Cytokines profile and their related genotypes in COVID-19: Correlation with disease severity and outcome in Egyptian patients

Abstract

Background and Aims: COVID-19-related pulmonary inflammation is linked to elevated plasma levels of a group of proinflammatory cytokines. We aim to identify the association between IL-6 rs1800795, IL-17 rs2275913, and IL-37 rs3811046 gene polymorphisms and COVID-19 severity and prognosis. Methods: Two hundreds adult COVID-19-confirmed patients (100 patients with non-severe and 100 patients with severe or critical COVID-19) and 100 healthy individuals were enrolled in this cross-sectional study. Clinical and laboratory evaluations were performed, including liver and kidney functions, complete and differential blood counts, C-reactive protein, and D-dimer. Genotyping for IL-6 (rs1800795), IL-17 (rs2275913), and IL-37 (rs3811046) was conducted using allelic discrimination real-time PCR assay via TaqMan probes. The levels of IL-6, IL-17, and IL-37 were estimated by enzyme-linked immunosorbent assay (ELISA). Results: Serum levels of IL-6 and IL-17 were increased while IL-37 declined with ongoing COVID-19 severity. IL-6 rs1800795 genotypes and alleles did not differ significantly between the studied groups. Meanwhile, IL-17 rs2275913 GA (heterozygous) and AA (homozygous) genotypes and A allele showed significantly higher frequencies in the control group compared to those in the patients’ groups and were proposed as protective factors against COVID-19 occurrence and increased severity. Notably, IL-37 rs3811046, GT and TT variants, and T allele were more prevalent in the patients’ groups than in the control group and might be related to both disease occurrence and progression. Conclusion: Both GG genotype and G allele of IL-17 (rs2275913) and TT genotype and T allele of IL-37 (rs3811046) and their serum levels are potential risk factors for COVID-19 infection and severity, making them excellent disease management targets.