Abstract
Background: 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. Methods: Plasma collected from Senegalese female sex workers prior to the COVID-19 pandemic was screened for SARS-CoV-2 and human coronavirus (hCoV) antibodies by virion immunoblots. For antibody-reactive plasma, paired peripheral blood mononuclear cells were stimulated by fusion proteins and IFN-γ cellular responses were assessed via ELISPOT. Results: We observed substantial levels of pre-existing cross-reactive immunity to SARS-CoV-2, stemming from prior exposure to seasonal hCoVs. Our antibody analysis revealed a 23.5% (47/200) seroprevalence rate against SARS-CoV-2 nucleocapsid (N). These samples were then probed for antibodies against hCoV spike (S) and/or N antigens; 85.1% (40/47), 70.2% (33/47), and 95.7% (45/47) were antibody reactive against hCoV-229E, hCoV-OC43, or hCoV-HKU1, respectively. Our analysis of cellular responses also demonstrated cross-reactivity to SARS-CoV-2 with 80.0% (36/45) and 82.2% (37/45) showing IFN-γ responses against S and N, respectively. A unique pre-pandemic subject had cross-reactive SARS-CoV-2 S antibodies with detectable neutralization and cross-reactive cellular responses. Conclusion: These findings suggest that prior hCoV exposure may induce cross-reactive adaptive immunity, potentially contributing to protection against COVID-19. Our study provides unique data on the dynamics of hCoV and SARS-CoV-2 immunity in Senegal and underscores the importance of understanding the role of pre-existing immunity in shaping COVID-19 outcomes globally.