Identification of Serum Antibodies Cross-Reactive with Pathogenic Betacoronavirus Amongst Rural Communities Within the Forested Region of the Republic of Guinea

Objectives: The SARS-CoV-2 pandemic caused major morbidity, mortality, and economic disruption, highlighting the need to better understand zoonotic spillover risks posed by coronaviruses. We investigated whether archived human sera from forested Guinea contained evidence of prior exposure to coronaviruses antigenically related to known pathogenic human coronaviruses. Methods: Archived sera collected in 2017–2018 from wildlife hunter communities in Guinea were analysed using serological assays against spike glycoproteins from SARS-CoV, SARS-CoV-2, MERS-CoV, and seasonal human coronaviruses. Binding responses to receptor binding domains were also assessed, together with spatial and subgroup analyses. Results: Pre-pandemic sera showed IgG cross-reactivity to SARS-CoV, SARS-CoV-2, and MERS-CoV spike antigens. A distinct subgroup demonstrated strong binding to both SARS-CoV and MERS-CoV receptor binding domains. Conclusions: These findings highlight the utility of sero-epidemiology in identifying potential zoonotic spillover. However, further investigation is needed to identify these viruses and determine their homology to known pathogenic coronaviruses.