Association Between Genetic Variants in , , and Genes and Severity of COVID-19: A Cross-Sectional Study of Patients from Southern Brazil.

Genetic variants in cytokine genes such as , , and may influence inflammatory responses to SARS-CoV-2 and affect disease severity. This study investigates the role of these variants in relation to COVID-19 outcomes, including hospitalization, ICU admission, and mortality. A total of 500 unvaccinated individuals from southern Brazil diagnosed with COVID-19 via RT-PCR were analyzed. DNA was extracted from nasopharyngeal swabs and genotyped for functional variants selected based on evidence of regulatory function and prior associations with inflammatory outcomes- (rs4848306, rs1143623, rs16944, rs1143627), (rs1800795, rs2069832, rs2069840, rs2069845), and (rs1799964, rs1800630, rs1799724, rs1800629, rs361525). Multivariate logistic regression analysis, adjusted for sex and age, was employed to assess the association between these genetic variants and severe clinical outcomes. The results indicated that the rs16944-AG (OR: 1.98 [95% CI: 1.22-3.23], = 0.006) and rs1799964-CT (OR: 1.97 [95% CI: 1.22-3.22], = 0.006) genotypes were associated with the need for hospitalization, while TNF rs1800630-AA (OR: 2.37 [95% CI: 1.08-5.33], = 0.034) was associated with ICU admission. Additionally, the CC genotype of rs1799964 was associated with a higher risk of mortality (OR: 3.73 [95% CI: 1.21-14.37], = 0.034). Genetic variants-specifically rs16944 and rs1143627, and rs1799964 and rs1800630-were associated with COVID-19 severity and should be further investigated in larger studies to evaluate their potential as predictive markers of severe outcomes in COVID-19.