Abstract

Coronavirus disease 2019 (COVID-19) is a fatal pandemic disease that is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of 13 December, 2020, over 70,000,000 cases and 1,500,000 deaths have been reported over a period of several months; however, the mechanism underlying the pathogenesis of COVID-19 has not been elucidated. To identify the novel risk genetic biomarker for COVID-19, we evaluated the correlation between the case fatality rate of COVID-19 and the genetic polymorphisms of several potential COVID-19-related genes, including interferon-induced transmembrane protein 3 (IFITM3), the angiotensin I converting enzyme 2 (ACE2) gene, transmembrane protease, serine 2 (TMPRSS2), interleukin 6 (IL6), leucine zipper transcription factor-like protein 1 (LZTFL1), and the ABO genes, in various ethnic groups. We obtained the number of COVID-19 cases and deaths from the World Health Organization (WHO) COVID-19 dashboard and calculated the case fatality rate of each ethnic group. In addition, we obtained the allele distribution of the polymorphisms of the IFITM3, ACE2, TMPRSS2, IL6, LZTFL1, and ABO genes from the 1000 Genomes Project and performed Log-linear regression analysis using SAS version 9.4. We found different COVID-19 case fatality rates in each ethnic group. Notably, we identified a strong correlation between the case fatality rate of COVID-19 and the allele frequency of the rs6598045 single nucleotide polymorphism (SNP) of the IFITM3 gene. To the best of our knowledge, this report is the first to describe a strong correlation between the COVID-19 case fatality rate and the rs6598045 SNP of the IFITM3 gene at the population-level.

Highlights

  • Coronavirus disease 2019 (COVID-19) is a fatal acute respiratory disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1,2]

  • To find the novel genetic biomarker for the severity of COVID-19, we evaluated a correlation at the population-level between the case fatality rate of COVID19 and genetic polymorphisms of several potential COVID-19-related genes, including interferon-induced transmembrane protein 3 (IFITM3), angiotensin I converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), interleukin 6 (IL6), leucine zipper transcription factor-like protein 1 (LZTFL1), and the ABO genes

  • We selected a total of 26 polymorphisms, which have been previously reported for relationship with SARS-CoV-2, influenza A H1N1 pandemic 2009 virus and chronic obstructive pulmonary disease (COPD) [6,8,9,10,11,12,13]

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Summary

Introduction

Coronavirus disease 2019 (COVID-19) is a fatal acute respiratory disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1,2]. TMPRSS2 is a serine protease and plays a role in the spike protein priming of SARS-CoV-2 for viral invasion [4,5]. In a previous study, the genetic polymorphisms affecting the expression level of the TMPRSS2 gene have been suggested as novel candidates in the severity of COVID-19 in Italy [6]. A previous study did not observe an association between the genetic polymorphisms of the ACE2 and TMPRSS2 genes and SARS-CoV-2 infection [7]. A recent genome-wide association study (GWAS) reported that two polymorphisms, the rs11385942 insertion/deletion polymorphism of the leucine zipper transcription factor-like protein 1 (LZTFL1) gene and the rs657152 SNP of the ABO gene, are related to severe COVID-19 cases with respiratory failure [10]. An association between genetic variants and the case fatality of COVID-19 has not been determined

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