Cytokine profiles, genetic polymorphisms, and systemic inflammatory markers in type 1 diabetes patients with COVID-19: IL-18 a predictor of disease severity

Background: Patients with Type 1 Diabetes Mellitus (T1DM) are at increased risk for severe COVID-19 due to chronic inflammation, immune dysregulation, and impaired antiviral responses. However, the combined contribution of cytokine imbalance, host genetic variation, and systemic inflammation on COVID-19 severity in this population remains incompletely understood. This study aimed to investigate inflammatory biomarkers, interleukin profiles and immunogenetic factor associated with COVID -19 outcomes in T1DM patients. Methods: A total of 220 individuals were enrolled, including 160 T1DM patients with confirmed COVID-19 and 60 healthy controls. Serum concentrations of IL-6, IL-10, IL-12A, and IL-18 were quantified using ELISA, along with clinical inflammatory markers (CRP, D-dimer, and NLR). Genetic polymorphisms in the IL-10, IL-12A, IL-6, and IL-18 genes were analyzed using PCR-ARMS. Statistical analyses included group comparisons and correlation analysis. In addition, supervised machine-learning (ML) approaches (Decision Tree and Random Forest) were applied within the T1DM COVID-19 cohort to identify biomarkers predictive of disease severity. Results: Patients exhibited significantly elevated cytokine levels and inflammatory markers compared to controls (all p < 0.001). The IL-10 polymorphism (rs1800872) was significantly associated with increased disease susceptibility, with the G allele conferring a higher risk (p