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

## TL;DR

This study finds that IL-18 is a strong predictor of severe COVID-19 in patients with type 1 diabetes, along with other inflammatory markers and genetic factors.

## Contribution

The study identifies IL-18 as a novel biomarker for predicting disease severity in T1DM patients with COVID-19.

## Key findings

- T1DM patients with COVID-19 had significantly higher cytokine levels and inflammatory markers compared to controls.
- The IL-10 polymorphism rs1800872 was associated with increased disease susceptibility in T1DM patients.
- Machine learning identified IL-18, CRP, and IL-6 as key biomarkers for predicting disease severity.

## Abstract

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.

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.

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).

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.