Association of the IL6 rs1800795 polymorphism with COVID-19 clinical severity in a Brazilian population

A dysregulated inflammatory response is a central mechanism underlying severe COVID-19, with elevated serum IL-6 and TNF-α levels consistently associated with increased disease severity and mortality. Growing evidence indicates that host genetic factors influence individual susceptibility to adverse outcomes. We investigated the association of the rs1800795 (IL6) and rs1800629 (TNF) polymorphisms with COVID-19 severity in patients from Northeast Brazil with confirmed SARS-CoV-2 infection. This cross-sectional study included 642 patients classified as critical (n = 224), severe (n = 306), or convalescent controls (n = 112). Genotyping was performed using TaqMan assays. Genetic analysis revealed significant differences in rs1800795 allele frequency (p = 0.018) and in the CC versus GC + GG genotype comparison (adjusted p = 0.032) across clinical groups. Multinomial logistic regression showed that carriers of the GC or GG genotypes had an increased risk of severe (OR = 5.84; 95% CI = 1.93-17.7; p = 0.002) and critical COVID-19 (OR = 3.57; 95% CI = 1.15-11.1; p = 0.028) compared with CC carriers, independent of major confounders. No significant association was observed for TNF rs1800629. These findings support an association between the IL6 rs1800795 polymorphism and COVID-19 clinical severity, highlighting the relevance of immunogenetic factors in COVID-19 outcomes.