Compartmentalised mucosal and blood immunity to SARS-CoV-2 is associated with high seroprevalence before the Delta wave in Africa.

BACKGROUND: The reported number of SARS-CoV-2 cases and deaths are lower in Africa compared to many high-income countries. However, in African cohorts, detailed characterisation of SARS-CoV-2 mucosal and T cell immunity are limited. We assessed the SARS-CoV-2-specific immune landscape in The Gambia during the presence of the pre-Delta variant in July 2021. METHODS: A cross-sectional assessment of SARS-CoV-2 immunity in 349 unvaccinated individuals from 52 Gambian households was performed between March-June 2021. SARS-CoV-2 spike (S) and nucleocapsid (N) specific binding antibodies were measured by ELISA, variant-specific serum neutralizing-antibodies (NAb) by viral pseudotype assays and nasal fluid IgA by mesoscale discovery assay. SARS-CoV-2 T-cell responses were evaluated using ELISpot assay. RESULTS: We show that adjusted anti-Spike antibody seroprevalence is 56.7% (95% confidence interval (CI) 49.0-64.0), with lower rates in children <5 years (26.2%, 13.9-43.8) and 5-17 years (46.4%, 36.2-56.7) compared to adults 18-49 years (78.4%, 68.8-85.8). Among spike-seropositive individuals, NAb titres are highest against Alpha variant (median IC50 110), with 27% showing pre-existing Delta variant titres >1:50. T-cell responses are higher in spike-seropositive individuals, although 34% of spike-seronegative individuals show responses to at least one antigen pool. We observe strong correlations within SARS-CoV-2 T-cell, mucosal IgA, and serum NAb responses. CONCLUSIONS: High SARS-CoV-2 seroprevalence in The-Gambia induce mucosal and blood immunity, reducing Delta and Omicron impact. Children are relatively protected from infection. T-cell responses in seronegative individuals may indicate either pre-pandemic cross-reactivity or individuals with a T-cell dominated response to SARS-CoV-2 infection with absent or poor humoral responses.