Cytokine storm polymorphisms in nonvaccinated COVID-19 patients

Cytokines and chemokines are essential for establishing an appropriate immune response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Variations in the genes encoding cytokines and chemokines strongly influence the immune response to pathogenic challenges and disease outcomes. This study was carried out to determine the associations of polymorphisms in the TNF-, IL-6, IL-8, IL-10, and CCL5 genes with COVID-19 severity. A total of 627 unvaccinated COVID-19 patients were classified according to WHO disease severity. We evaluated the levels of IFN-, IFN-{gamma}, TNF-, IL-1R, IL-6, IL-7, IL-10, CCL2, CCL3, CXCL8, CXCL10 and GCSF in the serum and were compared among COVID-19 disease severity groups and stratified by polymorphism alleles. This study revealed a significant increase in IL-2, IL-6 and CCL-2 levels in the dead group. However, the IL-10 levels were higher in the moderate group than in the mild group. Logistic regression analysis revealed that five polymorphisms were associated with an increased risk of severe COVID-19: the TNF- (rs1800610) A allele (OR=1.50; 95% CI: 1.01-2.24); the IL-6 (rs1800796) C allele (OR=1.64; 95% CI: 1.05-2.57); the IL-10 (rs1800871) T allele (OR=1.94; 95% CI: 1.24-3.04) and the IL-10 (rs1800872) A allele (OR=1.87; 95% CI: 1.21-2.89); and the CCL5 (rs3817656) G allele (OR= 1.64; 95% CI: 1.02-2.65)). The IL-10 (rs1800871 and rs1800872) and IL-6 (rs1800796 and rs18049563) gene polymorphisms were also associated with COVID-19 severity. Increases in IL-6 and CCL-2 serum levels in carriers of the risk allele rs1049953. In contrast, the IL-10 levels were not associated with any of the SNPs.