COVID-19 has caused the recent pandemic of respiratory infection, which threatened global health. The severity of the symptoms varies among affected individuals, from asymptotic or mild signs to severe or critical illness. Genetic predisposition explains the variation in disease severity among patients who suffer from severe symptoms without any known background risk factors. The present study was performed to show the association between APOE genotype and the severity of COVID-19 disease. The APOE genotype of 201 COVID-19 patients (101 patients with asymptomatic to mild form of the disease as the control group and 100 patients with severe to critical illness without any known background risk factors as the case group) were detected via multiplex tetra-primer ARMS-PCR method. Results showed that the e4 allele increased the risk of the COVID-19 infection severity more than five times and the e4/e4 genotype showed a 17-fold increase in the risk of severe disease. In conclusion, since our study design was based on the exclusion of patients with underlying diseases predisposing to severe form of COVID-19 and diseases related to the APOE gene in the study population, our results showed that the e4 genotype is independently associated with the severity of COVID-19 disease. However, further studies are needed to confirm these findings in other nations and to demonstrate the mechanisms behind the role of these alleles in disease severity.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been responsible for the recent pandemic since early 2020. Due to the wide range of clinical symptoms of this disease, from asymptomatic to severe and critical forms, it seems that genetic differences among patients, along with other factors (such as gender, age, and underlying diseases), can explain part of the variation in disease symptoms. The TMPRSS2 enzyme plays a vital role in the early stages of the interaction of the SARS-CoV-2 with the host cells by facilitating viral entry. There is a polymorphism in the TMPRSS2 gene, called rs12329760(C to T) as a missense variant, which causes the replacement of valine to methionine in the TMPRSS2 protein at position 160. The present study investigated the association between the TMPRSS2 genotype and the severity of the Coronavirus disease 2019 (COVID-19) in Iranian patients. The TMPRSS2 genotype of 251 COVID-19 patients (151 patients with asymptomatic to mild and 100 patients with severe to critical symptoms) was detected on genomic DNA extracted from patients’ peripheral blood via the ARMS-PCR method. Our results showed a significant association between the minor T allele and the severity of the COVID-19 (P-value = 0.043) under the dominant and additive inheritance model. In conclusion, the results of this study showed that the T allele of the rs12329760 in the TMPRSS2 gene is a risk allele for severe form of COVID-19 in Iranian patients in contrast to most previous studies on this variant in European ancestry populations which suggested this variant as a protective allele. Our results reiterate to the ethnic-specific risk alleles and hidden unknown complexity behind the host genetic susceptibility. However, further studies are needed to address the complex mechanisms behind the interaction of the TMPRSS2 protein and the SARS-CoV-2 and the role of rs12329760 polymorphism in determining the disease severity.

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