The most comprehensive study of COVID-19 pediatric patients to date show that children play a larger role in the community spread of virus

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In the most comprehensive study of COVID-19 pediatric patients to date, Massachusetts General Hospital (MGH) and Mass General Hospital for Children (MGHfC) researchers provide critical data showing that children play a larger role in the community spread of COVID-19 than previously thought.

In a study of 192 children ages 0-22, 49 children tested positive for SARS-CoV-2, and an additional 18 children had late-onset, COVID-19-related illness.

The infected children were shown to have a significantly higher level of virus in their airways than hospitalized adults in ICUs for COVID-19 treatment.

“I was surprised by the high levels of virus we found in children of all ages, especially in the first two days of infection,” says Lael Yonker, MD, director of the MGH Cystic Fibrosis Center and lead author of the study, “Pediatric SARS-CoV-2: Clinical Presentation, Infectivity, and Immune Reponses,” published in the Journal of Pediatrics.

“I was not expecting the viral load to be so high. You think of a hospital, and of all of the precautions taken to treat severely ill adults, but the viral loads of these hospitalized patients are significantly lower than a ‘healthy child’ who is walking around with a high SARS-CoV-2 viral load.”

Transmissibility or risk of contagion is greater with a high viral load.

And even when children exhibit symptoms typical of COVID-19, like fever, runny nose and cough, they often overlap with common childhood illnesses, including influenza and the common cold.

This confounds an accurate diagnosis of COVID-19, the illness derived from the SARS-CoV-2 coronavirus, says Yonker. Along with viral load, researchers examined expression of the viral receptor and antibody response in healthy children, children with acute SARS-CoV-2 infection and a smaller number of children with Multisystem Inflammatory Syndrome in Children (MIS-C).

Findings from nose and throat swabs and blood samples from the MGHfC Pediatric COVID-19 Biorepository carry implications for the reopening of schools, daycare centers and other locations with a high density of children and close interaction with teachers and staff members.

“Kids are not immune from this infection, and their symptoms don’t correlate with exposure and infection,” says Alessio Fasano, MD, director of the Mucosal Immunology and Biology Research Center at MGH and senior author of the manuscript.

“During this COVID-19 pandemic, we have mainly screened symptomatic subjects, so we have reached the erroneous conclusion that the vast majority of people infected are adults.

However, our results show that kids are not protected against this virus.

We should not discount children as potential spreaders for this virus.”

The researchers note that although children with COVID-19 are not as likely to become as seriously ill as adults, as asymptomatic carriers or carriers with few symptoms attending school, they can spread infection and bring the virus into their homes.

This is a particular concern for families in certain socio-economic groups, which have been harder hit in the pandemic, and multi-generational families with vulnerable older adults in the same household.

In the MGHfC study, 51 percent of children with acute SARS-CoV-2 infection came from low-income communities compared to 2 percent from high-income communities.

In another breakthrough finding from the study, the researchers challenge the current hypothesis that because children have lower numbers of immune receptors for SARS-CoV2, this makes them less likely to become infected or seriously ill.

Data from the group show that although younger children have lower numbers of the virus receptor than older children and adults, this does not correlate with a decreased viral load.

According to the authors, this finding suggests that children can carry a high viral load, meaning they are more contagious, regardless of their susceptibility to developing COVID-19 infection.

The researchers also studied immune response in MIS-C, a multi-organ, systemic infection that can develop in children with COVID-19 several weeks after infection.

Complications from the accelerated immune response seen in MIS-C can include severe cardiac problems, shock and acute heart failure.

“This is a severe complication as a result of the immune response to COVID-19 infection, and the number of these patients is growing,” says Fasano, who is also a professor of Pediatrics at Harvard Medical School (HMS).

“And, as in adults with these very serious systemic complications, the heart seems to be the favorite organ targeted by post-COVID-19 immune response,” adds Fasano.

Understanding MIS-C and post-infectious immune responses from pediatric COVID-19 patients is critical for developing next steps in treatment and prevention strategies, according to the researchers.

Early insights into the immune dysfunction in MIS-C should prompt caution when developing vaccine strategies, notes Yonker.

As MGHfC pediatricians, both Yonker and Fasano are constantly fielding questions from parents about the safe return of their children to school and daycare.

They agree that the most critical question is what steps the schools will implement “to keep the kids, teachers, and personnel safe.” Recommendations from their study, which includes 30 co-authors from MGHfC, MGH, HMS, Massachusetts Institute of Technology, Brigham and Women’s Hospital and Harvard T.H. Chan School of Public Health, include not relying on body temperature or symptom monitoring to identify SARS-CoV-2 infection in the school setting.

The researchers emphasize infection control measures, including social distancing, universal mask use (when implementable), effective hand-washing protocols and a combination of remote and in-person learning.

They consider routine and continued screening of all students for SARS-CoV-2 infection with timely reporting of the results an imperative part of a safe return-to-school policy.

“This study provides much-needed facts for policymakers to make the best decisions possible for schools, daycare centers and other institutions that serve children,” says Fasano.

“Kids are a possible source of spreading this virus, and this should be taken into account in the planning stages for reopening schools.”

Fasano fears that a hurried return to school without proper planning could result in an uptick in cases of COVID-19 infections.

“If schools were to reopen fully without necessary precautions, it is likely that children will play a larger role in this pandemic,” the authors conclude.


Epidemiology and disease characteristics of COVID-19 in children

As of 26 July 2020, children made up a very small proportion of the 744 448 cases reported to TESSy as case- based data in the EU/EEA and in the UK; 31 380 (4%) were children aged under 18 years. Of these, 7 044 (24% of children) were below five years of age, 9 645 (32%) between five and 11 years and 13 020 (44%) between 12 and 18 years.

The age distribution of cases observed in the EU/EEA and the UK reflects testing policies and case definitions, which usually include the presence of symptoms.

It is possible that the small proportion of cases reported among children reflects a lower risk of children developing COVID-19 symptoms or the fact that children are generally not prioritised for testing as they commonly experience milder symptoms.

There might also be a lower tolerability/acceptance for testing children, given the invasiveness of nasopharyngeal swabbing.

Pooled and country-specific TESSy data are available in an online report series, published weekly on the ECDC website: https://covid19-surveillance-report.ecdc.europa.eu/.

Common signs and symptoms in children

COVID-19, like SARS and MERS, is observed less frequently in children, who tend to present milder symptoms and have a better overall outcome than adults [20-24].

The most commonly reported symptoms in children are fever and cough [21,22,25]. Other symptoms include gastrointestinal symptoms, sore throat/pharyngitis, shortness of breath, myalgia, rhinorrhoea/nasal congestion and headache, with varying prevalence among different studies [21,22,25,26].

In a cohort of 582 paediatric cases of SARS-CoV-2 infection from 21 European countries, signs and symptoms upon presentation at healthcare institutions included fever (pyrexia) (65%), upper respiratory tract infection (54%), headache (28%), lower respiratory tract infection (25%) and gastrointestinal symptoms (22%) [27].

Correspondingly, studies from Italy [4,5,28,29], Germany [30], UK [31], Turkey [32] and Sweden [33] described similar symptoms and reported fever and cough as the most commonly observed symptoms. Gastrointestinal symptoms were more prevalent in children with severe COVID-19 than in those with mild disease [34].

Asymptomatic infection in children has been described in several large case series from China, which reported 4% to 28% asymptomatic paediatric cases among cases tested based on symptoms, signs or contact tracing [35,36].

A recent systematic review presenting data on 2 914 paediatric patients with COVID-19 from China, Spain, Iran, the Republic of Korea and the United States identified 14.9% asymptomatic cases in children [22].

Others have reported 18% asymptomatic cases in a meta-analysis of 551 laboratory-confirmed cases in children [37] and 16% asymptomatic cases among a European cohort of 582 children [27]. Similar observations were made for infants and neonates, 16% of whom were asymptomatic in a review of 160 infants with confirmed COVID-19 [25].

One explanation for why children might have milder symptoms of COVID-19 than adults is that children have a much more effective innate immune response than adults or elderly people. The observation of virus transmission by asymptomatic cases is strengthening the scientific evidence that the highly effective innate immune response against viruses, such as in children, provides a sufficient suppression of virus replication to prevent the development of COVID-19 specific symptoms [38].

Another explanation for milder symptoms in children is the possibility of cross-immunity against SARS-CoV-2 developed through previous seasonal coronavirus infection. The evidence regarding cross-immunity from prior seasonal coronavirus infection and anti-SARS-CoV-2 antibody levels is conflicting [39,40].

Severity and complications

Among children reported by EU/EEA countries and the UK to TESSy, the proportion of cases hospitalised were lowest in the age groups 5-11 years and 12-18 years (3% and 4% respectively) and highest among 0-4 year olds (10%).

Among adults, the proportion of hospitalised cases increased with age and was highest among 70-79 and 80-89 year olds (39% and 35% respectively) (Figure 2a). Deaths among cases under 18 years were extremely uncommon; only six out of a total of 19 654 (0.03%) deaths reported in TESSy were among children (for countries reporting complete data on outcome).

This corresponds to a crude case-fatality of 0.03% among those aged under 19 years, compared to 5.8% among those aged 18 years and above, driven largely by deaths in cases aged 60 years and above, where case-fatality rates increase to 36% among those aged 90 years or above (Figure 2b). I

n weekly monitoring of all-cause mortality in 24 participating European countries or regions, mortality among 0-14 year olds has not exceeded background rates, in stark contrast to the significant excess mortality among the older adult age groups [41].

Severe or critical illness has been reported among 2.5% to 5% of paediatric cases from China [35,42], and more recently, 4% of cases were reportedly as severe or critical in a systematic review [43] and meta-analysis [21] of

4 857 and 2 855 children, respectively. Infants and neonates were described as more vulnerable to severe COVID‐ 19 than other paediatric groups in recent literature reviews [22,25,44], although in most cases a low mortality rate (0.006%) with favourable outcomes was reported for this group [25,27].

Pre-existing medical conditions have been suggested as a risk factor for severe disease and ICU admission in children and adolescents [26,27].

Several countries affected by the COVID-19 pandemic reported cases of children who were hospitalised in intensive care units due to a rare paediatric inflammatory multisystem syndrome (PIMS) or multisystem inflammatory syndrome in children (MIS-C) [45-47], characterised by a systemic disease involving persistent fever, inflammation and organ dysfunction following exposure to SARS-CoV-2 [48-50]. For further information on PIMS in SARS-CoV-2

patients, please refer to the ECDC rapid risk assessment [51]. Paediatric patients have also been reported with cardiovascular involvement [52-55], namely myocarditis, as well as with renal dysfunction [56,57].

Viral shedding of SARS-CoV-2 among children

The detection of viral RNA by PCR does not directly indicate infectivity. Nevertheless, the detection of viral RNA and the measure of viral load are potentially useful markers for infectiousness, as well as for assessing disease severity and prognosis.

Overall for COVID-19 patients, SARS-CoV-2 viral RNA has been detected in most bodily fluids including blood [58-60], saliva [58,59], nasopharyngeal specimens [61], urine [62], and in stool [63,64].

Based on the limited case data, shedding of viral RNA through the upper respiratory tract may be of shorter duration in children than adults. In contrast, children show prolonged viral shedding via the gastrointestinal route after clearing the virus from the respiratory tract [65].

Further, a recent study suggests that the viral load in children under five years with mild to moderate COVID-19 symptoms is higher than in older children and adults [66].

There does not appear to be a significant difference in viral RNA load between symptomatic children and symptomatic adults, indicating that children shed viral RNA (whether viable or not) in a similar manner to adults [67].

This does not, however, indicate whether children transmit the infection to an equal extent, given that the exact load of viable virus is unknown and that it will depend on the specimen from which the virus is identified (e.g. upper respiratory tract versus gastrointestinal). Children have been shown to develop neutralising antibodies after SARS-CoV-2 infection [68].

Infectiousness of children in household settings

In a manuscript (as yet not peer reviewed) relating to contact tracing efforts carried out during school closures in Trento, Italy, the attack rate among contacts of 0-14 year old cases was 22.4%, which is higher than that of working-age adults (approximately 13.1%) [69].

In this study, not all asymptomatic contacts were tested. South Korea has permissive testing recommendations for contacts identified during contact tracing, meaning that more secondary cases are identified among children than in other settings.

The attack rate among household contacts of index cases aged 0-9 years and 10-19 years was 5.3% and 18.6%, respectively, indicating transmission potential in both children and adolescents, and possibly more effective transmission in adolescents than in adults [70].

These results, consistent with unpublished data from EU/EEA and UK contact tracing efforts, support the transmission potential of children, in household settings.

Seroprevalence of COVID-19 antibodies among children

Seroprevalence studies aim to determine the proportion of population groups that have detectable antibodies against SARS-CoV-2, in order to provide an indication of how many people have been infected with the virus.

A number of seroprevalence studies have been undertaken in the EU/EEA region, while others are still ongoing. Table 1 summarises preliminary results found in literature searches or on countries’ official websites. All studies were conducted after the peak of the first wave at various points in time, depending on national response measures (before, during or after lockdown).

Table 1. Descriptions and results of sero-epidemiological studies including children in EU/EEA Member States and Switzerland from public sources, as of 24 July 2020
  Country  Number (n)  Type of study  Age groupTime of sampling (in 2020)  Timing  Laboratory methodProportion of positive samples (%)
Seroprevalence studies designed for children and adolescent populations
France (Paris area)* [71]605 childrenProspective cross sectional multi-centre ambulatory paediatric clinics0-15 years14 April-12 MayAfter peak of first wave – during lockdownBiosynex COVID-19 BSS test IgG/IgM10.7
Germany (Baden- Württemberg)* [72]2 466 childrenCross sectional private diagnostic labs – 2 collections0-20 years30 March – end AprilDuring lockdownEuroimmun IgG5
France (Oise)* [73]242 studentsRetrospective closed cohort in high school14-17 years30 March-4 AprilAfter school outbreak – during lockdownMultiple assays10.2
Germany (Saxony)* [74]1 538 studentsCross sectional in 13 Schools of the region14-17 years25 May-30 JuneAfter peak of first wave – after lockdownDiasorin LIAISON, CMIA and Abbott0.7
General population seroprevalence studies
Spain [75]6 527 childrenNationwide population based household random sampling – 2 collectionsHousehold Focus: 0- 19 years27 April – 11 MayAfter peak of first wave – during lock downPOC (Orient Gene Biotech COVID-19 IgG/IgM) & Immunoassay (Abbott Laboratories)3.4- 3.8
Spain (Barcelona) [76]Overall sampling 311 individualsRandom age stratified population (asymptomati c children)0-14 and 15-29 years21 April – 24 AprilAfter peak of first wave – During lock downRapid lateral flow immunoassay IgG/IgM0 and 10
Switzerland (Geneva) [77]214 childrenRepeated population based household sampling5-19 yearsThree weekly samplings in AprilAfter peak of first waveEuroimmun IgG6.1
Belgium [78]N/ANational prospective cross sectional residual sera from private diagnostic labs – 2 collections0-20 years30 March – end AprilDuring lockdownEuroimmun IgG5
Germany (Gangelt) [79]405 householdsRandom sample household study5 years-14 years and 15-34 years30 March – 7 AprilAfter peak of first wave – before lockdownEuroimmun IgG9.1 and 15.4
  Country  Number (n)  Type of study  Age groupTime of sampling (in 2020)  Timing  Laboratory methodProportion of positive samples (%)
Germany (Neustadt-am- Rennsteig) [80]58 childrenPopulation- based cohort – household samplingChildren- adolescents12-22 MayAfter peak of first wave -after lockdownCombination of ELISA and CLIA/CMIA tests1.7
Netherlands [81]Overall sampling 2 096 individualsNationwide random population sample0-19 years31 March – 13 AprilDuring lockdownNA1-2%
Sweden (multiple regions) [7]1 600 childrenResidual sera from outpatients presenting for non-COVID related consultation0-19 yearsweeks 18- 21No lockdownBead-based multiplex serology assay4.7-7.5

Two studies, conducted by France and Germany [71-74] had a special focus on children (0-10 years) and two on adolescents (14-17 years) in school settings. Both studies in France found a prevalence of SARS-CoV-2 antibodies of around 10%, whereas in Germany the results were <1% among the younger population.

A number of SARS-CoV-2 seroprevalence studies have been conducted in the general population. The methodology used in these studies was mainly a random household sampling, while others used convenience samples (e.g. leftover sera).

When extrapolating seroprevalence results for the young age group (0-18 years), the actual denominators for this population were not always shown in detail, or included very small sample sizes. This is a limitation for the current synthesis and interpretation.

As described above, the seroprevalence results in the general population within the EU/EEA region vary from 0-10%. Although the sampling time-frames differ among the countries performing the studies (in relation to local lockdowns), the extent of mitigation measures deployed does not seem to significantly affect the level of seroprevalence in the young population.

Results from Sweden, which did not close schools or enforce mandatory lockdown measures, show a presence of 4.7-7.5% of SARS-CoV-2 antibodies among the young population over a period of four weeks, which is comparable to seropositivity among adults [7].

In general, the majority of countries report slightly lower seroprevalence in children than in adult groups (20-55 years), however these differences are small and uncertain.

The lower seroprevalence in children can be an indication that children are less susceptible to infection and/or less frequently infected than adults, and therefore play a less significant role in the spread of the virus [81].

A population seroprevalence study in Geneva [77] estimated that in young children aged 5–9 years the risk of being seropositive was lower (RR 0.32 (CI 0.11–0.63) than in those aged 20–49 years.

A study from Paris, including a relatively large number of children (>600), combined RT-PCR SARS-CoV-2 and serology results to assess the spread of SARS-CoV-2 infection (i.e. the study captures both people with ongoing viral infection and those with antibodies from past exposure to the virus).

Less than 2% were positive for RT-PCR for SARS-CoV-2, while seropositivity was much higher (10.7%). No significant difference was seen in the proportion of positive RT-PCR or serology results between asymptomatic and pauci-symptomatic children.

However, asymptomatic children with no history of symptoms during the preceding weeks accounted for two thirds of children with positive serology results (28/41). This supports the hypothesis that asymptomatic infections are more frequent in the young than in older age groups.

In summary, cross-sectional epidemiological studies show a tendency towards lower proportions of antibodies among children and adolescents than in adults.

The study done in Sweden did not show a difference between those under 19 years and working-age adults. More specialised studies need to be performed, with a focus on this population to better understand infection as well as antibody dynamics.

Evidence relating to the role of childcare and school settings in COVID-19 transmission

Evidence related to the role of childcare and school settings in COVID-19 transmission between children and adults relies on detection of potential cases or clusters, followed by extensive contact tracing and follow-up to determine if any close contacts develop symptoms and test positive for SARS-CoV-2 within the 14-day incubation period. In the following sections, evidence is provided from Member State reports to a country survey and from scientific literature.

Overview of outbreaks and transmission in childcare school settings: experiences from Member States

Of 31 EU/EEA and UK countries, 151 replied to the survey. To gather more detailed information and clarification of their replies, five countries2 were invited to participate in a follow-up phone call.

Of the 15 countries responding to the survey, six countries specifically reported having identified COVID-19 outbreaks in school settings and nine countries reported not having identified any outbreaks.

Of the nine countries not having observed outbreaks in educational facilities, four countries specified not having seen any cases at all and the remaining five reported that individual cases in pupils and/or adults had been identified, but with no evidence of secondary transmission.

The fact that four of the countries had not seen any cases may partly be linked to their schools having been closed early in the pandemic.

The six countries reporting that clusters had been identified in educational settings all said that these were limited in number; only involving a few secondary cases. Only one country reported a cluster of more than 10 cases (13 confirmed, four students and nine staff), however this event was seen as an exception rather than the norm.

Ten countries replied that they did not have strong indications of children-to-adult transmission, whether in schools (all 10 countries) or in other settings (six of these 10 countries). One country reported knowledge of a single event in which one child transmitted the infection to both parents. The remaining four countries said that they could not give a specific reply to the question.

The above findings were expanded on through follow-up calls with five countries. Only one of the five countries described one or two events in which secondary transmission had been identified in a school setting.

Several of the countries with whom follow-up was arranged said that their schools had, at some point during the peak of their outbreaks, been closed as a mitigation measure, and recognised this in itself could be an explanation as to why school outbreaks had not occurred.

However, these countries highlighted the fact that, up until their schools were closed (and if their schools re-opened before the summer break), outbreaks in schools had still not been observed or identified.

Two of the five countries further explained that there were challenges in achieving adequate capacity for contact tracing and outbreak investigation at some point during their epidemic peak and, therefore, perhaps not all outbreaks were identified and/or traced.

However, even taking this into account, they did not consider that many school outbreaks would have been missed since their national surveillance systems would have been sensitive enough to have picked up any signals indicating that children and schools were substantially affected.

In summary, clusters in educational facilities were identified in several of the 15 reporting countries, however those that occurred were limited in number and size, and were rather exceptional events. Several countries specifically said that they had no indication that school settings played a significant role in the transmission of COVID-19.

Secondary transmission in schools, either from child-to-child or from child-to-adult, was perceived to be rare. Countries where schools had re-opened by the time of the survey stated that they had not seen an increase in cases in these settings. Responses from the countries suggest that, so far, schools have not been a major outbreak environment for COVID-19 in the EU/EEA and UK.

Overview of outbreaks and transmission in school settings: evidence from the literature

One overall limitation of surveillance and contact tracing studies is that surveillance is often symptom-based, thereby often omitting possible asymptomatic cases in children. To supplement surveillance and outbreak study data provided by countries, ECDC performed a literature review (see Methods) to assess the evidence for SARS- CoV-2 transmission between different actors in the school setting and the evidence for school closures on overall COVID-19 transmission (Figure 3).

Note: solid arrows represent routes of transmission where there is strong evidence for transmission, dashed lines represent routes of transmission where there is variable or mixed evidence of transmission between individuals within the childcare and school settings and to the community/household outside of educational settings.

What is the evidence of transmission between children within the school setting?

Available evidence appears to suggest that transmission among children in schools is less efficient for SARS-CoV-2 than for other respiratory viruses such as influenza [82]. However, this evidence is mainly derived from school outbreaks which tend to rely on detecting symptomatic cases only and will therefore underestimate the number of infected, asymptomatic, and potentially infectious children in these outbreaks.

In France, a carefully documented study identified an infected child (age nine years) who had interactions with a large number of contacts in three different schools and did not transmit the disease, as evidenced by the large number of negative results of tested symptomatic and asymptomatic contacts [83].

In Ireland, transmission within schools was investigated prior to school closures and no evidence of secondary transmission within the school setting was found. Among the 924 child contacts and 101 adult contacts of the six cases (three children, three adults) in the school setting, there were no confirmed cases identified during the 14- day follow-up period [84]. It is important to note that this study did not consider asymptomatic infections.

In Finland, no secondary cases were identified in contact tracing and testing of 89 out of 121 contacts of a 12-year case who had attended school during their illness [85].

In Australia, a contact tracing study in 15 primary and high schools, where nine student COVID-19 cases were detected, found one secondary positive case in a primary school student (out of 735 close child contacts who were followed up) [86].

In Singapore, two preschools and one secondary school identified child index cases and tested close contacts. In a case where a preschool child was the index case (mean age 4.9 years), 34 preschool student contacts developed

potential COVID-19 symptoms during the incubation period, however all 34 symptomatic cases tested negative for SARS-CoV-2. In a case where the index child was in secondary school (mean age 12.8 years), a total of eight out of 77 students developed symptoms and were screened for SARS-CoV-2 during the incubation period. All eight symptomatic student contacts from the school tested negative [87,88].

In Israel, a first large school outbreak emerged ten days after re-opening all schools with requirement for daily health reports, hygiene, face masks, social distancing and minimal interaction between classes. The first two cases were registered on 26 May and 27 May, having no epidemiological link. Testing of the complete school community revealed 153 students (attack rate: 13.2%) and 25 staff members (attack rate: 16.6%) who were COVID-19 positive. Overall, some 260 persons were infected (students, staff members, relatives and friends) [88].

In summary, in children where COVID-19 was detected and contacts followed-up, only one child contact in the school setting was detected as SARS-CoV-2 positive during the follow-up period. The conclusion from these investigations is that child-to-child transmission in schools is uncommon and not the primary cause of SARS-CoV-2 infection of children whose infection onset coincides with the period during which they are attending school.

What is the evidence of transmission from children (students) to adults (teacher/staff) within the school setting?

In an Irish study, 101 adult contacts in the school setting of three SARS-CoV-2 positive children resulted in no additional cases [84]. It is important to note that this study did not consider asymptomatic infections.

In Australia, a contact tracing study in 15 primary and high schools where nine student COVID-19 cases were detected found no evidence of any transmission to 128 adult close contacts in the school setting [86].

In the Netherlands, as of June 2020, there had been no reports of possible COVID-19 clusters linked to schools or reports of employees infected by children [81].

In summary, where COVID-19 in children was detected and contacts followed-up, no adult contacts in the school setting have been detected as SARS-CoV-2 positive during the follow-up period. The conclusion from these investigations is that children are not the primary drivers of SARS-CoV-2 transmission to adults in the school setting.

What is the evidence of transmission from adults (teacher/staff) to children (students) within the school setting?

There is very little documented evidence of potential transmission from adults to children within the school setting. In Ireland, three adult cases had a total of 102 child contacts that did not result in detection of any secondary child cases although, only symptomatic individuals were referred for follow-up testing [84].

The outbreak in a high school in Israel did not specify the age of the index cases, making identification of adult-to-student transmission within the school setting impossible without further information [88].

In Australia, a contact tracing study in 15 primary and high schools where nine staff-member-COVID-19 cases were detected found one secondary positive case in a secondary school student (among 735 child close contacts who were followed up) [86].

In Finland, following exposure to an infected teacher, seven out of 42 exposed students developed antibodies or were PCR positive, however household or community transmission may have been the source in some of these [85].

There is ample evidence that if a child is infected by an adult, it is likely to be in the household setting. In an Italian cohort, contact with an infected person outside of the family was rarely reported and 67% of children had at least one parent who tested positive for SARS-CoV-2 infection [4,5].

It is also important to note that interactions between children and adults are different in the school setting to those in the household setting.

In summary, while there is evidence of transmission from adults to children in household settings, there is little evidence of this occurring within the school setting.

What is the evidence of transmission between adults (teacher/staff) within the school setting?

There is limited evidence within the peer-reviewed literature documenting transmission between adults within the school setting. In Sweden, where schools for children younger than 16 years remained open, the Public Health Authority analysed occupational groups within the school and found that teachers were at no higher risk of COVID- 19 than the general public.

Relative risks were: preschool teachers (0.7), compulsory school teachers (1.1), senior high school teachers (0.7), recreation staff (0.8), student assistants (1.1), other educators (1.0), and childcare providers (1.0) [9].

Recommendations for Swedish schools were that everyone with mild symptoms remain at home, to practise physical distancing, to cancel mass gatherings within the school setting, and to practise hand hygiene while in the school setting. See Box 1 for more information on the Swedish approach.

A study documenting an apparent school outbreak of 50 people in Chile describes an index case, a teacher, participating in multiple parent conferences about five days prior to the peak of the outbreak [89]. However, the

designation of the index case is based on testing as a result of symptoms and might therefore have missed asymptomatic children.

Serology results 8-10 weeks after the outbreak suggest comparable levels of infections among children and adults at the school, but these infections might have occurred outside of the school setting, as the school in question was closed down rapidly after the index case was detected.

The conclusion from these investigations is that adults are not at higher risk of SARS-CoV-2 within the school setting than the risk in the community or household.

What is the effect of school openings on transmission to the community/household?

While there is a growing body of evidence to suggest that transmission between children and between children and adults within schools has been relatively uncommon, there have been very few studies that have assessed the impact of school closure or opening on transmission outside the school. Among those that have been published, the following have suggested that schools closure or opening could impact on community incidence:

A recently published study on the association between school closures and community incidence in the USA [90] has suggested that school closures could have been associated with up to 128.7 fewer cases per 100 000 population over 26 days and with up to 1.5 fewer deaths per 100 000 population over 16 days in areas with low starting incidence.

However, these closures occurred at the time of the introduction of many other non- pharmaceutical interventions, and the authors note that it was “impossible to fully isolate potential effects of school closure”, and that “some non-pharmaceutical interventions, such as increased handwashing, could not be included due to lack of available data.”

The authors also note that “The degree to which the associations with school closure relate to decreased spread of SARS-CoV-2 by children or a combination of child and adult factors is unclear.”

In Israel, a first large school outbreak emerged ten days after re-opening all schools with requirement for daily health reports, hygiene, face masks, social distancing and minimal interaction between classes [88].

The author’s report that 87 additional confirmed COVID-19 cases occurred among close contacts of the first school’s cases, including siblings attending other schools, friends and participants in sports and dancing afternoon classes, students’ parents and family members of school staff.

However, the authors do not comment on the likely sequence of infection in these cases, and also note that distancing among students and between students and teachers within the school was not possible.

Moreover, as a consequence of a heatwave that occurred at the time of re-opening, there was an exemption from the use of facemasks, and air-conditioning functioned continuously in all classes.

Much of the other evidence that exists on the impact, or the lack thereof, of school opening and closures on community transmission derives from observational studies and a survey undertaken by ECDC of contact points in national public health institutes in EU Member States.

Denmark reopened childcare and primary education on 15 April, with moderately high overall notification rates at national level, and did not report any increase in the reproductive number, or detect important school outbreaks.

Denmark recommended splitting classes into smaller groups, keeping two metres between children, hand hygiene, and teaching more classes outside. Similarly, the Netherlands did not see a sudden increase in their reproductive number or detect significant outbreaks, when primary schools and childcare facilities opened on 11 May, with moderately high notification rates at national level.

Children up to and including 12 years did not have to keep 1.5 metres apart from each other or from adults, and this measure was applied in childcare and primary education settings.

Children aged 13 to 18 years did not have to physically distance from one another. Physical distancing was recommended for all adults – staying 1.5 metres apart from others as often as possible [81].

Since the beginning of the pandemic, 41% of Ireland’s 576 cases in children were linked to outbreaks in private family homes, followed by outbreaks in workplaces (n=25; 18.1%), travel related outbreaks (n=19; 13.7%), outbreaks in residential institutions (n=12; 8.7%), extended family (n=11; 8.0%) and in the community (n=8; 5.8%). None of the COVID-19 cases have been linked to outbreaks in school or childcare facilities [personal communication Ireland].

Iceland also kept both childcare institutions and primary schools open throughout the spring term and the rates of SARS-CoV-2 in children <15 years remained low compared to rates in the older age groups. Physical distancing rules did not apply to childcare institutions and primary school children and they were not limited in their leisure, sports, or music activities.

Access to hand-washing facilities and disinfection was mandatory and adults had to respect the two-metre distancing rules and not gather in groups over 200 [91]. Similarly, in Sweden, the 14-day incidence for children <15 years has remained lower than all of the other age groups, even when Sweden expanded their testing policy to include mild cases (see Box 1 for further details) [6].

In summary, there is limited evidence that schools are driving transmission of COVID-19 within the community, however there are indications that community transmission is imported into or reflected in the school setting.

Given that all countries have implemented additional non-pharmaceutical interventions in addition to school closures, it is difficult to assess the true impact of school closure/opening on transmission of SARS-CoV-2 within the community from the school setting itself.

The report from Israel underscores the importance of the rigorous implementation of physical distancing in order to reduce exposure in school settings where COVID-19 is circulating in the community.

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More information: Journal of Pediatrics (2020). DOI: 10.1016/j.jpeds.2020.08.037

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