tetano
Editor, Senior Moderator
Front Immunol
. 2026 Apr 7:17:1733695.
doi: 10.3389/fimmu.2026.1733695. eCollection 2026.
Cytokine-driven modulation of peripheral immune cell populations in Coronavirus disease 2019 patients
Tanaka Arthur Choto[SUP] 1 [/SUP], Bongiwe Ndlovu[SUP] 2 [/SUP], Thajasvarie Naicker[SUP] 1 [/SUP], Takafira Mduluza[SUP] 1 3 [/SUP]
Affiliations
Introduction: 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.
Methods: In this study, we investigated associations between tumour necrosis factor-α (TNF-α), interferon-γ (IFN-γ), 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.
Results: Compared with controls, COVID-19 patients exhibited marked CD4[SUP]+[/SUP] lymphopenia and leucocytosis driven by neutrophilia and elevated immature granulocytes. Significantly higher expression of IFN-γ (p = 0.0153), IL-6 (p < 0.0001), IL-10 (p < 0.0001), IL-17A (p = 0.0310), and TNF-α (p = 0.0034) was observed in COVID-19 patients compared to uninfected participants. Cytokine-based stratification revealed that CRP was negatively associated with TNF-α (p = 0.0289) and positively associated with IL-10 (p = 0.0046) expression. Furthermore, TNF-α positivity correlated with altered distributions of eosinophils (p = 0.0217), monocytes (p = 0.0063), CD45[SUP]+[/SUP] lymphocytes (p = 0.0252), and CD19[SUP]+[/SUP] B cells (p = 0.0152). While, IFN-γ and IL-17A expression was linked to neutrophilia (p = 0.0439 and p = 0.0075 respectively). IL-10 positivity was associated with elevated immature granulocytes (p < 0.0001), CD16[SUP]+[/SUP]CD56[SUP]+[/SUP] natural killer cells (p = 0.0116), and neutrophils (p = 0.0227). Following Benjamini-Hochberg correction for multiple comparisons, immature granulocytes remained the only immune cell subset with a significant distribution difference across IL-10-defined groups (q = 0.001). A Spearman's 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 (r[SUB]s[/SUB] = 0.4071, p = 0.0169) and IL-6 and platelet count showed a moderately negative connection (r[SUB]s[/SUB] = -0.3770, p = 0.0234), these correlations were no longer significant following Benjamini-Hochberg correction for multiple comparisons.
Conclusions: 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.
Keywords: COVID-19; COVID-19 hospitalised patients; IFN-γ; IL-10; IL-17A; SARS-CoV-2; leucocyte; lymphocyte.
. 2026 Apr 7:17:1733695.
doi: 10.3389/fimmu.2026.1733695. eCollection 2026.
Cytokine-driven modulation of peripheral immune cell populations in Coronavirus disease 2019 patients
Tanaka Arthur Choto[SUP] 1 [/SUP], Bongiwe Ndlovu[SUP] 2 [/SUP], Thajasvarie Naicker[SUP] 1 [/SUP], Takafira Mduluza[SUP] 1 3 [/SUP]
Affiliations
- PMID: 42023234
- PMCID: PMC13096067
- DOI: 10.3389/fimmu.2026.1733695
Introduction: 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.
Methods: In this study, we investigated associations between tumour necrosis factor-α (TNF-α), interferon-γ (IFN-γ), 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.
Results: Compared with controls, COVID-19 patients exhibited marked CD4[SUP]+[/SUP] lymphopenia and leucocytosis driven by neutrophilia and elevated immature granulocytes. Significantly higher expression of IFN-γ (p = 0.0153), IL-6 (p < 0.0001), IL-10 (p < 0.0001), IL-17A (p = 0.0310), and TNF-α (p = 0.0034) was observed in COVID-19 patients compared to uninfected participants. Cytokine-based stratification revealed that CRP was negatively associated with TNF-α (p = 0.0289) and positively associated with IL-10 (p = 0.0046) expression. Furthermore, TNF-α positivity correlated with altered distributions of eosinophils (p = 0.0217), monocytes (p = 0.0063), CD45[SUP]+[/SUP] lymphocytes (p = 0.0252), and CD19[SUP]+[/SUP] B cells (p = 0.0152). While, IFN-γ and IL-17A expression was linked to neutrophilia (p = 0.0439 and p = 0.0075 respectively). IL-10 positivity was associated with elevated immature granulocytes (p < 0.0001), CD16[SUP]+[/SUP]CD56[SUP]+[/SUP] natural killer cells (p = 0.0116), and neutrophils (p = 0.0227). Following Benjamini-Hochberg correction for multiple comparisons, immature granulocytes remained the only immune cell subset with a significant distribution difference across IL-10-defined groups (q = 0.001). A Spearman's 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 (r[SUB]s[/SUB] = 0.4071, p = 0.0169) and IL-6 and platelet count showed a moderately negative connection (r[SUB]s[/SUB] = -0.3770, p = 0.0234), these correlations were no longer significant following Benjamini-Hochberg correction for multiple comparisons.
Conclusions: 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.
Keywords: COVID-19; COVID-19 hospitalised patients; IFN-γ; IL-10; IL-17A; SARS-CoV-2; leucocyte; lymphocyte.