Association of IL6 Gene Polymorphisms with COVID-19 Susceptibility and Inflammation in Pregnant Women

<b>Background/Objectives:</b> Pregnancy is characterized by complex immunological adaptations that may increase susceptibility to infections, including SARS-CoV-2. Interleukin-6 (IL-6), a key pro-inflammatory cytokine, plays a crucial role in the immune response and has been strongly implicated in the pathogenesis of COVID-19. Genetic variations in the <i>IL6</i> gene, particularly single-nucleotide polymorphisms (SNPs) in the promoter region, can modulate IL-6 expression and potentially influence individual susceptibility to viral infections. This study aimed to evaluate the relationship between promoter region <i>IL6</i> gene polymorphisms and COVID-19 susceptibility, as well as the inflammatory response, in pregnant women. <b>Methods:</b> We enrolled in this study 204 pregnant women with evidence of SARS-CoV-2 infection in pregnancy and 134 pregnant women with no evidence of SARS-CoV-2 infection in the past. Genotyping was conducted for the two functional SNPs in the <i>IL6</i> promoter region, rs1800796 and rs1800797, via Sanger sequencing, and for associations with COVID-19 susceptibility and IL-6 levels were analyzed. <b>Results:</b> No significant association was found between <i>IL6</i> polymorphisms and COVID-19, IL-6 levels, age, or immunization status. IL-6 levels > 5 pg/mL were more frequent in SARS-CoV-2-negative pregnant women than in SARS-CoV-2-positive pregnant women (<i>p</i> = 0.032). Among vaccinated participants, IL-6 levels were significantly higher in SARS-CoV-2-negative pregnant women (<i>p</i> = 0.044), while no difference was observed in the unvaccinated group. <b>Conclusions:</b><i>IL6</i> polymorphisms rs1800797 and rs1800796 were not associated with infection susceptibility or IL-6 levels. These results highlight the complex immunological interplay between pregnancy, infection, and genetic background and support the need for further research in larger cohorts.