• Abdelazeem Elhabyan, Saja Elyaacoub, Ehab Sanad, Abdelwahab Abukhadra, Asmaa Elhabyan, and Valentin Dinu.
• College of Health Solutions, Arizona State University, Scottsdale, AZ, USA; Faculty of Medicine, Tanta University, Gharbia, Tanta, Egypt. Electronic address: aelhabya@asu.edu.
• Virus Res. 2020 Nov 1; 289: 198163.

BackgroundSusceptibility 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).ObjectiveIdentify the candidate genes that are likely to aid in explaining severe COVID-19 and provide insights to understand the pathogenesis of severe COVID-19.MethodsIn 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.ResultsWe 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).ConclusionThis 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.Copyright © 2020 Elsevier B.V. All rights reserved.

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