreme leader to abandon his nuclear weapons project, then in its th year. but alongside the threat of a military strike, the sanctions apparently deterred iran from either testing its bombs or miniaturizing them to fit on missiles. in turn, restraint helped pave the way for the joint comprehensive plan of action (jcpoa). less appreciated is the impact of us and allied sanctions, plus unpublicized on-again, off-again support from china, in limiting north korea's nuclear ambitions. kim jong un almost certainly could have conducted additional long-distance missile tests and detonated more powerful bombs. but the coupling of us-led and chinese sanctions, along with the high-profile june and june meetings with president trump in singapore and the dmz respectively, may have stayed kim's hand. again, perhaps a win for deterrence, though well short of a win for nuclear disarmament. most recently, reciprocal us and chinese sanctions over beijing's absorption of hong kong into the mainland legal regime stand no chance of swaying chinese policy nor of curtailing us criticism. moreover, it's not obvious that these sanctions will deter further episodes in the new cold war. but to determine whether deterrence was achieved in these and other cases requires persuasive counterfactual scenarios, not easy to construct. retribution. again, retribution is not new, but it features prominently in post- cases. thanks to digital technology, nsa and cia sleuths, along with their european counterparts, can identify "bad guy" individuals and firms. in turn, the "bad guys" can be singled out for "special designation" status that hits their wallets and persona. for example, in the wake of the jared khashoggi's murder in istanbul, the us revoked visas of saudis connected to the assassination squad. this will inconvenience the designated individuals, even though the chief instigators, likely including crown prince mohammed bin salman, will not be brought to justice. on a much larger scale, in response to russia's annexation of crimea and intervention in ukraine, dozens of well-connected firms and elite russians were subject to financial, trade and travel sanctions. careful research by ahn and ludema ( ) plus fresh analysis presented at the workshop, shows that russian firms were severely affected, on average losing a quarter of their sales. but their pain will not persuade putin to vacate crimea or withdraw support from dissidents in eastern ukraine. indeed, as new research by ahn and ludema ( ) shows, putin shielded some "strategic firms" from the brunt of sanctions, at a cost calculated at nearly a half of the total pain imposed on russian firms by the targeted measures. as a rule, retribution against individuals and firmsa common response --does not achieve lofty foreign policy goals but it may deter future misdeeds. in fact, severe sanctions against major powers (russia and china) and against small countries with entrenched autocrats (north korea and cuba) rarely achieve advertised goals, but they do punish the targets. and this is important. in democracies, influential constituentsgiven voice in parliament and congressinsist on punishing foreign countries for their misdeeds. retribution is its own goal, and punishment gives satisfaction. justice is served. whether sanctions stand a chance of altering policies abroad is a secondary matter. rehabilitation. "mission impossible" aptly describes the role of rehabilitation in major episodes of the st century. russia will not abandon imperial aspirations, nor will cuba and north korea transition to democratic states. but by far the most ambitious goals of st century sanctions are to arrest china's military, economic, and technological rise. if anything, us trade, investment and technology sanctions will spur china's efforts, commercially divorced from the united states, to deepen cooperation with russia and a few western countries, and to rely on its own ample resources. former german chancellor helmut schmidt was scornful of sanctions on russia, calling them 'nonsense'. travel bans and asset freezes, he claimed, are symbolic and "affect the west as much as the russians". if chancellor schmidt were still alive, he would probably have still more scathing words for the current us economic campaign against china. at the workshop scholars presented new theoretical models designed to generate hypotheses worthy of testing against the findings recorded in new databases. the models have two common features: they are mathematically demanding, and they build on costs or benefits incurred by senders and targets. the models often distinguish between threats and imposition, drawing on insights from thomas schelling's famous canoe trip. in this section, new databases and new analyses by various scholars from the workshop are summarized to bring attention to their contributions. quoted by gerald schneider at the workshop. original source is at derek scally, "schmidt attacks western sanctions on russia as 'nonsense '," irish times, may , . thomas schelling ( ) . new and more comprehensive datasets have been constructed since research in the s and s. the main databases now used for empirical research include: • hufbauer, schott, elliott and oegg ( ) lord rutherford, the distinguished british scientist at the turn of the th century, declared, "all science is either physics or stamp collecting". rutherford might have classified the databases mentioned above as "stamp collecting". however, a priori hypotheses as to the impact of sanctions, often held with great conviction by leading statesmen, can only be tested with the benefit of these collections. first, ahn and ludema ( ) add to their own pioneering work that analyzed the cost to russian firms of us and eu sanctions in the wake of the crimean annexation and ukrainian occupation. collecting firm/individual data from the bureau van dijk (bvd) orbis and lexisnexis worldcompliance databases, the authors developed a model to assess the impact of sanctions at the firm level that features domestic government shielding of "strategic" firms from foreign measures. their results showed that strategic firms systemically outperformed non-strategic firms under sanctions, implying a cost to the regime that adds to the total cost of sanctions. besedes, goldbach and nitsch ( ) fresh research by grauvogel and attia ( ) revealed an additional and unexpected positive outcome from the termination of sanctions. political stability in the target country improved, if the country had resisted strong demands from the sender. resistance evidently enhanced the ability of political leaders to ward off internal rivals. in an innovative piece of workshop research, weber and schneider ( ) found that unilateral threats are more persuasive, but multilateral imposition stands a higher chance of success. the reasoning is that a unilateral sender, typically the united states, shows more resolve than a heterogenous group of senders, each with a different agenda. but when threats fail to convince the target, multilateral action brings greater heft to the bargaining table. meanwhile, joshi and mahmud ( ) presented a model that demonstrate how the frequency of sanctions and the frequency of violations of international norms depends on unilateral or multilateral actions using network structure theory. miromanova ( ) investigated whether sanctions on products identified at the -digit level of the harmonized system exerted a greater impact on the number of importing firms in the target country (the extensive margin) or on the import flow per affected firm (the intensive margin). she found that the extensive margin is the more important channel. portela and sanguinetti (forthcoming) found that single-party regimes are resistant to sanctionsand single party regimes are common across the globe. however, in countries where two or more parties compete for power there is less resistance, but no significant difference whether the government of the day is a military or personal regime, or a democracy. morgan (forthcoming) observed that the cost of sanctions might be better thought of as the enforcement cost (on the part of senders) and adjustment costs (on the part of targets) rather than more traditional metrics such as the volume of trade curtailed. he emphasized that threats are a bargaining tool, but that actual imposition means that diplomacyin other words, bargaining between two sovereignsfailed. president trump, with bipartisan support, has now proclaimed a second cold war, this time with china, letting the press use the term and not denying its essential accuracy. chinese provocations, according to trump, are the theft and appropriation of us technology, and commercial malfeasance by running an annual bilateral trade surplus of several hundred billion dollars. in the second cold war, unlike the first, trump is leading with economic sanctions, but a military buildup is likely to follow, whether trump or a democrat wins the presidential election. trump's sanctions take the form of high tariffs, both imposed and threatened, that could eventually cover nearly all us imports from china; a star chamber screening process, under cfius auspices, that will deny chinese investment in any us firm with a technology flavor; and criminal charges against the world's leading telecom company, huawei, and its chief financial officer, meng wanzhou, for stealing trade secrets and evading economic sanctions on iran; and the forced sale of tiktok assets in the united states. beyond these immediate measures, many americans are gripped with fear that china will dominate st century technologyquantum computing, g telecommunications, artificial intelligence, robotics, and much more. the response is to "decouple" (meaning divorce) us high-technology firms, as well as individual scientists and engineers, from their chinese counterparts. the us effort to constrict huawei's leadership in g technologyby denying components and marketsis only the first installment of a broad campaign. in addition, trump amplified such efforts by issuing executive orders that prevent the use of two chinese mobile apps, wechat and tiktok. broad restrictions on us technology exports to china, the access to chinese mobile products, and scientific cooperation with chinese institutions, are in the works. by far, this makes china the largest target of sanctions in the st century. as well, the nature of sanctions between the four great powersthe united states, china, russia and the european unionis changing. when one of the great powers targets a smaller countrysay mexico, south korea, georgia or equatorial guineait can use the traditional range of trade and financial measures. when the great powers target each other, more ingenuity is required. history has shown that great powers are relatively impervious to sanctions: they are not immune to economic damage, but they are highly resistant to changing course. military conflict between the great powers runs the risk of nuclear escalation, to be avoided at all costs. hence themes raised in this essay play an important role when great powers are at odds. of special note are financial restrictions, cyber assaults against leading firms and through social media, offers hard to refuse directed at private firms, weaponized tariffs and kindred investment and technology restrictions, and measures against specially designated leaders. conclusions st century sanctions practice has the flavor of evolution more than revolution. new weapons reflect, in part, new technologies (finance and cyber), and in part new statecraft (offers hard to refuse, weaponized tariffs and positive measures). as the geopolitical world shifted from a single hegemon to a system of great powers, players besides the united states became significant actors, with new target choices. pinpoint sanctions aimed at "bad guys" are popular, partly because they avoid moral qualms, partly because digital technology makes them effective. the new cold war was largely responsible for conflating commercial policy and sanctions policy. evaluated against traditional standards of "success"in other words, was the foreign goal achieved and did sanctions materially contribute to the outcome? - st century innovations have not made sanctions more effective. indeed, weber and schneider ( ) conclude that the effectiveness of eu, us and un sanctions for concluded episodes did not change much during the years between and . these finding echoes analysis done by huebauer, schott, elliott and oegg ( ). to be sure, measured by traditional standards, sanctions often promote regime change and humanitarian objectives in small or chaotic countries. but in big cases, goals appear to be evolving, leading practitioners to stress different metrics. deterrence, whether actual or imagined, looms large. as does punishment for its own sake. rehabilitation, often remote, has diminished as a measure of success. after this essay was written, covid- swept the world, creating the biggest economic downturn since the great depression of the s. it remains to be seen whether economic sanctions are more less numerous, and more or less effective, in dramatically different circumstances. china and economic sanctions: where does washington have leverage china's response to u.s.-south korean missile defense system deployment and its implications the magnitsky act, explained why iran will never give up on nuclear weapons trump and kim arrive in singapore for historic summit meeting us to revoke visas of saudis implicated in killing of writer crozet and hinz ( ) and haidar ( ); for capital flows iron curtain" speech transcript, the history place edges toward new cold-war era with china us trade balance in goods and services with china was $ huawei and top executive face criminal charges in the u.s the sword and the shield: the economics of targeted sanctions department of state the office of the chief economist (oce) working paper series cheap talk? financial sanctions and non-financial activity you're banned! the effect of sanctions on german cross-border financial flows collateral damage: the impact of russia sanctions on sanctioning countries' exports on target? the incidence of sanctions across listed firms in iran on the effects of sanctions on trade and welfare: new evidence based on structural gravity and a new database how do international sanctions end? towards a processoriented, relational, and signalling perspective sanctions and export deflection: evidence from iran. economic policy china's use of coercive economic measures the rd edition of economic sanctions reconsidered examining the debt implications of the belt and road initiative from a policy perspective sanctions in networks: the most unkindest cut of all the effects of embargoes on international trade: evidence from russia the new deterrent: international sanctions against russia over the ukraine crisis mds bury their mistakes, we don't have to: learning from empirical findings that suggest your theory is wrong the threat and imposition of economic sanctions - : updating the ties dataset arms and influence the response of russian security prices to economic sanctions: policy effectiveness and transmission aid sanctions and autocratic rule: does regime type matter helms-burton and canadian-american relations at the crossroads: the need for an effective, bilateral cuban policy making the world safe for liberalism? evaluating the western sanctions regime with a new dataset key: cord- -c s f f authors: arab-mazar, zahra; sah, ranjit; rabaan, ali a.; dhama, kuldeep; rodriguez-morales, alfonso j. title: mapping the incidence of the covid- hotspot in iran – implications for travellers date: - - journal: travel med infect dis doi: . /j.tmaid. . sha: doc_id: cord_uid: c s f f nan travel medicine and infectious disease journal homepage: www.elsevier.com/locate/tmaid after the first two months of the epidemics of coronavirus disease in the world [ , ] , caused by the severe acute respiratory syndrome coronavirus- (sars-cov- ), multiple epidemiological assessments in countries from asia, pacific, europe, and north america have been published [ , ] . nevertheless, there are countries, with a rapid increase and a high number of cases, with a lack of studies. this is the case of iran in the middle east. for these reasons, we have developed epidemiological maps of cases but also of incidence rates using official populations, by provinces, for covid- in iran using geographical information systems (gis). surveillance cases data from february to march , , officially reported by the iranian health authorities were used to estimate the cumulated incidence rates using reference population data on sars-cov- confirmed infections (cases/ , pop) and to develop the maps by provinces, using the gis software kosmo® . . during the first days of epidemics, cases of covid- were reported in the country, for a cumulated rate of . cases/ , population, reaching up to cases during march , ( fig. ). all the provinces have been affected, and rates ranged from . (boushehr) to . cases/ , population (qom) (fig. ). at qom, the first two cases were reported. covid- arrived at iran from china. the highest number of cases have been reported in tehran, ( fig. ) , followed by qom, , and by mazandaran, with . qom is the border with markazi and semnan, provinces with rates from . to . cases/ , population. from the gis-based maps, it is clear that spreading in the country is occurring from north-central provinces such as tehran and qom. till march , , there have been deaths ( . %, case fatality rate). while the number of cases seems to decrease during the last three days, this is not occurring with fatalities ( fig. ) . iran is the third country with the highest number of reported covid- cases after china, and italy, up to march , with , cases, being the first in the middle east region, and maybe becoming a significant source of imported cases in this area, in countries such as iraq, afghanistan, and pakistan, among others. while the highest number of covid- cases has been reported in the capital city, using gis and estimating the incidence/attack rates per province, that one is placed as the seventh, having more cases per population at qom, semnan, and markazi, among other provinces (fig. ) . a recent study, based on imported cases from iran, estimated that , ( % confidence interval: to , ) covid- cases would have had to occur in the country [ ] , assuming an outbreak duration of . months. even if it were considered that all imported cases of iran were identified in all states with certainty, the "best case" outbreak size was substantial ( , % ci: - cases), and far higher than reported case counts in february . all confirmed cases in saudi arabia are imported from iran and one from iraq and other cases are close contacts to those confirmed cases. imported cases from iran have been diagnosed at kuwait, bahrain, iraq, oman, qatar, among other asiatic countries, but also georgia, estonia, belarus, and even new zealand [ ] . the capital city of khorasan razavi ( . cases/ , population), mashhad, is the second-largest holy city in the world, attracting more than million tourists and pilgrims every year [ , ] , many of whom come to pay homage to the imam reza shrine (the eighth shi'ite imam). regardless of this epidemiological scenario, the iran outbreak of covid- is still beginning and complex. authorities have limited travel, and schools and universities have closed, as also have occurred in italy and spain, until the start of the holiday for persian new year nowruz on march , , as measures for spreading of this coronavirus [ ] . as there are severe limitations in the medical supplies available in the iranian public health system to deal with the current sars-cov- outbreak, international support, additionally to be provided from the world health organization, is needed in the country to mitigate the impacts of this epidemic, and to avoid additional spreading. for the moment of the proofs correction of this article, iran reached , cases, of them , in tehran, , in esfahan, and , in qom (march , ). going global -travel and the novel coronavirus history is repeating itself, a probable zoonotic spillover as a cause of an epidemic: the case of novel coronavirus the first novel coronavirus case in nepal an interactive web-based dashboard to track covid- in real time estimation of covid- burden and potential for international dissemination of infection from iran travelers give wings to novel coronavirus ( -ncov) covid- : preparing for superspreader potential among umrah pilgrims to saudi arabia covid- -the role of mass gatherings zahra arab-mazar infectious diseases and tropical medicine research center key: cord- -dfma kqc authors: badshah, syed lal; ullah, asad; badshah, syed hilal; ahmad, irshad title: spread of novel coronavirus by returning pilgrims from iran to pakistan date: - - journal: j travel med doi: . /jtm/taaa sha: doc_id: cord_uid: dfma kqc nan iran was initially reluctant to close its borders with its neighbors as religious tourism is a big part of its revenue generation and the international community has already imposed economic sanctions over it due to its nuclear program. every year approximately . million shia sect muslims from pakistan visit for a pilgrimage to various shrines in the cities of iran that include qom, tehran, tabriz, and mashhad. it has been estimated that there are over eight thousand sacred sites in iran alone and every year around eight million foreigners visit these shrines ( figure ). the pilgrimage mostly includes visits to cities like karbala, najaf, kufa, samara, and baghdad in iraq and several places in damascus in syria. these religious visits peak around the birth and death anniversaries of various religious leaders. besides these specific anniversaries, the early spring season is a favorable time for the pilgrimage to these holy estimation of coronavirus disease (covid- ) burden and potential for international dissemination of infection from iran covid- battle during the toughest sanctions against iran isolation, quarantine, social distancing and community containment: pivotal role for old-style public health measures in the novel coronavirus ( -ncov) outbreak the positive impact of lockdown in wuhan on containing the covid- outbreak in china the authors declared no conflict of interest. no funding was utilized for this work. key: cord- - puccigu authors: maarefvand, masoomeh; hosseinzadeh, samaneh; farmani, ozra; safarabadi farahani, atefeh; khubchandani, jagdish title: coronavirus outbreak and stress in iranians date: - - journal: int j environ res public health doi: . /ijerph sha: doc_id: cord_uid: puccigu iran has faced one of the worst covid- outbreaks in the world, and no studies to date have examined covid- -related stress in the general iranian population. in this first population-based study, a web-based survey was conducted during the peak of the outbreak to assess stress and its correlates in the iranian population. a -item, valid, and reliable questionnaire, including items on demographic characteristics and past medical history, stress levels, awareness about signs and symptoms of covid- , knowledge about at-risk groups and prevention methods, knowledge about transmission methods, trust in sources of information, and availability of facemasks and sanitizers, was deployed via social and mass media networks. a total of iranians participated in the study where the majority of the participants were females ( . %), employed ( . %), from developed provinces ( . %), without chronic diseases ( . %), and with ≥ years of formal education ( . %). the mean age of study participants was . years (range = – ), and the average stress score was . (sd = ± . ). stress score was significantly higher for females, those who were – years old, housewives, those with chronic diseases, individuals who were aware that there is no vaccine to prevent covid- , those who could not get facemasks or sanitizers, and individuals with higher knowledge about at-risk groups (p < . ). there was a significant correlation of stress scores with knowledge about prevention methods for covid- (r = . , p = . ) and trust in sources of information about covid- (r = − . , p = . ). all of the predictors, except knowledge of two important at-risk groups and education, had a significant effect on stress scores based on a multivariate regression model. the covid- outbreak could increase stress among all population groups, with certain groups at higher risk. in the high-risk groups and based on experience with previous pandemics, interventions are needed to prevent long-term psychological effects. professional support and family-centered programs should be a part of pandemic mitigation-related policymaking and public health practices. since the emergence of the covid- outbreak in china in december , the disease has rapidly spread across the world [ ] [ ] [ ] [ ] [ ] [ ] [ ] . by june , covid- had affected more than million people who tested positive, and almost half a million people died worldwide [ ] . iran reported its first confirmed case of covid- infection in february in qom [ ] . soon after, other provinces in iran reported covid- cases, and as a result, schools and universities were closed in the affected provinces, and several cultural, sports, and religious gatherings were canceled as well. in early april , there were covid- -associated deaths worldwide, with a large proportion of deaths being reported from iran [ ] . travel and other types of warnings and advisories have been issued by the iranian government regularly since the first case was found [ ] . despite growing attempts to increase public awareness on prevention, people around the world were suffering from widespread fear, stress, and anxiety. this could be more prominent in areas of peak transmission and spread, with people feeling stressed and anxious about the transmission of the disease. for example, a major psychological burden on the public was identified during the peak of the covid- outbreak in china [ ] [ ] [ ] . young people, people who spent too much time searching for information or working on the frontlines, healthcare workers with exposure to confirmed or suspected cases, and survivors of covid- had the highest levels of anxiety, depression, and mental distress [ ] [ ] [ ] . the outbreak itself and the control measures may lead to widespread fear and panic, especially stigmatization and social exclusion of confirmed patients, survivors, and family members, which may escalate into further negative psychological reactions, including adjustment disorder and depression [ ] . during the covid- pandemic, chinese individuals, especially those who were quarantined and had limited access to face-to-face communication, experienced serious psychological problems (e.g., anxiety, psychosis, depression). [ ] . in the published literature, post-traumatic stress disorder (ptsd) and depressive disorders have been reported as prevalent long-term psychological consequences of epidemics [ ] . patients with confirmed or suspected covid- may experience fear of the consequences of infection with a potentially fatal new virus, and those in quarantine might experience boredom, loneliness, and anger. for example, in the early phase of the sars outbreak, a range of psychiatric morbidities, including persistent depression, anxiety, panic attacks, psychomotor excitement, psychotic symptoms, delirium, and even suicidality, was reported [ ] . however, much of the evidence on covid- relating to the stress of the pandemic has emerged from china, and few studies have examined the burden of covid- -related stress in the general population from other countries. one of the worst covid- outbreaks was reported from iran, and no studies have examined the stress in the general iranian population or in the middle east. thus, the purpose of this study is to measure iranians' stress levels and the associated factors during the covid- outbreak. a web-based cross-sectional study was conducted in the general iranian population, targeting internet-using volunteers. a multi-item online questionnaire was deployed via the main page of the iranian scientific association of social work to the general public. this valid and reliable questionnaire was developed based on a comprehensive literature review and expert panel guidance to measure perceptions and distress during an influenza pandemic [ , , , ] . study participants were recruited using social networks such as telegram, whatsapp, and instagram. this questionnaire was online for days (from february to march ), and iranians took the survey. the questionnaire could be taken online using a secure html interface, where all security conditions for data and personal information were provided to potential study participants. each questionnaire could be completed only once per device. respondents were required to answer every question. they were able to review or change their answers before submitting final responses to the questionnaire. participants were informed about the purpose of the study and emphasized that their participation was voluntary and anonymous. this study was approved by the iranian scientific association of social work ( /p/ ) for ethical procedures and scientific protocols. a -item questionnaire was used to collect data and information in this study . the questionnaire included items about demographic characteristics and past medical history, stress levels, awareness about signs and symptoms of covid- , awareness about at-risk groups, knowledge about covid- transmission methods, knowledge about effective covid- prevention methods, awareness of the lack of a vaccine to prevent covid- , trust in information sources about covid- , and availability of facemasks and sanitizers. the questionnaire included six questions about demographic characteristics and past medical history to assess gender, age, province of residence, years of formal education, employment status (full-time, part-time, unemployed, housewife, student, or retired), and chronic diseases (including respiratory problems such as asthma and lung disease, cancer, stroke, diabetes, heart diseases such as heart failure and high blood pressure, kidney diseases such as kidney failure, liver diseases such as hepatitis and cirrhosis, psychiatric illnesses such as depression and anxiety, and alcoholism or drug addiction). stress-related data was collected by asking five questions about the level of feeling calm, tense, upset, relaxed, and worried. studies show that participants who receive short questionnaires are more likely to respond [ ] . hence, the expert panel chose a brief set of stress-related questions that have been used in an epidemic situation [ ] . for each question, participants could select responses from a set of options (very high, high, moderate, low, and very low, with a score range of - for each question). the mean of the responses on the five questions measures the stress level of individuals, and a higher score indicates higher stress. internal consistency reliability of the stress scale was assessed by computing cronbach's alpha from the total sample of participants and was found to be high (α = . ). additionally, there were five questions about awareness of signs and symptoms of covid- (true or false, with a score range of - for each question), two questions about the awareness of at-risk groups (true or false, with a score range of - for each question), four questions about the knowledge about covid- transmission methods (true/false/not sure with a score range of - for each question), and one statement about the awareness of lack of covid- prevention vaccine: "there is no vaccine for covid- " (true/false/not sure with a score range of - ). a group of questions (n = ) was included about the knowledge of effective covid- prevention methods (true/false/not sure, with a score range of - for each question). the internal consistency reliability for this scale (n = questions) was assessed by computing cronbach alpha and was found to be reasonable (α = . ). ten questions were about the participants' trust in various sources of information about covid- . sources of information included people they interact with (such as family, friends, and colleagues), health professionals, official websites (such as the ministry of health website), health centers (such as hospitals and public health centers), social networks (such as whatsapp, telegram, and instagram), television, radio, newspapers, online news agencies, and international websites such as who website. participants could indicate their level of trust in each of these sources using a -point likert scale (very much, much, moderate, low, very low, and not trustable, with a score range of - for each question). the mean of the score on the trust-related questions was the average of individual scores of trust in sources of information about covid- . to assess the internal consistency reliability of this scale on trust in sources of information, we computed a cronbach alpha from the final sample of respondents, and the reliability was found to be high (α = . ). the questionnaire also included questions about the availability of facemasks and disinfectant gel and sanitizers to assess the individuals' access to these protective strategies (yes/no, with a score range of - for each question). data were in excel file and were checked for duplicates and any errors before importing and analyzing using ibm spss (chicago, il, usa). in the primary approach, a descriptive analysis of demographic and background characteristics of study participants was conducted. next, we compared the average stress scores using t-tests or anova based on demographic characteristics, awareness about signs and symptoms of covid- , awareness about at-risk groups, knowledge about covid- transmission methods, knowledge about covid- prevention methods, awareness about the unavailability of covid- prevention vaccine, trust in sources of information, and the availability of facemasks and sanitizers. the effect of the predictor variables on stress was assessed by univariate and multivariate generalized linear models. first, each predictor variable was entered into the univariate model separately, then the variables that had p-values < . were entered into the multivariate model simultaneously. statistical significance was assumed at p < . . a total of iranians with a mean age of . years (range = - years) participated in the study. table illustrates the demographic characteristics of the study population and average stress scores differences among groups. the majority of the study population were females ( . %), employed ( . %), from developed provinces ( . %), without chronic diseases, and had more than or more years of formal education ( . %). the majority of participants reported that during the last week, they could not get facemasks ( %) or sanitizers and disinfectant gel ( . %). less than half ( . %) of the participants were aware of at least three important symptoms of covid- , and most of them ( . %) knew that elderly people and individuals with background diseases have a higher risk of infection. the majority of participants had very good knowledge about covid- transmission ( %) and prevention ( . %) methods and knew that there is no approved vaccine for covid- ( . %). most of the participants reported that they had high trust in various sources of information about covid- ( . %). the average scores of participants' knowledge about the transmission and prevention methods for covid- were . (± . ) and . (± . ), respectively. the average score on trust in the sources of information about covid- was . (sd = ± . ). the average stress score for the study population was . (sd = ± . ). the relationship between demographic characteristics and stress was measured by t-test and anova. the mean of stress scores was significantly higher for females, people in the age group of - years, housewives, those with chronic diseases, individuals who were aware that there is no vaccine to prevent covid- , those who could not get facemasks or sanitizers, and individuals who knew about at-risk groups (p < . ) ( table ) . anova was performed to study the relationship between stress and awareness about symptoms and at-risk groups. the mean of stress scores was statistically significantly different by levels of knowing two important at-risk groups (p < . ), but there was no significant difference by knowledge on five important symptoms (p > . ). pearson's correlation coefficients showed that participants' knowledge about transmission methods of covid- did not correlate with stress scores (r = . , p = . ), whereas there was a statistically significant correlation of stress scores with knowledge about prevention methods for covid- (r = . , p = . ) and trust in sources of information about covid- (r = − . , p = . ). univariate and multivariate generalized linear models were fitted on the stress scores. demographic variables (including gender, age, employment, education, province, awareness of no approved vaccine for covid- , background disease), knowledge about transmission and prevention methods, awareness about signs and symptoms and at-risk groups, and trust in sources of information about covid- were individually entered in the univariate models. subsequently, variables that had p-values < . were simultaneously entered in the multivariate model ( table ). all of the variables, except knowledge on the two important at-risk groups and education, were significantly associated with stress scores in the multivariate model. in this first large national study from iran, high-levels of stress were reported by the general public during the covid- outbreak. unfortunately, the long-term effect of such high levels of stress, resulting in serious mental health issues, would be an additional burden on the iranian public and healthcare system as an aftermath of the pandemic. our findings provide further evidence of the mental health crises created by emerging infectious disease pandemics. following the outbreaks of hiv, ebola, and sars in other countries, the prevalence of psychological symptoms was reported, and many individuals had experienced long-lasting psychiatric problems [ , [ ] [ ] [ ] . there is an interaction between external conditions (threat) and internal ones (vulnerability) that influences the level of risk for debilitating stress that could lead to mental health problems [ ] [ ] [ ] [ ] . in this study, we identified unique groups with high stress. first, across various studies, women have reported high stress. in this study and given the pandemic, it is highly likely that women face multiple and additional stressors, including work, taking care of others in the household, arranging for materials and supplies for the household, and arranging school work and education for children. their routines have been dramatically changed and profoundly disrupted, causing more stress. second, individuals with chronic diseases have higher stress in general, and this could be accentuated by the lack of sanitizers, protective masks, and the awareness of lack of a vaccine to prevent covid- infection. the lack of protective supplies and heightened awareness could have severely impacted even those without chronic diseases or lifestyle problems. third, those in the middle age groups and working-class could have more stress due to multiple social, economic, and personal stressors. it could be possible that they are worried about losing their jobs or their income. those who had part-time jobs were more stressed than those who had full-time jobs. the instability of part-time jobs, low incomes, and lack of savings could affect some groups more than others. additionally, healthcare access, coverage, and the ability to pay are influenced by employment, and this could be a major stressor for middle-aged working-class individuals. fourth, there is an interesting relationship between education and stress levels. individuals with lower stress had the lowest and highest education levels compared to those who had - years of formal education. one possible reason could be that during the covid- outbreak in iran, there was a lot of misinformation circulating on social media networks. those with lesser education were not generally able to read the information in other languages (such as english) and had lesser access to mass media and technology to use social media. however, with increasing education, this stress seemed to have been alleviated, possibly due to the ability to screen for and use authentic information [ ] [ ] [ ] [ ] [ ] [ ] . similar to many epidemics in the past and the response of various governments, it appears that mental health care is not a priority for governments during such national crises, epidemics, and disasters. in addition, factors such as the rural-urban divide, lack of access to technology and authentic information, income inequality, availability of healthcare or other resources, lack of awareness, and literacy could pose additional burdens and cause psychological distress [ ] [ ] [ ] [ ] , [ ] [ ] [ ] . [ , [ ] [ ] [ ] [ ] . during these epidemics, the consequences on the psycho-social well-being of at-risk communities were largely overlooked. for example, in the ebola-affected regions, few measures were taken to address the mental health needs of confirmed patients, their families, medical staff, or the general population, and this resembles the responses to all recent epidemics. the absence of mental health and psycho-social support systems and the lack of well-trained psychiatrists and/or psychologists in these regions increased the risks of psychological distress and progression to psychopathology [ ] [ ] [ ] [ ] [ ] . continuous surveillance and monitoring of the psychological consequences for outbreaks should become a part of disaster and pandemic preparedness efforts worldwide. moreover, interventions should be geared towards the most affected and vulnerable individuals as a part of a population mental health promotion strategy [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . currently, according to the notification of basic principles for emergency psychological crisis interventions by the national health commission of china, mental health care should be provided for patients with covid- , close contacts, suspected cases who are isolated at home, patients in fever clinics, families and friends of affected people, health professionals caring for infected patients, and the public [ ] [ ] [ ] [ ] . however, xiang and colleagues claim that the mental health needs of patients with confirmed covid- , patients with suspected infection, quarantined family members, and medical personnel have been poorly handled and believed that the organization and management models for psychological interventions in china must be improved [ ] . similar challenges are now being seen across the severely affected countries and will continue to emerge in regions that will be severely affected with covid- or any future pandemics and epidemics [ ] [ ] [ ] . social media, fear and misinformation, myths, and rumors have added to the global burden of information overload and psychological distress [ ] [ ] [ ] . pandemic response policies should include mental health promotion practices as a key initiative in dealing with the psycho-social burden of pandemics. additional research is needed in the form of long-term prospective studies to assess the causal mechanisms and impact of stress caused by the covid- pandemic. the results of this study are subject to several potential limitations. first, the study results are restricted by all traditional limitations of cross-sectional study designs (e.g., reliance on self-reported behaviors, recall bias in participants, socially desirable responses, and the inability to establish cause-and-effect relationships). second, this study measured the prevalence of variables rather than incident cases, and we were unable to assess the levels of variables before covid- outbreak in iran as a control. third, stress patterns in individuals often have a variety of simultaneous influences that need to be accounted for. fourth, a major threat to external validity is that the sample is limited in nature and extent (e.g., dominated by female participants, those who were employed and < years old, and from developed provinces). this would mean that the results of the study cannot be generalized to several groups of individuals across the region and other countries. despite these limitations, our study is the first and largest study across the middle east, with robust measures, of covid- -associated stress and the factors associated with stress during the pandemic. based on our field experiences and a comprehensive review of literature, we recommend the following strategies for mental health promotion and disease mitigation in communities during the covid- pandemic or any future epidemics or disasters [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . people may speculate and/or spread rumors, myths, and misinformation about covid- or infectious disease agents. this has been a major problem with the current pandemic, given the widespread use of mass and social media methods, increasing stress and spreading panic. it is essential to encourage the public not to spread misinformation and inform them of verified and credible sources of information. governments should engage in effective and efficient risk communication and share information regarding disease prevention methods and strategies. governments and scientific organizations should provide clear information about covid- or any infectious disease-related symptoms, signs, transmission methods, and prevention strategies through scientific websites, daily briefings, and public awareness campaigns. this will help citizens deal with pandemics more effectively and also mitigate the chain of transmission and spread of disease. denying epidemics and the associated population health risks will cause a loss of confidence in the government and credibility of scientific organizations, which poses an additional burden on disease management and population health services. lack of effective flow of information and disease-related data and statistics has been a major problem worldwide with the covid- pandemic. people may be worried, anxious, and depressed due to the constantly changing alerts, media cycle, and social or mass media coverage regarding the spread of covid- . therefore, providing psychological support services by volunteer social workers, psychologists, psychiatrists, and counselors could help alleviate stress and persistent excessive arousal. in this regard, long-distance psycho-social support (including telecounseling and online services) can be deployed. because people's routines may change dramatically during pandemics and quarantine periods, they should receive compassionate services and guidance on becoming familiar with alternative programs and lifestyles. opening online platforms with audio-and video-based information and demonstrations and providing counseling services and telephone helplines for those with new-onset symptoms or existing mental illnesses can be used until routine mental healthcare services are available. grief counseling for people who have lost their family members due to covid- , or those who lose family members due to other epidemics and disasters, is critical. strategies such as stress reduction, conflict resolution, crisis call centers, child protection, and custody conflict mitigation are some areas of emphasis for psycho-social service providers. it is also so important to pay attention to the possibility of deprived families who have infected members due to the stigma caused by the disease, and provide special support for them to ensure their access to essential facilities and services. while our study did not specifically look at frontline workers, and essential service and healthcare professionals, existing evidence indicates the heavy toll that pandemics such as covid- can take on the physical and mental health of certain at-risk groups. disrupted sleep-wake cycle, patient and client overflow, long working hours, changing practice protocols, fractured communication, and shortage of materials, equipment, and supplies can cause high stress among these populations in disasters and pandemics. individual-level, intrapersonal, and organizational level interventions to reduce stress and burnout should be implemented (e.g., shift rotations, work hours limitation, employee assistance programs, enforcing protocols, coordinated workflow and information processes, just to name a few). a major stressor among individuals and families during epidemics is financial or economic. governments should support employers and strengthen social protection, especially for vulnerable families (including elder people, disabled or sick people, and female-headed households). family-friendly policies and programs are necessary to support affected people during the covid- pandemic (including employment and income protection, flexible working arrangements, paid leave to care for family members and access to health care and medical services, direct benefit transfers, food distribution for needy families, among others). governments across the world have rolled out stimulus plans and advisories for tax and debt moratoriums that should provide temporary assistance to needy families. voluntary activities during this period can significantly contribute to social solidarity and social cohesion. it is recommended that these activities be encouraged. skilled volunteer professionals could be involved in a wide range of activities to reduce the economic, social, and health impacts of the epidemic. nonprofit organizations can play a key role in mobilizing skilled volunteer professionals. the no-harm principle is essential to providing volunteer services during an epidemic. the covid- outbreak has severely increased psychological distress among people in iran. it has changed people's routines in several aspects and made it difficult to cope with the new situation. affected people, especially vulnerable groups, need professional support and community-based mental health promotion services to deal with the multiple stressors and burden imposed by the current pandemic. family-centered social and economic policies and programs are necessary to support people during the covid- epidemic. employment and income protection, flexible working arrangements, paid leave to care for family members and access to medical services, cash transfers, and food distribution for low-income or no-income families, and providing long-distance psycho-social interventions are some examples of family-friendly policies to support people during this pandemic or any future epidemics of a regional or global nature. outbreak of pneumonia of unknown etiology in wuhan china: the mystery and the miracle early transmission dynamics in wuhan, china, of novel coronavirus-infected pneumonia a 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intervention for public mental health crisis this article is an open access article distributed under the terms and conditions of the creative commons attribution (cc by) license we acknowledge all participants involved in this study. ronaghi voluntarily assisted us in developing the online questionnaire and supported the research team in preparing a page on the isasw website. authors would also like to thank lili derakhshan, maryam latifian, anis rookhosh, roghayyeh yazdani, leila fatehi, fatemeh nourshargh, zahra khanlary, mahboubeh tavakoli, samaneh mohebbi, and ayoub mohammadi for their support and efforts for the survey announcement. the authors declare no conflicts of interest regarding this study. key: cord- -j bf eme authors: ghalyanchi langeroudi, arash; karimi, vahid; tavasoti kheiri, masoumeh; barin, abbas title: full-length characterization and phylogenetic analysis of hemagglutinin gene of h n virus isolated from broilers in iran during – date: - - journal: comp clin path doi: . /s - - -x sha: doc_id: cord_uid: j bf eme h n avian influenza a viruses (aiv) have become panzootic in eurasia over the last decade and are endemic in iran since , and inactivated vaccine has been used in chickens to control the disease. the hemagglutinin (ha), one of eight protein-coding genes, plays an important role during the early stage of infection. to study their evolution and zoonotic potential, we conducted an in silico analysis of h n viruses that have infected broiler in tehran province, iran between and . the complete coding region of ha genes from nine h n subtypes isolated from chicken flocks in tehran province during – was amplified and sequenced. sequence analysis and phylogenetic studies of h n subtype viruses on the basis of data of viruses in this study and selected strains are available in the genbank. sequence and phylogenetic analyses revealed a large number of similar substitution mutations and close evolutionary relation among sequences of ha. the isolates possessed two types of amino acid motif –r–s-s-r/g-l- and -r-s-n-r/g-l- at the cleavage site of ha. the results showed that all nine representative h n isolates belong to low pathogenic aivs since none of the amino acid sequences at the cleavage site of the ha of the isolates possessed the basic motif required for highly pathogenic viruses (r-x-r/k-r). six out of these nine isolates possessed leucine at position , which prevails in the sequences found in human strains. phylogenetic analysis showed that all our isolates belonged to the g -like sublineage. also, these isolates showed some degree of homology with other h n isolates, e.g., . – . . % with qu/hk/g / and . – . % with pa/narita/ a/ . the available evidence indicates that ha genes of h influenza virus circulating in iran during the past years were not well conserved. our finding emphasizes the importance of reinforcing aiv surveillance, especially after the emergence of high pathogenicity in poultry in iran. h n viruses have widely circulated in the world since their first detection from turkeys in wisconsin in (homme and easterday ) . h n influenza viruses have become panzootic in eurasia during the past decade and have been isolated from terrestrial poultry worldwide. the h n subtype virus is a conspicuous member of the influenza family because it can infect not only chickens, ducks, and pigs but also humans (kwon et al. b ). avian influenza viruses (aiv) are segmented, negative-sense, single-stranded rna viruses of the family orthomyxoviridae and are divided into five genera: influenza a, b, c, thogtovirus, and isavirus (fields et al. ). the aiv genome consists of eight segments of negative-sense, single-stranded rna that encode at least ten proteins including two surface glycoproteins [hemagglutinin (ha) and neuraminidase (na)], nucleoprotein, three polymerase proteins (polymerase basic , pb , and polymerase acidic), two matrix (m and m ) proteins, and two non-structural (ns and ns ) proteins. influenza a viruses are classified into a number of subtypes based on antigenic differences in their two surface glycoproteins, ha ( subtypes) and na (nine subtypes) (fields et al. ; harder and werner ) . one of the surface viral proteins, ha, undergoes frequent antigenic variation and plays a crucial role in the pathogenicity of influenza viruses. analysis of receptor specificity of ha has indicated that ha is very important for virus transmission and is a major determinant in host range. ha is involved in the early stages of infection, causing the binding of the sialic acid receptor present on the host cell surface, and leading to fusion of the viral and endosomal membrane and subsequent entry into the host cell. the ha genes have vital relation to viral pathogenicity, antigenicity, and host range of influenza viruses, although some researchers indicated that these traits are polygenic (jordan ; swayne ; webster et al. ) . aivs in poultry have been categorized into two groups according to their ability to produce clinical signs and the severity of disease, the low-pathogenicity aivs and highly pathogenic aivs. the difference in the pathogenicity is mainly determined by the ha gene and the presence of additional basic amino acids at the proteolytic cleavage site. ha of low-pathogenicity aivs is cleaved by trypsin-like proteases that are associated with respiratory and intestinal epithelial cells, confining the infection to these sites. in contrast, ha from hpaivs can be cleaved by the aforementioned proteases and also by ubiquitous furin proteases, leading to a generalized infection (alexander ; jordan ; swayne ) . globally, there are two major, distinct gene pools of h n avian influenza viruses: the north american and the eurasian. the eurasian lineage can be further divided into three major sublineages-the g lineage, represented by a/ quail/hong kong/g / (g -like); they lineage, represented by three prototype viruses a/duck/hong kong/y / (y -like), a/chicken/beijing/ / (bj -like), and a/ chicken/hong kong/g / (g -like); and the korean lineage, represented by a/chicken/korea/ -p / (korean-like) and a/duck/hong kong/y / (y -like) (guan et al. ; matrosovich et al. ) ; generally, the h n -affected chickens show mild to severe respiratory signs, edema of the head and the face, and decreased egg production accompanied with soft-shelled or misshaped eggs. the mortality is usually - % depending on the type of husbandry. coinfection of h n viruses with bacteria such as staphylococcus aureus and haemophilus paragallinarum or with attenuated coronavirus vaccine exacerbated the disease (jordan ; xu et al. ) . in iran, the h n virus was first isolated from chicken in in qazvin province and is now the most prevalent subtype of influenza virus in poultry in iran. mortality rates in some broiler farms in iran are up to % (nili and asasi ; nili and asasi ; vasfi marandi et al. ) . however, the isolate was characterized as non-highly pathogenic in the laboratory. mixed infections of influenza virus with other respiratory pathogens have been found to be responsible for such a high mortality, resulting in great economic losses. mosleh et al. ( ) showed that the iranian h n influenza viruses had the ability to replicate in some organs like the spleen, kidney, and other organs, which was previously unexpected for low virulence avian influenza virus. these results indicated that iranian h n virus may cause some changes in their structure (mosleh et al. ). the association of high mortality in recent years and report ofh n and h n in wild birds in iran raised the probability of a new genetically modified avian influenza virus (shoushtari et al. ). in the present study, the ha gene of h n ai viruses that has been isolated from commercial chickens in iran during - was sequenced. the aim of the present research was to elucidate the phylogenic and evolutionary relationships of ha genes (full length) of h n among these isolates and examine the relationships among these viruses and other viruses isolated from avian in the neighboring countries or areas. sample collection (tracheal swabs and fecal samples) was performed according to the standard method from suspected broiler (showed clinical signs) specimens in tehran province in . specimens were stored at − °c until use. samples were collected in a × phosphate buffer solution (ph . ) containing antibiotics ( , iu/ml penicillin and mg/ml streptomycin sulfate) and an antifungal ( iu/ml nystatin). other virus isolates (four from nine) were available at the central lab of the department of clinical science, faculty of veterinary medicine, university of tehran (swayne et al. ; peiris et al. a ). ten-day-old specific pathogen-free (spf) embryonated chicken eggs were inoculated. these eggs were incubated at °c for up to days, embryonic death was monitored, and then allantoic fluid was collected under routine conditions, and the presence of viruses was determined by hemagglutination assay (ha). the identification of virus subtype was determined by a standard hemagglutination inhibition and neuraminidase inhibition tests using polyclonal chicken antisera. the allantoic fluids containing virus were harvested and stored at − °c until use. ha test negative samples were given two more passages and tested again before being declared negative for aiv isolation. the chicken isolates produced severe disease signs such as tracheitis, respiratory congestion, and rapid mortality (capua and alexander ). viral rna was extracted from infected allantoic fluid using rnx reagent according to the manufacturer's instruction. briefly, in an rnaase-free . -ml tube, μl of rnx tm-plus solution (cinnagen, iran) was added to -μl allantoic fluids. after shaking, μl of chloroform was added, and the mixture was centrifuged at , ×g at °c for min. equal volume of isopropanol was added to the upper phase in a new tube. the mixture was centrifuged at , ×g at °c for min. the supernatant was discarded, and μl of % ethanol was added to the pellet. after centrifugation at , ×g for min at °c, the supernatant was discarded, and the pellet was dried at room temperature for few minutes. finally, the pellet was diluted in μl depc water. to help in dissolving, the tube was placed in − °c water bath for min and stored at − °c for rt-pcr reaction (sambrook et al. ). reverse transcription was done by using oligonucleotide influenza universal primer uni : -agc aaa agc agg- with revertaid first strand cdna synthesis kit (fermentas, canada). amplification of the ha gene was carried out by pcr as described by using one pair of specific primers. primer sequences are available upon request. the reaction mixture ( μl) contained μl of cdna, pmoles of forward and reverse primers ( μl), and cinnagen master mix (cinnagen, iran). the amplification protocol was : one step of denaturation at °c for min, cycles of °c/ s, °c/ s, and °c/ s, and final extension at °c for min. the pcr products were separated by electrophoresis in % agarose gel. pcr products were purified with the qiaquick gel extraction kit (qiagen, valencia, ca, and usa) (capua and alexander ; hoffmann et al. ; peiris et al. a ). purified pcr products for sequencing were cloned into plasmid for ta cloning with inst/a cloning kit (fermentas, canada) according to the manufacturer's instruction. plasmid extraction from positive clone was carried out by qia miniprep plasmid extraction kit (qiagen, valencia, ca, usa). following digestion with ecori (fermentas, canada) to confirm the insertion, the nucleotide sequences were analyzed by plasmid sequencing on an automated dna sequencer (applied biosystems, foster city, ca). the sequences were resolved using the abi prism collection program (perkin-elmer, foster city, ca) with m (forward and reverse) universal primer (sambrook et al. ). phylogenetic analysis was carried out by analyzing the data obtained here with those of other sequences of aiv belonging to the main h n lineages, ( ) sequences of h n viruses isolated in iran and asian and european countries from the genbank database (table and fig. ). nucleotide and deduced amino acid sequences were edited with the clc main workbench software. full length of the amino acid ( aa) of the ha gene was used to study and construct the respective phylogenetic trees. the phylogenetic analysis was performed with the mega (phylogeny inference package) software, version . distance-based neighbor-joining trees were constructed using the tamura-nei model available in the program mega, version . the robustness of the phylogenetic trees was assessed by , bootstrap replicates. bootstrap values lower than were omitted. the percentage similarity/difference in nucleotide sequence was estimated using clc main workbench software (clc, denmark). all amino acids were expressed by a single-letter code. identification and comparison o f n-glycosylation sites into reported protein sequences of ha were performed by an online server scanprosite (http:// prosite.expasy.org/scanprosite) (dudley et al. ) . the amino acid sequences for all h n influenza viruses used in this study are available in the genbank under accession numbers aca through aca (presented in table ). a total of nine viruses were sequenced from chickens from to in tehran province, iran. nine viruses were sequenced and compared with other h n sequences available in genbank. these isolates were compared with those of some available full-length genomes of h n strains isolated during the period - and deposited in the genbank database. the amino acid sequences of the ha were deduced from the nucleotide sequences. the positions of each amino acid residue were numbered according to the ha sequence of human h subtype isolate/aichi/ / . the deduced amino acid sequences of the ha proteins in cleavage site were aligned and compared among the h n avian influenza viruses. amino acid sequences at the cleavage site of the ha of the isolates possessed -p-a-r-s-s-r-g-l-motif, except for two isolated: th (a to t) and fig. phylogenetic relationships of ha genes of representative influenza a viruses isolated in iran, middle eastern, eurasian countries, and usa. the amino acid ranges of segments that were used for drawing phylogenic trees were the following: ha ( - ). trees were generated by the neighbor-joining method with the mega software. numbers above branches indicate neighbor-joining bootstrap values. h n viruses that were characterized in this study are indicated by red circles, iranian pink rectangles, and euroasian lineage green triangles. virus name and abbreviations are shown in table th (s to n). all changes in region of coding cleavage site are available in table . analysis of potential n-glycosylation (glycosylation) site (pgs) motifs n-x-s/t in the ha molecule of mentioned study viruses through psoeitscan revealed seven pgss: (aa to ), (aa to ), (aa to ), (aa to ), (aa to ), (aa to ), and (aa to ) were all the same: nst, nvs, nrt, ntt, nvs, ngt, and ngs, respectively, except in th and th ( , , , , and in ha and and in ha in h numbering; table ). in the present study, seven from nine h n iranian isolates possessed amino acid -l (numbered according to h ) at the receptor binding site, indicating its potential to infect humans. of the three eurasian-sublineage reference strains studied, amino acid -l is found in qa/hk/g / , human isolate hk/ / , and the dk/hk/y / (wan and perez ) . receptor binding sites of the isolates in this study are somewhat similar to human isolate (h ) which could be a danger. in our nine isolates, the amino acid residues of − , , , , , , in receptor binding sites are identical (table ) . evolutionary relationships of ha amino acid sequences were determined by comparing h n isolates from - with the established eurasian h n lineages: namely, the g , g , y , and y presented by their respective prototype viruses. iranian h n isolates from broiler formed a single group, which was subdivided into two subgroups. our study showed that the has of most isolates from commercial chickens in iran from to belonged to one lineage as well as those of hk/g / strains (g -like). also, these isolates showed some degree of homology with other h n isolates, e.g., . - . . % with g and . - . % with narita-parakeet . the aa sequences of this study were compared with prototype a/turkey/wisconsin/ . the results indicated that aa homology among these isolates with wisconsin- was between . % (th ) and . % (th ). amino acid comparisons of isolates that were sequenced in this study showed a range of minimum homology ( . %) between th and th isolates to maximum homology ( . %) between th and th . in recent years, avian influenza (ai) has caused major economic harms in iranian poultry industry. the latest iranian h n isolate has been reported to be low pathogenic for spf chickens (data not shown). however, recent h n outbreaks have caused up to % mortality rate and are the only influenza subtype in the chicken population in iran (nili and asasi ; nili and asasi ) . although the pathogenicity of avian influenza viruses is a polygenic property, the amino acid sequence of the connecting peptide of ha is considered to be its major determinant. a virus name and abbreviations as shown in table b numbered according to h ha numbering the pathogenicity of h and h influenza viruses is associated with the presence of multiple basic amino acids at the cleavage site of ha, yet no motif standards have been established to evaluate the high or low pathogenic h subtype viruses. however, guo et al. supposed that only one nucleotide substitution could change serine to arginine and produce the basic motif required for highly pathogenic viruses (guo et al. ). however, the presence of this particular motif also emphasizes that these viruses have the potential to become pathogenic should they acquire any further nucleotide substitutions in the ha-connecting peptide region. the finding suggests that the h n influenza viruses circulating in poultry in iran have the potential to become highly pathogenic. all the h viruses tested (except th and th ) in this study possessed the motif of -p-a-r-s-s-r/g-l-, which was identical to the sequences of gl and y . all recurrent h n viruses possessed the single basic amino acid at the cleavage site, and they were classified as lpai viruses. the nucleotide sequence of the ha cleavage sites of these viruses showed that only one additional nucleotide substitution (t or c to a) is needed at two positions to change serine (s) to arginine (r) and produce the basic motif required for highly pathogenic viruses (r/k-x-r-r); cleavage site motif in th is similar to isolates of israel such as aaz and aaz . parsnrg motif is specific to isolates of israel (peiris et al. b ). this motif does not exist in iranian isolation before . amino acid in cleavage site of th (ptrssrg) is found in isolates with accession numbers aal and abv . these isolates are in chinese isolates group (perk et al. a) . during years of observation, -r-s-s-r-motif predominated among the iranian isolates (kianizadeh et al. ; toroghi and momayez ; karimi et al. however, the presence of this particular motif also emphasizes that these viruses have the potential to become pathogenic should they acquire any further nucleotide substitutions in the ha-connecting peptide region. these isolates show some levels of substitution, indicating antigenic drift (ghadi et al. ). glycosylation of ha and na can affect the host specificity, virulence, and infectivity of an influenza strain either directly, by changing the biological properties of ha and na, or indirectly, by attenuating receptor binding, masking antigenic regions of the protein, impeding the activation of the protein precursor ha via its cleavage into the disulfidelinked subunits ha and ha , and regulating catalytic activity (sun et al. ; gallagher and henneberry ) . generally, h viruses vary in the number of glycosylation sites on ha (six in duck viruses and as many as eight in quail and chicken viruses) (xu et al. ) . the glycosylation at position was observed among h and h viruses isolated from chickens but not from aquatic birds, and it was suggested to be a feature of chicken viruses (kwon et al. a) . one potential glycosylation site at position ( in h ) was lost compared with representative reference strains of the g lineage, the y lineage, the korean lineage, and the prototypic pakistani isolate ck/pakistan/ / . loss of an additional glycosylation site at position , compared with the prototype g virus a/qa/hk/g / , was observed; this was also seen in h n viruses from the middle east in - . the loss of potential glycosylation sites may represent a selected adaptation of h n within poultry since alteration in glycosylation pattern has been suggested to influence adaptation of avian influenza table +, glycosylation site present; _, glycosylation site absent viruses to poultry (iqbal et al. ). also, deletion of one amino acid residue at position in th and in th led to the loss of one potential glycosylation site on the ha molecule . ghadi et al. report a similar deletion in their studies on live bird marketing h n isolates. they suggest that these differences represent mutations that could have occurred in markets; there was no additional glycosylation site that could induce virus virulence (ghadi et al. ) . high similarity in the amino acid sequences in glycosylation sites of these nine isolates provides further evidence of their similar nucleotide sequences. a major determinant of host range is the affinity of the viral ha protein to the sialic acid (sa) receptor of the host cell. a change of preference for the avian influenza virus for a ( , )-linked gal to a ( , )-linked gal for the sa receptor is highly related to host specificity. wan and perez ( ) also demonstrated that the glu to leu substitution at amino acid position in ha allows h n viruses to replicate more efficiently in human airway epithelial cells cultured in vitro. the substitution of gln for leu at residue and the change of ala to thr at position occurred in the receptor binding site of those h n variants that have previously been reported to be involved in the binding specificity to receptors in host cells. therefore, further studies are needed to understand the role of these mutations in the receptor binding site in restricting the host range of these h n variants. these viruses at prevalence might have had the ability of infecting humans without pigs as intermediate hosts, which suggested that h n aiv would become of greater risk to public health in the coming years (wan and perez ) . the left edge of binding pocket (aa - ) in this study isolates had the three types of motif, in which ngligr motif is similar to human isolates (liu et al. ) . data have been shown in table . a study about left edge of binding pocket reveals that three isolates in this study (th , th , and th ) have motif that is similar to h n isolates that were isolated from humans. this finding alerts this subject that iranian isolates have a tendency to infect humans. this kind of motif had been seen in other iranian isolates that were obtained from genbank. one chicken isolate (th ) from tehran in contained a q- instead of l- in ha receptor binding site and thus was not a potential to infect humans. l- substation has been seen in some sequences of ha gene of iranian h n isolates and recently in isolates th , th , and th ; thus, these isolates can be bound to human receptors (a- , ) and may infect human populations. this substitution has been seen in some sequences of ha gene of iranian h n isolates. another ha marker, amino acid (receptor binding site) in one isolate, th , conserve to new motif in iranian isolate. also, the right edge of binding pocket (aa - ) in iranian isolates has been detected .two kinds of motif gtska and gtsks were detected in this study. viruses that were isolated after show new motif in this region (th , th , th , th ) (liu et al. ; lu et al. ) . signal peptide (aa ), bottom of globular head (aa ), and adjacent receptor binding site (aa ) are three important positions for characterization of ha (lu et al. ) . these positions are available in table .the mentioned positions are a, n(r), and h, respectively, in duck isolate. according to our results, th (base on bottom of globular head position) and th (based on adjacent receptor binding site) may be originated from ducks. overall, the presence of h n viruses of the sequence known to bind to human-type receptors in these iranian poultry and the presence of h n antibodies in the human population of iran showed that it is possible for circulating h n avian influenza viruses in iran to infect humans. hence, extensive surveillance of h n in this country is highly recommended. according to the phylogenetic analysis of h genes, the h n iranian isolates fell into a single g -like lineage, together with all of the middle eastern and some asian viruses that were examined in the present study. the phylogenetic analysis based on the amino acid sequence of a ha region showed that the isolates from iran, pakistan, india, and saudi arabia clustered together, indicating a close relationship. interestingly, the isolates from each particular country formed a homogenous group, revealing that these viruses probably had a single source (banks et al. ; aamir et al. ; zhao et al. ; perk et al. b; butt et al. ; tosh et al. ) . these results are basically in agreement with previous studies. the presence of the middle east isolates on this lineage may be due to a close geographical relationship between these countries that had given the impression that the outbreaks seen in these countries were the result of a major epizootic caused by the spread of a single virus. the first scientific report of phylogenetic analysis of iranian h n isolates was done by karimi were very similar to those from saudi arabia, germany, and pakistan. it is postulated that, except for some chinese isolates, the pathogenicity of iranian isolates seems to be similar to that of other eurasian isolates . phylogenetic analysis that was carried out by homayounimehr showed that all their h n isolates from commercial chickens in iran ( iran ( - belonged to the g -like sublineage. on the basis of phylogenetic and molecular characterization evidence, they concluded that the h n subtype influenza viruses circulating in chicken flocks in iran since - had a common origin (homayounimehr et al. ). ghadi et al. in a molecular surveillance of h n in live bird market report that h n viruses isolated from live bird markets were highly similar to viruses isolated from industrial poultry being circulated as early as . they suggest that a common source of h n viruses is circulating in iran (ghadi et al. ) . shahsavandi et al. analyzed the full-length ha genes of h n ai strains isolated from chickens in asia during the period - . they showed that g -like viruses circulated in the middle east and indian subcontinent countries, whereas other sublineages existed in far east countries. it also revealed g -like viruses with an average . % identity clustered into two subgroups largely based on their time of isolation (shahsavandi et al. (h n ))] was located in y- . a/garganey/iran/g / (h n ) was isolated from a garganeyin, the southern part of iran which was suspected to have been kept together with backyard poultry for a short time before sampling (fereidouni et al. ) . our present study has demonstrated that low-pathogenic h n influenza viruses have been permanently circulating in the middle east region, including iran, during the last decade. according to a previous report, on the basis of phylogenetic evidence, it is proposed that the emergence of h n avian influenza infection in iran originated in pakistan, and it was due to low quarantine measures in the international boundaries. due to the high percentage of h n homology isolates of iran with other isolates, namely a/quail/hongkong/g , in genbank and based on published reports for high similarity with infecting human h n isolates, it seems that the potential of iranian avian influenza isolates to infect human should be considered. live bird markets as already mentioned are believed to be one of the best environments for keeping avian influenza viruses and transmission between species and productive source for mixing and reassortment of new viruses with higher pathogenicity. it is possible that an elevation in mortality rate under field condition could be caused by coinfection of recent isolates with the bacteria such as mycoplasma, escherichia coli, and ornithobacterium rhinotracheale rather than by an emerging pathogenic h n subtype of the virus. the present findings also indicate that the ha genes of the h influenza virus circulating in tehran province were not also well conserved and in recent years have dominant changes. especially from , a dominant change had been produced in iranian isolates. continuous surveillance would improve our understanding of the role of various avian hosts in ecology of influenza viruses and thus the underlying phenomena in emergence of pandemic strains. also, according to an h n case report in non-industry birds, it is very critical for h n monitoring for probable changes in h n isolates. characterization of avian h n influenza viruses from united arab emirates a review of avian influenza in different bird species phylogenetic analysis of h haemagglutinin subtype influenza a viruses comparative sequence, antigenic and phylogenetic analysis of avian influenza (h n ) surface proteins isolated in pakistan between and avian influenza and newcastle disease: a field and laboratory manual mega : molecular evolutionary genetics analysis software-version . avian influenza virus monitoring in wintering waterbirds in iran fields virology, vols and glycosylation requirements for intracellular transport and function of the hemagglutinin of influenza virus genetic analysis of hemagglutinin protein of h n isolated from live bird markets in tehran province in molecular characterization of h n influenza viruses: were they the donors of the "internal" genes of h n viruses in hong kong? characterization of hemagglutinin gene of influenza a virus subtype h n universal primer set for the full-length amplification of all influenza a viruses sequence and phylogenetic analysis of the haemagglutinin genes of h n avian influenza viruses isolated from commercial chickens in iran avian influenza virus infections. i. characteristics of influenza a/turkey/wisconsin/ virus novel genotypes of h n influenza a viruses isolated from poultry in pakistan containing ns genes similar to highly pathogenic h n and h n viruses amino acid sequence analysis of hemagglutinin protein of h n isolated from broilers in tehran sequence analysis and phylogenetic study of hemagglutinin gene of h n subtype of avian influenza virus isolated during - in iran pathogencitiy and haemagglutinin gene sequence analysis of iranian avian influenza h n viruses isolated during molecular epizootiology of recurrent low pathogenic avian influenza by h n subtype virus in korea molecular epizootiology of recurrent low pathogenic avian influenza by h n subtype virus in korea genetic conservation of hemagglutinin gene of h influenza virus in chicken population in mainland china phylogenetic analysis of eight genes of h n subtype influenza virus: a mainland china strain possessing early isolates' genes that have been circulating h n influenza a viruses from poultry in asia have human virus-like receptor specificity evaluation of h n avian influenza virus dissemination in various organs of experimentally infected broiler chickens using rt-pcr avian influenza (h n ) outbreak in iran natural cases and an experimental study of h n avian influenza in commercial broiler chickens of iran influenza a h n : aspects of laboratory diagnosis human infection with influenza h n genetic characterization of the h n influenza viruses circulated in the poultry population in israel ecology and molecular epidemiology of h n avian influenza viruses isolated in israel during - epizootic evolutionary characterization of hemagglutinin gene of h n influenza viruses isolated from asia mortality of wild swans associated with naturally infection with highly pathogenic h n avian influenza virus in iran glycosylation site alteration in the evolution of influenza a (h n ) viruses a laboratory manual for the isolation and identification of avian pathogens biological and molecular characterization of avian influenza virus (h n ) isolates from iran genetic analysis of h n avian influenza viruses isolated from india a seroe-pidemiologic study of avian influenza (h n ) in iran amino acid in the hemagglutinin of h n influenza viruses determines cell tropism and replication in human airway epithelial cells evolution and ecology of influenza a viruses evolutionary characterization of influenza virus a/duck/hubei/w / (h n ) isolated from central china sequence and phylogenetic analysis of the haemagglutinin genes of h n avian influenza viruses isolated in central china during key: cord- -fpjhkb g authors: sharifi, hamid; jahani, yunes; mirzazadeh, ali; ahmadi gohari, milad; nakhaeizadeh, mehran; shokoohi, mostafa; eybpoosh, sana; tohidinik, hamid reza; mostafavi, ehsan; khalili, davood; hashemi nazari, seyed saeed; karamouzian, mohammad; haghdoost, ali akbar title: estimating the number of covid- -related infections, deaths and hospitalizations in iran under different physical distancing and isolation scenarios: a compartmental mathematical modeling date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: fpjhkb g background: iran is one of the countries that has been overwhelmed with covid- . we aimed to estimate the total number of covid- related infections, deaths, and hospitalizations in iran under different physical distancing and isolation scenarios. methods: we developed a susceptible-exposed-infected-removed (seir) model, parameterized to the covid- pandemic in iran. we used the model to quantify the magnitude of the outbreak in iran and assess the effectiveness of isolation and physical distancing under five different scenarios (a: % isolation, through e: % isolation of all infected cases). we used monte-carlo simulation to calculate the % uncertainty intervals (ui). findings: under scenario a, we estimated , , (ui , , - , , ) infections to happen till mid-june with , (ui , - , , ) hospitalizations and , (ui , - , ) deaths. successful implantation of scenario e would reduce the number of infections by % (i.e. , ) and change the epidemic peak from , on june th to , on march st. scenario e also reduces the hospitalizations by % (i.e. , ), and deaths by % (i.e. , ). interpretation: with no approved vaccination or therapy, we found physical distancing and isolation that includes public awareness and case-finding/isolation of % of infected people can reduce the burden of covid- in iran by % by mid-june. evidence before this study: iran has been heavily impacted by the covid- outbreak, and the virus has now spread to all of its provinces. iran has been implementing different levels of partial physical distancing and isolation policies in the past few months. we searched pubmed and preprint archives for articles published up to april , that included information about control measures against covid- in iran using the following terms: ("coronavirus" or " -ncov" or "covid- ") and "iran" and ("intervention" or "prevention" or "physical distancing" or "social distancing"). we found no studies that had quantified the impact of policies in iran. given the scarcity of evidence on the magnitude of the outbreak and the burden of covid- in iran, we used multiple sources of data to estimate the number of covid- infections, hospitalizations, and deaths under different physical distancing and isolation scenarios until mid-june. we showed that implementing no control measures could lead to over five million infections in iran; ~ % of whom would be hospitalized, and ~ % would die. however, under our most optimistic scenario, these estimates could be reduced by ~ %. with no effective vaccination or treatment, advocating and enforcing physical distancing and isolation along with public education on prevention measures could significantly reduce the burden of covid- in iran. nonetheless, even under the most optimistic scenario, the burden of covid- would be substantial and well beyond the current capacity of the healthcare system in iran. the covid- was declared a pandemic on march , and the disease is now expected to spread worldwide. the risk is relatively low for the general population, although people aged years and over, those with suppressed immune systems, and people with underlying medical conditions (e.g., cardiovascular or respiratory diseases) are at increased risk of adverse outcomes. the case fatality rate of the infection is estimated to be around % ( % ci: - %) and as of april , , a total number of , , confirmed cases, , recovered cases, and , death have been reported worldwide. iran is one of the hardest hit countries by covid- and has been struggling with controlling the disease for over two months. the first confirmed cases of covid- -related deaths were reported on january in the city of qom; km away from iran's capital city of tehran. as of april , , a total number of , confirmed cases, , recovered cases, and , death have been reported and covid- has spread to all of its provinces; figures that are highest among the eastern mediterranean region countries. the susceptible-exposed-infected-removed (seir) model provides a mathematical framework to explain the spread of infectious diseases and has previously been used for estimating the epidemiological parameters of several infectious diseases such as measles, ebola, and influenza. [ ] [ ] [ ] seir could also help evaluate the impact of implementing various interventions (e.g., isolation and physical distancing policies) aimed at controlling the growth of the pandemic and flattening the epidemic curve. physical distancing (also called social distancing) control measures are policies that aim to minimize close contacts within communities and include individual-level (e.g., quarantine, isolation) and community-level (closure of educational and recreational settings, nonessential businesses, and cancellation of public/mass/crowded gatherings) approaches. , in iran, the physical distancing and isolation interventions were scaled up in late february and early march by nationwide closure of schools/universities, cancellation of sports events and friday/congregational prayers as well as the closure of all non-essential services, tourism sites, and shopping malls (figure ). iran also closed its holy shrines in mashhad and qom in mid-march. moreover, while there were no mandatory shelter-in-place or lockdown orders, people were encouraged to stay at home. people were also asked to avoid travelling during the new year holidays (i.e., nowruz) from march to ; however, no restrictions for domestic (via flight, train or bus) or international travels (i.e. no border closure) were imposed. despite implementing various physical distancing control measures, our understanding of their impact on the magnitude of covid- -related new infections, hospitalization, and death remains limited. in this study, we aim to provide an estimate of these epidemiological parameters and approximate the peak date of the epidemic in iran under different physical distancing and isolation scenarios. these estimates are of particular importance for covid- -related health policy, planning, and financing purposes in iran. we formed a compartmental model to estimate the total number of covid- patients, hospitalizations and deaths in iran and its capital city of tehran ( figure ). we used an extended susceptible-exposed-infected/infectious-recovered/removed (seir) model that divides the target populations (i.e., iran and tehran as the capital) into different compartments. the conceptual framework of the covid- transmission model is presented in appendix aa. in brief, we considered the following comportments: a) susceptible, referring to the total number of individuals . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted april , . . https://doi.org/ . / . . . doi: medrxiv preprint (i.e., hosts) who have been susceptible to covid- . we assumed the entire population as susceptible in our model; b) exposed, referring to individuals who are exposed to covid- while they are asymptomatic and not yet infectious; c) infected, referring to infected people who demonstrate clinical symptoms after their incubation period and have the potential to transmit the disease to other susceptible individuals; and d) recovered/removed, depending on the severity of the disease. we assumed that the infected people will i) be recovered and immune from re-infection and therefore, no longer transmit the infection, or ii) have mild to moderate clinical symptoms while they follow home-isolation guidelines without requiring hospitalization, iii) have severe clinical symptoms and require hospitalization. these individuals would either be recovered (and then discharged) or fail to respond to treatment and pass away (removed) from the model. monte carlo method was used to build the % uncertainty intervals (ui) around the point estimates of the total expected numbers. to do this, we used the statistical distribution of a set of parameters obtained from both the existing evidence and expert opinion (listed in table appendix bb). data were analyzed using vensim dss . e software. based on the country's official reports and available epidemiological data, january , was considered as the initial day of the covid- outbreak in iran. we used several parameters as inputs for the model and obtained their values from a comprehensive literature review and published articles in relation to covid- , as well as some corresponding parameters and values considered for the similar epidemics, in particular, h n influenza. we first shared the initial values of the parameters with iran's national and scientific committees and experts, and then made the necessary adjustments. we compared the revised values of these parameters with the literature as well as the pattern of the epidemic in iran. we then made the final revisions for the values of . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted april , . . https://doi.org/ . / . . . doi: medrxiv preprint the parameters used as input for the predicted number of covid- infected cases and its associated deaths using the extended seir model. input parameters and their brief descriptions are presented in tables and in appendix bb. the impact of seasonality (a sinuses' function) was considered in calculating the transmission probability (beta coefficient) of the disease, indicating the potential for some level of change in transmissibility of the virus from one season to another.( ) therefore, we assumed that covid- might behave the same as influenza such that the transmission of the virus may tend to reduce by approaching to warm seasons (i.e., spring and summer). we then considered the end of december in winter with the most transmission probability and the end of june in summer with the least transmission probability. the minimum and maximum values of the seasonal changes were considered to be . and . , respectively. a time-varying state was considered for the effective contact rate (c parameter). we first incorporated value of in the tehran model and in the national model in the early weeks of the epidemic. [ ] [ ] [ ] [ ] [ ] after the announcement of the epidemic by the officials, multiple public health measures implemented as a response to the epidemic to reduce contact rates and then transmission rates in public. approaching the assumed end of the epidemic, we considered value of for this parameter, with some fluctuations due to nowruz holidays within this period ( table in appendix bb). five possible scenarios were considered for isolation of the infected cases (table ) . . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . our modeling exercise showed that with no intervention (i.e., scenario a), more than five million covid- infections would occur in iran till mid-june, of whom . % would be hospitalized and . % would die. however, under the best-case scenario (i.e., scenario e), the number of infected cases could be reduced by %, hospitalizations by %, and deaths by %. our projection in scenario c, which is a middle ground scenario, appeared to be aligned with the current statistics from the national reports. even under scenario c, the burden of the epidemic in iran will be large, last for several months and might surpass the current capacity of the healthcare system. is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . https://doi.org/ . / . . . doi: medrxiv preprint approaches towards lifting the physical distancing restrictions is extremely difficult and varies across countries with different economic and healthcare infrastructures, it is critical to follow an evidence-informed approach to avoid the second and further waves of covid- epidemics in iran. a modeling study from china for example, showed that a stepwise ( % of the workforce working in weeks to , % of the workforce working in weeks to , and % of the workforce working and school resuming from week forward) return to work or school at the beginning of april (about five months after the first case reported from china), is much more effective than the beginning of march. this study estimated that just a one-month delay in the stepwise lifting of the physical distancing measures would reduce the magnitude ( % by mid- , % by end- ) the epidemic and delay its peak by two months and therefore avoid overwhelming the healthcare systems. in iran, a recent executive order from the government lifted the restrictions on nationwide business shutdown and allowed most people to return to work only . months after the identification of the first covid- case in iran. , the government has also planned to reopen schools in lowrisk cities and non-essential low or medium-risk jobs (e.g., all production units in industrial, business, technical service, and distributional sections), as well as removing the shelter-in-place order and resuming domestic and international travels. these decisions are mainly derived from the iranian government's economic challenges that have been elevated by the comprehensive sanctions imposed by the usa. , while these concerns are understandable and longer shutdown of an already overstretched economy is a tough decision and would be very taxing on the government and the public, our findings as well as lessons learned from china, , , suggest that this approach is not justified by evidence and would most likely risk overwhelming the healthcare systems with soon-to-come second and further waves of covid- epidemic in iran; costs that . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . https://doi.org/ . / . . . doi: medrxiv preprint might surpass the marginal economic benefits of opening businesses and schools a few months sooner. nonetheless, it is fortunate that the iranian cdc is now planning to shift from physical distancing to targeted case-finding, intensify contact tracing and careful isolation of identified cases as well as self-quarantine of symptomatic people. our study had three major limitations. first, some of the key parameters (e.g. hospitalization rate, incubation period, transmission probability) that were used in the model were from other countries or expert opinion, but not from empirical data from iran. to address this limitation, we reported a range of uncertainty intervals. second, the uncertainty intervals are fairly wide for most of our with no approved vaccination, prophylaxis or therapy, we found physical distancing and isolation that includes public awareness and case-finding/isolation of % of the infected cases could reduce the burden of covid- in iran by % by mid-june. except for the senior author, dr. ali akbar haghdoost, who is the deputy minister of health and the head of national covid- committee, the rest of the authors declare no conflict of interest, real or perceived. the authors received no funding for this work. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . iranian press review: iranians ignore coronavirus travel warning ahead of nowruz holiday. available from: https://www.middleeasteye.net/news/iran-press-review-coronavirus-nowruztravel-warning-ignore ghaffarzadegan n, rahmandad h. simulation-based estimation of the spread of covid- in iran. medrxiv. . iran reports its first cases of the new coronavirus. available from: https://www.timesofisrael.com/iran-reports-its-first- -cases-of-the-new-coronavirus/ healthcare . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . isolation for the entire period of the epidemic was considered to be % (the worst scenario) policy interventions were at the level of encouragement and the overall mean of isolation for the entire period of the epidemic was considered to be % isolation was considered to be % from january to february , % after the initiation of the epidemic from february to march , and finally % from march to june , , which are the results of the minimal possible interventions of the health system, behavior change of the public, and containment strategies isolation was considered to be % from january to february , % after the initiation of the epidemic from february to march , and finally % from march to june , , which are the results of the moderate possible interventions of the enhanced health system, social and behavioral change of the public (e.g., social distancing, hand washing), and containment strategies (e.g., closing schools and universities) isolation was considered to be % from january to february , % after the initiation of the epidemic from february to march , and finally % from march to june , , which are the results of the maximum possible interventions of the health system, behavior change of the public, and containment strategies. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . where β(t) indicates transmissibility of the virus, and c(t) indicates the contact rates, and ii(t) refers to the total number of infected people who transmit the infection, calculated as infect (t)+( . ×temporary isolation units)+( . ×hospital) (explained below). b) individuals who are exposed (e(t)): refers to individuals who are exposed to the infection, but they are not yet infectious. these individuals are asymptomatic in this period. the differential equation of this compartment is shown in equation : eq. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . https://doi.org/ . / . . . doi: medrxiv preprint ii) infected individuals who will have mild to moderate clinical symptoms, but they will be home-isolated without requiring hospitalization (is(t)), and they will be recovered (isolated box in fig ) . equation iii) infected individuals who will have severe clinical symptoms requiring hospitalization (hospitalized box in fig ) . these individuals will have two possible outcomes: i) some hospitalized cases will be recovered and then discharged (t box in fig ) , or ii) some will not respond to the medical care and die (death box in fig ) . equations and show the differential equation of hospital box (h(t)) and t box (t(t)) respectively: eq. ( ) = . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted april , . . the values of these parameters are reported in appendix bb table . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted april , . . https://doi.org/ . / . . . doi: medrxiv preprint selected findings of the national population and housing census risk estimation and prediction by modeling the transmission of the novel coronavirus (covid- ) in mainland china excluding hubei province. medrxiv active monitoring of persons exposed to patients with confirmed covid- -united states modelling of h n flu in iran estimation of the time-varying reproduction number of covid- outbreak in china social contacts and mixing patterns relevant to the spread of infectious diseases social contacts, vaccination decisions and influenza in japan an updated estimation of the risk of transmission of the novel coronavirus ( -ncov) projecting social contact matrices to different demographic structures a systematic values references an infected individual contact with an uninfected individual ) seasonality distribution: (((sin ( × . × (time + ) / )) + ) × (( . - . ) / )) + . infected individuals with the potential to infect uninfected peoplethe average number of people from susceptible individuals are added to exposed individuals (per day)the average number of people from exposed individuals are added to infected individuals (per day)the average duration taken for an exposed individual becomes an infected individual [ ] [ ] [ ] [ ] [ ] from jan , , to jan , from jan , , to feb , from feb , , to feb , from feb , , to feb , from mar , , to mar , from mar , , to mar , * * from apr , , to june , * contact rates were assumed to increase due to the nowruz holidays within these periods key: cord- - h rcih authors: sharififar, simintaj; jahangiri, katayoun; zareiyan, armin; khoshvaghti, amir title: factors affecting hospital response in biological disasters: a qualitative study date: - - journal: med j islam repub iran doi: . /mjiri. . sha: doc_id: cord_uid: h rcih background: the fatal pandemics of infectious diseases and the possibility of using microorganisms as biological weapons are both rising worldwide. hospitals are vital organizations in response to biological disasters and have a crucial role in the treatment of patients. despite the advances in studies about hospital planning and performance during crises, there are no internationally accepted standards for hospital preparedness and disaster response. thus, this study was designed to explain the effective factors in hospital performance during biological disasters. methods: qualitative content analysis with conventional approach was used in the present study. the setting was ministry of health and related hospitals, and other relevant ministries responsible at the time of biologic events in islamic republic of iran (ir of iran) in . participants were experts, experienced individuals providing service in the field of biological disaster planning and response, policymakers in the ministry of health, and other related organizations and authorities responsible for the accreditation of hospitals in ir of iran. data were collected using semi-structured interviews in persian language. analysis was performed according to graneheim method. results: after analyzing interviews, extraction resulted in common codes, subcategories, and categories, which are as follow: detection; treatment and infection control; coordination, resources; training and exercises; communication and information system; construction; and planning and assessment. conclusion: hospital management in outbreaks of infectious diseases (intentional or unintentional) is complex and requires different actions than during natural disasters. in such disasters, readiness to respond and appropriate action is a multifaceted operation. in ir of iran, there have been few researches in the field of hospital preparation in biologic events, and the possibility of standardized assessment has be reduced due to lack of key skills in confronting biological events. it is hoped that the aggregated factors in the groups of this study can evaluate hospital performance more coherently. the deadly pandemics of infectious diseases are rising worldwide. in the twentieth century, have caused death of more than million people in many parts of the world ( ) . in the last relatively mild h n pandemic in , - of people were killed who were not necessarily in high-risk groups ( ) . according to the report of www.warontherocks.com, about cbrn events were reported between and ( ) . also, the possibility of using microorganisms as biological weapons is a real and increasing probability all around the world ( , ) . increasing the tendency to use biological weapons due to increased terrorist attacks, their relative convenience use, and low cost have led to many health concerns ( , ) . between and , - persons were killed in major terrorist incidents nearly every months ( ). hospitals are vital organizations during biological disasters and play a crucial role as a place of care and treatment for such patients ( , , ) . hospitals should have an essential role in biological disasters ( ) ( ) ( ) ( ) . having specialists and staff with knowledge and skills relevant to biological events can play a significant role in reducing mortality and morbidity in the community, especially in the first few hours, which is called the golden time. the result is hospital preparedness to deal with biological events, which improves the response rate and accelerates the process of rehabilitation ( ) . hospital services are differentiated from other institutions by their types of activities, resources, staff, multiple specializations, and equipment used ( ) . the response of hospitals has a multidimensional function (approach) ( , ) . despite the advances in studies about hospital planning and performance during crises, there are no internationally accepted standards for hospital preparedness and disaster response ( ) . to date, there has been no valid methodology for assessing the preparedness of hospitals for disasters ( ) . however, after the onset of disasters, it is necessary that hospitals be prepared to deal with the new circumstance and surge capacity ( , ) . disaster preparedness is recognized as one of the top priorities in the medical field ( ) . this process varies in cbrn events ( ) . according to the recommendation in the process of planning, preparing, and responding to disasters in the health system, it is necessary to use the "all-hazards" approach ( ) . however, in practice, this approach does not seem to be suitable for man-made and technologic disasters such as biological, chemical, or nuclear events. nevertheless, evaluating hospitals' performance during crises, especially the one caused by biological disasters (eg, the epidemic of diseases whether natural or intentional), is a topic that has been dealt with inadequately. since in the face of disasters and biological threats different conditions prevail in hospitals, thus, evaluating the performance of hospitals in such situations requires a different mechanism. in addition, no comprehensive plan has been developed to manage biological events in iran. therefore, the present study was conducted to identify factors affecting hospital response in biological disasters. qualitative content analysis with conventional approach was used in this study. the qualitative content analysis approach was used for subjective interpretations of text data by systematic classification process, coding, identifying categories, or patterns. using this approach, the researcher avoids classification with background thoughts and allows categories formation during the research process ( ) ( ) ( ) . hospitals under the supervision of ministry of health and other relevant ministries responding to biologic events in ir of iran at (including the defense ministry) were included in this study. participants in this project were experts, experienced individuals providing services in the field of biological disaster planning and response, policymakers in ministry of health, and other related organizations and authorities responsible for the accreditation of hospitals in ir of iran. data were collected through conducting semi-structured interviews in persian language with the aim of explaining factors affecting the performance of hospitals in response to biologic threats. initially, the researcher met each participant and presented the research goals and obtained their consent for participation. three participants did not respond to the request and introduced another person as an expert in the field of research. two participants stated that these questions were not in their field of expertise. a total of interviews were done. the age range of the participants was - years. the purpose of the interviews was to explain and explore the factors influencing hospital performance in response to biologic threats. interviews began with simple and general topics and went on to specific questions. some questions were changed during the research (after completing the third interview and analyzing the data). types of questions were as follow: open questions, based on the default, and case-by-case. some of the interview questions were as follow: . what are the effective factors in assessing hospital performance at the time of biological events? . what are the management problems that you have experienced or may experience during a biological threat? . what are the strengths and weaknesses in assessing a hospital's performance of biological threats? . what is the difference between assessing the performance of hospitals in natural disasters and in biological distasters? during the interview, the researcher observed and noted the participants' interactions with the environment and their reactions, which were considered in the data analysis. the number of participants was determined based on the saturation of the obtained codes, so that the new codes were not extracted by new interviews. sampling was done using purposeful and snowball method. the interview took about - minutes. at first, interviews were conducted with the participants, their voice was recorded, and transcription was done a short while after each interview. data analysis began after the first transcription. to analyze the data, the researcher studied the data deeply, reread, and considered the text of the interview, gained understanding of the data, and finally completed the analysis ( ) . after each interview, transcription was done and field observations notes were reviewed several times. the final text was approved by each participant (member check). after the third interview, the questions were redesigned. in this study, interviews and field notes were the analysis units. the texts were divided into content areas and meaning units. meaning units were summarized and codes were extracted. multiple codes were compared with each other in terms of differences and similarities; then, categories and subcategories were formed. the extracted categories were discussed by scholars; finally, the basic and essential meanings of the categories were edited. data collection continued until saturation was reached for each concept. in a qualitative research, rigor shows concepts of credibility, dependability, transferability, and different dimensions of trustworthiness ( ) . to achieve maximum credibility, the research team used a range of expert participants. participants were among authorities of health in ir of iran, officials and staff of biologic laboratories, and some experienced officials from civil and military organizations with a history of managing infectious disasters. after each interview, transcription of texts was performed in a short interval. interviews were listened repeatedly, and the researcher extracted the meaning units. then, based on the condensation and abstracting of meaning units, the codes were extracted. similar codes were placed in subcategories, and the categories were formed according to the similarities and differences between subcategories. in the case of extraction of codes, subcategories, and categories, expert opinions were taken from the research team, and agreement was reached among researchers, experts, and participants about the differences. this study has been conducted in the context of ir of iran. according to researchers' view, the results can be generalized to other countries, but the choice has been left to readers ( ) . this study was approved by the national committee of ethics of ir of iran (code number: ir.sbmu.retech. rec. . ). all participants were aware of the research objectives. informed consent was taken from all participants and their participation was kept confidential. all interviews were recorded with participants' permission and were fully transcribed within a short period after the interview. analysis was done simultaneously. the demographic characteristics of the participants are presented in table . participants answered all the questions during the interview. after analyzing interviews, codes were extracted. codes were categorized in subcategories after analysis. according to the similarities and differences in nature of subcategories, categories were extracted: detection; treatment and infection control; coordination; resources; training and exercises; communication and information system; construction; and planning and assessment. the graphic diagram of the extracted categories and subcategories is shown in figure . table contains extracted categories, subcategories, and common codes by content analysis. after analyzing the data, it was found that all participants considered the ability to detect biologic outbreaks or emergencies in hospitals as an effective factor in hospital performance. the first step in controlling a biologic emergency is to detect the event in a hospital. the subcategories of determining the type of event (intentional or unintentional) and early detection were extracted. - : according to the participants, the delay in diagnosis with subsequent possibility of developing outbreaks of communicable diseases could be a major factor in hospital performance. one of the participants (p ) mentioned, "rapid detection is an important factor in proper performance in biological disasters. in the crimean-congo fever epidemic, if diagnosis was not established on time, the disease would have spread further". - : determining the deliberate or unintentional cause of a biological event can affect hospital performance. in intentional events, the biologic agent may still exist in the environment which will cause the disaster to be continued. another participant (p ) said, "it is difficult to diagnose the cause of deliberate biological events because there is less experience about it. treatment has been discussed on the textbooks, but the bioterrorism detection has not reviewed extensively, and it is very difficult". from the participants' perspective, the ability to treat and control the infection in the hospital was considered as an important factor in the proper hospital performance in biological disasters. the obtained subcategories were as follow: the ability to manage the biologic event and treat patients; the ability to care for the patients; the ability to decontaminate the injured people and surfaces; the ability to perform biologic triage; and pre and post exposure prophylaxis in affected individuals. - : drug therapy of patients and pre and post exposure prophylaxis: the extracted common codes according to participants' interviews were possibility of appropriate response after a biological event in a hospital, prompt and suitable treatment of the patients, having an efficient team of rapid response, the ability to discharge if necessary, pharmaceuticals prescription, having adequate stockpiles, and the ability to perform pre and post exposure prophylaxis. one participant (p ) said, "if prevention is not imminent with different medications and appropriate vaccines, the disease would spread. for example, if respiratory anthrax or plague becomes prevalent, vaccination and appropriate therapeutic prophylaxis are the only way to prevent the disease progress in the community". - : nursing: the presence of skilled and capable nurses was one of the subcategories obtained in this study. nurses who are trained, skilled, and familiar with personal protective equipment may have positive effects on hospital performance. one of the participants (p ) mentioned: "having skilled nurses to care for infectious patients is valuable as patients' treatment in epidemics. one day i went to the hospital for a visit and saw the aids patient wearing a mask. the head-nurse had told him to do so". - : isolation: according to the participants, the ability to isolate patients with communicable diseases in the hospital and in the designated sites for group isolation was an important component of infection control. one participant (p ) said, "isolation spaces are needed based on the causative agent (such as droplet or airborne isolation). in emergency situations, metal partitioning is better, and if not possible, minimal isolation should be executed even with curtains". - decontamination: most participants considered the ability to decontaminate victims efficiently as one of the important factors in hospital performance dealing with biological disasters, which is an important step in decontaminating patients, surfaces, and equipment in proper response to such disasters. one of the participants (p ) stated, "environmental health authorities should be active in tackling the issue. notifications should be declared as soon as possible. environmental decontamination is needed for each disease". - : triage: according to participants, the use of specialized triage in biological events affecting many victims will enhance hospital performance. biological triage which has a different mechanism than other triage systems helps to reduce infection transmission and provide high-speed treatment for people with high-priority care. it also provides the most services in the least amount of time to the largest number of victims. one participant (p ) said, "all hospitals should have a triage system and special checklists." biological triage is necessary. there are no triage systems for infectious diseases in my hospital, so there is not any sorting during an outbreak". - : infection control: participants considered infection control as an essential criterion for hospital performance in biological disasters. the common codes derived from these subcategories are as follow: the ability to control infections during deliberate or natural biological outbreaks; the availability of preventive drugs at a predetermined time during an epidemic of communicable diseases; appropriate vaccination of people at risk; and the safety of hospitalized or outpatients patients in the outbreak of infectious diseases; and waste management. one participant (p ) stated, "to see how a hospital performs, we need to see how much patient's safety is considered. sometimes, with a simple maneuver such as washing hand, transmission of the infection would be prevented". participants considered inter-sectoral and intra-sectoral coordination as an important factor in the proper hospital performance during biological disasters. - : intra-sectorial coordination: a common subcategory was coordination and collaboration within the hospital during a biological disaster, including predetermined inter-organizational tasks. one participant (p ) said, "when epidemics occur, it is highly important that internal parts of the hospital (such as laboratory, radiology, emergency departments, and others) be coordinated. in the early days of influenza epidemic, we did not know where to send the patients' samples for definite diagnosis, which made the process more complicated". - : inter-sectorial coordination: the common codes in this subcategory were as follow: existence of memoranda between hospitals and partner centers (such as organizations for corpses burial, drug production companies, vaccines and personal protective equipment producers, reference laboratories, buildings' owners that can be used for mass storage or isolation). one of the participants (p ) stated, "if there is a suspicious anthrax case and the hospital is a regional one, they should know which laboratory would help, and there should be an accepted guideline for referral". according to participants' viewpoint, the availability of appropriate human resources, necessary equipment, appropriate physical structure, and enough funding has a beneficial effect on hospital performance in biological disasters. these subcategories created the category of resources. - : human resources: according to the participants' perspective, one of the most important factors affecting hospital performance was the availability of human resources in biological emergencies in terms of quality and quantity. defining an organized structure of the staff for the response, duty description for the team, the right staff, and an efficient manager in the hospital seemed necessary at the time of biological disasters. one participant (p ) said, "sometimes we have cases of flu, meningitis, and tuberculosis, but the hospital performance is not appropriate and practical. although training was provided and relative preparedness was expected, during the swine flu outbreak, all staff were afraid and wore masks in hospitals. even the staff in the infectious diseases ward wore masks, which was not necessary and only caused horror. only those who are within a meter of the patient should wear a mask". . : physical structure: based on participants' viewpoint, appropriate physical structure of hospitals to respond to biological disasters is an effective factor in dealing with biological disasters. the proper physical structure of a hospital, enough space for biologic triage, suitable isolation space considering the type of agent, a proper radiology and laboratory structure, and a standard lab were effective subcategories of this category. one participant (p ) said, "one of the performance evaluation factors is whether the hospital has been standardized; having a triage space and decontamination room before entering to the main ward and isolation from the emergency department are highly important. in the influenza epidemic, all hospitals were ordered to separate the patients upon arrival at hospitals, but this was not possible in some hospitals". - : equipment: the subcategories were equipping some ambulances ready for a biologic event, having special and practical equipment when dealing with biological disasters, adequate personal protective equipment, and the ability to maintain laboratory biosafety. one participant (p ) recommended, "having enough equipment to be able to provide good biosecurity is of significant importance. there is not a special stretcher for contagious patients in our hospital, and the lack of a special stretcher for carrying infected patients can impair performance". - : budget: according to the participants' opinion, allocation of appropriate budget for hospital was an effective factor in assessing the hospital performance during biological disasters. insurance of staff and the hospital, and proper allocation of funds were the common subcategories of this category. one of the participants (p ) said, "my hospital manager is concerned about the financial aspect, and he has limitations on training and recruiting human resources. we do not have financial resource even for equipment and training, and our managers do not believe in spending money for managing these disasters. they prefer to deal with tangible issues rather than intangible issues such as biological disasters that have not yet happened". training and exercise influence hospital performance. the subcategories were appropriate educational content in accordance with the up-to-date changes in the field and intermittent exercises. - : educational content: the following subcategories were extracted: having rich and up-to-date educational content with emphasis on biological group a & b agents; providing training on how to use personal protective and prevention equipment, triage, isolation, secure area, control, and treatment; and providing training for misbelief correction. one of the participants (p ) said, "there should be an educational content related to the subject; it can be a part of hospital accreditation. some employees even do not know the correct pronunciation of diseases". - : training: all participants considered staff training as one of the most important factors in hospital performance. the extracted subcategory was receive training in the field of biological agents, including continued and regular education, up-to-date training, and training about preventive and personal protective equipment (mask types and time), isolation types, triage, secure area, and group a & b agents. one participant (p ) recommended, "up-to-date training should be available for staff with an interval of maximum of up to year. our personnel have been graduated many years ago, and their training has not been updated at all". - : exercise: by analyzing the data, intermittent and proportional exercises were obtained as common codes in the exercise subcategory. according to participants, the factors of this subcategory included the need to conduct a biological exercise in the hospital, and presence of a range of exercises such as top table exercise for managers and coordinators and other types of exercises, and execution of intermittent drills within a specified time schedule. one of the participants (p ) declared, "our managers did not have any experience in biological disaster management, even in the form of a drill. we should exercise and learn what we lack". another participant (p ) said, "there should be an exercise index for evaluation (drills about personal protective equipment) ". according to the results of the data analysis, the risk communication system, information security, risk understanding, and surveillance system were subcategories of the communication and information system category. - : risk communication systems: having a risk communication system, information security, risk understanding, and a surveillance system were determined as subcategories of this category. - : information security: information security is important in an outbreak of infectious diseases in hospitals, as non-patients may go to the hospital for fear of panic or patients may not come to the hospital for fear of stigma. the common codes were as follow: the possibility of sending written reports or internal automation to senior officials, laboratories, and the ministry of health, and lack of public notification in some instances. one of the participants (p ) said, "a false outbreak would occur without proper communication with the economic authorities. each time after a rumor about an infectious disease, many will come to hospitals as false patients, and controlling such situations would be very difficult". - : risk understanding: this subcategory was also derived from the information and communication category. participants believed that developing a positive attitude towards the possibility of biological disasters in hospital managers is crucial, because if a manager or staff does not believe in the possibility of biological disasters, there would be no possibility of necessary and timely action. one participant (p ) declared, "hospital managers do not have a proper attitude about this kind of problems. even after being trained by senior officials, they still do not have a good perception of the biologic disasters". - : surveillance system: according to participants, the use of surveillance systems in hospitals and the active registration of infectious diseases were considered as effective factors in hospital performance. one participant (p ) said, "the center for diseases control of ministry of health has a tradition of its own. in the health sector, they have a disease expert who will inform you if something happens. they themselves do not actively seek out any disease". the existence of an appropriate hospital incident command system (hics) for biological events was one of the main obtained categories in this study. extracted categories were the need for existence of a code for the biological crisis, type of system activation, existence of a unique command, use of qualified advisors in a commanding system, and proper organization of the staff. one of the participants (p ) announced, "having an incident command plan during a biological disaster is highly important. commanding systems do not work well in our hospitals in important and dangerous disasters such as earthquake and floods". planning and assessment were among the other key elements that influenced hospital performance during emergencies. risk assessment in hospitals was identified as a basic point in evaluation of hospitals. in the absence of a risk assessment in a hospital, finding priorities for risk reduction measures can lead to resources loss and parallel work. participants considered the factors that impacted hospital performance: the existence of qualified self-assessment mechanisms along with appropriate indicators in assessment checklist and a well-defined cutoff point. extracted subcategories were existence of updated instructions and guidelines, a special response and recovery plan for biologic threats, using the all-hazards approach to preparedness, and a lab plan. another participant (p ) said, "readiness assessment checklist must be completed every - months for each center. our hospitals do not have any assessment checklist for infectious diseases". in this qualitative study, which was done using content analysis, the effective factors for hospital performance in biological emergencies in ir of iran were identified as follow: diagnosis; treatment and control of infection; resources; coordination; training and practice; communication and information systems; construction; and planning and assessment. detecting a biologic event is one of the primary influencing factors in hospital performance. early diagnosis is one of the important factors for initiating immediate action and response to prevent further development of a biological agent ( ) . controlling hospital outbreaks requires rapid diagnosis and search for clusters; then, appropriate controls are executed ( ) . early diagnosis of the disease prevents its spread and can be effective in the timely treatment of exposed individuals and doing biologic triage. while an epidemic is rapidly discovered, its spread can be prevented by isolating patients and prompt prophylaxis. also, recognizing the type of biological disaster (intentional or unintentional) aspect may have an impact on hospital function because management of such biological emergencies may en-counter many complications considering type of agent, genomic manipulation, event location, geological and climatic conditions, and disease spread in the community prior to definitive diagnosis ( ) . over the past decades, the intentional enhancement of using biological agents has increased the demand for risk assessment and monitoring of such events, which often involves modeling approaches based on certain assumptions such as the ability to generate, store, and distribute. the ability to release a biological agent as a weapon does not only result in the creation of airborne transmissible microorganisms but can be transmitted from human to human and spread. management of deliberate transmissible is different from that of non-transmissible epidemics ( ) . another effective factor in hospital performance in biological events is treatment and infection control. in a biologic emergency, treatment measures and timely response to the event are important factors. triage is an important factor in controlling hospital infection during a biological emergency ( ) . most triage systems deal with traumatic or kinetic injuries ( ) . such systems are not applicable to other types of disasters, including biologic emergencies, because some factors (eg, exposure and symptoms) do not affect the infection control and make rapid diagnosis and treatment more difficult. victims are unlikely to be harmed, and there may not be a particular scene of disaster ( ) . therefore, it is necessary to consider a special system of triage instead of conventional systems ( ) . in accordance with burkle's recommended method, biologic triage is used for patients in an incident with a large number of injured people and divides them into groups: ( ) susceptible but not exposed; ( ) exposed but not yet infectious; ( ) infectious; ( ) removed by death or recovery; and ( ) protected by vaccination or prophylactic medication ( ) . in settings where infectious diseases are easily transmitted, deaths from infectious diseases are more likely than traumatic events ( ) . therefore, applying biologic triage is vital for controlling transmission. during biologic emergencies, triage makes it easier to control and treat the patients, prevents loss of resources, and reduces the probability of transmission of communicable diseases, and decreases the burden of hospitalization by reducing the number of visits to hospitals ( , ) . in this regard, access to drug and vaccine supplies and appropriate measures can reduce the number of patients or decrease the disease severity. effective actions in performance are hand washing and self-protection methods for staff, and proper isolation based on the type of disease ( , ) . providing care for patients within the hospital is an important part of patients' treatment and infection control at treatment centers ( ) . therefore, having competent nurses and trained infection control specialists as well as self-protection methods are other measures related to performance improvement ( ) ( ) ( ) ( ) ( ) . in biologic emergencies, one means of differentiation with other common emergencies is the need for self-protection methods of staff, especially physicians and nurses who have close contact with the patients ( , priate measures stops the transmission of the infection between patients and staff, including nurses ( , , , ( ) ( ) ( ) ( ) ( ) ( ) . decontamination spaces of biological patients will make these disasters distinct from others. decontamination is less important in disasters with large number of traumatic patients, but in biological disasters (especially man-made), the entry of noncontaminated patients into hospitals and the implementation of individualized and collective quarantine are of great importance ( , , ) . risk management approaches for infectious disasters are necessary to reduce the risk of secondary contamination with regards to decontamination measures and surveillance ( ) . based on the results of this study, human and financial resources, physical structures of hospitals, and equipment (including personal protective equipment, laboratory, appropriate vaccine, and antibiotics) are effective factors in the proper functioning of hospitals. these findings were consistent with those of other studies ( , ( ) ( ) ( ) ( ) . an appropriate response requires access to laboratory facilities ( ) . decontamination facilities and access to personal protective equipment for triage and decontamination teams are among the limitations of performance in biological events ( , , ) . adequate budget is usually not allocated due to the high cost of preparedness and performance measures in infectious disasters. several studies have shown that the number of public health staff may decrease at the time of biological disasters (such as flu pandemics) ( ) ( ) ( ) . typically, volunteers will meet the required human resources (efficient and trained personnel) in disasters ( , ) ; however, this would not be the case in biological disasters. although the amount of motivation to work during biological disasters varies from country to country, the total amount of motivation is lower than in other events ( , ) . this drop in staff motivation is also evident in the number of volunteers ( ) . however, more research is needed to study the willingness of public health staff in disasters ( ) . therefore, one of the most important factors in biological disasters is the provision and management of manpower required in hospitals. previous studies have shown that male gender, being a physician, having a full-time job, self-protection, and communication equipment for staff, and basic needs such as water have a positive impact on the willingness to work in such events ( , , ) . motivation facilitators for working in infectious emergencies include access to vaccination and personal protective equipment, flexible work shift, taking care of staff children, and information sharing ( ) . regarding the release of a biologic agent, the strategic storage of the vaccines as well as pharmaceuticals for treatment of the agent can be important because easy access to antibiotics and vaccines is very effective. access to ventilators for the management of infectious respiratory disasters is a necessity ( , ) . there are currently antiviral drug storages for responding epidemics that cost a lot ( ) . the lack of funding and financial resources is a major obstacle to the preparedness and proper performance in infectious disasters ( , ) . appropriate supply strategies, adaptation to the severity of the event, and the type of microorganism have a preventive and controlling role in infection from person to person ( , ) . also, having a proper physical structure to respond to biological events is important for proper functioning. this factor has been mentioned in numerous articles ( ) ( ) ( ) ( ) . examples which may be presented here are the existence of a separate entrance door for the emergency department, proper design of the rooms and the hospital, and proper equipment (eg, separate ventilators in the emergency department) ( ) . based on the findings of this study, staff training was one of the main elements of the proper functioning of hospitals in biological events. reviewing articles also indicated that education and training are key elements in disaster preparedness ( , ) . many efforts have been made to explain the capabilities and design of training curricula for management and response to cbrne events, but there is still lack of capability-based plans ( ). emergency department physicians, nurses, and support staff are the main groups for training and education. hospitals will not be able to respond appropriately in disasters without the upgraded educational guides ( ) . training is an important challenge in managing disasters which was obvious in events such as ebola outbreak. control of communicable diseases such as ebola and other infections may be affected by lack of educational materials, curricula (educational curriculum, development of educational contents, training resources, and tools), and educational contents ( ) . most of training courses (during and after ebola epidemic) have been performed for infection control staff and has not been addressed for other stakeholders ( ) . best practices for ebola education are engaging all stakeholders (eg, crisis managers, infectious disease control staff, and health workers) in educational programs. the most important educational challenges are annual budget and misdeclaration of sufficient training in an organization ( , ) . sustained education for combating the spread of infectious diseases requires annual budget, full support of the organization management, and engaging all stakeholders ( ) . the reports show poor knowledge about disaster planning and biological events in emergency departments around the world ( , , ) . it is imperative to ensure full recognition of risk reduction plans in infectious disasters for all those responsible for reducing the risk. in an egyptian study, medical residents had less training on personal protective equipment than specialists and counselors ( ) . however, education in this regard is one of the key points in infection transmission and control. occupational and non-occupational stresses in physicians were more than nurses, indicating the need for further training on the nature of pandemics, the results, complications, and methods of infection prevention ( , ) . in the absence of comprehensive support and failure to address the motivation or needs of professionals, effective education and the use of educational opportunities would be a challenge ( ) . developing educational standards and guidelines for a medical response to disasters (especially cbrn) has a major impact on emergency response to disasters ( content, determining the type of training, and evaluation of tools. a review article of cbrne training courses between - indicated that course evaluation was not done by any study ( ) . essential elements of education are personal protective training, hospital incident commanding systems for emergencies, surge capacity, and assessment and risk determination in accordance with biological disasters ( ) . coordination is one of the disaster management requirements in communities and hospitals. disaster management occurs in a complex context. this complexity is the result of a variety of different functions of the external and internal sectors in a hospital. coordination of these sectors would result in proper disaster management. in this study, internal and external coordination were key factors in response to biologic disasters. the presence of the emergency coordinator promotes health sector preparation activities. coordinators also provide a road map for moving in and out of hospital-crisis-related factors. avery et al indicated that the presence of a coordinator increases the level of readiness in the health sector in a disaster ( ) . this is evident especially in infectious disasters which require more coordination between infectious disease control centers and security sectors. jones et al showed that the coordinator had a direct relationship with the readiness of hospitals in pandemics. the connection was not linked to readiness in other settings such as casualty incidents, general preparedness of the hospital, and inefficiency of the hospital infrastructure. this could be a sign of the difference in infectious disasters. management requirements of such events include provision of vaccines, drugs, and personal protective equipment, and sufficient equipment and personnel resources at local, national, and international levels. memoranda of agreements (moas), memoranda of understanding (mous), and planning partnerships with other hospitals, health centers, government, local authorities, and other providers of support services are examples of out of organization coordination ( ) . capability of hospital external evacuation also requires external organization coordination, which according to the review of articles in the field of interhospital memoranda, has the lowest rate for children and infants ( ) . risk communication is one of the central components of proper performance of hospitals during infectious disasters ( ) . communications and information systems were derived as one of the main categories in this study. when an outbreak occurs and general public health is compromised, direct interventions and treatment options may be limited due to lack of time and the need for resources. therefore, communication, notification, and guidance are often the most important tools of public health in risk management during such events ( ) . communication readiness reduces the response time of the crisis ( ) . other impacts of communication and information systems during disasters are confidence of people in managers and acceptance of protective behaviors, disease surveillance, and reduction of confusion ( ) . to effectively respond, information should be organized in a timely fashion and be disseminated through multiple channels along with appropriate training ( ) . health communication includes key elements: message, receiver, source of information, and the channel for information exchange. the above elements should exist and function properly in any health-related communication plan. communication would be implemented in the field of informing the public as well as in health systems, especially with respect to infectious disasters ( ) . public health stakeholders, although not directly involved in public health emergency management, will take timely decisions, plan, and control timely access to information ( ) . moreover, to effectively implement communication in these disasters, standardized educational content, clear national guidelines, and pre-prepared plans in the field of communication in hospitals are required ( ) . ineffective communication is one of the potential reasons for the failure of infection control in health workers ( ) . hospital communications should be completely clear, scientific, and understandable. health workers are an important criterion for community's trust in resources and their knowledge and dealing with the situation will affect the trust of the community ( ). bonneux et al suggest that the management of unpredictable panic of hospital staff is more difficult than controlling the spread of disease ( ) . the clear release of information can prevent the fear of staff and society ( ) , and a long negative impact will occur with no on time intervention on hospital performance ( ) . understanding the proper risk from leading risk is a decisive factor in disaster management. today, in a world where the information transfer (whether right or wrong) is done at a rapid pace, the perception of risk from truly risky cases is less than estimated, and the risk of rare cases is overestimated ( ) . understanding the risk is related to the mental sensation of control. the threat of an epidemic may in part be frightening because of feeling lack of control that leads to an unwanted activity ( ) . verbal communication and standard communications (eg, guidelines, education, electronic communications, and marketing) are definitive communication pathways in infectious disasters. experiences indicate that traditional methods are unsuccessful in changing and maintaining the best performance in infection control, although newer methods (such as electronic communications and marketing) have some problems. some approaches (eg, involving health staff in the communication processes or up-down communication) can improve communication methods ( ) . the timely identification of cases of infectious diseases with increased patients over a given period of time is a critical necessity for the ipcs. survival systems in hospitals are currently focusing on a small set of microorganisms such as methicillin-resistant staphylococcus aureus, carbapenem-resistant enterobacteriaceae, and clostridium difficile ( ) . there are several pathways for the transmission of pathogens (staff to patient, environment to patient, patient to patient, visitors to patient, etc.) due to dynamic health care in hospitals. better monitoring of the epidemics onset would be implemented by operating the modern and multifunctional surveillance systems, including observing symptom reports in specific time spots, syndromic surveillance systems, prediagnosis and nonspecific criteria monitoring, and health behaviors observation (eg, absenteeism from work or school, pharmacy referral or even search rate in search engines with specific words that indicate an increase in the incidence of infectious diseases) ( ) . although more modern systems such as electronic surveillance systems have high sensitivity, their positive predictive value is low ( ) . united states has conducted surveillance systems and epidemiological surveillance with a large budget in the framework of biowatch program to monitor the deliberate propagation of biological agents ( ) . in this study, an incident management commanding structure in accordance with biological emergencies was found to be the proper structure of the main element of performance. hospital incident command systems are used as a model for disaster response in some countries. this system is an attempt for standard performance of hospitals in disasters ( , ) . in recent years, incident command system has been implemented for iranian hospitals to manage disasters with an all-hazards approach ( ) . application of this system is part of the requirements for the accreditation of hospitals in ir of iran. however, this system has limitations such as not addressing the vulnerability of hospitals and not assessing the hospital performance in disasters ( ) . the participants considered the incident command system (consistent with biological events) as an effective element of hospital performance in biological events. use of the incident command system is part of an appropriate response to cbrn events ( , ) . the hospital incident commanding system is an integrated structure that despite the volume and effects of the events can provide coordination, control, operations, planning, support, and other necessary functions for event management, if properly implemented. it also explains responsibilities clearly leading to appropriate response ( ) . the effectiveness of this system has been indicated in outbreaks of infectious diseases ( , ) . if the response to biological emergencies will be designed as a systematic approach, it would lead to faster response by establishing coordination, speed of communication, recalling staff, etc. ( ) . this adaptation could include selection of specialized infectious and epidemiologic consultants, proper planning, operations based on infection control requirements, treatment and care, and other requirements for managing biological crises. in addition, matching these systems with biological emergencies can speed up the response by increasing external and intra-organizational coordination of multiagent organs ( ) . planning was one of our extracted main categories. the existence of disaster management plans in hospitals is essential to ensure preparedness and response, even before the emergence of events. a disaster management plan is a set of procedures, policies, interactional patterns, roles, and contingencies which are developed to prepare and implement appropriate response to a crisis ( ) . this plan includes staff training plans, responding to potential biologic agents, pollution prevention, rapid communication plans, potential quarantine exposure (individual and group), resource production and planning, and rapid diagnostic plans ( , ) . the existence of evidence-based guidelines is one of the deficiencies in infection control in iranian hospitals. self-assessment, external evaluation, and the use of intra-organizational and external experts for scientific review of guidelines and plans can have a positive effect on improving hospital performance. however, performance evaluation can be assessed in real terms after disasters and from lessons learned ( ) . security issues affecting the health and national systems and context of intentional biologic events were limitations of the present study, which did not allow all selected managers to participate in the study. however, the limitation was resolved by continuing the interviews with the main managers, determining the alternative ones, and continuing the interviews until saturation. hospital management in outbreaks of infectious diseases (intentional or unintentional) is complex and requires different planning than natural disasters such as earthquakes, floods, etc. in such disasters, 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for responding to chemical, biological, radiological, and nuclear incidents organization of a hospital-based victim decontamination plan using the incident command structure incident command structure using a daily management system and the centers for disease control and prevention's patient notification toolkit drives effective response to an infection control breach lessons learned from implementing an incident command system during a local multiagency response to a legionnaires' disease cluster in sydney sars and the hospital emergency incident command system (heics): outbreak management as the mother of invention we would like to thank all of participants who spent their valuable time for interviews and other surveys. all authors disclose that there is not any actual or potential conflict of interest, including any financial, personal, or other relationships with relevant authorities or organizations within years of starting the study. key: cord- -nqvuas p authors: afshar jahanshahi, a.; mokhtari dinani, m.; nazarian madavani, a.; li, j.; zhang, s. x. title: the distress of iranian adults during the covid- pandemic - more distressed than the chinese and with different predictors date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: nqvuas p background early papers on the mental health of the public during the covid- pandemic surveyed participants from china. outside of china, iran has emerged as one of the most affected countries with a high death count and rate. the paper presents the first empirical evidence from iranian adults during the covid- pandemic on their level of distress and its predictors. methods on march - , , a dire time for covid- in iran, we surveyed adults from all provinces in iran using the covid- peritraumatic distress index (cpdi). findings the distress level of iranian adults (mean: . ; s.d.: . ) was significantly higher (mean difference: . ; t= . ; p< . ; % ci: . to . ) than that of chinese adults (mean: . ; s.d.: . ) as reported in a prior study with the same measure of covid- peritraumatic distress index (cpdi). we also found the predictors of distress in iran vary from those in china. interpretation our findings that the predictors of distress in iran vary from those in china suggest the need to study the predictors of mental health in individual countries during the covid- pandemic to effectively identify and screen for those more susceptible to mental health issues. keywords: coronavirus; -ncov; distress; mental health; psychiatric screening; identifiers of mental issues in covid- pandemic; iran; early evidence covid- disrupts lives and work and causes psychological distress to the general public [ ] [ ] [ ] [ ] . the covid- outbreak first triggered public panic and mental health distress in china . early research has found working adults in more affected areas in china had worse health conditions, more distress and lower life satisfactions . researchers at shanghai mental health center developed a covid- peritraumatic distress index (cpdi) to assess the distress level specific to covid- . such research on mental health during the covid- pandemic is critical to identify and screen people psychiatrically based on their distress levels to prioritize assistance , . the identification of those who are more likely to suffer mentally enables more targeted assistance from caregivers and policymakers, especially given the limited resources relative to the scale of the pandemic , . one of the countries most affected by covid- is iran . when we started our survey on march , , iran had one of the highest national counts of covid- confirmed cases ( , ) and deaths ( ), and a mortality rate of . %, as reported by the iranian government. however the figures reported by bbc persian for iran were much higher. the covid- outbreak in iran has been compounded by the ongoing decade-long us-led sanctions on iran. a lancet correspondence noted that "all aspects of prevention, diagnosis, and treatment are directly and indirectly hampered, and the country (iran) is falling short in combating the crisis. lack of medical, pharmaceutical, and laboratory equipment such as protective gowns and necessary medication has been scaling up the burden of the epidemic and the number of casualties" . we provide the first empirical evidence on iranian adults' level of distress and identify several predictors of their distress under the covid- pandemic. we surveyed iranian adults aged and above march - , . on those four days, there were , , , , , and , total confirmed cases and , , and deaths respectively in iran. the situation was dire. for instance, on march , iranian media reported that about people died due to methanol poisoning in a desperate hope that drinking alcohol kills the virus, even though the islamic state of iran forbids the sale of alcohol for drinking. on march , prisoners in several prisons were distressed enough that they clashed with guards, set prisons on fire, and somehow escaped. given the dire situation in iran and the lockdown to contain the virus, we delivered the survey online across all provinces in iran. the survey got the ethics approval (# ) at tsinghua university. we promised the respondents confidentiality and anonymity of their responses. participants answered the survey on their gender, age bracket, education level, number of children, whether they had covid- , exercise hours per day in the past week, working situation (work from home; work in office, etc.), employment status (employed, unemployed, studying, and retired) and the covid- peritraumatic distress index (cpdi) . cpdi is an index of questions designed to capture the frequency of specific phobias and stress disorders relevant to covid- , including anxiety, depression, specific phobias, cognitive change, avoidance and compulsive behavior, physical symptoms and loss of social functioning . cpdi ranges from to . cpdi was originally developed in chinese, and we had the index translated from its english version to persian. the english and persian versions of cpdi can be found in the appendix. our online survey received responses from all provinces in iran. table contains the descriptive characteristics of the participants. of the participants, . % were female, ( . %) reported being free from the disease, ( . %) reported having covid- , and ( . %) were unsure of their disease status. in the past week, . %, . % and . % of the participants exercised on average , and hours per day respectively, . % of them did not exercise in the past week, and the remaining . % exercised hours or more per day. by employment status, . % were employed, . % were unemployed, . % were studying, and the rest . % were retired. by working situations, . % were working/studying from home, . % were not working/studying due to the outbreak, . % were not working/studying before and during the outbreak, and . % still worked in an office. the participants reported their distress level in the past week using cpdi, which had a cronbach's alpha of . . the mean (sd) score of cpdi in the sample was . ( . ), higher than the cpdi of . ( . ) reported . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . https://doi.org/ . / . . . doi: medrxiv preprint in china from january to february , . the difference in the mean values between iranian and chinese samples is . (t= . ; p< . ; % ci: . to . ). based on the cut-off values of distress in cpdi, respectively . % and . % of the iranian adults experienced mild to moderate and severe psychological distress, compared to . % and . % respectively in the chinese sample . . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . ci - . to . ) did not predict distress as they did in the chinese sample . adults with more children felt less distress (β=- . , p= . , % ci - . to - . ). adults who were unsure whether they had covid- reported higher distress than those who reported being free from the disease (β=- . , p= . , % ci - . to - . ). there is no significant difference between those who reported having the disease and the rest, possibly due to the very small number ( ) of confirmed covid- cases in our sample. adults who exercised more reported lower distress (β=- . , p= . , % ci - . to - . ). adults who were not working due to the covid- pandemic reported higher distress than those who worked from home (β=- . , p= . , % ci - . to - . ), at the office (β=- . , p= . , % ci - . to . ), or who were not working even before covid- (β=- . , p= . , % ci - . to - . ). the unemployed reported higher distress than the employed (β=- . , p= . , % ci - . to - . ) and students (β=- . , p= . , % ci - . to - . ). there is no significant difference in distress between the retired and the rest of the sample. although covid- is expected to wreak havoc on the mental health of the public - , there is little evidence of it, especially outside of china. our findings show that iranian adults experienced significantly more distress (mean cpdi= . ) than chinese adults (mean cpdi= . ). in late march , a staggering . % and . % of iranians in our sample reported mild to moderate and severe distress -also more severe than in china . our findings suggest that the predictors of distress are likely to vary across countries. while gender and exercise hours predicted distress in both iran and china , , age and education predicted distress in china but not in iran . it is worth noting another study also found age was not a significant predictor of distress among working adults in china during covid- . moreover, iranian adults who worked from home, at the office, or had not worked during and before covid- all reported lower distress that those who were not working due to the covid- pandemic. in comparison, in china, only individuals who worked at an office reported significantly lower distress than those who were not working due to covid- . the differences in the predictors of distress during the covid- pandemic across iran and china are understandable, as different countries vary in their medical systems, the availability of personal protective equipment (ppe), cultures, labor and employment conditions, the policies of lockdown, the ease of working from home and maintaining a living in a pandemic, and the information in both mainstream and social media, to name just a few. the results therefore suggest we need to identify useful predictors of mental health in individual countries during the covid- pandemic. lastly, individuals who were unsure whether they had covid- reported higher distress than individuals who reported not having the disease, suggesting we need to pay attention to those individuals who might be anxious without knowing their specific covid- status, as people can be asymptomatic or take time to develop symptoms. one solution is to test such individuals if conditions permit, as otherwise these individuals can experience high distress. the study has certain limitations. first, we conducted this study using an observational cross-sectional survey, so our findings are predictive instead of causal. second, our sample is not nationally representative, as our focus was to identify for policymakers and potential caregivers who in the population might need more help. third, even though our sample contained adults who reported having covid- , the number of infected cases in our sample is too small, and moreover we suspect they would belong to the majority of covid- infected cases that have mild symptoms, as people with more severe symptoms would not be able to answer our survey. in sum, this paper provides the first empirical evidence of the level of distress of iranian adults during the covid- pandemic. the results suggest adults in iran are experiencing more distress than adults in china, with level of distress predicted by different factors, suggesting future research needs to examine mental health and the predictors in individual countries to effectively identify and screen those who are more susceptible to mental health issues during the covid- pandemic. timely mental health care for the novel coronavirus outbreak is urgently needed -ncov epidemic: address mental health care to empower society unprecedented disruptions of lives and work: health, distress and life satisfaction of working adults in china one month into the covid- outbreak a nationwide survey of psychological distress among chinese people in the covid- epidemic: implications and policy recommendations iranian mental health during the covid- epidemic covid- battle during the toughest sanctions against iran none. we declare no competing interests. key: cord- -ykko al authors: takian, amirhossein; raoofi, azam; kazempour-ardebili, sara title: covid- battle during the toughest sanctions against iran date: - - journal: lancet doi: . /s - ( ) - sha: doc_id: cord_uid: ykko al nan number of casualties. despite who and other international humanitarian organisations dispatching supplies and medical necessities, the speed of the outbreak and the detrimental effects of sanctions have resulted in reduced access to life-saving medicines and equipment, adding to the health sector's pre-existing requirements for other difficult health conditions. it is shameful that besides the lives lost to this deadly virus, extreme sanctions limit access to necessary materials and therefore kill even more iranian people. although sanctions do not seem to be physical warfare weapons, they are just as deadly, if not more so. jeopardising the health of populations for political ends is not only illegal but also barbaric. we should not let history repeat itself; more than half a million iraqi children and nearly venezuelans were killed as a result of un security council and us sanctions in and - , respectively. the global health community should regard these sanctions as war crimes and seek accountability for those who impose them. given the covid- pandemic and its alarming outcomes in iran, the international community must be obliged to stand against the sanctions that are hurting millions of iranians. it is essential for the un security council and the usa to ease, albeit temporarily, the barriers to providing life-saving medical supplies to iran. in the future, the global community must anticipate possible impacts of sanctions on humanitarian aid and move to prevent further disasters from happening. viruses do not discriminate, nor should humankind. introduction of preventive measures such as social distancing to reduce the pace of the spread, providing valuable time for upgrading of the medical services, and preparing the community. if the use of the term pandemic is delayed too long, the declaration of the pandemic could convey a message to the public that the authorities have lost control, generating irrational panic reactions. since it is expected, and even perhaps desirable, that the public experience some fear during a pandemic, an early declaration of a pandemic might be helpful in mitigating panic. recruiting public cooperation is much more feasible when the society in general and the health services in particular are not yet under considerable pressure, and there is time for appropriate explanations to the public as to how the pandemic will be controlled. the question remains as to what is the optimal timing for declaring a pandemic. following the h n pandemic, morens and colleagues provided useful criteria for defining a pandemic. they included the following components: the cause should be a new virus that has not circulated in humans previously, the disease should be widespread geographically, there should be clear person-to-person spread, and outbreaks should be explosive in nature, with a relatively high casefatality rate. it seems to me that for some time, the covid- outbreak met all these criteria. since there continues to be a lack of consensus about when it is appropriate to use the term pandemic, i suggest that a multi-disciplinary group of epidemiologists, infectious disease specialists, risk communicators and health administrators be convened to create new, clearer, expanded definitions of the terms outbreak, epidemic, and pandemic. i declare no competing interests. the economic loss caused by the spread of covid- in iran coincides with the ever-highest politically induced sanctions against the country. although various sanctions have been in place for the past four decades, since may, , the unilateral sanctions imposed by the usa against iran have increased dramatically to an almost total economic lockdown, which includes severe penalties for non-us companies conducting business with iran. the iranian health sector, although among the most resilient in the region, has been affected as a consequence. all aspects of prevention, diagnosis, and treatment are directly and indirectly hampered, and the country is falling short in combating the crisis. lack of medical, pharmaceutical, and laboratory equipment such as protective gowns and necessary medication has been scaling up the burden of the epidemic and the www.thelancet.com vol march , of the disease and evidence pertaining to effective public health interventions is increasingly available. however, this is only advantageous if we incorporate the best available evidence from observations elsewhere and use the time this affords us to refine a comprehensive response based on input and scrutiny from a broad base of scientific experts. with the uk increasingly becoming an outlier globally in terms of its minimal social distancing populationlevel interventions, transparency is key to retaining the understanding, cooperation and trust of the scientific and health-care communities as well as the general public, ultimately leading to a reduction of morbidity and mortality. we declare no competing interests. most other countries are responding globally, including elsewhere in europe. as the government has stressed, it is imperative to delay and flatten the epidemic curve to ensure the national health service can cope. this is particularly essential for the uk, which only has · hospital beds per population, fewer than in italy ( · per ), france ( · ), and germany ( · ). initial data from italy have shown that - % of actively infected patients with covid- required intensive care during the first days of march, . it is not clear how the uk's unique response is informed by the experiences of other countries, particularly those that have achieved relative control over the virus as a result of widespread testing, contact tracing, and state-imposed social distancing measures, such as singapore, hong kong, taiwan, and south korea. the who-china joint mission on coronavirus disease shows very clearly that only immediate and decisive public health responses worked to prevent or delay hundreds of thousands of cases in china, and who has advised that it is vital to tackle the virus at the early stages with social distancing. we welcome the uk government's announcement that the modelling and data considered by its scientific advisory group for emergencies will be published in the future. however, we request that the government urgently and openly shares the scientific evidence, data, and models it is using to inform current decision making related to covid- public health interventions within the next h and then at regular intervals thereafter. time is a luxury we simply do not have as we face this critical public health crisis. as we have already seen in other countries, a matter of a few days can prove critical in terms of saving lives and avoiding health system collapse. as the uk was not the first country to face a covid- outbreak, knowledge the uk government asserts that its response to the coronavirus disease (covid- ) pandemic is based on evidence and expert modelling. however, different scientists can reach different conclusions based on the same evidence, and small differences in assumptions can lead to large differences in model predictions. our country's response to covid- is demonstrably different from how who-directorgeneral-s-opening-remarks-at-the-mediabriefing-on-covid iranian ministry of health and medical education so near, so far: four decades of health policy reforms in iran, achievements and challenges assessment of the effects of economic sanctions on iranians' right to health by using human rights impact assessment tool: a systematic review how countries in crisis can prepare for a coronavirus epidemic who. who team arrives in tehran to support the covid- response impacts of international sanctions on iranian pharmaceutical market the harsh effects of sanctions on iranian health who. novel coronavirus ( -ncov) situation report - we declare no competing interests. key: cord- -jspfwuqu authors: farangi, mostafa; asl soleimani, ebrahim; zahedifar, mostafa; amiri, omid; poursafar, jafar title: the environmental and economic analysis of grid-connected photovoltaic power systems with silicon solar panels, in accord with the new energy policy in iran date: - - journal: energy (oxf) doi: . /j.energy. . sha: doc_id: cord_uid: jspfwuqu in recent years, authorities in iran have introduced supporting policies for renewable energy resources but there is no comprehensive and updated survey from this perspective. this work aims to give a comprehensive survey on the country’s background from energy outlook and its prominent policies for renewable energy resources. due to the high co( ) emissions alongside with the high solar energy harvesting potential in iran, we have presented a clear simulation on kw and mw grid-connected photovoltaic (pv) power plants using retscreen software to determine the environmental and economic aspects based on the net greenhouse gases (ghg) emissions reduction, the annual electricity exported to the grid, the cumulative cash flows, and the payback period for the initial investment. according to this simulation, the annual ghg emissions reduction and the annual electricity exported to the grid for kw and mw pv power plants are . tco( ), tco( ), mwh, and mwh, respectively. from the economic outlook, based on the new feed-in tariff for power plants and the supposed initial costs, the payback period for the initial investments are between and , and years for kw and mw pv power plants, respectively. farangi and ebrahim asl soleimani conceived of the presented idea. farangi developed the theory and performed the computations. mostafa zahedifar, omid amiri and jafar poursafar verified the analytical methods. all authors discussed the results and contributed to the final manuscript. introduction worldwide primary energy demand increased at a rate of . % in , nearly double its -year average of . % from to , which is the highest rate since [ ] . due to this increasing demand for energy and burning of more fossil fuels, global warming has become one of the greatest consequential dilemmas facing the human being with considerable social, environmental and economic outcomes. there are three outstanding ethical dilemmas, making difficult the climate change discussions: how to settle the rights and obligation of the developed and developing countries; how to estimate geo-engineering schemes planned to slow or reverse climate change; and how to test our obligation to next generations who must struggle with an inferior climate we are changing today. in recent years, public awareness, the number of communities, national and international meetings about global warming have raised around the world. as prominent examples of international meetings, we can mention the paris agreement [ ] and the kyoto protocol [ ] as the two most important conventions by the united nations on climate change. at the same time, worldwide carbon emissions from energy consumption increased by . % in , again the highest rate for seven years, with emissions raising by around . gigatonnes. to a significant extent, the increase in carbon emissions is clearly a direct outcome of the growth in energy consumption [ ] . due to the important role of coal in carbon dioxide (co ) emissions, in , more countries obligated to phasing out or moving away from the coal consumption for electricity production (e.g., canada, france, etc.) [ , ] or do not more funding coal utilization (e.g., brazil's development bank) [ ] . opposing this trend, but several countries declared programs to increase coal production and utilization [ ] . however in there was a significant move back to coal with both production ( . %) and consumption ( . %) [ ] . in large number of countries, the emission quotas referring to each power company are limited. with the emission trading pattern they can determine the most preferred solution after achieving the pareto solution set regarding different emission quotas. this technique is economically useful for countries with this ability [ ] . the emission trading approach can be employed as a useful pattern by the power companies to maximize their profitability [ ] . comparatively low worldwide prices for coal, natural gas and oil, keep challenging renewable energy markets, particularly in the heating and transport sectors [ , ] . subsidies for fossil fuels, which stayed remarkably greater than renewable energy subsidies, also continued to influence renewable energy development. in over countries had obligated to phasing out subsidies for fossil fuels due to international commitments [ ] . also, subsidy revises were instituted in in several countries such as brazil, egypt, india, iran, nigeria, saudi arabia, sierra leone, thailand, tunisia, ukraine, venezuela [ ] . in the energy sector, the world needs novel trends that are secure, sustainable and favorable to all, and one of the most beneficial procedures is the utilization of sustainable energy resources instead of fossil fuels. the progression and consumption of sustainable energy resources are a fundamental alternative to climate change and global energy demand. utilization of sustainable, reliable and inexpensive energy will determine most standard aspects of life, in the future. as of , many countries directly provided renewable energy development and deployment with a broad range of policies. these policies prepare direct and indirect support, in an effort to economy-wide economic progression, environmental conservation, and national security. technology developments, descending costs and growing utilization of renewable energy resources are the results of these policies. in each country, authorities promote policies to merge renewable generation into their conventional national energy systems. due to the power sector is keeping to gain the most attention in energy subject, policymakers have introduced various support procedures and reformed existing policies to improve this sector by the utilization of renewable energy resources. these policies can be listed as follows: feed-in tariff (fit) policy is an energy-supply policy concentrated on supporting the progress of renewable energy plans by proposing long period purchase arrangements for the sale of renewable energy electricity. these arrangements propose purchasing every kilowatt-hour electricity for - years. the proposed payment levels for each kilowatt-hour can be distinguished by various factors such as project size, resource quality, technology type, and project location to properly cover main project costs. policymakers can also arrange the payment levels to decrease for installations in the following years, which will both follow and encourage changes in technology. the two most ordinary fit policies are the fixed fit and the feed-in premium. in the fixed fit, which is the most widely used fit design, payment quantity stays independent of the market price for electricity, proposing a guaranteed payment for a clearly described period. in the feed-in premium, which is being increasingly used, the payment quantity is based on a premium proposed above the market price for electricity and this premium can either vary, dependent upon a sliding scale, or it can be constant. several countries, especially in europe and asia, have shifted away from fit policies to auction and tender policies to support large-scale renewable energy project deployment. in spite of the fact that support for large-scale renewable energy projects is changing to a different mechanism in a growing number of countries, but fit policies continue to be valid in many countries for the deployment of small-scale renewable energy installations. policy designers continue to change fit rates as the technologies become more cost-competitive in each country. auctions and tenders are the most rapidly extending scheme of supporting mechanism for deployment of renewable energy projects and are becoming the preferred policy for supporting large-scale projects. generally, they are on the basis of the cost of electricity generation; although in auctions, the price is the only factor to be considered, tenders may contain extra criteria. net metering is a metering and billing agreement designed to compensate small-scale system owners for any electricity production that is exported to the grid. net metering allows utility customers with on-site distributed energy generation to offset the electricity they extract from the utility grid during the billing cycle (e.g., one month) and they pay for the net electricity consumed from the grid. net metering customers directly utilize the electricity produced on-site by their generation systems. if the amount of generation exceeds the utilized electricity, the excess electricity is exported to the utility grid. if a customer utilizes more electricity than distributed energy generation system produces, he or she imports electricity from the utility grid and pays the full retail rate for that amount of electricity, exactly similar to a traditional utility customer. renewable portfolio standard (rps) policy is a regulatory mandate to raise energy generation from renewable resources and it's also called a renewable electricity standard. the rps procedure usually places an obligation on power supply companies to generate a clearly described fraction of their power production from renewable energy resources. besides these main policies, some countries provided public funds by grants, loans or tax incentives to guide investment in renewable energy development. however, most of these incentives have been decreased or canceled in recent years in reaction to tightening fiscal budgets and/or reducing technology costs. although in recent years, policymakers in iran have introduced different supporting policies for renewable energy resources but there is no collective and updated survey from this point of view. this study examines the country background from energy outlook and some of its important policies for energy subject and introduces current supporting policy for various renewable and clean energy resources. due to the serious co emissions and air pollution in large cities of the country alongside with the high solar energy harvesting potential and growing trend of utilization of pv technology in iran, we investigate environmental and economic aspects of two different scales of pv systems, kw as a candidate for small-scale (for residential and commercial users) and mw as a candidate for large-scale (utility-scale) grid-connected pv power systems in tehran, iran, using retscreen software based on the new feed-in tariff policy. country background and energy policy . . iran iran, an asian country, is the th largest and th most populated country in the world. in this territory, population and technology growth has driven to the necessity for more energy production; while electricity production is mainly controlled by its fossil fuel resources. this country has the second-largest proven natural gas reserves ( . trillion cubic meters) and the fourth-largest proven crude oil reserves ( . thousand million barrels) in the world, around % and . % of the world's total reserves, respectively [ , ] . it has an outstanding regional occasion because it is surrounded by several countries which are more opportune for international economic progression due to their vast and various energy resources, tourism market, passenger and freight transportation. this occasion could be managed more appropriately in the energy field with a suitable energy business strategy to accomplish electrical, gas pipeline, and crude oil pipeline loops between neighboring countries and iran [ ] . energy policy however, iran's immense fossil fuel energy resources alongside with subsidization, have resulted in growing consumption of energy without seriously being worried about energy efficiency and the negative influences on the environment. during recent years, it has embarked several policies for production and consumption of energy. four remarkable policies that have affected energy demand, can be mentioned as: i. the first and the most prominent energy policy in iran is the large energy consumption subsidization, particularly in households and transport sectors. there are several distinctive approximations for energy subsidies in iran (between . to percent of gdp); however, it is accepted that iran's energy subsidies are one of the top-ranking energy subsidies in the world. ii. the second policy is assigning of oil production capacity in accord with the opec endorsements. meanwhile, faced with capital restrictions, iran identified the important role of international investment in the oil sector to develop new fields and improve the recovery factor in the existent fields, hence presented a "buy-back" contract to international investors. this contract permitted international companies to finance in oil and gas fields in iran and to share profits with the domestic counterparts. iii. the third prominent energy policy in iran has been the noticeable consumption and progression of natural gas fields from the s so far. this policy reinforced, especially when iran discovered its share of the south pars gas field, the world largest gas reservoir, which is located in the persian gulf. iran has been using most of its ever-growing gas production to replace relatively cheap and environmentally friendly natural gas for domestic consumption of crude oil products in various sectors. in , its energy consumption based on natural gas was . million tonnes of oil equivalent (mtoe) [ ] . iv. the fourth important energy policy in iran is providing rural areas with electricity by new transmission lines. this policy has assisted a lot of rural communities to receive clean and cheap energy and decrease environmental problems like for example deforestation. some other prominent policies in the energy sector in iran can be listed as follows: although high-impact low-probability (hilp) events such as earthquakes, hurricanes, and consequent flooding have prominent influence on power generation companies [ ] and the number of these natural disasters has increased in recent years in iran, but there is not a comprehensive and clear policy for these situations. generally government decides based on the event impact on local people life and, for example, provide them with free fuel and power for a certain period of time. as another example for emergency situation, during covid- crisis in iran the authorities have postponed the payments due for water and power bills in the country. renewable energy policy similar to other countries in the world, there has been a growing trend toward the utilization of sustainable energies in iran, too. besides enormous fossil fuel reserves, iran enjoys a perfect potential of using renewable energies (energy resources that are naturally inexhaustible and replenished) such as solar, wind, geothermal, biomass and hydropower. in iran, electrical customers participate in an electricity market and buy electricity generated from fossil fuels. due to the current levelized cost of electricity (lcoe) prices, production of electric power based on renewable energy resources is not economical on its own yet. therefore, the progression of the renewable energy division in iran is leaned upon the government incentive attitude and its encouraging policy on this subject. from the environmental aspects, noticeable troubles in iran are co emissions and air pollution. in , co emissions in iran were . million tonnes, increased by . % growth rate per annum that is above double its -year average of . % from to [ ] . so recently, the authorities have paid basic investment in harnessing renewable energies and laid down the new supporting policies to inspire people to use clean energy resources. due to the huge investments in hydropower, a large share of renewable power generation in iran is hydroelectricity, around . mtoe in [ ] . although in recent times, it has been financing on others, such as wind and solar power, too. solar energy as a worthwhile renewable energy source has attracted a lot of attention nowadays. living things, including the human being, depend on solar energy for warmth and food. however, the human being also harnesses solar energy in many distinctive ways. they use solar energy either indirectly as the form of fossil fuels, biomass, wind, hydropower, and … or directly by utilization solar thermal technology (using solar energy to generate low-cost, environmentally friendly thermal energy) and pv technology. pv devices or solar cells directly convert energy from the sunlight into electricity by the pv effect quietly, with no pollution or moving parts. a pv system is working differently than most electric-generating systems because it generally doesn't need a technician to be on-site for daily direct management due to its automated operation, and it just needs insignificant and slight oversight, monitoring, and maintenance. these systems are designed modularly and can be built on different scales. fortunately, solar energy is broadly achievable in most areas of iran, specifically in the southern and central regions (fig. ) . this country is potentially one of the best regions for solar energy harvesting because located in the global sunbelt, and experiences three hundred sunny days per year on over two-thirds of its land area, according to satba (renewable energy and energy efficiency organization), the ministry of energy, iran [ ] . the radiation distribution varies between . kwh/m in the southeast part to . kwh/m in central parts. in a country-wide analysis of irradiance, it is estimated that on percent of iran's land area, solar irradiance is between - kwh/m /year [ ] . the calculations show that the applicable solar radiation hours in iran surpasses hours per year [ , ] . according to the reports, by covering only % of the deserts in the country by solar collectors, the output energy would be five times greater than its annual gross electricity output [ , ] . besides iran's solar energy harvesting potential, several factors such as the price of fossil fuels in electricity generation and import of expensive pv instruments have limited applying pv technology in iran. as mentioned above, new supporting policies such as different feed-in tariff and subsidies have been described to stimulate using of renewable energies and turn them to competitive technologies with common electricity production methods based on the burning of fossil fuels. according to the new supporting policy of the government, the latest prices for electricity based on the feed-in tariff by offering long-term contracts to renewable energy resources are shown in table [ ]. the selected currency in this study is the iranian rial (irr) which can be converted to us dollar (usd) easily ( usd ≈ irr). according to table , the government will buy electricity from the producers at two prices: during the first years, the purchasing price is relatively high to investors gain their investment as soon as possible. however, during the second years, the price will be decreased to % of the prime bid for all resources except the wind systems (the price will be calculated according to their capacity factors), and after years the electricity can be sold in energy exchange. so, investments in different renewable and clean energy resources (especially pv technology) with different scales, are fostered by the new feed-in tariff to decrease consumption of fossil fuels in iran. known as turbo-expander or expansion turbine ( . ) ( . ) * the highest level capacity for the wind and solar farms will be determined by the policy of the ministry of energy on renewable and clean energy development policy, which is following up to , mw in a year by the private sector. ** during the second decade, the contract fee will calculate based on the capacity factor. for wind farm with capacity factors ≥ % and ≤ % during the first years, the prime fee will multiply in . and , respectively. for capacity factors between - %, the prime fee will multiply in a number proportionally. regarding the growing trend in using of pv technology around the globe, there is a considerable requirement for relatively simple, and user-friendly software packages, for the designing and performance assessment of pv systems by installers particularly during the prime design phases of a project. this requirement has led to the progress of many pv software packages such as pvwatts, pvsyst, polysun, homer, retscreen, pv jedi with various capabilities for analyzing these power systems. generally, simulation and analyzing of each pv power system include main divisions such as technology and performance analysis, energy systems analysis, environmental analysis, and economic and financial analysis. in this article the simulation has been carried out by applying retscreen, a clean energy management program for energy efficiency, renewable energy and cogeneration project feasibility examination and also ongoing energy performance analysis [ ] . this is an extremely user-friendly software and provides decisionmakers with primary or even meticulous detailed information about the project. one of the main advantages of this software is that it makes the project assessment procedure easier and a great number of projects have been investigated by this software. the investigated case of the pv installation is the grid-connected pv system with easy installation, and in locations with trustworthy grid power, it generally doesn't need the battery equipment for backup power. after installation, these systems do not need extra care and service, do not generate co and air pollution, and they are as quiet as the sun. a schematic diagram of the simulated grid-connected pv power system is shown in fig. . fig. . schematic diagram of a grid-connected pv power system. retscreen software is provided with nasa's satellite-derived meteorological data (developed by nasa' langley research center in collaboration with canmetenergy) for any location and the nasa prediction of worldwide energy resource (power) project. this data set is a helpful option when there is no access to ground-based data or itemized resource maps for the project location; it is calculated from data collected for a -year period starting in july , applying a -degree cell (at mid-latitudes ( °) the cell dimensions is around x km). solar rediation parameters are derived using satellite data of the atmosphere and earth's surface. the other meteorological values are adapted from goddard earth observing system (geos) meteorological analysis by the nasa's global modeling and analysis office (gmao). the selected site for this simulation is mehrabad national airport which its elevation, latitude, and longitude coordinates are m, . ˚ and . ˚ respectively. climate data for this site is gathered from the weather station and nasa database in retscreen ( table ). the capacity factor of pv module (the ratio of the average power produced by the power system over a year to its rated power capacity) is vital for selecting a proper site and solar system, and its quantity is . % for the fixed solar array in tehran [ ] . we used yingli silicon solar pv modules (mono-si-panda-yl c- b) wp with a module efficiency of . % for this simulation. the numbers of pv modules for kw and mw pv power plant are and modules, respectively. according to the pv market in iran, the estimated initial and periodic costs (due to the inverter replacement) for these two systems are shown in table . several factors such as site location, type of pv technology, maintenance and … may affect these estimated prices. kw pv power plant the first case, kw pv power plant, is a candidate for small-scale pv power plants. a small-scale pv system is normally mounted on places like residential or commercial roofs, the ground in backyards, or facade of the building, etc. along with the grid, these systems can take advantage of the battery equipment for backup power during a power outage, or while the sun is not shining. however, this advantage comes with intensified complexity, price, and maintenance. hence, in locations with trustworthy grid power, ignoring the battery backup system is the logical choice. table . equivalent cases substitute for kw pv power plant based on net annual ghg emissions reduction in iran. cars & light trucks not used liters of gasoline not consumed , barrels of crude oil not consumed . as mentioned before, global warming has become one of the greatest consequential dilemmas facing the human being in this century, thereby researching on ghg emissions is necessary for any power project. an emissions analysis worksheet is provided in retscreen to help studies on the ghg emissions mitigation potential of renewable energy projects. the main ghgs are water vapour, co , methane (ch ), nitrous oxide (n o), ozone (o ) and fluorinated gases. ghgs that are considered for energy project analysis are co , ch and n o which are expected in the retscreen emission reduction analysis. results from the ghg equivalence tool in the retscreen are presented in terms of the annual amount of co that would be equivalent to the total emission reduction, regardless of the actual gases. and it's done by converting ch and n o emissions to the equivalent co emissions based on their global warming potential. in table , one can find interesting data about kw pv power plant from net annual ghg emissions reduction outlook. in this table, important equivalent cases from the environmental perspective, such as the number of cars & light trucks that are not used, liters of gasoline not consumed, barrels of crude oil not consumed, people reducing energy use by %, acres of forest absorbing carbon, hectares of forest absorbing carbon, tons of waste recycled are mentioned. according to this simulation, the annual ghg emissions reduction and the annual electricity exported to the grid for kw pv power plant are . tco and mwh, respectively. a financial analysis worksheet in retscreen is provided to aid feasibility investigation of renewable energy projects. by considering a new supporting policy of the government for renewable energy resources, a financial analysis was carried out based on the new feed-in tariff for pv electricity in iran (table ) and estimated initial and periodic costs for kw pv power plant (table ). the cumulative cash flows from the simulation are plotted versus time in fig. . according to this figure the estimated initial costs for kw pv power plant is . birr based on the pv market in iran. after starting operation, the gained annual interest income is above mirr so the payback period for the initial investment is between - years. the change in linear trend of this plot is related to the estimated periodic costs ( mirr) for replacing invertors and other necessary services after years. following this payment, the same annual interest income can be gained till years. the average annual interest rate for this investment is about . % over years, base on the new feed-in tariff for this scale of pv power plant. the second case, mw pv power plant, is a candidate for large-scale pv power plants. large-scale (utilityscale) pv power plants, also known as solar parks, farms, or ranches (particularly when they are located in agricultural areas) are power stations that provide a considerable amount of electrical energy to great numbers of consumers. large-scale pv power plants are ground-mounted, usually with fixed tilted solar panels instead of utilizing expensive tracking systems. a similar examination was carried out on mw, same as kw pv power plant. first, the ghg emissions mitigation was studied and related data are presented in table . according to this simulation, the net annual ghg emissions reduction and the annual electricity exported to the grid for mw pv power plant are tco and mwh, respectively. table . equivalent cases substitute for mw pv power plant based on the net annual ghg emissions reduction in iran. fig. . according to this figure the estimated initial costs for mw pv power plant is birr and after starting operation, the obtained annual interest income is above birr so the payback period for the initial investment is about years. the change in linear trend of this plot is related to the estimated periodic costs ( . birr) for replacing invertors and other necessary services after years. following this payment, the same annual interest income can be gained till years. the average annual interest rate for this investment is about % over years, base on the new feed-in tariff for this scale of pv power plant. we have simulated two different scales of the pv power plant and investigated them from the environmental and economic aspects based on co emissions, and the cumulative cash flows after the new feed-in tariff, respectively. from the environmental (co emissions) and electricity generation perspective, a comparison between these two scales of pv power plant shows us that co emissions and the annual electricity exported to the grid, have a linear relationship with the scale of the power plant. we can reduce the quantity of co emissions by using pv technology as multiple small-scale pv power plants (by residential and commercial users), or a large-scale pv power plant (by the governments) in the same impact. from the economic outlook, there isn't a linear relation in cumulative cash flows rate and the average annual interest rate with the scale of the pv power plant. with a comparison between these two cases, as candidates for small-scale and large-scale pv power plants, we can realize that this difference comes from various amounts of the feed-in tariff for different scales of pv power plants in iran. according to the supposed initial costs, the payback period for the initial investments are between - , and years for kw and mw pv power plants, respectively. hence, in accord with the high initial costs for pv power plants, the ministry of energy in iran has formulated an incentive and supporting policy to persuade people, spatially residential or commercial users or private sector to invest in small-scale pv power plants. therefore, residential and commercial customers will have considerable long-term benefits, from taking part in an electricity market and selling their pv systems output. while those pv systems generally do not need a technician to be on-site for daily direct management due to its automated operation, and they just need insignificant and slight oversight, monitoring, and maintenance. on the other hand, the government itself has taken responsibility to set up large-scale pv power plants around the country. by focusing on these two procedures in pv subject, iran takes its first steps in lessening reliance on fossil fuels consumption and its related environmental issues. in future research, we will examine the various feasible renewable energy projects in iran, for different scales from the environmental and economic aspects in terms of this new feed-in tariff for each technology categories and scales. also, the authors will try to provide data from available operational cases to check the impacts of this supporting policy in reality. in conclusion, the intent of this paper is to give a brief and comprehensive survey on various energy policies and provide a technical outlook from the environmental and economic aspects for two different scale gridconnected pv power systems according to the new supporting policy for renewable energy resources in iran. we have presented a clear and efficient simulations on kw and mw grid-connected pv power plants using retscreen software to illustrate the mentioned aspects based on the net ghg emissions reduction, the annual electricity exported to the grid, the cumulative cash flows, and the payback period for the initial investment. from the environmental (co emissions) and electricity generation perspective, a comparison between these two scales of pv power plant demonstrates that co emissions and the annual electricity exported to the grid, have a linear relation with the scale of the power plant. from the economic outlook, due to varying amounts of the feed-in tariff for different scales of pv power plants, there isn't a linear relation in cumulative cash flows rate with the scale of the pv power plant. according to the supposed initial costs, the payback period for the initial investments are between - , and years for kw and mw pv power plants, respectively. hence, in accord with the high initial costs for pv power plants, the ministry of energy in iran has formulated an incentive and supporting policy to persuade residential, commercial users, and private sector to invest in small-scale pv power plants. furthermore, the government has taken responsibility to set up large-scale pv power plants around the country. it can be concluded that, by focusing on these two procedures in pv subject, iran takes its first steps in lessening reliance on fossil fuels consumption and its related environmental issues. coal and lignite production data | world coal production | enerdata n canada set to phase out coal-fired power by | the independent n france to shut down all coal-fired power plants by | the independent n update -brazil development bank scraps financing for coal-fired plants n coordinated wind-thermal-energy storage offering strategy in energy and spinning reserve markets using a multi-stage model cooptimized bidding strategy of an integrated wind-thermal-photovoltaic system in deregulated electricity market under uncertainties how do oil prices, macroeconomic factors and policies affect the market for renewable energy? natural gas prices | natural gas fossil-fuel subsidy reform : critical mass for critical change global subsidies initiative n.d iran's oil development scenarios by the potential of harnessing solar radiation in iran: generating solar maps and viability study of pv power plants solar photovoltaic power plants in five top oilproducing countries in middle east: a case study in iran risk-based probabilistic-possibilistic self-scheduling considering high-impact low-probability events uncertainty download free solar resource maps | solargis n solar potential and irradience map in iran | renewable energy and energy efficiency organization (satba) n.d estimation of height-dependent solar irradiation and application to the solar climate of iran environmental, technical and financial feasibility study of solar power plants by retscreen, according to the targeting of energy subsidies in iran wind and solar energy development in iran technical and economic assessment of the integrated solar combined cycle power plants in iran reference to any special commercial product, trademark, manufacturer, and so on, does not necessarily infer or insist on its confirmation, or approval by the writers. • we presented a brief and comprehensive survey on various energy policies in iran.• new incentive and supporting policy in iran for renewable energy resources is examined.• two different scales of grid-connected pv power systems are simulated by retscreen.• simulation results include annual ghg emission reduction and electricity production.• based on the payback period, its feed-in tariff policy targets low-capacity pv power systems. ☒ the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.☐the authors declare the following financial interests/personal relationships which may be considered as potential competing interests: key: cord- -ojfrvtuy authors: bagheri, s. h. r.; asghari, a. m.; farhadi, m.; shamshiri, a. r.; kabir, a.; kamrava, s. k.; jalessi, m.; mohebbi, a.; alizadeh, r.; honarmand, a. a.; ghalehbaghi, b.; salimi, a. title: coincidence of covid- epidemic and olfactory dysfunction outbreak date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: ojfrvtuy background recent surge of olfactory dysfunction in patients who were referred to ent clinics and concurrent covid- epidemic in iran motivated us to evaluate anosmic/hyposmic patients to find any relation between these two events. methods this is a cross-sectional study with an online checklist on voluntary cases in all provinces of iran between the th and th march, . cases was defined as self-reported anosmia/hyposmia in responders fewer than weeks later (from start the of covid- epidemic in iran). variables consist of clinical presentations, related past medical history, family history of recent respiratory tract infection and hospitalization. results in this study participants aged . +/- . ( - ) years, . % female and . % non-smoker completed online checklist. they reported . % a history of a trip out of home town and . % hospitalization due to respiratory problems recently. from family members . % had a history of severe respiratory disease in recent days and . % had anosmia/hyposmia. correlation between the number of olfactory disorder and reported covid- patients in all provinces till th march was highly significant (spearman correlation coefficient= . , p-value< . ). the onset of anosmia was sudden in . % and till the time of filling the questionnaire in . % of patients decreased sense of smell was constant. also . of this patients had decreased taste sensation in association with anosmia. conclusions it seems that we have a surge in outbreak of olfactory dysfunction happened in iran during the covid- epidemic. the exact mechanism of anosmia/hyposmia in covid- patients needs further investigations. . cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint abstract background recent surge of olfactory dysfunction in patients who were referred to ent clinics and concurrent covid- epidemic in iran motivated us to evaluate anosmic/hyposmic patients to find any relation between these two events. this is a cross-sectional study with an online checklist on voluntary cases in all provinces of iran between the th and th march, . cases was defined as self-reported anosmia/hyposmia in responders fewer than weeks later (from start the of covid- epidemic in iran). variables consist of clinical presentations, related past medical history, family history of recent respiratory tract infection and hospitalization. in this study participants aged . ± . ( - ) years, . % female and . % nonsmoker completed online checklist. they reported . % a history of a trip out of home town and . % hospitalization due to respiratory problems recently. from family members . % had a history of severe respiratory disease in recent days and . % had anosmia/hyposmia. correlation between the number of olfactory disorder and reported covid- patients in all provinces till th march was highly significant (spearman correlation coefficient= . , p-value< . ). the onset of anosmia was sudden in . % and till the time of filling the . cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint olfactory dysfunction following the upper respiratory tract infections also named post-viral anosmia has been reported in previous studies , . epithelial damage and central nervous system involvement, have been presented as the probable causes, however, the exact pathogenesis remains unclear , . generally, post-viral anosmia is more common in women and middle-aged or older individuals are more affected . whilst the olfactory impairment can be permanent, this is often not the case and this kind of anosmia has more favorable prognosis than the other different aspects of the disease will be released daily , ; however, an update on its clinical and laboratory presentations has reported fever, respiratory symptoms, cough, fatigue, myalgia, arthralgia and breathing difficulties as the common presentations of the confirmed cases . to our knowledge, in none of the updates after the covid- outbreak, anosmia is mentioned as one of the most prominent symptoms. islamic republic of iran is one of the countries which has reported laboratory-confirmed cases of covid- with total deaths up to march , . since no published scientific evidence reported olfactory and taste disorders . cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint following the covid- pandemic till now; the aim of present study is an assessment of the frequency of olfactory disorder and patients' characteristics in our country. this is a cross-sectional study on cases in all provinces of iran between the th and th march, . participants were cases with problems in decreased sense of smell recently (the last month) invited to voluntarily respond to an online checklist, which was distributed in social the primary outcome of the study was anosmia-/-hyposmia of responders which measured by closed questions and scored by numerical scales at the commencement of their problem and its condition at the time of response to questionnaire. secondary outcomes were clinical manifestations of participants such as flu or cold symptoms before anosmia, headache (which needed pain reliever drug), nasal stiffness, fever and chills, prominent cough, orbital (periorbital) pain, facial fullness and sinus pain, rhinorrhea, dyspnea, nasal irritation, parosmia, nasal pruritus, history of hypothyroidism, otalgia, sneezing (frequent), purulent nasal discharge, history of asthma, cheeks pain, , previous sinus surgery or septorhinoplasty, unilateral facial palsy and history of hypertension, diabetes mellitus and hyperthyroidism. to check about validity of data, questions cross-validated with each other. for example, if a person says that they have hyposmia but in semi-quantitative assessment by our numerical scale . cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint pointed out the zero score, he/she was deleted from the analysis. to prevent data duplication, personal information of responders was compared in the analysis phase and to exclude incomplete responses to questionnaire the records with more than % missing data were . cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint during this period the online questionnaire viewed by people from who have had anosmia/hyposmia and answered the questions. some participants' information was excluded from analysis; people who did not respond to more than questions (out of questions in the form), records which were duplicated in personal information, persons whose duration of disease was more than days. so the final analysis is representative of responders. in demographic data; age distribution ranged from to years old ( . ± . ), . % were female and . % non-smoker. most responders were from gilan ( . %), tehran ( . %), mazandaran ( . %), golestan . cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint during the last month (march ), concurrent with covid- epidemic, the number of patients with olfactory dysfunction was increased in different provinces of iran. so we decided to assess the prevalence of this olfactory disorder by an online questionnaire. till now results indicate the widespread prevalence of anosmia/hyposmia around the country and a significant linear correlation between prevalence of covid- and olfactory impairment. the recent great outbreak of olfactory dysfunction following flu like symptoms ( %), higher incidence in women ( %), and high incidence of anosmia in family members ( . %) are suggestive of a post-viral epidemic olfactory dysfunction in iran. although our study could not confirm that covid- is the definite cause of anosmia, but there is no other recent virus or flu epidemics in iran except covid- . so, it seems that the recent anosmia outbreak in iran is highly correlated to covid- . common covid- symptoms such as fever, cough and dyspnea were less common in the participants with anosmia / hyposmia compliant ( . % vs . %, . % vs . % and . % vs . % respectively) and only about . % of study population were hospitalized due to respiratory problems recently. studies of the prevalence of olfactory dysfunction in consecutive cases at olfactory clinics in the usa, europe and japan showed that the most common etiologies are: post-viral upper respiratory tract infections ( - % of the clinical population) followed by nasal/sinus disease ( - %), head trauma ( - %), toxins/drugs ( - %) and congenital loss ( - %) . by now, we found no studies to report a high frequency of olfactory disorder coincidence with covid- virus epidemic and this study could be the first report of an epidemic of covid- with simultaneous olfactory dysfunction. in the study of mao et al. , detailed neurologic . cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. cns findings were the significant form of neurological damage in patients with covid- in their study . the movement of the covid- virus into the brain through the cribriform plate near to the olfactory bulb could be a route that would enable the virus to enter and influence the brain. furthermore, the findings such as anosmia or hyposmia in an uncomplicated early stage covid- patient should necessitate a thorough assessment for cns involvement . our data is collected via an online self-reported questionnaire. the responders were part of the population who are literate and have access to the internet, personal computers or smart-phones. we announced the patients to answer this questionnaire via social networks so the participants are limited to those who use social networks. however, because of high prevalence of using . cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint smart phone even by housekeepers and people with education level lower than diploma, representativeness of the results does not seem to be affected by this bias. another limitation of this study is that no definite test for covid- infection was included. as this is an online survey, the main goal was to confirm the outbreak of anosmia during the covid- epidemic. as the study was self-reported, we used some of questions to check others to increase the questionnaire response validity. based on the findings of this study it seems that we have a surge in outbreak of olfactory dysfunction happened in iran during the covid- epidemic, that correlates with the number of patients infected with covid- across the country. as olfactory dysfunction can affect the quality of life in affected patients, it needs to be assessed worldwide by further clinical studies to find out the exact correlation, pathogenesis, prognosis, and any correlation between disease severity and olfactory dysfunction. . cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint re-establishment of olfactory and taste functions. gms current topics in otorhinolaryngology, head and neck surgery smell and taste disorders. gms current topics in otorhinolaryngology, head and neck surgery biopsies of human olfactory epithelium therapeutic options for the novel coronavirus coronavirus disease (covid- ): situation report the epidemiology and pathogenesis of coronavirus disease (covid- ) outbreak covid- : an update on the epidemiological preventive and therapeutic evidence and guidelines of integrative chinese-western medicine for the management of novel coronavirus disease complaints of olfactory disorders: epidemiology, assessment and clinical implications neurological manifestations of hospitalized patients with covid- in wuhan, china: a retrospective case series study identification of viruses in patients with postviral olfactory dysfunction postviral olfactory loss postviral olfactory loss. taste and smell disorders behavioural deficits and serotonin depletion in adult rats after transient infant nasal viral infection effect of olfactory bulb ablation on spread of a neurotropic coronavirus into the mouse brain evidence of the covid- virus targeting the cns: tissue distribution, host-virus interaction, and proposed neurotropic mechanisms. acs chemical neuroscience .. cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity.is the (which was not peer-reviewed) the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint key: cord- -yt cscf authors: haji-abdolvahab, habibbolah; ghalyanchilangeroudi, arah; bahonar, alireza; ghafouri, seyed ali; vasfi marandi, mehdi; mehrabadi, mohammad hosein fallah; tehrani, farshad title: prevalence of avian influenza, newcastle disease, and infectious bronchitis viruses in broiler flocks infected with multifactorial respiratory diseases in iran, – date: - - journal: trop anim health prod doi: . /s - - -z sha: doc_id: cord_uid: yt cscf in this study, the prevalence and spatial distribution of newcastle disease, infectious bronchitis, and avian influenza have been evaluated in commercial broiler farms in provinces in iran. in this survey, a total of affected broiler chicken farms were sampled. the infectious bronchitis virus (alone) was detected with highest frequency in farms, and separately or combined with other agents, in farms; newcastle disease virus, separately, was detected in farms, and in farms separately or combined with other infectious agents; and avian influenza h n was detected in farms separately and in farms separately or concomitant with other infectious agents. the sample tested negative for all h serotypes. the results of the present study show that the most prevalent avian viral infectious disease contributing to respiratory syndromes in broiler farms in iran was infectious bronchitis due to infectious bronchitis virus serotypes variant and /b. on the other hand, combined with the alternation of dominant viruses and circulating strains, flocks are exposed to unremitting anamorphic viral infections. thus, the permanent monitoring of cases that have occurred and the review of vaccination plans of affected flocks every year are some of the necessary measures needed for strategic control of respiratory syndrome in broilers. it is noteworthy that execution of epidemiologic examinations on the cogent factors of prevalence of this syndrome and defeat of vaccination strategy in the flocks is urgent and has to be fulfilled on the definite causes of time. over the past years, the iranian poultry industry, and specially the broiler breeding, has grown significantly, in the way that the production of poultry meat has risen from , tons in to , tons in . the development of this industry has increased the density (concentration) of poultry farms in some parts of the country. poultry farming ranging from extensive free range to intensive integrated production systems has provided conditions for the incidence of complex multifactorial infections such as bacterial, mycoplasma, and viral ones. in many cases, respiratory problems are due to infection with several infectious factors rather than with single one (swayne et al. ) . avian influenza (ai), newcastle disease (nd), and infectious bronchitis (ib) are the major viral infections in broilers that present with respiratory signs. in iran, respiratory diseases in poultry due to aiv, ndv, and ibv cause constant mortality in broilers especially. these infections occur either in the solitary form or in combination with multifactorial infections. evidence indicates that most of these factors are synergistic and potentate themselves in infected flocks. in recent years, despite national and domestic prevention and control measures against ai, nd, and ib, coupled with widespread usage of diverse vaccines, outbreaks of these viral diseases still cause respiratory syndromes in broiler flocks resulting in high mortalities annually. based on available statistics from the iran veterinary organization (ivo), maximum economic damage in broiler flocks is related to losses arising from respiratory complications (ebadzadeh et al. ) . avian influenza caused by strain h n is endemic in many asian and the middle east countries including iran (naeem et al. ; nili and asasi ) . the causal agent is avian influenza virus type a that belongs to the orthomyxoviridae family. newcastle disease caused by avian paramyxovirus i (apmv-i) is also endemic in asian and the middle east countries. co-infections in broiler flocks with aiv and ndv result in great economic losses due to severe morbidity and mortality rates. a third co-infection with ibv worsens the scenario. the causal agent of this disease belongs to the coronavirus subtype and the gamma coronavirus genus (oie ) . in this study, the evaluation of prevalence and spatial distribution of newcastle disease, infectious bronchitis, and avian influenza h n subtype has been carried out for commercial broiler farms in iran. the industrial broiler farms are present in iranian provinces. based on the geographical information system database of poultry diseases of ivo (iran vet gis), there are nearly , broiler farms in the country, of which (according to the ministry of agriculture statistics) , have formal operating certificates (ebadzadeh, ahmadi, mohammadnia afruzi, taghani, moradi eslami, and yari ) . based on iran vet gis, on an annual average, nearly , farms of the total , broiler farms are active with about four breeding periods in a year. the aggregation of broiler farms in the various provinces of iran shows that the highest number is located in mazandaran and esfahan provinces. in addition, the number of breeding periods in these farms during each year is distinct on disparate zones (different areas of the country), so that it varies from three times in most central provinces with warm and dry climate up to five times in the northern provinces with moderate and wet climate, on average per year. the study population included all active (in production) broiler farms (based on iran vet gis) that were infected with respiratory diseases as a new case during the study period. a farm infected with respiratory disease was defined as a flock with core clinical signs such as depression, snickering, sneezing, coughing, dyspnea, rattling, and nasal discharges with or without diarrhea or central nervous system signs (wing paralysis, legs paralysis, or twisted neck) that entailed rising mortality rates for at least days. the sampling period in this cross-sectional study was from st of april to th of march . all broiler farms in iran are under the supervision of a private vet as a farm vet or clinician, in groups of one to several, based on farm population and location. the farmers and their vet supervisors must give online prompt report (registered in gis) when a farm is involved in serious problems, including important diseases as defined by ivo as a national assignment. so the study population including infected farms was self-reported by farmers or their private vets supervisor, in addition to farms that were reported following the active surveillance programs of ivo by state vets. according to data registered with the iranian vet gis, the prevalence of ib, nd, and ai in the previous year in our study was . %, . %, and . %, respectively. thus, the prevalence of ib ( . %) was chosen to calculate the total sample size, with % accuracy and % confidence level. in this survey, the sampling method was proportional random sampling based on the proportion of each province broiler farms that were in production. the number of required samples for each province was assigned according to the proportion of its active (in production) broiler farms present for at least past years, according to iranian vet gis. so all the infected farms were listed by the province and then samples were selected using the simple random selection from each province list. based on the calculated sample size of , a total population of , and size of x (proportion of each province) and using the formula, the number of farms to be sampled per province is calculated as follows: number of farms to be sampled in each province in each affected farm, - recently dead birds or birds with clinical symptoms were sampled. the collected samples consisted of trachea tissue, lungs, brain, spleen, cecal tonsil, and kidneys. the samples were delivered to the ivo central laboratory. after recording the complete characteristics, the samples were preserved and stored at a − °c freezer for further examinations. after completion of the tests, the related results were received from the ivo central laboratory, along with the data of total sample mortalities at the end of that particular breeding season. in this study, the samples of the trachea and lung; the samples of the spleen, cecal tonsil, and kidney; and brain samples from each farm were segregated, after which % pbs suspensions were prepared. after centrifugation at a low rate, ml of supernatant was collected and used for tests. the tests were conducted parallelly and all samples from each farm were tested. we considered a test positive if the result of each sample was positive regardless of other sample results. for cases with clinical nervous signs, the brain samples underwent additional testing. rna extraction was done on the prepared suspensions using a high pure viral nucleic acid kit (roche, germany) according to the manufacturer's protocol. the extracted rna was divided into three equivalent parts and each part was used for ai, ib, and nd virus diagnostic tests. for diagnosis of avian influenza, infectious bronchitis, and newcastle disease, molecular testing was done according to recommended methods. for diagnosis of h n and h avian influenza, we used the method of real-time rt-pcr (monne et al. ) . for nd detection, the rt-pcr method using two pairs of primers was performed as described by kant et al.; ab primers were used to confirm the existence of the nd virus. to confirm nd velogenic viruses, the positive samples were then tested by rt-pcr using ad primers. if a sample in the first rt-pcr was positive but negative in the second, the detected virus was classified as a velogenic (kant et al. ) . for ibv detection, real-time pcr was done based on ′ utr. we used the amplification kit (bioneer, south korea), with the forward primer ′gcttttgagcctagcgtt ′, reverse primer ′gccatgttgtcactgtctattg ′, and taqman® dual-labeled probe famcaccaccagaacct gtcacctc-bhq (callison et al. ) . for ibv genotyping, a nested pcr assay was done and then sequencing was performed with the primers (both directions) as used in the pcr (bioneer co., korea). we did nucleotide blast (ncbi) the results of edited obtained sequences for detection of ibv genotypes. a total of infected broiler farms were sampled in the study. all farms were vaccinated for nd and ib but for ai-h n , some farms were vaccinated. the sizes of farms were different from to , , birds. the breeding system of the farms was different too based on the region and the farm building date. the most sampled farms were from mazandaran, esfahan, and khorasan razavi with , , and farms, respectively. the provinces of tehran, north khorasan, sistan-baluchestan, and southern kerman with only one farm each were the lowest sampled. the distribution of sampled farms is shown in table province-wise. the mean disease start age for broiler farms infected to ib was rd day ( % ci - ), for nd was th day ( % ci - ), and for h n was th day ( % ci - ). alone, the infectious bronchitis virus was detected of highest concentration in farms ( . %) and alone or together with the other agents, in farms ( . %). a total of farms ( . %) were positive for newcastle viruses with velogenic cases; as lone virus, it was detected in farms ( %), and in farms ( %) alone or together with the other infectious agents; and avian influenza h n was detected in farms ( . %) alone and in farms ( . %) alone or concomitant with the other infectious agents (table ). all samples were tested negative for h subtype viruses (fig. ) . out of isolated infectious bronchitis viruses, viruses ( . %) were /b genotype, viruses ( . %) were variant genotype (is/ ), viruses ( . %) were massachusetts, five viruses ( . %) were qx genotype, three viruses ( %) were ir genotype, three viruses ( %) ir genotype, and another three viruses ( %) were of mix variants. the highest mean mortality rate was . % as observed in the farms infected with h n ai, ndv, and ibv, simultaneously; the lowest mean mortality rate with . % was observed in the farms affected with h n ai (chart ). the highest percentage of mortality was in sistan-baluchestan ( %) and kohgiluyeh-boyerahmad provinces ( . %), and the lowest percentages were in lorestan ( . %), bushehr ( . %), and northern khorasan ( . %). over the past years, respiratory diseases have been one of the most critical problems for national commercial broiler farms. of these, infectious bronchitis, newcastle disease, and h n influenza have been the major endemic diseases in iran with numerous studies carried out in this regard (hadipour and golchin ; hosseini et al. ; hosseini et al. ; pourbakhsh et al. ; seifi et al. ) . furthermore, these diseases were found to be some of the most critical factors for infections in the poultry industry, particularly in broilers, in other countries too (hassan et al. ; naeem et al. ; xia et al. ) . this study showed infectious bronchitis to be the most significant agent of frequent respiratory syndrome of the studied farms in spite of widespread vaccination drives at these sites. previous studies have recognized the contrasting serotypes of bronchitis in the country. in iran, mass serotype plus genotype /b have been reported (jackwood ) . in the present investigation as well as in several other studies in iran, /b was detected as the dominant serotypes and the principal virus of circulation. pourbakhsh et al. conducted a study in farms, wherein infectious bronchitis was found to be the dominant virus in % cases. in their study, the genotype /b was detected in % of farms, which were ib positive. in addition, another identified genotype was massachusetts (pourbakhsh et al. ) . in a study in in iran, % of sampled farms ( farms out of ) were infected with infectious bronchitis, samples were genotype / , and only one case was massachusetts (seifi et al. ) . in the investigation of hosseini et al. carried out over the period - , the serotype /b was tracked as the dominant serotype in the country (hosseini et al. ) . in study that was done by modiri et al., bronchitis has posed to be a challenge in broiler farms of iran's neighboring countries as well (modiri hamadan et al. ) . in an experiment relevant to iraq during the years - , samples of ib virus were identified from samples collected. this survey also identified variant as the dominant virus (seger in egypt (hassan et al. ) , infectious bronchitis alone and combined with other factors infected with respiratory diseases in . % and %, respectively, has been pinpointed in broiler chicken farms. furthermore, the concomitant infection of bronchitis with avian influenza h n was found to be the most common infection with . % (hassan et al. ) . after conclusive testing in iran, the flocks of infected birds have been vaccinated against infectious bronchitis (aghakhan et al. ) . however, the main challenge in control of ib is the circulation of variable genotypes of virus in different locations and in diverse time intervals. in addition, there is no vaccination available for establishing cross immunity among disparate exploited genotypes. recently, a different vaccine of ib, containing h and / , has been frequently used, but, notwithstanding this issue, again infectious bronchitis is being counted as a critical complication of broiler farms. through complete fact-findings over the past years, it seems like the circulating serotypes were in morphism, with serotypes /b and variant showing the most capacity and frequency on incidence of the disease (ghalyanchi-langeroudi et al. ) . the continuous observations of circulating viruses and using vaccines similar to these circulating strains, along with observation of health principles and biosecurity issues, are strategies that can be implemented for reduction of disease morbidity to infectious bronchitis. apart from infectious bronchitis, newcastle disease has also had a momentous role in the incidence of respiratory syndromes in the country's broiler farms. velogenic nd is endemic in iran and in spite of widespread vaccination, every year, there are outbreaks of newcastle disease nationwide (hosseini et al. ) . in this study, infectious bronchitis, avian influenza, and newcastle disease were detected in % of the broiler farms surveyed. recently, distinctive analyses have allowed researchers to understand the active newcastle disease virus genotype variants in the nation (hosseini et al. ; mayahi and esmaelizad ; mehrabanpour et al. ; sabouri et al. ) . the above-mentioned probes indicate that, despite huge vaccination drives against the disease in broiler farms, we still witness sporadic occurrence of this disease in the country. newcastle disease has been a major challenge for poultry breeding farms, not only for iran but also for other countries as well. in a study executed in broiler farms of egypt, velogenic nd viruses were diagnosed in % of the studied farms. in pakistan, numerous velogenic newcastle genotypes were isolated in different species of birds (wajid et al. ) . furthermore, during the period of - , outbreaks of velogenic nd were observed in israel, indonesia, and pakistan (miller et al. ) . molecular epidemiological studies show that these new virus strains from the various geographic regions can replace the dominant strains of individual countries (miller et al. ) . backyard poultry is a reservoir of velogenic newcastle disease in many countries and it has a critical role in transmitting contamination to commercial farms (a awan et al. ) . iran also has backyard poultry in many provinces, including the northern provinces where the numbers of industrial poultry and backyard poultry are both high. since there is a lack of regular and organized vaccination in backyard poultry, the spread of disease from this poultry to industrial poultry is possible. according to our current exploration, in spite of extensive vaccination in most farms, this disease is one of the most challenging problems in the poultry breeding industry of iran for diverse reasons including low biosecurity in farms and inadequate vaccination programs in some other farms. the constant monitoring of farms for assessment of virus variations, reviewing of farm vaccination programs, and increasing the biosecurity level are among the essential measures required for control of disease in the country. avian influenza h n subtype is also regarded as one of the cogent viral factors in the incidence of respiratory diseases in broiler farms of the nation. the disease is endemic in the country, and apart from this fact that the virus is low pathogenic, co-infection with ibvor ndv results in great economic losses due to severe morbidity and mortality rates in broiler flocks (nili and asasi ; pourbakhsh et al. ). avian influenza is endemic not only in iran but also in neighboring countries. the disease has great economic and public health burdens on national and international trade and travel. in a study done in egypt, the h n influenza strain was diagnosed in % of samples, and together with infectious bronchitis, the prevalence showed maximum cases of co-infection at . % (hassan et al. ). in the united arab emirates during - , the h n influenza virus was isolated from broilers and quails with mortality (aamir et al. ). in pakistan, this disease has become endemic since , and its annual occurrence has caused the poultry industry there to suffer great economic losses (cameron et al. ; lee et al. ) . in iran, vaccination against h n is being done in breeders and layers as well as in many broiler flocks; however, this disease continues to be destructive. in the current exploration, the mortality of infectious bronchitis alone was at %, and the co-infection of ibv with ndv had risen to %, the concomitant infection of ib, nd, and ai hit %, but co-infection mortality of ib with h n influenza was at %, while it is in contrary with the study of seifi et al. ( ) and the study of hassan et al. ( ) that show mortality of co-infection of ib and aiv-h n is more than that of ib alone. the results of the present study show that the most critical factor in the prevalence of respiratory syndromes in iran, specifically at the time of doing this groundwork, has been the bronchitis virus with its frequency caused by two serotypes of variant and /b. furthermore, the roles of h n influenza and velogenic newcastle viruses in the outbreak of respiratory syndromes are distinct, while their simultaneous infection is the cause of virulence in the farms. on the other hand, due to arguments of distinct strains, combined with alternation of dominant viruses, the serotypes, genotypes, and circulation of strains between viruses are also exposed to unremitting anamorphic conditions. thus, necessary measures for strategic control of this process include permanent monitoring of respiratory syndrome cases that have occurred as well as the review of vaccination plans for affected flocks in each year. it is recommended that epidemiologic studies should be conducted frequently on risk factors of prevalence of these diseases and effectiveness of vaccination strategy in the flocks. the epidemiology of newcastle disease in rural poultry: a review characterization of avian h n influenza viruses from united arab emirates studies on avian viral infections in iran development and evaluation of a real-time taqman rt-pcr assay for the detection of infectious bronchitis virus from infected chickens h n subtype influenza a viruses in poultry in pakistan are closely related to the h n viruses responsible for human infection in hong kong agricultural statistics. (center for information and communication technology genotyping of infectious bronchitis viruses in the east of iran serosurvey of h n avian influenza virus during respiratory disease outbreaks in broiler flocks in dezful, southern iran prevalence of avian respiratory viruses in broiler flocks in egypt molecular characterization and phylogenetic study of newcastle disease viruses isolated in iran epidemiology of avian infectious bronchitis virus genotypes in iran review of infectious bronchitis virus around the world differentiation of virulent and non-virulent strains of newcastle disease virus within hours by polymerase chain reaction h n low pathogenic avian influenza in pakistan molecular evolution and epidemiological links study of newcastle disease virus isolates from to in iran phylogenetic characterization of the fusion genes of the newcastle disease viruses isolated in fars province poultry farms during identification of new sub-genotypes of virulent newcastle disease virus with potential panzootic features genotyping of avian infectious bronchitis viruses in iran ( - ) reveals domination of is- like virus development and validation of a one-step real-time pcr assay for simultaneous detection of subtype h , h , and h avian influenza viruses avian influenza in pakistan: outbreaks of low-and high-pathogenicity avian influenza in pakistan during natural cases and an experimental study of h n avian influenza in commercial broiler chickens of iran avian influenza (h n ) outbreak in iran ninetythree b type, the predominant circulating type of avian infectious bronchitis viruses - in iran: a retrospective study characterization of a novel viil sub-genotype of newcastle disease virus circulating in iran genotyping of infectious bronchitis viruses from broiler farms in iraq during natural co-infection caused by avian inflfl uenza h subtype and infectious bronchitis viruses in broiler chicken farms diseases of poultry repeated isolation of virulent newcastle disease viruses in poultry and captive non-poultry avian species in pakistan from genetic and antigenic evolution of h n subtype avian influenza virus in domestic chickens in southwestern china acknowledgements the researchers express their appreciation to the department of health and management of poultry diseases of iranian veterinary organization and other related poultry departments of the provinces as well as the national central diagnostic lab of ivo for the implementation of this project. conflict of interest the authors declare that they have no conflict of interest. key: cord- -majpfxqn authors: saadat, yousef; bozorgmehri fard, mohammad hassan; charkhkar, saied; hosseini, hossein; shaikhi, nariman; akbarpour, bijan title: molecular characterization of infectious bronchitis viruses isolated from broiler flocks in bushehr province, iran: - date: - - journal: vet res forum doi: nan sha: doc_id: cord_uid: majpfxqn the aim of this study was to provide information on the molecular characteristic and the phylogenic relationship of infectious bronchitis viruses (ibv) strains in bushehr province in comparison to other strains reported in the middle east. samples were collected from broiler flocks in bushehr province during - . these flocks had respiratory problems such as gasping, sneezing and bronchial rales. a number of tracheal swabs were taken from fifteen flocks (nine swabs per flock). each three swabs collected from each flock were pooled in one tube (finally, we had three tubes for each flock). the samples were subjected to reverse transcription polymerase chain reaction (rt-pcr). the pcr products of positive samples were analyzed by sequencing of a ( bp) segment of the spike gene and the related results were compared with the other ibv sequences in genbank database. samples from twelve farms ( . %) were found to be positive. the viruses from seven farms ( . %) were identified as field viruses closely related to variant . the viruses from three farms ( . %) were characterized as mass type and were related to vaccine strains. two different ib viruses (variant and mass) were detected in samples from two farms ( . %). the variant genotype detected in bushehr had high similarity to variant reported from the middle east. these variants displayed homologies ranging from . % to . %, and . % to . % with h and / , respectively. it is necessary to design vaccination program of poultry farms using ibv strains circulating in the region. infectious bronchitis (ib) is an acute and highly contagious respiratory disease of chickens characterized by respiratory signs, and in young chickens by severe respiratory distress and a decrease in egg production in layers. the chicken was considered the only natural host of infectious bronchitis virus (ibv) but recently pheasants has been introduced as the other natural host for ibv. the disease is transmitted by the respiratory route, direct contact and indirectly through mechanical spread. the virus belongs to coronaviridae, order nidovirales. the ibv and other avian coronaviruses of turkeys and pheasants are classified as group coronaviruses. its genome consists of about kb and codes for four structural proteins: the spike (s) glycoprotein, the membrane (m) glycoprotein, the nucleocapsid (n) phosphoprotein, and the envelope (e) protein. , the spike glycoprotein (s) is anchored in the viral envelope and is post-translationally cleaved into two proteins s and s . the s protein is very diverse in terms of both nucleotide sequence and deduced primary protein structure, especially in the upstream part of s . three hypervariable regions (hvrs) have been identified in the s subunit. [ ] [ ] [ ] the s subunit induces neutralizing, serotype-specific, and haemagglutinationinhibiting antibodies. [ ] [ ] [ ] [ ] [ ] [ ] amino acid changes in the spike (s) glycoprotein lead to the generation of genetic variants. , the high frequency of new ibv variants is a distinguished characteristic of this virus among other coronaviruses. many ibv serotypes have been described probably due to the frequent point mutations that occur in rna viruses and also recombination events. therefore, the characterization of virus isolates which exists in the field is very important. more than serotypes of ibv have been identified and new variants continued to emerge despite the use of live attenuated and killed ibv vaccines. [ ] [ ] [ ] the usage of live attenuated vaccines is the most important preventive measure of the disease, but antigenically different serotypes and newly emerged variants from field chicken flocks sometimes cause vaccine breaks. , the ibv massachusetts (mass) type was first detected in iran by aghakhan et al. in , a virus similar to the european /b type was isolated in iran (iran/ b/ / ). in recent years, new variants of ibv have been reported from different part of the country. [ ] [ ] [ ] the aim of this study was to provide information on the molecular characteristic and the phylogenetic relationship of prevalent ibv genotypes circulating in chicken flocks in bushehr province, iran. sampling. samples were collected from broiler flocks in different regions of bushehr province as mentioned in table during - . these flocks showed respiratory problems such as gasping, sneezing and bronchial rales. a number of tracheal swabs were taken from fifteen flocks (nine swabs per flock). each three swabs collected from each flock were pooled in one tube and submitted to veterinary diagnostic laboratory (tehran, iran). rna extraction viral rna was extracted from the directly pooled tracheal swabs in rlt buffer (qiagen, hilden, germany) and μl -mercaptoethanol (merck, darmstadt, germany) per ml buffer using rneasy mini kit (qiagen), according to the manufacturer's protocol. reverse transcription the reverse transcriptation (rt) reaction was performed using reveraid™ first strand cdna synthesis kit (thermo scientific, burlington, canada), according to the product manual. the resultant cdna was immediately used in a pcr or stored at - ˚c for later use. amplification of the spike gene nested reverse transcription polymerase chain reaction (rt-pcr) was performed using spike gene primers as described previously to amplify bp fragment of the spike gene. the first round of amplification ( bp) was performed using sx ( ʹ-cacctagaggtttgt/cta/tgcat-´ ) and sx ( ʹ-tccacctctataaacaccc/ttt-´ ) primers. the pcr reaction was performed in μl reaction mixture containing μl dntp ( mm), . μl of each primer ( pmol μl - ), μl mgcl ( mm), . μl x pcr buffer, . μl taq dna polymerase, . μl cdna and . μl dh o (all from sinaclon, tehran, iran). the amplification was performed using thermal cycles including ˚c for sec, ˚c for sec, and ˚c for sec. the pcr product was used as template for the second round of amplification in which sx ( ´-taatactggc/taattt ttcaga-´ ), and sx ( ʹ´aatacagattgct tacaaccacc- ) primers were used. the pcr reaction was carried out under the above condition. agarose gel electrophoresis. the pcr products were electrophoresed on % agarose gel and visualized by staining with . μg ml - ethidium bromide by uv transilluminator (m- ; uvp, upland, usa). pcr product purification. the pcr products were purified using pcr purification kit (roche, mannheim, germany) according to kit's manufacture instructions. nucleotide sequencing, deduced amino acid analysis and phylogenetic tree. purified rt-pcr products were sequenced by abi prism bigdye terminator cycle sequencing ready reaction kit (applied biosystems, foster city, usa) in a forward direction using primer sx and in a reverse direction using primer rx . nucleotide sequence of the pcr product ( bp), which was submitted to ncbi, were compared with the ibv sequences in genbank database and sequence similarities were analyzed by blast. multiple sequence alignments were carried out with clustal w and phylogenetic tree was constructed with mega software (version ; biodesign institute, tempe, usa) using the neighbor-joining tree method with bootstrap. genbank accession number of ibv sequence. the partial s gene sequences of ibvs were submitted to the genbank database under accession numbers kx -kx . the rna was extracted and cdna was synthesized, and further a ( bp) segment of the s gene was amplified by nested rt-pcr (fig. ) . samples from twelve farms ( %) found to be positive (table ) . on the base gene sequences, phylogenetic tree was constructed from the nucleotide sequences of the s glycoprotein gene, revealing that the sequences of the recent iranian strains formed two main groups (fig. ) . the first group was subdivided into two subgroups: one including kurdistan-sulaymania/ , egypt/beni suef/ , turkey/ rs- / , is/var - , variant_ , eg/ clevb- /ibv/ , ir/bu/variant /sh . it is imperative to recognize the prevalent strain(s) of infectious bronchitis virus in a region or country, and to select the best vaccine strain and the vaccination program for controlling the disease. the major problem in the immunization against ibv is the presence of various ibv serotypes in the field against available vaccines which fig. . the phylogenic tree for ibv strains detected in the current study and other related isolates in the gene bank middle east sequences using mega- program. analyses were based on s gene bp nucleotides. cannot induce proper immunity. the aim of the present study was to detect and identify the type of prevailing ibv strains in bushehr province. previous studies comparing conventional and nested rt-pcr methods indicated that nested rt-pcr was more sensitive for detection of ibv. [ ] [ ] [ ] the implementation of nationwide genotyping of ibv strains is necessary to determine the distribution of virus genotypes and to develop and adopt suitable vaccination strategies. antigenic characterization of ibv isolates is important for selecting new and appropriate vaccines for the corresponding geographical regions. new serotypes or variant strains may emerge due to only a few changes in the amino acid sequence of the s protein. therefore, the s gene of the isolates should be determined to differentiate field and vaccine isolates. regarding the results obtained, ibv isolates were identified. phylogenetic analysis based on s gene nucleotide sequences showed that most of the iranian isolates belonged to two distinct groups. based on nucleotide sequencing of the s gene, a number of field isolates in the present study showed maximum similarity to variant (is/ / like strain). this is the first report of ibv variant in the broiler flocks of bushehr province. these variants displayed homologies ranging from . % to . %, and . % to % with h and / , respectively ( table ) . the second group included three strains which were closely related to massachusetts (mass) type strains. in the present study, ir/variant viruses (is/ / like) were recognized as major dominant genotypes and the most important ibv type in bushehr province chicken flocks. homayounimehr et al. reported ir/ / , r/ / , and ir/ / isolates which appeared different from najafi et al. reported variant -like viruses (is/ / like) that were the most predominant ibv type in iranian chicken flocks. they shared the highest identity of . % with is/ / , turkey/tr , and eg/ clevb- /ibv/ . these findings had high similarity with our results. our findings are also in agreement with several other studies carried out in the middle east countries between and . some iraqi researchers studied circulating viruses in broiler farm and showed that these strains belong to variant (is/ -lik) that had high nucleotide sequence identity with ibv isolates from iran, israel, egypt, turkey, and kurdistan. the ib viruses in egypt, jordan, turkey and libya showed a close relationship to israeli variants. , [ ] [ ] [ ] [ ] [ ] following the first report by meir et al., the variant has been reported from some middle east countries such as iran. [ ] [ ] [ ] , since these countries have close connections (e.g. through language, religion, relationship, holy places, sectarian war, economic exchange, immigration etc.), so these connections can play an important role in spreading of this variant. the first isolation of ibv in iranian chicken flocks was reported in . the present study is the first report on var is/ / in bushehr province, in iran, confirming the presence of the var genotype. ma , h , and attenuated / ibv-based vaccination strategies have been applied to ib control on poultry farms in iran recently, , and despite their use, diagnosis of ib in the vaccinated chickens is common. the results of this study may partially explain the failure of massachusetts-type vaccines and therefore necessitates revising the iranian vaccination strategy against infectious bronchitis. the low identity between most of iranian isolates with mass-type vaccine strain, the presence of variant , and other new genotypes / can be regarded as the causes of vaccination failure. moreover, secondary infections and immunosuppressive agents like infectious bursal disease virus and chicken anemia virus may also lead to vaccination failure and consequently ibv outbreaks among poultry flocks. these substantial reasons can result in immune failure, poor cross-protection between the field virus and vaccine strain, and the continual emergence of new variants. genotypes found in sulaymania-kurdistan, iraq, included group a (very similar to iranian isolates), and group c (similar to is/ and egypt/beni-seuf/ isolates). these findings are in agreement with the present study. cross-protection between ibv strains depends on the amino acid similarity of s . based on s glycoprotein amino acid sequence, iranian ibv's homology with h vaccine, massachusetts vaccine and /b vaccine ranges from . % to . %, from . % to . % and from . % to . %, respectively. these findings explain the poor vaccine performance in the field and show that the disease outbreaks were associated with ibv variants, which circumvent vaccination immunity. further, the findings emphasize the need for new control strategies of ibv in iran. in summary, the present study is the first report of ibv in bushehr, iran, illuminating the circulation of a variant of ibv genotype in chicken farms. heterogeneity with vaccine strains can explain a poor vaccination performance and disease outbreak in this area. the results emphasize the need for new control strategies and re-arrangement of preventative measure of ibv in bushehr, iran. one of a series of the veterinary medicine-large animal clinical sciences department, florida cooperative extension service avian infectious bronchitis virus detection and molecular characterization of infectious bronchitis virus isolated from recent outbreaks in broiler flocks in thailand severe acute respiratory syndrome vaccine development experiences of vaccination against avian infectious bronchitis coronavirus coronaviruses: structure and genome expression cloning and sequencing of genes encoding structural proteins of avian infectious bronchitis virus structural characterization of the spike protein the coronavirus surface glycoprotein amino acids within hypervariable region of avian coronavirus ibv (massachusetts serotype) spike glycoprotein are associated with neutralization epitopes antigenic domains on the peplomer protein of avian infectious bronchitis virus: correlation with biological functions identification of amino acids involved in a serotype and neutralization specific epitope within the s subunit of avian infectious bronchitis virus structural polypeptides of coronavirus ibv coronavirus proteins: structure and function of the oligosaccharides of the avian infectious bronchitis virus glycoproteins molecular biology and pathogenesis of coronaviruses monoclonal antibodies to the s spike and membrane proteins of avian infectious bronchitis virus coronavirus strain massachusetts m coronavirus ibv: removal of spike glycopolypeptide s by urea abolishes infectivity and hemagglutination but not attachment to cells coronaviridae: the virus and their replication location of the amino-acid differences in the s spike glycoprotein subunit of closely related serotypes of infectious bronchitis virus location of antigenic sites defined by neutralizing monoclonal antibodies on the s avian infectious bronchitis virus glycopolypeptide molecular epizootiology of avian infectious bronchitis in russia complete genomic sequence analysis of infectious bronchitis virus ark dpi, strain and its evolution by recombination coronavirus avian infectious bronchitis virus a survey of the presence of a new infectious bronchitis virus designated / ( b) genetic diversity of avian infectious bronchitis coronavirus strains isolated in china between studies on avian viral infections in iran isolation and identification of infectious bronchitis viruses in chickens between - in iran epidemiology of avian infectious bronchitis virus genotypes in iran ( - ) molecular characterization of infectious bronchitis viruses isolated from broiler chicken farms in iran detection and identification of infectious bronchitis virusby rt-pcr in iran detection of the italy strain of infectious bronchitis virus in the uk molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods molecular analysis of the /b serotype of ibv in great britain relationship between sequence variation in the s spike protein of infectious bronchitis virus and the extent of cross-protection in vivo molecular studies on infectious bronchitis virus isolated in poland factors influencing the outcome of infectious bronchitis vaccination and challenge experiments genotypes of infectious bronchitis viruses circulating in the middle east between isolation and molecular characterization of sul/ / avian infectious bronchitis virus indicates the emergence of a new genotype in the middle east genotyping of infectious bronchitis viruses from broiler farmsin iraq during - emergence of a novel genotype of avian infectious bronchitis virus in egypt al saad s. presence of infectious bronchitis virus strain ck/ch/ldl/ i in the middle east presence of is/ / genotype-related infectious bronchitis virus in breeder and broiler flocks in turkey detection and molecular characterization of infectious bronchitis viruses isolated from broiler and layer chicken farms in egypt during detection of variant infectious bronchitis viruses in broiler flocks in libya identification of a novel nephropathogenic infectious bronchitis virus in israel phylogenetic study of iranian infectious bronchitis virus isolates during - using glycoprotein s gene a survey of the prevalence of infectious bronchitis virus type / in iran investigation and molecular characterization of avian infectious bronchitis virus in suspected broiler farms in slemani governorate key: cord- - i y kc authors: bagheri, seyed hamidreza; asghari, alimohamad; farhadi, mohammad; shamshiri, ahmad reza; kabir, ali; kamrava, seyed kamran; jalessi, maryam; mohebbi, alireza; alizadeh, rafieh; honarmand, ali asghar; ghalehbaghi, babak; salimi, alireza; dehghani firouzabadi, fatemeh title: coincidence of covid- epidemic and olfactory dysfunction outbreak in iran date: - - journal: med j islam repub iran doi: . /mjiri. . sha: doc_id: cord_uid: i y kc background: the occurrence of anosmia/hyposmia during novel coronavirus disease (covid- ) may indicate a relationship between coincidence of olfactory dysfunction and coronavirus disease (covid- ). this study aimed to assess the frequency of self-reported anosmia/hyposmia during covid- epidemic in iran. methods: this population-based cross sectional study was performed through an online questionnaire from march to , . cases from all provinces of iran voluntarily participated in this study. patients completed a -item patient-reported online questionnaire, including smell and taste dysfunction and their comorbidities, along with their basic characteristics and past medical histories. the inclusion criteria were self-reported anosmia/hyposmia during the past weeks, from the start of covid- epidemic in iran. results: a total of participants aged . ± . ( - ) years took part in this study, of them . % women and . % nonsmokers completed the online questionnaire. the correlation between the number of olfactory disorders and reported covid- patients in all provinces up to march , was highly significant (spearman correlation coefficient = . , p< . ). a sudden onset of olfactory dysfunction was reported in . % of the participations and persistent anosmia in . % from the start of covid epidemic. in addition, . % of participants reported concomitant olfactory and gustatory dysfunctions. conclusion: an outbreak of olfactory dysfunction occurred in iran during the covid- epidemic. the exact mechanisms by which anosmia/hyposmia occurred in patients with covid- call for further investigations. olfactory dysfunction following the upper respiratory tract infections also named postviral anosmia has been fre- quently reported in previous studies ( , ) . epithelial damage and central nervous system involvement have been postulated as the probable reasons, however, the exact pathogenesis remains unclear ( , ) . generally, postviral anosmia is more common in middle-aged women ( ) . coronaviruses are a large family of viruses that have been presented as the causative agents of different clinical manifestations that range from a common cold to severe and great global public health concerns such as middle east respiratory syndrome (mers-cov) and severe acute respiratory syndrome (sars-cov). sars-cov is a new strain from this family, which has commenced in the world in ( , ) . the world health organization (who) has reported confirmed cases of covid- with deaths by march , globally ( ) . as the virus has newly been identified, new reports about the various aspects of the disease are released almost every day during this pandemic ( , ) . however, an update on its clinical and laboratory presentations has reported fever, respiratory symptoms, cough, fatigue, myalgia, arthralgia, and breathing difficulties as the common presentations of the confirmed cases ( ) . although olfactory loss had not been mentioned as a presentation of covid- until march , , several anecdotal reports were made by iranian otolaryngologists regarding an outbreak of olfactory loss in social media. the first, albeit was not a peer-reviewed study, was from china reporting a frequency of . % for smell loss ( ) . this study was designed to assess the prevalence of olfactory dysfunction in iran during the covid- pandemic as a preliminary epidemiologic study. an online questionnaire was developed by a board, including otolaryngologists and epidemiologists, from ear, nose, throat and head and neck surgery research center of iran university of medical sciences with the cooperation of iran medical council. the software incorporated into the website of iran medical council for corona epidemics (www.corona.ir). the full online questionnaire, which is in google document format (go.irimc.org/smelltest), contains questions, of which are about any changes in smell or taste and most of the related comorbidities, about basic characteristics of participants (age, date of birth, gender, city of residence, medical history, habitual history, family history), and multiple-choice questions about past medical history (asthma, diabetes, thyroid disease, hypertension, epilepsy, and parkinson's disease). participants were asked to report their ability to smell and taste before and during the covid- disease quantitatively via point visual analogue scales. questions about olfactory and gustatory dysfunctions can be seen in the appendix . to check the validity of the data, the questions were cross-validated with each other. for example, if participants mentioned that they had hyposmia but pointed to the zero in the likert scale in the questionnaire, they were excluded from the analysis. to detect and omit duplicated entries, personal information (age, gender, and location) was compared be-fore data analysis. furthermore, to exclude incomplete responses to the questionnaire, the records with more than % missing data were deleted. this cross sectional study was conducted on cases in all provinces of iran from march to , . participants were cases with decreased (hyposmia) or loss of sense of smell (anosmia) during the past weeks, who voluntarily responded to the online questionnaire via the internet (go.irimc.org/smelltest). the inclusion criteria were olfactory dysfunctions in responders within the weeks of the start of covid- epidemic in iran. specific groups in the populations were underrepresented because they had less access to the internet, personal computers, or smartphones, or were disable or illiterate to use the internet. the primary outcome of the study was olfactory dysfunction of the responders at the onset of their problem and its condition at the time of their response to the questionnaire, which was measured by closed questions and scored by likert scale. secondary outcomes were clinical manifestations of participants such as flu or cold symptoms before anosmia, headache that needed a pain reliever drug, nasal stiffness, fever and chills, prominent cough, orbital (periorbital) pain, facial fullness and sinus pain, rhinorrhea, dyspnea, nasal irritation, parosmia, nasal pruritus, history of hypothyroidism, otalgia, sneezing (frequent), purulent nasal discharge, history of asthma, cheeks pain, previous sinus surgery or septorhinoplasty, unilateral facial palsy, and a history of hypertension, diabetes mellitus, and hyperthyroidism. informed consent was obtained from the participants prior to filling online questionnaire in an anonymous way and in a group (pooled) fashion. the study was approved by the ethics committee of iran university of medical sciences (ir.iums.rec. . ). categorical variables were reported as counts and percentages and quantitative variables as means and standard deviations (otherwise mentioned). the relationship between the number of participants and the number of confirmed covid- patients (from national reports) was analyzed by the spearman correlation coefficient. this part of the assessment has been considered as an ecological study because data were not at individual level. the results are based on the reported cases of anosmia or hyposmia in an were excluded from the analysis: participants who did not respond to more than questions (from total of questions), duplicated records that were similar in personal information, and participants in whom the duration of disease was more than days. thus, the final analysis represented responders. based on demographic data, age distribution ranged from to years ( . ± . ), . % were female and . % nonsmoker. most responders were from gilan ( . %), tehran ( . %), mazandaran ( . %), golestan ( . %), and qom ( . %) provinces. despite a significant difference in the number of responders from multiple geographical areas, the distribution of demographic and clinical variables was homogenous among different provinces of iran. the number of cases of anosmia was compared to the official report of patients with covid- in various provinces until march , (fig. ) , and a significant correlation was found between frequency of anosmia and covid- in various provinces (spearman coefficient: . , p< . , fig. ) . from the clinical point of view, . % of the responders reported complete loss of sense of smell. the onset of anosmia was sudden in . %, and . % also reported some decrease in their sense of taste. the clinical findings are summarized in table . approximately, . % of the responders had a history of a trip out of their home town before the onset of their olfactory dysfunction, and about . % were hospitalized due to recent respiratory problems. from the family point of view, in . % of the responders, one of the close relatives had a history of severe respiratory disease in recent days, and in . % at least one of their family members was hospitalized due to respiratory problem. in . % of responders, at least one of the family members reported a recent history of anosmia. at the time of the response to the questions, the duration of anosmia ranged from (the same day of onset) to days ( . ± . , median = . ). use of a numerical scale which coded as (no smell/taste, significantly decreased quality of life) to (full smell/taste, normal quality of life) showed that a significant number of patients still had smell and taste problems at the time of responding to the questionnaire; however, some improvements could also be noted (figs. and ). the quality of life was obviously affected due to olfactory dysfunction (fig. ) . during march , the number of patients with olfactory dysfunction was increased in different provinces of iran, concurrent with covid- epidemic. thus, we decided to assess the prevalence of this olfactory dysfunction disorder by an online questionnaire in this population-based study. the results of this study showed a widespread olfactory dysfunction all over the country. also, a significant linear correlation between prevalence of covid- and olfactory impairment that was published online on march , ( ) . the recent outbreak of olfactory dysfunction following flu-like symptoms ( %), higher incidence in women ( %), and a high incidence of anosmia in family members ( . %) are suggestive of a postviral epidemic olfactory dysfunction in iran. although our study could not establish that covid- was the definite cause of olfactory dysfunction, there are no other recent viral epidemics in iran except covid- . thus, as the covid- pandemic rises in parallel with olfactory dysfunction, it can be suggested that these are intimately linked. however, later studies in patients with definite diagnosis of covid- showed that olfactory dysfunction had a considerable prevalence in these patients ( ) ( ) ( ) . ( ) . although the exact pathophysiology of postviral anosmia is unclear, injury may happen at the level of the neuroepithelium of olfactory receptor cells in the nasal roof or in central olfactory routs. however, many studies have focused on the neuroepithelial changes in patients with postviral olfactory dysfunction because of the accessibility of the olfactory cleft. various animal studies explained that different viruses could damage central olfactory routs and other regions of the brain ( ) ( ) ( ) ( ) . it has been found that . % of patients with covid- had a variety of neurological symptoms involving central and peripheral nervous system. in addition, central nervous system findings were a more significant form of neurological damage in patients with covid- . ( ) thus as sars-cov- can reach the brain through the cribriform plate ( ) , anosmia or hyposmia in an uncomplicated covid- case may also need to be considered. there are some limitations to our study. as our data were collected via an online self-reported questionnaire, it was limited to the population who was literate and had access to the internet, personal computers or smart-phones, and were active in social networks. another limitation of this study is that the participants had not been evaluated for sars-cov- test. as this was an online survey, the main goal was to confirm the outbreak of olfactory dysfunction during the covid- epidemic. we encountered an outbreak of olfactory dysfunction in iran during the covid- epidemic, which correlates with the number of patients infected with covid- all over the country. as olfactory dysfunction can affect the quality of life in affected patients, it needs to be assessed worldwide by further clinical studies to find pathogenesis, prognosis, and any correlation between disease severity and olfactory dysfunction. also, we recommend that sudden onset of anosmia be considered in routine work-up and screening for covid- infection. position paper on olfactory dysfunction re-establishment of olfactory and taste functions smell and taste disorders biopsies of human olfactory epithelium world health organization therapeutic options for the novel coronavirus ( -ncov) who. coronavirus disease (covid- ): situation report the epidemiology and pathogenesis of coronavirus disease (covid- ) outbreak covid- : an update on the epidemiological, clinical, preventive and therapeutic evidence and guidelines of integrative chinese-western medicine for the management of novel coronavirus disease neurological manifestations of hospitalized patients with covid- in wuhan, china: a retrospective case series study coincidence of covid- epidemic and olfactory dysfunction outbreak. medrxiv association of chemosensory dysfunction and covid- in patients presenting with influenza-like symptoms. int forum allergy rhinol a primer on viralassociated olfactory loss in the era of covid- . int forum allergy rhinol the use of google trends to investigate the loss of smell related searches during covid- outbreak. int forum allergy rhinol olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (covid- ): a multicenter european study loss of smell and taste in combination with other symptoms is a strong predictor of covid- infection. medrxiv smell dysfunction: a biomarker for covid- . int forum allergy rhinol denneny j. covid- anosmia reporting tool: initial findings. otolaryng head neck identification of viruses in patients with postviral olfactory dysfunction postviral olfactory loss postviral olfactory loss behavioural deficits and serotonin depletion in adult rats after transient infant nasal viral infection effect of olfactory bulb ablation on spread of a neurotropic coronavirus into the mouse brain virus targeting the cns: tissue distribution, host-virus interaction, and proposed neurotropic mechanisms authors wish to thank patients for their participation and kind cooperation. the authors declare that they have no competing interests. http rate your ability to smell during the first days of your olfactory dysfunction. line scale( - ) rate your ability to taste during the first days of your olfactory dysfunction. line scale( - ) how many days have you had olfactory dysfunction? - rate your ability to smell right now (at the time of filling this questionnaire). line scale( - ) rate your ability to taste right now (at the time of filling this questionnaire). line scale( - ) did you use any medication for your olfactory dysfunction? key: cord- -svgw ic authors: ayati, nayyereh; saiyarsarai, parisa; nikfar, shekoufeh title: short and long term impacts of covid- on the pharmaceutical sector date: - - journal: daru doi: . /s - - - sha: doc_id: cord_uid: svgw ic background: the novel coronavirus disease (covid- ) was characterized as a global pandemic by the who on march th, . this pandemic had major effects on the health market, the pharmaceutical sector, and was associated with considerable impacts; which may appear in short and long-term time-horizon and need identification and appropriate planning to reduce their socio-economic burden. objectives: current short communication study assessed pharmaceutical market crisis during the covid- era; discussing short- and long-term impacts of the pandemic on the pharmaceutical sector. results: short-term impacts of covid- pandemic includes demand changes, regulation revisions, research and development process changes and the shift towards tele-communication and tele-medicine. in addition, industry growth slow-down, approval delays, moving towards self-sufficiency in pharm-production supply chain and trend changes in consumption of health-market products along with ethical dilemma could be anticipated as long-term impacts of covid- pandemic on pharmaceutical sector in both global and local levels. conclusion: the pandemic of covid- poses considerable crisis on the health markets, including the pharmaceutical sector; and identification of these effects, may guide policy-makers towards more evidence-informed planning to overcome accompanying challenges. [figure: see text] in december , the novel coronavirus disease (covid- ) was discovered and identified in wuhan, china. on march th, the covid- outbreak was characterized as a global pandemic by the world health organization (who) [ ] . in the following months, covid- rapidly spread around the globe and infected about . million people by april , [ ] . the covid- pandemic affected world economics, including the pharmaceutical sector. while currently there is no definitive treatment for this novel infectious disease, pharmaceutical industry is assisting governments to address the covid- unmet needs, from research and development actions on potential treatment strategies to balancing medicines supply chain in the time of crisis. along this, pharmaceutical sectors are struggling to maintain natural market flow; as the recent pandemic affects access to essential medicines at an affordable price, which is the main goal of every pharmaceutical system [ ] . alongside of evaluation the pharmaceutical system challenges in global level, the situation analysis of this industry in developing country with pharmaerging market, because of diversities, could highlight more impacts. assessment of iran as a developing country that was extremely affected by covid- disease could be a good example for demonstration. to the best of our knowledge, this is the first to identify these challenges in the context of a developing country with a pharmerging market. iran, as a developing middle-income country, has a generic-based pharmerging market [ ] ; which is regulated under local national drug policy (ndp), last updated on . the main components of iran's ndp are generic-based medicine policy, promotion of local production, price control and formulation-based national industry [ ] . iran ministry of health (moh) supported local production aiming to improve availability and affordability of medicines; which are resulted in improved access to the quality medicines in iran [ ] . although more than % (in terms of sale volume) of marketed pharmaceuticals in iran are produced locally [ ] , but the dependence of the production of these medicines on the import of raw materials is a challenging issue. currently, more than half of the active pharmaceutical ingredient (api) are produced in the country, and the remaining are supplied by reputable companies in india and china, and in some cases by some european and eastern european companies [ ] . the dependence of medicine production on the importation of raw materials from countries such as china, which are affected by covid- , is one of the serious concerns of pharmaceutical sector. as of april , , the number of people infected with the sars-cov- in iran was . million [ ] with death ratio of . %; which was consistent with the adjusted statistics of the world [ ] . the overall cumulative covid- -associated hospitalization rate was from < . % in [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] year-olds to . % in - year-olds and doubled in - year-olds to . % based on worldwide data [ ] . current short-communication study assessed pharmaceutical market crisis during the covid- era; discussing shortand long-term impacts of the pandemic on pharmaceutical market natural flow and regulations, first at the global and then at iran's national level as a case in point for developing countries. identification of these effects is essential for policymaker guidance towards more evidence-informed planning to overcome accompanying challenges. covid- may be seen as a century's opportunity for pharmaceutical industry; as it increases the demand for prescription medicines, vaccines and medical devices. this can be seen as one of the main short-term effect of covid- epidemic; however, there are more short and long-term implications to it; which will be discussed below: short-term impacts demand change, supply shortages, panic buying and stocking, regulation changes and shift of communication and promotions to remote interactions through technology and research and development (r&d) process changes can be seen as short-term impacts of covid- on the health market. . demand change, which leads to shortage, in the case of induced demand and panic-buying of oral homemedications especially for chronic disease may be due to the pandemic (covid- -related), and also shortages due to supply-chain inconsistencies. & covid- -related: increased hospitalization, incidence of covid- -related pneumonia and increased demand for assigning patients to ventilators, contributes to related prescription medicine shortages. a medicine shortage is defined as a "supply issue that affects how the pharmacy prepares or dispenses a drug product or influences patient care when prescribers must use an alternative agent" [ ] . on the global levels, many regulatory authorities announced confirmed shortage list, mostly including potential covid- treatments and also associated pneumonia. for example, united states food and drug administration (fda) shortage list included anti-covid- potential pharmacotherapies, hydroxychloroquine (hqc) and chloroquine (qc), and also frequently prescribed medications for covid- hospitalized patients with respiratory signs in critical care units, azithromycin, dopamine, dobutamine, fentanyl, heparin, midazolam, propofol and dexmedetomidine [ ] . in addition, the american society of health-system pharmacists (ashp) announced an medicine list of shortage; which mainly included hospital level antibiotics and anesthetic medications; including meropenem, ceftazidim, ampicillin and doxycycline, as antibiotics and vecuronium, rocuronium, as anesthetics. also, this list included albuterol and fluticasone which are used to open airways in the lungs [ ] . in global levels, the impact on medicine shortage was differed by medicine access level, retail and hospital-only, and type. use of medicines currently being investigated in trials but not yet fully approved by fda or so-called investigational treatmentsincluding hydroxychloroquine, lopinavir+ritonavir, tocilizumab and sarilumab-had seen a two-fold increase in use over the past month, with times higher use in hospitals [ ] . medicines used in hospitals for covid- -including respiratory treatments, sedatives and pain treatments-had experienced an increase of % to %, since the beginning of january [ ] . in local levels, iran food and drug administration (ifda) sale's data indicates that hq, qc and lopinavir+ritonavir experiences , and times increase in their monthly sale volume, respectively; however, ifda's list of medicine shortage for emergency-supply did not report any shortage of aforementioned medicines and/or the drugs required by pneumonia-related hospitalized covid- patients. one of the explanations for this may be the high stock of raw materials; which is justified by the market uncertainties due to iran's economic and political factors, which leads companies to over-stock. the other reason was currency allocation to importation of covid- required medications, by the government. for example, lopinavir+ritonavir accounted for . % ( of billion us dollars) of six-month approved currency order by ifda to iran central bank, for raw materials, finished pharmaceuticals and dietary formula. this covid- related shortage also affected the health market for medical devices and personal protective equipment (ppe), which includes protective goggles and visors, mouth-nose protection equipment, and protective clothing and gloves, that made countries to legislate regulations in this regards. the market entry facilitation and export restrictions of ppe and selected medical devices european commission ( / of march ) is one example, in global levels [ ] . in iran on march st , national medical device directorate of iran announced that restrictions on ppe export is legislated by iran custom office [ ] . also, in order to expedite the supply of required goods and also to reduce the number of face-to-face visits, the process of issuing emergency licenses for medical equipment supplies has been accelerated by sending them to the online communication system and receiving initial approval within one business day. customs measures to combat this pandemic included banning the export of masks, medical gown, gloves, disinfectants, soap, detergents and alcohol, and also expediting the issuance of clearance permits for imported items related to coronavirus and exemptions from costume tariffs [ ] . & induced demand and panic buying: induced demand for stocking medication by public, which is called "panic buying", may cause periodic shortage in the market; especially for chronic disease medications. studies reported that induced demand in global pharmaceutical market, mainly due to "panic buying" of pharmaceuticals for chronic disorders, was estimated to be + . %, by march [ ] . an study in usa indicated that from th to the st of march , asthma medications spiked by %, and type diabetes medications increased by % [ ] . similarly, medicines treating high cholesterol, migraine, and hypothyroidism also saw a noteworthy increase in claims [ ] . also, in usa, excess buying for hypertension, diabetes, respiratory, and mental health and anxiety was . %, . %, . %, . % and . % respectively [ ] . in australia, a one-month-stock regulation for dispensing of prescription medicines, is somehow handling the situation of panic-buying [ ] . in germany, german federal institute for drugs and medical devices (bfarm) published an allocation order on the storage and demanddriven supply of human medicines, on march . the allocation order requested the pharmaceutical companies and wholesalers not to supply medicines beyond the usual demand [ ] . in contrast, the "stay at home" order in some countries may have caused a decrease in demand; however, in iran, due to lack of such regulation only induced demand was reported informally by retail pharmacies. & supply shortage of both active pharmaceutical ingredients (apis) and finished products: china and india are the world's main supplies of apis, key starting materials (ksms) and also finished pharmaceuticals. as they are struggling with the disease and also a slow-down in production, this may have contributed to shortage and also price increase in essential prescription medicines, including antibiotics. this is more critical when nonsubstitutional essential apis, such as amoxicillin, potassium clavulanate, ceftriaxone potassium sterile, meropenam, vancomycin, gentamycin and ciprofloxacin are being concerned. in india, the indian pharmaceutical alliance (ipa) asked government to restrict of all pharmaceutical products, apis and formulation to domestic consumption only. this shortage has already begun to affect api and bulk prices in indian party trades. the average increase was reported to be about - %; however, may reach to % in some cases [ ] . in global levels, to avoid shortages, fda and european commission proposed and published regulations focusing on both demand optimization and rational supply [ ] . these regulation revisions include: & fast-track approvals for covid- -related treatments; in iran, this is in terms of iran medicine list (iml) inclusion and registration process. & compulsory licensing for potential covid- treatments; however, this is in the context of countries who are world trade organization (wto) members and are following intellectual property laws; and it is not subjected to iran. & more regulations to enhance importation, in order to maintain integration of supply chain; however, regarding the economic crisis and currency shortage in iran and also iran's ndp component on enhancing local production and importation minimization, this regulation is not subjected to current context. in iran, again due to over-stocking based on economic and political uncertainties, this impact has not yet to be sensed completely; however, as about % of sale volume and % of sale-value of finished pharmaceuticals [ ] and about % of the api are being imported into the country [ ] , this shortage type will impact the local pharmaceutical industry. in both global and local levels, due to the social distancing precautions, marketing and promotions of health-care products to providers are being shifted from face-to-face towards remote interactions and tele-communications; for both promotional and patient-support acts. in usa, the number of patients who have visited physician offices or clinics reduced by to % [ ] . in iran insurance coverage for tele-medicine is legislated for the first time by high council of insurance on may . this may lead to long-term behavioral changes in the health market. in global levels, at least medicines or regimens and vaccines are in research and development pipelines or active clinical trials, as therapeutics for patients diagnosed with covid- [ ] . as of april , , there are about ongoing trials in the world for the treatment of covid- . only % of these studies are based on conventional rct methods, double-blind and multicenter randomized with comparator arm, but about % are not even randomized [ ] . in iran, hcq is available through local production with five active suppliers and a price of . us$ and is being investigated in moh-registered clinical trials on covid- patients. cq, which is also available by one local manufacturer with the price of . us$, is the intervention arm in iran moh trials and lopinavir/ritonavir, which is included in iran local covid- management guideline for high risk patients as an additive to cq or hcq regimen [ ] and is available through generics importation from indian suppliers with a registered price of . us$ per unit, is being investigated in iran moh trials on patients with confirmed covid- . in addition, multiple clinical trials are being conducted to test non-iml-included medications; naming favipiravir and remdesevir. favipiravir is currently being tested through three moh-supervised clinical trials in iran and three local manufacturers are conducting pharmacokinetic and stability analysis on aforementioned pharmaceutical strategy. also, remdesivir which is an antiviral in first steps of drug development, is being under clinical investigation through iran moh-registered clinical trials [ , ] . this medication was obtained emergency authorization approval by the fda on may st, for hospitalized patients with severe disease condition [ ] . above being noted, there is a dilemma regarding pseudo-researches and industrial investments on medicines which will be identified as non-effective in the near future; which may eventually pose a considerable burden on the health system. ethical considerations must be taken into account within the excited decision making about the use of the treatment strategies based on the results of these pseudo-researches [ ] . long-term impacts approval delays, moving towards selfsufficiency in pharm-production supply chain, industry growth slow-down and possible trend changes in consumption could be seen as long-term impacts of covid- on the health and pharmaceutical market. delayed approvals for non-covid-related pharmaceutical products; as all countries, including iran, are being under pressure of the crisis and their priority is covid- management, approval delays may be seen due to several month of application review postponements. in iran, due to economic crisis, iml inclusion, registrations and reimbursement decisions was being made with a considerable delay; and this situation may maximize it. it also is affected by about one-month semi-closure of regulatory agencies. moving towards self-sufficiency in pharma industry; potential shortages due to export bans in india and china, who are main suppliers of api and generics, made governments of many countries to consider self-sufficiency in supply chain and they have announced regulations to avoid shortages in such crisis [ ] . in this regards, on march the european commission has published a new guideline concerning foreign direct investment and free movement of capital from third countries; stating that foreign investments, especially those which affect the health market, in european union (eu), must be subjected to risk-assessments to avoid any harmful impact on the eu's capacity to cover the health needs of its citizens [ ] . in iran, due to sanctions and difficulties in importation, iran's pharmaceutical industry was going towards selfsufficiency prior to this crisis; however, covid- pandemic may lead to more importation restrictions and further regulation incentives for local manufacturing. coronavirus pandemic resulted in economical slowdowns for many countries and this will possibly lead to pharma industry growth slow-down, which are sensitive to country economic growth; especially, in countries with pharmerging markets, like iran. this slowdown in market growth is more due to the entry of newer medications. because the priorities of pharmaceutical companies change in their portfolio. however, it should be noted that in previous recessions, there were cases in which the health industry was less sensitive to slowing economic growth and did not always follow this trend [ ] . ethical considerations: one of the long-term effects of growing clinical research related to the current pandemic is the use of poorly evidence centered therapies. ethical issues should be considered in the use of these medicines as off-label [ ] . in confirming the proposed therapies, the long-term clinical effects of the use of these strategies in the coming years should be examined and healthcare providers should make informed decisions on using off-label therapies in clinical practice. . consumption trend changes in health-related products: changing habits related to consumption and refilling prescriptions, especially in chronic disease therapeutic areas, might happen; and may also be further affected by the emerging tele-medicine. currently, public is concerned with personal hygiene maintenance; using mainly nose/mouth protection, antiinfections material for environment and clothing and hand sanitizers. due to extended period of pandemic, this consumption may remain in behavioral acts of the public, globally and locally. the short-term and long-term effects discussed in this paper can be seen in many reported trends around the world [ , , ] , and in countries in other regions, such as africa, these effects will be predictable with increasing the covid- prevalence. the reported impacts shown in table . the covid- global pandemic can may be associated with numerous short-and long-term impacts on the health market, mainly the pharmaceutical sector; which can be seen from both global and local perspectives. identifying these impacts may guide policy-makers in evidence-informed planning and decision-making to combat associated challenges. for proper planning to prevent long-term complications, short-term impacts should be identified and further be measured with appropriate data-analysis. identification of these effects is essential for policy-maker guidance towards more evidence-informed planning to overcome accompanying challenges; and this may be more important in the context of developing countries with more scares healthcare resources and pharmerging markets. title of subordinate document how to design and implement a national drug policy. geneva: world health organization trend analysis of the pharmaceutical market in iran; - ; policy implications for developing countries trends in iran pharmaceutical market evaluation of availability, accessibility and prescribing pattern of medicines in the islamic republic of iran new national drug policy in iran leading to expanded pharmaceutical market and extended access of public to medicines iran moh guildeline update for covid- . ministry of health and medical education (iran) the lancet infectious diseases: comprehensive covid- hospitalization and death rate estimates help countries best prepare as global pandemic unfolds drug shortages root causes and potential solutions title of subordinate document title of subordinate document title of subordinate document. in: shifts in healthcare demand, delivery and care during thecovid- era recommendation (eu) / : on conformity assessment and market surveillance procedures within the context of the covid- threat: european commission export ban on personal protective equipment: national medical device directorate of iran title of subordinate document title of subordinate document title of subordinate document in: ensuring continued access to medicines during the covid- pandemic title of subordinate document covid- impact: government panel lists essential drugs that can run out. the economic times title of subordinate document title of subordinate document a single-arm multicenter clinical trial to evaluate the safety and efficacy of remdesivir in covid- patients with progressive severe acute respiratory syndrome coronavirus (sars-cov- ) covid- and off label use of drugs: an ethical viewpoint title of subordinate document guidance to the member states concerning foreign direct investment and free movement of capital from third countries, and the protection of europe's strategic assets, ahead of the application of regulation (eu) / (fdi screening regulation title of subordinate document title of subordinate document title of subordinate document publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations availability of data and material (data transparency) not applicable. authors' contributions all authors contributed in the design and preparation of the manuscript. conflicts of interest/competing interests all the authors declare no conflict of interests which may affect our objectivity.code availability not applicable. key: cord- -k qq qgg authors: sahafizadeh, ebrahim; sartoli, samaneh title: epidemic curve and reproduction number of covid- in iran date: - - journal: j travel med doi: . /jtm/taaa sha: doc_id: cord_uid: k qq qgg covid- was first reported in iran on february, . we estimated the initial basic reproduction number to be . . with increasingly stringent public health measures, the effective reproduction number declined to below after months. late , a novel coronavirus causing coronavirus disease (covid- ) emerged in wuhan, china, and rapidly spread globally. iran reported the first confirmed cases of covid- on february in qom which is located about km to the south of tehran. the outbreak then quickly moved to other parts of iran. the aim of this study was to describe the epidemic curve and estimate the reproduction number of covid- in iran. for this purpose, the sir (susceptible-infected-removed) epidemic model was used to fit the reported data. the differential equations of the sir model are given as: where s(t), i(t) and r(t) are the number of susceptible, infected and removed people. β is the infection rate, and γ is the remove rate which is the inverse of infectious period. the basic reproduction number, r , is the average number of the secondary individuals in a complete susceptible population infected by a single infected person during its spreading life. when r > , the virus spreads through the population, and when r < the outbreak will stop due to decreasing the number of new cases. r can be calculated as the following: n is assumed to be the population of iran in (https://data.worldbank.org). we model epidemic spreading in the period from february to may using reported data by mohme. the runge-kutta method is used to solve the ordinary differential equations in matlab. as shown in figure , we estimated the r to be . in the first week of the outbreak which is significantly higher than that reported for many other regions. iran suffered from inadequate testing kits in the early stages and had to conduct tests in a few laboratories in tehran. hence obtaining the test results was delayed. however, as of march , labs were capable of conducting tests every day. in response to the exponential increase in cases, the iranian government closed all schools in the first week. by the end of the first week, friday prayers were cancelled and all mosques were closed. in the second week, universities were closed and the government reduced the working hours. however, by the end of the second week, the virus spread to all provinces in iran. the government then implemented 'stay at home' policies. social network users created campaigns and public messaging to stay at home and do social distancing. in the second week, r t reduced from . to . and then to . in the third week. figure illustrated the decline of the effective reproduction number over time as increasingly nonpharmaceutical interventions. the effective reproduction number further decreased to . between march and april , most likely due to increasingly stringent measures for social distancing, and 'stay at home' policies, but also the enforcement of quarantine of household and other contacts of confirmed cases. as nowruz, persian new year, arrived on march , many businesses as well as government offices closed, and the government restricted travelling between provinces for almost weeks. as a result, as shown in figure , the effective reproduction number further declined to between april and april . it can be seen that the reproduction number has been less than since april , indicating that the epidemic has been curbed. previous studies showed that the basic reproduction number of covid- was estimated to range from . to . during the early outbreak in wuhan city, china. in iran, the reproduction number was likely higher due to high social mixing during social events. the beginning of the outbreak coincided with the beginning of the new semester for universities when students travelled from their hometowns to their universities. many students live in dormitories where the risk of spreading was high due to close social intermixing. the closure of universities, discontinuation of religious gatherings and prohibition of social events and increasingly additional public health interventions including contact tracing, quarantine and travel restrictions within the country led to a decline of the effective reproduction number to below . unless mitigation strategies continue, covid- will resurge in iran. social distancing, active case detection, prompt isolation of all cases, contact tracing and quarantining of contacts will need to be maintained until an effective and safe vaccine becomes available. covid- poses a tremendous burden on iran's health care system, economy and society, especially at a time of us sanctions. potential for global spread of a novel coronavirus from china a contributions to the mathematical theory of epidemics the reproductive number of covid- is higher compared to sars coronavirus covid- pandemic and comparative health policy learning in iran preliminary estimation of the basic reproduction number of novel coronavirus ( -ncov) in china, from to : a data-driven analysis in the early phase of the outbreak covid- battle during the toughest sanctions against iran e.s. conducted the simulation experiments, analysed the results and wrote the manuscript; s.s. collected the reported case data and revised and edited the manuscript. all authors read and approved the final manuscript. the authors received no specific funding for this work. the authors declare that they have no competing interests. key: cord- - x dp vv authors: ahmadi, mohsen; sharifi, abbas; dorosti, shadi; ghoushchi, saeid jafarzadeh; ghanbari, negar title: investigation of effective climatology parameters on covid- outbreak in iran date: - - journal: sci total environ doi: . /j.scitotenv. . sha: doc_id: cord_uid: x dp vv abstract sars cov- (covid- ) coronavirus cases are confirmed throughout the world and millions of people are being put into quarantine. a better understanding of the effective parameters in infection spreading can bring about a logical measurement toward covid- . the effect of climatic factors on spreading of covid- can play an important role in the new coronavirus outbreak. in this study, the main parameters, including the number of infected people with covid- , population density, intra-provincial movement, and infection days to end of the study period, average temperature, average precipitation, humidity, wind speed, and average solar radiation investigated to understand how can these parameters effects on covid- spreading in iran? the partial correlation coefficient (pcc) and sobol’-jansen methods are used for analyzing the effect and correlation of variables with the covid- spreading rate. the result of sensitivity analysis shows that the population density, intra-provincial movement have a direct relationship with the infection outbreak. conversely, areas with low values of wind speed, humidity, and solar radiation exposure to a high rate of infection that support the virus's survival. the provinces such as tehran, mazandaran, alborz, gilan, and qom are more susceptible to infection because of high population density, intra-provincial movements and high humidity rate in comparison with southern provinces. since late december , patients presenting with viral pneumonia due to an unidentified microbial agent were reported in wuhan, china. it was an outbreak of the novel coronavirus disease named novel coronavirus (covid- ; previously known as -ncov). the disease has rapidly spread from wuhan to other areas and affected countries worldwide by march , , which raised intense attention internationally (chen et al., ; lu et al., ; phan et al., ; xu et al., ) . it is really important to find out all the factors that play a role in covid- spreading in urban. the transmission of viruses can be affected by many factors, including climate conditions (such as temperature and humidity), population density and medical care quality (wang et al., ) . therefore, understanding the relationship between the geographical features of a country and the transmission of covid- is key to making the best decision to control and prevent the pandemic. in other words, the discipline of geography is playing in the fight against the virus sars-cov- , which causes coronavirus disease . therefore, urban geography can be very helpful in that the spatial organization of the city determines the spatial pattern of the spread of the disease (boulos and geraghty, ; wang et al., ) . while a set of health experts are banking on warmer weather conditions to slow down, if not completely halt, the coronavirus, it is yet not clear whether the coming months will bring any respite to the world. based on recent research, which has yet to be peer-reviewed, indicated that two factors include high temperature and humidity, directly correlated with the spreading of covid- in a region (wang et al., ) . (araujo and naimi, ) . however, the spreading of covid- virus in hot and humid conditions will not stop entirely. malaysia has confirmed more than , cases of the virus; more than people are infected in indonesia; and in singapore, where the average temperature is around j o u r n a l p r e -p r o o f year-round, despite rigorous detection methods and strict quarantine rules. the results of the research show that longer-term dramatic change of solar flux of ionizing radiation leads to provide an opportunity to create nono-metrical viruses like sars and mers (qu and wickramasinghe, ) . also, high solar radiation prevents an outbreak with inactivating (or semi-infectious) coronaviruses (gupta et al., ; qu and wickramasinghe, ) . based on the results of (qu and wickramasinghe, ) identified. finally, the discussion and conclusion presented. the main variables in this study include geographical indicators with averaged data from february to march from weather spark online web service ("the typical weather anywhere on earth -weather spark," n.d.). variables including the number of infected people with covid- reported by ("who | world health organization," n.d.), population density, intra-provincial movement, infection days to end of the study period, average temperature( • c) (yuan et al., ) , average precipitation (mm) (araujo and naimi, ) , humidity(%) (wang et al., ) , wind speed (km/h) (yuan et al., ) and average solar radiation (kwh/m ) (qu and wickramasinghe, ) in the study period. the infection rate as a dependent variable defined as eq. ( ). this variable indicates the rate of infection or speed of the covid- spreading. table shows the descriptive statistical and meteorological data of iran from february to march . ( ) where p is average annual precipitation (mm), t is the average annual temperature ( • c) and i is de martonne aridity coefficient. in this equation, the evaporation is indirectly considered. this method is more widely used in iran for two reasons. the first availability of the factors and second the classification of this method can define diverse climates (zareiee, ) . the de martonne classification is shown in table . iran can be divided into at least four different climate zones. different clustering current climate regions in iran shown in fig. a . more than half of iran's area is arid and consists of lands with high average temperature shown in orange color. however, the semi-arid area includes high mountain and agricultural lands. this area is gray in fig. a . also, three provinces of iran have the mediterranean, wet and very wetlands consisting of jangles and grasslands. the outbreak of covid- based on the first case of observation is shown in the geographical map ( fig. b ). the first case of covid- infection occurred in qom and then spread to all provinces over the days period. regarding the figure, qom and tehran can be described as the center of outbreaks that have spread throughout the south and north. in some provinces, this outbreak has occurred earlier, which has been spectacularly significant in terms of intra-provincial movement. in some provinces, this outbreak has occurred after days, which can be attributed to a lack of awareness of the people. in order to get a better understanding of the covid- outbreak in the iranian provinces and the study of geographical factors, the meteorological data recorded in the study period are referred. the results of pearson correlation analysis between the variables are shown in table . in this study, the infection rate was defined as the independent variable and its correlation with geographical variables analyzed. do these results show whether the rate of disease outbreaks in the provinces depends on geographical factors or not? using these results, we can infer the meteorological impact scenario on the outbreak of covid- . according to table in this part of the research, sensitivity analysis between variables is discussed. therefore, we use two methods of partial correlation coefficient (pcc) and sobol'-jansen method to examine the importance of variables and prioritize it. in the pcc method, a linear regression must be made between the independent variables of the problem and the infection rate. on this basis, the basic geographical data should first be standardized. linear regression is created after changing data range between - and . table ). we are not satisfied with linear regression, to investigate these variables more consistently, we will continue to use one of the most powerful methods for identifying in this paper, we used the multi-layer perceptron (mlp) technique with hidden neurons to create a more accurate model. we used % of the data for training, % testing, and % model validation, to obtain the best model with the highest accuracy (r = %). the results were recorded as shown in fig. . by applying the mlp model on sobol'-jansen method, results are depicted in fig. d. figure figure shows the contour infection rate of covid- disease concerning geographic variables (population density and movement). the higher value of the population density and intra-provincial movement leads to a higher value of infection rate so that in high-density provinces, the rate of disease growth reaches people per day. figure b also shows the bubble plot of the average temperature and relative humidity over the study period. the size of bubbles also indicates the rate of infection, and the bubbles have different colors for different climates from iran. results show that in arid and semi-arid regions, disease rates are higher in areas with low humidity than in areas with high humidity. however, two wetlands of mazandaran and gilan are places with a high rate of infection. because these provinces are areas with very high population density. with the classification of the area to different climates, the average rate of disease spread in wetlands is higher than in other areas of iran (fig. c) . figure illustrates the governing variables involved in the change of coronavirus covid- spreading rate. the maps are depicted and colored based on data quartiles. figure i shows the covid- infection rate over the study period. observations show that the infection rate in the provinces of central iran is higher than in the border regions, and these provinces are both high in population density and movement. a comparison of the virus infection rate charts and meteorological maps can justify the results obtained in the aforementioned methods. according to fig. f, it can be seen that the humid area includes north, west, and northwest of iran. however, the main part of the outbreak is in humid, very humid, and semi-arid (or mountainous) areas. the wind direction in most parts of iran is from the west and in the northeast to west. wind speeds are low in most parts of the country. based on fig. h solar radiation in central iran is lower than southeast with a low infection rate. we can conclude that where the infection rate is high, the population density and movement are high. also, in this area humidity, wind speed and solar radiation have a reverse relationship with the rate of the disease spreading. the the in that the spatial organization of the city determines the spatial pattern of the spread of the disease. iran is one of the countries with different types of climate. the infection rate in provinces is different; therefore, understanding the main variables that play an important role in this various spreading rate is crucial. in this study, the correlation of nine main variables includes the number of infected people, population density, intra-provincial movement, days of infection, average temperature, average rain, humidity, wind speed, and solar radiation with infection rate analyzed. the sensitivity analysis between variables determined by two methods partial correlation coefficient (pcc) and sobol'-jansen to examine the importance of variables and prioritize it. based on the pcc method, the population density, intra-provincial movement, day of infection have a direct relation with infection outbreak. conversely, wind speed, humidity, and solar radiation have an indirect correlation with the infection rate. however, in two humid regions of iran, the rate of virus spreading is high. the sobol'-jansen method also approved the aforementioned results and confirmed that the main variables that play an important role in the covid- outbreak are population density, intra-provincial movement, wind spread of sars-cov- coronavirus likely to be constrained by climate. medrxiv geographical tracking and mapping of coronavirus disease covid- /severe acute respiratory syndrome coronavirus (sars-cov- ) epidemic and associated events around the world: how st century gis technologies are supporting the global fight against outbr the effects of temperature and relative humidity on the viability of the sars coronavirus epidemiological and clinical characteristics of cases of novel coronavirus pneumonia in wuhan, china: a descriptive study application of gene expression programming and sensitivity analyses in analyzing effective parameters in gastric cancer tumor size and location do sunspot numbers cause global temperatures? evidence from a frequency domain causality test genomic characterisation and epidemiology of novel coronavirus: implications for virus origins and receptor binding importation and human-to-human transmission of a novel coronavirus in vietnam sars, mers and the sunspot cycle variance based sensitivity analysis of model output. design and estimator for the total sensitivity index the typical weather anywhere on earth -weather spark high temperature and high humidity reduce the transmission of covid- who | world health organization pathological findings of covid- associated with acute respiratory distress syndrome a climatologic investigation of the sars-cov outbreak in beijing, china. am evaluation of changes in different climates of iran, using de martonne index and mann key: cord- - uxq xrs authors: alavi, maryam; moghanibashi-mansourieh, amir; radfar, seyed ramin; alizadeh, sepideh; bahramabadian, fatemeh; esmizade, sara; dore, gregory j.; sedeh, farid barati; deilamizade, abbas title: coordination, cooperation, and creativity within harm reduction networks in iran: covid- prevention and control among people who use drugs date: - - journal: int j drug policy doi: . /j.drugpo. . sha: doc_id: cord_uid: uxq xrs an unprecedented public health crisis confronts the world. iran is among the hardest-hit countries, where effects of the covid- pandemic are stretched across society and felt by the most marginalised people. among people who use drugs, a comprehensive response to the crisis calls for broad collaboration, coordination, and creativity involving multiple government and non-government organisations. this commentary provides early insights into an unfolding experience, demonstrating the operational and policy impact of an initiative, bringing together a diverse array of harm reduction stakeholders to address the pandemic. in the context of lived experiences of social and economic marginalization, this initiative intends to lead efforts in developing an equitable response to the covid- pandemic. in iran, the first two cases of infection with severe acute respiratory syndrome coronavirus (sars-cov- ) were confirmed on february , . by april , iran had the ninth and seventh-highest numbers of infections and deaths in the world, respectively (johns hopkins university, ). among people who use drugs (pwud), numbers of sars-cov- infections and deaths are unknown; however, the scale of the pandemic and vulnerability of pwud underscore the need for relevant and timely action, if the threat is to be controlled among this population. drug use is a significant public health issue in iran. in , an estimated . million people had used drugs in the previous year (nikfarjam et al., ) . since the revolution, iran has gradually shifted from zero-tolerance policies towards drug use to adopting harm reduction initiatives in the late s and drug law reforms in s (alam-mehrjerdi, abdollahi, higgs & dolan, ; ekhtiari et al., ) . by , opioid agonist therapy and needle exchange programs were available in more than clinics and nearly centres, respectively (national aids committee secretariat, ) . the non-government sector has played a significant role in this trajectory, in promoting a sharper focus on harm reduction vs punitive/criminal justice approaches, and in providing access to care among the most marginalised pwud (ghiabi, b) . in recent years, the harm reduction infrastructure has been utilised to scale-up therapeutic interventions among pwud mirzazadeh et al., ) , and is wellpositioned for provision of covid- control measures too, given appropriate public health leadership in policy development and allocation of resources. the government has a limited capacity for leading efforts in identifying and corresponding to the specific needs of pwud during a pandemic (farhoudian et al., ) . years of unilateral economic sanctions imposed by the united states, the rise of socially austere https://doi.org/ . /j.drugpo. . policies within a weakened economy, and ongoing restrictions on humanitarian trade transactions have contributed to significant shifts in priorities and reduced the potential for a comprehensive covid- public health strategy (ameli, ; kokabisaghi, ; murphy, abdi, harirchi, mckee & ahmadnezhad, ; takian, raoofi & kazempour-ardebili, ) . the necessity to act against the pandemic and gaps in covid- public health policy prompted a major non-government organization (ngo) to initiate administrative action and develop the covid- prevention and control working group, bringing together a diverse range of representatives from private and public sectors. this working group aims to enable greater collaboration between government and non-government sectors and develop an equitable covid- response among pwud. since early march, the government has implemented several physical distancing policies; these strategies are primarily in line with recommendations on continuity of care among pwud, including increases in take-home doses of opioid agonist therapy (farhoudian et al., ; united nations office on drugs & crime, b). decisions to close public parks and temporarily release more than , people from prisons, were made to reduce community and in-custody transmission (kinner et al., ) , although without significant oversight. many individuals from the lower socioeconomic background were not linked to adequate financial, harm reduction, and housing support postrelease from prison; and among many people without stable housing, closure of parks limited access to water and sanitation facilities. subsequently, on april , tehran municipality welfare, services & social participation organization published images of pwud and homeless people on twitter (@swsctehran), gathering in large groups in shoosh neighbourhood of south tehran (fig. ) . magnified on various media platforms, these photographs and similar video footage, instigated social panic and presumption of heightened transmission among this transient and marginalised community. these images and broader societal reaction reflected on the need for proactive and robust civil society response, enabling the development of public health policies within the context of underlying social and economic disadvantages of pwud. development of the working group was primarily a spontaneous response to an unprecedented challenge. this initiative was inspired by the principles of asset-based community development (mathie & cunningham, ; mcknight & russell, ) ; rebirth charity society (rebirth charity society, ), a well-known local organization, mobilised the existing networks among harm reduction stakeholders, to create a collective vision for equitable covid- response among pwud, garner broad support, and activate institutional resources. the working group was established using popular messaging applications. these platforms provided an accessible space to discuss critical issues, including covid- policy updates, scientific information and education, and service provision among peer-support workers and people attending community-based drop-in centres, homeless shelters, and mobile and outreach services. the leading group comprise members, including ngo representatives ( peer-support workers and management and coordination staff), three clinicians, three social workers, psychologist, sociologist, academic researcher, journalist, two members of an intergovernmental organization, and a representative from the state welfare organization. all members work in addiction care and pwud health, or associated fields; the majority ( %) have a history of drug use. several methods are used to mobilise members around the common goal. all members, particularly peersupport workers, are encouraged to collect and share stories of community success, including reports, video, and photographs of daily activities across the country. these stories are crucial in positioning and discussing supply shortages and priority actions. given the scarcity of resources, actions that solve existing issues within the community are ideal. disagreement about priority areas and solutions are not uncommon and are mostly resolved through open discussion (text, voice messages, or calls) on the working group messaging application. faceto-face meetings are rare, considering physical distancing guidelines. tasks are assigned to smaller groups, including fundraising, purchases, media releases, development of educational material, and publication of findings, reports, and recommendations. allocation of tasks is mainly volunteer-based. in all steps, from sharing of community stories to implementation of actions, inclusive participation of all members is profoundly meaningful. historically, peer-support workers are directly engaged in service delivery and play a limited role in the process of decision making. to address this issue, members who occupy leadership positions or those with perceived importance (e.g. highly educated individuals) ensure contributions of everyone, particularly peer-support workers, are valued. these efforts are reflected in highlighting community achievements, inviting peer-support workers to express their views and thoughts on specific needs of the community, and encouraging them to share their skills, passions, and social and associational networks with all members. where needed, knowledge, activities, resources, and investments from outside the group are sought. emerging as an immediate response to a health crisis, the working group has not developed a terms of reference for members; however, as the covid- pandemic unfolds in iran, members aspire to focus on experiences and successes of the past and continue to promote change that would improve health outcomes among pwud. direct care services for people who use drugs between march and april , the working group coordinated distribution of covid- prevention equipment and education booklets, personal items, food, and water among people attending community-based drop-in centres, homeless shelters, and eight mobile and outreach services (visiting street-based drug markets) in four provinces. on average, each person received face masks, two litres of hand sanitiser, five litres of surface disinfectant, five education booklets, meals and snacks, and three small bottles of water (excluding people in fars province) ( table ) . the working group collaborated with the united nations office on drugs and crime country office and state drug control headquarters to develop content for three covid- prevention education podcasts and a booklet. podcasts were prepared professionally, presented by a wellknown iranian producer (united nations office on drugs & crime, a). among people attending community-based drop-in centres, shelters, and mobile and outreach services, trained peer-support workers held face-to-face education sessions. they played the podcasts on speakers while displaying prevention measures, including hand washing. these sessions were held recurrently, and booklets were distributed among attending individuals. among people attending community-based drop-in centres, shelters, and mobile and outreach services, peer-support workers have carried out routine checks to identify people with common symptoms of sars-cov- infection, including fever, cough, and shortness of birth. thus far, five people were referred to hospitals, who did not test positive for infection. in addition to services directly to people in need, the working group actioned necessary support for peer-support workers. between march and april , the working group coordinated the distribution of covid- prevention equipment among peer-support workers in four provinces. on average, each person received facial masks, pairs of gloves, and litres of hand sanitiser (table ) . many pwud and homeless people access clean water through shelters and community-based drop-in centres (bastani, marshall, rahimi-movaghar & noroozi, ) . however, among those with limited engagement with these services, interrupted access to water deepens the experience of stigma and social marginalization. the recent closure of public parks, as a physical distancing measure, further stressed the need to resolve this issue. through a successful fundraising campaign, the working group has received water tanks, -liter capacity each, as well as commitment for ongoing free refills. peersupport workers and project coordinators were appointed to locate high-priority areas, organize logistics of transportation and installation of tanks, and educate people on the maintenance of their water source. working group policy advocacy violation of physical distancing by pwud and homeless people in tehran in early april marked the beginning of a campaign by several government organisations, led by factions within the state drug control headquarters, proposing swift capture and hold of these individuals in designated shelters for the duration of the pandemic. working group members noted several limitations within this proposal, including shortcomings in contextual relevance, and issues directly related to covid- , namely lack of separate quarantine facilities for people with and without covid- symptoms on arrival, suboptimal infrastructure for covid- prevention and treatment, and potential interruptions in access to opioid agonist therapy. the working group took several subsequent steps to ) initiate mainstream and social media debates on principles of equity, respect, and diversity in public health strategies; and ) participate in proposal revisions and development of covid- policies that are adjusted to the needs of marginalised people. the working group partnered with the state welfare organization, to develop a joint report of current covid- prevention activities and put forward a set of recommendations on an appropriate response to the pandemic among pwud and homeless people. as public discussion swirled on various media platforms (deilamizade, ; moghanibashi-mansourieh, ; mohammadi, ; nouri, ; radfar, ) , state welfare organization participated in several meetings with other government organisations, including the office of the presidency, to present the joint report and discuss concerns raised by the working group. in late april, the state drug control headquarters withdrew the initial proposal. they published the finalised protocol for the accommodation of pwud and homeless people, endorsing the recommendations of the working group on transportation, housing, medical, and harm reduction needs of these populations. several concerns remain about adequate implementation of this policy over the coming months, supporting the need for continued monitoring of health outcomes among people in government facilities and ongoing collaborations between the working group and government organisations, to inform future policies. in the past several months, many examples of civil society response to the covid- pandemic have been recorded in iran. the experience of the working group is among numerous grassroots initiatives that have enabled communities to organize, manage common problems, and develop a new understanding of government responsibilities and capacities (ghiabi, a) . among working group members, thus far the successful experience of covid- response provided much-needed space to develop an innovative model of cooperation within the harm reduction network and explore new ways of engagement with broader government organisations. grounded in values of equity and inclusion, members were able to share their expertise in identifying specific needs of vulnerable populations and participate in developing immediate and long-term solutions. the experience of collaboration within a nonjudgemental and inclusive environment was new to many members, given the common hierarchical culture of organisations in iran. use of messaging applications was an inexpensive method to increase the accessibility of information for all, enable faster communication about field and policy updates, reduce delays in decision making and implementation, and promote a platform for all members to contribute different types of knowledge and skills. inspired to share this experience with other members of the harm reduction community, working group is developing digital communication platforms to promote peoplecentred education and advocacy material for people in regional and rural areas. currently, the capacity of the working group in gathering member opinions and concerns and facilitating an active interaction with policymakers is built upon decades of working relationships among senior harm reduction stakeholders. key connections with government organisations are pivoted around influential individuals, particularly those within the state welfare organization who have longstanding ties within the community and non-profit sector. ongoing contribution to creating more effective governance systems would require the working group to maintain these connections while investing on developing a balanced organisational structure, involving components for a broader member base and policymakers who join the harm reduction network (albareda, ) . in the unprecedented times of a pandemic, iran finds itself in a difficult position to respond to a significant public health crisis and provide adequate care and support for its large population of vulnerable people. in most middle-income countries, including iran, control of the pandemic requires resolving significant financial and technical challenges (bedford et al., ; hopman, allegranzi & mehtar, ) ; however, the experience of this working group reflects on how greater collaboration among stakeholders and between government and nongovernment sectors could bring individual and population health benefits at the operational and policy levels. in support of equitable public health interventions among marginalised populations, particularly in settings with limited resources, the function of this working group highlights the need for empowerment of civil society, enhanced use of existing community assets, and meaningful collaboration in decision making. this manuscript is a commentary, reflecting on the experience of civil society responding to the covid- pandemic in iran. ethics approval was not necessary. authors have no commercial relationships that might pose a conflict of interest in connection with this manuscript. drug use treatment and harm reduction programs in iran: a unique model of health in the most populated persian gulf country an intervention to improve hcv testing, linkage to care, and treatment among people who use drugs in tehran, iran: the enhance study connecting society and policymakers? conceptualizing and measuring the capacity of civil society organizations to act as transmission belts sanctions and sickness the risk m iran: a qualitative study covid- : towards controlling of a pandemic the evolution of addiction treatment and harm reduction programs in iran: a chaotic response or a synergistic diversity proposed protocol for arrest and hold of people who use drugs contrasts realities on the ground (in farsi) covid- and substance use disorders: recommendations to a comprehensive healthcare response. an international society of addiction medicine (isam) practice and policy interest group position paper basic and clinical neuroscience mutual aid and solidarity in iran during the covid- pandemic. middle east research and information project: critical coverage of the middle east since under the bridge in tehran: addiction, poverty and capital managing covid- in low-and middleincome countries prisons and custodial settings are part of a comprehensive response to covid- assessment of the effects of economic sanctions on iranians' right to health by using human rights impact assessment tool: a systematic review from clients to citizens: asset-based community development as a strategy for community-driven development a one-stop community-based approach for hcv screening, diagnosis and treatment among people who inject drugs in iran: the rostam study the four essential elements of an asset-based community development process. what is distinctive about asset-based community process three key points about government proposal on arrest and hold of people who use drugs (in farsi). tasnim news, article code state welfare organization: there will be a massacre if people who use drugs are arrested and held. police: we are ready to proceed. elaheh mohammadi interviewes farid baratisedeh (in farsi) ministry of health and medical education. islamic republic of iran aids progress report on monitoring of the united nations general assembly special session on hiv national population size estimation of illicit drug users through the network scale-up method in in iran will covid- clear people who use drugs off streets? addiction experts disgaree with government proposal. marzieh nouri interviews abbas deilamizade and seyed ramin radfar (in farsi) dysfunctional government and role of non-government organisations in crisis management (in farsi) unodc iran developed assistance package on covid- for people who use drugs at hotspots in iran unodc suggestions about treatment, care and rehabilitation of people with drug use disorder in the context of the covid- pandemic we would like to acknowledge the united nations office on drugs and crime, country office in the islamic republic of iran, iranian drug control headquarters, as well as several ngo members of the covid- prevention and control working group, for playing a key role in all operational and strategic activities of the working group, including noore sepid hedayat (http://www.nooresepid.com/en/); siamaye sabz rahaye (http://simayesabz.org/?lang=en); payam avaran_e_hamyari (chatra) (https://www.chatrango.com/); toloo bineshanha society (https://toloo.org/); nasim mehr afarin; navid ham razi (https://nhi.org.ir/); khaneh khorshid (http://www. khanehkhorshid.ir/), and society for recovery support (http://srsorg. com/). key: cord- -gns omyb authors: kafieh, rahele; arian, roya; saeedizadeh, narges; minaee, shervin; amini, zahra; kumar yadav, sunil; vaezi, atefeh; rezaei, nima; haghjooy javanmard, shaghayegh title: covid- in iran: a deeper look into the future date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: gns omyb the novel corona-virus (covid- ) has led to a pandemic, affecting almost all countries and regions in a few weeks, and therefore a global plan is needed to overcome this battle. iran has been among the first few countries that has been affected severely, after china, which forced the government to put some restriction and enforce social distancing in majority of the country. in less than months, iran has more than , confirmed cases, and more than , death. based on the official statistics from iran's government, the number of daily cases has started to go down recently, but many people believe if the lockdown is lifted without proper social distancing enforcement, there is a possibility for a second wave of covid- cases. in this work, we analyze at the data for the number cases in iran in the past few weeks, and train a predictive model to estimate the possible future trends for the number of cases in iran, depending on the government policy in the coming weeks and months. our analysis may help political leaders and health officials to take proper action toward handling covid- in the coming months. an outbreak of a pneumonia with unknown origin is reported in the last days of december in wuhan, china [ ] . the world health organization named this disease covid- after that genetic sequencing revealed the same origin of the etiologic agent with coronaviruses [ ] .the mean incubation period of this virus is estimated to be . days ( - days) and the infected patient is asymptomatic in the incubation period [ , ] . patients infected with this work is licensed under the creative commons by-nc-nd . international license. visit https://creativecommons.org/licenses/by-nc-nd/ . / to view a copy of this license. for any use beyond those covered by this license, obtain permission by emailing info@vldb.org. copyright is held by the owner/author(s). publication rights licensed to the vldb endowment. proceedings of the vldb endowment, vol. , no. issn - . doi:xx.xx/xxx.xx this virus have flu-like symptoms, including fever, cough, fatigue and dyspnea [ ] . the overall death rate is estimated to be . % but is higher in elderly and those with comorbidities [ ] . although public health measures have already implemented in china, but more than million people in almost all countries and territories are infected during a -month period [ ] . one of the most important concerns in dealing with the influenzalike illness (ili) pandemics such as covid- is early identification and short-term (online) estimation of its final size and peak time. this early prediction using mathematical models and combining with a small amount of existing data would effectively help the governments and public health officials to put in place appropriate prevention and control strategies. for answering this issue many mathematical models are already used for prediction ili pandemics. two approaches are generally considered in the literature on forecasting ili pandemics. the first is focused on short-term estimation, and the others try to predict a long-term estimation. based on some prominent studies in this filed [ , ] , deep learning methods conquered other classical models in short-term estimation of pandemics. in special case of covid- , given the novelty of the subject, most studies have already focused on short-term prediction; however, to the best of our knowledge, no work is already published on prediction of occurrence of covid- using deep learning models. limited number of works have already used deep learning in diagnosis of covid- using medical images [ ] . in this study, we provide a deep learning based prediction method that can assist medical and governmental institutions to prepare and adjust as pandemics unfold. to this end, we develop multiple models describing epidemic and compare their performance and effective features in forecasting. to make sure our methodology is generalize-able, in addition to iran's data (which is our main focus in this paper), we also apply this framework to several other countries and show consistent finding for all of them. figure provides an overview on countries selected for performance evaluation in this paper. the structure of the rest of this paper is as follows. section provides a overview of some of the representative works which are relevant to this work. section presents the details of the data sources used in this study. section gives a quick introduction to the machine learning algorithms used for training a predictive model. section provides a detailed quantitative and qualitative all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . https://doi.org/ . / . . . doi: medrxiv preprint analysis of the accuracy of our forecasting model, and some of the possible future trends for covid- situation in iran and other countries. finally the paper is concluded in section by providing a discussion on the current situation and the future of covid- in iran based on the current data. two approaches are generally considered in the literature on forecasting ili pandemics. the first is focused on short-term estimation, and the others try to predict a long-term estimation. based on some prominent studies in this filed [ , ] , deep learning methods conquered the other competitors in short-term estimation of pandemics. in special case of covid- , given the novelty of the subject, most studies have already focused on short-term prediction; however, to the best of our knowledge, no work is already published on prediction of occurrence of covid- using deep learning models. here we go over some of the representative ones. in [ ] , fan et al. investigated the effect of early recommended or mandatory measures on the reducing the crowd infection percentage, using a crowd flow model. in [ ] , hu et al. developed a modified stacked auto-encoder for modeling the transmission dynamics of the epidemics. using this framework, they forecasted the cumulative confirmed cases of covid- across china from jan , to april , . in [ ] , roosa et al. used phenomenological models that have been validated during previous outbreaks to generate and assess short-term forecasts of the cumulative number of confirmed reported cases in hubei province, the epicenter of the epidemic, and for the overall trajectory in china, excluding the province of hubei. they collected daily report of cumulative confirmed cases for the -ncov outbreak for each chinese province from the national health commission of china. they provided , , and day forecasts for five consecutive days, with quantified uncertainty based on a generalized logistic model. in [ ] , liu and colleagues used early reported case data and built a model to predict the cumulative number of cases for the covid- epidemic in china. the key features of our model are the timing of implementation of major public policies restricting social movement, the identification and isolation of unreported cases, and the impact of asymptomatic infectious cases. in [ ] , kucharski et al. combined a mathematical model of severe sars-cov- transmission with four datasets from within and outside wuhan, and estimated how transmission in wuhan varied between december, , and february, . they used all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . https://doi.org/ . / . . . doi: medrxiv preprint these estimates to assess the potential for sustained human-tohuman transmission to occur in locations outside wuhan if cases were introduced. in [ ] , peng and colleagues analyzed the covid- epidemic in china using dynamical modeling. using the public data of national health commission of china from jan. th to feb. th, , they estimated key epidemic parameters and make predictions on the inflection point and possible ending time for different regions. in [ ] , remuzzi analyzed the covid- situation in italy, and mentioned if the italian outbreak follows a similar trend as in hubei province, china, the number of newly infected patients could start to decrease within - days, departing from the exponential trend, but stated this cannot currently be predicted because of differences between social distancing measures and the capacity to quickly build dedicated facilities in china. in [ ] , sajadi et al. tried to predict potential spread and seasonality for covid- based on temperature, humidity, and latitude information. they found that the distribution of significant community outbreaks along restricted latitude, temperature, and humidity are consistent with the behavior of a seasonal respiratory virus. this study uses four data sources to predict covid- disease, including covid- data, basic information, detailed information for each country, as well as sars data. the covid- data (by john hopkins university) contains daily number of confirmed/ death / recovered people. the basic information contains the information about date/country/province of the cases. the more details on how the data is used, is as follows. we collected the covid- data from john hopkins university [ ] and [ ] . the dataset contains cumulative number of confirmed, death and recovered covid- cases in various locations across the world for different dates. basic information (date, country, province) were also provided by john hopkins university. we also added more detailed information for each country; this includes region, population, area, etc. detailed information for each country is according to information in [ ] . different combinations of the involved data are evaluated on proposed models and "the most effective combination" and "optimal lag parameter" are selected based of effectiveness in data modeling (section ). in this work, we propose to show the performance of different deep learning (dl) and machine learning (ml) models for covid- data prediction for above mentioned dataset. to have a successful prediction using deep learning based models, it is essential to have a large-scale dataset. however, since covid- is a recent disease in the world, the available of data is limited and training a deep learning model from scratch on this dataset becomes very challenging. therefore, with respect to intrinsic similarities of covid- to pandemics like sars , we also use a public dataset: [ ] from november to july on sars data. we first train the model with largescale data for sars; the weights of the trained model are then used as pre-trained network and transfer learning is then utilized by training the weights of the last fully connected layers using covid- dataset. the overall framework of the proposed model is shown in figure . first the relevant information are extracted and processed from data sources. then the model is pre-trained on sars data (since more labeled data is available on sars). those models are then fine-tuned (re-trained) on covid- data. finally the models' performances are measure using mean average percentage error (mape) metric. we experimented with more than machine learning models, but to be concise, only report the result of four promising ones, which includes, random forest (rf) [ ] , multi-layer perceptron (mlp) [ ] , long short-term memory (lstm) [ ] for each of these models, different structures (hyper-parameters and parameters) are examined and best performing architectures are summarized in table where is the actual value and˜is the corresponding estimated value for ℎ sample from all n available samples. all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. one of the models used in our work is random forest (rf). rf is essentially an ensemble of decision trees, i.e. it predicts the target value by training several decision tress and combining their results. one nice feature of rf is that it can be used for both regression and classification problems. once the model is trained, the average predicted score of different trees can be used to predict the value of test samples. figure shows the overall diagram of a rf. multi-layer perceptron (mlp) (also known as feedforward network) is a popular neural network, which uses a cascade of several nonlinear transformations (or layers) to make a prediction. the input features are sometimes called input layer, and the intermediate transformations are called hidden layer. all nodes in hidden layers use a nonlinear activation function (figure ). figure shows the overall structure of a mlp model. unlike static data (such as images), time series also adds the complexity of a sequence dependency among the input variables [ ] (figure ) , and ideally require a model with sequential processing capability. the vanilla neural networks (such as mlp) do not have the sequential processing power. however their is an extension of feed-forward neural networks for this purpose, called recurrent neural networks, where at each step the input from the current time and the hidden state from the previous time-stamp is used to make a prediction. figure shows the architecture of rnn models. figure shows the high-level architecture of a single lstm unit. an alternate time series problem is the case where there are multiple parallel time series and a value must be predicted for each. now, we may consider number of occurrences in all classes (confirmed/ death / recovered) as input data and predict the value for each of the three time series for the next time step (a multi-input and multi-output (mimo) format). the machine learning models are trained and tested based on , , and occurrences of daily number of confirmed, death, and recovered covid- cases. a lag of six days was applied to the data. the dataset is divided into training and test data sets. (data from january, til march was used as the training set and the data from march till april was used in test stage for performance evaluation of the proposed prediction method). the training data is further divided to train and validation subsets using ratio of : based on the dates. the networks are pre-trained with occurrences for daily number of confirmed, death, and recovered cases for sars data. each model is tested with many different architectures and the best performance is achieved all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . https://doi.org/ . / . . . doi: medrxiv preprint with architectures described in table . we used implementation in keras package in the python version . . [ ] . the performance of each model is evaluated on the test set of to provide a fair evaluation based on the mape value. the best lag is found by comparing mape values as discussed in . . the results also changed by feeding different input features to each candidate model (elaborated in table ) in section . . the best model/input combination is then found to forecast for next days in section . . the proposed models are tested utilizing time series data types. different time intervals, termed as "lag", can be considered before the prediction date to feed the occurrence data into the model. namely, with a sample lag equal to = , the model predicts the occurrence in st march is using input values in from l prior data points (in th, th, th and th march). figure is designed to show mape value for predicting occurrences of confirmed, death, and recovered cases from covid- when lags of - days are used on validation data in preparatory model to find the optimum lag. the lowest mape is found for lags of , , and days, , , and days, and , , and days for confirmed, death, and recovered cases, correspondingly. therefore, a lag of six days is found to be the "optimal lag parameter". three different types of models are chosen as candidates for this application as elaborated in section . to evaluate the performance of the models, it is important to consider different inputs fed into each model. for example, discussing about rf model, three scenarios can be assumed: using basic and detailed features, selecting lag (previous occurrences), and combining all features and lags. this can also be repeated for each model and the performances can be then evaluated. we selected the mape metric to compare different model/ input combinations. the mape metric provides the percentage of error on real value and is more reliable compared to mean absolute error which only demonstrates the value of the error (difference of the predicted and real values). for such an evaluation, a set of nine countries are selected; china is undoubtedly the main candidate as the starting point of covid- . iran, italy, spain, and usa are selected due to the report of high number of confirmed and death cases. germany and switzerland are also coming from different trend with high number of confirmed cases and controlled number of death. finally, korea and japan are also included for demonstrating the countries with high degree of control on the epidemic. table shows a summary of the performance on nine selected countries with different models and diverse combination of input features. with respect to results of table , we found a new set of parameters including basic and detailed feature plus lag (previous occurrences). furthermore, the results suggest that m-lstm is the best performing network for identifying the true magnitude of the pandemic with a mape value of . % for nine selected countries. this network, as elaborated in section , uses lag information from confirmed, death, and recovered cases to predict each next occurrence. this result shows that considering the mutual effect of these three occurrences can provide a better modeling and ignoring such dependence, leads to less performance. table also shows that lowest performance is obtained with rf. figure compares the ability of best and worst performing models in correct prediction of the test values. all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . https://doi.org/ . / . . . doi: medrxiv preprint to provide a forecasting on number of confirmed, death, and recovered cases in iran, we predict the upcoming days until july nd of . considering results in table , the best performing network (m-lstm) is selected with the best combination of the inputs (basic information, detailed information and lags from all three kind of occurrences). the forecasting is illustrated in figure . figure a and b show the predicted daily and cumulative number of confirmed, death, and recovered cases in iran. the performance of the forecasting is also presented after april and the values are compared to real reported values in figure c. to show the performance of the model on other countries, we also present the predictions by proposed method for japan and germany in appendix a. to show how the country actions may change the trend related to the number of infected people and show how older data may reveal the possible scenarios in case of different reactions by countries, we stopped the training process in three different time points and predicted the next-coming days. three main actions and occasions in iran are considered in this paper: • the nationwide closure of schools/universities, nationwide closure of non-essential services and bazaars and closure of metros in big cities before march . • persian new year in march and unfortunate start of travels (which was not banned officially and caused a great amount of transfer in iran) • closure of roads between cities from march to april by the police. as it can be seen in figure , the training of the model (for predcition of confirmed cases) is stopped in three dates (date march , march and april related to three above mentioned occasions). the blue curve in march indicates that without closure of schools/universities and non-essential services , the curve could raise in march th. on the other hand, the red curve shows a considerably lower peak could potentially happen if the travelings would not happen due to start of holidays in iran. finally, the green curve shows that closure of roads could reduce the number of affected people but since the curve was in downward route, its effect is not a raise in the predicted numbers. covid- pneumonia started in late december and pose a continuing and dynamic threat globally. the first case was confirmed by february th in iran. the main question of public and also politicians is the behavior of the epidemic including the peak day, peak number, end point and also daily number of new cases and death. being aware of real time behavior of epidemics is vital for efficient logistics in the outbreak response. forecast models will help the policy makers to speculate potential trajectory of the outbreaks and drive interventions as well as estimate the impact of interventions. several studies has promised efficient tools for forecasting infectious disease dynamics, but these tools are not completely responsible to critical public health needs or have not been evaluated on experimental data. different models were tested and based on the minimum mean absolute percentage error (mape) which is an index for accuracy, all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . https://doi.org/ . / . . . doi: medrxiv preprint m-lstm was the most accurate model found in this study. using this model we aimed to identify ) the intensity of the epidemic peak, ) the timing of the peak, and ) the total number of cases expected over the duration of the epidemic of covid- in iran. determining these outcomes could improve the allocation of resources for risk communication, primary prevention, secondary prevention and preparedness plans (e.g., planning medical staffs, preparing triage units, etc.). in this model we have used the best combination of inputs including lag, basic and detailed information features. in order to have a realistic prediction, three parameters of number of infected cases, number of deaths and number of recovered cases were used together to better shape the epidemic curve. our simulation model is trained based on publicly available data from all countries of the world and also official reports of the iranian ministry of health and medical education from january, till april . as illustrated in fig by considering the stability of outbreak response, the peak of the epidemic has already occurred around april st, with about new cases and the epidemic would be ended by early-may with a mape of . percent. the basic assumption of the models is stability of the environment measurements but as we do not live in controlled conditions, every decision would change the epidemic track. the effect of governmental decisions and public occasions is illustrated in figure . considering that it takes around - days (the median of incubation period) for the results of interventions to show up on new case numbers, the difference between blue and green line in between march th and th is the result of decisions on school and university closure and cancellation of cultural and religious events. also the difference between red and green line between march rd and april nd is because of new year holiday and travels. it means that by focusing on social distancing there would be a steady decline in new cases after april nd as shown by green line but changes in public health policies may change the epidemic track and postpone the end point as well. our result could be useful in preparing for future outbreaks as well as current one by considering the results in public health decision making. similar to other modeling technique, the approach presented here is subject to limitations, which include data quality associated with real-time modeling (as data is often subject to ongoing cleaning, correction, and reclassification of onset dates as further data become available), reporting delays, and problems related to missing data. here we present the predictions by the proposed model for japan and germany in figure and . as it can be seen from figure a (c) and (c), here is always a lag between the actual numbers and the predicted ones but model seems to work on a wide range of countries which is encouraging. all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . https://doi.org/ . / . . . doi: medrxiv preprint outbreak of pneumonia of unknown etiology in wuhan, china: the mystery and the miracle an interim review of the epidemiological characteristics of novel coronavirus severe acute respiratory syndrome coronavirus (sars-cov- ) and coronavirus disease- (covid- ): the epidemic and the challenges the epidemiology and pathogenesis of coronavirus disease (covid- ) outbreak influenza-like illness prediction using a long shortterm memory deep learning model with multiple open data sources the epidemiological characteristics of an outbreak of novel coronavirus diseases (covid- ) in china world health organization. coronavirus disease (covid- ) situation report- . world health organization a comparative study on predicting influenza outbreaks predictive modeling of influenza in new england using a recurrent deep neural network. theses deep-covid: predicting covid- from chest x-ray images using deep transfer learning how many infections of covid- there will be in the "diamond princess"-predicted by a virus transmission model based on the simulation of crowd flow artificial intelligence forecasting of covid- in china real-time forecasts of the covid- epidemic in china from february th to february th, . infectious disease modelling predicting the cumulative number of cases for the covid- epidemic in china from early data early dynamics of transmission and control of covid- : a mathematical modelling study. the lancet infectious diseases epidemic analysis of covid- in china by dynamical modeling covid- and italy: what next? the lancet temperature and latitude analysis to predict potential spread and seasonality for covid- preliminary flu outbreak prediction using twitter posts classification and linear regression with historical centers for disease control and prevention reports: prediction framework study a review of epidemic forecasting using artificial neural networks attention-based recurrent neural network for influenza epidemic prediction ant lion optimizer: theory, literature review, and application in multilayer perceptron neural networks key: cord- -t pab authors: mohammadzadeh, nima; shahriary, mahla; nasri, erfan title: iran’s success in controlling the covid- pandemic date: - - journal: infection control and hospital epidemiology doi: . /ice. . sha: doc_id: cord_uid: t pab nan to the editor-coronavirus disease (covid- ) is a respiratory tract infection ranging from mild respiratory illness (eg, respiratory symptoms, cough, fever, shortness of breath and breathing difficulties) to severe illness (eg, pneumonia, severe acute respiratory syndrome, kidney failure, and death) that has caused an unprecedented global crises in < days in all countries of the world. today, most of the world's major cities are in full quarantine and all social and economic behaviors have been limited due to the sars-cov- outbreak. controlling the spread of the virus has become one of the most important challenges for governments across the globe. the increase in covid- cases in the advanced industrial countries, including italy, germany, france, spain, and united states, reflects the rapid spread of the virus. as of april , , the following countries have been most affected: italy, with a populations of almost million, has~ , covid- patients ( is rapidly increasing. iran, with a population of almost million, has~ , covid- patients, with , deaths (fig. ) . although iran has been heavily sanctioned in all fields of industry and pharmacy, it has taken important steps from the earliest days of the outbreak to combat the virus. for example, italy, with an outbreak date similar to that of iran, has more than twice the disease incidence rate of iran. according to reports released by the ministries of health in iran and italy, , iran formed a headquarters for the covid- crisis on february , when the virus count was~ people per day. in contrast, in italy, the covid- crisis headquarters was formed on march , when the outbreak count was~ , per day. also, these countries' respective health ministries published safety and prevention guidelines for many locations, especially crowded centers including hospitals, clubs, transportation systems, schools, etc, in the early days of the outbreak. they also sought widespread collaboration with ngos and volunteers as well as extensive intragovernmental collaboration to ensure the observation of safety protocols to control the spread of disease. although traffic and concentration laws as well as heavy fines were not considered in the early days, these collaborations ultimately resulted in an % reduction in traffic between cities and as well as in social gatherings and even family gatherings. ultimately, all of these measures have led iran to better control the spread of the virus than other aforementioned industrialized countries. nevertheless, iran has a long way to go to achieve complete control of the pandemic. because iran is located among neighboring countries in a very high-risk area for many diseases, including tuberculosis, rabies, crimean congo fever, cholera, brucella, malaria, polio, and some others, it has been even more successful in controlling such diseases than the united states. this experience and history are expected to be very useful and effective in controlling covid- . early transmission dynamics in wuhan, china, of novel coronavirus-infected pneumonia covid- coronavirus pandemic. worldometer website covid- ) situation report- . world health organization website iranian ministry of health and medical education website italian ministry of health and medical education brief outcome of five decades of battle with infectious diseases in iran acknowledgments.financial support. no financial support was provided relevant to this article.conflicts of interest. all authors report no conflicts of interest relevant to this article. key: cord- -hnvf e authors: bandarian, fatemeh; namazi, nazli; amini, mohammad reza; pajouhi, mohammad; mehrdad, neda; larijani, bagher title: endocrinology and metabolism research institute from inception to maturity: an overview of -year activity date: - - journal: j diabetes metab disord doi: . /s - - - sha: doc_id: cord_uid: hnvf e endocrinology and metabolism research institute (emri) was founded in . emri progressed step by step from inception and reached to its maturation during the past years. emri has expanded and progressed in different aspects including human resources and infrastructures (laboratories and new technologies) and has obtained the first rank in the country in endocrinology research. it has also collaborated with regional and international organizations such as world health organization (who), international osteoporosis foundation (iof), and american association of clinical endocrinologists (aace). this article provides an overview of emri activities during a quarter of a century. endocrinology and metabolism research institute (emri) was founded for the first time years ago in in a small room in endocrine ward at third floor of dr. shariati hospital as one of the five research centers founded in the country at that time and entitled as "endocrinology and metabolism research center" (emrc). the research center was founded by four top endocrinologists university staffs in the country. eight to nine years earlier than establishment of emri ( ) ( ) , endocrine ward of dr. shariati hospital had been launched jointly with gastrointestinal ward with to beds and in the next years they increased to to beds (in ) . therefore, a primary background had been provided for research. following an increase in the numbers of bed for patients with diabetes, patients with thyroid and hypothalamic disorders were admitted in the ward as well. after a few years, thyroid cancer registry was launched in endocrine department and this department became a referral center for cushing disease. currently, endocrine ward w is working jointly with gastrointestinal ward and admits patients with different endocrine disorders. the purpose of this article is to review the activities of the endocrinology and metabolism research institute over a quarter of a century. after establishment, emrc started research with small epidemiological retrospective studies using hospital records with only one research fellow. most hospital records were incomplete at that time and there was no complete archive in the hospital. at the beginning of emri work, it faced with several limitations including space, budget and staff. when emri started, only five university staffs subspecialist in endocrinology were in emri and in the next years by graduation of more endocrinologists and joining to emri, the number of staffs increased. the first emri budget was allocated in by the university (governmental). the emri budget before that was provided by the institutes out of university. two years after establishment ( ), the center received official approval from the ministry of health and medical education. at the same year the center moved to a new place with - rooms out of endocrine ward at the th floor of dr. shariati hospital near the hormone and biochemical laboratory. in this new place, the center expanded for the first time and the number of research fellows and staffs increased to six to seven. seven years later (oct ), by providing a proper space at the same flat, a large new building was built and prepared and emri moved to the new building. this building contained a long corridor with multiple rooms that different research units were deployed there and required manpower was employed gradually. to expand research activities with limited budget and for more productivity, emri recruited young motivated newly graduated physicians covered by the human resources project (the ministry of health and medical education) with minimum payment that was supported by the ministry. by this policy, emri in order to advance the goals, used the potential of motivated young graduated human resources appropriately and expanded research activities. research products of emri in the first decade of its activity were limited [ ] [ ] [ ] [ ] [ ] [ ] [ ] and most of them published in local journals with persian language (fig. ) . in this decade, most activities were focused on building of infrastructures. activity of emrc in different subjects during those years was categorized in separate small research teams. the last two years of first decade ( and ) was associated with significant achievements that had decisive role in the future of emri. these important decisive achievements were as follows: evaluation of research centers launched by the ministry of health and medical education was one of the administrative events. at the first year of assessment, emri ranked th in razi festival. by further progress, emri obtained first rank in razi festival in the next year. afterward up to now (except one year), emri has obtained fist rank in the country consistently. allocation of an independent budget line to emri for the first time by the ministry was another important event in the same years that was the main achievement of emri. to facilitate multicenter studies and expand national research in the country, emri established "national diabetes research network" (ndrn) [ ] (http://emri.tums.ac.ir/ dmnet) and "iranian osteoporosis research network" [ ] (http://emri.tums.ac.ir/osteonet) that were endorsed by the ministry of health in the same years ( ). by cooperation fig. number of emri publications during the past -years of ndrn, local diabetes guideline was prepared and released for the country [ ] . currently, more than universities all over the country are member of these networks. at the same time, in the field of research expansion and internationalization, emri was approved as a collaborating center of world health organization (who) for diabetes and osteoporosis. collaboration with international osteoporosis foundation (iof) was also started. first emri journal entitled "diabetes and metabolic disorders" was published for the first time in in persian language in the first years and then changed to english in the next years and published by springer. notably, the journal has obtained many important achievements among local journals (fig. ). simultaneously ( - ), diabetes clinic affiliated to emri was launched in dr. shariati hospital to provide medical services for diabetic patients and to provide a research platform for emri as well [ ] [ ] [ ] [ ] . the second decade was the beginning of the emri jump and was associated with significant advances. at the beginning of second decade of activity, emri infrastructure, facilities, and human resources were acceptable and the related process was ongoing. by availability of such potentials in this space, research development was begun and accelerated. during the second decade of emri activity, improvement continued. following moving to new building and expansion of emri infrastructures and staffs, organizational chart of emri was developed and emri activities were categorized into education, research, administrative, and support sections. administrative and support section emri in promoted to research institute and research activities were organized in three main areas in three research centers including "diabetes research center", "osteoporosis research center" and "endocrinology and metabolism research center". other related research topics out of the aim and scope of the above mentioned research centers were considered as research groups and units within these research centers such as immunogenetic group [ ] , fasting group [ ] , nutrition unit [ , ] and so on. training ph.d by research students was started by emri for the first time in the country in and since then annually few talented interested eligible students are selected and admitted by emri for this program. these students have conducted practical research projects that lead to valuable outputs [ ] [ ] [ ] [ ] [ ] [ ] . in launching population sciences institute was a background for conducting population-based studies. by this background, emri collaborated in bushehr elderly health cohort for the first time in [ , ] and after that started and contributed in other population-based cohorts including imos [ ] , caspian study [ , ] , steps [ , ] and so on. during the last years of second decade diabetes clinic expanded to a sub-specialty diabetes clinic with multidisciplinary approach and moved to a new independent building. the main activity of emri was in research section as its intrinsic duty. during this period, an important policy in the research section was providing facility for theses of under graduate and post graduate students in the field of medicine that resulted in considerable improvement in research productions [ , [ ] [ ] [ ] [ ] [ ] . another policy of emri in the platform of diabetes clinic was collaboration with medicinal industries and taking research grants to support remarkable projects [ , , ] . at the beginning of second decade, publishing unit was launched in emri to provide professional counseling and facility, and to handle and support research product publication. this strategic policy caused a significant growth in research output of emri [ , , ] . during this period, staffs in basic sciences were employed by emri and following that policy, genetic, cellular, and molecular lab was setup and various molecular techniques including pcr, rt-pcr, epigenetic and methylation tests, etc., were launched. they provided a background for conducting invaluable research projects including genetics, molecular, and cellular studies [ , [ ] [ ] [ ] [ ] [ ] [ ] [ ] . by these available facilities in emri, taking post doc students was started that helped to expand collaborations with other research institutes [ ] . after , using available facilities, emri moved to high tech research in the edge of the frontiers of knowledge. in , cell therapy project was conducted on patients with diabetes for the first time in iran [ ] . in this study, fetal liver-derived hematopoietic stem cell allotransplantation was performed in a small number of patients with type or diabetes. in the mentioned study, after one year of transplantation, none of the patients became insulin free, transiently, or permanently [ ] . safety of fetal cell transplantation was evaluated three years later that showed no significant complications and confirmed long term safety [ ] . pancreas transplant project was started for the first time in emri in and first pancreas transplantation was performed [ , ] . educational activities of emri in this decade were in the area of professional and public education. professional medical education was provided by holding local, national, and international workshops, courses, seminars, and congress in the field of endocrinology with special programs in anniversary dates such as world osteoporosis day (on october each year) [ ] and world diabetes day (on november each year) [ ] . moreover, diabetes guideline [ ] , diabetic foot care guideline (approved by international working group on the diabetic foot/iwgdf) [ ] for physicians, and other care providers were prepared and published. patient education was provided for patients with diabetes by local workshops and face to face education as well as general conferences, especially in world diabetes day [ ] . in addition, many different booklets and brochures as well as guidelines for diabetic patients were published that are updated every few years. in the third decade of emri activity, improvement of infrastructure continued in different areas. following expanding emri activities, six years later than second promotion ( ), three new research centers including personalized medicine research center, metabolomics and genomics research center, cell therapy and regenerative medicine research center, and one another research institute (translational endocrinology) were added to emri with the aim of moving toward high tech molecular and cellular advanced research in the field of endocrinology and multidisciplinary studies and conducting research on the edge of the frontiers of knowledge [ ] [ ] [ ] . these new research centers contributed in knowledge production in the field of metabolomics, personalized medicine, and cell therapy, significantly [ , , ] and these progresses still continue in various aspects. emri to extend metabolomics research in recent years has provided infra-structures such as ms/ms for metabolom analysis and has launched zebrafish lab as animal model for various diseases and for basic science studies as well. research output and the numbers of citation increased continuously during a quarter of a century of emri activity and reached maximum in (fig. ) . launching and establishing registry programs for diabetes, thyroid cancer, and pituitary adenoma are examples of emri outstanding achievements in the past years that provide a big data for the future analysis of disease progress status and outcome as well. in the third decade, the collaboration of emr with international organizations such as who, international osteoporosis foundation (iof), and american association of clinical endocrinologists (aace) continued and recently it was approved as who collaboration center for non-communicable diseases (ncds). collaboration with international working group on the diabetic foot (iwgdf) was also approved in this decade. in order to extend diabetes education in national and regional level, iranian diabetes academy was launched in emri in this decade. face to face and electronic diabetes education programs were provided for health care providers and patients [ ] . different educational modules for different care of diabetes and its complications as well as for diabetic foot care were prepared and released for professionals and patients that is advantageous in these days of covid- pandemics. in this decade, in line of who program to control ncds mortality in the world up to , iran committed to follow who program. in collaboration with the ministry of health, emri prepared "national document for non-communicable diseases (ncds)" [ ] and "iranian national service framework for diabetes" and clarified the national targets to reach who goals in . in conclusion, research and development is ongoing in emri from inception up to present. this path continues with the advancement of research, science, and knowledge and a bright horizon is ahead of emri. data availability not applicable. declarations not applicable. ethics approval not applicable. number of publications and citation during the past -years by emri j diabetes metab disord baradar-jalili r. treatment of hyperfunctioning thyroid nodules by percutaneous ethanol injection comparison of fine-needle-nonaspiration with fine-needleaspiration technique in the cytologic studies of thyroid nodules diagnostic value of frozen section examination in thyroid nodule-surgery at the shariati hospital clinicopathological features of thyroid cancer as observed in five referral hospitals in iran-a review of cases metabolic and endocrinologic complications in beta-thalassemia major: a multicenter study in tehran cost analysis of different screening strategies for gestational diabetes mellitus adjunctive estrogen treatment in women with chronic schizophrenia: a double-blind iranian national diabetes research network project: background, mission, and outcomes iranian osteoporosis research network: background, mission and its role in osteoporosis management developing a clinical diabetes guideline in diabetes research network in iran psyllium decreased serum glucose and glycosylated hemoglobin significantly in diabetic outpatients potential risk factors for diabetic neuropathy: a case control study effect of vitamin d on insulin resistance and anthropometric parameters in type diabetes; a randomized double-blind clinical trial serum uric acid levels and risk of metabolic syndrome in healthy adults vegf gene polymorphism association with diabetic neuropathy the effect of nutritional education program based on health belief model (hbm) on the knowledge of fasting type diabetic patients effects of black seed (nigella sativa) on metabolic parameters in diabetes mellitus: a systematic review the effects of supplementation with conjugated linoleic acid on anthropometric indices and body composition in overweight and obese subjects: a systematic review and meta-analysis global dna methylation as a possible biomarker for diabetic retinopathy epigenetic alterations and exposure to air pollutants: protocol for a birth cohort study to evaluate the association between adverse birth outcomes and global dna methylation aberrant dna methylation patterns in diabetic nephropathy gmp-grade human fetal liver-derived mesenchymal stem cells for clinical transplantation meta-analysis of promoter methylation in eight tumor-suppressor genes and its association with the risk of thyroid cancer liquid biopsy as a minimally invasive source of thyroid cancer genetic and epigenetic alterations bushehr elderly health (beh) programme, phase i (cardiovascular system) bushehr elderly health (beh) programme: study protocol and design of musculoskeletal system and cognitive function (stage ii) prevalence of hypertension in an iranian population association between body mass index and perceived weight status with self-rated health and life satisfaction in iranian children and adolescents: the caspian-iii study association of fruit and vegetable intake with meal skipping in children and adolescents: the caspian-v study insulin pen use and diabetes treatment goals: a study from iran steps survey is salt intake reduction a universal intervention for both normotensive and hypertensive people: a case from iran steps survey burden of diabetes and it's complications in iran in year coronary heart disease and associated risk factors in qazvin: a population-based study insulinoma in iran: a -year review primary thyroid malignancies in tehran comparison of different screening tests for detecting diabetic foot neuropathy the efficacy of silybum marianum (l.) gaertn. (silymarin) in the treatment of type ii diabetes: a randomized, double-blind, placebo-controlled, clinical trial the clinical investigation of citrullus colocynthis (l.) schrad fruit in treatment of type ii diabetic patients: a randomized, double blind, placebo-controlled clinical trial insulin production by human stem cells curcumin inhibits in vitro mcp- release from mouse pancreatic islets gender-specific differences in the association of adiponectin gene polymorphisms with body mass index adenosine deaminase gene polymorphism is associated with obesity in iranian population severe acanthosis nigricans in a year-old female with partial lipodystrophic syndrome associations between hla-c alleles and papillary thyroid carcinoma expression level of circulating cell free mir- gene in serum of patients with diabetic nephropathy expression level of circulating mir- in serum of patients with diabetic nephropathy clinical microbiology study of diabetic foot ulcer in iran; pathogens and antibacterial susceptibility the effect of fetal liver-derived cell suspension allotransplantation on patients with diabetes: first year of follow-up evaluation of fetal cell transplantation safety in treatment of diabetes: a three-year followup establishing a cgmp pancreatic islet processing facility: the first experience in iran in vitro modulation of tcf l gene expression in human pancreatic cells world osteoporosis day: celebrating two decades of progress in preventing osteoporotic fractures in iran world diabetes day: celebrating two decades of progress in combating diabetes and its complications in iran a multidisciplinary team approach in iranian diabetic foot research group personalized treatment options for thyroid cancer: current perspectives the pathway from gene therapy to genome editing: a nightmare or dream precision medicine in non communicable diseases co-transplantation of human fetal mesenchymal and hematopoietic stem cells in type diabetic mice model amino acid profiling in the gestational diabetes mellitus conceptual map of diabetes education: necessity of establishing iran diabetes academy national action plan for noncommunicable diseases prevention and control in iran; a response to emerging epidemic publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations key: cord- - xslz bs authors: boroomand, zahra; jafari, ramezan ali; mayahi, mansour title: molecular detection and phylogenetic properties of isolated infectious bronchitis viruses from broilers in ahvaz, southwest iran, based on partial sequences of spike gene date: - - journal: vet res forum doi: . /vrf. . sha: doc_id: cord_uid: xslz bs infectious bronchitis (ib) is a highly contagious disease involving mostly upper respiratory tract in chickens, leading to significant economic losses in the poultry industry worldwide. one of the major concerns regarding to ib is the emergence of new types of infectious bronchitis viruses (ibvs). the purpose of this study was to identify the ibvs isolated from iranian broiler chickens with respiratory symptoms. twenty-five broiler flocks around ahwaz (southwest of iran) were examined for ibv. the specimens including trachea, lung, liver, kidney, and ceacal tonsil, were collected from diseased birds and inoculated into chicken embryonated eggs. harvested allantoic fluids were subjected to reverse transcription polymerase chain reaction (rt-pcr) using primers in order to amplify spike (s ) gene of ibv. the rt-pcr products of four ibv isolates were sequenced. the results showed that from examined flocks with respiratory disease, flocks ( . %) were positive for ibv. in phylogenetic analysis, our isolates were closely related to the qx-like viruses such as pcrlab/ / (iran), qx, hc , hc , ck/ch/gx/nn - , ck/ch/js/yc - , ck/ch/js/ / , ck/ch/js/ / (china), qx/sgk- , qx/sgk- (iraq) with nucleotide homology up to . %. this study indicates the role of ibvs in the respiratory disorders of broiler flocks located in southwest iran, and also the existence of a variant of ibv, which is distinguishable from the other iranian variants. infectious bronchitis (ib) is an acute contagious viral infection with low mortality and a significant reduction in performance in chicken. the causative agent of ib is infectious bronchitis virus (ibv) which is an enveloped, single-stranded, positive sense and rna virus belonging to the family coronaviridae, the genus gamma coronavirus. the virus consists of three important structural proteins: the nucleocapsid (n), the membrane (m), and the spike (s and s ) glycoproteins. the nucleotide sequence of the s gene is highly variable, which makes it prone to mutation and emergence of new variants of the virus. for this reason, the molecular classification of ibvs is based on the investigation of the s gene. vaccination is one of the best ways of immunization of susceptible birds. however, vaccinated flocks may experience disease involvement because there is almost no cross-protection among serotypes. consequently, the viral strains that exist in a different geographical area must first be identified and their pathogenicity should be determined in order to select an appropriate virus strain for vaccination. in iran, aghakhan et al. identified ibv by virus isolation and serological techniques. this isolate belonged to the mass serotype. in previous studies conducted to identify ibv serotypes in iran, the presence of / and massachusetts serotypes have been reported. , recently, a new isolate of ibv (irfibv ) was identified by boroomand et al. which had . % similarity to /b strains. the other ibv serotypes also exist in iran neighboring countries such as dutch strains in pakistan. in ahvaz (southwest iran), ibv vaccines including h and / are used in the vaccination program in broiler chicken flocks. however, ib continues to be responsible for the economic losses of the poultry industry in the region. the purpose of this study was to evaluate the role of ibv in broiler chicken respiratory complexes in ahvaz, and also to study the partial s sequences among field isolates of ibvs. sampling. during january to december , an attempt was made to reveal the role of ibvs in broiler chickens of ahvaz which suffered from severe respiratory distress, including nasal discharge, coughing, wet rale, lacrimation, gasping, and high mortality. twenty five broiler flocks aged - weeks old, some of which had a history of live vaccination against ibv were selected from different geographical parts of ahvaz (north, east, south and west). samples including trachea, lung, kidney, liver and cecal tonsil were obtained from dead birds, transferred in cold chain system to the faculty of veterinary medicine, shahid chamran university of ahvaz and stored at - ˚c until used. the homogeneous tissue samples were centrifuged at ˚c and , rpm for min. the supernatant was taken and antibiotics (penicillin, , iu ml - , streptomycin, μg ml - and gentamycin, μg ml - , all from sigma, st. louis, usa) were added to prevent the growth of bacteria and fungi. an amount of . ml of the suspension was inoculated into the allantoic cavity of -day-old embryonated chicken eggs. the eggs were incubated at ˚c and after hr, the allantoic fluid was harvested and examined for ibv using reverse-transcriptase polymerase chain reaction (rt-pcr). no bacterial and fungal contamination was observed in specific culture media. all experiments were carried out after approval by the animal committee of shahid chamran university of ahvaz, ahvaz, iran. extraction of rna from the allantoic fluid was carried out using rnx-plus solution (cinnagen, tehran, iran) according to manufacturer's instructions. the isolated rnas were stored at - ˚c. the cdna was synthesized using primescript tm rt reagent kit (takara, tokyo, japan) according to manufacturer's instructions. a fragment of the s gene ( bp) was amplified using a pair of specific primers including xce ( '-cactggtaatttttcagatgg- ') and xce ( '-ctctataaacacccttaca- '). the pcr reaction and its thermal condition were set up as previously described. the pcr products were electrophoresed on . % agarose gel. characterization of isolated ibvs. the ibv positive allantoic fluids were investigated for detection of influenza and newcastle disease viruses by rt-pcr using specific primers. out of positive samples, four samples from different flocks were found to be infected with ibv alone. for genotyping, pcr products (s gene) of these four ibv isolates were sequenced in forward direction by bioneer co. (seoul, south korea) and their nucleotide sequences of their partial s gene were compared with each other and with previously reported isolates from iran, neighboring countries, and reference strains of ibv (table ) in genbank by using nblast, and clustalw . the phylogenetic relationship was established by http://www.phylogeny.fr/simple_phylogeny.cgi. the phylogenic tree was constructed using the neighbor joining method and mega software (version . ; biodesign institute, tempe, usa). the topological stability of the tree was evaluated by bootstrap replications. the results showed that flocks ( . %) were positive for ibv (fig. ) . the nucleotide sequences of four isolates were submitted to the genbank sequence database and were given the accession numbers iribvb: kp , iribvc: kp , iribve: kp and iribvf: kp . a phylogenetic tree (fig. ) , based on the hypervariable region of s gene sequences of four ibv isolates from the present study and other strains of ibv retrieved from genbank, was generated. based on the phylogenetic analysis, these four isolates were clustered with qx-like viruses. the results demonstrated the occurrence of qx-like serotype/genotype in ahvaz, iran. the ibv isolates were closely correlated to pcrlab infectious bronchitis virus is one of the main pathogens of commercial and backyard chickens with several serotypes and genotypes circulating in the world. based on our findings, out of examined flocks ( . %) were found to be infected with ibv, which show the prominent role of the virus in respiratory involvement of ahvaz broiler flocks. the ibv isolates in the present study were completely different from ibv vaccine strains (h , ma and / ) used for vaccination in ahvaz, which indicates the incidence of ib infection despite stringent vaccination. the determination of the ibv genotype is necessary not only to understand the evolution of the virus but also for developing vaccines based on circulating ibv strains in the region. one of the significant features of the ib viruses is the emergence of new variants of the virus throughout the world. therefore, new serotypes and new variants of ibvs are still isolated from chickens, even from vaccinated flocks. , the new ibv serotypes should be identified quickly in order to develop an effective vaccination strategy. several years ago, massachusetts serotype was identified in poultry flocks of iran. in recent years, b or / serotype has been identified in iran by several researchers. , , furthermore, the distribution of different ibv genotypes (different from the vaccine strain; massachusetts) was already reported in iran. [ ] [ ] [ ] phylogenetic analysis showed that isolated ibvs in the present study clustered with qx-like viruses. for the first time, in , qx strain of ibv was identified in china, after which the occurrence of the qx-liked virus was informed and it became one of the most prevalent ibv genotypes in various countries. qx-like ibvs were extended from china, to europe and recently to the south of africa. also, in iraq, this genotype was also identified. the pcrlab/ / (jx ) strain of ibv was isolated in iran and classified as qx-like viruses. the findings of the present study revealed that qx strains of ibv may be originated from other countries (probably iraq) which has been transmitted to ahwaz. there is little information about the type of ibv spread between the middle east countries. however, borderline migrations of birds is probably an important factor. taken together, this is the first report indicating the circulation of qx-like viruses in ahvaz broiler chickens with respiratory signs. finally, a comprehensive study on the pathogenesis of these ibv isolates is suggested. infectious bronchitis severe acute respiratory syndrome vaccine development: experiences of vaccination against avian infectious bronchitis coronavirus studies on avian viral infections in iran isolation and molecular characterization of infectious bronchitis virus, isolate shiraz . ibv, by rt-pcr and restriction enzyme analysis isolation and identification of a new isolate of avian infectious bronchitis virus irfibv and study of its pathogenicity detection and seroprevalence of infectious bronchitis virus strains in phylogenetic tree generated based on the hypervariable region of s gene sequences of four ibv isolates from the present study and other strains of ibv retrieved from genbank using the neighbor joining method. commercial poultry in pakistan a laboratory manual for the isolation and identification of avian pathogens a new genotype of nephropathogenic infectious bronchitis virus circulating in vaccinated and non-vaccinated flocks in china molecular analysis of the /b serotype of infectious bronchitis virus in great britain factors influencing the outcome of infectious bronchitis vaccination and challenge experiments molecular epidemiology of infectious bronchitis virus isolates from china and southeast asia a survey of the prevalence of infectious bronchitis virus type / in iran epidemiology of avian infectious bronchitis virus genotypes in iran ( - ) genotyping of avian infectious bronchitis viruses in iran ( - ) reveals domination of is- like virus molecular characterization of infectious bronchitis viruses isolated from broiler chicken farms in iran the pathogenesis of a new variant genotype and qx-like infectious bronchitis virus isolated from chickens in thailand circulation of qxlike infectious bronchitis virus in the middle east genotyping of infectious bronchitis viruses from broiler farms in iraq during detection of the chinese genotype of infectious bronchitis virus (qx-type) in iran isolation and molecular characterization of sul/ / avian infectious bronchitis virus, indicates the emergence of a new genotype in the middle east the authors would like to express their gratitude to the dean for research of shahid chamran university of ahvaz for providing financial support for this work. the author disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: this study was supported by the research grant ( / / / ) provided by shahid chamran university of ahvaz. the authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. key: cord- - u si authors: salimi, rasoul; gomar, reza; heshmati, bahram title: the covid- outbreak in iran date: - - journal: journal of global health doi: . /jogh. . sha: doc_id: cord_uid: u si nan a ccording to the world health organization, as of april , , cases of coronavirus disease (covid- ), including deaths, have been reported worldwide [ ] . the outbreak began in iran after the detection of the first death associated with covid- , on feb , in qom, a holy city in central iran. after a short period, covid- has widely spread in all other provinces in iran. as of april , , of tested patients, people have been infected with covid- . of them, people have recovered, people are critically ill and people have died [ ] . the formal announcement of the outbreak in iran has generated public panic and anxiety. the sudden explosion in the number of suspected cases of covid- in the first week in several provinces has overwhelmed some designated hospitals very quickly. medical personnel faced shortages of protective equipment, essential medications and care facilities. people rushed to the stores to purchase masks, gloves and disinfectants. this created a black market, which some hospitals had to rely on to provide the protective equipment. furthermore, fake news and misinformation have increased public anxiety. to respond to the outbreak, the headquarter for coronavirus combat and prevention has been established. the main measures, such as stopping mass gatherings, closure of educational institutes, national coordination with volunteers, civilian and military forces, national screening program, and social distancing led to shortage management to some extent. it had a potential to alleviate some of the public fear. although the measures that were implemented to control the outbreak, along with some half-measures, may have made it harder to control the disease. at the same time, they could affect the economy through long term and avoidable burden of covid- . also, there was a question whether early stopping of the mass gatherings such as parliament election and restrict travel in qom could have acted to slow the spread of the disease through qom and into other cities. measures like the closure of schools, educational institutes, religious and sacred places (despite the opposition of some religious figures), and stopping mass gatherings -such as religious and sporting events -were the major pillar of the response to the outbreak. they caused reduction in the number of cov-id- super-spreading events in iran. authorities widely reminded the public of their role to control the outbreak. they strongly encouraged people to stay home and avoid social contact with family and friends. before the iranian new year festival, people were urged to strongly avoid familial gatherings and trips to celebrate the new year. most of the people followed these recommendations, but some ignored them. after the new year, on the th of march, , some trips did occur and some people left the cities to visit their hometowns. although travelers were screened with thermal scanners at the points of entry and exit to those cities, this was not a guarantee that the possible importation of the disease to other cities and rural areas would be prevented. the national covid- screening program in iran is a successful measure of the response to the outbreak. significantly reduced the massive influx of cases to the hospitals and has decreased the potential infection exposures in hospitals by limiting unnecessary visits. also, it was so helpful in early detection of new cases and consequently early isolation and treatment. sired effect and lead to flattening the epidemic curve. however, is seems that new year holidays missed due to avoidable delays and the question remained -if stricter measures were launched before the new year, could they have been more effective in the control of the outbreak? as one of the main measures, the national screening program was implemented on march , . it was set up to allow early detection, diagnosis, isolation, and treatment of the new cases, and to follow their contacts. the screening was performed by primary care providers or people themselves via website (https://salamat.gov.ir/) or a phone number ( ). screening was based on the questions about the symptoms of covid- . suspected people were referred to special -hour medical centers and screened by the covid- response teams based on body temperature, spo , respiratory rate, lung scanning (if available) and covid- diagnostic tests. subsequently, screened patients were isolated at home, at isolation centers or hospitalized in designated hospitals (figure ) . this measure significantly reduced the massive influx of infectious cases to emergency departments and hospitals. but without widespread testing, the screening could not be so helpful in cutting down the transmission chain. the response to covid- outbreak in iran faces some challenges. two of the main challenges that suffered painfully during the outbreak were sanctions against iran and the circulating fake news and misinformation on social media networks. the us unilateral economic sanctions against iran and the further recent sanctionary measures [ ] have restricted the import of essential goods. successful actions in stopping the outbreak required sufficient essential medicines and facilities. so, it was critical that sanctions and barriers to providing essential supplies to iran would be stopped, or to be postponed at least until in order to control the outbreak faster and efficiently in iran, social distancing must be more rigid, widespread testing must be performed to cutting down the transmission chain, and us unilateral economic sanctions must be restricted to import essential goods. the end of the covid- epidemic. on the other hand, fake news and misinformation imposed hardship on the health system. a fake news, "drinking alcohol has a protective role for covid- " disseminated through multiple social media channels, caused more than cases of poisoning and more than deaths associated with drinking fake alcohol to date [ ] . effective communication will help eliminate fake news and promotion of appropriate behavior. so, authorities should pay more attention to social media networks. all interventions during the outbreak helped to flatten the curve of covid- cases in iran. with some half-measures, control of the outbreak will prolongate and new waves will be expected. some aspects of the response to the outbreak need more attention. first, the number of diagnostic tests is very low. therefore, the scope of the outbreak in iran cannot be traced. widespread testing must be performed to interrupt new transmission chains and keep clusters under control. second, early reduction of the restrictions by the government to avoid severe economic impact, along with the fact that the prolonged duration of staying home had put many people at risk of depression and anxiety, can both lead to increased risk of premature end to restrictions. this can cause further waves of infection with varying intensity and duration. third, the government has promised people financial support. some promises have been postponed. delay to receiving timely support might lead to more stress and anxiety and can prevent effective action. finally, medical facilities shortages, prolonged disease outbreak, and the further waves of infection can increase the mortality risk among health care workers, more reporting of physical and mental exhaustion, irritability, poor work performance, reluctance to work, and burnout. world health organization national committee on covid- epidemiology. daily situation reports on coronavirus disease (covid- ) in iran office of the spokesperson. sanctions on entities trading in or transporting iranian petrochemicals. us department of state key: cord- -bzmhjvr authors: rassouli, maryam; ashrafizadeh, hadis; shirinabadi farahani, azam; akbari, mohammad esmaeil title: covid- management in iran as one of the most affected countries in the world: advantages and weaknesses date: - - journal: front public health doi: . /fpubh. . sha: doc_id: cord_uid: bzmhjvr covid- management is a hot topic due to its extensive spread across the world and the declaration of pandemic status. how a crisis is managed in each country is influenced by several factors, and various strategies are applied in accordance with these factors in order to manage the crisis. due to the rapid spread and increasing trend of the crisis and the fact that almost more than half of the countries are engaged in this pandemic, it is impossible to apply trial-and-error based strategies. one of the best strategies is to use the experiences of other countries in dealing with covid- . this report explores the advantages and weaknesses of the islamic republic of iran in the management of this crisis in regard with political economic and cultural issues, health service coverage, and the transparency of information that can be used as a model for other countries around the world. the islamic republic of iran, as the second country to declare two deaths due to coronavirus, within days after china on february , ( ), is still one of the countries to deal with most cases of covid- infection and the subsequent deaths ( ) . obviously, managing the disease, which is considered a pandemic according to the world health organization ( ) , requires specific strategies that may vary due to different factors in each country, which may either lead to effectively dealing with the disease or cause challenges. considering the fact that using global experience, especially in times of crisis, is one of the best crisis management mechanisms, a review of the strengths and weaknesses of the islamic republic of iran in the covid- management covering the political-economic aspects, health services coverage, cultural aspect, and the transparency of information can be used as a model by other involved countries, while at the same time benefiting from the strategies of countries with similar experiences. health is not only a biological, but also a political, social, cultural, and economic issue. "health is a political issue" has been a point of consensus for a long time ( ) . therefore, the ability of countries to manage covid- is strongly influenced by their political-economic conditions which can be considered both an advantage and a threat. thus, it can be said that sanctions as a political-economic factor, more than any other factor, have challenged iran's ability to cope with covid- . covid- spreads in iran at the same time as the most severe sanctions are imposed on iran. although over the past four decades various sanctions have always been imposed on iran, since may , the unilateral us sanctions against iran have been increased significantly ( ) . the iranian health system has been directly and indirectly impacted by these sanctions, although it is one of the most prominent health systems in the eastern mediterranean region ( ) . although it is believed that sanctions are imposed on the physical weapons of war and do not include medicines and medical equipment, due to difficulties in commercial and financial exchanges with most countries, some essential medicines and laboratory equipment especially diagnostic, medical, and protection kits are not sufficiently available. in addition, numerous sanctions in the field of publishing research articles impede the international community's awareness of the consequences of such sanctions. on the other hand, as an advantage, the influential presence of effective and socially acceptable positions such as the iranian supreme leader as the highest religious authority and commander-in-chief can be named which helped in facing many unbearable challenges rooted in the beliefs, the culture and the religion of iranian people, by taking measures such as ordering the general staff of the armed forces to assist with the implementation of the regulations made by the supreme national security council, thanking the medical community on many occasions, advising on the implementation and acceptance of the by-laws of coronavirus committee, and issuing the closures of sacred shrines and the suspension of friday prayer ( ) . in regard to the second dimension, the health system capacity and service coverage of iran have a suitable condition with schools/universities of medical sciences integrated with health services as the unique country in the world is responsible for covering the whole people's needs. in iran, where measures have been taken regarding the primary health care (phc) since years before the alma-ata declaration ( ) the use of the network system is considered as one of the main mechanisms of coping with covid- in a ratified the health system. however, upon the prevalence of covid- in the country, much potential was ignored, one of which was the capacity of the phc system with ∼ , centers in rural areas and ∼ , health centers in the governmental sector. however, after a while, part of the outpatient management protocol was assigned to this extensive network for home-to-home screening and the information on the health status of all iranians was registered in a system. therefore, it is possible to follow up on individuals by having access to the patients' contacts and other information ( ) . in addition, not assigning epidemiologists at the right time to determine indicators such as fatality and mortality was among the weaknesses that disturbed predictions for estimating care and diagnostic needs. although many research centers in the country have begun to develop high-sensitivity and specificity diagnostic kits and these experiments are carried out in laboratories, it is still not possible to perform tests on all potential cases. on the other hand, the dissemination of viruses firstly began in the central regions of the country and then intensively spread to other regions ( ). the sudden increase in the number of cases led to a shortage of hospital beds in the referral hospitals initially dedicated to these patients, although there are ∼ , private and public hospital beds in iran. this shortage, which has been a concern of the authorities in all provinces, has led to the establishment of care centers after the early discharge of patients from referral hospitals or outpatient admission prior to hospital admission. although the establishment of these centers took place in the middle of march, with the launch of command headquarters, it was attempted to refer patients to these centers after the acute period of the disease was passed if they could not be discharged to home, or to become a center for mild patients. an interesting point in the management of these centers is the combination of military staff and volunteer or hospital personnel that may be somewhat different from international standards as these centers should apparently be managed by military forces to prevent hospital personnel from being separated from their workplace. on the contrary to the above weaknesses, the diagnosis, treatment, and follow-up of symptomatic and infected patients have been free from the very beginning. a variety of therapeutic and diagnostic protocols have been developed in the form of clinical trials. in this regard, coronavirus molecular diagnostic network and anti-coronavirus scientific committee consisting of faculty members of the iranian universities of medical sciences, and specialists, and experts in various fields with the aim of collaborating with the ministry of health and medical education (mohme). the launch of mohme online patient screening system for screening more than million people so far and controlling the outbreak was among the effective measures taken to reduce referrals to health centers and reduce the risk of infection in healthy people, of which , were discovered and referred to health centers ( ) . as the third dimension, culture has always been considered one of the effective factors on health ( ), the importance of which is particularly clear in the covid- pandemic. the iranian new year's celebration (march th) is thousands of years old symbolizing renewal in all aspects for iranians. therefore, all people prepare for nowruz from the middle of february which is apparent from the high traffic and crowds of people walking in the streets and all parts of cities. on the other hand, the nearly -day holiday of nowruz is a time for iranians to make many trips. thus, the concurrency of covid- pandemic with these days, which happened similarly in china, led to possibly the highest rate of interpersonal contact in the community, and the city-to-city spread of the disease by nowruz travelers. although there is a lack of cooperation and attention to the health guidelines by some people, the cooperation of many other members of the community is exemplary. the adherence to the slogan "we stay at home" and avoiding social interactions, performing volunteer activities such as the disinfection of public areas, the voluntary presence at patients' bedside, gooddoers' helping provide and produce protective equipment such as scrubs and masks, changing factory production lines to manufacture and prepare disinfectants, gloves, etc., landlords' not receiving rental fees, and obeying the supreme leader's orders not to visit sacred shrines and sanctuaries are examples of the culture of sacrifice among iranian ( ) . the last point is that the information provided by iranian authorities is always regarded as the most reliable information unless, for some reason, this transparency is compromised. despite the daily reports of the number of the infected, recovered cases and deaths by the mohme, the negative propaganda in foreign media and cyberspace has been able to effectively worsen the community's attitude toward the iranian management. this negative wave targets a wide range of issues from the number of deaths reported by the authorities to the news of digging mass graves for the victims and even suggests iran as the center for spreading the disease through its international airports, even in cities with no airports. everything considered, while disturbing public opinion, this will lead to distrust toward iran's effectiveness in dealing with the outbreak in this country ( ) . overall, what has helped iran control the disease so far can be summarized in several factors: the managerial concept all governance, although delayed, was strongly implemented were religious leaders along with military forces and civil volunteers accompanied the mohme. on the other hand, the powerful phc infrastructure and therapeutic, care, and specialized workforce which is appropriately distributed, due to the spread of the universities of medical sciences all across the country, have played important roles in disease management. despite the actions taken to create an atmosphere of distrust, the honesty of the authorities even in regard to the shortage of resources and equipment is considered an advantage in iran. and finally, given iran's specific circumstances, the focus should be put on domestic production, rather than importing equipment, to soon change the country into an exporter of health goods. in regard with the weaknesses of the system in dealing with the disease, due to the shortage of diagnostic kits at the onset of the disease in the country and its impact on the infected cases and subsequent deaths, some contradictory statistics have been presented which have led to the misinterpretation of the statistics and influenced planning for hospital beds, and hospitalization and patient care facilities. the shortage of data, the epidemiologists' lack of engagement in investigating the disease trend, and presenting different scenarios have also contributed to this matter. the lack of personal protective equipment for the frontline staff and people is also a challenge for the health system that has resulted in the death of a number of physicians and nurses. furthermore, the lack of advanced equipment for the care of critically ill patients in intensive care units, as a result of sanctions, is what requires to be managed. in summary regarding the detection of new cases and rapid responses health authorities did the best by supporting people but tracing the cases were not in an appropriate status, they asked them to stay home by family responsibility, but it did not work in some cases and the infected cases were in touch with the public. we did not use the temporary care centers as a part of the phc facility, social distancing was were supported by other stakeholders not managing by health managers, which may not be promising effective in the future. ultimately, it is certain that the covid- pandemic will end as did all previous ones, although it obviously will not be the last. therefore, the lessons learned from managing it in each country and sharing it with other countries can help prepare the world to deal with future pandemics. all datasets presented in this study are included in the article/supplementary material. modeling and prediction of the coronavirus disease spreading in china incorporating human migration data. medrxiv coronavirus cases prevention ucfdca health is a political issue covid- battle during the toughest sanctions against iran the eastern mediterranean region: a decade of challenges and achievements thanks to the supreme leader for the efforts of physicians and nurses in the fight against the corona virus health information system in primary health care: the challenges and barriers from local providers' perspective of an area in iran daily statistics of covid- in iran people's screening system culture, behavior and health university-industry cooperation, a mechanism to deal with the corona virus estimation of covid- burden and potential for international dissemination of infection from iran. medrxiv all authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication. the authors would like to appreciate the managers of the shahid beheshti university of medical science for their support. key: cord- -izkz hz authors: eden, john-sebastian; rockett, rebecca; carter, ian; rahman, hossinur; de ligt, joep; hadfield, james; storey, matthew; ren, xiaoyun; tulloch, rachel; basile, kerri; wells, jessica; byun, roy; gilroy, nicky; o’sullivan, matthew v; sintchenko, vitali; chen, sharon c; maddocks, susan; sorrell, tania c; holmes, edward c; dwyer, dominic e; kok, jen title: an emergent clade of sars-cov- linked to returned travellers from iran date: - - journal: biorxiv doi: . / . . . sha: doc_id: cord_uid: izkz hz the sars-cov- epidemic has rapidly spread outside china with major outbreaks occurring in italy, south korea and iran. phylogenetic analyses of whole genome sequencing data identified a distinct sars-cov- clade linked to travellers returning from iran to australia and new zealand. this study highlights potential viral diversity driving the epidemic in iran, and underscores the power of rapid genome sequencing and public data sharing to improve the detection and management of emerging infectious diseases. from a public health perspective, the real-time whole genome sequencing (wgs) of emerging viruses enables the informed development and design of molecular diagnostic methods, and tracing patterns of spread across multiple epidemiological scales (i.e. genomic epidemiology). however, wgs capacities and data sharing policies vary in different countries and jurisdictions, leading to potential sampling bias due to delayed or underrepresented sequencing data from some areas with substantial sars-cov- activity. herein, we show that the genomic analyses of sars-cov- strains from australian returned travellers with covid- disease may provide important insights into viral diversity present in regions currently lacking genomic data. in late december , a cluster of cases of pneumonia of unknown aetiology in wuhan city, hubei province, china was reported by health authorities [ ] . a novel betacoronavirus, designated sars-cov- , was identified as the causative agent [ ] of the disease now known as covid- , with substantial human-to-human transmission [ ] . to contain a growing epidemic, chinese authorities implemented strict quarantine measures in wuhan and surrounding areas in hubei province. significant delays in the global spread of the virus were achieved, but despite these measures, cases were exported to other countries. as of march , these numbered more than countries, on all continents except antarctica; the total number of confirmed infections exceeded , and there were nearly , deaths [ ] . although the vast majority of cases have occurred in china, major outbreaks have also been reported in italy, south korea and iran [ ] . importantly, there is widespread local transmission in multiple countries outside china following independent importations of infection from visitors and returned travellers. in new south wales (nsw), australia, wgs for sars-cov- was developed based on an existing amplicon-based illumina sequencing approach [ ] . viral extracts were prepared from respiratory tract samples where sars-cov- was detected by rt-pcr using world health organization recommended primers and probes targeting the e and rdrp genes, and then reverse transcribed using ssiv vilo cdna master mix. the viral cdna was used as input for multiple overlapping pcr reactions (~ . kb each) spanning the viral genome using platinum superfi master mix (primers provided in supplementary table s ). amplicons were pooled equally, purified and quantified. nextera xt libraries were prepared and sequencing was performed with multiplexing on an illumina iseq ( cycle flow cell). in new zealand, the artic network protocol was used for wgs [ ] . in short, bp tiling amplicons designed with primal scheme [ ] were used to amplify viral cdna prepared with superscript iii. a sequence library was then constructed using the oxford nanopore ligation sequencing kit and sequenced on a r . . minion flow-cell. near-complete viral genomes were then assembled de novo in geneious prime . . or through reference mapping with rampart v . . [ ] using the artic network ncov- novel coronavirus bioinformatics protocol [ ] . in total, sars-cov- genomes were sequenced from cases in nsw diagnosed between january and march , as well as a single genome from the first patient in auckland, new zealand sampled on february (table ) . australian and new zealand sequences were aligned to global reference strains sourced from gisaid with mafft [ ] and then compared phylogenetically using a maximum likelihood approach [ ] . the australian strains of sars-cov- were dispersed across the global sars-cov- phylogeny ( figure a ). the first four cases of covid- disease in nsw occurred between and january , and these were closely related (with - snps difference) to the prototype strain mn /sars-cov- /wuhan-hu- , which is the dominant variant (supplementary figures s & s ) . technological advancements and the wide-spread adoption of wgs in pathogen genomics have transformed public health and infectious disease outbreak responses [ ] . previously, disease investigations often relied on the targeted sequencing of a small locus to identify genotypes and infer patterns of spread along with epidemiological data. as seen with the recent west african ebola [ ] and zika virus epidemics [ ] , rapid wgs significantly increases resolution of diagnosis and surveillance thereby strengthening links between clinical and epidemiological data [ ] . this advance improves our understanding of pathogen origins and spread that ultimately lead to stronger and more timely intervention and control measures [ ] . following the first release of the sars-cov- genome [ ] , public health and research laboratories worldwide have rapidly shared sequences on public data repositories such as gisaid [ ] (n = genomes as of march ) that have been used to provide near real-time snapshots of global diversity through public analytic and visualization tools [ ] . while all known cases linked to iran are contained in this clade, it is important to note the presence of two chinese strains sampled during mid-january from hubei and shandong provinces. it is expected that further chinese strains would be identified within this clade, and across the entire diversity of sars-cov- as this is where the outbreak started, including for the outbreak in iran itself. however, while we cannot completely discount that the cases in australia and new zealand came from other sources including china, our phylogenetic analyses, as well as epidemiological (recent travel to iran) and clinical data (date of symptom onset), provide evidence that this clade of sars-cov- is linked to the iranian epidemic, from where genomic data is currently lacking. importantly, the seemingly multiple importations of very closely related viruses from iran into australia suggests that this diversity reflects the early stages of sars-cov- transmission within iran. none declared. wuhan municipal health and health commission's briefing on the current pneumonia epidemic situation in our city a new coronavirus associated with human respiratory disease in china genomic characterisation and epidemiology of novel coronavirus: implications for virus origins and receptor binding an interactive web-based dashboard to track covid- in real time world health organisation coronavirus situation report - th evolution of human respiratory syncytial virus (rsv) over multiple seasons in new south wales, australia. viruses ncov- sequencing protocol, quick j an amplicon-based sequencing framework for accurately measuring intrahost virus diversity using primalseq and ivar mafft: a novel method for rapid multiple sequence alignment based on fast fourier transform a simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood whole genome sequencing-implications for infection prevention and outbreak investigations. curr infect dis rep virus genomes reveal factors that spread and sustained the ebola epidemic genomic insights into zika virus emergence and spread. cell unifying the epidemiological and evolutionary dynamics of pathogens tracking virus outbreaks in the twenty-first century org -novel coronavirus genome global initiative on sharing all influenza data -from vision to reality nextstrain: real-time tracking of pathogen evolution australia -mar- se asia key: cord- -p f el authors: ahmady, soleiman; shahbazi, sara; heidari, mohammad title: transition to virtual learning during the coronavirus disease– crisis in iran: opportunity or challenge? date: - - journal: disaster medicine and public health preparedness doi: . /dmp. . sha: doc_id: cord_uid: p f el covid- is a respiratory disease that can spread from one person to person. this virus is a novel coronavirus that was first identified during an investigation into an outbreak in wuhan, china. iran’s novel coronavirus cases reached , on march, while death toll reached approximately , . its first death was officially announced on february in qom. the coronavirus pandemic has affected educational systems around the world, also in iran, and led to the closure of face to face courses in schools and universities. therefore, virtual education can be seen as a turning point in education of these days in iran. t he coronavirus disease (covid- ) is a respiratory disease that can spread from person to another. the novel coronavirus, known as severe acute respiratory syndrome (sars-cov- ), was first identified during an investigation of an outbreak in wuhan, china. the disease has been spreading worldwide since its inception, as the world health organization declared an epidemic on march , . covid- cases in iran reached on march , while the death toll reached approximately . the first death to covid- was officially announced on february , , in qom. the covid- pandemic has affected educational systems in countries around the world, including iran, and led to the closure of face-to-face courses in schools and universities. therefore, virtual education can be seen as a turning point in education in iran due to covid- . virtual learning offers many benefits that traditional college degree programs do not provide, such as accessibility from anywhere at any time, asynchronous discussions with classmates, immediate feedback on tests, and flexibility. however, despite the benefits of virtual learning, it is not always easy to implement. in iran, virtual education for grade-school students is performed through scheduled programs through tv and mobile education through social media; and, in higher education, virtual instruction is performed through mobile messenger systems and learning management systems, such as navid, vesta, and moodle. in elementary and secondary school education in iran, conditions of achieving virtual education during the crisis of covid- are complex due to ( ) cultural and social contexts, ( ) lack of teachers' preparation for virtual teaching, ( ) lack of access to all infrastructures and equipment, ( ) willingness to hold presence classes (ie, in-person), ( ) impossibility of using mobile-based training for all age groups, ( ) lack of access to smartphones, ( ) insufficient literacy and technological capabilities, ( ) inability to virtualize all courses, and ( ) large number of learners and the limited time to prepare online courses. the universities in iran have adequate infrastructure, experience, and acceptances consistent with other global movements toward the context of virtual learning. this is an opportunity for higher education institutions to shift to virtual education. in spite of this, the main concern with the closing of higher education institutions is the impossibility of supporting courses that are fully operational and require in-person training and practice. therefore, it seems that culture building and in-service training for professors are essential, and there is a need for the coordination and empathy of the relevant authorities and managers to plan accurately and coherently. epidemiology and clinical characteristics of covid- dohmh) covid- response team. preliminary estimate of excess mortality during the covid- outbreak covid- pandemic and comparative health policy learning in iran closure of universities due to coronavirus disease (covid- ): impact on education and mental health of students and academic staff the influence of virtual learning environments in students' performance the authors have no conflicts of interest to declare. key: cord- -y pzrbdi authors: arab-zozani, morteza; ghoddoosi-nejad, djavad title: covid- in iran: the good, the bad, and the ugly strategies for preparedness – a report from the field date: - - journal: disaster medicine and public health preparedness doi: . /dmp. . sha: doc_id: cord_uid: y pzrbdi the emergence of coronavirus disease (covid- ), a novel unknown virus that is challenging whole countries all over the world, has prompted different strategies from various governments. iran, as one of the first countries to experience the onset of the virus outbreak, made and implemented some policies that should be assessed, so that lessons may be learned for the future. although some negative actions and policies, such as delays in cancellation of international flights especially from china, not taking the disease seriously and comparing it with seasonal influenza, and the like, are hard to ignore, some impressive actions are also vividly clear. policies, such as social distancing, dramatically increasing social awareness about preventive actions in terms of public health, and using masks and hand washing, were cost-effective policies that resulted in successful control of the virus in the first onset. while some quite clearly ineffective decisions were made by iranian authorities, the huge catastrophic effect of sanctions cannot be forgotten. possibly in level situations with similar countries, iran will have far better results regarding preparedness for future pandemics like covid- . h aving officially been labeled a pandemic, the coronavirus disease (covid- ) has so far devastated over countries and territories around the world and international conveyances. , this challenging, historic, and memorable phenomenon the world is experiencing is teaching us an extremely tough but useful lesson in the way we deal with potential disasters going forward, by making a case for the most effective policy-making and management practices. the importance of policy analysis, during times of crisis and especially with pandemics, is highly valuable. taking the wrong steps in combination with inadequate policies has the power to endanger the lives of many. considering the level of contagiousness, as well as its international reach, this virus has the potential to affect lives not just in country but the population of the entire world. , emerging from wuhan, china, in early december of , the virus has spread all over the world. iran was one of the first countries affected by the virus, and although the authorities' initial reaction at the beginning of the epidemic was to "keep calm, and ignore the seriousness of the situation by comparing it to seasonal influenza," they subsequently had to change their position and consider tougher controls in the cities, as the course of the virus outbreak seemed to be out of control. iran's health system, under overwhelming pressure because of covid- , is experiencing a unique situation in which very novel and yet valuable lessons can be learned for the years to come. in this regard, we are going to assess iran's steps and actions to assess these proceedings as well as outline and evaluate its impact. on a time-based approach, the first and foremost event was a delay in canceling all flights from china, while other countries simultaneously shut down all air travel from that region. this resulted in an increased risk of spreading the disease by infected people entering the country. authorities are speculating that it was the students from wuhan who were the main reason for spreading the virus into guilan province, a northern province of iran. clearly, given the high contagious characteristic of the virus in combination with communications and travel (air transport in particular), this had a potential to easily accelerate the spread of such diseases. , the next event that increased the rate of disease prevalence is the demonstration on independence day, february th - bahman in the persian calendar, while china had officially announced infection by the virus and were taking the measures of disallowing all travel from the region; this might have flattened the curve of the disease brought by the travelers who had not yet shown any symptoms. numerous studies have shown that close contact, as well as disregarding the importance of social distancing, could be one of the factors causing the virus to spread rapidly. , , , due to the political importance of this event and the lack of awareness of the disease within the country at the time, allowing such ceremonies to be held on a regular basis and with no distancing protocol could be another reason for a drastic increase of the spread of the disease in the country. moreover, despite the official announcement of the presence of the first infected patients with covid- , the decision to hold the parliament election turned out to be the third major factor in increasing the spread of the virus. large gatherings of people in voting centers, despite all cautions about the covid- , took place, and this led to a further spread of the virus. the fourth, and some would say the most important factor, was deciding not to quarantine qom, the first city in which the virus was officially announced. the presence of a large number of religious school students from diverse ranges of countries, especially from china, made qom the first city with a widespread prevalence of covid- . given that the majority of students from different cities in iran are present in qom as well, it was not so hard to understand the virus would have travelled widely, with the city not being quarantined. while quarantine prevents the spread of contamination, it is one of the most primitive ways of controlling such diseases, inasmuch as in wuhan, china, this strategy turned out to be very effective. despite authorities' primary denial of the covid- incidence, the disease gradually was spreading to other cities. consequently, with increasing concerns about the virus, schools and universities sent their students home. delay in shutting the universities resulted in sending potentially contaminated students from big cities back to their homes, some of them small towns. continuous disregard of the seriousness of pandemic presence within the society was partially, however, due to the primitive approaches of social media. national tv called it less fatal than influenza, and having announced the decision to impose several days off work to the public, some people took the opportunity to go on trips, mostly to northern parts of the country, which had already been red-marked in terms of the virus epidemic. after that, in the very last hours of the friday, the government changed the plan by suspending the days-off work policy, but it was clearly too late. concurrent with questionable actions of the public authorities, some opportunistic jobbers who claimed traditional medicine, they called it islamic medicine, prescribed various alternative solutions that were in contrast with the practice of modern scientific medicine. this, alongside a bewilderment of public authorities, resulted in a confused population, which added to the ill handling of controlling the pandemic. one thing about lack of collaboration in various sections was obvious. for example, while the ministry of health authorities did their best to inform the public about the disease by advising people to stay at home on national tv, just after the speech, the tv played an advertisement promoting a sale event for one of the biggest chain stores in iran, which clearly contradicted the messages from health-related authorities, like they were living in a whole another country. however, the effect of international sanctions on the economy of the country cannot be ignored. lack of basic supplies, such as masks and general personal protective equipment (ppe), as well as inadequate numbers of beds per capita compared with other developed countries, caused a shock to the health system, particularly in hospital care and more specifically in intensive care unit (icu) beds. lack of medical equipment, such as computed tomography scanners and ventilators, forced healthcare managers to resort toward inevitable rationing. not being able to screen everybody with symptoms due to limited availability of diagnostic kits was one of the main reasons for the world health organization (who) statement declaring that the official statistics in iran are probably far less than the real figures. on the bright side, participation and voluntary collaboration of people's efforts to decontaminate public spaces, spreading information about the disease, and several tele-medical approaches for screening people, were positive steps in controlling the disease. what is more, although during the new year holiday (nowruz) there were concerns about travelling to various provinces such as isfahan, yazd, and fars, and at first no serious regulations were imposed as authorities resorted to advising the public, rather than enforcing the law, on the last days of the holidays, however, the government decided to put serious limitations in place, and although rather late, this might just be better late than never. another positive aspect of iran's authorities' actions was focusing on primary healthcare policies that are proven to be more cost-effective than just clinical tertiary care. increasing public knowledge, promoting their attitude, and also improving their practices resulted in a somehow successful management of the virus in the first onset. last but not least was the dedication and commitment of the personnel of the health-related centers, including primary, secondary, and tertiary levels of encountering the virus and infected people. given the horrifying situations the virus can cause, these people proved their value, and it was one covid- , iran, preparedness of the most memorable moments in the history of health care in iran. to summarize the above, it seems that, although some good actions are hard to ignore, in aggregate, iran's crisis management procedures, in terms of handling epidemics, are far from perfect. there is a lot to be learned from this event to better prepare for any similar events in the future. after all, the cruel heavy sanctions imposed on the government hurt the common people; its role should be considered when judging iran's policy-making decisions about managing covid- . coronavirus cases features and limitations of litcovid hub for quick access to literature about covid- responding to covid- -a once-in-a-century pandemic? history in a crisis-lessons for covid- characteristics of and important lessons from the coronavirus disease (covid- ) outbreak in china: summary of a report of cases from the chinese center for disease control and prevention covid- battle during the toughest sanctions against iran mapping the incidence of the covid- hotspot in iran-implications for travellers the epidemiological characteristics of an outbreak of novel coronavirus diseases (covid- ) in china world health organization knowledge, attitudes, and practices among the general population during covid- outbreak in iran: a national cross-sectional survey disaster medicine and public health preparedness the authors thank christina ovsenik for revising this article in terms of english writing. the authors have no conflicts of interest to declare. key: cord- -ll pnl authors: saberi, m.; hamedmoghadam, h.; madani, k.; dolk, h. d.; morgan, a.; morris, j. k.; khoshnood, k.; khoshnood, b. title: accounting for underreporting in mathematical modelling of transmission and control of covid- in iran date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: ll pnl background: iran has been the hardest hit country by the outbreak of sars-cov- in the middle east with , confirmed cases and , deaths as of april . with a relatively high case fatality ratio and limited testing capacity, the number of confirmed cases reported is suspected to suffer from significant under-reporting. therefore, understanding the transmission dynamics of covid- and assessing the effectiveness of the interventions that have taken place in iran while accounting for the uncertain level of underreporting is of critical importance. we use a mathematical epidemic model utilizing official confirmed data and estimates of underreporting to understand how transmission in iran has been changing between february and april . methods: we developed a compartmental transmission model to estimate the effective reproduction number and its fluctuations since the beginning of the outbreak in iran. we associate the variations in the effective reproduction number with a timeline of interventions and national events. the estimation method also accounts for the underreporting due to low case ascertainment by estimating the percentage of symptomatic cases using delay adjusted case fatality ratio based on the distribution of the delay from hospitalization to death. findings: our estimates of the effective reproduction number ranged from . to . between february and april , with a median of . . we estimate a reduction in the effective reproduction number during this period, from . ( % ci . - . ) on march to . ( % ci . - . ) on april , due to various non-pharmaceutical interventions including school closures, a ban on public gatherings including sports and religious events, and full or partial closure of non-essential businesses. based on these estimates and given that a near complete containment is no longer feasible, it is likely that the outbreak may continue until the end of the if the current level of physical distancing and interventions continue and no effective vaccination or therapeutic are developed and made widely available. interpretation: the series of non-pharmaceutical interventions and the public compliance that took place in iran are found to be effective in slowing down the speed of the spread of covid- within the studied time period. however, we argue that if the impact of underreporting is overlooked, the estimated transmission and control dynamics could mislead the public health decisions, policy makers, and general public especially in the earlier stages of the outbreak. funding: nil. evidence before this study since the outbreak of sars-cov- in late , several studies have attempted to understand its transmission and control dynamics. the majority of the existing studies reported the dynamics and initial estimates of the effective reproduction number from china followed by a few other studies using data from other countries including italy, spain, south korea, germany, france and iran among others. however, none of the previous work has taken into account the impact of possible underreporting of cases in estimation of the effective reproduction number. also, no other study reported the time-dependent association between the interventions and variations in the effective reproduction number for iran as the hardest hit country in the middle east. we use a mathematical model to estimate the transmission and control dynamics of covid- in iran, taking into account the significant underreporting of cases. we estimated the time-dependent effective reproduction number in association with a timeline of events and interventions that took place. we showed that if underreporting is overlooked, the estimated dynamics could mislead the public health decisions and general public. the impact of control measures on the effective reproduction number could also significantly be overestimated unless under-reporting is taken into account. the estimation of transmission and control dynamics of covid- in any country highly depends on the quality of the reported data. however, in the presence of high uncertainty in the number of confirmed cases, it is of crucial importance to take into account the impact of underreporting when interventions are to be introduced or lifted. the outbreak of sars-cov- in iran was first officially announced in february , two months after the initial outbreak in wuhan, china. iran's patient zero is believed to have been a merchant from qom who had travel history to china. despite the initial signs of a spread in qom, the government declined to place the city under quarantine to contain the epidemic at an early stage for various technical, socio-economic, religious, and security reasons. the first local non-pharmaceutical interventions such as schools and universities closure were put in place a few days after the official acknowledgement of the first cases in qom and tehran. since then, various public health control measures at the local and national levels were taken that are believed to have altered the course of the outbreak. see figure for a spatial illustration of the spread throughout the country by province in the first week since the official announcement of the first case (appendix p ). the relatively high case fatality ratio (cfr), defined as the total number of deaths over the total number of infected cases, in iran's official reports after the first week since the official declaration of the first case ( . %) has raised questions on the true number of cases in the country. , the testing protocol in iran at the early stages of the outbreak was limited to hospital admissions of the patients with severe symptoms. while iran has extended the covid- diagnostic testing capacity later on to patients with milder symptoms, it is believed that under-ascertainment of cases still remains high. this study aims to understand the transmission dynamics of covid- in iran and to assess the effectiveness of the control measures that were put in place over time through estimation of the effective reproduction number ܴ ሺ ‫ݐ‬ ሻ defined as the average number of susceptible persons infected by an infected person during its infectious period at a given time in the course of the epidemic. we assessed ܴ ሺ ‫ݐ‬ ሻ in relation to a timeline of national events and non-pharmaceutical interventions. in the absence of timely and reliable data, modelling can provide helpful answers, including the degree of plausible uncertainty in different estimates and the effectiveness of non-pharmaceutical interventions. by providing explicit and clear information about model assumptions and parameters, modelling can also foster scientific discussion of data gaps and what can be done to improve outbreak-related estimates by borrowing information available elsewhere. finally, models can be developed and presented using both average estimates and measures of their uncertainty or, alternatively, as scenarios that can illustrate possible developments of the epidemic under various conditions. we use official time-series reports of the number of confirmed cases, recovered, and deaths from the world health organization (who) and iran's ministry of health and medical education . the first confirmed case was reported on february which is assumed as the beginning of the outbreak of covid- in iran. we describe the dynamics of spread using a variation of the susceptible-exposed-infected-recovered (seir) model, distinguishing between fatality and recovered cases combined with an estimate of the percentage of symptomatic cases using delay-adjusted cfr (appendix p ). see figure . the model . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint accounts for the time between exposure-to-onset of symptoms (or confirmation), also known as incubation period, assuming a gamma distribution with an average of . days and a standard deviation of . days. we also assume the time from symptoms onset-to-death and -to-recovery both follow a gamma distribution with an average of . days and a standard deviation of . days and an average of . days and a standard deviation of days, respectively. the size of the initial susceptible population is assumed to be million. to estimate the parameters of the developed seir model, we formulate an ordinary least squares (ols) minimization. we use pattern search as a derivative-free global optimization algorithm to find the model parameters that minimizes the sum of the normalized root mean squared error (rmse) of the number of infected ߝ , recovered ߝ and removed cases ߝ . the basic reproduction number, ܴ , a fundamental measure in infectious disease epidemiology and public health, is defined as the average number of susceptible persons infected by an infected person during its infectious period in a fully susceptible population. ܴ ௧ is defined similarly to ܴ but is not limited to the assumption of a completely susceptible population. here, we use empirical data from iran to trace changes in ܴ ௧ over a rolling day period since the beginning of the covid- outbreak and describe its association with various interventions (e.g. school closures, social distancing, and bans on public gatherings) that took place by the public and government. various methods exist to estimate ܴ (and ܴ ௧ ). , here, we use the same framework described in figure in which the parameters of the formulated seir model are inferred through an optimization problem. ܴ ௧ is calculated using a rolling time window of days to capture the evolving trend of the spread over time due to various changes in the social network contact rate. the calculated ܴ ௧ may be overestimated during the early stage of an outbreak due to different reasons including the impact of imported cases and heterogeneity in subpopulations (e.g. older than years old) with higher transmission rates. we account for the under-reporting of the number of infected cases in the official confirmed data using delay-adjusted case fatality ratio (cfr) approach. this approach assumes that the time from hospitalization-to-death has a known statistical distribution and uses this distribution to estimate when the people who died from covid- would have been reported as being infected. the case fatality ratio is the ratio of the numbers of deaths over the numbers of reported infections calculated at the time of reporting not the time of death. this is extremely important for rapidly evolving epidemics. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . the method, however, does not account for underreporting in fatality cases. the distribution of the time from confirmation-to-death is assumed to follow the same distribution as of the time from hospitalization-to-death, following a lognormal distribution with a mean of days and a standard deviation of . days. here, we assume that the estimate for percentage of symptomatic covid- cases reported for iran follows a lognormal distribution (same distribution type as of the time from hospitalization-to-death) with a mean of . % and a standard deviation of % based on the latest estimates in the literature. this is based on the assumption of a baseline cfr of . %. we assume the underreporting level remains constant over time. we estimated that the cfr on february , before adjusting for the time from diagnosis-to-death, was . %. with more data emerging after the second week, the cfr dropped to . % on the th day since the declared beginning of the outbreak on february , . later, between march and april , the cfr stabilized between . % and . % with a mean of . %. see figure (c). with the wider spread of covid- across the country, the cfr increased to . % on march . however, the cfr declined and plateaued around . % between and april . the relatively high cfr could correspond to a significant level of under-reporting of the infected cases and an overwhelmed health system. given the wide distribution of the time from confirmation-to-death of covid- , we also explore the delay-adjusted cfr with -and -day delay period, as examples. the dynamics of the delay-adjusted cfr with -day delay suggests that the cfr has been gradually reducing in iran from . % on march to . % on april . when underreporting of infected cases is overlooked, the estimated effective reproduction number began from . ( % ci . - . ) on march and reduced to . ( % ci . - . ) on april suggesting the outbreak peak has already occurred on april when ܴ ௧ goes below , about days from the confirmation of the first case. the outbreak is also likely to continue until the end of . see figure . the estimates of the effective reproduction number were consistently larger during the early stage of the outbreak when underreporting is overlooked compared to when underreporting is taken into account. however, the estimated effective reproduction numbers converged as the number of infected cases approached the peak. the convergence of the estimates can be partly explained by the fact that the effective reproduction number is more dependent on the rate of change in the infected and recovered cases rather than their absolute numbers. results also suggest that the impact of control measures on the effective reproduction number is significantly overestimated when under-reporting is taken into account. with the gradual reduction of the effective reproduction number to below one and the increasing pressure on an already fragile economy because of the implemented control measures, the government is seeking an exit strategy and is considering easing some of the restrictions. here, we conduct a scenario analysis to understand how three different scenarios could change the projected outlook of the outbreak in iran: i) maintaining the same level of control measures as of april , ii) intensifying the measures to increase physical distancing represented by a % reduction in the reproduction number, and iii) partially lifting the restrictions to ease physical distancing represented by a % increase in the reproduction number. to estimate the number of icu beds needed, we assume % of the confirmed cases require intensive care. we found that in all scenarios the projection of patients requiring icu admission exceeds the original icu capacity. note that no official information is available on the expanded icu capacity. as of april , both projected curves start above the icu capacity. easing the restrictions can quickly push the peak to a level that is five times higher than the scenario where the current level of control measures is maintained and puts additional pressure on the health system. results clearly suggest that with further restrictions . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint (scenario ii), the projected curve quickly goes back under the icu capacity while it takes more than days for the curve to go back under the icu capacity in scenario i and iii. with % ci over a -day rolling window when underreporting is taken into account. (c) estimated cfr with and without delay adjustment over the same time period in a semi-log scale. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . the projected number of icu beds needed under the three scenarios. the original icu capacity is assumed between to beds. in this study, we used a mathematical epidemic model to provide the first estimates of the changing transmission of sars-cov- infection in iran when underreporting of cases are considered. we used official data and adjusted our estimates for underreporting based on delay-adjusted cfr. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . we used a variation of the seir model combined with an estimate of the percentage of symptomatic cases using delay-adjusted cfr based on the distribution of the time from confirmation-to-death . in contrast to previous models of the epidemic , we did not assume any prior information on the distribution of the effective reproduction number. this combined with the use of a series of distributions allowed us to take into account more appropriately the uncertainty and the random variation in both input data and model outcomes. the outbreak of covid- in iran is claimed to have been started in qom province with the first case officially reported on february . as shown earlier in figure (a) , according to the official data, it only took two days, for four more provinces, including tehran, markazi, mazandaran, and gilan (guilan) to report their first cases. the first non-pharmaceutical intervention took place on february with the closure of schools and universities in qom followed by the capital city of tehran after a day. with the school closures in the capital and yet low level of social awareness about the potential risks of covid- , a surge in the number of holiday trips from tehran to northern provinces of mazandaran and gilan was observed. soon after, with no restriction on the inter-city travels the number of identified cases in gilan and mazandaran grew rapidly, and the infection spread throughout the rest of the country. the second major non-pharmaceutical intervention occurred on february with a wide campaign to disinfect public spaces and closure of all schools and universities across all provinces. on march , the government announced an increase in the covid- testing capacity. on march , sporadic closure or reduction of working hours in government offices and banks across the country was reported. on march , two often crowded religious shrines in qom and mashhad were closed to visitors. the increased physical distancing as the result of interventions and increase in public awareness of the crisis through major official and unofficial information campaigns, especially on social media, gradually showed its impact by slowing down the speed of the spread as shown earlier in figure (b) . the estimated effective reproduction number increased from . on march to . on march , perhaps due to the increase in case ascertainment and delay in early interventions to show their impact. the effective reproduction number decreased consistently to . on march . on march , only a few days before the persian new year (nowruz, march ), in the absence of strict travel restrictions, millions of iranians began making road trips to various destinations across the country despite the warnings from the government and many hotels, restaurants and the general hospitality industry's refrainment to provide services to any traveller. this is believed to have increased the speed of the spread of covid- in iran, increasing the effective reproduction number to . on march . on march , government announced more restrictive non-pharmaceutical interventions leading to closure of all non-essential businesses for at least two weeks, followed by further intensified interventions on march , including restrictions on entry and exit to affected provinces and cities, closure of parks, pools and all recreational places, and a ban on public gatherings including sport, cultural, and religious events. these restrictions pushed the effective reproduction number further down to . on april and . on april . iran has had one of the highest case fatality rates (cfr) among the affected countries in the world. while the cfr is known to vary significantly between countries due to various reasons including testing frequency and population age distribution , the cfr is still higher in iran despite having a younger population with the median age of . years old compared to china with % cfr and the median population age of . and south korea with % cfr and the median population age of . . perhaps a comparable country in the middle east region with similar population characteristics (median age of . ) is turkey. the cfr in turkey as of april was %, three times lower than that of iran. while the evidence is indirect, it suggests that the official number of cases reported by iran may has been significantly under-reported, possibly due to relatively low case-ascertainment and under-reporting of identified cases. the continuous reduction in the delay-adjusted cfr shows a different trend compared to the cfr with no consideration of the time from confirmation-to-death. the continuous reduction could be explained by the improving case identification practice in iran over time with various initiatives including a national coronavirus helpline (the " " service), established in late february to self-report symptoms and identify suspected cases. our results confirmed the significant impact of underreporting in describing the story of the covid- outbreak in iran, especially in the early stages. we showed how overlooking underreporting can drastically affect estimation of ܴ ሺ ‫ݐ‬ ሻ and overestimate the impact of control measures. our results also showed the reduction in effective reproduction number, a measure of infection transmission, during this period. this decrease was most likely due to the increased physical distancing as the result of multiple non-pharmaceutical public health interventions, including school closures, ban on public gatherings, travel restrictions, full/partial closure of non-essential businesses, as well as major awareness campaigns over social media. based on the latest trends, while the first peak of covid- in iran occurred on april , the post-peak period may continue to the end of . however, these projections assume the continuation of the current level of control measures and the absence of effective therapeutic treatment or vaccination programs. hence, they can be subject to important shifts depending, in particular, on the public's willingness to continue and the government's success in implementing social distancing measures or easing the restrictions. our model provides tangible evidence of the association between the different non-pharmaceutical interventions and their impact on the course of the outbreak. the results showed how the acceptance and hence effectiveness of the interventions endorsed by the iranian government aimed at "flattening the curve" depended in part on the public's level of awareness of the principles behind governmental policies and their trust in the government and its control measures. for example, closure of schools and businesses in the capital city of tehran near the time of the persian new year was followed by a surge of holiday trips to gilan and mazandaran and a subsequent increase in the number of cases in these provinces and in other parts of the country. this observation shows how interventions may be associated with unintended and at times counterproductive consequences. these negative consequences can be prevented when there is open and credible communications by competent officials and mutual trust between public and government. moreover, intervention measures need to be developed, implemented and enforced as a whole, for example by strict reinforcement of travel restrictions in conjunction with school and workplace closings. there is no substitute for high quality data -complete, accurate, and timely -as a basis for public policy. however, in the absence of such data, modelling of the type presented here can help provide reasonable estimates as well as realistic bounds of their uncertainty. the range of uncertainty can be viewed as the margin of error in the model's predictions of the number of cases, icu admissions or deaths. modeling can also illustrate different scenarios --pessimistic vs. optimistic vs. realistic --of how the epidemic may evolve in relation to current and future public health measures and the possible compliance of the public over time. in conclusion, using a stochastic model of the sars-cov- epidemic in iran, we assessed the dynamic of the epidemic in relation to public health measures to increase social distancing. we took into account both the inherent uncertainty in the data and the possible impact of under-reporting of true cases due to low case ascertainment and reporting. in the absence of consistently reliable data, the modelling approach as presented here can help generated reasonable estimates of key public health metrics such as the number of cases and case fatality ratio. in turn, these metrics and scenarios can help serve the dual purpose of informing public policy and the public and fostering discussions and improvements of epidemic modelling. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint coronavirus disease (covid- ) world economic forum. finding 'patient zero': the challenges of tracing the origins of coronavirus coronavirus could break iranian society iran takes emergency measures after two coronavirus deaths in qom cross-country comparison of case fatality rates of covid- /sars-cov- why is iran's reported mortality rate for coronavirus higher than in other countries? iran's ministry of health and medical education. daily covid- epidemic reports the incubation period of coronavirus disease (covid- ) from publicly reported confirmed cases: estimation and application report : severity of -novel coronavirus (ncov) inverse problem for coefficient identification in sir epidemic models analysis of generalized pattern searches complexity of the basic reproduction number (r ) effective reproduction numbers are commonly overestimated early in a disease outbreak the effective reproduction number as a prelude to statistical estimation of time-dependent epidemic trends the estimation of the basic reproduction number for infectious diseases on the exact measure of disease spread in stochastic epidemic models incubation period and other epidemiological characteristics of novel coronavirus infections with right truncation: a statistical analysis of publicly available case data centre for mathematical modelling of infectious disease, london school of hygiene & tropical medicine the centre for evidence-based medicine characteristics of and important lessons from the coronavirus disease (covid- ) outbreak in china: summary of a report of cases from the chinese center for disease control and prevention centre for mathematical modelling of infectious disease, london school of hygiene & tropical medicine key: cord- -xolksoy authors: pourghasemi, hamid reza; pouyan, soheila; farajzadeh, zakariya; sadhasivam, nitheshnirmal; heidari, bahram; babaei, sedigheh; tiefenbacher, john p. title: assessment of the outbreak risk, mapping and infection behavior of covid- : application of the autoregressive integrated-moving average (arima) and polynomial models date: - - journal: plos one doi: . /journal.pone. sha: doc_id: cord_uid: xolksoy infectious disease outbreaks pose a significant threat to human health worldwide. the outbreak of pandemic coronavirus disease (covid- ) has caused a global health emergency. thus, identification of regions with high risk for covid- outbreak and analyzing the behaviour of the infection is a major priority of the governmental organizations and epidemiologists worldwide. the aims of the present study were to analyze the risk factors of coronavirus outbreak for identifying the areas having high risk of infection and to evaluate the behaviour of infection in fars province, iran. a geographic information system (gis)-based machine learning algorithm (mla), support vector machine (svm), was used for the assessment of the outbreak risk of covid- in fars province, iran whereas the daily observations of infected cases were tested in the—polynomial and the autoregressive integrated moving average (arima) models to examine the patterns of virus infestation in the province and in iran. the results of the disease outbreak in iran were compared with the data for iran and the world. sixteen effective factors were selected for spatial modelling of outbreak risk. the validation outcome reveals that svm achieved an auc value of . (march ), . (march ), and . (april ) that displays a good prediction of outbreak risk change detection. the results of the third-degree polynomial and arima models in the province revealed an increasing trend with an evidence of turning, demonstrating extensive quarantines has been effective. the general trends of virus infestation in iran and fars province were similar, although a more volatile growth of the infected cases is expected in the province. the results of this study might assist better programming covid- disease prevention and control and gaining sorts of predictive capability would have wide-ranging benefits. a a a a a in december , several pneumonia infected cases were reported in wuhan, china [ , ] . in january , a novel coronavirus ( -ncov) that was later formally named covid- was approved in wuhan [ ] . it was announced that the disease is a severe acute respiratory syndrome coronavirus (sars-cov- ). the virus elevated concerns within china as well as the global community as it was believed to be transmitted from human to human [ ] . initially, china witnessed the largest outbreak in hubei and other nearby provinces. the spread in china was controlled soon thereafter through stringent preventive measures, but other parts of the world (europe, the middle east, and the united states) were increasingly affected by the outbreak through transmission by infected travellers from china. a similar outbreak soon followed in other asian countries [ ] . its global spread to more than countries led to the declaration in mid-march that covid- was a pandemic [ ] . by june , , there were nearly . million cases worldwide, with deaths attributed to covid- [ ] . currently, the united states ( ), brazil ( ) and russia ( ) have the largest number of confirmed cases, whilst the united states ( ), brazil ( ) and uk ( ) have the highest number of casualties, respectively [ , ] . iran with recorded cases and deaths is the most affected country in the middle east (as of june , ) and infected cases are expected to surge in the coming days [ , ] . the outbreak of covid- has disrupted and depressed the world economy, whereas iran is among the most severely affected by massive economic losses, largely compounded by politically motivated sanctions imposed by other governments [ ] . the problem has been exacerbated as no specific medicine is yet realized for covid- disease treatment, though there are a few pre-existing drugs that are being tested, so regions are presently concentrating their efforts on maintaining the infection rate in a level that assists in reducing virus spread [ ] . this has led to most states imposing lockdowns, encouraging social distancing, and restricting the sizes of gatherings to limit transmission [ ] . there is a pressing necessity for scientific communities to aid governments in their efforts to control and prevent transmission of the virus [ ] . during previous virus outbreaks stemming from zika, influenza, west nile, dengue, chikungunya, ebola, marburg, and nipah, geographic information systems (giss) have played significant roles in providing significant insight via risk mapping, spatial forecasting, monitoring spatial distributions of supplies, and providing spatial logistics for management [ ] . in this current situation, risk mapping is critical and may be used to aid governments' need for tracking and management of the disease as it spread in places with the highest risk. sánchez-vizcaíno et al. [ ] used a multi-criteria decision making (mcdm) model to map the risk of rift valley fever in spain. traditional statistical techniques had also been used to detect the risk of an outbreak [ ] . reeves et al. [ ] employed an ecological niche modelling (enm) technique for mapping the transmission risk of mers-cov; the middle eastern name for the coronavirus known as sars-cov- . similar techniques have been in the nyakarahuka et al. [ ] study to map ebola and marburg viruses risks in uganda. they assessed the importance of environmental covariates using the maximum entropy model. more recently, the use of machine learning algorithms (mlas) for mapping the risk of transmission of viruses has been increasing which is due to the demonstrated superior (and more accurate) predictive abilities of the mla models over traditional methods [ ] . jiang et al. [ ] employed three mlas-backward propagation neural network (bpnn), gradient boosting machine (gbm), and random forest (rf)-to map the risk of an outbreak of zika virus. tien bui et al. ( ) compared different mlas-artificial neural network (ann) and support vector machine (svm) with ensemble models including adaboost, bagging, and random subspace-for modelling malaria transmission risk. similarly, gbm, rf, and general additive modelling (gam) were used by carvajal et al. [ ] to model the patterns of dengue transmission in the philippines. mohammadinia et al. [ ] employed geographically weighted regression (gwr), generalized linear model (glm), svm, and ann to develop a forecast map of leptospirosis; gwr and svm produced highly accurate predictions. saba and elsheikh [ ] , also used the nonlinear autoregressive ann model to forecast covid- outbreak. another statistical-based model that recently has been applied to forecast the behaviour of covid- outbreak and death cases is arima in which the forecast process is as a function of time. recently, the significant ability of this model to forecast covid- outbreak in egypt [ ] and coronavirus related deaths in iran [ ] has been reported. benvenuto et al [ ] performed arima model on the johns hopkins epidemiological data and they found that the spread of virus tends to be slightly decreasing. however, ahmar and del val [ ] combined the α-sutte indicator with arima and developed a model to forecast covid- outbreak in spain. their combined model presented more accurate forecast compared to the arima model. the literature shows that very few studies have tried to use gis for analysis of covid- outbreak in human communities. kamel boulos and geraghty [ ] described the use of online and mobile gis for mapping and tracking covid- whilst zhou et al. [ ] revealed the challenges of using gis for sars-cov- big data sources. to our knowledge, there has been no study with a focus on mapping the outbreak risk of the covid- pandemic. the aims of the present study were to analyze the risk factors of coronavirus outbreak and test the svm model for mapping areas with a high risk of human infection with the virus in fars province, iran. in addition, the growth trend of the covid- infestation in fars province was analyzed and compared with the growth rate (gr) of iran and several other countries. the outcome of the present study lays a foundation for better planning and understanding the factors that accelerate the virus spread for use in disease control plans in human communities. the methodology of this research can be used for mapping the outbreak risk of covid- and for detecting the trend of covid- infections in other parts of the world. this study also can aid local authorities in imposing strict social distancing measures in the regions with high outbreak risk. furthermore, this study can be helpful in determining the significant effective factors that influence the covid- outbreak risk. the study area is in the southern part of iran with an area of square kilometres located between ˚ and ˚ n and between ˚ and ˚ e. fars is the fourth largest province in iran ( . % of total area) with a population density of (based on in report). fars province is divided into counties, districts, and cities (fig ) . the multi-phased workflow implemented in this investigation (fig ) is described comprehensively below. a dataset of active cases of covid- in fars was prepared to analyze the relationships between the locations of active cases and the effective factors that may be useful for predicting outbreak risk. the data utilized in this research (s file) was collected on april , from iranian's ministry of health and medical education (imhme: http://ird.behdasht.gov.ir/). choosing the appropriate effective factors to predict the risk of pandemic spread is vital as its quality affects the validity of the results [ ] . since, there have been no previous studies of risk for covid- distribution, the selection of effective factors is a quite challenging task. also, there is no approved universal factors for mapping the outbreak risk of covid- . ongoing research on the pandemic has revealed that local and community-wide transmission of the virus largely happens in public places where the most people are likely to come into contact with largest number of potential carriers of the infection [ ] . wang et al. [ ] indicated that meteorological conditions, such as rapidly warming temperatures in cities around the world resulted in a decline of covid- cases. accordingly, in this research, we selected sixteen most relevant effective factors for the outbreak risk mapping of covid- in fars province of iran, which includes minimum temperature of coldest month (mtcm), maximum temperature of warmest month (mtwm), precipitation in wettest month (pwm), precipitation of driest month (pdm), distance from roads, distance from mosques, distance from hospitals, distance from fuel stations, human footprint, density of cities, distance from bus modelling outbreak risk and infection behavior of coronavirus stations, distance from banks, distance from bakeries, distance from attraction sites, distance from automated teller machines (atms) and density of villages. all the effective factors employed in this research are generated using arcgis . . a few studies have established that variation in temperature would impact the transmission of covid- [ ] . it has also been reported that alteration in temperature would have impacted the sars outbreak, which was caused by the identical type of coronavirus as sars-cov- [ ] . recently, ma et al. [ ] disclosed that surge in temperature and humidity conditions have resulted in the decline of death caused by sars-cov- . thus, climatic factors such as temperature and precipitation can have an impact on the outbreak of sars-cov- . the temperature and precipitation data, namely mtwm, mtcm, pdm and pcm of fars province is acquired from world climatic data (https://www.worldclim.org/). in this study, the mtwm of the fars province ranges from . ˚c to . ˚c (fig ) whereas mtcm ranges between - . ˚c and . ˚c (fig ) . the pwm of the study area varies between mm and mm (fig ) , and also the pdm is presented in fig . the proximity to various public places including roads, mosques, hospitals, fuel stations, bus stations, banks, bakeries, attraction sites, and atms where people come in close contact to each other can also be considered as significant factors that influence the distribution of covid- . the data was acquired from open street map (https://www.openstreetmap.org). the distance from roads ranges from to in the study area (fig ) whereas the distance from mosques varies between and . (fig ) and the distance from fuel stations spans to . (fig ) . the distance from bus stations, banks, bakeries, attraction sites, and atms of fars province have the minimum value of and maximum value of . , . , . , . , and . respectively (figs , ) . since humans are the potential carriers of the covid- , the use of human footprint (hfp) can aid in understanding the terrestrial biomes on which humans have more influence and access [ ] . in this study, hfp of the study area is acquired from the global human footprint dataset. the hfp of fars province ranges from to (fig ) where the minimum value represents the places having least access by humans, and the maximum value refers to those regions having highest human influence and access. the density of population is also considered to be an important factor for the spread of the disease [ , ]. gilbert et al. [ ] revealed that the number of covid- cases was proportional to the population density in africa. accordingly, in this research, density of cities and villages were assessed, and the outcome displays that density of cities in fars province ranges between and . ( fig ) while the density of villages varies from to . (fig ) . the distance from hospitals ranged from to . ( fig ) . the association among the location of covid- active cases and effective factors were evaluated using ridge regression in order to assess the significance of individual effective factor in predicting the outbreak risk [ ] . to our knowledge, no previous study in epidemic outbreak risk mapping has utilized ridge regression in determining the significance of effective factors. however, the ridge regression algorithm has been utilized for modelling purposes in various fields [ ] . it was first given by hoerl and kennard [ ] which exploits l norm of regularization for lessening the model complication and controlling overfitting. ridge regression was also developed to avoid the excessive instability and collinearity problem caused by leastsquare estimator [ ] . the 'caret' package (https://cran.r-project.org/web/packages/caret/ caret.pdf) of r . . was utilized for assessing the variable importance using ridge regression. support vector machine. svm is an extensively exercised mla in diverse fields of research that functions on the principle of statistical learning concept and structural risk minimization given by vapnik [ ] , which is utilized for classification as well as regression intricacies [ , ] . svm has high efficacy in classifying both linearly separable and inseparable data classes [ ] . it utilizes an optimal hyperplane to distinguish linearly divisible data, whereas kernel functions are employed for transforming inseparable data into a higher dimensional space so that it can be easily categorized [ ] . assume a calibration dataset to be (s m , t m ), where m is , , . . ., x; s m refers to the sixteen independent factors; t m denotes and that resembles risk and non-risk classes and x represents the total amount of calibration data. this algorithm tries to obtain an optimal hyperplane for classifying the aforementioned classes by utilizing the distance between them, which can be formulated as follows [ ]: where, kpk denotes the rule of normal hyperplane; a refers to a constant. when lagrangian multiplier (λ m ) and cost function is introduced, the expression can be given as follows [ ]: in case of an inseparable dataset, a slack covariate δ m is added into the previs eq ( ) that is provided as follows [ ] : accordingly eq ( ) can be described as follows [ ]: moreover, svm contains four kernel functions (linear, polynomial, radial basis function: rbf and sigmoid) for making an optimal margin in case of inseparable dataset [ ] . mohammadinia et al. [ ] revealed that rbf kernel type produces high prediction accuracy than other kernel types for epidemic outbreak risk mapping. thus, in this study, rbf is used for creating decision boundaries, and the kernel function is expressed as follows [ ]: where, k(z a , z b ) refers to kernel function and v represents its parameter. analysis of growth rate for active and death cases of covid- . in this study, the growth rate (gr) of active and death cases around the world, iran, and fars province were evaluated using the data acquired from who and imhme between february , and june , for active cases and from march , to june , for death cases. validation of outbreak risk map. the cross-checking of the calibrated model using untouched testing data is vital for determining the scientific robustness of the prediction [ ] . in this research, we utilized roc-auc curve values for the validation of covid- outbreak risk map generated using the svm model. it is a widely utilized validation technique for analyzing the predictive ability of a model [ ] . a model is determined to be perfect, very good, good, moderate and poor if the auc values were . - . , . - . , . - . , . - . and . - . , respectively [ ] . models for infection cases trend. the behavior of the variable infection cases in fars province was captured by a third-degree polynomial or cubic specification while for those of iran the fourth-degree polynomial specifications was found to be more appropriate as follows: where, infection(t) represents the total infected cases in day t and t denotes the days starting from th of february for iran and one week later for fars province. a quadratic specification was examined and based on the fitted model, the cubic form (for fars province) and fourthdegree polynomial (for iran) were selected. in the literature, the cubic form of specification has been applied by aik et al. [ ] to examine the salmonellosis incidence in singapore. we also used an arma model to compare the process generating the variable for iran and fars province. this model includes two processes: autoregressive (ar) and moving average (ma) process. an arma model of order (p,q) can be written as [ ] : where x is the dependent variable and ε is the white noise stochastic error term. in the applied model, x shows the total infected cases and t is the days starting from the first day of happening infection cases. in building a time series model, the data are expected to be stationary [ ] . in other words, the model (eq ) is based on the assumption that the data series are stationary. briefly, a time series process x(t) is stationary if the mean and variance are constant and independent of time and the covariance between x(t) and x(t+s) (x with s period apart) is time-invariant or is dependent only upon the distance between the two time periods considered [ , ] . thus, if a time series have time-varying mean or a time-varying variance or both will be nonstationary. using nonstationary time series for the forecasting purposes has little practical value. if the applied time series data is not stationary, after differencing it d times an stationary time series was obtained. this series is called integrated of order d. after differencing d times, we may apply the arma (p, q) model which is called arima (p, d, q) [ ] . the arima (p,d,q) model is an arma(p,q) that applies d times differencing data. benvenuto et al. [ ] applied an arima model to predict the epidemiological trend of covid- . also, saba and elsheikhb [ ] used this model to forecast the outbreak of covid- in egypt. the analysis of variable importance using ridge regression revealed that distance from bus stations, distance from hospitals, and distance from bakeries have the highest significance whereas distance from atms, distance from attraction sites, distance from fuel stations, distance from mosques, distance from road, mtcm, density of cities and density of villages exhibit moderate importance. the effective factors such as distance from banks, mtwm, hfp, pwm and pdm were the least influential factors (fig ) . the covid- outbreak risk map generated using svm displays that risk of sars-cov- ranges from - . to . (march ) and - . to . (april ) where - . and - . represent the lower risk of sars-cov- outbreak and . and . indicates the regions of fars province which is likely to experience a higher risk of covid- outbreak (fig a and b) . it can be observed from fig b (april ) that shiraz county and its surrounding counties including firouzabad, jahrom, sarvestan, arsanjan, marvdasht, sepidan, abadeh, khorrambid, rostam, larestan and kazeron of fars province has the highest risk of being the epicentre of sars-cov- outbreak. apart from which counties like eghlid, and fasa also lie in the high risk zone. the results of gr of active cases in the world, iran, and fars province are presented in table . percentage of death cases in china was related to february , whereas for iran and fars province it is related to march and may , respectively. table show that age class > years old lie in the highest class of death rate. so, this age class of above years is highly sensitive to covid- . the roc-auc curve cross-validation technique is utilized in this research for validating the covid- outbreak risk map generated by svm. the model achieved an auc value of . and a standard error of . indicating a good predictive accuracy when cross-verified using the remaining % testing dataset collected on march , (fig and table ). when tested with active case locations on march , , the model achieved an increased auc value of . which proves the stable and good forecast precision of the outbreak risk map (fig and table ). also, change detection on april , show that accuracy of the built models is increased to . % (auc = . ) (fig and table ). two tools have been applied to compare the general trend of infection in fars province and iran. the first includes a third-degree (for fars province) and a fourth-degree (for iran) polynomial models that are presented in fig . another quantitative model is an arima model presented in table . fig shows the trend of infection cases in iran and fars province, where predicted values extraordinarily keep pace with the actual values. coefficients of determination () values also indicate that estimated models have significant predictive power. the infection cases are increasing over the selected horizon. the first derivative of the estimated model represents the daily infection cases. based on the daily infection model, there is a turning point for both iran and provincial cases. it was found that the turning point for provincial daily infection is . in other words, after days the decreasing trend in the daily infection is expected. however, the corresponding value for iran is much higher than the provincial one. there are some evidences showing that a turning point in infection is expected. for instance, it has been reported for sars incidence [ ] , hav [ ] , ari [ ] , and for a (h n )v. it is worth noting that a turning point means that after passing the peak, it is expected to show a decreasing trend. in the th day of infection, fars province accounts for around . % of the total iranian cases while its population share is more than % (statistical center of iran, ). regarding the values obtained for turning points and the infection share, up to the present, the measures taken by the provincial government may be considered more effective than those taken in other provinces as a whole. however, it should be taken into consideration that fars province experienced its first infection cases days after qom and tehran, provinces that are considered as starting point for virus outbreak in iran. this might have given the provincial governmental body and the households to take measures to cope with the widespread outbreak. it is worth noting that the comparison of the specified models is more appropriate to investigate the effectiveness of the measures taken by the corresponding health body rather than using it to predict future values. the arima time series models for infection variables of the fars province and iran are presented in table . these models may show the generating process of the variables in time horizon. it is worth noting that in order to have more comparable models, a -day time horizon is selected. this is the period of time that data are available, starting on th of february for iran and one week later for fars province. as shown in table , provincial data are generated by an arima ( , , ) process while arima ( , , ) was found more appropriate for iran's data. regarding the orders for ar and ma processes, the country model shows more complicated behaviour. in addition, the fars data was applied after differencing since it was not stationary; indicating a more explosive process of an increasing trend for fars province compared to those of iran in the following days. the provincial data indicated more volatility which was captured by variance-related variable garch that was not easily captured in the trends as shown in fig . benvenuto et al. [ ] also used an arima model and found that covid- spread tends to reveal a slightly decreasing spread. generally speaking, the diagnostic statistics indicate that the estimated models are acceptable since q-statistics reveal that the residuals are not significantly correlated and the jarque berra statistic supports the normality of residuals at conventional significance level. in addition, all ar and ma roots were found to lie inside the unit circle, indicating that arima process is (covariance) stationary and invertible. there is a great necessity for new robust scientific outcomes that could aid in containing and preventing the covid- pandemic from spreading. the spatial mapping of covid- outbreak risk can aid governments and policy-makers in implementing strict measures in certain regions of a city or a country where the risk of an outbreak is very high. it is, therefore crucial to identify the regions that would have high outbreak risk through predictive modelling with the help of machine learning algorithms (mlas). in recent times, mlas have demonstrated promising results in forecasting the epidemic outbreak risk [ ] . in this research, the svm model showing good forecast accuracy was used for mapping the outbreak risk of covid- . similarly, mohammadinia et al. [ ] revealed that gwr and svm had the highest precision in mapping the occurrence of leptospirosis. ding et al. [ ] employed three mlas including svm, rf and gbm, for mapping the transmission risk assessment of mosquito-borne diseases and disclosed that all three mlas acquired excellent validation outcome. machado et al. [ ] also applied rf, svm and gbm in modelling the porcine epidemic diarrhoea virus and demonstrated % specificity values in case of svm. tien bui et al. [ ] stated that svm achieved an auc value of . in mapping the susceptibility to malaria. the ability to classify inseparable data classes is the greatest benefit of the svm model [ ] . it is among the most precise and robust mla [ ] . svm can be useful and has higher prediction accuracy when it comes to handling a small dataset. however, huang and zhao [ ] demonstrated that svm also yields excellent precision in predictive modelling when a large dataset is utilized. the algorithm has a very low probability of overfitting and is not disproportionately impacted by noisy data [ ] . behzad et al. [ ] revealed that svm had huge capacity in simplification and had enduring forecast accuracy. it should also be noted that the predictive exactness of svm model largely depends on the choice of kernel function [ ] . among the four kernel functions of svm, rbf has been proved to generate high accuracy models [ ] . svm includes diverse kinds of categorization functions which are responsible for assessing overfitting and simplifying data that needs a minor tuning of model parameters [ ] . the significance of each effective factor employed in this research is assessed using ridge regression. since, there is no previous study in covid- that outlines the proper effective factors. the outcome of this research can be very helpful for scientists in experimenting the same and additional effective factors for covid- outbreak risk mapping. the proximity factors including distance from bus stations, distance from hospitals, distance from bakeries were most influential in forecasting the covid- outbreak risk whereas other proximity factors such as distance from atms, distance from attraction sites, distance from fuel stations, distance from mosques and distance from road had the moderate influence which is followed by mtcm, density of cities and density of villages. it should be noted that climatic factors including mtwm, pwm and pdm had the least significance in mapping the outbreak risk. from this, it can be concluded that precipitation factors pwm and pdm are not associated with the transmission of covid- in fars province whereas in case of temperature factors mtcm had moderate influence in mapping covid- outbreak risk but mtwm exhibited a least significance. this outcome reveals that proximity factors had high influence in the transmission of sars-cov- . in addition, the study conducted disclosed that increase in temperature will not decline the sars--cov- cases, although it has been also revealed that increase in temperature and absolute humidity could decrease the death of patients affected by covid- [ ] . the polynomial and arima models were applied to examine the behaviour of infection in fars province and iran. the general trend of infection in iran and fars province are similar while more volatility for provincial cases is expected. the methodology and effective factors used in this research can be adapted in studies investigated in other parts of the world for preventing and controlling the outbreak risk of covid- . mapping of sars-cov- outbreak risk can aid decision-makers in drafting effective policies to minimize the spread of the disease. in this research, gis-based svm was used for mapping the covid- outbreak risk in fars province of iran. sixteen effective factors including mtcm, mtwm, pwm, pdm, distance from roads, distance from mosques, distance from hospitals, distance from fuel stations, human footprint, density of cities, distance from bus modelling outbreak risk and infection behavior of coronavirus stations, distance from banks, distance from bakeries, distance from attraction sites, distance from automated teller machines (atms) and density of villages were selected along with the locations of active cases of sars-cov- . the results of ridge regression revealed that distance from bus stations, distance from hospitals, and distance from bakeries had the highest influence in covid- outbreak risk mapping whereas the climatic factors had the lowest influence. the generated model using svm had a good predictive accuracy of . and . when verified with the locations of active cases during march and march , . however, the weakness of the svm model lies in managing a very large dataset and inferring with the model outcome that is due to the black box nature of the model. the gr average for active cases in fars for a period of days was . , whilst it was . in the country and the world. the iranian government should take restrict preventive measures for controlling the outbreak of sars-cov- in shiraz as a tourism destination and the counties having high risk. based on the results of polynomial and an arima model, the infection behavior is not expected to reveal an explosive process, however; the general trend of infection will last for several months especially in iran as a whole. a more slowly trend is expected in fars province, demonstrating extensive home quarantine and travel and movement restrictions were good strategies for disease control in fars province. the main policy implication is that the infection cases, to some extent, may be controlled using more effective measures. although, the estimated models may be used to predict the infection in following days, however; this contribution is less significant than the other implications derived from them. generally speaking, it is expected to encounter a decreasing trend, however; this may be reversed if the ongoing attempts are slowed down, pointing out the need to keep the measures like quarantine or even to try more restricting attempts. as a policy implication, it is worth noting that the applied models clearly show the extent that the measures taken by the central and provincial governments body have been efficient, allowing them to consider more effective measures. this contribution will be more valuable when the dynamic and the complicated nature of the virus is taken into consideration. several extensions may be recommended for further investigation. it is possible to apply the developed models to examine the behaviour of other related variables including recovered cases and critical cases. if more detailed data is provided, the effectiveness of the location-specific measures deserves to be investigated more deeply. supporting information s file. (xlsx) early transmission dynamics in wuhan, china, of novel coronavirus-infected pneumonia effects of temperature variation and humidity on the death of covid- in wuhan clinical features of patients infected with novel coronavirus in wuhan, china. the lancet a novel coronavirus outbreak of global health concern. the lancet world health organization declares global emergency: a review of the novel coronavirus (covid- ) who characterizes covid- as a pandemic who, b. coronavirus disease covid- and italy: what next? the lancet mapping the incidence of the covid- hotspot in iran-implications for travellers. travel medicine and infectious disease covid- battle during the toughest sanctions against iran chloroquine and hydroxychloroquine in the treatment of covid- with or without diabetes: a systematic search and a narrative review with a special reference to india and other developing countries mass gathering events and reducing further global spread of covid- : a political and public health dilemma. the lancet covid- : challenges to gis with big data. geography and sustainability identification of suitable areas for the occurrence of rift valley fever outbreaks in spain using a multiple criteria decision framework. veterinary microbiology mers-cov geography and ecology in the middle east: analyses of reported camel exposures and a preliminary risk map ecological niche modeling for filoviruses: a risk map for ebola and marburg virus disease outbreaks in uganda understanding spatial variations of malaria in vietnam using remotely sensed data integrated into gis and machine learning classifiers mapping the transmission risk of zika virus using machine learning models machine learning methods reveal the temporal pattern of dengue incidence using meteorological factors in metropolitan manila prediction mapping of human leptospirosis using forecasting the prevalence of covid- outbreak in egypt using nonlinear autoregressive artificial neural networks spatial modelling, risk mapping, change detection, and outbreak trend analysis of coronavirus (covid- ) in iran (days between application of the arima model on the covid- epidemic dataset suttearima: short-term forecasting method, a case: covid- and stock market in spain climate variability and salmonellosis in singapore-a time series analysis applied econometric times series the mcgraw−hill has sars infected the property market? evidence from hong kong hepatitis a incidence, seroprevalence, and vaccination decision among msm in amsterdam, the netherlands a computational approach to investigate patterns of acute respiratory illness dynamics in the regions with distinct seasonal climate transitions mapping the spatial distribution of aedes aegypti and aedes albopictus identifying outbreaks of porcine epidemic diarrhea virus through animal movements and spatial neighborhoods testing a new ensemble model based on svm and random forest in forest fire susceptibility assessment and its mapping in serbia's tara national park prioritization of effective factors in the occurrence of land subsidence and its susceptibility mapping using an svm model and their different kernel functions review on landslide susceptibility mapping using support vector machines. catena comparative study of svms and anns in aquifer water level prediction text categorization with support vector machines: learning with many relevant features association between ambient temperature and covid- infection in cities from china key: cord- -ko wjf authors: omidi, mona; maher, ali; etesaminia, samira title: lessons to be learned from the prevalence of covid- in iran date: - - journal: med j islam repub iran doi: . /mjiri. . sha: doc_id: cord_uid: ko wjf nan corona virus, a pandemic infection ( ) , has involved the global community, especially health policymakers. coronaviruses (cov), a large family of viruses and a subset of the coronaviridae, were first discovered in ( ) and found to cause illnesses ranging from the common cold to more severe diseases such as middle east respiratory syndrome (mers-cov) and severe acute respiratory syndrome (sars-cov) ( ). new coronavirus is perhaps the most ambitious, agile, and aggressive disease in history ( ) . on december , , the who office in china was informed of cases of pneumonia with unknown etiology (unknown cause) in wuhan, hubei province, china ( ). china made several interventions against this epidemic. for example, national authorities searched for active cases in all provinces. the search expanded for additional cases both inside and outside wuhan for active and retroactive cases. accordingly, the human seafood wholesale market closed down in wuhan on january st for environmental sanitation as well as disinfecting measures. also, public education and environmental hygiene was strengthened ( ). in a recent report from china, chest ct scan showed a sensitivity of % for diagnosing covid- , which was superior to rt-pcr ( ). on january , , national ihr focal point (nfp) for republic of korea reported the first case of covid- . the patient was a -year-old female, chinese national who resided in wuhan, hubei province, in china ( ) . the republic of korea responded to this public health epidemic by taking various measures. contact tracing and other epidemiological investigations were done, the government scaled up the national alert level from blue (level ) to yellow (level out of -level national crisis management system), and the health authorities increased the surveillance for pneumonia cases in health facilities nationwide as of january , . moreover, quarantine and screening measures were enhanced for travelers from wuhan at the entry points (poe) ( , ). on january , , the first confirmed cases of covid- acute respiratory diseases were reported in italy; both cases had a travel history to wuhan. then, days after the first report of covid- in italy, the government took important steps to quarantine million people in provinces in the north of the country to prevent the spread of the virus throughout the country ( ). for example, traveling in and out of an area was only possible under certain conditions; people with symptoms of respiratory diseases and fever of . celsius or above were strongly encouraged to stay at home; gatherings were prohibited; all schools, universities, museums, and cultural places, shopping centers, etc. were closed; and all sporting events and competitions were suspended ( ). this epidemic also shocked the italian political leaders, as cities in northern italy were officially quarantined (quarantine at levels) and residents were threatened to quarantine if they tried to break any levels of the quarantine ( ). in iran, on february , , the ministry of health and medical education confirmed covid- cases in qom as the epicenter of the disease ( ). then, due to insufficient information and the lack of awareness about the spread of the virus and not believing in vulnerability, the disease spread rapidly in tehran as a commercial center and in the northern parts of iran because of their tourism and travel attraction. the behavior of the virus is unknown due to its novelty, and given that the information released by china had many shortcomings and was incomprehensible, more research is needed. in iran, covid- spread more rapidly due to the arrival of the persian new year (nowruz). most of health care personnel encountered the illness at levels: low, moderate, and severe. unfortunately, a significant number of nurses and service personnel died of covid- . in addition, iran was not prepared to deal with this epidemic crisis due to the us sanctions, lack of logistics and protective equipment, insufficient disinfecting supplies, lack of specialized beds and internal specialists, and poor primary health care (phc) in cities. the available facilities do not correspond to the increasing prevalence of the disease in the community. measures taken so far include equipping hospitals to accommodate covid- patients, increasing the capacity of hospitals, and taking steps to develop field hospitals.the relationship between levels and based on the health intelligent management system, creating an online screening system, and contact tracing, along with proper handwashing training campaigns have been effective in controlling the spread of the virus. meanwhile, the closure of schools, universities, and public event centers, and most importantly, the creation of an integrated health information database have led to an effective management of the crisis so far. also, during the grassroots movement, a group of citizens have taken impressive steps toward preventing the spread of the disease; for instance, a group of doctors started treating patients online to stop the flood of patients to clinics and hospitals. women can join this movement by sewing masks and donating them to medical centers. also, people can disinfect urban facilities like atms at nights to prevent the spread of this virus. the spread of the virus to other cities can be prevented by actively screening and focusing on nonvirtual and virtual activities and recommending quarantining the entire country. the medical personnel are the most susceptible carriers of the disease in the community, and if not protected, they can spread the virus first to their families and then to the whole community. therefore, investing in the protection of these people and separating them from the public transport is one of the priorities in the fight against this disease outbreak in iran. for this purpose, medical staff can use hotels; moreover, patient safety measures should be improved ( ) . face to face, communication can have a direct impact on the mortality rate of covid- if social distancing is not taken seriously. therefore, it is imperative for all countries to quarantine their epicenter right from the start to prevent the rapid spread of the disease, which will have irreparable consequences. covid- : too little, too late? editorial cultıvatıon of a novel type of common-cold vırus in organ cultures novel coronavirus ( -ncov): situation report- correlation of chest ct and rt-pcr testing in coronavirus disease (covid- ) in china: a report of cases novel coronavirus -republic of korea (ex-china) novel coronavirus ( -ncov): situation report- developing strategies for patient safety implementation: a national study in iran the authors declare that they have no competing interests. key: cord- - a z ryz authors: karatayev, marat; hall, stephen title: establishing and comparing energy security trends in resource-rich exporting nations (russia and the caspian sea region) date: - - journal: resources policy doi: . /j.resourpol. . sha: doc_id: cord_uid: a z ryz abstract in the international arena, it is often the case that in countries which largely depend on foreign resources, energy security, and its key components i.e. security of energy supply, environment, technology, geopolitical and economic factors, is a subject of concern. however, due to the abundance of fossil fuel resources in resource-rich exporting nations, there is a lack of understanding of the risks around energy security and accordingly often a policy vacuum. conceptualising energy security from different geopolitical vantage points will allow future concerns around energy supply security, climate change, and regional economic crises to be evaluated. by using policy documents and developing a time series approach and normalized z-scores for a range of comparable metrics this article compares the energy security performance in six caspian sea countries individually and collectively. the article results show that azerbaijan, iran, kazakhstan made significant progress in energy security since , while energy security indicators in russia, uzbekistan, and turkmenistan regressed. iran has a leading position in energy security performance, while uzbekistan and turkmenistan have the lowest level of the energy security indicators compare to other region countries. this article both contributes a replicable definition of energy security that can be undertaken for other global regions, and begins to incorporate diversification and renewables development to enhance domestic energy security assessment. over the last years, the concept of energy security (es) attracts a strong attention academia, policymakers as well as business. the number of publications on es research is growing year-on-year due to the importance of energy for economic development (ang et al., a, b; azzuni & breyer, a, b) . however, most of the published literature on es deals with resource-poor, energy-importing countries and regions (ec, baltic states, asean, visegrad group, eastern block) and focuses on the resource availability (un, ; iea, ; mi� sík, ) , economic prices (nurdianto and resosudarmo, ) , energy diversity (goldthau and sovacool, ) , environmental impact, climate change, sustainability, nuclear waste management (müller-kraenner, ; mouraviev and koulouri, ) . while the concept of energy security has received less attention in resource-rich countries with high exports, global geopolitical, environmental, and energy transition trends, mean energy security is gaining political importance for resource-rich energy-exporting countries. our contribution here is to establish a replicable energy security framework that responds less to a normative definition of what energy security should be as established by oecd scholars and respond more concretely to the es priorities of constituent nations with a comparative analytical framework. energy security in resource-rich, energy-exporting countries is vulnerable to external shocks which can have profound and multiplier impacts on non-resource sectors, capital formation, environmental programs, technology transfers, and overall economic growth (griffiths, ; nepal and paija, ) . this paper was written during the covid- pandemic which saw an unprecedented oil price shock with prices falling to zero in mid-april on some exchanges (becker, ) . in particular, there is strong interests in es in the caspian sea resource-rich countries, where the abundance of energy resources are the reason of environmental degradation, economic instability and a geopolitical game between china's western expansion and stable export markets in europe (kumar and chatnani, ; wrobel, ) . in recent years the reducing costs of renewable energy technologies mean central asian regions with high wind, solar or biomass potential must contend with a new factor in assessing domestic energy security. under the kyoto protocol, copenhagen and paris agreements, resource-rich energy-producing countries are mandated to reduce carbon emissions and explore alternative methods of energy supplies. in exploring these renewable resources alongside traditional fossil reserves, resource-rich energy-exporting regions face a more complex set of energy security options and may benefit from improved modeling and energy scenario analysis (de miglio et al., ) . in spite of this increased scholarly interest, here have been little comparative regional analyses on es across national contexts, and no replicable statistical framework has yet been developed to assess energy security performance in the caspian sea region. by using published literature, policy documents, and indicator-based approach, this article aims to answer the following questions: how es in this region is established in national policy frameworks? how es can be measured and compared across this region? how has es changed over recent decades, is the concept of es making progress or regressing? this article is structured as follows: section analyses the current socio-economic and energy background of caspian sea countries; section presents the meaning of es in context of caspian sea region, which is important for analysing past, current, and future es trends in study-region; section discusses indicator-based approach with a focus on key aspects of es covered in national es doctrines in resource-rich countries; section presents the empirical finding of es performance in caspian sea region and section provides concluding discussions. the caspian sea basin is composed of russia (rus), iran (irn), and former four soviet countries -azerbaijan (aze), kazakhstan (kaz), uzbekistan (uzb) and turkmenistan (tkm). all these countries except uzbekistan share the common sea coast and the region covers a land area of . million km , . % of the total land area of earth (table ) . the combined population of the region is approximately million people, . % of the world's population (wb, ) . russia had the highest gdp ( . trillion usd), while turkmenistan remains the country with the lowest gdp output ( billion usd). regarding the welfare of the population, russia and kazakhstan demonstrate the highest gdp per capita. the difference between russia and kazakhstan reached a minimum: . usd ( . thousand usd in russia and . thousand in kazakhstan). according to the forecast provided by world bank, gdp per capita in kazakhstan will increase to . thousand dollars in short-term perspectives. in russia, gdp per capita will drop to . thousand dollars (wb, ) . based on the imf definition, caspian sea countries can be classified as resource-rich countries. imf defines a country to be resource-rich when exports of non-renewable natural resources such as oil, gas, coal, minerals, and metals account for more than % of the value of the country's total exports (lashitew et al., ) . in azerbaijan exported . usd billion, the export of non-renewable natural resources was . billion usd or . % of total exports (oec, ). the top exports of azerbaijan were crude petroleum ( . usd billion) and petroleum gas ( . usd billion). according to oec ( ), the share of non-renewable natural resources in total exports accounts for . % (in kazakhstan), . % (in iran), . % (in russia), . % (in turkmenistan) and . % (in uzbekistan). while the region is 'resource-rich' there are differences across constituent nations in resource endowments and stages of economic development which make a comparative es analysis instructive. historically, the first international offshore oil production began in the caspian sea, in azerbaijan's offshore in . between and , about . million tons of oil and . billion cubic meters of gas were produced in azerbaijan's offshore (serikova and zulfugarova, ) . recently, according to bp statistical review, proven oil reserves of the caspian countries are: russia - . billion barrels, iran - . billion barrels, kazakhstan - . billion barrels, azerbaijan - . billion barrels (table ) (bp, ; tofigh and abedian, ) . the region has the second-largest natural gas reserve with . trillion cubic feet, following middle east reserves of . trillion cubic feet. the highest proved natural gas reserves are in russia ( % of global reserves) and iran ( . % of global reserves) (iea, ). kazakhstan and russia have also significant coal reserves. its total recoverable coal reserves were estimated at around . and . million short tons respectively in . after the collapse of the soviet union, one of the ways to overcome the economic difficulties faced by new independent states was the development of the oil and gas industry (kandiyoti, ) . attracting foreign investment mainly in the oil and gas industry made economies of caspian sea countries vulnerable to external shocks. economic growth trends over - demonstrate how caspian sea countries vulnerable to commodity price fluctuations in global markets (fig. ) . in fact, a decrease of oil prices on the global market shows dutch disease syndrome, where fossil resource discovery unbalances the economy towards its exploitation, then in shock conditions, the economy can be left in a worse condition that previously, in all caspian sea resource exporting countries, especially it has been well observed in azerbaijan and kazakhstan (hasanov, ; kutan and wyzan, ) . in azerbaijan, for example, crude oil, and oil products make up over % of national total energy exports, and gas makes up over % (ciarreta and nasirov, ) . during the middle of s in the period of high oil prices, the economy demonstrated . - . % of gdp growth which was the highest in the world (vidadili et al., ) . after decreasing oil prices, azerbaijan's gdp dropped by À . %. the same pattern exists for kazakhstan, russia, and iran. total primary energy consumption is an important indicator of energy security, energy consumption in the caspian sea countries in was . mtoe, % higher than in - (fig. ). final energy consumption has increased slowly since , while the significant energy consumption growth was especially higher in years of the economic boom between - and - . the biggest increases in gross inland consumption of energy between and were recorded in turkmenistan ( . % higher than in ), followed by kazakhstan ( . %), iran ( . %), russia ( . %) and azerbaijan ( %). the average primary energy consumption growth in iran was recorded at about . % per year over the last two decades. according to estimates, the final energy consumption in the region is estimated to increase at an average annual rate of . % in (hasanov et al., ) . this growth is very much higher than the world's average growth rate of . % per year in energy demand over - (iea, . the stable growth can be observed also in electricity consumption especially in iran and turkmenistan. the electricity consumption growth was recorded at about . % per year in iran and . % in turkmenistan (fig. ) . as for the structure of gross electricity consumption, fossil fuels remain the main resources in almost all caspian sea countries. while russia, iran, and turkmenistan are highly natural gas consumers, kazakhstan is mainly a consumer of coal. oil and gas despite significant renewable energy potential including wave and tidal energy potential of the caspian sea, the share of renewable energy sources in the energy mix has been negligible small in all caspian sea countries; it means that dependence on fossil fuels in energy production has remained very high in all caspian countries. energy security is a difficult concept to define and conceptualise due to multidimensional character. however, as stated by cherp and jewell ( ) and vald� es ( ), a well-defined meaning of es is an important prerequisite for analysing past, current, and future es trends. vald� es ( ) claims that most of the studies lack a formal or more concise definition of es, while azzuni & breyer ( a, b) show that most of es definitions are narrow and incomplete, many aspects of es (e.g., location, culture, literacy, cyber security, military, research and development expenditure) are not included. according to azzuni & breyer ( a, b) , there are up to - dimensions of es. some proposed concepts have practical challenges and limitations. valdes ( , p. ) notes that "in any methodology special attention should be devoted to present and discuss the definition … the importance of giving clear and contextualized definition of the concept lies in the identification of threats and risks that will define the indicators choice". furthermore, when considering the concept of es, vald� es ( ) points out that "the definition may also affect the election of the weighting method" (p. ) as well as the method to normalize and aggregate data. we first proceed with the definition utilized by sovacool et al. ( ) and sovacool ( ) and ( b) which has seven 'dimensions' "how to equitably provide available, affordable, reliable, efficient, environmentally benign, proactively governed and socially acceptable energy services to end-users"; these seven dimensions have components by which to measure them. in what follows we develop a hybrid set of components which are more concise, and respond to the various definitions given by the constituent nations of the region. we retain the spirit of the definition of energy security that focuses on availability, affordability, reliability, efficiency, environmental impact, proactive governance and a degree of social acceptance, but within the stated priorities of host countries to work with the following definition suited to resource-rich nations: sufficient level of presence of non-renewable resources of oil, gas, coal, nuclear and electricity first of all for domestic use and then for international export with expected maximum economic and social development benefits, progress towards exploiting low carbon source, pro-active scenario planning, and minimum environmental impact during production, transportation, transformation, and end-use application. it is to the definitions of es offered by each nation in the region that we now turn. in terms of importance es concept for resource-rich countries, only kazakhstan has a published suite of energy and climate change studies linked to nationally modeled scenarios. sarbassov et al. ( ) used markal-times model to show energy-saving potential. used the gis tool to estimate wind, solar and biomass energy potential in kazakhstan. also used a hierarchy model to analyse existing barriers to renewable energy development. ahmad et al. ( ) discussed the potential of the nuclear industry for electricity generation in long-term perspectives. to end-use consumers arising in the process of extracting, processing, transporting, trading and using energy resources". the definition shows the importance of availability and affordability of energy resources to satisfy national energy needs, while generating national income through the export of energy resources. there have been myriad studies focused on russia's energy sector and carbon emissions. mitrova ( ) , pristupa and mol ( ) , proskuryakova and filippov ( ) , evaluated the country's energy system sustainability, with a focus on renewable energy, natural gas, and nuclear power. both tursoy and resatoglu ( ) and sharmina ( ) made carbon emissions reduction and energy efficiency improvement scenarios for russia. bruusgaard ( ) , bogoviz et al. ( ) , ragulina et al. ( ) , bogoviz et al. ( ) used some es indicators to demonstrate historical trends on es performance in russia. bruusgaard ( ) tends to pay attention to external threat and conclusively suggests an interpretation of es from russian perspective where the es is best understood as "a situation in which the country, its citizens, society, state and economy are protected from threats posed to reliable fuel and energy delivery" (p. ). here, the focus is not on resource availability and economic prices but on the threats and risks. furthermore, according to bogoviz et al. ( ) , in russian parliament adopted national energy security doctrine up to (directive n � of december , ), where es is defined as "governmental policy mechanisms and actions to assurance regular energy supply for domestic and international energy markets and protect this energy supply from external and internal threats that can potentially bring serious damages to national economy and energy sector". furthermore, russia's es doctrine seeks mechanisms to guarantee of security energy demand from importing countries. these guarantees should include competitive economic prices for energy resource supply. the es has special importance for russia due to facts that domestic energy consumption is growing, while the export of energy resources is an important part of national income and most of the country's social, economic, and military-technological programs depend on revenues from oil and gas sectors. therefore, the weakening of the competitiveness of russia's energy sector is seen in doctrines as a threat to the economic and political security of the country. in this respect, russia's es doctrine sets long-term targets to increase the availability of resources and get access to modern technologies for resource extraction especially in deep-sea and arctic sea zones. a number of studies have evaluated energy and climate policy under different trajectories in iran. bahrami and abbaszadeh ( ) , najafi et al. ( ) , afsharzade et al. ( ) , khojasteh et al. ( ) analysed renewable energy potential including wave and tidal energy, policy and barriers in iran. other academics (tofigh and abedian, ; barkhordari and fattahi, ; katal & fazelpour, ) made a comprehensive analysis of energy prices and energy efficiency potential in iran. according to fazelpour et al. ( ) , es in iran can be regarded as "national economic model, which is able to satisfy the needs of the economy with available, affordable and acceptable energy resources at any time to counteract the negative impact of internal and external threats, and in the case of the impact of these threats to minimise the damage from this impact". this definition of es shows that process of management of the national economic module involves going through evaluation of the current situation in the energy sector, identification external and internal threats affecting the es, analysis the possible consequences of these threats and development measures for prevention and overcoming these threats. the most important areas highlighted in national doctrine are market regulation, a transformation of the electric power industry, and sustainable use of energy resources. as cases of russia and kazakhstan, the security of external energy demand is also a core of iran's energy policy as the economy is largely depends in export of energy resources. the national economic vision "iran " stated that "using country's energy rich potential, first of all, for country economic needs, at the same time, for export needs to other countries for the purpose to guarantee additional national income". some recent works (ciarreta and nasirov, ; vidadili et al., ) ) . these programs reflect four aspects of es. first, es is understood as a complex issue, where the main indicator of es is the sufficiency and availability of primary energy resources for the needs of the country's economy. secondly, es requires the availability of technical equipment for the utilization of primary energy into final energy. third, availability and sufficiency of transportation infrastructure for each type of energy including primary and final energy. lastly, es requires the environmental acceptability of various types and forms of energy during the extraction, conversion, transportation, utilization, and consumption. these programs aim to develop efficient and environmentally friendly energy technologies and increase the use of renewable energy sources as stated in concept "to satisfy current and future national energy demand". energy security in uzbekistan and turkmenistan like in the case of russia and kazakhstan needs to be understood in the context of concerns of availability of resource and external energy demand. an additional important feature of uzbekistan and turkmenistan's es concept is water-energy nexus approach due to the high water problem in both countries. according to energy security programme for - (directive n � of may , ) national es is defined as "national control of energy production, diversification of fuel and energy resources, the involvement of renewable energy sources in the national energy mix, and broad cooperation with neighboring countries in the field of sustainable water use". here is the place to characterize these definitions in table , simple tick boxes for 'protection from external threats' 'ensuring export capacity' 'ensuring domestic sufficiency' 'ensuring domestic affordability' 'diversifying domestic sources' 'planning for an energy transition'. inconsistent conceptual definitions on energy security go hand in hand with a lack of an accepted set of indicators and unifying methodology for energy security assessment. the above review has proposed a definition by sovacool et al. ( ) and has reflected this against the inconsistent definitions used by nations constituting the region. below we explore how others in the field draw metrics from various es definitions and then use in country definitions cited above and the wide debate to create a framework we argue is more suited to the priorities of the regional actors, and one that is easily replicable. there has been considerable debate as to how es index should be constructed and how indicators should be selected and calculated with using different normalization, weighting and aggregation procedures, as "the way in which indicators are selected and constructed affects the evaluation in a significant way" (valdes, p. , ) . meanwhile, indicator-based research is often a preferred quantitative method used for investigation energy security in different geographical regions and different periods. however, there is no universal agreement on the number of indicators to measure energy security. instead, it is often investigated using a set of indicators that characterize the various dimensions mainly a's dimensions -availability, applicability, affordability, and acceptability (kruyt et al., ; ren and sovacool, ; yao and chang, ; tongsopit et al., ; zaman and brudermann, ) . some academics proposed more than a's dimensions. both von hippel et al. ( ) and sovacool ( ) works have made a huge contribution to energy security concepts and its measurement methodologies proposing 's dimensional framework i.e. availability, affordability, efficiency, sustainability, and governance. similarly, bellos ( ) proposed the fifth a's to a's energy security concept, namely adaptability. here adaptability explained by bellos ( ) as the existence of adaptive programs and measures within national energy systems. in addition to concepts by von hippel et al. ( ) and sovacool ( ) , chuang and ma ( ) shared their views on vulnerability and dependence dimensions of energy security. in general, azzuni and breyer ( b) applied a -dimensional framework for assessing energy security in the context of new technology implication. in terms of indicators for assessing energy security, its numbers are also different. vivoda ( ) proposed dimensions and indicators. according to sharifuddin ( ) , energy security can be measured by indicators. in contrast to sharifuddin ( ) , who focused on five aspects of energy security i.e. availability, stability, affordability, efficiency, and environmental impact, wec ( ) proposed indicators. augutis's ideas on a number of indicators based on technical, economic, and socio-political systems and includes indicators (augutis et al., ; narula et al. ( ) measured energy security through indicators related to availability, acceptability, affordability, and efficiency dimensions. martchamadol & kumar ( ) works greatly focuses upon the economic aspect of energy security which had proposed indicators. zhang et al. ( ) applied a five-dimensional framework with energy security indicators, while ang et al. ( b) proposed three dimensions and used indicators. it has shown in (sovacool, ; sheinbaum-pardo et al., ; anwar, ; chung et al., ) that a number of indicators might vary from to . according to b€ ohringer and bortolamedi ( ) and vald� es ( ), indicator-based research method has both advantages and disadvantages. the advantages of the indicator-based methods are that it can be easily used in country self-assessment, scenario analysis, cross-country comparisons, ranking, and tracking progress. regarding the disadvantages of using indicators as a research method, firstly as stated by vald� es ( , p. ) "that individual indicators as the level of energy independence do not tell us very much about energy security levels of national economies". vald� es ( , p. ) concluded that "a more consistent approach is needed to make available indicators useful to design, implement and assess energy policies". b€ ohringer and bortolamedi ( ) highlighted that most of the energy security indicators are supply-oriented, thus, ignoring the demand-side aspect of energy security, economic cost, and external shocks. furthermore, according to matsumoto and shiraki ( ) , it seems challenging to develop a basket of indicators that will be applicable to all countries, primarily because there is not a definition of energy security which is clearly accepted by all and secondly because each country has a different endowment of energy resources, different economic growth, climate conditions, demographic indicators, priorities, and geopolitical position (radovanovi� c et al., ) . this article proposes that some of energy security indicators used by many academics and shown in detailed review (ang et al., a; azzuni and breyer, a) are also suitable for assessing energy security in resource-rich countries. for example, the indicators related to the physical existence of conventional hydrocarbon resources and renewable resources can be applied in resource-rich countries alongside environmental indicators such as energy-related carbon emissions. this type of indicators is reflected in national es doctrines of the caspian sea region. thus, this article develops an indicator-based approach with a focus on key aspects of es covered in national es doctrines in resource-rich countries. in this framework 'resource & dependency' reflects the quantitative level of domestic resource existence for national needs and international exports. it is also represented by the quantitative level of consumption of oil, gas, coal, nuclear and renewable energy resources. the proposed indicators are shown in table . 'intensity & sustainability' covers the capacity to improve existing energy system or create new system considering technological trends. it also captures energy-related carbon emissions, water consumption during energy production, transportation and use, flaring gas. 'cost & poverty' measures a final cost for all energy users in the residential and industrial sectors, prices for gasoline, diesel fuel, liquefied petroleum gas as well as energy poverty measured in percentage of the population have little or no access to electricity. as stated before, the measurement, analysis, and monitoring of es in resource-rich energy-exporting is critical for economic development and mapping sustainable energy transitions. for data collection, the study used data provided by different es in iran can be regarded as "national economic model, which is able to satisfy the needs of the economy with available, affordable and acceptable energy resources at any time to counteract the negative impact of internal and external threats, and in the case of the impact of these threats to minimise the damage from this impact". national economic vision "iran " (directive n � of may , ) es understood as "using country's energy rich potential, first of all, for country economic needs, at the same time, for export needs to other countries for purpose to guarantee additional national income". es is defined as "governmental policy mechanisms and actions to assurance regular energy supply for domestic and international energy markets and protect this energy supply from external and internal threats that can potentially bring serious damages to national economy and energy sector". for data calculation, the study applied z-score approach which has been used in a number of previous energy security studies with different sets of indicators at different countries, economic blocs and regions (e.g., brown and sovacool, ; sovacool and brown, ; brown et al., ; bogoviz et al., ; ragulina et al., ; bogoviz et al., ) . between and , resource & dependency indicators have improved in all caspian sea countries. the greatest improvement in resource & dependency indicators occurred in azerbaijan. azerbaijan has improved indicators on the availability of oil and gas resources, primary energy production and energy import dependency. according to ciarreta and nasirov ( ) , azerbaijan's proven gas reserves are estimated at about . trillion cubic feet, and the potential for changes is expected to be between . and . trillion cubic feet. furthermore, azerbaijan has turned from an energy-importing into an energy-exporting country. in , azerbaijan's energy import dependency was . thousand tonnes, while in it was À . (iea, ). apart from azerbaijan, the greatest improvements in resource & dependency indicators occurred in kazakhstan. the energy security performance in kazakhstan in relation to proven fossil fuel reserves (oil and gas) and energy import dependency was higher in than in . kazakhstan has almost doubled primary energy production and energy import dependency enhanced from À . in to À . in (iea, ) . russia also demonstrated an improvement in proven oil reserves, although indicators for gas and coal have deteriorated, but not significantly. after the collapsing soviet union, russia discovered new oil-and-gas fields. the average amount of deposits is , thousand million barrels as regards recoverable oil reserves, and . trillion cubic feet (iea, ). the largest new oil deposit is nertsetinskoye filed, located in the east european plain, which is estimated at . million tons of recoverable oil reserves and verkhneicherskoye field, located in the eastern siberia, with recoverable oil reserves of . million tons and . billion cubic meters of gas. the presence and development of new fossil fuel reserves allowed russia to improve energy import dependency status from À . in to À . in (iea, ). iran showed progress on the availability of fossil fuel reserves especially for gas and oil but the country worsened its position on energy import dependency from À . in to À . thousand tones in due to an increase in domestic energy consumption (iea, ). the resource reserves include about billion barrels of crude oil, billion barrels of condensate and billion barrels equivalent of natural gas (iea, ). uzbekistan and turkmenistan were also able to improve its resource & dependency indicators, uzbekistan has turned from an energy-importing into an energy-exporting country, . in and - . in . turkmenistan discovered new natural gas reserves at the galkynysh and halkabat sites in eastern turkmenistan. these two sites have an estimated total natural gas reserve of . trillion cubic meters. in , russia with coefficient . was the most resource-rich energy independent state among caspian sea countries (table ), followed by iran ( . ) and kazakhstan ( . ). uzbekistan and azerbaijan had the worst resource indicators in , - . and À . , respectively (fig. ) . in , russia and iran remain the most resource wealthy and energy independent states with a coefficient of . and . , respectively ( (fig. ) . intensity & sustainability represents environmental and safety dimension of energy security. this article chooses co emissions, nox emissions, grid efficiency, energy use per capita, freshwater usage, and flaring gas as main indicators. between and , in azerbaijan, kazakhstan, russia, and uzbekistan the average score of co emissions was lower than at the beginning of s, mostly due to a sluggish economy as a result of collapsing the soviet union. co emissions in azerbaijan, kazakhstan, russia, and uzbekistan accounted for , in and , kilotonnes in . however, indicators demonstrate that the environmental situation has worsened in turkmenistan and iran since . in fact, the co emissions in iran increased from . in to . kilotonnes in (iea, ). as with efficiency, between and , azerbaijan, uzbekistan, kazakhstan, and turkmenistan have the highest energy losses, with the average ratios at - % due to geographical conditions and poor efficiency of existing power generation and transmission technologies. furthermore, kazakhstan's energy consumption per capita is about . , which is higher than that of oecd countries ( . usd per kg oil equivalent). due to coal energy dominated the primary energy field, the effectiveness of plans and strategies is low. coal, which accounts for more than % of electricity generation in kazakhstan, is mostly combusted in power plants that are more than - years old. turkmenistan consumes on average . of total energy per capita in and . in (iea, . turkmenistan similar to kazakhstan has a large number of inefficient production facilities that remained not renovated after collapsing the soviet union. most of these facilities were constructed in the s. in iran, energy intensity is % higher than the global average consumption (afsharzade et al., ) . iran's economy is highly energy intensive, which along with the low energy prices has resulted in over-consumption of energy and low efficiency (afsharzade et al., ) . in the case of russia, the energy intensity indicator has slightly improved since , however, this level of energy intensity is still high compare to oead countries. at the same time, significant energy saving potential exists (wb, ) . in , iran was the most energy efficient and sustainable country with a coefficient of . (table ). due to the nature of the economy, russia and kazakhstan had the worst energy efficient indicators, À . and À . , respectively. in , iran worsened energy intensity and sustainability indicators, however, the country remains in better rank compare to other caspian sea countries (table ) . the energy security performance in the caspian sea region in relation to energy poverty indicator, all caspian sea countries demonstrated an improvement. caspian sea countries have million people, while according to official statistics, the population share without access to electricity is less than % (wb, ). azerbaijan has reduced energy poverty from . in to . % in , kazakhstan -from . in to . % in . regarding energy prices, the increase in electricity prices for industry and household sectors has been observed in all caspian sea countries, while electricity prices are still lover international average in all caspian sea countries. the energy security performance in the caspian sea region in relation to price for gasoline, diesel fuel, liquefied petroleum gas has become worse. kazakhstan has experienced a rise in the price of both gasoline and diesel fuel, because of unexpectedly high demand for gasoline and diesel fuel in russia itself. kazakhstan is largely depending on gasoline and diesel fuel from russia. four key russian oil companies -rosneft, gazprom neft, lukoil and tatneftexport on average . metric tons of high-octane kerosene per year to kazakhstan, meanwhile, three kazakhstani refineries (pavlodar, atyrau, and chimkent) produce around . metric tons of fuel per year (iea, ). in contrast, the total domestic demand in kazakhstan is about . metric tons. the same situation can be observed in azerbaijan, where baku oil refinery with production approximately . metric tons of gasoline does not satisfy the domestic demand, the significant amount of fuel products come from russia. in , russia and kazakhstan were the most energy price secure country ( . and . ), followed by iran ( . ). in , iran and kazakhstan remain the most economically secure states, . and . , while turkmenistan and uzbekistan had the worst indicators (table ) . regarding alternative energy supply, renewable energy indicators demonstrated improvement in azerbaijan, kazakhstan, and uzbekistan. kazakhstan increased renewable energy supply in total final energy consumption from . in to . % in , azerbaijanfrom . in to . % in , uzbekistanfrom . in to . % in . overall, the potential of renewable in all countries in the caspian region is high. for kazakhstan, the estimated potential of wind energy is about gw (ren , ). kazakhstan receives - h of sunlight per year, which equals - kw per m annually (ren , ). kazakhstan has set a target of raising the share of renewable resources in electricity production from % by to % by (koshim et al., ) . in azerbaijan, the figures are - kwh per m (vidadili et al., ) . the technical potential for wind electricity generation was estimated at approximately . mw (ren , ). azerbaijan aims to increase the share of res in the total energy sector by % at and share of res in the total final energy consumption by . % in with mw installed capacity of renewable-based generation equipment in (vidadili et al., ) . for iran, the amount of actual solar radiation hours in the country exceeds h per year, the technical potential of solar electricity was estimated to be . twe (najafi et al., ) . wind energy density was reported for iran is w per m (tofigh and abedian, ) , the technical potential for wind electricity generation was estimated at approximately . mw (bahrami and abbaszadeh, ) , for biomass pj (tofigh and abedian, ) . the iranian renewable energy roadmap has a renewable energy target providing - gw to total power generating capacity each year through (khojasteh et al., ; tofigh and abedian, ) . in the case of russia, the total technical bioenergy potential is estimated at . pj (namsaraev et al., ) . despite huge renewable energy potential, this potential is not fully used due to a number of specific barriers that resource-rich countries are facing so far (koshim et al., ; . in general, energy security index shows that azerbaijan, iran, kazakhstan have improved energy security since (table , fig. ) . according to obtained data, iran has made progress improving its energy security by . points for the studied period of - and this country has a leading position in energy security index, caused by availability of fossil fuel resources, cheap energy prices, and high level of access to energy services. however, iran performed poorly on intensity & sustainability dimension of energy security (table ) . russia and kazakhstan are more similar in their levels of energy security, with the overall energy security index being around . and . . both these countries have best performance on resource & dependency indicators, however, russia showed poor performance on the cost & poverty dimension of the energy security (table ). in , azerbaijan had a negative energy security coefficient, À . . in , azerbaijan improved its indicators with a score . . uzbekistan has the lowest level of energy security indicators. in terms of availability, uzbekistan has significant natural gas reserves in the caspian sea region, while the country's performance on intensity & sustainability and cost & poverty indicators of energy security is low. the key energy security issues in uzbekistan and turkmenistan are associated with high energy prices, high level of carbon emissions, the highest energy intensity among caspian sea countries. es is considered as a complex multidimensional issue in both importing and exporting countries. however, the view on es is different from country to country. some countries (kazakhstan, russia) see es as a means of availability and affordability of energy resources for social and economic prosperity, and others (azerbaijan and iran) as a technology and infrastructure opportunities for providing economic development and achieving geopolitical goals. es in uzbekistan and turkmenistan needs to be understood in the context of the environmental dimension. based on elements of es reflected in policy documents energy security in the context of resource-rich energy-exporting countries of caspian sea region can be defined as sufficient level of presence of non-renewable resources of oil, gas, coal, nuclear and electricity first of all for domestic use and then for international export with expected maximum economic and social development benefits, progress towards exploiting low carbon source, pro-active scenario planning, and minimum environmental impact during production, transportation, transformation, and end-use application. the proposed definition is broad and has similarities with definitions provided in (e.g., yao and chang, ) . yao and chang ( , p. ) suggested that national es in whatever importing or exporting countries is based on "affordable energy resources with an adequate amount of fossil fuels, nuclear energy, and renewable resources, technologies applicable to energy harnessing and utilization, and, at the same time, addresses social and environmental concerns". according to yao and chang ( ) , the key elements of es include energy resource availability (fossil fuel and renewables), energy production, energy transportation and demand, energy consumption, energy use efficiency and technologies, energy prices, and energy-related environmental pollution. the assessment of es in caspian sea countries has been conducted by using individual indicators to quantitatively measure three dimensions of energy security: resources & dependency, intensity & sustainability, cost & poverty. these dimensions reflected in the definition of es for resource-rich energy-exporting countries. based on the analysis, between and , the caspian sea countries experience a stable rise in the availability of all fossil fuel reserves except coal resources and res in total energy production and consumption. all caspian countries rely on fossil fuels to a great extent for their electricity generation and final energy consumption, while renewable energy potential is largely unused. despite the fact that all caspian countries are provided with fossil fuel sources, all these countries committed to the transition to low-carb energy systems (table ). the renewable energy targets are included in a number of strategic national documents. all caspian countries adopted national climate and energy targets, however, as it can be seen now, azerbaijan and russia failed to achieve its res targets, the current contribution of res including a hydro project in azerbaijan is . % and in russia is . % (jan., ), while countries' targets are % and . % by , respectively. the cost of electricity production in azerbaijan and russia based on renewable energy sources is still high. the core requirement for the growth of res in all caspian sea countries is extensive government involvement in the promotion of renewable energy technologies. the market financing of res projects like in eu countries is still impossible. there is a continued need to support scientific and technological developments and create conditions for the formation of an accessible and non-barrier res market taking into account the countries' domestic priorities. this is as much a factor of energy security as it is climate mitigation action and with the volatile markets for hydrocarbons exposing resource-rich nations to such volatile financial risks, building and maximizing renewables capacity utilizing export revenues during high price periods would contribute strongly to future energy security and domestic resilience. in terms of limitations, in our opinion, this research can be advanced in a number of ways. we indicated that using the z-score approach does not provide information on the relative importance of each component of the developed index. the role of each indicator to general energy security performance might be examined in future studies by applying the analytic hierarchy process (ahp). the ahp is both quantitative and qualitative analysis methodology that uses to order and rank the importance of each indicator and has the potential to assist decisionmakers in making choices (vaidya & kumar, ; brudermann et al., ) . furthermore, the study focuses on russia and the caspian sea region, however a comparison of results obtained from other resource-rich energy-exporting countries will provide additional insight, since climate change and energy security are nowadays global agenda. energy security score change furthermore, some problems associated with es, for example, the energy pricing model in the industry and household sectors have to be explored much further to be adequately rigorous. funding was received for this work. all of the sources of funding for the work described in this publication are acknowledged below: no conflict of interest exists. renewable energy 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response to that has resulted in any changes in their seizure control status. we also investigated factors potentially associated with the perceptions of difficulty in obtaining their drugs (e.g., polytherapy vs. monotherapy, taking imported drugs, and seizure status worsening). methods: . what has been your experience on obtaining your antiseizure medications in the past four weeks (compared to before)? . have you experienced any changes in your seizure control status in the past four weeks? results: we included patients ( male and female patients). in response to the question “have you had any difficulties in the past weeks to obtain your drugs?”, people ( %) expressed hardship obtaining their drugs. in response to the question “how has been your seizure control status compared with before?”, six people ( %) expressed worsening of their seizure control status in the past weeks. none of the patients reported symptoms of coronavirus infection. conclusion: about one‐third of patients with epilepsy expressed significant hardship obtaining their drugs after the intensification of the covid‐ outbreak in iran. the current covid‐ pandemic could be considered as a major shock to a nation that has already been under significant pressure (i.e., iran). epilepsy is a common chronic neurological disorder. the mainstay of treatment in people with epilepsy (pwe) is antiseizure medication (asm) therapy. daily medication regimen with asm(s) is necessary for pwe and non-adherence to this treatment strategy may have serious consequences (e.g., status epilepticus and death). recently, the world has been experiencing a catastrophic phenomenon; a pandemic of coronavirus disease (covid- ) that is caused by sars-cov . this virus has a high potential for transmission and implementation of social distancing measures has been advocated in almost all countries to control the outbreak. iran reported its first confirmed cases of sars-cov infection on february . as of april there were , covid- deaths with more than , confirmed infections in iran. strict quarantine measures have not been implemented in response to this outbreak in iran; however, the government's actions included cancellation of all public events, closure of schools, and shopping centres, and banning of festival celebrations. in addition, people have been encouraged by the authorities and the media to stay home and cancel all unnecessary travels. this deadly outbreak has created a lot of anxiety among the people, has disrupted many businesses, and has put the healthcare system under a significant hardship. in addition, the healthcare system in iran was already under pressure due to reimposition and intensification of the economic sanctions on iran by the usa. the aim of the current study was to investigate the effects of covid- pandemic on the patients' perceptions of hardship in obtaining their asms and if this pandemic and the social restrictions in response to that has resulted in any changes in their seizure control status. we also investigated factors potentially associated with the perceptions of difficulty in obtaining their asms (e.g., polytherapy vs. monotherapy with asms, taking imported asms, and seizure status worsening). we surveyed a random sample of pwe, who were registered in our database at shiraz epilepsy center, iran, on their perceptions on two issues: . what has been your experience on obtaining your antiseizure medications in the past four weeks (compared to before)? . have you experienced any changes in your seizure control status in the past four weeks? in a phone call interview to randomly selected patients on march - , , we tried to obtain the following information if patients agreed to participate and answer the questions (consented orally): age, sex, when was your last seizure, what are your drug(s), have you had any this article is protected by copyright. all rights reserved difficulties in the past weeks to obtain your drugs, how is your seizure control status compared with before, have you been staying home due to this outbreak, and have you been infected with this coronavirus? (table ) . we retrieved their demographic and clinical data from our database. we performed univariate analyses using fisher's exact test for the statistical analyses of the potential association between the perceptions of difficulty in obtaining asms and polytherapy vs. monotherapy with asms, taking imported asms, and seizure status worsening. a p value less than . was considered as significant. shiraz university of medical sciences review board approved this study. role of the funding source: shiraz university of medical sciences had no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. we included patients in this study ( male and female patients). their mean age (± standard deviation) was (± ) years (range: to years) and their age at diagnosis was (± ) years (range: to years). all included participants were diagnosed with epilepsy before march . forty-eight people had focal epilepsy syndromes, persons had idiopathic generalized epilepsies, patients had symptomatic (structural-metabolic) generalized epilepsies, and four people had unclassified epilepsies. forty-nine patients were seizure-free for more than one year and people reported having one or more seizures in the past months. forty-one patients were taking one asm and people were on polytherapy with two or more asms. in people, the drug regimen included one or more imported asms, while the rest of the patients were on iranian made drugs. fifty-three people have strictly observed the "stay home" advice in the past weeks (table ) . in response to the question "have you had any difficulties in the past weeks to obtain your drugs?", people ( %) expressed hardship obtaining their drugs (table ). in response to the question "how has been your seizure control status compared with before?", six people ( %) expressed worsening of their seizure control status in the past weeks. none of the patients reported symptoms of coronavirus infection (and none was tested for the infection). table shows factors potentially associated with experiencing difficulty in obtaining asms among the participants. this article is protected by copyright. all rights reserved in this study, we observed that about one-third of pwe expressed significant hardship obtaining their drugs during the past four weeks and after the intensification of the covid- outbreak in iran. more importantly, % of the patients expressed worsening of their seizure control status in the past weeks. seizure control status showed a trend to be worse among those who experienced difficulty obtaining their medicine. in a similar study of patients with epilepsy during the sars (severe acute respiratory syndrome) outbreak in in taiwan, % of the people did not receive their medication due to loss of contact with their healthcare providers; % of the patients suffered seizure status worsening during the outbreak (including two patients with status epilepticus). therefore, it seems that history repeats itself and we should learn to be prepared for any similar circumstances in the future. the observed difficulty obtaining drugs in pwe in the current study and also in the previous outbreak of sars in could have multiple reasons; strict quarantine measures in response to the outbreak, financial difficulties due to loss of employment, and disruption in production and distribution of drugs are some of these potential reasons. experiencing hardship obtaining drugs in people with any chronic medical condition, including epilepsy, creates a lot of anxiety for patients, their caregivers, and their healthcare providers, and may put the lives and well-being of the patients at great risk. , in addition, stress by itself is a common seizure trigger reported by pwe. we observed a similar scenario a couple of years ago and after reimposition and intensification of the economic sanctions on iran in . back then, % of the patients expressed significant difficulty and frustration obtaining their drugs and % perceived breakthrough seizures or worsening of their seizures after reimposition of the economic sanctions. therefore, the current outbreak has increased hardship on the people, who were already experiencing significant difficulties, and the current covid- pandemic could be considered as a major shock to a nation that has already been under significant pressure. since none of our study participants contracted covid- , we cannot comment on the potential direct effects of sars-cov infection on patients with epilepsy. however, neurotropic and neuroinvasive capabilities of coronaviruses have been described in humans and coronavirus infections have been associated with neurological manifestations including seizures and change in mental status. some patients with covid- may have nonspecific neurological symptoms, such as confusion and headache and a few may show more specific neurological manifestations, such as seizures. this article is protected by copyright. all rights reserved this study has some limitations including its self-report design. this is a study with a modest objective and a questionnaire that addressed specific issues (not a comprehensive survey since we evaluated a limited number of factors; for example, we did not assess their anxiety/stress). moreover, patients did not routinely keep a seizure journal (diary) and the changes in their seizure frequency were based on their recall and estimate (the seizure control information was only qualitative). reasons for uncontrolled seizures in adults; the impact of pseudointractability the epidemiology and pathogenesis of coronavirus disease (covid- ) outbreak impacts of the international economic sanctions on iranian patients with epilepsy the impact of sars on epilepsy: the experience of drug withdrawal in epileptic patients how economic sanctions compromise cancer care in iran drug adherence of patients with epilepsy in iran: the effects of the international economic sanctions self-perception of seizure precipitants and their relation to anxiety level, depression, and health locus of control in epilepsy neurological manifestations of hospitalized patients with covid- in wuhan, china: a retrospective case series study we thank shiraz university of medical sciences for supporting this study. research data are not shared. this article is protected by copyright. all rights reserved key: cord- -fgtatt authors: ghaffarzadegan, navid; rahmandad, hazhir title: simulation‐based estimation of the early spread of covid‐ in iran: actual versus confirmed cases date: - - journal: syst dyn rev doi: . /sdr. sha: doc_id: cord_uid: fgtatt understanding the state of the covid‐ pandemic relies on infection and mortality data. yet official data may underestimate the actual cases due to limited symptoms and testing capacity. we offer a simulation‐based approach which combines various sources of data to estimate the magnitude of outbreak. early in the epidemic we applied the method to iran's case, an epicenter of the pandemic in winter . estimates using data up to march th, , point to , ( % ui: k, . m) cumulative cases and , ( % ui: . k, . k) total deaths, numbers an order of magnitude higher than official statistics. our projections suggest that absent strong sustaining of contact reductions the epidemic may resurface. we also use data and studies from the succeeding months to reflect on the quality of original estimates. our proposed approach can be used for similar cases elsewhere to provide a more accurate, early, estimate of outbreak state. © system dynamics society the novel coronavirus (sars-cov- ), the pathogen that causes covid- infection, is exposing the world to one of its largest global health challenges of recent decades. from public understanding to policy choices, much depends on the data about the epidemics spread and models that integrate such data into actionable policies (kaplan et al., ; thompson et al., ) . yet the official data are highly uncertain, with large variations in quality depending on the country reporting it, and regularly offering lower bounds that have unknown error bounds compared to the reality on the ground. other sources of data, often based on smaller samples, travel screening, and anecdotal evidence may offer relevant hints, but they are not easily generalized or combined with official data. the current paper focuses on using a standard dynamic epidemiological model as a tool for incorporating various sources of data into a unified estimation of the actual trajectory of disease, applying the method to covid- outbreak in iran. our focus is on how well one can realistically estimate the magnitude of the epidemic in early stages when disease parameters are uncertain, data are limited, and projections are highly volatile. current information (as of may , ) point to the spread of covid- starting from a food market in wuhan china in mid-november . the epidemic initially spread mostly in china but has become a global pandemic by may with over million official cases and thousand deaths (worldmeters, ) . the situation may also be worse than official statistics portray. for example, despite a massive screening and response campaign in china, li and colleagues estimate that % of early cases in china were undocumented . the situation in iran, another early epicenter, is instructive. the first official cases were reported on february th, , in the city of qom (wikipedia, ). yet, later reports suggested the disease was likely circulating in iran as early as january (iran international, ) . thus from february th on the spread of disease was very rapid according to official statistics. by march th some , cases and , deaths were recorded. the question in the minds of policy makers and public was: how far will this epidemic go and what policies should be put in place to control and mitigate the risks? the answers heavily depend on understanding the true magnitude of the epidemic. any under-estimation is worrisome, but early in the exponential growth phase of an epidemic such errors could be extremely costly as those estimates drive the mobilization of public health resources and government responses. the risk of under-estimation is partly driven by the characteristics of the disease such as a potentially large population of unrecognized patients with mild symptoms (at least % of the cases have symptoms not very different from common cold or flu) (novel coronavirus pneumonia emergency response epidemiology, ). as a result no consensus also exists on other parameters of the disease, such as fatality rate (fauci et al., ; wu and mcgoogan, ) . moreover, the country-specific variations in measurement and reporting may exceed those due to the nature of the disease. to illustrate, in the next section we provide a quick survey of various early clues related to the magnitude of epidemic in iran, which we then build on in our analysis. there have been a few clues from iran which may inform efforts to estimate the true cases. first is the number of cases identified among travelers arriving in other countries from iran. screening of passengers from high-risk countries in airports is more reliable than most country-level screening statistics. one study in pre-print estimated , total cases of infected individuals in iran by february (tuite et al., ) . the method relied on estimation of cases in the whole country based on three diagnosed cases of infection upon individuals' arrival from iran in various international airports and the likelihood of such an incident given approximately daily outbound passengers from iran during those early days (fraser et al., ). this number was two orders of magnitude larger than official statistics at the time. later reports on the number of infected travelers from iran rose rapidly, to cases by february (radiofarda, ). an article in the atlantic, offered a series of back-of-the-envelope calculations which, with strong simplifying assumptions, estimated million accumulated cases of infected individuals by march th (wood, ) . one may expect the death statistics to be more reliable. but test kits for identifying have been in short supply, and post-mortem testing may not have been a priority of officials in iran. on february th a member of iran's parliament reported deaths only in qom, a city of . million (wikipedia, ) . several reports of government officials contracting the disease have also been released, including reports on infection of member of the iranian parliament (a body of members), as well as several deaths among officials (bbcpersian, b) . a bbc persian report on february th used interviews with an unspecified number of hospitals in iran to put the death from the disease at , an order of magnitude larger than official numbers at the time (bbcpersian, a). another news agency quoted similar sources for a total of deaths by march st (iran international, ) and by march th. we develop a dynamic simulation model of the spread of the disease in iran to estimate the likely trajectory of the disease that is consistent with the evidence summarized above. we start with the traditional seir (for susceptible, exposed, infectious, and recovered stocks representing population groups) model and incorporate feedbacks regulating endogenous changes in contact rate, screening, diagnosis, and reporting in response to risk perception and other relevant factors. thus not only reported statistics, but also the effective reproduction number (r e ), are endogenously generated and can change as people respond to the epidemic. we use this model, along with various strands of data, to weave together an estimate of disease trajectory early on, simulation-based estimation of the early spread of covid- in iran and offer projections for medium term future. keeping in mind the various uncertainties involved in this analysis, reflected in our wide uncertainty intervals (ui), we estimate over , ( % ui: k, . m) cumulative cases of the disease in iran as of march th, with over , ( % ui: . k, . k) deaths. we thus estimate that only . % of cases and . % of deaths are officially attributed to covid- , with the rest going undetected. these results point to extreme gaps between official data and actual trajectory of disease, which may lead to slow response and under-appreciation of risks of the diseases. the rest of the paper is largely focused on documenting the original estimates developed on march th. as a secondary goal we also consider their accuracy in light of the data and findings in the two months following original estimates. this latter exercise provides a window into the actual challenges and promises of conducting policy-relevant projections early in a crisis. figure offers a simple representation of the model's structure. model equations, and parameter values are documented in appendix a. the model builds on the well-known seir (susceptible, exposed, infectious, and recovered) framework. the model includes the 'infection' reinforcing loop (r ) which creates the initial exponential growth in the number of cases. we divide the population of infected to early infected and late infected, and assume that early infected, while largely asymptomatic, might also be infective though at a lower rate (bai et al., ) . the infected population will follow two different paths of recovery or death. a fraction of late infected are symptomatic (in the figure, the variable "symptomatic late infected"). to avoid proliferation of free parameters we use general population averages rather than disaggregating into population groups. to this basic epidemiological model we add two endogenous mechanisms. first, we formulate contact rate to be endogenously changing in response to perceived risk of infection (a function of death statistics). this feedback captures changes in social interactions, gatherings, self-isolation of suspected cases, and hygiene as well as government-mandated closure of events, schools, and businesses in response to perceived risk. we assume public risk perception depends on the number of recent reported cases of death. this balancing feedback (loop b) can bring down contact rate, potentially enough to slow down the epidemic. second, we explicitly model the endogenous changes in screening and reporting of cases over time. here, the increased understanding of risks leads to mobilization of screening resources that expand the fraction of cases that are tested and thus will show up in the official statistics. we note that even with good screening many mild cases will go undiagnosed and will not be in official statistics. this analysis is focused on understanding the spread of the disease in its early phases, about one month after first diagnosed cases, and the core estimations in this paper are based on data only from that early period, until march th, . we use time series data for official reports of death, recovered, and cumulative number of infection over time. we also use unofficial data points including four observations about the number of iranian passengers diagnosed with covid- upon arrival in international airports, and three estimates aggregated by healthcare providers in iran and reported by bbc and iran international news agencies about total cases of death from covid- . the model includes three biological parameters (early-stage exposed period, average duration of illness, and fractional infectivity of early-stage exposed group) which we specify based on prior literature novel coronavirus pneumonia emergency response epidemiology, ; wu and mcgoogan, ) . population size and travel scope are also input using existing data. nine uncertain parameters remain that are estimated using the above data. three of the parameters are used to specify how official measurement and reporting relates to "true" values of infection and death, three parameters estimate public reaction to the reports, and two parameters are for mortality rate among two different groups of patients. finally, the arrival time of first cases of the virus is estimated as a separate parameter. simulation-based estimation of the early spread of covid- in iran our calibration method is based on forming a likelihood function for observing the actual time series data conditional on model parameters. we then conduct a markov chain monte carlo (mcmc) simulation to estimate the joint posterior distribution of the model parameters subject to observed data. we define a likelihood function for change over time (net-inflow) of official reports on cumulative death, recovered and infection assuming they are count events drawn from model-predicted rates (poisson distribution). we use a similar poisson distribution assumption for number of infected passengers and unofficial reports of death as well, since they both fit well into a count measure framework. the mcmc method searches over the feasible ranges for the uncertain parameters and accepts combinations that are consistent with the observed data. similar methods are used frequently in estimating dynamic models in this domain . our prior experience with the use of mcmc methods in nonlinear dynamic models highlights the risk that uncertainty intervals do not capture model mis-specifications and thus may be too tight. we therefore downscale the likelihood function to expand the uncertainty intervals (details and sensitivity in the online supplement) to err on the side of caution in assessing uncertainties and structural nuances not explicitly modeled. more details are reported in appendix a. we follow the procedure described in the modeling section and calibrate our model using multiple data sources and find uncertainty ranges using mcmc. figure a compares best-fitting simulation results for official confirmed death, recovered, and cumulative cases of infection against data. root mean squared percentage error values of reported recovered, death, and cumulative infected are %, %, and %, and root mean squared error values are , , and . simulation runs almost perfectly correlate with data. table a in the appendix a reports estimated parameters along with those adopted from the literature. figure b shows how simulation runs replicate unofficial statistics including the number of infected travelers diagnosed before air travel patterns changed substantially, and medical community's counts of cumulative death reported by media sources. we use the calibrated simulation model to estimate cumulative number of infected (panel c in figure ), cumulative number of death (panel d), and current number of infected (panel e) until march , , starting from december st, (day in simulation). we find that total infected cases may have been closer to , , than the reported , on march th. cumulative deaths, over , , may also be an order of magnitude higher than official statistics and might have almost tripled in the last days of the analysis. there is also much uncertainty in these numbers: our baseline estimate for cumulative infected may be as low as , and as high as . million ( % uncertainty interval). similarly cumulative deaths is between and , ( % confidence interval). the wide uncertainty intervals are partly due to the nature of the data: absent data on testing coverage in iran it is very hard to fully know the underlying diffusion patterns based only on the formal statistics. the travel and informal estimates of death partially address these limitations, but much uncertainty remains. our conservative assumption on downscaling the likelihood function may also have contributed to this wide interval. nevertheless, even our lower bound are times the official statistics for total infections and times larger than the death statistics. there are some glimmers of hope in our estimates as well. the drop in contact rate in response to perceived risk, which we have captured in our model, might have reduced r e significantly, to just below as of late march (panel f). that reduction (which was confirmed by later data), if sustained, would help bring down the number of new cases. thus, figure e shows the number of currently infected cases may well be reaching its peak at the end of the simulation. the epidemic seems to have raged with a reproduction number close to . ( % ui: . - . ui) for more than six weeks before the behavioral and policy interventions have slowed down the diffusion rate starting in late february. some of this drop may also be attributed to weather, but current research is mixed on the impact of weather wang et al., ; xu et al. , ) so we did not include it in our estimation (but would explore it in the forward projection in the next sections). those factors, we estimate, brought down the aggregate contact rate to % ( % ui: %- %) of pre-epidemic levels by the date of analysis. this number may just succeed in bringing down the reproduction number below , which is the necessary condition for containment of the epidemic. whereas the case fatality rate in iran, based on official statistics until march th, is . %, our estimated infection fatality rate is . ( . )% (standard errors for estimates are in parentheses). this estimate is consistent with, and somewhat higher than, the . % reported by wu and mcgoogan ( ) based on tracing confirmed cases in china. if correct, the toll of epidemic in iran would have been larger than that in most other countries by the estimation date, and limits to healthcare services may explain the increased death rate. this finding is reinforced by the limited coverage of testing in iran that is indicated in our estimation. many cases go un-confirmed, and at its maximum, formal testing is covering only . ( . )% of infections. these estimates are consistent with qualitative media reports from iran on very limited availability of testing, the doctors' need for getting authorization before conducting tests, and the multi-day delays in receiving test results that render them ineffective in the clinical decision making processes. we estimate that hospital sources of news organizations who have offered alternative versions of actual death statistics in iran have had a much wider coverage of true death statistics ( ( )% of estimated true values). their count offers a lower bound for true deaths, is also close to our lower confidence bound, and suggests that the true number of cumulative cases, even with an infection fatality rate as high as . %, would not be lower than , . nevertheless, we estimate that even those medical community reports offer coverage significantly below %, consistent with the lessthan-perfect coverage of hospital reports by media sources, and anecdotal evidence that hospital system has been overwhelmed in many hot spots of the disease and many patients have died at home and been buried with no testing or proper association of cause of death to covid- . the model used prior estimates from the literature for three important parameters: the total duration of illness (d = days), the exposure (early infection) period (τ = days), and the fractional infectivity of the exposure period (θ = . ). noting significant uncertainty in such estimates early in an epidemic, we assess our projections' sensitivity to these structural assumptions by re-estimating the model for different values of each parameter. in this analysis we find a new set of best-fitting parameters and estimates for true cases given each different assumption on disease parameters. in table results are summarized as percentage changes in key estimates (cumulative infections and cumulative death until march th, ) compared to baseline best-fitting projections. results suggest these structural parameters are important in identifying the true magnitude of the epidemic and may propagate additional uncertainty in our projections due to limited early data on their exact values. specifically, a smaller fractional infectivity during exposure period (θ), a longer exposure period (τ), or a shorter duration of illness all significantly increase the projections for total cases and deaths. reductions in the estimates are less significant when parameters move in the opposite direction, though a very high level of θ would bring down the estimated cumulative cases notably. in lower values of θ, model calibration suggests earlier arrival of first cases of infection, which, in a few days, can make a difference in the number of late-infected, and increase exposure rate. current evidence for transmission during early infection (exposure) period is rather limited, and thus our baseline projections for total cases may be somewhat conservative. nevertheless, given our conservative treatment of the uncertainty intervals all the best-fitting projections with different disease parameters remain within the % bounds of our baseline projections. we run the model until july st of under six scenarios (three alternative assumptions about the impact of seasonality times two policy measures). specifically, our scenarios about seasonality include no effect (status quo), moderate effect (infectivity of the virus decreases linearly from may st and halves by june st, then stays the same for the rest of the simulation), and very strong mitigating effect (infectivity of the virus decreases from may st to a quarter of its base value by june st, then stays the same for the rest of the simulation). for policy, our focus is on contact rate, and we include two conditions of status quo (i.e. only behavioral responses) and aggressive efforts to decrease contact rate by half what it would be otherwise. these six conditions provide intuitions for a potentially wide range of cases. both intervention and weather impacts are assumed to include rather strong options to inform the range of possibilities, and should not be interpreted as predictions. moreover, we also note that the wide cone of uncertainty in the baseline simulations will continue and expand in future projections. keeping the uncertainty considerations in mind (but not graphed due to clutter), figure shows results based on best-fit parameters. if our best case scenario on the reduction of contacts and benefits of seasonality for containment materialize, the number of infected cases would be expected to peak soon after the analysis date at approximately , ( % ui: k- k), and will go down later on. this optimistic scenario will still lead to over a million infections and some , deaths ( % ui: k- k) by the end of june. the less aggressive scenarios point to continued spread of the epidemic at large rates. a reduction in contagion is realized only when reproduction number remains below one as a result of reduced physical contact, government interventions, and seasonality. among these three, the first (behavioral response) is endogenous to recent death rate. when death rate comes under control (due to the combination of all three factors), our model assumes the contract rate rebounds, weakening the first channel and increasing the transmission. economic pressures, normalization of death, and behavioral modeling after those not practicing distancing (or those already recovered and thus presumably immune) could all weaken the behavioral response when the perceived risks fade. the increased transmission would then, with a delay, bring up the death rate close to levels sustaining a reproduction number around one. this creates a strong attractor in the dynamics where in steady state contact rate is high enough to sustain the contagion but not so high to lead to the rapid infection of all the population. it may also lead to oscillations in peak transmission. therefore it is only with strong weather and/or government interventions that reduced reproduction number brings the epidemic under control. this dynamic offers a cautionary tale against declaring victory early in the fight against the epidemic. however the actual magnitude of such rebound effect is not known in this setting and our data offers no guidance on the relevant parameters. therefore these results are only qualitatively suggestive but not quantitatively reliable. this research was conducted under extreme urgency to inform decisions amidst crisis. the primary objective of the analysis was to understand the magnitude of the outbreak during early stages of infection when uncertainties are large and major decisions at stake. the main analysis of this paper was completed on march th and first reported publicly on march th on medrxiv pre-print server. thus we intentionally leave those projections untouched to avoid post-hoc justification and corrections that would cover the true uncertainties involved in real world modeling projects targeting fast evolving situations. furthermore, given that march th marks the end of the winter and beginning of persian new year, emerging annual reports can be used to assess some of our findings. in this section we summarize a few such tests and observations made based on findings post initial analysis. first, our estimates can be partially tested against official all-cause mortality data which are reported seasonally by the iranian government. the data for winter were released on may th, during the final preparations of this manuscript. based on a regression analysis on the all-cause mortality data we find that covid- related deaths are likely . ( % ci: . , . ) times more than official death counts for the disease (see appendix c). our simulation-based estimates, suggesting . ( % ci: . , . ) times more deaths than official data, are consistent with this new information. a second study informed the true magnitude of epidemic in one of the provinces of iran using anti-body testing. specifically, testing for covid- antibodies informs whether a person has been previously infected by the disease, offering estimates for cumulative infection when randomly conducted on a population. we have found one such study conducted on a random population of iran's guilan province (population of . million) (shakiba et al., ) . these researchers estimate that - % of guilan residents were infected by late april. we did not simulate our model at the province level, but our march th estimate of times undercounting, combined with confirmed cases in guilan ( . % of the residents), gives an estimate of % prevalence at the end of winter. our model estimates about %- % growth in cases over the following month (see figure b ), so our estimate of cumulative infections in guilan, at %- % for late april, are still five to ten times lower than this new study. these findings would suggest that a rather high fraction of cases were asymptomatic and/or not included in any of the data sources for infection that we used (official data and infected traveler counts). incidentally, if we assume that our estimates for infection were times below true numbers, the infection fatality rate for covid- in iran goes down to close to . %, a number much closer to some recent estimates for this key parameter (basu, ) . third, we can test model's capability in projecting confirmed cases. although prediction of official cases was not the purpose of the model, we present this out-of-sample test as an indirect way of assessing the model's predictive power. the model was calibrated with days of data, and since the pre-print, days of more data on confirmed cases and deaths have become available, which we use to compare the model's predictive performance for official, reported cases. these results are provided in appendix b, and show that while qualitative trends are consistent, the model misses a major increase in the number of cases right after the first days. confirmed death projections are closer to data. two mechanisms may explain this gap. first, our simple formulation for testing only tracks the fraction of cases tested, saturating that fraction at a maximum. that formulation is fine in capturing growth in test capacity during the rise of epidemic, but would underestimate cases when the growth slows down and milder cases can be found with the already enhanced test capacity. indeed since estimation we have found that initial test capacity in iran grew to about tests per day, stayed at that level for the later part of our estimates, and then jumped to , tests per day; similar increasing patterns of tests are seen across nations globally. thus, the testing formulation likely introduces under-counting in simulating official cases later in the epidemic, but this does not mean the model is under-predicting the actual infections and deaths. a second factor may explain why our model predicted an earlier peak, by about two weeks. iran's new year holiday season, nowruz, which starts on march th, is a major time of travel, family visits, and social interaction. those activities may well have increased contact rates in later march, but we decided against post hoc introduction of a nowruz parameter in the model. finally, we note that our model predicted a resurgence of the epidemic in early may due to reduced risk perception, which is consistent with a rise in cases in the real world in may. it is harder to fully assess the impact of these discrepancies on future estimation of true cases, had we decided to extend those estimates beyond the original timeline. nevertheless, it seems our model is somewhat conservative in predicting the 'reported' infections and deaths after the estimation period, and a more explicit account of physical test capacity would add value in longer term projections. finally, upon the release of the first draft of the paper we have received reports from a few hospitals and officials in iran that confirm: a) unofficial death counts by hospital sources that continue to be about five times the official death statistics, and in some states of iran are close to our estimates; and b) the low sensitivity (false negative risk) of tests, at about %, when conducted by hospital staff. moreover, availability of tests even in major hospitals is limited, covering about % of those clinically diagnosed using other methods (often ct scans). it is important to note that some evidence from random testing in other countries (including iceland and germany) point to a very high asymptomatic fraction of patients, which would not be captured in any of our data sources and is consistent with our comparisons with the guilan study. furthermore, new evidence suggests we might have used under-estimates for the delay between exposure to onset of symptoms (about days), from onset to testing (another days), and from testing to resolution (about days) (lauer et al., ; linton et al., ) . adjusting for these parametric assumptions would increase our estimated case count as discussed in the sensitivity analysis and may bring our overall estimates closer to the new evidence on the cumulative infections. in this paper we provide a more sobering picture of the covid- outbreak in iran using a dynamic model that goes beyond official statistics. integrating data from various sources we suggest that the official statistics are at least an order of magnitude below actual spread of the epidemic, and even in optimistic scenarios the burden of disease will be large and lasting for many months. implementing and sustaining strong policies that target physical distancing offers the main hope for containing the epidemic until a vaccine becomes available. the gap between official statistics and our estimates may be due to various complications in measurement as well as policy choices. the availability of testing infrastructure has been a major bottleneck for detecting cases in iran. citizens with suspicious symptoms have had no easy way for getting tested; most tests are conducted on hospitalized patients, require specific authorization, and are processed in a few centralized labs adding significant delays to the process. not only mild cases are missed, but also many critical patients have been unable to access the care they need due to hospital congestion. the fact that majority of cases have mild symptoms similar to flu (wu and mcgoogan, ) adds to the risk of under-counting even if the testing capacity was ample. in fact many mild or moderately sick patients may have preferred to stay home than risk being infected upon visiting a congested hospital, further reducing demand for testing. finally, false negative test results seem to be common among covid- patients in iran, with healthcare providers indicating sensitivity levels as low as % due to challenges in sample extraction and varying concentration of viral load over the course of disease. the problem of undercounting cases of infection and death is not limited to iran. due to the relatively long period of incubation, a considerable proportion of asymptomatic cases, significant fraction of false negatives in existing tests, and especially the limits on test capacity, the undercounting problem is common, but its magnitude would vary across different countries. even with ample test capacity, the undercounting of infection is likely large due to both the asymptomatic patients (estimated to be more than % (mizumoto et al., ; nishiura et al., ) ) and those cases with false negative results (about % of positives in case of pcr based covid- tests (fang et al., ) ). for example a pre-print paper estimates that in the us less than % of cases of infection were diagnosed until march (pei and shaman, ). others have made similar claims about official data of china . the undercounting of deaths may be less in magnitude, but still very common. under significant strain, limited testing capacity may not be allocated to post-mortem testing of suspected cases, and thus country-specific routines for categorizing death in those cases may lead to large variations. we suspect this is a major reason why iran's official death counts may be significantly below the actual numbers. but other countries may have similar issues. for example a recent article estimates much higher number of deaths in italy than official numbers (stancati and sylvers, ) . moreover, recent investigative reporting by financial times, new york times, wall street journal, and economist has used all-cause death data of different countries and cities and estimated that globally, as much as % of covid- death cases are missed (burn-murdoch et al., ) . for example italy's excess death in march is , , out of which only , is attributed to covid. jakarta (indonesia) had excess deaths in march and april, with only attributed to covid. absent extended testing capacity, expanded post-mortem testing, and random testing in the population, policymakers may face a significant undercount of existing cases and thus miscalculate their response. we hope that our proposed approach can be used for similar cases elsewhere to de-bias such estimates. methodologically, we faced important challenges to estimation and projection of s-shaped behavior based on early data that are worth highlighting here. first, estimating s-shaped curves before observing their inflection point can be unreliable. minor changes in the slope of the cumulative curve can significantly change the estimated future trajectory when simple curve-fitting is pursued. overcoming this risk requires a more mechanistic model that is fitted to the flow (infections in this case) rather than cumulative stock, so that the slope is constrained by physical mechanisms determining the flow variable (e.g. the size of the susceptible population). the calibration should also properly weigh different data points so that the larger numbers during peak period do not overwhelm the signal from other periods. in our case we achieved this using poisson log-likelihood error. other promising alternatives may include negative binomial log-likelihood, among others. a second challenge is teasing out the various potential reasons for reduction in new infections. for example those may include a reduction in susceptible population, a change in contact rate due to social distancing, or exogenous changes such as weather. while mechanistically proper model specification can partially address this challenge, one needs to be cognizant of the uncertainty in estimated parameters, e.g. by using mcmc methods to identify the various combinations of those effects that are broadly consistent with the data. the problem is rapidly changing, and timely estimation is critical. therefore we have made several simplifying assumptions that readers should be aware of in interpreting our results. first, consistent with prior findings (rahmandad and sterman, ) we have focused on capturing behavioral feedbacks in contacts and testing and have adopted a formal estimation process, but have done so at the cost of abstracting away from much detail complexity and heterogeneity in populations and risks. we converged on the current model structure in an iterative process, attempting to keep the model simple and feasible to estimate, but not missing components that would qualitatively change the results. for example we tested the inclusion of healthcare capacity, test accuracy, and physical test capacity (rather than as a percentage of cases) and decided against including them explicitly because they did not change the conclusions qualitatively and our data did not offer reliable ways to estimate those effects beyond what is informed by our current structures. generally, a more detailed model may be appealing, but if the purpose is to offer quantitative estimates and projections, constraining additional model parameters during calibration would be a major constraint that should be weighed against the value of additional structure. second, during the early periods of infection, there is considerable uncertainty in most data sources. for example, infected passenger data, while useful, is a not a perfect data source for modeling. it can be argued that exposed to more travel, this population may be exposed earlier than a random sample. on the other hand, this is typically a higher income and more educated population that may be more aware of, and responsive to, infection risks. similar issues can be raised for informal death reports in the media, which are based on potentially limited samples of hospitals and may include subjective assessments of medical cases. such uncertainties are part of any emerging, fastmoving situation, and one should be cognizant of these factors in interpreting modeling results. third the model is scoped only around iran --we ignore potential effects of global spread of the disease on iran, including the risk of reintroduction of cases in future. forth, we assumed that the recovered population are immune during our simulation horizon. fifth, we ignore mutations in the virus which may change its contagiousness and case fatality rate. despite these limits we hope the paper offers an accurate assessment of the risks and scope of the epidemic for iran and beyond. we also hope other researchers build on this work using the publicly available data, models, and replication instructions provided in the online supplement. finally, we hope that the study contributes to the system dynamics modeling literature. there are a wide range of epidemic models with different levels of dynamic and detailed complexity (darabi and hosseinichimeh, ) and a large number of models have been built in response to covid- . while epidemic models with interesting and relevant feedback mechanisms could be built rather quickly, their results depend heavily on the parameters regulating the strength of contagion, behavioral response, testing, and other mechanisms. for example reputable research groups have offered models with forecasted cumulative deaths that vary significantly (ferguson et al., ; murray and ihme, ) . without quantitative estimation methods, different models may point to starkly different conclusions, with little guidance on how to select the appropriate analysis. our contribution is to offer a model-based estimation approach during an on-going pandemic where data are uncertain and limited. this requires combining all sources of available data with different levels of uncertainty, each one, potentially an imperfect indicator of the reality, yet collectively providing a better picture. our data-driven approach is consistent with recent calls for detailed data-informed modeling approaches (sterman, ) , and combining different methods and techniques to enrich dynamic modeling (duintjer tebbens and thompson, ; ghaffarzadegan and larson, ) . we hope the methods used in this paper can be extended to a variety of other system dynamics applications where actionable insights rely on rigorous combination of feedback rich models and quantitative data. data sources to study dynamic problems in organizational and health domains. as the number of infected cases increase, the probability of infection increases given the increased number of contacts between infected and susceptible populations. some of these contacts lead to new cases of infection (loops r and r ). infections may be due to a fraction of early infected cases who can infect others (bai et al., ) , and the late infected population. exposure rate (i e ) is formulated as following: we set e at (no seasonal effect) for historical calibration, and later for scenario analysis, check different functions that give lower values during summer. the equation has two degrees of freedom, and since the actual value of c and i are not independently knowable, we assume i = . and vary c to fit the model output against data (details below). death and recovery rates are estimated using fractional death rate. we have, where the disease duration is assumed to be total of τ e (early-stage asymp- contact rate can change in response to the progression of the disease and consequently change infection rate (see figure a ). the impact of perceived risk on contact rate captures not only the endogenous changes in social interactions, gatherings, self-isolation of suspected cases, and hygiene, but also government mandated closure of events, schools, and businesses to name a few. we assume public risk perception depends on reported cases of death. finding infected cases is challenging given that many cases remain mild and unknown, yet potentially infectious. furthermore, especially early on, many cases were misdiagnosed as healthcare providers were unaware of the existence of the virus in the country. as the first cases are revealed and reported, a higher fraction of cases are found (loop r ). there are three death-rate-related variables: actual death rate ( c is inversely related to o d . we bound c between and c max , and use the following sigmoid function to represent c: ρ represents the impact of other policy measures beyond the perception of death that may impact c (e.g. various government interventions) and is set to for base run simulations but experimented with for policy analysis. o à d and s represent the relation between o d and c. conceptually o à d is a threshold for public report of death, at which contact rate endogenously declines to half of c max and s is the sensitivity of public behavior to the reported death rate. the free parameters, o à d ,s, and c max , are estimated. we assume only symptomatic cases of patients can be diagnosed. let f symp < be the fraction of late-infected individuals that develop symptoms. let α be the fraction of symptomatic who are tested, then αf symp is the fraction of i l who will be tested. more severe cases are more likely to be diagnosed, so mortality rate of diagnosed cases(f ), is likely to be higher than average fatality rate (f). death rate of diagnosed individuals is f (αf symp i l )/τ l , with the constraint αf symp f ≤ f. we assume no post-mortem diagnosis. including first cases of death discovery diagnosed early on (x): where d is the cumulative reported cases of death. x is equal to on t =february th and for the rest of the simulation it is zero. we set α = min ad, À Á Á α max , and let the model estimate α max , and a through calibration (explained below). for reported cases of recovered (r), we use the following equations: is reported cases of recovery per day. this formulation assumes the reporting of recovered cases happens with the same rate (α) as the reporting of infections and death. while iran's data are supportive of this assumption, exploration of statistics from other countries suggests many do not track the recovered cases. for total infected (i), cumulative cases (i cum ) and reported cumulative cases of infection (i cum ) we have: we set f symp = . , but the model is not sensitive to the value of f symp , as any change in f symp will be compensated by α to match the simulation with simulation-based estimation of the early spread of covid- in iran the data, and calculate total fraction of infected who are diagnosed. the reproduction number is estimated asr = ( τ e + τ l )(i e /i). besides the official data, we use a few unofficial data points: four observations about number of iranian passengers diagnosed with covid- upon arrival in international airports (p ), and three unofficial estimations from bbc and iran international news sources about cumulative death from covid- (d u ) early in the epidemic. in our model, we estimate them as following: where d u, = , and μ is the ratio of number of passengers going from iran abroad in early days of the outbreak. the term (t + − t ) represents days since the first cases of infection were diagnosed. it is assumed that the daily number of passengers is fixed and death is minimum, thus this estimation only works during the first few days of the outbreak. for d u , we assume γ represents the fraction of actual deaths identified by these sources. note that the unofficial reports for death cases in media are based on unofficial reports from the medical community with limited samples, thus γ is likely below one. γ will be estimated through model calibration. we initialize the model as i e, = i l, = r = d = , and s = million people. we set r = d = . new infected cases are injected to the model through i f , at time t , to be estimated through model calibration. although we are not aware of number of foreign patients entering iran, since t is also unknown, we have two degrees of freedom, and one can be assumed and the other estimated through model calibration. we set i f equal to patients per day at t , and throughout the rest of the simulation. we run the model from t = , december , , and our time unit is a day. t , the time first cases are diagnosed, is february , . we have time series data for d, r, i cum , and a few data points for p and d u . our method is mainly based on forming a likelihood function for observing the actual time series data conditional on model parameters. we then conduct a markov chain monte carlo (mcmc) simulation to estimate the joint posterior distribution of the model parameters subject to observed data. we define a likelihood function for change over time (net-flow) of d , r , i cum assuming they are count events drawn from model-predicted rates (poisson distribution). we use a similar poisson distribution assumption for p and d u as well, since they both fit well into a count measure framework. the mcmc method searches over the feasible ranges for nine uncertain parameters in our model. these include: three data-related parameters of α max , a, and γ; three public-behavior-related parameters of c max , o à d , and s; and three disease-related parameters of fractional death rate (f and f ) and time for the injection of first cases of infection into the population (t ). prior experience and this exercise point to rather tight confidence intervals coming from mcmc methods directly applied to large nonlinear models. the problem could be addressed using filtering (e.g. extended kalman filtering or particle filter) methods or heuristics that scale the likelihood function in mcmc method to be consistent with model's predictive performance. in light of the computational costs of the former and time sensitivity of the research topic, we chose the latter option. to be conservative, we therefore downgrade our confidence in the data, scaling the likelihood function by a factor of . , which allows the algorithm to explore the parameter space much more freely. this approach is a heuristic we use to avoid putting too much confidence in our estimation results; however, without strong theoretical reasons to support the specific scaling factor, we caution against a strong interpretation of these results. with this caveat in mind, the mcmc method offers % confidence intervals for joint-distribution of the parameters. we conducted additional sensitivity analysis to this downscaling parameter choice. the rest of the parameters are specified based on the literature. the counter factual of "what is expected absent covid- " is. a simple counter-factual would compare deaths in previous winters with that in winter . yet, depending on which previous years one includes in such counter-factual, excess deaths between to thousands could be estimated. however, the released death data is disaggregate at the province level ( provinces). this provides a unique opportunity to more accurately estimate the excess deaths in iran by comparing the variations in death in different provinces and how those variations could be explained by the official death toll in each providence. formally, we run the following regression to estimate the undercounting of covid- related deaths: excessdeath i = β + β :pastdeath i + β :confcoviddeath i: where excessdeath i is the difference between death in winter and winter in province i, and pastdeath i is a vector of death in past seasons (e.g., winter , , etc.) in province i. confcoviddeath i is an estimation for confirmed death cases based on confirmed total cases for each province which were available for the analysis (iran does not provide province level death statistics for covid, but did provide province level cumulative infection statistics; scaling total death based on province level infections we calculate "confcoviddeath"). β will represent death undercounting factor. our estimate of , ( % ui: . k, . k) death implies that this ratio should be around . ( % ci: . , . ). our regression models are reported in table a . based on the best regression model (in terms of adjusted r-squared), we find that β = . ( % ci: . , . ). this ***p < . , **p < . , *p < . . presumed asymptomatic carrier transmission of covid- estimating the infection fatality rate among symptomatic covid- cases in the united states: study estimates the covid- infection fatality rate at the us county level corona virus has at least claimed lives in iran who, among political and government figures, have contracted the corona virus? global coronavirus death toll could be % higher than reported. financial times system dynamics modeling in health and medicine: a systematic literature review using integrated modeling to support the global eradication of vaccine-preventable diseases sensitivity of chest ct for covid- : comparison to rt-pcr covid- -navigating the uncharted impact of non-pharmaceutical interventions (npis) to reduce covid- mortality and healthcare demand pandemic potential of a strain of influenza a (h n ): early findings sd meets or: a new synergy to address policy problems the number of deaths from corona virus in iran reach db% c%d %b %d %a %d % -%d %a %db% c%d % %d %aa% d %b %d % %d %b %d % %d %a %d % -%d %b %d % % d %a %d %b -%d %ac%d %a %d % %e % % c%d %a %d % a %d %ae%d %aa%da%af%d %a %d % -%da%a %d %b %d % %d % %d %a -%d %af%d %b -%d %a %db% c%d %b %d % a %d % -%d %a %d % -%db%b %db%b %db%b -%d % %d % %d %b -%d %b %d %b %db% c%d %af emergency response to a smallpox attack: the case for mass vaccination the incubation period of coronavirus disease (covid- ) from publicly reported confirmed cases: estimation and application substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (sars-cov- ) incubation period and other epidemiological characteristics of novel coronavirus infections with right truncation: a statistical analysis of publicly available case data the role of absolute humidity on transmission rates of the covid- outbreak estimating the asymptomatic proportion of coronavirus disease (covid- ) cases on board the diamond princess cruise ship forecasting covid- impact on hospital bed-days, icudays, ventilator-days and deaths by us state in the next months novel coronavirus pneumonia emergency response epidemiology team. . the epidemiological characteristics of an outbreak of novel coronavirus diseases (covid- ) in china initial simulation of sars-cov spread and intervention effects in the continental us who chief says cases of coronavirus in countries originated from iran heterogeneity and network structure in the dynamics of diffusion: comparing agent-based and differential equation models seroprevalence of covid- virus infection in guilan province italy's coronavirus death toll is far higher than reported system dynamics at sixty: the path forward the risks, costs, and benefits of possible future global policies for managing polioviruses estimation of covid- burden and potential for international dissemination of infection from iran temperature significant change covid- transmission in cities wikipedia. . coronavirus outbreak in iran iran has far more coronavirus cases than it is letting on. the atlantics nowcasting and forecasting the potential domestic and international spread of the -ncov outbreak originating in wuhan, china: a modelling study characteristics of and important lessons from the coronavirus disease (covid- ) outbreak in china: summary of a report of cases from the chinese center for disease control and prevention weather conditions and covid- transmission: estimates and projections. medrxiv we are thankful to mohammad akbarpour, narges doratoltaj, babak heydari, hamed ghoddusi, and tse yang lim for their thoughtful feedback on various drafts of this paper. navid ghaffarzadegan is an associate professor in the department of industrial and systems engineering at virginia tech. he develops system dynamics simulation models to study complex social systems and policy problems. the main application areas of his research include science policy and health policy.hazhir rahmandad is an associate professor of system dynamics at mit sloan school of management. he combines simulation models and various simulation-based estimation of the early spread of covid- in iran basic model architecturethe model uses a country-level system of differential equations to capture the dynamics of contagion ( figure a ). the infected population is first asymptomatic and is represented as "early infected" and later becomes "late infected" with the majority being symptomatic.the following equations represent the aging chain:appendix b: out of sample prediction testour main analysis in this paper is done based on data up to march th, (total of days). since then days of new data have become available which we use to conduct an out-of-sample test of our model's projection for confirmed cases. figure a shows the results. the model is better at replicating reported cases of death (panels c and d) than reported infection (panels a and b) and recovery (panels e and f). it appears that by increased testing, milder cases of infection are diagnosed in iran than we predicted, while confirmed death rate is still in the same range as our model's prediction. in recovery data we see a peak on a specific day (panel f) that might relate to some follow-up or closing active cases. the data for all-cause death, which in iran is reported seasonally, were released on may th, , during the final preparation of this manuscript. winter ends on march th, thus seasonal reports on all-cause number is lower than our estimate for death, but of comparable magnitude, and falls within our confidence intervals. it is worth noting that the covid-related excess death may not be all attributed to covid- alone. for example social distancing policies in response to covid may reduce traffic-accidents and death due to air pollution (both major causes of mortality in iran), leading to an under-estimate of covid- deaths in this approach. on the other hand hospital congestion may increase death due to other conditions, leading to over-estimation of covid- deaths using this method. we do not have data to correct for these potential biases, but overall we suspect that they are a second order effect and the true magnitude of covid- death is captured by the excess mortality data. additional supporting information may be found in the online version of this article at the publisher's website.appendix s : supporting information appendix s : supporting information simulation-based estimation of the early spread of covid- in iran key: cord- -fkjmzpuw authors: pishgar, elahe; mohammadi, alireza; bagheri, nasser; kiani, behzad title: a spatio-temporal geodatabase of mortalities due to respiratory tract diseases in tehran, iran between and : a data note date: - - journal: bmc res notes doi: . /s - - - sha: doc_id: cord_uid: fkjmzpuw objectives: respiratory tract diseases (rtds) are among the top five leading causes of death worldwide. mortality rates due to respiratory tract diseases (mrrtds) follow a spatial pattern and this may suggest a potential link between environmental risk factors and mrrtds. spatial analysis of rtds mortality data in an urban setting can provide new knowledge on spatial variation of potential risk factors for rtds. this will enable health professionals and urban planners to design tailored interventions. we aim to release the datasets of mrrtds in the city of tehran, iran, between and . data description: the research data include four datasets; (a) mortality dataset which includes records of deaths and their attributes (age, gender, date of death and district name where death occurred), (b) population data for districts (age groups with years interval and gender by each district). furthermore, two spatial datasets about the city are introduced; (c) the digital boundaries of districts and (d) urban suburbs of tehran. © the author(s) . this article is licensed under a creative commons attribution . international license, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the creative commons licence, and indicate if changes were made. the images or other third party material in this article are included in the article' s creative commons licence, unless indicated otherwise in a credit line to the material. if material is not included in the article' s creative commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. to view a copy of this licence, visit http://creativecommons.org/licenses/by/ . /. the creative commons public domain dedication waiver (http://creativecommons.org/publicdomain/zero/ . /) applies to the data made available in this article, unless otherwise stated in a credit line to the data. respiratory tract diseases (rtds) have a major impact on disease burden including death across the world [ ] . rtds are among the top five leading causes of death worldwide and covid- has brought rtds in focus [ , ] . more than . million deaths globally are attributed to rtds with four million premature death per year [ , ] . previous research demonstrated possible links between mortality rates due to respiratory tract diseases (mrrtds) and environmental risk factors [ ] . urbanization, air pollution and sedentary lifestyle are associated with an increased risk of asthma and respiratory diseases in urban areas compared to the rural regions [ ] . tehran is the capital city of iran and is the nd most populous city in the world with a population of million people at daytime. it has the highest mrrtds in iran [ ] . the high population size, the natural diversity of the surrounding areas (windswept deserts, plains, and mountains) and the existence of industries have extensively increased the level of air pollution in this mega-city [ ] . it is necessary to conduct a spatiotemporal analysis of the current epidemiological patterns of mrrtds in tehran to identify the potential links between mrrtds and environmental risk factors. spatio-temporal analyses of mortality data can provide new knowledge on spatial variation of mrrtds and potential open access bmc research notes *correspondence: kiani.behzad@gmail.com drivers of this variation. to support research in this field we aim to release the datasets of mrrtds in tehran, between and . geographical information system (gis) has a great capacity to integrate diverse data from different sources including spatial, temporal and descriptive components into one framework. [ , ] . spatial component represents information about the physical location of health event and the shape of geometric objects. temporal data refer to the time of occurrence and descriptive information relates to attribute data about the event (i.e. age, gender and cause of death) [ , ] . gis provides appropriate tools for collecting, geo-linking, analysing and visualising geographical patterns and spatio-temporal relationships in the distribution of rtds or deaths with potential environmental factors [ , ] . data on , death events due to rtds from september to september were obtained from the behesht-e zahra organization, a local health department under the supervision of the tehran municipality [ ] . this dataset includes date of death, age, gender, cause of death and urban district where death was occurred (dataset ). population data were obtained from the statistical centre of iran and they contain the annual population size by district in tehran from to . we categorised the gender as male and female. age of people was categorised into five groups including - , - , - , - and > years old (dataset ). the digital boundaries of districts data (data file ) and districts' map sheets were obtained from the municipality of tehran (data file ) [ , ] . table shows the details of each dataset and provides access links to these data. the datasets provided in this study can be used by researchers in different disciplines such as health geography, urban planning, medicine and healthcare ecosystem research. descriptive choropleth maps can be produced to highlight the mrrtds distribution in tehran during - . choropleth map is a common map used to represent data on predetermined geographic areas [ ] . researchers may use empirical bayesian procedures for smoothing mortality rates in the case of a choropleth map. empirical bayesian also help to identify local clusters of more/less affected areas [ ] . high-mortality clusters (hot spots) show the regions having a significantly greater mortality rate and low-mortality clusters reveal the regions with a significantly lower mortality rate (cold spots) in tehran. global moran's index can be used to show the degree of spatial autocorrelation in the pattern of mrrtds. in other words, it can test whether the mortalities distribute randomly or follow a spatial pattern [ ] . in addition to spatio-temporal analyses, these data can be linked to the contextual factors such as climate status, air pollution and smoke to further investigated the impact of environmental risk factors on mrrtds. the research outputs can inform health policymakers and urban planners to develop appropriate strategies to reduce the risk of mrrtds across communities. this study offers tehran's mrrtds data for the period - . further, covid- disease has become a pandemic disease in late and our data provide a new opportunity for researchers to quantify and assess the impact of covid- disease on mrrtds burden in tehran. tehran is a mega city with an area of km and comprises districts. in this study, we aggregated the data at district level which is relatively a coarse geography and may mask variation at finer geography level such as mesh blocks. rtds: respiratory tract diseases; mrrtds: mortality rates due to respiratory tract diseases; gis: geographical information system. the global burden of chronic respiratory disease in adults covid- : pandemonium in our time covid- : time for paradigm shift in the nexus between local, national and global health cd in respiratory diseases ambient air pollution and respiratory mortality in xi'an, china: a time-series analysis impact of air pollution on respiratory diseases in urban areas: a systematic review daniele ignazio la milia national organization for civil registration (nocr) cross-sectional associations between ambient air pollution and respiratory signs and symptoms among young children in tehran comparing spatiotemporal distribution of the most common human parasitic infections in iran over two periods access to dialysis services: a systematic mapping review based on geographical information systems multiple-scale spatial analysis of paediatric, pedestrian road traffic injuries in a major an age-integrated approach to improve measurement of potential spatial accessibility to emergency medical services for urban areas colorectal cancer risk factors in northeastern iran: a retrospective cross-sectional study based on geographical information systems, spatial autocorrelation and regression analysis. geospatial health spatial analysis of colorectal cancer incidence in hamadan province, iran: a retrospective cross-sectional study tehran: tehran municipality, organization i tehran's online noise pollution data archive. tehran: tehran municipality atlas of tehran metropolis. tehran an evaluation of visualization methods for population statistics based on choropleth maps bayesian disease mapping: hierarchical modeling in spatial epidemiology spatial modeling, prediction and seasonal variation of malaria in northwest ethiopia data for: mortality due to respiratory tract diseases in tehran iran between we would like to express our deepest gratitude to behesht-e zahra organization of tehran, affiliated to the tehran municipality for providing and offering the data. key: cord- - q itegc authors: bisaillon, laura; khosravi, mehdi; jahandoost, bahareh; briskman, linda title: clever covid- , clever citizens- : critical and creative reflections from tehran, toronto, and sydney date: - - journal: j bioeth inq doi: . /s - - - sha: doc_id: cord_uid: q itegc our world suffers. some people suffer more than others. since the first part of , ours is justly described as a time of uncertainty, threat, and upheaval. in this article, we offer reflections threaded narratively, told from the specificity of our societal contexts in iran, canada, and australia. what might we learn in the present and anticipated future from people living chronically within conditions of uncertainty and immobility and also those experiencing uncertainty and immobility for the first time? we argue that reflexive comparative analysis bridging social and visual analysis, anchored in embodied conditions of such people, offers a way to learn from responses to covid- while also being an exercise in ethical research practice. this reflection builds on and extends from our scholarly collaborations that have been ongoing since . our title recognizes this specific virus as stealthy. importantly, our choice of words identifies resident iranians—whose experiences were the original impetuses for this paper, and whose lives provide its empirical basis ( is iran’s country code)—as equally steely. our world suffers. some people suffer more than others. since the first part of , ours is justly described as a time of uncertainty, threat, and upheaval. in this article, we offer reflections threaded narratively, told from the specificity of our societal contexts in iran, canada, and australia. what might we learn in the present and anticipated future from people living chronically within conditions of uncertainty and immobility and also those experiencing uncertainty and immobility for the first time? we argue that reflexive comparative analysis bridging social and visual analysis, anchored in embodied conditions of such people, offers a way to learn from responses to covid- while also being an exercise in ethical research practice. this reflection builds on and extends from our scholarly collaborations that have been ongoing since . our title recognizes this specific virus as stealthy. importantly, our choice of words identifies resident iranians-whose experiences were the original impetuses for this paper, and whose lives provide its empirical basis ( is iran's country code)-as equally steely. iran is a land of myths and rituals. most myths have been inscribed in persian literature. our central cultural celebration is nowruz, iranian new year, through which we welcome spring. this ritual dates back , years. in the shahnameh or book of kings, the jewel in the crown of persian literature, king jamshid of the pishdadian dynasty calls for nowruz to happen on the first day (hormoz) of the first month (farvardin) in iran's calendar. at its heart, nowruz is a celebration of the equilibrium between earth and nature, and this idea is central in iranian mythology and storytelling (bahar ; joneidi ) . after four hundred years of mending, learning, and creating, jamshid greeted spring on hormoz with a wish: for people to live in peace, to avoid suffering, and to harbour no resentment. nowruz is a celebration of community. people gather to show appreciation to god, wish for health and wealth, pray for the dead, and cook together. they also set a table, haft seen. they put seven (haft) items as symbols of sacred plants said to stimulate wellness and steadiness: airborne leaves symbolize balance, roots groundedness, and vegetation is associated with ethical properties (ameshaspand). such rituals have been repeated for millennia, and there are local and regional variations in the way people in iran and its bordering countries and their diasporas enact nowruz and the haft seen. in , iranians needed to change how we celebrated nowruz. the act of gathering ran the risk of imperilling life itself. this is where and when we modified traditions and gathered virtually. we struggled to reconcile ancient cultural practices with contemporary imperatives to distance. at the same time, within my extended family, we recognized these changes as ways of caring for each other and thus dovetailing with the spirit of nowruz. figure is my screen shot of our family's haft seen: four arrangements of items, carefully curated, under separate roofs rather than one roof. this is the first time in our lives that we did not gather in person. in my role as educator and professional naqqal, which means storyteller in persian, i am used to directing and performing or enacting cultural rituals on stages in iran and around the world (bisaillon b) . for the purposes of our collective analysis, though, i have used my camera's lens, creating an assemblage of images as a means to offer the opportunity to reflect on and question how our society's cultural and religious customs post-covid- will or must be modified. what will haft seen and performance rituals consist of in the wake of this disease? what i strongly suspect is that we iranians will be faced with making all sorts of heretofore unseen shifts in the ways we carry out customary practices in private and public spheres at nowruz and other times of the year. being deprived of formal learning during times of crisis can have long-term effects. this current moment in time shows us how the propagation of a weird and unpredictable virus disrupts people's daily routines globally. while workers in many vocational and professional milieus are not going to their workplaces, some services continue because they are considered core social goods. one of these is formal education. e-learning becomes a valuable mode of transmitting knowledge. can elearning meet people's learning needs and replace inperson contact partially or fully? i am a graduate student currently enrolled in courses that i take via e-learning. i am also an independent journalist and social activist living in tehran. i have been listening attentively to debates about virtual education, all the while watching schools and universities in iran close their doors. elearning poses serious challenges in iran. the technical infrastructure needed to support elearning is not fully available to us in this country. there is unequal supply and access to the internet, and limits to connectivity are especially pronounced in rural and remote villages. for another thing, the iranian internet is supplied by the state. from a security perspective, it is not possible to provide people with stable online access, since disconnections and disruption to internet supply are common. teachers and students have yet to receive training in the online strategies, tools, and techniques on which e-learning relies. updated online programmes are state filtered. in practice, multinational technology companies that could provide internet services are reluctant to do so because of international political sanctions against the iranian state. beyond issues of technical impediment, the domestic tools we have at our disposal have serious privacy concerns. in iran, teachers and learners alike consider screenmediated learning rather a luxury. many resist the idea, let alone the practice, of such a shift. recently, anticipated problems with being able to create workable and sustainable e-learning arrangements resulted in students mobilizing against the imposition or roll-out of electronic forms of teaching and learning. frustrated, learners protested and criticized the medium. as a result, protest hashtags mushroomed throughout iran. to illustrate this point, i took two screen shots, seen below. the first shows student slogans against the imposition of online learning (fig. ) and the second, state coverage of student mobilization (fig. ) . students designed the former as a poster, which they disseminated using social media. they specified their concerns, demanding that the state address them. their hashtag "no virtual learning" went viral, as the saying goes. their movement spread, rapidly becoming twitter's top persian-language trend. on the twitter account of its news agency, the government issued an official response to the students' campaign ( fig. ) . technical internet problems and student and teacher inexperience with online learning systems were reasons cited for its inability to improve virtual infrastructure. in the weeks following protests, the state upgraded the online infrastructure and learning systems it makes available to students throughout the country. using the internet to entertain, communicate, and engage with social media are integral parts of what many of us in iran do every day. much money and time are spent on these activities. yet, there is a long way to go before virtual education is broadly accepted here. as i observe changes to dominant ways of doing things in my country, triggered by covid- , i see that nimbleness and experimenting with new pedagogical approaches and tools are vital. changes to usual ways of receiving knowledge, using e-learning, and making selfeducation feasible, are important moves. i now muse about how we iranians will rise to the challenges that such changes are imposing. people who have left their countries as forced migrants are always "socially distanced" from their kin. family members have often had no choice but to fan out across the world. meanwhile, other family members are left behind because they have no other option but to stay back. as a sociologist and institutional ethnographer, i carry out inquiries from within routine, perhaps overlooked, and otherwise taken-for-granted practices of daily life. grounded in the social margins, i problematize cultural, economic, and bureaucratic relations that people in these places experience as problematic. since the first part of , my spouse and i have stayed still, steady, and sedentary. this is a new fig. separate, but together: changing haft seen and nowruz practices to care for each other within conditions imposed by covid- experience for us, who have shared a roof for more than a decade. during this time, we have listened to mainstream canada talk and talk (since we live in societies where texting, tweeting, and talking happen tirelessly). i have paid ethnographic attention to how people i have observed in person or virtually speak about what "social distancing" entails and feels like for them. masked pedestrians divert in half circles as they approach others on sidewalks. people have taken to referring to these practices as "a new normal." family members unmasked see and get seen via desktop and handheld screens. yet when we juxtapose the mainstream's generalized angst about such temporary impositions and the impossibility of meeting and greeting in the flesh in particular, a deep divide renders: vast numbers of inhabitants across canada have no choice but to create and participate in family life coordinated by screens permanently. i felt compelled to bring this point to life during a recent call with faraway family members (fig. ) . my kin are people who were forced from their countries by diabolical men in military suits backed by other diabolical men in aligned and non-aligned superpower suits. they are people who spent their first decades stranded, suspended, sponsored: becoming refugees-racialized migrants, people of diaspora; being poor-scraping by, supporting faraway kin (moussa ) . producing and reproducing family life deploying "social distancing" techniques are skills that former forced migrant families possess by necessity. we all suffer from the presence and effects of covid- . yet, some of us suffer more than others. the origins of the suffering i evoke arise structurally and includes pains induced by health-based prejudice in immigration law carried out in state practices (bisaillon a) . some among us know uncertainty, threat, and upheaval as stable features of our lives (albaih ) . mine is a call to pay ethnographic attention to teachings that our fellow inhabitants in societies whose populations increase through immigration, canada and australia for example, have to offer. having endured contingency and struggle imposed by chaos, disorientation, and anxiety beyond fig. the state on students against virtual learning: upgrading online infrastructure and learning systems their control, forced migrants have the hard-earned expertise to help people, families, and communities brace for, adapt to, and accept the uncertainty, confusion, and arbitrariness that covid- has thrusted on us and will continue to thrust on us. australia is the land "down under." its location in the recesses of the southern hemisphere, however, offers minimal protection from covid- . increasing international two-way travel exacerbates risk of disease spreading from person to person. i am a human rights social worker, deeply interested in the politics of disadvantage and in traversing the boundaries between civil and political rights and economic and social rights. as a somewhat privileged observer of the pandemic, i see opportunity for reflection and activism not previously apparent. i am cautiously optimistic that the time may be ripe for overhauling dominant discourses about structural disadvantage. in so doing, i ponder the impact of the pandemic in australia at three distinct yet interconnected levels, joined by ideas of justice and injustice: market economy, compassionate community, and citizen restrictions. much publicity around the impact of covid- is confined to the middle classes alone-classes who have previously benefited handsomely from unfettered capitalism and rampant consumerism. but, there is a hint that reliance on the market economy is showing cracks. there is now less judgement of those experiencing unemployment, with the current conservative government bolstering social security as the previously affluent are plummeting into poverty (king ) . my hope is for future political transformation that is attentive to seeing universal economic rights as essential to a fully functioning society. the second relates to the rebuilding of society based on compassionate community. what are the limits, however? i use an example from my research and advocacy, namely asylum seeker detention, where neither government nor media nor community present a compassionate and human rights affirming response. stopping asylum seeker boats has been a mantra of successive governments in australia, a country that shamefully criminalizes and warehouses would-be immigrants who, on board boats, aim to land and remain (briskman, latham, and goddard ) . migrants continue to be detained despite the risk of virus spread in closed environments. in an ironic turnabout since the outbreak of covid- , leisure-time luxury liners are now stopped and passengers detained (quarantined) for two weeks in hotels to prevent disease spread. i render this irony overt in figure . i took the top image with my telephone during fieldwork. in it, we see migrant people on a boat. i have deliberately concealed their faces so we cannot identify them. below it is a photo in the public domain: the ruby princess cruise ship moored in sydney harbour. in juxtaposing these images, i pinpoint differential treatment of arrivals at australia's shores. in the former, people seeking state protection are rounded up, their vessel headed for an immigration detention centre, their future uncertain. in the latter, privileged passengers disembark freely. after they do, they are exposed to covid- , contract infection, and death follows for many. these twinned images are meant to provoke. will complaints about containment, albeit in comfortable settings for a limited time, generate empathy for asylum seekers warehoused in prison-like settings who also, and importantly, have committed no crime? the final area where i am less hopeful is also in the realm of civil rights. with extraordinary powers acceded to the state in the interest of public health, can we be assured that these will be reversed in good times? we are observing a rise in neighbourhood policing to ensure social distancing rules are respected. civil libertarians point out that targets are disadvantaged localities and over-policed groups, including indigenous communities. measures in some jurisdictions, such as excessive fines for minor breaches and threats of imprisonment or tagging, are being supplemented nationally with the covidsafe app, which although said to be voluntary, is underpinned by persuasive rhetoric and enacted through surveillance practices. arising from the preliminary reflections gathered in our article, we proffer some insights into what covid- may cast upon the world, drawing from distinct contexts and bearing in mind that this essay is greater than the sum of its parts. we predict lives and ways of being will be transformed post-pandemic, driven by new ways of being and relating that many of us have not previously encountered. will nowruz return to a continuation of its origins, or will virtual celebration of significant events, such as easter and passover, transmute into new relationships of restoring health and equilibrium with less travel and more inclusivity? will the ideas that underpin education metamorphize into online dominance with current inequities being redressed across the world for people who are not the disadvantaged? will those who have long known dislocation from family connection teach us new ways of restoring and maintaining ties of kinship? might the isolation we all now experience lead us to become less acquisitive and more relational and cooperatively focused? in looking at possibilities, we suggest that idealism about the future be tempered with criticality, recognizing the bleak prospect that we may well just revert to the previous unequal status quo while seeing an escalation of the erosion of civil liberties for us all. your "new normal" is our "old normal from myth to history finally, some changes to health-based discrimination in canadian immigration law. the conversation human rights overboard: seeking asylum in australia measurement in ancient iran there's new income support if you've lost work due to covid- . here's who is eligible, and how to apply storm and sanctuary: the journey of ethiopian and eritrean women refugees publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations