key: cord-347734-0z2kin6r
authors: Armann, J. P.; Unrath, M.; Kirsten, C.; Lueck, C.; Dalpke, A.; Berner, R.
title: Anti-SARS-CoV-2 IgG antibodies in adolescent students and their teachers in Saxony, Germany (SchoolCoviDD19): very low seropraevalence and transmission rates
date: 2020-07-17
journal: nan
DOI: 10.1101/2020.07.16.20155143
sha: 
doc_id: 347734
cord_uid: 0z2kin6r

Background: School closures are part of the SARS-CoV-2 pandemic control measures in many countries, based on the assumption that children play a similar role in transmitting SARS-CoV-2 as they do in transmitting influenza. We therefore performed a SARS-CoV-2 seropraevalence-study in students and teachers to assess their role in the SARS-CoV-2 transmission. Methods: Students grade 8-11 and their teachers in 13 secondary schools in eastern Saxony, Germany, were invited to participate in the SchoolCoviDD19 study. Blood samples were collected between May 25th and June 30th, 2020. Anti-SARS-CoV-2 IgG were assed using chemiluminescence immunoassay technology and all samples with a positive or equivocal test result were re-tested with two additional serological tests. Findings: 1538 students and 507 teachers participated in this study. The seropraevalence for SARS-CoV-2 was 0.6%. Even in schools with reported Covid-19 cases before the Lockdown of March 13th no clusters could be identified. 23/24 participants with a household history of COVID-91 were seronegative. By using a combination of three different immunoassays we could exclude 16 participants with a positive or equivocal results after initial testing. Interpretation: Students and teachers do not play a crucial role in driving the SARS-CoV-2 pandemic in a low prevalence setting. Transmission in families occurs very infrequently, and the number of unreported cases is low in this age group, making school closures not appear appropriate as a strategy in this low prevalence settings. Funding: This study was supported by a grant from the state of Saxony

Methods: Students grade 8-11 and their teachers in 13 secondary schools in eastern Saxony, Germany, were invited to participate in the SchoolCoviDD19 study. Blood samples were collected between May 25th and June 30th, 2020. Anti-SARS-CoV-2 IgG were assed using chemiluminescence immunoassay technology and all samples with a positive or equivocal test result were re-tested with two additional serological tests.

Findings: 1538 students and 507 teachers participated in this study. The seropraevalence for SARS-CoV-2 was 0.6%. Even in schools with reported Covid-19 cases before the Lockdown of March 13 th no clusters could be identified. 23/24 participants with a household history of COVID-91 were seronegative. By using a combination of three different immunoassays we could exclude 16 participants with a positive or equivocal results after initial testing.

Interpretation: Students and teachers do not play a crucial role in driving the SARS-CoV-2 pandemic in a low prevalence setting. Transmission in families occurs very infrequently, and the number of unreported cases is low in this age group, making school closures not appear appropriate as a strategy in this low prevalence settings.

Funding: This study was supported by a grant from the state of Saxony . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted July 17, 2020. . https://doi.org/10.1101/2020.07.16.20155143 doi: medRxiv preprint

Introduction:

Since the identification of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as the cause of COVID-19 in December 2019 1 , the virus spread rapidly around the world, leading to the declaration of a pandemic by the World Health Organization on March 12 th 2020. By March 18 th 2020, 126 countries-including Germany-had implemented school closures as part of their pandemic control measures, with the number of countries peaking at 194 on April 10 th 2020 and more than 90% of the world's student population being affected at this point 2 .

These actions were mainly based on the assumption that children play a similar role in transmitting SARS-CoV-2 as they do in transmitting influenza during outbreaks, for which evidence exists that school closures reduce the peak of the outbreak 3 . However, there is reason to believe that children play a less significant role in SARS-CoV-2 transmission compared to influenza, making control measures focused on this age group less effective: Most countries-including Germany-report a much lower proportion of cases in children compared to their population size 4-6 . In addition a recent report from Australia could only identify a very limited spread of COVID-19 in primary schools, with no evidence of children infecting teachers 7 .

However, currently available data is insufficient to rule out that children are as likely as adults to be infected by and to transmit SARS-CoV-2, but simply show little to no symptoms of the disease.

We therefore aimed to quantify the proportion of adolescent schoolchildren and teachers in Saxony, one of the eastern Federal States of Germany, that already have developed antibodies against SARS-CoV-2. In Saxony, the infection rates were comparatively low with 139 laboratory-confirmed SARS-CoV-2 infections per 100,000 inhabitants as of 13 July 2020.

After the reopening of the schools in Saxony on May 18 th , 2020 students grade 8-11 and their teachers in 13 secondary schools in eastern Saxony were invited to participate in the SchoolCoviDD19 study. After teachers, students, and their legal guardians provided informed consent, 5 mL of peripheral venous blood were collected from each individual during visits at each participating school between May 25 th and June 30 th , 2020. In addition, participants were asked to complete a questionnaire on age, household size, previously diagnosed SARS-CoV-2 infections in themselves or their household contacts, comorbidities and regular medication. In addition, students were asked about regular social contacts outside their household or classroom. The SchoolCoviDD19 study was approved by the Ethics Committee of the Technische Universität (TU) Dresden (BO-EK-156042020) and has been assigned clinical trial number DRKS00022455.

We assessed anti-SARS-CoV-2 IgG antibodies in all samples using a commercially available chemiluminescence immunoassay (CLIA) technology for the quantitative determination of anti-S1 and anti-S2 specific IgG antibodies to SARS-CoV-2 (Diasorin LIAISON® SARS-CoV-2 S1/S2 IgG Assay). Antibody levels > 15.0 AU/ml were considered positive and levels between 12.0 and 15.0 AU/ml were considered equivocal.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted July 17, 2020. .

All samples with a positive or equivocal LIAISON® test result, as well as all samples from participants with a reported personal or household history of a SARS-CoV-2 infection, were re-tested with two additional serological tests: These were a chemiluminescent microparticle immunoassay (CMIA) intended for the qualitative detection of IgG antibodies to the nucleocapsid protein of SARS-CoV-2 (Abbott Diagnostics® ARCHITECT SARS-CoV-2 IgG ) (an index (S/C) of < 1.4 was considered negative whereas one >/= 1.4 was considered positive) and an ELISA detecting IgG against the S1 domain of the SARS-CoV-2 spike protein (Euroimmun® Anti-SARS-CoV-2 ELISA) (a ratio < 0.8 was considered negative, 0.8-1.1 equivocal, > 1.1 positive) Participants whose positive or equivocal LIAISON® test result could be confirmed by a positive test result in at least one additional serological test were considered having antibodies against SARS-CoV-2.

Analyses were performed using IBM SPSS 25.0 and Microsoft Excel 2010. Results for continuous variables are presented as medians with interquartile ranges (IQR) and categorical variables as numbers with percentages, unless stated otherwise.

The funder of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.

A total of 1538 students and 507 teachers from 13 different schools participated in this study. Demographic data is shown in Table 1 .

The number of participants ranged from 21 to 573 per individual school. Twelve participants-11 students and one teacher-had detectable antibodies against SARS-CoV-2 in at least two different assays and were considered seropositive. In 7/13 schools, seropositive participants could be identified, with four seropositive participants in one school as the maximum. The seroprevalence ranged from 0 to 2. Table 3 .

The findings from this unique study in older students and their teachers indicate that the prevalence of IgG antibodies against SARS-CoV-2 remains extremely low after the first wave of the corona pandemic in Germany. While this finding is consistent with local surveillance data 8 that shows a prevalence of PCR-confirmed cases of 0,15%, it clearly indicates that schools did not develop into silent hotspots of SARS-CoV-2 transmission during this first wave of the pandemic. In fact, 5 of the 12 participants with antibodies against SARS-CoV-2 had a personal or household history of COVID-19, yielding a ratio of unidentified to identified cases of 2.4, which is much smaller than that previously assumed by some authors 9 . We could not detect a single cluster of infections in the participating schools, even though at least three schools did have confirmed SARS-CoV-2 cases before the March 13 th lockdown in Saxony. This is consistent with findings from the 2003 SARS outbreak 10, 11 , and calls the effectiveness of transmission control measures focused mainly on the student population into question. This is especially relevant since there are clearly described adverse effects of school closures, as loss of education, loss of social contacts and social control, nutritional problems in children who rely on school meals, increases in harm to child welfare in vulnerable populations, as well as economic harm caused by loss to productivity due to parents being forced from work to childcare 12, 13 . Additionally, even with school closures in place, social contacts continue as informal child care and non-school gatherings 14 , thereby reducing the potential benefit of school closures further. Our data support this finding this finding since an overwhelming majority of not less than 80% of the participating students in our study reported to have regular social contacts outside their household or classroom.

Close contact with COVID-19 patients-especially in the same household-has been shown to increase viral transmission 15 . However, in our study, only one out of 24 participants with a confirmed SARS-CoV-2 infection in the same household became indeed infected as measured by antibody production. This suggests that either the transmissibility of the virus is lower than previously assumed or that there are certain quarantine and separation measures than can effectively reduce the probability of viral transmission even in close contact situations.

Currently no gold standard serological testing strategy for SARS-CoV-2 exists. Even though immunoassays yield better performance than rapid point-of-care tests 15 and the targeted SARS-CoV-2 S protein and nucleoprotein show a similarity of less than 30% to endemic betacoronaviruses 16 , false positive results are still a concern, especially in low-prevalence populations and when interpreting results on a personal rather than a population-based level. By using a combination of three different immunoassays and only regarding participants with at least two positive results as seropositive for SARS-CoV-2, we could exclude ten participants with a positive and six with an equivocal initial test by negative confirmatory testing. In our population a positive predictive value of 42.9% could be observed which was nearby an expected PPV of 45.3% for a prevalence of 0.59% population and the given test characteristics (sensitivity 97.6%, specificity 99.3%). By using this approach, we could reliably identify patients with confirmed seropositivity against SARS-CoV-2 in a low-prevalence population.

As for now, students and teacher do not seem to play a crucial role in driving the SARS-CoV-2 pandemic in Germany. Transmission in families appears to occur very infrequently, and the number of unreported cases obviously is low in this age group. Therefore, social distancing strategies such as the reduction of students of different classes mixing at school paired with symptom-based screening strategies, contact tracing and quarantine measures for identified cases are likely as effective as full school closures, with less adverse effects on the student population.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted July 17, 2020. . https://doi.org/10.1101/2020.07.16.20155143 doi: medRxiv preprint

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All authors declare no conflict of interests