Household Respiratory Virus SARS-CoV-2 Transmission and Immunity Sub-Study (HRTS)

The pandemic created by the novel human coronavirus SARS-CoV-2 has generated manyunanswered questions on the best practices for prevention and treatment for those with COVID-19 disease. The mechanism behind the lack of apparent disease susceptibility in children is alsounresolved. To answer these most critical questions, we require data on how the host immunesystem responds to SARS-CoV-2 infection and COVID-19 disease. Longitudinal cohortsestablished in naive populations are necessary for careful profiling of immune responses,disease severity, and the generation of protective memory. Disease presentation and outcomehas been highly variable among age groups and those with various underlying conditions,complicating study design. Large well-characterized human cohorts are costly to initiate anddifficult to develop quickly. In this study, we propose to use the DIVINCI Consortium cohorts,three geographically distinct human birth cohorts, which are already established andsuccessfully running to be able to immediately begin sampling individuals with suspected orconfirmed SARS-CoV-2 infection. Importantly, all three cohorts have the ability to collecthousehold samples, providing insights into immunity and disease progression across a broadage range. We propose to collect respiratory samples, breast milk, stool/rectal swab, andserum/PBMC samples, and from those samples, exhaustively assay the host immune responseto SARS-CoV-2. Based on the study design, we will be able to compare naive time points tothose during active infection as well as samples from individuals who remained asymptomaticcompared to those who develop varying degrees of symptoms. Our study proposes tocomprehensively measure immune cell populations in the peripheral blood in naive (baseline)samples and convalescent samples (after infection.) We propose to develop novel reagents formeasuring SARS-CoV-2-specific T and B cells. Further, we propose to measure SARS-CoV-2viral diversity and evolution. Finally, we will be able to extensively assay serological samples todetermine measurable differences in the response between individuals with mild and severeinfection and asymptomatic and symptomatic infection, and track their subsequent susceptibilityto re-infection. The DIVINCI consortium is uniquely situated to have immediate response to theSARS-CoV-2 pandemic with the ultimate goal of a more complete understanding of the virusand the disease.