ArticleFrontiers in immunology2026
Cytokine profiles, genetic polymorphisms, and systemic inflammatory markers in type 1 diabetes patients with COVID-19: IL-18 a predictor of disease severity.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
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<0.0001, OR = 2.85 CI95% [1.83-4.43]). IL-12 correlated positively with IL-18 (r = 0.41, p < 0.001) and negatively with IL-6 (r = -0.22, p = 0.005). ML analyses identified IL-18, CRP, and IL-6 as the most informative biomarkers of COVID-19 severity, with IL-18 showing the highest feature importance (0.276, 0.202, and 0.175, respectively). Conclusion: This study highlights the critical role of inflammatory biomarkers and host genetic factors in COVID-19 severity among T1DM patients and identifies IL-18 as a robust and clinically relevant biomarker for risk stratification.
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