27. April 2021

 – Policy Brief

The role of children (≤12 years of age) and adolescents (13-17 years of age) in the SARS-CoV-2 pandemic: A rapid review

Questions

This review updates the reviews in the policy briefs from 23 April 2020, 10 May 2020 and 12 August 2020.[1] It addresses three key questions about the epidemiology of SARS-CoV-2 infection and COVID-19 in children and adolescents. The review emphasizes the importance of trying to differentiate between different age groups: younger children, including infants and small children (0-5 years), school children (6-12 years) and adolescents (13-17 years). In this update, we assess available evidence relevant to children and adolescents, including new SARS-CoV-2 variants, which are more transmissible than the previous variants circulating in Switzerland. The key questions are:

  1. How do children and adolescents present when infected with SARS-CoV-2?
  2. Is the risk of children and adolescents becoming infected by SARS-CoV-2 comparable to that of adults? Does the probability of infection differ between age groups (0-5, 6-12, 13-17 years)?
  3. Can children and adolescents transmit SARS-CoV-2 and is the risk comparable to that of adults? Does the probability of transmission differ between age groups (0-5, 6-12, 13-17 years)?

Appropriate preventive measures in schools should be in place. These are now dealt with in a separate policy brief

[1] The role of children and adolescents (0-18 years of age) in the transmission of SARS-CoV-2: a rapid review (23 April 20; 10 May 20; 12 August 20 – EN)

Summary, including new findings

Children of all ages and adolescents can be infected by, and can transmit, SARS-CoV-2. They usually have fewer and milder symptoms of SARS-CoV-2 than adults, which results in less testing and underdiagnosis. The precise relationship between age and the acquisition and transmission of SARS-CoV-2 remains unclear for two main reasons. First, there are inherent methodological challenges in differentiating between the biological effects of age and the external influences of level of community transmission and strength and nature of preventive measures. These challenges are exacerbated by poor reporting of contextual factors. Second, differences between studies in analysis and reporting by age make it hard to synthesize findings across studies.

  1. Younger children, school children and adolescents usually have fewer and milder symptoms of SARS-CoV-2 than adults and are less likely than adults to experience severe COVID-19. A hyperinflammatory syndrome, called pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in Europe and multisystem inflammatory syndrome in children (MIS-C) in the USA can complicate recovery from COVID-19. Children and adolescents can experience prolonged clinical symptoms (known as long COVID, or post-acute sequelae of SARS-CoV-2 infection), but the frequency and characteristics are still under investigation. The severity of disease caused by new variants of SARS-CoV-2 in children and adolescents, in comparison with previous lineages, is under investigation.
  2. The risk of becoming infected with SARS-CoV-2 is a combination of susceptibility (host biological factors), environmental factors associated with exposure type (work, shopping, schools etc.) and exposure intensity (level of community transmission and of preventive measures). In studies in which all household members are exposed to an infected person, the proportion becoming infected with SARS-CoV-2 increases with age.  The detailed relationship between age and susceptibility to infection requires further investigation. More detailed epidemiological information about the factors influencing susceptibility of children and adolescents to the new SARS-CoV-2 variants is needed.
  3. Infectious SARS-CoV-2 has been cultured in children as young as 7 days. Amongst diagnosed individuals tested at the same time point after symptom onset, SARS-CoV-2 viral load appears similar in children, adolescents and adults. The relationship between age, viral load and transmission across the full symptom spectrum of SARS-CoV-2 infection has not been comprehensively investigated because people with no, or mild, symptoms are seldom tested systematically. The relative transmissibility of SARS-CoV-2 at different ages remains uncertain, largely because of the challenges involved in disentangling the influences of biological, host and environmental factors. More detailed epidemiological information about the factors influencing transmissibility of the new SARS-CoV-2 variants in children and adolescents is needed.

More studies about the role of testing at all school levels and well-designed prospective longitudinal studies that can address questions about SARS-CoV-2 transmission at school and household level are urgently needed.

Main text

The role of children and adolescents in the transmission of SARS-CoV-2 is still uncertain. The uncertainties affect policy decisions, such as how to keep schools, kindergartens or day care facilities open safely and guidance about intergenerational contacts in general. Children and adolescents were observed early on in the pandemic to manifest mostly mild symptoms, with few cases of severe COVID-19, the disease caused by SARS-CoV-2 (Hoang et al., 2020; Morand et al., 2020; Mustafa and L, 2020). While a less severe course of infection is beneficial for young people, milder clinical manifestations are of public health importance if they result in unknowing and undetected infection transmission.

Understanding the characteristics of SARS-CoV-2 infection and spread by age is important for developing, adapting and improving control measures. There are ongoing debates, however, about the results and interpretation of research studies. Since January 2020, when COVID-19 was first described, the types of research evidence available and the design of research studies have changed, allowing a reassessment of earlier findings. Many early studies had to rely, of necessity, on clinically apparent cases in healthcare settings with limited diagnostic testing. These studies made important observations, but underestimated the proportion of children amongst all COVID-19 cases because the milder symptoms resulted in under-detection of infection (Accorsi et al., 2021). Over time, it has become possible to design, conduct and analyze studies to reduce the risk of some of the biases in selection and measurement. Even so, the context in which a study is conducted (level of community transmission, control measures in place) cannot be changed. Differences between studies that attempt to address the same research question about SARS-CoV-2 in children may result both from differences in the circumstances under which studies were done and in study methodology.

We conducted an extensive literature review, with periodic searches of Pubmed and MedRxiv, up to January 21st, 2021, supplemented by inclusion of papers highlighted by experts until March 29th, 2021. The search strategy is described in the Appendix. Only studies in German and English were included in this report.

We screened 2778 studies up January 21st 2021 (peer-reviewed and preprints), of which 31 were deemed relevant to our review questions. From a manual search (also including reports and grey literature) we included another 36 articles (23 published, 13 not yet published or peer-reviewed or both). Of these 67 articles, 23 were case reports, 19 were cross sectional studies, 8 were cohort studies, 6 were narrative reviews or viewpoints, 10 were systematic reviews and 1 was a modelling study (see annex with tables on search and description of studies). Some studies cited in earlier versions of this review have been updated, where we found more relevant studies in recent searches.

The studies included describe the age distribution of study participants in very different ways. Reported age groups between studies often overlap, or report a finding for a wide age range, e.g. all below 18 years of age. It is not possible to summarize findings using consistent age categories or to adapt the results consistently according to school stage. Where the data are available, we try to report these for categories of younger children, including infants and small children (around 0-5 years), school children (around 6-12 years) and adolescents (around 13-17 years). 

Question 2. Is the risk of children and adolescents becoming infected by SARS-CoV-2 comparable to the risk of adults? Does the probability of infection differ between age groups (0-5, 6-12, 13-17 years)?

The risk of becoming infected with SARS-CoV-2 is a combination of susceptibility (host biological factors), environmental factors associated with exposure type (work, shopping, schools etc.) and exposure intensity (level of community transmission and of preventive measures) and agent factors, including the variant of SARS-CoV-2. It is often difficult to disentangle the influences of these factors on the risk of children and adults becoming infected. Research studies about levels of SARS-CoV-2 infection in people of different ages therefore report on the total combined risk (susceptibility, exposure and pathogen factors) of infection. Interpretation depends on study methodology and the detail with which contributing factors are reported.

The risk of SARS-CoV-2 infection at different ages can be investigated in different study types. The least biased design would be to follow a random sample of the population with repeated frequent virological testing for SARS-CoV-2 to determine incidence at different ages and to place the findings in the epidemiological context in which the study was done. Repeated cross-sectional samples of a population can also give this information, assuming that the population structure remains stable. In contact tracing studies of transmission in households or during outbreaks the secondary attack rate in children and adults can be compared. In these studies, all household members theoretically have a comparable level of exposure. They are still at risk of chance effects and bias because adults are more likely to be the index case because they have symptoms more often. Different biases in household studies of secondary attack rate can result in underestimation or overestimation of the contribution of children (Accorsi et al., 2021). Seroprevalence studies give information about the proportion of people who have been infected since the start of the pandemic but do not give information about who infected whom, or when. Studies that use surveillance or registry data about cases that are diagnosed and reported should not be used to examine age differences in the risk of SARS-CoV-2 because children are less likely to be symptomatic and less likely to be tested in routine practice.

2.1 Population studies/cross-sectional studies using virological testing

The first detected case of COVID-19 in Italy was a resident from Vo’, northern Italy, who died of pneumonia in February 2020 (Lavezzo et al., 2020). A 14-day quarantine was imposed at the beginning of a lockdown and a majority of the population was tested (85.9% at the first stage, 71.5% 14 days later) for SARS-CoV-2, irrespective of symptoms. There were no cases in 217 children aged 0-10 years and 3 cases in 250 11-20 year olds (1.2%), compared with 1.1% to 6.0% in adults in older 10-year age bands. This survey is at low risk of bias; nearly all residents were tested, there were no restrictions before the lockdown and children and adults lived in the same households. The COVID-19 Infection Survey (CIS) where randomly selected members of the British population aged 2 years and older, submit repeated swabs for SARS-CoV-2 testing, has found differences in SARS-CoV-2 positivity over time. Greater increases in positivity in children aged 2 to 24 years than in older adults coincided with school opening in September 2020 (Children’s Task and Finish Group, 2020).

 

2.2 Contact tracing/household studies

We identified three relevant systematic reviews. Viner et al., 2021 included 18 studies based on contact tracing in any setting up to July, 28th 2020. They found a lower risk of infection for younger children <10 years of age (odds ratio, OR 0.52, 95% CI 0.33-0.82)) than adults (reference group), but not for older children and adolescents >10 years of age (OR 0.72, 95% CI 0.46-1.10). Zhu et al., 2020 included 14 household studies up to 24th  August 2020 (4 of which were included by Viner et al., 2021), with comparable findings. The risk of infection was lower among all <18 year olds than in adults (relative risk, RR 0.62, 95% CI 0.42-0.91). Madewell et al., 2020 analyzed 15 household studies up to October, 19th 2020 (7 of which were also included in Viner et al., 2021. They compared the SAR within each study and found the summary proportion of participants with SARS-CoV-2 was higher in adult contacts (28.3%, 95%CI, 20.2%-37.1%) than in child and adolescent contacts of all ages (<18 years of age) (16.8%; 95%CI, 12.3%-21.7%).

Most of the studies in these reviews were conducted during times of strict social distancing. There is a risk of bias in levels of exposure for adults and for children. Adults were at risk of infection outside their homes e.g. while shopping or at work, whilst children stayed mostly at home. Children were, however, likely in contact with adults within the families. A limitation of these reviews is the different age groups studied, resulting in large, and sometimes overlapping groups.

Some household studies (some of which are included in the systematic reviews) distinguish between narrower age groups. A cohort study by Li et al., 2020 analyzing 392 household contacts of 105 index patients in China, calculated secondary attack rates of 2.3% (1/44) for younger children (aged 0-5 years), 5.4% (3/56) for school children and adolescents (aged 6-17 years) and 17.1% (60/292) for adults. In Singapore, Yung et al., 2020 described 213 children in 134 households, of which 13 became infected with SARS-CoV-2: 0-4 years old, 1.3% (1/77); 5-9 years, 8.1% (6/68); and 10-16 years, 9.8% (6/55). Somekh et al., 2020 also found older children and adolescents (aged 5-17 years) in family household settings in Israel being 61% less likely to be infected with SARS-CoV-2 than adults, with the risk for younger children 0-4 years of age being 47% lower than the risk for adults.

2.3 Seroprevalence studies

We found several seroprevalence studies. Studies conducted in nationally representative samples of the population using methods that reduce the risks of bias in selection, measurement and analysis of antibody status will provide the most robust estimates of cumulative incidence up to the time at which the survey was done (Accorsi et al., 2021). Differences between studies that are at low risk of methodological biases are then more likely to be explained by contextual factors, such as levels of exposure to infection.

In a nationally representative seroprevalence survey in Spain (April-May 2020), seroprevalence was lowest in the youngest age groups (Pollan et al., 2020). This study was done when a strict national lockdown was imposed in Spain with schools and kindergartens closed and children were mostly exclusively at home.[1]

In Germany, Debatin et al., 2020 invited volunteers through newspaper and social media adverts and analyzed antibody levels in 5042 parent-child pairs in April-May 2020 during a strict lockdown (schools were closed and children and parents were almost exclusively at home, but children from essential workers could still attend daycare facilities). They found a higher proportion of parents (1.8%; 95%CI: 1.3-2.4%) than children (1-5 years, 0.6%; 95%CI: 0.3-1.3) with SARS-CoV-2 antibodies. Torres et al., 2020 analyzed a school outbreak of 52 RT-PCR positive cases in Chile and measured seroprevalence in a random sample of students and staff 8-10 weeks after the outbreak. The index case was a staff member in the pre-school department. The authors thought it likely that the staff member infected both pre-school children at school and parents and colleagues during parent-teacher meetings. They found 16.6% (95% CI 12.1-21.9%) of staff had antibodies. A higher percentage of younger children (pre-school 12.3%, 95% CI 7.8-18.6%) than high school students (5.7%, 95% CI 3.6-8.9%) had antibodies.

2.4 Studies done in Switzerland

The SEROCoV-POP seroprevalence study in Geneva, Switzerland analyzed randomly selected participants from a past cohort study and their household members (>5 years old) in April-May 2020. The risk of antibody positivity for children <10 years of age was lower (risk ratio 0.32, 95%-CI: 0.11-0.65) than that for adults >20 years of age. Seroprevalence among children aged 10-19 years was similar to that of >20 year olds (risk ratio 0.86, 95%-CI: 0.57–1.22) (Stringhini et al., 2020). As this was a retrospective study that was conducted when Swiss schools were closed, individual sources of infection were not analyzed. The lower risk in children could be due to less exposure to SARS-CoV-2 than adult household members. Another survey round was done in November-December 2020, after the second peak of the pandemic. Seroprevalence became similar for school children and adolescents (6-11 year olds, 22.8%, 95%-CI 18.7-27.1%; 12-17 year olds, 23.6%, 95%-CI 19.6%-28.0%) and adults (25-34 years, 25.9%, 95%-CI 21.8-30.2%), but was lower for children aged 0-5 years (14.9, 95% CI 10.7-19.6) (Stringhini et al., 2021). During the study period, Geneva imposed a regional lockdown, where most shops were closed, but schools and the border were open and inter-cantonal travel to cantons with less strict measures was common.

[1] Other population-based seroprevalence studies have been published since summer 2020 (e.g. Hippich, Holthaus et al. 2021; Konsortium der Medizinischen Universität Graz, 2020). Hippich et al., 2020, reported similar seroprevalence in 0 to 6 years (66 of 7,821, 0.84%) and children aged 7 to 18 years (14 of 1,425, 0.98%) from April to July 2020 in Bavaria, Germany. Seroprevalence was 6 times higher than numbers of diagnosed and reported SARS-CoV-2 cases in children, but no adults were tested in that study. The same applies to the Austrian study by the Konsortium der Medizinischen Universität Graz, 2020, where the prevalence in students (0.37%, 95% CI 0.26-0.53%) was compared to the prevalence of their teachers (0.57%, 95% CI 0.25-1.32%), but not with adults in the same households again, excluding the household settings. This weakens the certainty of these studies’ findings.

Question 3. Can children and adolescents transmit SARS-CoV-2 and is the probability of transmission comparable to that of adults? Does the probability of transmission differ between age groups (0-5, 6-12, 13-17 years)?

Children and adolescents can transmit SARS-CoV-2 in both household, school and out of school settings. The relative transmissibility of SARS-CoV-2 at different ages remains uncertain, largely because of the challenges involved in disentangling the influences of biological, host and environmental factors. For example, school children and adolescents are more mobile and generally have more close contacts among themselves than younger children (Mossong et al., 2008).[1] On the other hand, measures aimed at limiting virus transmission, such as wearing masks in school settings, have been more widely recommended and implemented among adolescents than school children ≤12 years old. The timing of studies is an important consideration. For example, in Switzerland, restrictions in extra-curricular activities in early 2021 were limited to children older than 12 years. If this type of information is not reported, study findings may be misinterpreted.

There are different study designs to investigate the infectiousness and resulting transmission potential at different ages. Comparisons between children and adults in estimates of viral load, which are usually based on RT-PCR cycle threshold values, can indicate differences in infectiousness. These studies provide partial information because the probability of transmission is also influenced by the probability of being diagnosed, by levels of symptoms (e.g. cough increases the risk of aerosol transmission) and by physiological features (e.g. children having less lung capacity than adults). Studies that estimate the secondary attack rate can also be used to study transmission from a child or adult to their close contacts (either in households or schools). Methodological issues in study design, which generally arise from misclassification of the index case or the contact, can result in biased estimates, however (Accorsi et al., 2021). Since children display fewer symptoms than adults (see question 1), they might be less likely to be classified as an index cases and more likely to be classified as a contact, which would underestimate the transmission risk from children. Environmental factors (e.g. culture, community transmission, lockdown without any contacts except essential contacts e.g. while shopping or at work) also make extrapolation to different settings difficult and might lead to an overestimation of transmission if the contacts were actually infected elsewhere. Regular repeated testing of people within households can identify the first infected person in a chain of transmission, which helps to understand who infected whom. Even this study design can only be interpreted appropriately if the epidemiological context is reported.

3.1 Laboratory-based studies of infectiousness

L’Huillier et al., 2020 showed that infectious SARS-CoV-2 can be isolated from children as young as 7 days old. Amongst 23 children <16 years old in Geneva, virus was cultured in 12. The same group in Geneva found comparable viral load levels, by age group, in laboratory samples taken within 5 days of symptom onset and tested between March-May 2020 (53/405 aged <16 years) Baggio et al., 2020. In a large study of samples sent to a laboratory in Germany, Jones, Mühlemann, et al., 2020 used two different testing systems, and found an association between increasing age and increasing viral load on one (Roche Cobas system), but a negative association on the other system (Roche LC480 system). Jones, Mühlemann et al. 2020 did not specify the type of specimen from which the viral RNA was isolated in adults and in children. As Zou et al., 2020,Yu et al., 2020 and Wang et al., 2020 show, RT-PCR cycle threshold values, which were used to calculate the viral loads of different specimens, are not comparable. A different statistical analysis of the same data found that viral load increased with age (Held, 2020).

These studies do not allow the relationship between age and viral load to be determined across the full spectrum of SARS-CoV-2 infection. A major limitation of studies based on collections of samples in diagnostic laboratories is that inclusion in a study depends on having been tested. Since testing for SARS-CoV-2 concentrates on detection of infection in people with symptoms, children who are included in these sample collections are unlikely to be representative of all those infected. The study by Baggio et al., 2020 is restricted to a defined group of symptomatic people, but the study by Jones, Mühlemann et al. 2020 does not stratify the results about age and viral load by the severity of the patient’s symptoms.

Prospective studies that reduce the risk of selection bias by including representative samples across the spectrum of SARS-CoV-2 infection, and document age, symptom status, specimen and assay type, viral load and culturability would allow a more detailed assessment, since severity of disease is potentially directly associated with infectiousness, viral loads and thus SARS-CoV-2 transmission (Luo et al., 2020; Liu, Yan, et al., 2020; Han et al., 2020; Zheng et al., 2020).

3.2 SARS-CoV-2 studies in family and schools/day care centers

A meta-analysis by Zhu et al., 2020 analyzing household clusters up to August, 24th 2020 found that a child or an adolescent (<18 years) was identified as the first case in 4% (8/13) of these clusters. The pediatric index cases also led to fewer secondary cases than adult index cases (4% vs. 96% of 398 secondary cases). Acknowledging the potential undercounting of children as index cases, the authors included asymptomatic children as possible index cases, and the proportion of clusters with an index case <18 years increased to 19% (30/211) and the proportion of secondary cases increased to 22% (80/395 contacts). A regularly updated review that includes studies with contact tracing data up to January 21st, 2021 reported very limited transmission from younger children in school settings, but found potential outbreaks in school children and adolescents (without further clarification of the respective age groups), especially during times of higher community transmission (Boast, Munro, and Goldstein, 2020).

Several studies have described large clusters of SARS-CoV-2 involving schools and school camps. Fontanet et al., 2020 described an outbreak of SARS-CoV-2 in a school in northern France in early 2020. In a serosurvey in one high school, seroprevalence higher in adolescents (82/205 in 15-17 year olds) than adults (88/415 in >18 years olds). As neither the sampling methodology is known nor were the supposed index cases laboratory confirmed SARS-CoV-2 cases, the extent of spread in the school compared with outside is not known. Further studies by Szablewski et al., 2020, Pray et al., 2020 and Stein-Zamir et al., 2020 describe clusters of cases in overnight camps/retreats in the USA and a school in Israel. While Pray, Gibbons-Burgener et al. 2020 and Stein-Zamir et al., 2020 describe outbreaks in high schools (ages 12 and older), the camp outbreak described by Szablewski et al., 2020 included children and adolescents aged 6-17 years and found similar attack rates in 6-10 year olds (51/100, 51%) and 11-17 year olds (180/409, 44%). Outbreak investigations did not test close contacts before or after camps (Szablewski, Chang et al. 2020 and Pray, Gibbons-Burgener et al. 2020) or provide information about contact histories with other potential cases (Stein-Zamir, Abramson et al. 2020) so the numbers of cases infected outside the camps or schools are not known.[2]

Other studies from schools have found limited transmission when community transmission was comparably low, even in secondary education facilities. Potential protective measures in most reports were not described. In Singapore, Yung et al., 2021 described three school settings in which no child contacts became infected: 0/8 symptomatic contacts of an infected 12 year old; 0/34 symptomatic contacts of an infected 5 year old; and 0/77 preschool pupils where a total of 16 staff members were infected (Yung et al., 2021). In Australia, 18 index cases (9 students and 9 teachers) in 15 different schools (primary and high schools) had close contact with 735 fellow students and 128 staff. None of the 128 staff contracted SARS-CoV-2 and the 2 initial cases (1 student and 1 staff) only infected two fellow students (one in a high school, and one in a primary school). At the time of the study, children were advised to receive online learning at home, so reduced attendance could have influenced transmission (NCIRS), 2020). Heavey et al., 2020, describe six index cases in schools in Ireland before preemptive school closures during the 2020 spring wave. Three students, aged 10-15 years, and three adults did not infect any of the 1001 child contacts tested (924 school contacts, 77 non-school-related contacts), including those with only mild symptoms. Ehrhardt et al., 2020 described 137 index cases aged <19 years in Baden-Württemberg, Germany from May-August 2020. From more than 2300 contacts, 11 infections in classmates were found (three in childcare facilities, one in elementary school, 4 in secondary school and three in vocational school). None of these secondary cases infected any other students. There were several hygienic control measures in place (e.g. reduced class size, exclusion of sick children, etc.). Link-Gelles et al., 2020 and Yoon et al., 2021 also found a low risk of infection from adult and pediatric index cases in childcare settings in Rhode Island, USA and South Korea.

A study from the England (Ismail et al., 2021) reports on 177 COVID-19-associated events in educational settings (preschool, primary and secondary) involving 130 confirmed cases in children and 213 in staff members. Most outbreaks were small (median number of cases, 2, interquartile range 2-5). The maximum size of outbreaks was lower when the index case was a child (median 1, maximum 6) than when the index case was a staff member (median 1, maximum 12). Although the number of cases was low overall, there was a strong association with regional incidence of reported COVID-19; for every 5 new cases per 100000 inhabitants the risk of an outbreak increased by 72% (95% CI 28-130). In most outbreaks, a staff member was the index case (staff to staff in 26/55 outbreaks, staff to student in 8/55 outbreaks, student to staff in 16/55 outbreaks, and student to student in 5/55 outbreaks). The same pattern of index cases was seen in Georgia, USA, where nine clusters were described in elementary schools from December 2020-January 2021. Of these nine clusters four were started by teachers, one by a student and four were unknown. (Gold et al., 2021)

In schools, as in other settings, however, children might be under-counted as the index case because they are less likely than adults to present with symptoms.

3.3 Studies of new SARS-CoV-2 variants

The characteristics of SARS-CoV-2 variants of concern, such as B.1.1.7, first identified in England, in different age groups are not yet known.

The British Children’s Task and Finish Group describes an increase in infection prevalence between September-October 2020, which was most marked in the age group 16/17-24, followed by 12-16 year olds, based on the ONS COVID-19 Infection Survey. The School Infection Survey, conducted in November 2020 found that despite more testing the level of infection in schools is low even in times of high community transmission (students, 1.24%, 95%-CI 0.96-1.58%; staff, 1.29%, 95%-CI 0.96-1.68%) (Group, 2020). This report was written before the increased transmissibility of B.1.1.7 was confirmed. A modeling study by Volz et al., 2021 predicted that under 20 year olds could have been affected more by the new SARS-CoV-2 variant B.1.1.7 than by the previous variants, but this could have resulted from increased transmission when schools were open during a lockdown period, from increased susceptibility, or from increased symptoms leading to more testing. Further research about the impact of B.1.1.7 on children is needed.

3.4 Studies done in Switzerland

In addition to the laboratory-based studies (section 3.1), a longitudinal seroprevalence study has been done in schools in Zurich (Ciao Corona study) in June/July and October/November 2020 (Ulyte et al., 2021). The study follows children aged 6-16 years in 55 schools and 275 classes during a period when hygienic measures were in place (e.g. mask wearing for teachers and students >12 years of age). In 7 classes in 5 schools ≥3 students had SARS-CoV-2 antibodies, in periods of moderate to high community transmission, when seroprevalence itself increased from 2.4% to 4.5% in schools. It is not known whether the students were infected as part of an outbreak, or were sporadic cases, nor whether the infections were acquired or transmitted in the school.

In the Canton of Vaud, schools are investigated if ≥2 SARS-CoV-2-positive children are detected in the same school within 5 days (personal communication, Valérie d’Acremont). During 3 weeks in January-February 2021, testing was carried out in 32 of 6135 (0.5%) classes: 325 of 124,818 (0.3%) children and adolescents were tested, of whom 18 (5.5%) were positive. Of the diagnosed cases, ⅔ were in primary schools, ⅓ in secondary schools and none were in post-compulsory schools. Three primary school classes were put in quarantine. Clusters of ≥5 persons occurred once in one class and once in teachers from one school in which no case in children was found.

[1] https://www.fhi.no/en/op/novel-coronavirus-facts-advice/facts-and-general-advice/advice-and-information-for-children-and-adolescents/

[2] Media reports describe several SARS-CoV-2 school outbreaks in Germany. Most of these reports describe cases appearing at schools but do not provide enough information to determine the source or direction of transmission. In one secondary school, transmission was proven to have happened at school with one person infecting 25 students and 15 teachers. There is no data about the age of the index case. The case study suggests that adolescents can become infected in school settings when protective measures (masks etc.) are not taken. (https://www.abendblatt.de/hamburg/article231223608/Corona-Ausbruch-an-Schule-Eine-Person-steckte-Dutzende-an.html)

Conclusions

Children are susceptible to SARS-CoV-2 infection and also transmit the disease. The extent of transmission depends on various factors, including for example the level of community transmission, the measures implemented and also biological factors (possible less transmission among younger children; type of variant present). The precise role of children and adolescents in the overall transmission still requires further investigation, especially as there is a lack of more detailed epidemiological information on the transmission dynamics of the new SARS-CoV-2 variants. More testing amongst children of all ages and adolescents, and well-designed longitudinal studies in school and household settings, are urgently needed. Appropriate preventive measures should be consistently implemented in schools.

Authors: Margarethe Wiedenmann, Nicola Low and members of expert groups

References

(NCIRS), The National Centre for Immunisation Research and Surveillance. 2020. “COVID-19 in schools – the experience in NSW.” doi: Click here

Accorsi, E. K., X. Qiu, E. Rumpler, L. Kennedy-Shaffer, R. Kahn, K. Joshi, E. Goldstein, M. J. Stensrud, R. Niehus, M. Cevik, and M. Lipsitch. 2021. “How to detect and reduce potential sources of biases in studies of SARS-CoV-2 and COVID-19.”  Eur J Epidemiol 36 (2):179-196. doi: 10.1007/s10654-021-00727-7.

Baggio, S., A. G. L’Huillier, S. Yerly, M. Bellon, N. Wagner, M. Rohr, A. Huttner, G. Blanchard-Rohner, N. Loevy, L. Kaiser, F. Jacquerioz, and I. Eckerle. 2020. “SARS-CoV-2 viral load in the upper respiratory tract of children and adults with early acute COVID-19.”  Clin Infect Dis. doi: 10.1093/cid/ciaa1157.

Balduzzi, A., E. Brivio, A. Rovelli, C. Rizzari, S. Gasperini, M. L. Melzi, V. Conter, and A. Biondi. 2020. “Lessons after the early management of the COVID-19 outbreak in a pediatric transplant and hemato-oncology center embedded within a COVID-19 dedicated hospital in Lombardia, Italy. Estote parati.”  Bone Marrow Transplant 55 (10):1900-1905. doi: 10.1038/s41409-020-0895-4.

Boast, A., A. Munro, and H. Goldstein. 2020. “An evidence summary of Paediatric COVID-19 literature.”  Don’t Forget the Bubbles. doi: https://doi.org/10.31440/DFTB.24063.

Boulad, F., M. Kamboj, N. Bouvier, A. Mauguen, and A. L. Kung. 2020. “COVID-19 in Children With Cancer in New York City.”  JAMA Oncol 6 (9):1459-1460. doi: 10.1001/jamaoncol.2020.2028.

Buitrago-Garcia, D., D. Egli-Gany, M. J. Counotte, S. Hossmann, H. Imeri, A. M. Ipekci, G. Salanti, and N. Low. 2020. “Occurrence and transmission potential of asymptomatic and presymptomatic SARS-CoV-2 infections: A living systematic review and meta-analysis.”  PLoS Med 17 (9):e1003346. doi: 10.1371/journal.pmed.1003346.

Buonsenso, Danilo, Daniel Munblit, Cristina De Rose, Dario Sinatti, Antonia Ricchiuto, Angelo Carfi, and Piero Valentini. 2021. “Preliminary Evidence on Long COVID in children.”  medRxiv:2021.01.23.21250375. doi: 10.1101/2021.01.23.21250375.

Castagnoli, R., M. Votto, A. Licari, I. Brambilla, R. Bruno, S. Perlini, F. Rovida, F. Baldanti, and G. L. Marseglia. 2020. “Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Children and Adolescents: A Systematic Review.”  JAMA Pediatr 174 (9):882-889. doi: 10.1001/jamapediatrics.2020.1467.

Debatin, K.-M., P. Henneke, G. F.  Hoffmann, and H.-G. Kräusslich. 2020. “Prevalence of COVID-19 in children in Baden-Württemberg – Preliminary study report.” doi: https://www.klinikum.uni-heidelberg.de/fileadmin/pressestelle/Kinderstudie/Prevalence_of_COVID-19_in_BaWu__.pdf.

Dong, Y., X. Mo, Y. Hu, X. Qi, F. Jiang, Z. Jiang, and S. Tong. 2020. “Epidemiology of COVID-19 Among Children in China.”  Pediatrics 145 (6). doi: 10.1542/peds.2020-0702.

Dufort, E. M., E. H. Koumans, E. J. Chow, E. M. Rosenthal, A. Muse, J. Rowlands, M. A. Barranco, A. M. Maxted, E. S. Rosenberg, D. Easton, T. Udo, J. Kumar, W. Pulver, L. Smith, B. Hutton, D. Blog, H. Zucker, State New York, Control Centers for Disease, and Team Prevention Multisystem Inflammatory Syndrome in Children Investigation. 2020. “Multisystem Inflammatory Syndrome in Children in New York State.”  N Engl J Med 383 (4):347-358. doi: 10.1056/NEJMoa2021756.

Dumpa, V., R. Kamity, A. N. Vinci, E. Noyola, and A. Noor. 2020. “Neonatal Coronavirus 2019 (COVID-19) Infection: A Case Report and Review of Literature.”  Cureus 12 (5):e8165. doi: 10.7759/cureus.8165.

Ehrhardt, J., A. Ekinci, H. Krehl, M. Meincke, I. Finci, J. Klein, B. Geisel, C. Wagner-Wiening, M. Eichner, and S. O. Brockmann. 2020. “Transmission of SARS-CoV-2 in children aged 0 to 19 years in childcare facilities and schools after their reopening in May 2020, Baden-Wurttemberg, Germany.”  Euro Surveill 25 (36). doi: 10.2807/1560-7917.ES.2020.25.36.2001587.

Ferrari, A., M. Zecca, C. Rizzari, F. Porta, M. Provenzi, M. Marinoni, R. F. Schumacher, R. Luksch, M. Terenziani, M. Casanova, F. Spreafico, S. Chiaravalli, F. Compagno, F. Bruni, C. Piccolo, L. Bettini, M. D’Angio, G. M. Ferrari, A. Biondi, M. Massimino, and A. Balduzzi. 2020. “Children with cancer in the time of COVID-19: An 8-week report from the six pediatric onco-hematology centers in Lombardia, Italy.”  Pediatr Blood Cancer 67 (8):e28410. doi: 10.1002/pbc.28410.

Fontanet, Arnaud, Laura Tondeur, Yoann Madec, Rebecca Grant, Camille Besombes, Nathalie Jolly, Sandrine Fernandes Pellerin, Marie-Noëlle Ungeheuer, Isabelle Cailleau, Lucie Kuhmel, Sarah Temmam, Christèle Huon, Kuang-Yu Chen, Bernadette Crescenzo, Sandie Munier, Caroline Demeret, Ludivine Grzelak, Isabelle Staropoli, Timothée Bruel, Pierre Gallian, Simon Cauchemez, Sylvie van der Werf, Olivier Schwartz, Marc Eloit, and Bruno Hoen. 2020. “Cluster of COVID-19 in northern France: A retrospective closed cohort study.”  medRxiv:2020.04.18.20071134. doi: 10.1101/2020.04.18.20071134.

Gale, C., M. A. Quigley, A. Placzek, M. Knight, S. Ladhani, E. S. Draper, D. Sharkey, C. Doherty, H. Mactier, and J. J. Kurinczuk. 2021. “Characteristics and outcomes of neonatal SARS-CoV-2 infection in the UK: a prospective national cohort study using active surveillance.”  Lancet Child Adolesc Health 5 (2):113-121. doi: 10.1016/S2352-4642(20)30342-4.

Gold, J. A. W., J. R. Gettings, A. Kimball, R. Franklin, G. Rivera, E. Morris, C. Scott, P. L. Marcet, M. Hast, M. Swanson, J. McCloud, L. Mehari, E. S. Thomas, H. L. Kirking, J. E. Tate, J. Memark, C. Drenzek, S. Vallabhaneni, and K. School Covid-Investigation Team Georgia. 2021. “Clusters of SARS-CoV-2 Infection Among Elementary School Educators and Students in One School District – Georgia, December 2020-January 2021.”  MMWR Morb Mortal Wkly Rep 70 (8):289-292. doi: 10.15585/mmwr.mm7008e4.

Gordon, M., T. Kagalwala, K. Rezk, C. Rawlingson, M. I. Ahmed, and A. Guleri. 2020. “Rapid systematic review of neonatal COVID-19 including a case of presumed vertical transmission.”  BMJ Paediatr Open 4 (1):e000718. doi: 10.1136/bmjpo-2020-000718.

Group, Children’s Task and Finish. 2020. Children’s Task and Finish Group: update to 4th Nov 2020 paper on children, schools and transmission.

Han, M. S., M. W. Seong, N. Kim, S. Shin, S. I. Cho, H. Park, T. S. Kim, S. S. Park, and E. H. Choi. 2020. “Viral RNA Load in Mildly Symptomatic and Asymptomatic Children with COVID-19, Seoul, South Korea.”  Emerg Infect Dis 26 (10):2497-2499. doi: 10.3201/eid2610.202449.

Heavey, L., G. Casey, C. Kelly, D. Kelly, and G. McDarby. 2020. “No evidence of secondary transmission of COVID-19 from children attending school in Ireland, 2020.”  Euro Surveill 25 (21). doi: 10.2807/1560-7917.ES.2020.25.21.2000903.

Held, L. 2020. “A discussion and reanalysis of the results reported in Jones et al. (2020).” doi: https://osf.io/bkuar/.

Hippich, M., L. Holthaus, R. Assfalg, J. Zapardiel-Gonzalo, H. Kapfelsperger, M. Heigermoser, F. Haupt, D. A. Ewald, T. C. Welzhofer, B. A. Marcus, S. Heck, A. Koelln, J. Stock, F. Voss, M. Secchi, L. Piemonti, K. de la Rosa, U. Protzer, M. Boehmer, P. Achenbach, V. Lampasona, E. Bonifacio, and A. G. Ziegler. 2021. “A Public Health Antibody Screening Indicates a 6-Fold Higher SARS-CoV-2 Exposure Rate than Reported Cases in Children.”  Med (N Y) 2 (2):149-163 e4. doi: 10.1016/j.medj.2020.10.003.

Hoang, A., K. Chorath, A. Moreira, M. Evans, F. Burmeister-Morton, F. Burmeister, R. Naqvi, M. Petershack, and A. Moreira. 2020. “COVID-19 in 7780 pediatric patients: A systematic review.”  EClinicalMedicine 24:100433. doi: 10.1016/j.eclinm.2020.100433.

Hrusak, O., T. Kalina, J. Wolf, A. Balduzzi, M. Provenzi, C. Rizzari, S. Rives, M. Del Pozo Carlavilla, M. E. V. Alonso, N. Dominguez-Pinilla, J. P. Bourquin, K. Schmiegelow, A. Attarbaschi, P. Grillner, K. Mellgren, J. van der Werff Ten Bosch, R. Pieters, T. Brozou, A. Borkhardt, G. Escherich, M. Lauten, M. Stanulla, O. Smith, A. E. J. Yeoh, S. Elitzur, A. Vora, C. K. Li, H. Ariffin, A. Kolenova, L. Dallapozza, R. Farah, J. Lazic, A. Manabe, J. Styczynski, G. Kovacs, G. Ottoffy, M. S. Felice, B. Buldini, V. Conter, J. Stary, and M. Schrappe. 2020. “Flash survey on severe acute respiratory syndrome coronavirus-2 infections in paediatric patients on anticancer treatment.”  Eur J Cancer 132:11-16. doi: 10.1016/j.ejca.2020.03.021.

Ismail, S. A., V. Saliba, J. Lopez Bernal, M. E. Ramsay, and S. N. Ladhani. 2021. “SARS-CoV-2 infection and transmission in educational settings: a prospective, cross-sectional analysis of infection clusters and outbreaks in England.”  Lancet Infect Dis 21 (3):344-353. doi: 10.1016/S1473-3099(20)30882-3.

Jones, Terry C., Barbara Mühlemann, Talitha Veith, Guido Biele, Marta Zuchowski, Jörg Hofmann, Angela Stein, Anke Edelmann, Victor Max Corman, and Christian Drosten. 2020. “An analysis of SARS-CoV-2 viral load by patient age.”  medRxiv:2020.06.08.20125484. doi: 10.1101/2020.06.08.20125484.

Jones, V. G., M. Mills, D. Suarez, C. A. Hogan, D. Yeh, J. B. Segal, E. L. Nguyen, G. R. Barsh, S. Maskatia, and R. Mathew. 2020. “COVID-19 and Kawasaki Disease: Novel Virus and Novel Case.”  Hosp Pediatr 10 (6):537-540. doi: 10.1542/hpeds.2020-0123.

Konsortium der Medizinischen Universität Graz, der Medizinischen Universität Innsbruck, der Medizinischen Fakultät der JKU Linz und der Universität Wien in Zusammenarbeit mit dem Bundesministerium für Bildung, Wissenschaft und Forschung. 2020. “Ergebnisse der Erstuntersuchung der Schul-SARS-CoV-2-Monitoringstudie.” doi: https://www.i-med.ac.at/pr/docs/Schul-SARS-CoV-2-Studie-Analyse_Abstract_PA.pdf.

Kyle, M. H., M. E. Glassman, A. Khan, C. R. Fernandez, E. Hanft, U. N. Emeruwa, T. Scripps, L. Walzer, G. V. Liao, M. Saslaw, D. Rubenstein, D. S. Hirsch, M. K. Keown, A. Stephens, I. Mollicone, M. L. Bence, A. Gupta, S. Sultan, C. Sibblies, S. Whittier, W. Abreu, F. Akita, A. Penn, J. S. Orange, L. Saiman, M. G. Welch, C. Gyamfi-Bannerman, M. S. Stockwell, and D. Dumitriu. 2020. “A review of newborn outcomes during the COVID-19 pandemic.”  Semin Perinatol 44 (7):151286. doi: 10.1016/j.semperi.2020.151286.

L’Huillier, A. G., G. Torriani, F. Pigny, L. Kaiser, and I. Eckerle. 2020. “Culture-Competent SARS-CoV-2 in Nasopharynx of Symptomatic Neonates, Children, and Adolescents.”  Emerg Infect Dis 26 (10):2494-2497. doi: 10.3201/eid2610.202403.

Lavezzo, E., E. Franchin, C. Ciavarella, G. Cuomo-Dannenburg, L. Barzon, C. Del Vecchio, L. Rossi, R. Manganelli, A. Loregian, N. Navarin, D. Abate, M. Sciro, S. Merigliano, E. De Canale, M. C. Vanuzzo, V. Besutti, F. Saluzzo, F. Onelia, M. Pacenti, S. G. Parisi, G. Carretta, D. Donato, L. Flor, S. Cocchio, G. Masi, A. Sperduti, L. Cattarino, R. Salvador, M. Nicoletti, F. Caldart, G. Castelli, E. Nieddu, B. Labella, L. Fava, M. Drigo, K. A. M. Gaythorpe, Covid-Response Team Imperial College, A. R. Brazzale, S. Toppo, M. Trevisan, V. Baldo, C. A. Donnelly, N. M. Ferguson, I. Dorigatti, A. Crisanti, and Covid-Response Team Imperial College. 2020. “Suppression of a SARS-CoV-2 outbreak in the Italian municipality of Vo’.”  Nature 584 (7821):425-429. doi: 10.1038/s41586-020-2488-1.

Li, W., B. Zhang, J. Lu, S. Liu, Z. Chang, C. Peng, X. Liu, P. Zhang, Y. Ling, K. Tao, and J. Chen. 2020. “Characteristics of Household Transmission of COVID-19.”  Clin Infect Dis 71 (8):1943-1946. doi: 10.1093/cid/ciaa450.

Link-Gelles, R., A. L. DellaGrotta, C. Molina, A. Clyne, K. Campagna, T. M. Lanzieri, M. A. Hast, K. Palipudi, E. Dirlikov, and U. Bandy. 2020. “Limited Secondary Transmission of SARS-CoV-2 in Child Care Programs – Rhode Island, June 1-July 31, 2020.”  MMWR Morb Mortal Wkly Rep 69 (34):1170-1172. doi: 10.15585/mmwr.mm6934e2.

Liu, W., Q. Zhang, J. Chen, R. Xiang, H. Song, S. Shu, L. Chen, L. Liang, J. Zhou, L. You, P. Wu, B. Zhang, Y. Lu, L. Xia, L. Huang, Y. Yang, F. Liu, M. G. Semple, B. J. Cowling, K. Lan, Z. Sun, H. Yu, and Y. Liu. 2020. “Detection of Covid-19 in Children in Early January 2020 in Wuhan, China.”  N Engl J Med 382 (14):1370-1371. doi: 10.1056/NEJMc2003717.

Liu, Y., L. M. Yan, L. Wan, T. X. Xiang, A. Le, J. M. Liu, M. Peiris, L. L. M. Poon, and W. Zhang. 2020. “Viral dynamics in mild and severe cases of COVID-19.”  Lancet Infect Dis 20 (6):656-657. doi: 10.1016/S1473-3099(20)30232-2.

Lu, X., L. Zhang, H. Du, J. Zhang, Y. Y. Li, J. Qu, W. Zhang, Y. Wang, S. Bao, Y. Li, C. Wu, H. Liu, D. Liu, J. Shao, X. Peng, Y. Yang, Z. Liu, Y. Xiang, F. Zhang, R. M. Silva, K. E. Pinkerton, K. Shen, H. Xiao, S. Xu, G. W. K. Wong, and Team Chinese Pediatric Novel Coronavirus Study. 2020. “SARS-CoV-2 Infection in Children.”  N Engl J Med 382 (17):1663-1665. doi: 10.1056/NEJMc2005073.

Luo, Lei, Dan Liu, Xin-long Liao, Xian-bo Wu, Qin-long Jing, Jia-zhen Zheng, Fang-hua Liu, Shi-gui Yang, Bi Bi, Zhi-hao Li, Jian-ping Liu, Wei-qi Song, Wei Zhu, Zheng-he Wang, Xi-ru Zhang, Pei-liang Chen, Hua-min Liu, Xin Cheng, Miao-chun Cai, Qing-mei Huang, Pei Yang, Xing-fen Yang, Zhi-gang Han, Jin-ling Tang, Yu Ma, and Chen Mao. 2020. “Modes of contact and risk of transmission in COVID-19 among close contacts.”  medRxiv:2020.03.24.20042606. doi: 10.1101/2020.03.24.20042606.

Madewell, Z. J., Y. Yang, I. M. Longini, Jr., M. E. Halloran, and N. E. Dean. 2020. “Household Transmission of SARS-CoV-2: A Systematic Review and Meta-analysis.”  JAMA Netw Open 3 (12):e2031756. doi: 10.1001/jamanetworkopen.2020.31756.

Marlais, M., T. Wlodkowski, M. Vivarelli, L. Pape, B. Tonshoff, F. Schaefer, and K. Tullus. 2020. “The severity of COVID-19 in children on immunosuppressive medication.”  Lancet Child Adolesc Health 4 (7):e17-e18. doi: 10.1016/S2352-4642(20)30145-0.

Minotti, C., F. Tirelli, E. Barbieri, C. Giaquinto, and D. Dona. 2020. “How is immunosuppressive status affecting children and adults in SARS-CoV-2 infection? A systematic review.”  J Infect 81 (1):e61-e66. doi: 10.1016/j.jinf.2020.04.026.

Morand, A., A. Fabre, P. Minodier, A. Boutin, N. Vanel, E. Bosdure, and P. E. Fournier. 2020. “COVID-19 virus and children: What do we know?”  Arch Pediatr 27 (3):117-118. doi: 10.1016/j.arcped.2020.03.001.

Mossong, J., N. Hens, M. Jit, P. Beutels, K. Auranen, R. Mikolajczyk, M. Massari, S. Salmaso, G. S. Tomba, J. Wallinga, J. Heijne, M. Sadkowska-Todys, M. Rosinska, and W. J. Edmunds. 2008. “Social contacts and mixing patterns relevant to the spread of infectious diseases.”  PLoS Med 5 (3):e74. doi: 10.1371/journal.pmed.0050074.

Mustafa, N. M., and A. Selim L. 2020. “Characterisation of COVID-19 Pandemic in Paediatric Age Group: A Systematic Review and Meta-Analysis.”  J Clin Virol 128:104395. doi: 10.1016/j.jcv.2020.104395.

Nathan, N., B. Prevost, and H. Corvol. 2020. “Atypical presentation of COVID-19 in young infants.”  Lancet 395 (10235):1481. doi: 10.1016/S0140-6736(20)30980-6.

Pollan, M., B. Perez-Gomez, R. Pastor-Barriuso, J. Oteo, M. A. Hernan, M. Perez-Olmeda, J. L. Sanmartin, A. Fernandez-Garcia, I. Cruz, N. Fernandez de Larrea, M. Molina, F. Rodriguez-Cabrera, M. Martin, P. Merino-Amador, J. Leon Paniagua, J. F. Munoz-Montalvo, F. Blanco, R. Yotti, and Ene-Covid Study Group. 2020. “Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study.”  Lancet 396 (10250):535-544. doi: 10.1016/S0140-6736(20)31483-5.

Pray, I. W., S. N. Gibbons-Burgener, A. Z. Rosenberg, D. Cole, S. Borenstein, A. Bateman, E. Pevzner, and R. P. Westergaard. 2020. “COVID-19 Outbreak at an Overnight Summer School Retreat – Wisconsin, July-August 2020.”  MMWR Morb Mortal Wkly Rep 69 (43):1600-1604. doi: 10.15585/mmwr.mm6943a4.

Rawson, A., A. C. Wilson, A. L. Schwaderer, E. Spiwak, B. Johnston, S. Anderson, C. Nailescu, S. Gupta, J. C. Christenson, D. S. Hains, and M. C. Starr. 2021. “Coronavirus disease 2019 (COVID-19) in two pediatric patients with kidney disease on chronic immunosuppression: A case series.”  Hemodial Int 25 (1):E1-E5. doi: 10.1111/hdi.12876.

Richard, A., A. Wisniak, J. Perez-Saez, H. Garrison-Desany, D. Petrovic, G. Piumatti, H. Baysson, A. Picazio, F. Pennacchio, D. De Ridder, F. Chappuis, N. Vuilleumier, N. Low, S. Hurst, I. Eckerle, A. Flahault, J. L. Kaiser, A.S. Azman, I. Guessous, and S. Stringhini. 2020. “Seroprevalence of anti-SARS-CoV-2 IgG antibodies, risk factors for infection and associated symptoms in Geneva, Switzerland: a population-based study.”  medRxiv.

Riphagen, S., X. Gomez, C. Gonzalez-Martinez, N. Wilkinson, and P. Theocharis. 2020. “Hyperinflammatory shock in children during COVID-19 pandemic.”  Lancet 395 (10237):1607-1608. doi: 10.1016/S0140-6736(20)31094-1.

Sheth, S., N. Shah, and V. Bhandari. 2020. “Outcomes in COVID-19 Positive Neonates and Possibility of Viral Vertical Transmission: A Narrative Review.”  Am J Perinatol 37 (12):1208-1216. doi: 10.1055/s-0040-1714719.

Somekh, E., A. Gleyzer, E. Heller, M. Lopian, L. Kashani-Ligumski, S. Czeiger, Y. Schindler, J. B. Lessing, and M. Stein. 2020. “The Role of Children in the Dynamics of Intra Family Coronavirus 2019 Spread in Densely Populated Area.”  Pediatr Infect Dis J 39 (8):e202-e204. doi: 10.1097/INF.0000000000002783.

Stein-Zamir, C., N. Abramson, H. Shoob, E. Libal, M. Bitan, T. Cardash, R. Cayam, and I. Miskin. 2020. “A large COVID-19 outbreak in a high school 10 days after schools’ reopening, Israel, May 2020.”  Euro Surveill 25 (29). doi: 10.2807/1560-7917.ES.2020.25.29.2001352.

Stringhini, S., A. Wisniak, G. Piumatti, A. S. Azman, S. A. Lauer, H. Baysson, D. De Ridder, D. Petrovic, S. Schrempft, K. Marcus, S. Yerly, I. Arm Vernez, O. Keiser, S. Hurst, K. M. Posfay-Barbe, D. Trono, D. Pittet, L. Getaz, F. Chappuis, I. Eckerle, N. Vuilleumier, B. Meyer, A. Flahault, L. Kaiser, and I. Guessous. 2020. “Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Geneva, Switzerland (SEROCoV-POP): a population-based study.”  Lancet 396 (10247):313-319. doi: 10.1016/S0140-6736(20)31304-0.

Stringhini, S., M. E. Zaballa, J. Perez-Saez, N. Pullen, C. de Mestral, A. Picazio, F. Pennacchio, A. Wisniak, A. Richard, H. Baysson, A. Loizeau, J. F. Balavoine, D. Trono, D. Pittet, K. Posfay-Barbe, A. Flahault, F. Chappuis, O. Kherad, N. Vuilleumier, L. Kaiser, A. S. Azman, I. Guessous, and Covid Study Group Specchio. 2021. “Seroprevalence of anti-SARS-CoV-2 antibodies after the second pandemic peak.”  Lancet Infect Dis. doi: 10.1016/S1473-3099(21)00054-2.

Swann, O. V., K. A. Holden, L. Turtle, L. Pollock, C. J. Fairfield, T. M. Drake, S. Seth, C. Egan, H. E. Hardwick, S. Halpin, M. Girvan, C. Donohue, M. Pritchard, L. B. Patel, S. Ladhani, L. Sigfrid, I. P. Sinha, P. L. Olliaro, J. S. Nguyen-Van-Tam, P. W. Horby, L. Merson, G. Carson, J. Dunning, P. J. M. Openshaw, J. K. Baillie, E. M. Harrison, A. B. Docherty, M. G. Semple, and Isaric C. Investigators. 2020. “Clinical characteristics of children and young people admitted to hospital with covid-19 in United Kingdom: prospective multicentre observational cohort study.”  BMJ 370:m3249. doi: 10.1136/bmj.m3249.

Szablewski, C. M., K. T. Chang, M. M. Brown, V. T. Chu, A. R. Yousaf, N. Anyalechi, P. A. Aryee, H. L. Kirking, M. Lumsden, E. Mayweather, C. J. McDaniel, R. Montierth, A. Mohammed, N. G. Schwartz, J. A. Shah, J. E. Tate, E. Dirlikov, C. Drenzek, T. M. Lanzieri, and R. J. Stewart. 2020. “SARS-CoV-2 Transmission and Infection Among Attendees of an Overnight Camp – Georgia, June 2020.”  MMWR Morb Mortal Wkly Rep 69 (31):1023-1025. doi: 10.15585/mmwr.mm6931e1.

Tan, W., Y. Lu, J. Zhang, J. Wang, Y. Dan, Z. Tan, X. He, C. Qian, Q.   Sun, Q. Hu, H. Liu, S. Ye, X. Xiang, Y. Zhou, W. Zhang, Y. Guo, X.- H.  Wang, W. He, X. Wan, F. Sun, Q.  Wei, C.  Chen, G. Pan, J.  Xia, Q. Mao, Y.  Chen, and G. Deng. 2020. “Viral Kinetics and Antibody Responses in Patients with COVID-19.”  medRxiv.

Team, Cdc Covid- Response. 2020. “Coronavirus Disease 2019 in Children – United States, February 12-April 2, 2020.”  MMWR Morb Mortal Wkly Rep 69 (14):422-426. doi: 10.15585/mmwr.mm6914e4.

Torres, J. P., C. Pinera, V. De La Maza, A. J. Lagomarcino, D. Simian, B. Torres, C. Urquidi, M. T. Valenzuela, and M. O’Ryan. 2020. “SARS-CoV-2 antibody prevalence in blood in a large school community subject to a Covid-19 outbreak: a cross-sectional study.”  Clin Infect Dis. doi: 10.1093/cid/ciaa955.

Ulyte, A., T. Radtke, I. A. Abela, S. R. Haile, C. Berger, M. Huber, M. Schanz, M. Schwarzmueller, A. Trkola, J. Fehr, M. A. Puhan, and S. Kriemler. 2021. “Clustering and longitudinal change in SARS-CoV-2 seroprevalence in school children in the canton of Zurich, Switzerland: prospective cohort study of 55 schools.”  BMJ 372:n616. doi: 10.1136/bmj.n616.

Vardhelli, V., A. Pandita, A. Pillai, and S. K. Badatya. 2021. “Perinatal COVID-19: review of current evidence and practical approach towards prevention and management.”  Eur J Pediatr 180 (4):1009-1031. doi: 10.1007/s00431-020-03866-3.

Viner, R. M., O. T. Mytton, C. Bonell, G. J. Melendez-Torres, J. Ward, L. Hudson, C. Waddington, J. Thomas, S. Russell, F. van der Klis, A. Koirala, S. Ladhani, J. Panovska-Griffiths, N. G. Davies, R. Booy, and R. M. Eggo. 2021. “Susceptibility to SARS-CoV-2 Infection Among Children and Adolescents Compared With Adults: A Systematic Review and Meta-analysis.”  JAMA Pediatr 175 (2):143-156. doi: 10.1001/jamapediatrics.2020.4573.

Volz, Erik, Swapnil Mishra, Meera Chand, Jeffrey C. Barrett, Robert Johnson, Lily Geidelberg, Wes R Hinsley, Daniel J Laydon, Gavin Dabrera, Áine O’Toole, Roberto Amato, Manon Ragonnet-Cronin, Ian Harrison, Ben Jackson, Cristina V. Ariani, Olivia Boyd, Nicholas J Loman, John T McCrone, Sónia Gonçalves, David Jorgensen, Richard Myers, Verity Hill, David K. Jackson, Katy Gaythorpe, Natalie Groves, John Sillitoe, Dominic P. Kwiatkowski, Seth Flaxman, Oliver Ratmann, Samir Bhatt, Susan Hopkins, Axel Gandy, Andrew Rambaut, and Neil M Ferguson. 2021. “Transmission of SARS-CoV-2 Lineage B.1.1.7 in England: Insights from linking epidemiological and genetic data.”  medRxiv:2020.12.30.20249034. doi: 10.1101/2020.12.30.20249034.

Wang, W., Y. Xu, R. Gao, R. Lu, K. Han, G. Wu, and W. Tan. 2020. “Detection of SARS-CoV-2 in Different Types of Clinical Specimens.”  JAMA 323 (18):1843-1844. doi: 10.1001/jama.2020.3786.

Wei, M., J. Yuan, Y. Liu, T. Fu, X. Yu, and Z. J. Zhang. 2020. “Novel Coronavirus Infection in Hospitalized Infants Under 1 Year of Age in China.”  JAMA 323 (13):1313-1314. doi: 10.1001/jama.2020.2131.

Yoon, Y., G. J. Choi, J. Y. Kim, K. R. Kim, H. Park, J. K. Chun, and Y. J. Kim. 2021. “Childcare Exposure to Severe Acute Respiratory Syndrome Coronavirus 2 for 4-Year-Old Presymptomatic Child, South Korea.”  Emerg Infect Dis 27 (2):341-347. doi: 10.3201/eid2702.203189.

Yu, F., L. Yan, N. Wang, S. Yang, L. Wang, Y. Tang, G. Gao, S. Wang, C. Ma, R. Xie, F. Wang, C. Tan, L. Zhu, Y. Guo, and F. Zhang. 2020. “Quantitative Detection and Viral Load Analysis of SARS-CoV-2 in Infected Patients.”  Clin Infect Dis 71 (15):793-798. doi: 10.1093/cid/ciaa345.

Yung, C. F., K. Q. Kam, C. Y. Chong, K. D. Nadua, J. Li, N. W. H. Tan, S. Ganapathy, K. P. Lee, K. C. Ng, Y. H. Chan, and K. C. Thoon. 2020. “Household Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 from Adults to Children.”  J Pediatr 225:249-251. doi: 10.1016/j.jpeds.2020.07.009.

Yung, C. F., K. Q. Kam, K. D. Nadua, C. Y. Chong, N. W. H. Tan, J. Li, K. P. Lee, Y. H. Chan, K. C. Thoon, and K. C. Ng. 2021. “Novel Coronavirus 2019 Transmission Risk in Educational Settings.”  Clin Infect Dis 72 (6):1055-1058. doi: 10.1093/cid/ciaa794.

Zhang, Z. J., X. J. Yu, T. Fu, Y. Liu, Y. Jiang, B. X. Yang, and Y. Bi. 2020. “Novel coronavirus infection in newborn babies aged <28 days in China.”  Eur Respir J 55 (6). doi: 10.1183/13993003.00697-2020.

Zheng, S., J. Fan, F. Yu, B. Feng, B. Lou, Q. Zou, G. Xie, S. Lin, R. Wang, X. Yang, W. Chen, Q. Wang, D. Zhang, Y. Liu, R. Gong, Z. Ma, S. Lu, Y. Xiao, Y. Gu, J. Zhang, H. Yao, K. Xu, X. Lu, G. Wei, J. Zhou, Q. Fang, H. Cai, Y. Qiu, J. Sheng, Y. Chen, and T. Liang. 2020. “Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study.”  BMJ 369:m1443. doi: 10.1136/bmj.m1443.

Zhu, Y., C. J. Bloxham, K. D. Hulme, J. E. Sinclair, Z. W. M. Tong, L. E. Steele, E. C. Noye, J. Lu, Y. Xia, K. Y. Chew, J. Pickering, C. Gilks, A. C. Bowen, and K. R. Short. 2020. “A meta-analysis on the role of children in SARS-CoV-2 in household transmission clusters.”  Clin Infect Dis. doi: 10.1093/cid/ciaa1825.

Zou, L., F. Ruan, M. Huang, L. Liang, H. Huang, Z. Hong, J. Yu, M. Kang, Y. Song, J. Xia, Q. Guo, T. Song, J. He, H. L. Yen, M. Peiris, and J. Wu. 2020. “SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients.”  N Engl J Med 382 (12):1177-1179. doi: 10.1056/NEJMc2001737.

Type of document: Evidence review

Date of request: 30/03/2020

Date of response: 20/04/2020

1st Up-date:   23/4/2020

2nd Up-date:  10/5/2020

3rd Up-date:   12/8/2020

4th Up-date:   09/04/2021

In response to request from: NCS-TF Advisory Board and Federal Office of Public Health

Experts involved: Public Health, with input from other groups

Contact persons: Margarethe Wiedenmann, Nicola Low