Influence of IL-6 rs1800795 and IL-8 rs2227306 polymorphisms on COVID-19 outcome

Abstract

Introduction: Severe coronavirus disease 2019 (COVID-19) is mainly precipitated by an uncontrolled inflammatory response and cytokine storm. Pro-inflammatory cytokines such as IL-6 and IL-8 levels were markedly increased in complicated cases. Genetic polymorphisms may have a role in this dysregulated expression during SARS-CoV-2 infection. Our aim was to assess the influence of IL-6 and IL-8 single nucleotide polymorphisms (SNPs) on COVID-19 outcomes.

Methodology: 240 subjects were involved in the study; 80 cases with severe COVID-19, 80 cases with mild COVID-19, and 80 healthy subjects. IL-6rs1800795(G/C) and IL-8 rs2227306(C/T) genotyping was performed using real-time polymerase chain reaction (PCR).

Results: Ages ranged between 20-67 years in all groups. There was a statistically significant association between the male gender and severe COVID-19. A significantly higher expression of IL-6rs1800795GG and IL-8rs2227306CC genotypes was observed among patients with severe COVID-19 than other groups. At the allele level, IL-6rs1800795G and IL-8rs2227306C alleles were more frequent among patients with severe COVID-19 when compared with other groups. Haplotypes' frequency clarified that the coexistence of IL-6 rs1800795G and IL-8rs2227306C alleles in the same person increased the risk of severe COVID-19 outcomes. Carriers of IL-6rs1800795C and IL-8 rs2227306T alleles are at lower risk of developing severe COVID-19. Multivariate logistic regression analysis showed that old age, male gender, IL-6 rs1800795CG+GG, and IL-8 rs2227306CT+CC genotypes could be independent risk factors for severe COVID-19 outcomes.

Conclusions: IL-6 rs1800795G and IL-8 rs2227306C alleles are significantly associated with severe COVID-19 outcomes, especially if they coexist. They may be used as prognostic markers for COVID-19.