Association Between Single-Nucleotide Polymorphism rs2287886 of CD209 Gene and Clinical Severity of COVID-19 in Unvaccinated Brazilian Patients

<b>Background:</b> Host genetic factors significantly influence individual susceptibility to severe COVID-19, potentially explaining the observed disparities in clinical outcomes across populations. One of the key effectors in innate immunity and antiviral defense is the CD209 gene. This study explored the potential correlation of the CD209 gene SNP rs2287886 with diverse COVID-19 patient outcomes. <b>Materials and Methods:</b> A total of 176 patients (87 in the moderate group and 89 in the severe/critical/death group) were included in the study. Genotyping of patients was performed using the qPCR methodology, through the TAQMAN system. The results were analyzed adopting a significance level of <i>p</i> < 0.05. <b>Results:</b> The GG genotype (compared to AG + AA) and the G allele (compared to the A allele) of the rs2287886 SNP were significantly associated with an increased severity of COVID-19 (<i>p</i> = 0.0005 and <i>p</i> < 0.0001, respectively). The G allele was more frequent in individuals with more severe clinical outcomes (49.43% vs. 25.28%). Furthermore, expression quantitative trait loci (eQTL) analysis indicated that the GG genotype of rs2287886 is associated with higher <i>CD209</i> gene expression. Furthermore, the observed interaction analysis suggests that the interactions between <i>CD209</i> and its associated proteins may play a role in modulating the immune response. <b>Conclusions:</b> Our findings suggest that Brazilian patients homozygous for the GG genotype of the rs2287886 polymorphism in the <i>CD209</i> gene may be at increased risk of severe COVID-19 in the Brazilian population and may act as a potential prognostic marker of disease severity.