Mucosal and systemic immune correlates of viral control after SARS-CoV-2 infection challenge in seronegative adults

The COVID-19 pandemic has provided unprecedented immunological insight into how humans fight respiratory virus infections, but the earliest stages of SARS-CoV-2 infection remain poorly characterized. Wagstaffe et al. conducted a human SARS-CoV-2 infection challenge study, enabling analysis of the innate and adaptive immune responses during the early postexposure period. Of 34 seronegative young adults inoculated, 18 developed sustained infections, which were accompanied by a systemic interferon-dominated inflammatory response preceding that in nasal lining fluid. Modeling of the immune response identified CD8+ T cell and early mucosal IgA responses as strongly associated with viral control, suggesting that vaccines that optimally induce these responses may help reduce transmission. —Claire Olingy