Association of the Rs179008 Polymorphism in the Tlr7 Gene With Covid-19 Severity in Patients From Southern Brazil: A Potential Genetic Risk Marker in Women

COVID-19, caused by SARS-CoV-2, is a global disease with profound impact on public health systems and the economy. It shows wide clinical variability, from asymptomatic to critical cases, with heterogeneity influenced by factors such as age, comorbidities, and genetic predisposition. The TLR7 receptor, from the Toll-like family, recognizes pathogen-associated molecular patterns, activating innate immunity. Encoded on the X chromosome, it is highly expressed in the lungs and spleen. The rs179008 polymorphism in the TLR7 gene affects receptor functionality, altering cytokine and type I interferon production, which may influence the response to viral infection. This study evaluated the association between the polymorphism and COVID-19 severity in patients from Southern Brazil. The study evaluated 315 patients with confirmed COVID-19 diagnosis: 191 non-hospitalized and 124 hospitalized. The study was approved by the Research Ethics Committee for Human Subjects. The rs179008 polymorphism was genotyped by real-time PCR. Genotype frequencies were evaluated for Hardy-Weinberg equilibrium. Variables with normal distribution were assessed using t-test, Mann-Whitney, or chi-square tests depending on the variable type and distribution. Univariate and multivariate logistic regression analyses were used to assess the association between the polymorphism and disease severity. Significance was set at p < 0.05. Analyses were performed using SPSS. Our results suggest that the AT genotype was significantly associated with risk of hospitalization for COVID-19 compared to the AA genotype (OR = 4.29; 95% CI 1.63–11.62; p = 0.003). After stratifying by sex, a similar pattern was found in women, in whom the AT genotype was also associated with higher hospitalization risk (OR = 4.32; 95% CI 1.15–11.94; p = 0.03). The presence of the T allele (TT + AT) in the female sample showed higher hospitalization risk (OR = 4.34; 95% CI 1.71–11.74; p = 0.03). The results suggest that the rs179008 polymorphism in the TLR7 gene is associated with an increased risk of hospitalization for COVID-19, especially in women. Additional studies with other TLRs are needed to further understand the influence of innate immunity on disease prognosis.