ORIGINAL RESEARCH article
Front. Immunol.
Sec. Viral Immunology
This article is part of the Research TopicThe Influence of SARS-CoV-2 Infection and Long-COVID on The Incidence of Viral CoinfectionView all 15 articles
Cytokine Profiles, Genetic Polymorphisms, and Systemic Inflammatory Markers in Type 1 Diabetes Patients with COVID-19: IL-18 a Predictor of Disease Severity
Provisionally accepted
Mohammed Yousif Abdullah1
Ahmed Baligh Laaribi1*
Wafa BABAY1
Farah Alhaddad2
Asma Mehri1
Imene Hadda OUZARI1
Sonia Marghali1- 1Faculty of Sciences of Tunis, Tunis El Manar University, Tunis, Tunisia
- 2Erciyes Universitesi, Talas, Türkiye
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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 analysed 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.
Keywords: COVID-19, Cytokine profiles, Genetic polymorphisms, IL-18, Inflammatory markers, machine learning, predictive biomarkers, T1DM
Received: 30 Oct 2025; Accepted: 09 Feb 2026.
Copyright: © 2026 Abdullah, Laaribi, BABAY, Alhaddad, Mehri, OUZARI and Marghali. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ahmed Baligh Laaribi
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