Cytokine Signatures and Hematological Alterations as Predictors of Covid-19 Severity and Mortality in a Brazilian Cohort From Central-south Mato Grosso

Hyperinflammation is a key driver of diffuse alveolar damage in COVID-19. This cohort study investigated the association between cytokine dysregulation, hematological parameters, and disease severity in 137 unvaccinated hospitalized COVID-19 patients. The mild group (n = 36) showed decreased IL-6, IP-10, and MCP-1 (p < 0.001) and increased IFN-γ, IL-7 (p < 0.001), IL-2 (p < 0.05), IL-10, IL-12p70, and TNF-α (p < 0.001) compared with the moderate group (n = 36). The severe group (n = 65) had elevated IL-4, IL-6, IL-7, IL-8, TNF-α (p < 0.001), IL-2, IP-10, MCP-1, and GM-CSF (p < 0.001), but reduced IFN-α2 (p < 0.01), IFN-γ (p < 0.05), and IL-7 (p < 0.01) compared to the moderate group. Increased IL-6, IL-8, MCP-1, IL-10, IP-10, and TNF-α correlated with metabolic, respiratory, and cardiovascular comorbidities. Higher IL-6, IL-8, IL-10, IP-10, MCP-1, TNF-α (p < 0.01), and IL-7 (p < 0.02) levels were associated with mortality (64.2%). Negative correlations were observed between erythrocyte count, hemoglobin, and TNF-α, IL-6, IFN-α2 (p < 0.05); hematocrit and TNF-α (p < 0.05); lymphocytes and MCP-1 (p < 0.01). Positive correlations occurred between leukocyte and neutrophil counts with IL-8, MCP-1, TNF-α; CRP with IL-6, IL-8, MCP-1, TNF-α; and platelets with IL-17A and TNF-α (all p < 0.05). These findings indicate that elevated pro-inflammatory cytokines are linked to hematological markers typical of severe COVID-19—lymphopenia, anemia, and neutrophilic leukocytosis—contributing to poor outcomes. Conversely, IL-4, IL-7, and IFN-α may play protective roles associated with milder disease and recovery. The study underscores immune balance as critical in COVID-19 progression and highlights potential biomarkers for prognosis and therapeutic targeting.