Association of polymorphisms in tumor necrosis factors with SARS-CoV-2 infection and mortality rate: A case-control study and in silico analyses.

Abstract

The present coronavirus disease 2019 (COVID‐19) is spreading rapidly and existing data has suggested a number of susceptibility factors for developing a severe course of the disease. The current case‐control experiment is aimed to study the associations of genetic polymorphisms in tumor necrosis factors (TNFs) with COVID‐19 and its mortality rate. A total of 550 participants (275 subjects and 275 controls) were enrolled. The tetra‐amplification refractory mutation system polymerase chain reaction technique was recruited to detect −308G>A TNFα and +252A>G TNFβ polymorphisms among the Iranian subjects. We demonstrated that carriers of the G allele of TNFβ‐252A/G, rs909253 A>G were more frequent in COVID‐19 subjects compared to the healthy group and this allele statistically increased the disease risk (odds ratio [OR] = 1.55, 95% confidence interval [CI] = 1.23–1.96, p < 0.0001). At the same time, the A allele of TNFα‐311A/G, rs1800629 G>A moderately decreased the risk of COVID‐19 (OR = 0.68, 95% CI = 0.53–0.86, p < 0.002). Also, we analyzed the various genotypes regarding the para‐clinical and disorder severity; we found that in the AA genotype of TNFβ‐252A/G (rs909253 A>G), the computed tomography scan pattern was different in comparison to cases carrying the AG genotype with p 1 < 0.001. In addition, in the severe cases of COVID‐19, leukocyte and neutrophil count and duration of intensive care unit hospitalization in the deceased patients were significantly increased (p < 0.001). Moreover, the TNFα‐311A/G (rs1800629 G>A) variant is likely to change the pattern of splicing factor sites. Our findings provided deep insights into the relationship between TNFα/TNFβ polymorphisms and severe acute respiratory syndrome coronavirus 2. Replicated studies may give scientific evidence for exploring molecular mechanisms of COVID‐19 in other ethnicities.