Abstract

Induction of an early IFN-gamma cellular response and high plasma levels of SDF-1alpha are inversely associated with COVID-19 severity and residence in rural areas in Kenyan patients

Wanjiku, P. Orindi, B. Kimotho, J. Sayed, S. Shah, R. Saleh, M. Mwacharo, J. Maronga, C. Olouch, V. Karanu, A. Shah, J. Nneka, Z. Ochola-Oyier, L. I. Abdi, A. I. Dunachie, S. Bejon, P. Nduati, E. W. Ndungu, F. M.
PLoS One. 2025; 20e0316967

Permanent descriptor

https://doi.org/10.1371/journal.pone.0316967

INTRODUCTION: COVID-19 was less severe in Sub-Saharan Africa (SSA) compared with Europe and North America. It is unclear whether these differences could be explained immunologically. Here we determined levels of ex vivo SARS-CoV-2 peptide-specific IFN-gamma producing cells, and plasma cytokines and chemokines over the first month of COVID-19 diagnosis among Kenyan COVID-19 patients from urban and rural areas. METHODS: Between June 2020 and August 2022, we recruited and longitudinally monitored 188 COVID-19 patients from two regions in Kenya, Nairobi (urban, n = 152) and Kilifi (rural, n = 36), with varying disease severity - severe, mild/moderate, and asymptomatic. IFN-gamma secreting cells were enumerated at 0-, 7-, 14- and 28-days post diagnosis by an ex vivo enzyme-linked immunospot (ELISpot) assay following in vitro stimulation of peripheral blood mononuclear cells (PBMCs) with overlapping peptides from several SARS-CoV-2 proteins. A multiplexed binding assay was used to measure levels of 22 plasma cytokines and chemokines. RESULTS: Higher frequencies of IFN-gamma-secreting cells against SARS-CoV-2 spike peptides were observed on the day of diagnosis among asymptomatic compared to patients with severe COVID-19. Higher concentrations of 17 of the 22 cytokines and chemokines measured were positively associated with severe disease, particularly interleukin (IL)-8, IL-18 and IL-1ra (p < 0.0001), while a lower concentration of SDF-1alpha was associated with severe disease (p < 0.0001). Concentrations of 8 and 16 cytokines and chemokines including IL-18 were higher among Nairobi asymptomatic and mild patients compared to their respective Kilifi counterparts. Conversely, concentrations for SDF-1alpha were higher in rural Kilifi compared to Nairobi (p = 0.012). CONCLUSION: In Kenya, as seen elsewhere, pro-inflammatory cytokines and chemokines were associated with severe COVID-19, while an early IFN-gamma cellular response to overlapping SARS-CoV-2 spike peptides was associated with reduced risk of disease. Living in urban Nairobi (compared with rural Kilifi) was associated with increased levels of pro-inflammatory cytokines and chemokines.