The role of host genetics in susceptibility to severe viral infections in humans and insights into host genetics of severe COVID-19: A systematic review

Abdelazeem Elhabyan, Saja Elyaacoub, Ehab Sanad, Abdelwahab Abukhadra, Asmaa Elhabyan, Valentin Dinu

Research output: Contribution to journalReview articlepeer-review

17 Scopus citations

Abstract

Background: Susceptibility to severe viral infections was reported to be associated with genetic variants in immune response genes using case reports and GWAS studies. SARS-CoV-2 is an emergent viral disease that caused millions of COVID-19 cases all over the world. Around 15 % of cases are severe and some of them are accompanied by dysregulated immune system and cytokine storm. There is increasing evidence that severe manifestations of COVID-19 might be attributed to human genetic variants in genes related to immune deficiency and or inflammasome activation (cytokine storm). Objective: Identify the candidate genes that are likely to aid in explaining severe COVID-19 and provide insights to understand the pathogenesis of severe COVID-19. Methods: In this article, we systematically reviewed genes related to viral susceptibility that were reported in human genetic studies (Case-reports and GWAS) to understand the role of host viral interactions and to provide insights into the pathogenesis of severe COVID-19. Results: We found 40 genes associated with viral susceptibility and 21 of them were associated with severe SARS-CoV disease and severe COVID-19. Some of those genes were implicated in TLR pathways, others in C-lectin pathways, and others were related to inflammasome activation (cytokine storm). Conclusion: This compilation represents a list of candidate genes that are likely to aid in explaining severe COVID-19 which are worthy of inclusion in gene panels and during meta-analysis of different variants in host genetics studies of COVID-19. In addition, we provide several hypotheses for severe COVID-19 and possible therapeutic targets.

Original languageEnglish (US)
Article number198163
JournalVirus research
Volume289
DOIs
StatePublished - Nov 2020

Keywords

  • C-lectin pathways
  • COVID-19
  • COVID-19 GWAS
  • COVID-19 pathogenesis
  • Coronavirus
  • Cytokine storm
  • Host genetics
  • Host immune defenses
  • Inborn errors of immunity
  • Inflammasome
  • Interferon
  • Interleukins
  • SARS-coronavirus 2
  • TLR pathway
  • Viral susceptibility

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases
  • Cancer Research

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