Pre-pandemic cross-reactive T-cell responses are associated with subsequent protection against SARS-CoV-2 infection, but not against symptomatic illness 2345

Abstract Description There was a relatively low burden of COVID-19 disease in sub-Saharan Africa (SSA) during the first pandemic wave. We hypothesized that pre-existing immune responses to SARS-CoV-2 induced by prior seasonal coronavirus infections would protect against infection and/or symptomatic disease. Female Sex Workers (FSWs) from Nairobi, Kenya had blood collected mid-2019 (pre-pandemic) and approximately 1 year later. SARS-CoV-2 infection was defined by the presence of antibodies against ≥2/3 SARS-CoV-2 antigens. ELISPOT was used to define pre-pandemic T-cell responses against comprehensive peptide pools covering SARS-CoV-2 structural proteins and defined non-structural epitopes. Pre-pandemic serology for the 4 seasonal coronaviruses was also performed using a multiplex immunoassay. We matched 100 cases who were infected during the first wave with 100 controls, based on age (±5 years) and sample date (±2 weeks). Our primary endpoints and analysis approach were predefined, and all assays were run blind. We found that both the presence and frequency of pre-pandemic IFNy-secreting T-cell responses against structural (but not non-structural) proteins were associated with significant protection against SARS-CoV-2 infection, but not with reduced symptoms among cases. IgG antibodies recognizing seasonal coronaviruses were ubiquitous. These results suggest that cross-reactive cellular responses induced by prior seasonal coronavirus infections may protect against SARS-CoV-2 infection Funding Sources CIHR MMI-174919 Topic Categories Viral Immunology (VIR)