Association Between Genetic Variants in TNF, IL6, and IL1B Genes and Severity of COVID-19: A Cross-Sectional Study of Patients from Southern Brazil

<b>Background/Objectives:</b> Genetic variants in cytokine genes such as <i>IL1B</i>, <i>IL6</i>, and <i>TNF</i> 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. <b>Methods:</b> 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-<i>IL1B</i> (rs4848306, rs1143623, rs16944, rs1143627), <i>IL6</i> (rs1800795, rs2069832, rs2069840, rs2069845), and <i>TNF</i> (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. <b>Results:</b> The results indicated that the <i>IL1B</i> rs16944-AG (OR: 1.98 [95% CI: 1.22-3.23], <i>p</i> = 0.006) and <i>TNF</i> rs1799964-CT (OR: 1.97 [95% CI: 1.22-3.22], <i>p</i> = 0.006) genotypes were associated with the need for hospitalization, while TNF rs1800630-AA (OR: 2.37 [95% CI: 1.08-5.33], <i>p</i> = 0.034) was associated with ICU admission. Additionally, the CC genotype of <i>TNF</i> rs1799964 was associated with a higher risk of mortality (OR: 3.73 [95% CI: 1.21-14.37], <i>p</i> = 0.034). <b>Conclusions:</b> Genetic variants-specifically <i>IL1B</i> rs16944 and rs1143627, and <i>TNF</i> 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.