Systemic and mucosal immune signatures of protection against SARS-CoV-2 transmission in humans.

Binding and neutralizing antibodies against the spike (S) protein of SARS-CoV-2 have been associated with a reduced risk of symptomatic infection. However, precise immune protection thresholds remain unclear. We aim to define systemic and mucosal antibody correlates of protection against SARS-CoV-2 infection. Our household COVID-19 cohort (the CIDS) consists of 52 families (52 index cases and 139 exposed contacts). Immunoglobulin subtyping against S of SARS-CoV-2 and HCoV-OC43 in the serum and upper respiratory tract is quantified to assess the protection provided by virus-specific pre-existing immunity. Logistic regression analyses indicate that multiple antibody isotypes are associated with reduced infection risk. Specifically, multivariable models show that systemic anti-SARS-CoV-2 S1 IgG and anti-OC43 S2 IgM independently correlate with protection. Besides, local mucosal anti-SARS-CoV-2 S IgG and HCoV-OC43 S IgA antibodies add protective potential. However, an integrated analysis reveals that systemic antibodies against SARS-CoV-2 remain the best predictor against virus infection.