Cytokine-driven modulation of peripheral immune cell populations in Coronavirus disease 2019 patients

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.

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.

Compared with controls, COVID-19 patients exhibited marked CD4⁺ 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⁺ lymphocytes (p = 0.0252), and CD19⁺ 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⁺CD56⁺ 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_s  = 0.4071, p = 0.0169) and IL-6 and platelet count showed a moderately negative connection (r_s = -0.3770, p = 0.0234), these correlations were no longer significant following Benjamini-Hochberg correction for multiple comparisons.

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.