West African pre-pandemic cross-reactive antibody and cellular responses against SARS-CoV-2

The COVID-19 pandemic had a severe impact globally, yet African populations exhibited unexpectedly lower rates of severe disease and mortality. We investigated the potential role of pre-existing immunity in shaping the epidemiology of COVID-19 in Africa. Leveraging paired plasma and peripheral blood mononuclear cells collected from Senegalese female sex workers prior to the COVID-19 pandemic, we observed substantial levels of pre-existing cross-reactive immunity to SARS-CoV-2, stemming from prior exposure to seasonal human coronaviruses (hCoVs). Our antibody analysis revealed a 23.5% (47/200) seroprevalence rate against SARS-CoV-2 nucleocapsid (N). Of these SARS-CoV-2 N-reactives, 85.1% (40/47), 44.7% (21/47), and 95.7% (45/47) showed antibody reactivity against hCoV-229E or hCoV-OC43 spike (S) and/or N or hCoV-HKU1 S. Our analysis of cellular responses also demonstrated cross-reactivity to SARS-CoV-2 with 82.2% (37/45) and 84.4% (38/45) showing IFN-γ responses against S and N, respectively. These findings suggest that prior hCoV exposure may induce cross-reactive adaptive immunity, potentially contributing to protection against COVID-19. A unique pre-pandemic subject had cross-reactive SARS-CoV-2 S antibodies with detectable neutralization and cellular responses. Our study provides unique insights into the dynamics of hCoV and SARS-CoV-2 immunity in West African populations and underscores the importance of understanding the role of pre-existing immunity in shaping COVID-19 outcomes globally.