Association of polymorphisms of IL-6 pathway genes (IL6, IL6R and IL6ST) with COVID-19 severity in an Amazonian population.

Abstract

Interleukin-6 have been recognized as a major role player in COVID-19 severity, being an important regulator of cytokine storm. Hence, the evaluation of the influence of polymorphisms in key genes of IL-6 pathway, namely IL6, IL6R and IL6ST, may provide valuable prognostic/predictive biomarkers on COVID-19. The present cross-sectional study genotyped three Single Nucleotide Polymorphisms - SNPs (rs1800795, rs2228145 and rs7730934) at IL6, IL6R and IL6ST genes, respectively, in 227 COVID-19 patients (132 hospitalized and 95 non-hospitalized). Genotype frequencies were compared between these groups. As control group, published data on gene and genotype frequencies was gathered from published studies from before the pandemic started. Our major results point to an association of IL6 C allele with COVID-19 severity. Moreover, IL-6 plasmatic levels were higher among IL6 CC genotype carriers. Additionally, the frequency of symptoms was higher at IL6 CC and IL6R CC genotypes. In conclusion the data suggest an important role of IL6 C allele and IL6R CC genotype on COVID-19 severity, in agreement with indirect evidences from literature about association of these genotypes with mortality rates, pneumonia, heightening of protein plasmatic levels proinflammatory driven effects.