key: cord-1053816-bzbr9ios
authors: Anastassopoulou, Cleo; Spanakis, Nicholas; Tsakris, Athanasios
title: SARS-CoV-2 transmission, the ambiguous role of children and considerations for the reopening of schools in the fall
date: 2020-09-03
journal: Future Microbiol
DOI: 10.2217/fmb-2020-0195
sha: a8bf37c3169a9f89118c5538528a73a9cca10c19
doc_id: 1053816
cord_uid: bzbr9ios

Tweetable abstract The reopening of schools in the fall entails risks given the controversies in pediatric COVID-19 pathogenesis and the ambiguous role of children in transmission.

transmission of both SARS coronaviruses leading to super-spreading events is plausible [17] . However, accumulating evidence shows that, in contrast to SARS-CoV-1, SARS-CoV-2 is transmitted before the onset of symptoms by symptomatic persons and even by asymptomatic individuals [18, 19] . Droplets of saliva and other secretions are expelled from the respiratory tract (the mouth and nose) not only during such obviously forceful expiratory activities as sneezing and coughing, but also during breathing, particularly during intense physical exercise, talking, laughing and singing. We cannot help but wonder whether the extrovert nature of people from the south of Europe, who typically speak loudly and have increased and often demonstratively affectionate social contacts not only with significant others, but also with friends and acquaintances and, notably, with extended family members, including elderly grandparents, has contributed to the devastating trajectories of the epidemic in countries like Italy and Spain.

Respiratory exhalations do not solely consist of mucosalivary droplets that follow short-range semi-ballistic emission trajectories allowing for a dichotomy between large and small droplets, as the still adopted by the WHO and other agencies transmission model originally proposed by William F Wells for tuberculosis in the 1930s had suggested. Instead, according to the new model for respiratory emissions, exhalations consist of clusters of varying in size droplets, trapped in a multiphase turbulent gas (a puff ) cloud of a locally moist and warm atmosphere that prevents evaporation, thereby considerably extending the time and distances virus particles can travel [20] . The implication of the current model is that a multiplicity of biophysical parameters determines the rates at which droplets of all sizes settle out or evaporate, depending not only on their size, but also on the degree of turbulence and speed of the gas cloud, coupled with the properties of the ambient environment (temperature, humidity and airflow), further perplexing the matter. Airborne transmission of aerolized virus particles, which has just been identified as an additional, if not the dominant, spreading route of COVID-19, appears to have contributed to the successful propagation of the novel coronavirus [21] . This latest finding prompted 239 scientists from 32 countries to urge the WHO and other bodies to address this potential in conjunction with contact transmission and mandate face covering in public to mitigate the airborne microdroplet transmission, in an open letter published on 6 July [22] . Hence, the correlates of the sustained human-to-human transmission of SARS-CoV-2 have not been clearly defined yet.

School closures that are commonly suggested for mitigating epidemics of respiratory infection were among the first social distancing measures implemented during this pandemic. Decreases in COVID-19 cases were indeed noted after school and daycare closures in many communities, even though modeling studies predicted that school closures alone would prevent only 2-4% of deaths, much less than other social distancing interventions, according to a review from the UK led by University College London [23] .

From the early phases of the outbreak, it became apparent that adult pathogenesis varies with age and gender since older men with comorbidities (e.g., diabetes or cardiovascular disease) were at higher risk for severe illness from COVID-19 [24] [25] [26] . At the other end of the spectrum, children generally experience less severe disease and have better prognosis after infection with SARS-CoV-2 [27] , although a multisystem inflammatory syndrome (MIS-C) resembling Kawasaki Disease and toxic shock syndrome-like conditions has been observed in pediatric patients [28] . In addition, infants and preschool-aged children may be prone to more significant illness than older children [29, 30] . Several explanations have been suggested for the typically low morbidity and mortality in children, including fewer underlying medical conditions and healthier respiratory tracts because of less exposure to cigarette smoke and air pollution and stronger innate immune responses [31] . An alternative explanation for the generally benign disease course in pediatric cases pertains to the less mature, and thus of decreased functionality (e.g., binding potential)-ACE2 protein receptors for SARS-CoV-2 entry into cells. In agreement with this reasoning, data suggest that SARS-CoV-2 infections in children involve the upper rather than the lower respiratory tract, the typical site of severe COVID-19 disease where ACE2 receptors are more abundant [29] .

The role of children in the transmission of the novel coronavirus is unclear [32] . By fitting an age-structured mathematical model to epidemic data from China, Italy, Japan, Singapore, Canada and South Korea, Davies et al. estimated that susceptibility to infection in individuals under 20 years of age was approximately half that of adults aged over 20 years and that interventions aimed at children might have a relatively small impact on reducing SARS-CoV-2 transmission, particularly in settings where the transmissibility of subclinical infections is low [33] . Studies from Israel and Greece that examined the dynamics of COVID-19 transmission within families showed significantly lower infection rates in children compared with adults residing in the same household [34, 35] . In a study of young children from northern France [36] , SARS-CoV-2 infection was found to be largely mild or asymptomatic and there was no evidence of onwards transmission from children in the school setting in line with previous studies from Australia, Ireland and France [37] [38] [39] . Primary or elementary school children aged 6-11 years were less likely to transmit the virus compared with high school aged children who could transmit the virus as efficiently as adults. A large, carefully conducted study from South Korea corroborated these results [40] . The reason why children younger than 10 years might transmit to others much less often than adults could be because of the air volume, and therefore of the virus-laden air, normally exhaled by children that is smaller or closer to the ground, making it less likely that adults would breathe it in. Older children in middle and high school, who can be as tall as adults and yet may have some of the same unhygienic habits as young children, were found to be even more likely to infect others compared with adults by this South Korean study [40] .

Analysis of 3303 COVID-19 pediatric patient sputum samples by Christian Drosten's group in Germany using two different PCR systems to assess viral load, determined that children under the age of 19 produce virtually the same average levels of viral RNA as adults [41] . Another study from Chicago showed that children younger than 5 years had tenfold to 100-fold greater amount of SARS-CoV-2 viral RNA, which correlates with infectious virus [42] , in their upper respiratory tracts compared with older children aged 5-17 years or adults aged 18-65 years [43] . Sampling bias due to the increased possibility of asymptomatic infection in children that reduces the chances of being tested early in infection when virus levels in the nasopharynx are high, could explain the disparity in results from different studies. Since viral RNA levels in the feces remain high for more than three weeks after the onset of symptoms in contrast to viral RNA in the nose and saliva that decline drastically within 1-2 weeks, analyzing stool samples for transmissible virus from mildly symptomatic and asymptomatic children could provide the experimental data to validate this argument [44] . Viral replication in the GI tract and prolonged fecal shedding by infected children, particularly for infants and younger children who are not toilet-trained, may have substantial implications for community spread in day-care centers, schools and homes [29, 32] .

Further studies are needed to clarify the role of children in the transmission of the novel coronavirus. In this respect, a large prospective NIH-funded study of 6000 people from 2000 US families in 11 cities, called human epidemiology and response to SARS-CoV-2, will help determine the incidence of novel coronavirus infection in children in the USA and whether rates differ between children who have asthma or other allergic conditions and children who do not [45] .

The new US Centers for Disease Control and Prevention (CDC) guidelines on education and child care support the opening of schools in the fall. The main arguments in favor of the return to in-person schooling come from early reports that suggest that children are less likely to be infected than adults (at least based on nasopharyngeal viral RNA detection as discussed in the previous subsection), and when they do contract COVID-19, they generally have less serious illness. As of 21 July 2020, children and adolescents under 18 years old accounted for under 7% of COVID-19 cases and less than 0.1% of COVID-19-related deaths in the USA.

Schools, an important part of the infrastructure of communities, are indeed critical for the socialization and education of children, especially for students who rely on special education services (e.g., speech and occupational therapy). However, the evidence about whether returning to school results in increased transmission or outbreaks is inconclusive. Transmission in schools appears to mirror rates in the community and, therefore, school reopenings seem to be safe when community SARS-CoV-2 transmission rates are low, as shown by international studies that have assessed how readily COVID-19 spreads in schools [46] . School children are nonetheless anticipated to contribute to the community transmission of SARS-CoV-2 through their large numbers of daily social contacts, some of which are intergenerational, with older age groups where the risk for more severe illness is increased. Hence, the reopening of schools should be considered carefully, with continuous monitoring of possible resurgence in infections through frequent testing and isolation of infected -and perhaps more importantly of infectious -students, educators and other staff, for their safety and for the safety and wellbeing of their families. The current Centers for Disease Control and Prevention guidelines do not recommend universal screenings by schools; instead, they strongly encourage parents or caregivers to monitor their children every day for 'signs of infectious illness', most likely referring to symptoms that, if present at all, are perceived differently by infected individuals, and to keep sick students at home.

When schools reopen, additional strategies to limit transmission should be implemented as at other essential workplaces, including hand hygiene, physical distancing considering the recent advances in the biophysics of host-to-host respiratory disease transmission, respiratory etiquette and masks for older children. Such mitigation measures would also help contain other respiratory infections in the community. Alternative plans for virtual learning should be in place in the event of a school closure if community transmission levels cannot be controlled. Finally, an alternative consideration that could provide both direct and indirect benefit given that children may contribute to adult infections and develop life-threatening disease themselves, is that vaccine development efforts for COVID-19 should perhaps also consider the pediatric population.

Until we have safe and efficient prophylactic vaccines or therapeutics, or until SARS-CoV-2 becomes endemic, we have to continue to expect the unexpected from this novel coronavirus, the even brief encounter of which with our species, has changed the world forever.

No specific funding was obtained for this study. The authors declare no competing interests. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia

Coronavirus disease 2019 (COVID-19): situation report

warns of 'dangerous phase' of pandemic as outbreaks widen

A pneumonia outbreak associated with a new coronavirus of probable bat origin

Hosts and sources of endemic human coronaviruses

Recombination, reservoirs, and the modular spike: mechanisms of coronavirus cross-species transmission

Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS-coronavirus 2

Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model

Infection and rapid transmission of SARS-CoV-2 in ferrets

Simulation of the clinical and pathological manifestations of coronavirus disease 2019 (COVID-19) in golden Syrian hamster model: implications for disease pathogenesis and transmissibility

Transmission of SARS-CoV-2 in domestic cats

Respiratory disease in rhesus macaques inoculated with SARS-CoV-2

Pathogenesis and transmission of SARS-CoV-2 in golden hamsters

SARS-CoV-2 infection in farmed minks

Infection of dogs with SARS-CoV-2

European advisory board on cat diseases. SARS-coronavirus (CoV)-2 and cats

Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1

Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections

Temporal dynamics in viral shedding and transmissibility of COVID-19

Turbulent gas clouds and respiratory pathogen emissions: potential implications for reducing transmission of COVID-19

Identifying airborne transmission as the dominant route for the spread of COVID-19

It is time to address airborne transmission of COVID-19

School closure and management practices during coronavirus outbreaks including COVID-19: a rapid systematic review

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

Clinical features of patients infected with 2019 novel coronavirus in Wuhan

Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China

Systematic review of COVID-19 in children shows milder cases and a better prognosis than adults

Multi-system inflammatory syndrome in children (MIS-C) following SARS-CoV-2 infection: review of clinical presentation, hypothetical pathogenesis, and proposed management

COVID-19 in children: initial characterization of the pediatric disease

Epidemiology of COVID-19 among children in China

Are children less susceptible to COVID-19?

The role of children in transmission of SARS-CoV-2: a rapid review

Age-dependent effects in the transmission and control of COVID-19 epidemics

The role of children in the dynamics of intra family coronavirus 2019 spread in densely populated area

Transmission dynamics of SARS-CoV-2 within families with children in Greece: a study of 23 clusters

SARS-CoV-2 infection in primary schools in northern France: a retrospective cohort study in an area of high transmission

No evidence of secondary transmission of COVID-19 from children attending school in Ireland

Cluster of coronavirus disease 2019 (Covid-19) in the French Alps

NCIRS. COVID-19 in schools -the experience in NSW

Contact tracing during coronavirus disease outbreak, South Korea

An analysis of SARS-CoV-2 viral load by patient age. medRxiv

Culture-competent SARS-CoV-2 in nasopharynx of symptomatic neonates, children, and adolescents

Age-related differences in nasopharyngeal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) levels in patients with mild to moderate coronavirus disease

Epub ahead of print)

Viral RNA load in mildly symptomatic and asymptomatic children with COVID-19

The National Institute of Allergy and Infectious Diseases (NIAID)

School openings across globe suggest ways to keep coronavirus at bay, despite outbreaks