Elsevier

Virus Research

Volume 289, November 2020, 198163
Virus Research

Review
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

https://doi.org/10.1016/j.virusres.2020.198163Get rights and content

Highlights

  • 40 candidate genes might be associated with severe COVID-19.

  • Inflammasome (NLRP1) as a possible cause of cytokine storm in COVID-19.

  • IL-18, CCR1, CCR9 and EndoU(coronavirus protein) inhibition as possible treatment for COVID-19.

  • DC-SIGN (Lectin pathway) and MxA expression might explain SARS-CoV-2 latency and reactivation in some cases.

  • Case report as study design for discovering novel monogenic cases(with low minor allele frequency) of severe COVID-19.

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.

Abbreviations

GWAS
genome wide association studies
SARS-CoV-2
SARS Coronavirus 2
SARS-CoV
SARS Coronavirus
IUIS
International Union of Immunological Societies
OMIM
Online Mendelian Inheritance in Man (OMIM)
HSE
herpses simplex encephalitis
HSV-1
Herpes Simplex Virus 1
MeSH
medical subject heading
dsRNA
double-strand RNA
DC-SIGN
Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin
LDH
lactate dehydrogenase
IL-18BP
IL-18 binding protein
PBMCs
peripheral blood mononuclear cells
endoU
coronavirus endoribonuclease

Keywords

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

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