Persistent humoral immunity in children and adolescents throughout the COVID-19 pandemic (June 2020 to July 2022): a prospective school-based cohort study (Ciao Corona) in Switzerland

Objectives: To assess the longitudinal development of humoral immunity in children and adolescents during the COVID-19 pandemic, with a particular focus on how anti-spike IgG antibodies and neutralising response changed during the first Omicron peak (December 2021 to May 2022). Design: Prospective school-based study during the COVID-19 pandemic (June 2020 to July 2022) including five testing rounds with corresponding cross-sectional cohorts and a longitudinal cohort who participated in at least four rounds. Setting: 55 randomly selected schools in the Canton of Zurich, Switzerland. Participants: Between 1875 to 2500 children and adolescents per testing round and 751 in the longitudinal cohort. Main outcome measures: Development of SARS-CoV-2 seroprevalence, anti-spike IgG antibodies and neutralising antibody response over time, persistence of antibodies and variation of antibody levels in individuals only infected, vaccinated or with hybrid immunity during the early Omicron period. Results: By July 2022 96.9% (95% credible interval [CrI] 95.2 to 98.1%) of children and adolescents had anti-spike IgG antibodies against SARS-CoV-2. The substantial increase in seroprevalence during the first peak of the Omicron wave was largely driven by primary infections in mostly unvaccinated children under the age of 12 (28.4% [95% CrI 24.2 to 33.2%] in December 2021, to 95.7% [95% CrI 93.4 to 97.4%] in July 2022). This stands in contrast to adolescents aged 12 years and older (69.4% [95% CrI 64.0 to 75.4%] in December 2021 to 98.4% [95% CrI 97.3 to 99.2%] in July 2022), who were eligible for vaccination since June 2021. Children and adolescents with hybrid immunity or immunity from vaccination had high anti-spike IgG titres (median Mean Fluorescence Intensity (MFI) ratio of 136.2 [Inter Quartile Range [IQR]: 121.9 to 154.3] and 127.6 [IQR: 114.1 to 151.0]) and strong neutralising responses (e.g., anti-Omicron 98.9% [95% Confidence Interval [CI] 96.0 to 99.7%] and 81.6% [95% CI 74.9 to 86.9%]). Meanwhile, infected but unvaccinated children and adolescents had substantially lower anti-spike IgG titres (median MFI ratio of 54.8 [IQR: 22.8 to 89.8]) and neutralising responses (e.g., anti-Omicron 64.9% [95% CI 59.8 to 69.7%]). Conclusion: These findings show that the Omicron wave and the rollout of vaccines led to almost 100% seropositivity and boosted anti-spike IgG titres and neutralising capacity in children and adolescents. This was particularly driven by unvaccinated children (<12 years), who became seropositive due to the highly infectious Omicron variant. Nevertheless, during the entire study parents of only one adolescent reported hospital stay of less than 24 hours related to a possible acute infection. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The Ciao Corona study was embedded in the nationally coordinated research network Corona Immunitas, coordinated by the Swiss School of Public Health (SSPH+). The Ciao Corona study was funded by fundraising of SSPH+, which included funds of the Swiss Federal Office of Public Health as well as private funders (the SSPH+ ethical guidelines for funding will be considered), by the Cantons of Switzerland (Vaud, Zurich, and Basel), by institutional funds of the Universities. Additionally, the University of Zurich Foundation provided funding specific to this study. The funder played no part in neither the planning and implementation of the study; nor the collection, management, analysis, and interpretation of the data; nor the writing, reviewing, and approving of the manuscript; nor the choice to submit the manuscript for publication. All authors were able to fully access the output of the data analysis and take responsibility for integrity and accuracy. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Ethics Committee of the Canton Zurich, Switzerland, approved the study (2020-01336). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.