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. Highlights Tumor necrosis factors play pivotal functions in coronavirus disease 2019 (COVID‐19) progression and pathogenesis. The host genetics plays a fundamental role in the immune response to the SARS‐CoV‐2 virus and influences the risk of COVID‐19, severity and outcome in affected patients. we reported an association between either TNFα or TNFβ polymorphisms and COVID‐19 risk and outcome.
【저자키워드】 COVID‐19, ARDS, SARS‐CoV‐2, polymorphism, tumor necrosis factor, CT pattern, 【초록키워드】 coronavirus disease, Necrosis, Tumor, coronavirus, immune response, Mutation, Pathogenesis, intensive care, Hospitalization, severity, host genetics, variant, risk, progression, outcome, molecular mechanism, COVID‐19, Computed tomography, Patient, Genotype, experiment, mortality rate, patients, function, association, TNF, Evidence, Genetic polymorphism, Deceased, Odds ratio, leukocyte, acute respiratory syndrome, Factor, 95% confidence interval, subject, neutrophil count, participant, Severe case, TNFα, allele, G allele, disorder, SARS‐CoV‐2 virus, carrier, controls, polymerase chain, Course, enrolled, analyzed, affected, detect, recruited, reported, addition, the disease, provided, subjects, demonstrated, suggested, A allele, influence, statistically, the healthy, 【제목키워드】 Necrosis, Mortality, in silico, Analysis, Factor, SARS‐CoV‐2 infection,