SARS-CoV-2 Serosurveillance Reveals Pre-pandemic Cross-Reactivity and Pandemic Seroprevalence Trends in Senegal

The relatively mild impact of COVID-19 in sub-Saharan Africa has raised questions about the role of pre-existing immunity in the region. One hypothesis for this unexpected observation is the presence of pre-existing cross-protective immunity, potentially induced by prior exposure to seasonal and zoonotic coronaviruses. However, the prevalence and functional relevance of such antibodies in the Senegalese population are not fully known. To investigate this, we conducted a cross-sectional seroprevalence study using 822 plasma samples collected in Senegal before (2017-2019) and during (2020-2022) the pandemic, across regions of high (Kédougou) and low (Thiès) malaria endemicity. Samples were screened for anti-SARS-CoV-2 spike 1 IgG using enzyme-linked immunosorbent assay (ELISA), and a subset of the pre-pandemic IgG-positive samples was further tested for neutralizing activity using a surrogate virus neutralization test (sVNT). Pre-pandemic SARS-CoV-2 IgG positivity was 39.1% [34.6 - 43.7]. No significant differences were observed in terms of age, sex, region, or malaria status. However, only 5.1% of pre-pandemic IgG-positive samples showed neutralizing activity, with 1.3% [0.1 - 6.7] in Kédougou and 9.2% [4.5 - 17.8] in Thiès. During the pandemic, IgG seroprevalence increased from the baseline around 40% in 2020 (37.3 % [27.7 - 48.1] in Kedougou and 50%[29.03 - 70.9%] in Thies), peaking near 99% of the study population by 2022 with 98.2% [93.8 - 99.5] in Kedougou and 98.8% [93.6 - 99.7] in Thies. These results indicate widespread pre-pandemic cross-reactivity to SARS-CoV-2 in Senegal, likely driven by exposure to related coronaviruses. However, their poor neutralizing activity implies limited cross-protection. These findings highlight the need for further investigation into the origins, nature, and immunological significance of these cross-reactive antibody responses.