Protective effects of IL18-105G>A and IL18-137C>G genetic variants on severity of COVID-19

Abstract Objective and Design: A cross-sectional study evaluated the IL18 -105G > A (rs360717) and IL18 -137C > G (rs187238) variants on Coronavírus Disease 2019 (COVID-19) severity. Subjects and Methods: 528 patients with COVID-19 classifed with mild (n = 157), moderate (n = 63) and critical (n = 308) disease were genotpyed for the IL18 -105G > A and IL18 -137C > G variants. Results The IL18 -105G > A was associated with severe disease (moderate + critical), with effects of the GA genotype in the codominant [Odds ratio (OR), (95% confidence interval) 0.55, 0.34–0.89, p = 0.015], overdominant (0.56, 0.35–0.89, p = 0.014) and the AA + GA genotypes in the dominant (0.60, 0.38–0.96, p = 0.031) models. The IL18 -137GC was also associated with severe disease with effects in the codominant (0.55, 0.34–0.89, p = 0.015), and overdominant models (0.57, 0.36–0.91, p = 0.018), and the GG + CG genotypes in the dominant model (0.59, 0.37–0.93, p = 0.025). IL18 -105 GA coupled with age, chest computed tomograhy scan anormalities, body mass index, heart diseases, type 2 diabetes mellitus, hypertension, and inflammation may be used to predict the patients who develop severe disease with an accuracy of 84.3% (sensitivity: 83.3% and specificity: 86.5%). Conclusion The IL18 -105G > A and IL18 -137C > G variants contribute to COVID-19 severity and the effects of IL18 -137C > G may be modulating IL-18 production and Th1-mediated immune responses.