The association of COVID-19 severity and susceptibility and genetic risk factors: A systematic review of the literature

Gene. 2022 Aug 20;836:146674. doi: 10.1016/j.gene.2022.146674. Epub 2022 Jun 14.


Background: COVID-19 is associated with several risk factors such as distinct ethnicities (genetic ancestry), races, sexes, age, pre-existing comorbidities, smoking, and genetics. The authors aim to evaluate the correlation between variability in the host genetics and the severity and susceptibility towards COVID-19 in this study.

Methods: Following the PRISMA guidelines, we retrieved all the relevant articles published until September 15, 2021, from two online databases: PubMed and Scopus.

Findings: High-risk HLA haplotypes, higher expression of ACE polymorphisms, and several genes of cellular proteases such as TMPRSS2, FURIN, TLL-1 increase the risk of susceptibility and severity of COVID-19. In addition, upregulation of several genes encoding for both innate and acquired immune systems proteins, mainly CCR5, IFNs, TLR, DPPs, and TNF, positively correlate with COVID-19 severity. However, reduced expression or polymorphisms in genes affecting TLR and IFNλ increase COVID-19 severity.

Conclusion: Higher expression, polymorphisms, mutations, and deletions of several genes are linked with the susceptibility, severity, and clinical outcomes of COVID-19. Early treatment and vaccination of individuals with genetic predisposition could help minimize the severity and mortality associated with COVID-19.

Keywords: COVID-19 severity; Genetic Susceptibility; Host genetics; Polymorphisms; SARS-CoV-2.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • COVID-19* / genetics
  • Genetic Predisposition to Disease
  • Haplotypes
  • Humans
  • Polymorphism, Genetic
  • SARS-CoV-2