Dataset Information

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.

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.

SUBMITTER: Elhabyan A

PROVIDER: S-EPMC7480444 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Publications

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.

Elhabyan Abdelazeem A Elyaacoub Saja S Sanad Ehab E Abukhadra Abdelwahab A Elhabyan Asmaa A Dinu Valentin V

Virus research 20200909

<h4>Background</h4>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 varian ...[more]

PMID: 32918943

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Project description:BackgroundThe World Health Organization has identified studies of the role of host genetics on susceptibility to severe influenza as a priority. A systematic review was conducted to summarize the current state of evidence on the role of host genetics in susceptibility to influenza (PROSPERO registration number: CRD42011001380).Methods and findingsPubMed, Web of Science, the Cochrane Library, and OpenSIGLE were searched using a pre-defined strategy for all entries up to the date of the search. Two reviewers independently screened the title and abstract of 1,371 unique articles, and 72 full text publications were selected for inclusion. Mouse models clearly demonstrate that host genetics plays a critical role in susceptibility to a range of human and avian influenza viruses. The Mx genes encoding interferon inducible proteins are the best studied but their relevance to susceptibility in humans is unknown. Although the MxA gene should be considered a candidate gene for further study in humans, over 100 other candidate genes have been proposed. There are however no data associating any of these candidate genes to susceptibility in humans, with the only published study in humans being under-powered. One genealogy study presents moderate evidence of a heritable component to the risk of influenza-associated death, and while the marked familial aggregation of H5N1 cases is suggestive of host genetic factors, this remains unproven.ConclusionThe fundamental question "Is susceptibility to severe influenza in humans heritable?" remains unanswered. Not because of a lack of genotyping or analytic tools, nor because of insufficient severe influenza cases, but because of the absence of a coordinated effort to define and assemble cohorts of cases. The recent pandemic and the ongoing epizootic of H5N1 both represent rapidly closing windows of opportunity to increase understanding of the pathogenesis of severe influenza through multi-national host genetic studies.

Dataset Information

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.

Background

Objective

Methods

Results

Conclusion

Publications

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.

Similar Datasets

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