Pre-COVID-19 ex vivo cross-reactive IFN-γ cellular response to SARS-CoV-2 spike overlapping peptides is more prevalent among Kenyan compared to Swedish adults.

BACKGROUND: Global WHO data indicate that Sub-Saharan African (SSA) countries, such as Kenya, experienced reduced coronavirus disease 2019 (COVID-19) severe-morbidity and mortality burdens relative to their more affluent counterparts in Europe, Asia, and North America. METHODS: We analysed peripheral blood mononuclear cells (PBMC) samples collected from Kenya and Sweden before and during COVID-19. Pre-COVID-19 samples were available for 80 adults and 10 infants from Kenya, and 20 adults from Sweden. COVID-19 samples were available for 39 Kenyan adults. The samples were analysed for ex vivo IFN-γ secretion using an Enzyme-Linked Immunosorbent (ELISpot) assay following in vitro stimulations with overlapping SARS-CoV-2 spike-protein peptides. T-cells expressing IFN-γ, IL-2, TNF-α, CD154, and CD107a were assessed following similar stimulations, using intracellular cytokine staining (ICS) and multiparameter flow cytometry. RESULTS: 55.7% of the Kenyan pre-COVID-19 adult samples were classified as responders by ELISPOT responses to spike-protein peptides, compared with 28% of Swedish pre-COVID-19 adult sample (p = 0.04). The frequencies for SARS-CoV-2 spike-specific TNF-α CD4+, TNF-α CD8 + and IFN-γ CD8 + T-cell responses, tended to be higher in the Kenyan adults although these differences did not reach statistical significance. CONCLUSION: Pre-COVID-19 T-cell responses could contribute to lower morbidity and mortality associated with SARS-CoV-2 infections in SSA relative to Europe, Asia, and North America. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-026-12582-6.