Association of Inflammatory Cytokines as Predictors of Severity in Covid-19 Patients

SARS-CoV-2 infection can result in a wide variety of clinical outcomes, from asymptomatic cases to severe pneumonia and death, largely due to differences in patients’ immune responses. During infection, cytokines and chemokines are produced simultaneously and interact within a complex network that can favor or inhibit disease progression. We investigated the immunological profile of hospitalized COVID-19 patients to identify immune signatures associated with disease severity. This cross-sectional study analyzed serum samples from 76 hospitalized, unvaccinated COVID-19 patients from the state of Pernambuco, classified into two groups: Critical/deaths (n = 43) and severe (n = 33). For analysis of pro-inflammatory cytokines, patients were subdivided into four groups: critical/deaths, severe, deaths, and recovered. Quantification of 80 soluble mediators was performed using the Human Immune Response ProcartaPlex 80-plex panel with the MAGPIX System (Merck, USA), based on Luminex xMAP technology. Data normality was assessed (Shapiro-Wilk test) and cytokine levels were compared between groups using the Mann-Whitney test. Analyses were performed in GraphPad Prism 8.0.1, with significance set at p < 0.05. To evaluate differential regulation between groups, log2 fold change of medians was calculated (upregulated/downregulated). Twelve inflammatory cytokines showed significant differences. MDC, CCL17, CCL11, and CCL8 were elevated in the severe and survivor groups, suggesting a more regulated immune profile in moderate cases. HGF, CXCL9, CXCL13, PTX3, CCL19, CCL1, IL2R, and M-CSF were elevated in critical cases, indicating possible immune hyperactivation associated with disease severity. The chemokines MDC, CCL17, CCL11, and CCL8 may be considered possible markers for moderate disease, whereas cytokines/chemokines/growth factors HGF, CXCL9, CXCL13, PTX3, CCL19, CCL1, IL2, and M-CSF may serve as markers for more critical disease and COVID-19-related death. These findings reinforce the importance of dysregulated inflammation in the progression of SARS-CoV-2 infection. Identifying these biomarkers may help stratify patients, monitor severity, and guide therapeutic strategies.