# 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

## TL;DR

Kenyan adults showed stronger pre-COVID-19 immune responses to SARS-CoV-2 spike peptides compared to Swedes, possibly explaining lower disease severity in Africa.

## Contribution

The study identifies a higher prevalence of pre-existing cross-reactive T-cell responses to SARS-CoV-2 in Kenyan adults compared to Swedes.

## Key findings

- 55.7% of Kenyan pre-COVID-19 adults showed ELISpot responses to SARS-CoV-2 spike peptides versus 28% in Sweden.
- Kenyan adults had higher frequencies of SARS-CoV-2 spike-specific T-cell responses, though not statistically significant.
- Pre-COVID-19 T-cell responses may explain lower morbidity and mortality in Sub-Saharan Africa.

## Abstract

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.

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.

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.

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.

The online version contains supplementary material available at 10.1186/s12879-026-12582-6.