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

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+ 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 (rs  = 0.4071, p = 0.0169) and IL-6 and platelet count showed a moderately negative connection (rs = -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.