Antibody signatures of COVID-19 protection 3824

Description We present a household human cohort study of COVID-19 designed to understand the relative contribution of host factors that can drive transmission, and the level of immunity required to prevent infection. We enrolled 52 families: 52(26%) index cases and 139(74%) exposed individuals. Serum and nasal swabs (NPS) were collected for 1 month follow-up. Immunoglobulin subtyping (IgG, IgM, IgA, sIgA) against full-length or S1/S2 domains of the S protein of SARS-CoV-2 and OC43 was performed. Ninety-nine (71%) of the exposed susceptible contacts were infected during the follow up. Serum anti-S2 antibodies were high at baseline for both SARS-CoV-2 and OC43 for all immunoglobulin subtypes. However, SARS-CoV-2 S1 domain showed immunodominance over S2. Besides, a robust response for IgA and sIgA was detected in the upper respiratory tract against SARS-CoV-2 S. Additionally, anti-OC43 antibody levels were also detected in the mucosal compartment. Interestingly, baseline antibody levels against SARS-CoV-2 S were higher in those subjects that did not become infected. A binomial logistic regression of log10 immunoglobulin values showed that the probability of disease occurrence decreased with increased antibody titers. However, a logistic regression model adjusted by all potential serocorrelates demonstrated that only anti-S1 correlated with protection from SARS-CoV-2 transmission. Our predictive model indicated that a threshold of protective immunity based on anti-S1 IgG could be feasible. Funding Sources This work is partly funded by CRIPT (Center for Research on Influenza Pathogenesis and Transmission) and NIAID-funded Center of Excellence for Influenza Research and Response (CEIRR, contract # 75N93021C00014) to A.G.-S and T.A. T.A. was also funded by the American Lung Association: ALA grant # COVID-1034091.