TLR7 polymorphisms are associated with COVID-19 susceptibility and severity

Objectives SARS-CoV-2 infection causes an innate immune response that is activated through pattern-recognition receptors (PRRs), including Toll-like receptors (TLRs) and retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs). Endosomal TLR7/8 detects viral ssRNA, while TLR3 also recognizes dsRNA formed during viral replication. Both RIG-I and MDA5 recognize SARS-CoV-2 RNA in the cytoplasm of infected cells. PRR pathways recruit essential downstream adapter proteins to induce type I interferons (IFNs) and inflammatory cytokines. While genetic variations in host PRRs may influence SARS-CoV-2 infection, immune response, and COVID-19 severity, their specific role in triggering these processes remains unclear. This study analyzes the frequency of specific polymorphisms within PRR genes in COVID-19 patients to evaluate their impact on disease severity. Methods We genotyped ten PRR polymorphisms in 261 individuals, including 166 patients hospitalized for COVID-19, and evaluated their associations with clinical parameters and serum cytokine profiles. Single-nucleotide polymorphisms (SNPs) of TLR3 (rs3775290 and rs3775291), TLR7 (rs179008, rs3853839, and rs5741880), TLR8 (rs3764879 and rs3764880), IFIH1 rs1990760, and DDX58 rs73479410 were genotyped using qPCR allelic discrimination, while TLR3 rs3775296 was analyzed by PCR-RFLP. Cytokine concentrations were quantified using MILLIPLEX Magnetic Bead Panels and Luminex xMAP technology. Results In this case-control study, the recessive G/G genotype of the TLR7 rs3853839 SNP was associated with an increased risk of hospitalization. The presence of at least one recessive T allele for the TLR7 rs179008 SNP was associated with lower cytokine levels (IP-10, IL-10, TNF-α) and a decreased risk of severe symptoms in hospitalized patients. Conclusions Our findings suggest that the TLR7 rs3853839 SNP may represent a genetic risk factor for severe COVID-19, whereas the missense TLR7 rs179008 SNP (Q11L) may contribute to less severe symptoms among these patients.