Study population characteristics
In total 1,466 children and their caregivers were invited to the study of whom 632 (43.1%) volunteered, 376 were enrolled, and 362 had a blood sample taken. The online questionnaire was completed by 341 (94.2%) caregivers and the additional questionnaire by 257 (71.0%) caregivers. The sample included 175 (48.3%) boys and 187 (51.7%) girls (table 1). The mean age at the time of sampling was 10.9 years (range 5.7 – 14.7 years), with a comparable distribution according to sex and municipality. The number of children per grade in primary school (six grades in total) ranged from 27 to 32 (13 to 16 boys; 12 to 18 girls). In secondary school, 80 (43 boys), 76 (32 boys) and 25 (11 boys) were enrolled in the first, second and third grade, respectively. The third grade of secondary school was only sampled in Alken. In total, 5.8% of children had a chronic condition, 14.1% had a family member with a condition that increases the risk of severe COVID-19 infection (e.g. high blood pressure, diabetes…), and 3% lived in a household with a person at or above 65 years of age. A PCR-confirmed infection was reported for 4 children in the survey (all in March 2020), while parents of 294 participants reported no known history of infection and parents of 43 children reported not knowing whether their child had been infected or not.
Socio-economic characteristics and potential risk factors for SARS-CoV-2 infection are listed in Table 1. These did not differ between the regions or between primary and secondary school, except for use of public transport and summer camps. While rare (< 10%) in Pelt, almost 30% of school children in Alken use public transport at least once per week (p < 0.001). Public transport is almost exclusively used by secondary schoolchildren (n = 55/165, 33.30%), versus one out of 176 (0.6%) primary schoolchildren. Overnight camps were reported more frequently in secondary school (98/165, 59.4%) compared to primary school (53/176, 30.1%). In contrast, day camps were reported more frequently in primary school (53/176, 47.7%) compared to secondary school (9/165, 5.5%). In total 290 (85.0%) children participated at least one hour per week in extracurricular activities, with an equal distribution by region (Table1) and in primary (148/176, 84.1%) and secondary (142/165, 86.1%) school. About 17.6% of these activities implied an increased risk (no mask and no distance), and 129 (52.7%) children participated in indoor activities.
Seroprevalence
The prevalence of SARS-CoV-2 antibodies by municipality and type of school is listed in Table 2. None of the primary schoolchildren in Pelt were seropositive, however, 8.9% (8/90) had SARS-CoV-2 antibodies in secondary school. In Alken, we found 13.3% (12/90) seropositive children in primary and 15.4% (14/91) seropositive young-adolescents in secondary schools. The overall adjusted RR of having SARS-CoV-2 antibodies was 3.2 (95%CI: 1.3 – 7.9; p = 0.01) in Alken compared to Pelt and 1.6 (95%CI: 0.7 – 3.8; p = 0.3) in secondary schools compared to primary schools. The RR of seropositivity in secondary schoolchildren in Alken versus Pelt was 1.7 (95%CI: 0.7 – 4.1; p = 0.2), and the RR in secondary versus primary school in Alken was 1.1 (95%CI: 0.4 – 1.6; p = 0.9). Comparisons with primary schoolchildren in Pelt are not estimable due the absence of cases. No significant difference was observed in boys versus girls (RR 0.8; 95%CI 0.4 – 1.5). All but two seropositive children had antibody titers above the upper limit of quantification. All four participants for whom a PCR-confirmed infection was reported in the survey were found seropositive. Among the 294 participants for whom no confirmed infection was reported, 22 (7.5%) were seropositive, as well as 7 (16.3%) among the 43 whose parents were not sure if their child had been infected. In total, for 60.1% of all pupils, at least one of the following symptoms were reported from February 2020 until data sampling: fever, cough, difficulty breathing, loss of taste, loss of smell, headache, runny nose, sore throat, ear pain, myalgia, asthenia, bellyache, diarrhea, nausea, rash, hyperemia or painful eyes. Importantly, none of the seropositive participants experienced a severe disease requiring hospitalization.
Risk factors for seropositivity
Table 3 gives an overview of risk factors for SARS-CoV2 seropositivity. We found that children whose caregivers are healthcare workers who were in contact with covid-19 patients are more likely to be seropositive (RR: 2.2; 95%CI: 1.0 – 4.6). Also, children who have at least one hour per week of extracurricular activities are more likely to be seropositive (RR: 5.6; 95%CI: 1.2 – 25.3). Based on the second survey we could not establish an association between activities with a high (indoor, without masks, no physical distance) versus low risk (data not shown). Seroprevalence was also higher in children who had contact with a confirmed case (RR: 3.8; 95%CI: 1.7 – 8.3), had a high-risk contact with a confirmed case (RR:3.7; 95%CI: 2.0 – 6.7) or had a high-risk contact with a confirmed case within the household (RR: 5.1; 95%CI: 2.9 – 9.2). The presence and number of young children, adolescents, adults and elderly persons in the family were not statistically significant associated with the prevalence (risk) of having SARS-CoV-2 antibodies in this cohort.
Even though the study was not designed to investigate clusters, we found an intraclass correlation of 0.15 (SE 0.1). There were 118 classes or clusters in total (mean size is 3.1, range 1 – 14), but the 91 secondary school students were distributed over 55 clusters (mean cluster size 1.6, range 1 – 4) In total, we found four classes with more than one case. Respectively, two out of four, three out of four, four out of seven and three out of eight children of these classes were seropositive. Assuming an overall prevalence of 9.4%, the binomial probability of observing these numbers varies between 3/1000 and 1/10000.