Association of IL4 and IL17A genetic polymorphisms with COVID-19 severity in a southern Brazilian population

COVID-19 has demonstrated marked differences in clinical manifestations and outcomes, with severe cases presenting excessive inflammatory responses known as cytokine storms. Polymorphisms in cytokine genes, such as interleukin-4 (IL4) and interleukin-17A (IL17A), may influence immune responses and contribute to disease severity. This study investigated the association between the IL4 -34C/T and IL17A -197G/A polymorphisms and COVID-19 severity in a population from Southern Brazil. A total of 528 individuals were included, with 157 severe and 371 mild cases. DNA was extracted from buccal swabs and blood samples, and genotyping was performed using TaqMan assays. Associations were assessed using univariate and multivariate logistic regression analyses, adjusted for confounders. The IL4 -34C/T TT genotype was significantly associated with a reduced risk of severe COVID-19 (OR = 0.33, P = 0.036), suggesting a protective role. This polymorphism was also linked to dysgeusia and anosmia (PR = 1.46, P = 0.020), symptoms more common in mild cases. Conversely, the IL-17A -197G/A GG genotype was associated with increased risk of severe disease (OR = 2.66, P = 0.028) and respiratory symptoms (PR = 1.27, P = 0.048). These findings highlight the role of IL4 and IL17A polymorphisms in modulating COVID-19 severity and clinical presentation, underscoring the complexity of immune responses to SARS-CoV-2.