Namuniina, AnnemarieMuyanja, Enoch S.Biribawa, Victoria M.Ssemaganda, AloysiousNanteza, AnnBagaya, Bernard SsentaloGalwango, Ronald M.Redd, Andrew D.2023-03-062023-03-062023Namuniina, A., Muyanja, E. S., Biribawa, V. M., Okech, B. A., Ssemaganda, A., Price, M. A., ... & Redd, A. D. (2023). High proportion of Ugandans with pre-pandemic SARS-CoV-2 cross-reactive CD4+ and CD8+ T-cell responses. medRxiv, 2023-01.https://doi.org/10.1101/2023.01.16.23284626https://nru.uncst.go.ug/handle/123456789/8087The estimated mortality rate of the SARS-CoV-2 pandemic varied greatly around the world with multiple countries in East, Central, and West Africa having significantly lower rates of COVID-19 related fatalities than many resource-rich nations with significantly earlier wide-spread access to life-saving vaccines. One possible reason for this lower mortality could be the presence of pre-existing cross-reactive immunological responses in these areas of the world. To explore this hypothesis, stored peripheral blood mononuclear cells (PBMC) from Ugandans collected from 2015-2017 prior to the COVID-19 pandemic (n=29) and from hospitalized Ugandan COVID-19 patients (n=3) were examined using flow-cytometry for the presence of pre-existing SARS-CoV-2 cross-reactive CD4+ and CD8+ T-cell populations using four T-cell epitope mega pools. Of pre-pandemic participants, 89.7% (26/29) had either CD4+ or CD8+, or both, SARS-CoV-2 specific T-cell responses. Specifically, CD4+ T-cell reactivity (72.4%) and CD8+ T-cell reactivity (65.5%) were relatively similar, and 13 participants (44.8%) had both types of cross-reactive types of T-cells present. There were no significant differences in response by sex in the population. The rates of cross-reactive T-cell populations in these Ugandans is higher than previous estimates from resource-rich countries like the United States (20-50% reactivity). It is unclear what role, if any, this cross-reactivity played in decreasing COVID-19 related mortality in Uganda and other African countries, but does suggest that a better understanding of global pre-existing immunological cross-reactivity could be an informative data of epidemiological intelligence moving forward.enPre-pandemicSARS-CoV-2CD4+ and CD8+ T-cell responsesArticle