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

Abstract

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.

Keywords: IgG Seroprevalence; Neutralizing antibodies; Pre-pandemic immunity; SARS-CoV-2.

Figure 1:

Anti–SARS-CoV-2 IgG prevalence in pre-pandemic and pandemic periods. A) shows the seroprevalence of SARS-CoV-2 according to malaria status in Thies (samples collected in 2018). B) represents the Anti–SARS-CoV-2 IgG prevalence in Thies and Kedougou by year. C) IgG seroprevalence by age group and gender between pre-pandemic (2017-2019, blue) and D) by (2020–2022, orange) periods. All figures display error bars of 95% confidence interval and the Fisher's exact test p-value.

Figure 2:

SARS-CoV-2 sVNT inhibition percentage by group and period. Each dot represents an individual tested sample. The horizontal dashed red line marks the cutoff at 30% inhibition. Boxplots show the distribution of inhibition values within each group, with overlayed points representing individual samples. Groups include pre-pandemic localities (USA, Kedougou IgG+, Thies IgG+), pandemic samples stratified as Senegal IgG+, and ELISA-negative controls (Senegal IgG−).