{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T07:15:52Z","timestamp":1775546152746,"version":"3.50.1"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"\n Introduction<\/jats:title>\n Coronavirus disease 2019 (COVID-19) is characterized by a spectrum of immune dysfunction, from mild illness to life-threatening hyper-inflammation. However, the specific relationships between individual cytokine expression profiles and peripheral immune cell distributions remain poorly defined, particularly in African populations.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n In this study, we investigated associations between tumour necrosis factor-\u03b1 (TNF-\u03b1), interferon-\u03b3 (IFN-\u03b3), interleukin-10 (IL-10), and interleukin-17A (IL-17A) expression and circulating leucocyte subsets in hospitalised COVID-19 patients. Complete blood counts, C-reactive protein (CRP) levels, and lymphocyte subset profiles were measured, and cytokine concentrations were quantified by cytometric bead array.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Compared with controls, COVID-19 patients exhibited marked CD4\n +<\/jats:sup>\n lymphopenia and leucocytosis driven by neutrophilia and elevated immature granulocytes. Significantly higher expression of IFN-\u03b3 (\n p<\/jats:italic>\n \u00a0=\u00a00.0153), IL-6 (\n p<\/jats:italic>\n \u00a0&lt;\u00a00.0001), IL-10 (\n p<\/jats:italic>\n \u00a0&lt;\u00a00.0001), IL-17A (\n p<\/jats:italic>\n \u00a0=\u00a00.0310), and TNF-\u03b1 (\n p<\/jats:italic>\n \u00a0=\u00a00.0034) was observed in COVID-19 patients compared to uninfected participants. Cytokine-based stratification revealed that CRP was negatively associated with TNF-\u03b1 (\n p<\/jats:italic>\n \u00a0=\u00a00.0289) and positively associated with IL-10 (\n p<\/jats:italic>\n \u00a0=\u00a00.0046) expression. Furthermore, TNF-\u03b1 positivity correlated with altered distributions of eosinophils (\n p<\/jats:italic>\n \u00a0=\u00a00.0217), monocytes (\n p<\/jats:italic>\n \u00a0=\u00a00.0063), CD45\n +<\/jats:sup>\n lymphocytes (\n p<\/jats:italic>\n \u00a0=\u00a00.0252), and CD19\n +<\/jats:sup>\n B cells (\n p<\/jats:italic>\n \u00a0=\u00a00.0152). While, IFN-\u03b3 and IL-17A expression was linked to neutrophilia (\n p<\/jats:italic>\n \u00a0=\u00a00.0439 and\n p<\/jats:italic>\n \u00a0=\u00a00.0075 respectively). IL-10 positivity was associated with elevated immature granulocytes (\n p<\/jats:italic>\n \u00a0&lt;\u00a00.0001), CD16\n +<\/jats:sup>\n CD56\n +<\/jats:sup>\n natural killer cells (\n p<\/jats:italic>\n \u00a0=\u00a00.0116), and neutrophils (\n p<\/jats:italic>\n \u00a0=\u00a00.0227). Following Benjamini\u2013Hochberg correction for multiple comparisons, immature granulocytes remained the only immune cell subset with a significant distribution difference across IL-10\u2013defined groups (\n q<\/jats:italic>\n \u00a0=\u00a00.001). A Spearman\u2019s rank-order correlation analysis was performed to assess the correlation between serum IL-6 levels and peripheral blood leucocyte counts, including platelet counts. Although basophil count showed a moderately positive correlation (\n \n r\n s<\/jats:sub>\n <\/jats:italic>\n \u00a0=\u00a00.4071,\n p<\/jats:italic>\n \u00a0=\u00a00.0169) and IL-6 and platelet count showed a moderately negative connection (\n \n r\n s<\/jats:sub>\n <\/jats:italic>\n = \u22120.3770,\n p<\/jats:italic>\n \u00a0=\u00a00.0234), these correlations were no longer significant following Benjamini\u2013Hochberg correction for multiple comparisons.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n These findings reveal distinct cytokine-associated immunotypes marked by cell-specific shifts suggestive of emergency granulopoiesis and myelopoiesis. Our data provide an immunophenotypic framework for understanding COVID-19 pathogenesis and may inform targeted diagnostics and immunomodulatory strategies.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1733695","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T06:24:55Z","timestamp":1775543095000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cytokine-driven modulation of peripheral immune cell populations in Coronavirus disease 2019 patients"],"prefix":"10.3389","volume":"17","author":[{"given":"Tanaka Arthur","family":"Choto","sequence":"first","affiliation":[{"name":"Optics and Imaging, Doris Duke Medical Research Institute, College of Health Sciences, University of KwaZulu-Natal","place":["Durban, KwaZulu-Natal, South Africa"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bongiwe","family":"Ndlovu","sequence":"additional","affiliation":[{"name":"HIV 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