RECAST: Study Protocol for an Observational Study for the Understanding of the Increased REsilience of Children Compared to Adults in SARS-CoV-2 Infection.

Introduction The SARS-CoV-2 pandemic remains a threat to public health. Soon after its outbreak, it became apparent that children are less severely affected. Indeed, opposing clinical manifestations between children and adults are observed for other infections. The SARS-CoV-2 outbreak provides the unique opportunity to study the underlying mechanisms. This protocol describes the methods of an observational study that aims to characterise age dependent differences in immune responses to primary respiratory infections using SARS-CoV-2 as a model virus and to assess age differences in clinical outcomes including lung function. Methods and analysis The study aims to recruit at least 120 children and 60 adults that are infected with SARS-CoV-2 and collect specimen for a multiomics analysis, including single cell RNA sequencing of nasal epithelial cells and peripheral blood mononuclear cells, mass cytometry of whole blood samples and nasal cells, mass spectrometry-based serum and plasma proteomics, nasal epithelial cultures with functional in vitro analyses, SARS-CoV-2 antibody testing, sequencing of the viral genome and lung function testing. Data obtained from this multiomics approach are correlated with medical history and clinical data. Recruitment started in October 2020 and is ongoing. Ethics and dissemination The study was reviewed and approved by the Ethics Committee of Charite - Universitatsmedizin Berlin (EA2/066/20). All collected specimens are stored in the central biobank of Charite - Universitatsmedizin Berlin and are made available to all participating researchers and on request.