Wanjiku Perpetual, Orindi Benedict, Kimotho John, Sayed Shahin, Shah Reena, Saleh Mansoor, Mwacharo Jedidah, Maronga Christopher, Olouch Viviane, Karanu Ann, Shah Jasmit, Nneka Zaitun, Ochola-Oyier Lynette Isabella, Abdi Abdirahman I, Dunachie Susanna, Bejon Philip, Nduati Eunice W, Ndungu Francis M
Centre for Geographic Medicine Research (Coast), Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme, Kilifi, Kenya.
Aga Khan University Hospital, Nairobi, Kenya.
PLoS One. 2025 Sep 11;20(9):e0316967. doi: 10.1371/journal.pone.0316967. eCollection 2025.
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-γ 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.
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-γ 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.
Higher frequencies of IFN-γ-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-1α 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-1α were higher in rural Kilifi compared to Nairobi (p = 0.012).
In Kenya, as seen elsewhere, pro-inflammatory cytokines and chemokines were associated with severe COVID-19, while an early IFN-γ 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.
与欧洲和北美相比，撒哈拉以南非洲地区（SSA）的新冠病毒疾病（COVID-19）症状较轻。目前尚不清楚这些差异是否可以从免疫学角度进行解释。在此，我们测定了肯尼亚城乡地区COVID-19患者在确诊后的第一个月内，体外SARS-CoV-2肽特异性产生γ干扰素的细胞水平，以及血浆细胞因子和趋化因子水平。
在2020年6月至2022年8月期间，我们招募并纵向监测了来自肯尼亚两个地区的188例COVID-19患者，内罗毕（城市，n = 152）和基利菲（农村，n = 36），疾病严重程度各不相同——重症、轻/中度和无症状。在诊断后的0、7、14和28天，通过体外酶联免疫斑点（ELISpot）试验，在用几种SARS-CoV-2蛋白的重叠肽体外刺激外周血单个核细胞（PBMC）后，计数分泌γ干扰素的细胞。采用多重结合试验来测量22种血浆细胞因子和趋化因子的水平。
与重症COVID-19患者相比，无症状患者在诊断当天观察到针对SARS-CoV-2刺突肽的分泌γ干扰素细胞的频率更高。所测量的22种细胞因子和趋化因子中有17种的较高浓度与重症疾病呈正相关，特别是白细胞介素（IL）-8、IL-18和IL-1ra（p < 0.0001），而较低浓度的基质细胞衍生因子-1α（SDF-1α）与重症疾病相关（p < 0.0001）。在内罗毕无症状和轻症患者中，包括IL-18在内的8种和16种细胞因子和趋化因子的浓度高于基利菲相应患者。相反，基利菲农村地区的SDF-1α浓度高于内罗毕（p = 0.012）。
在肯尼亚，与其他地方一样，促炎细胞因子和趋化因子与重症COVID-19相关，而对重叠的SARS-CoV-2刺突肽的早期γ干扰素细胞反应与疾病风险降低相关。生活在内罗毕市区（与基利菲农村地区相比）与促炎细胞因子和趋化因子水平升高相关。
