Seroprevalence and Immunity of SARS-Cov-2 Infection in Children
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International Journal of Public Health https://doi.org/10.1007/s00038-020-01495-z (0123456789().,-volV)(0123456789().,-volV) ORIGINAL ARTICLE Seroprevalence and immunity of SARS-CoV-2 infection in children and adolescents in schools in Switzerland: design for a longitudinal, school-based prospective cohort study 1 1 2 1 1 1 Agne Ulyte • Thomas Radtke • Ire`ne A. Abela • Sarah R. Haile • Julia Braun • Ruedi Jung • 3 2 1 1 1 Christoph Berger • Alexandra Trkola • Jan Fehr • Milo A. Puhan • Susi Kriemler Received: 10 September 2020 / Revised: 17 September 2020 / Accepted: 17 September 2020 Ó The Author(s) 2020 Abstract Objectives This longitudinal cohort study aims to assess the extent and patterns of seroprevalence of severe acute res- piratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in school-attending children, and their parents and school personnel. It will examine risk factors for infection, the relationship between seropositivity and symptoms, and temporal persistence of antibodies. Methods The study (Ciao Corona) will enroll a regionally representative, random sample of schools in the canton of Zurich, where 18% of the Swiss population live. Children aged 5–16 years, attending primary and secondary schools, and their parents and school personnel are invited. Venous blood and saliva samples are collected for serological testing in June/July 2020, in October/November 2020, and in March/April 2021. Bi-monthly questionnaires will cover SARS-CoV-2 symptoms and tests, health, preventive behavior, and lifestyle information. Hierarchical Bayesian logistic regression models will account for sensitivity and specificity of the serological tests in the analyses and complex sampling structure, i.e., clustering within classes and schools. Results and conclusions This unique school-based study will allow describing temporal trends of immunity, evaluate effects of preventive measures and will inform goal-oriented policy decisions during subsequent outbreaks. Trial registration ClinicalTrials.gov Identifier: NCT04448717, registered June 26, 2020. https://clinicaltrials.gov/ct2/ show/NCT04448717. Keywords SARS-CoV-2 Á COVID-19 Á Children Á Adolescents Á School Á Protocol Introduction closures in response to the pandemic were partly guided by evidence of transmission of other viruses, such as Decisions on school openings or closures during the severe influenza (Cauchemez et al. 2009; Litvinova et al. 2019), acute respiratory syndrome coronavirus 2 (SARS-CoV-2) but the current reports suggest that the susceptibility and pandemic vary greatly across and within countries. While transmissibility of children may be largely different for some countries kept schools mostly open (e.g., Sweden, SARS-CoV-2 (Viner et al. 2020). Lower prevalence of Australia) or reopened early (e.g., Denmark), others opted SARS-CoV-2 infection is reported in younger children, for prolonged closures with decisions on reopening which could potentially be explained by less frequent pending (e.g., the USA, Italy, Ireland). Early school infection or underestimation due to more frequently asymptomatic infection course (Stringhini et al. 2020; Gudbjartsson et al. 2020; Polla´n et al. 2020). Although Agne Ulyte and Thomas Radtke have shared first authorship. children may infect others less often than adults, their Electronic supplementary material The online version of this exact role in transmission pathways is still not clear (Lee article (https://doi.org/10.1007/s00038-020-01495-z) con- and Raszka 2020). tains supplementary material, which is available to autho- Several studies have reported population-level sero- rized users. prevalence of SARS-CoV-2, including the subpopulation Extended author information available on the last page of the article of children, reflecting the cumulative incidence proportion 123 A. Ulyte et al. of the infection (Stringhini et al. 2020; Polla´n et al. 2020). 1 To repeatedly determine the seroprevalence of SARS- Such studies focused on households, leaving the roles of CoV-2 antibodies in school-aged children covering schools in SARS-CoV-2 transmission unclear, especially as grades one to eight (approximately 6–16 years old) in they were often conducted during school closures. As most June/July 2020 (after the semi-lockdown and the of school-aged children and adolescents’ social interactions subsequent reopening of schools), in October/Novem- take place in family and school (Mossong et al. 2008), ber 2020 (3 months after the start of the next school schools could play a crucial role in spreading the infection. year), and in March/April 2021 (after winter). However, most evidence of SARS-CoV-2 infection spread 2 To examine clustering of seropositive cases within in schools currently comes from anecdotal reports and case classes, schools and districts, and temporal evolution of studies (National Centre for Immunisation Research and the clusters. Surveillance (NCIRS) 2020; Fontanet et al. 2020). 3 To determine the proportion of asymptomatic children Many schools were or are still closed worldwide in and adolescents with SARS-CoV-2 antibodies. response to the pandemic, without solid arguments for or 4 To determine the duration of the acquired immunity by sufficient understanding of potential consequences of examining new infections in children with positive school closure policies (Masonbrink and Hurley 2020; serology and temporal persistence of detectable SARS- Silverman et al. 2020). 1.6 billion learners worldwide (90% CoV-2 antibodies. of all) were affected by school closure (UNESCO 2020). In 5 To identify sociodemographic, exposure, hygiene, the USA, school closures were coordinated on state and school- and family-based behavioral and environmen- district level, with all USA public schools eventually tal risk factors for SARS-CoV-2 infection; closing from March 25, 2020 (Education Week 2020). In 6 To assess how school-children and their families adjust Switzerland, schools were closed from March 16 to May their lives and adopt preventive measures for SARS- 10, 2020 (switching from regular in-person interaction to CoV-2 over extended periods of time. home and online schooling), then partly reopened until 7 To assess how quality of life is affected by the June 7 (e.g., teaching in half-classes, restricting larger epidemic and preventive measures imposed or recom- group activities), when regular teaching resumed again mended by health authorities. (Swiss National COVID-19 Science Task Force 2020). 8 To assess how schools adopt preventive measures for There is an urgent need for representative, population- SARS-CoV-2 infection over extended periods of time, based studies on children and adolescents, especially in and how they influence the infection rate; school settings, to answer questions about prevalence, 9 To assess seroprevalence, clustering, and possible infection routes, asymptomatic cases, risk factors, and routes of transmission to and from children, school duration of immunity to SARS-CoV-2 infection. This personnel, and parents. article reports on the design and protocol of a longitudinal school-based seroprevalence study conducted in Zurich, Study design the largest canton of Switzerland. The study is part of a larger nationally coordinated research network Corona This is a longitudinal, population-based observational study Immunitas, and one of the first and largest representative in a regionally representative cohort of children and ado- studies of SARS-CoV-2 spread in children and adolescents lescents from randomly selected schools and classes in the in schools, globally. canton of Zurich, Switzerland. The study is embedded in a Swiss-wide research program Corona Immunitas (www. Methods corona-immunitas.ch), where another 25’000 persons (mostly adults) will be enrolled in over 20 prospective studies with fully aligned study protocols (West et al. 2020). Study overview, design and population Children participants were enrolled from June 16 to July 9, 2020, whereas parents and school personnel are enrolled Study objectives from August 20 to September 5. The follow-up of the en- rolled classes of children, their parents, and school per- The study focuses on the seroprevalence and potential sonnel is planned until April 2021. clustering of SARS-CoV-2 infection in children and ado- The longitudinal design allows for monitoring the evo- lescents attending school, as well as history, symptoms, lution of the epidemic, as well as the impact of school- and risk factors for SARS-CoV-2, health, lifestyle, and based and other preventive measures. We pre-defined three quality of life outcomes. It aims to address the following phases, with the possibility for adaptation (i.e., adding objectives: Phase IV) according to the dynamic of the pandemic: 123 Seroprevalence and immunity of SARS-CoV-2 infection in children and adolescents in schools… • Phase I (June to September 2020): Baseline estimate of Ethical aspects seroprevalence of SARS-Cov-2 in school-children, parents, and school personnel shortly after the lock- The study was approved by the Cantonal Ethics Committee down and subsequent reopening of schools. Zurich (2020-01336). Written informed consent is obtained • Phase II (October/November 2020): Estimate of sero- from parents or legal guardians (referred to as parents prevalence in the same cohort of children after the further on) of participating children. Children aged summer holiday and 3 months of school. 14 years and older can confirm the consent themselves. • Phase III (March/April 2021): Estimate of seropreva- Additional informed