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Review
. 2020 Jul;34(7):8787-8795.
doi: 10.1096/fj.202001115R. Epub 2020 Jun 11.

Genetic gateways to COVID-19 infection: Implications for risk, severity, and outcomes

Monojit Debnath  1 , Moinak Banerjee  2 , Michael Berk  3   4
Affiliations
Review

Genetic gateways to COVID-19 infection: Implications for risk, severity, and outcomes

Monojit Debnath et al. FASEB J. 2020 Jul.

Abstract

The dynamics, such as transmission, spatial epidemiology, and clinical course of Coronavirus Disease-2019 (COVID-19) have emerged as the most intriguing features and remain incompletely understood. The genetic landscape of an individual in particular, and a population in general seems to play a pivotal role in shaping the above COVID-19 dynamics. Considering the implications of host genes in the entry and replication of SARS-CoV-2 and in mounting the host immune response, it appears that multiple genes might be crucially involved in the above processes. Herein, we propose three potentially important genetic gateways to COVID-19 infection; these could explain at least in part the discrepancies of its spread, severity, and mortality. The variations within Angiotensin-converting enzyme 2 (ACE2) gene might constitute the first genetic gateway, influencing the spatial transmission dynamics of COVID-19. The Human Leukocyte Antigen locus, a master regulator of immunity against infection seems to be crucial in influencing susceptibility and severity of COVID-19 and can be the second genetic gateway. The genes regulating Toll-like receptor and complement pathways and subsequently cytokine storm induced exaggerated inflammatory pathways seem to underlie the severity of COVID-19, and such genes might represent the third genetic gateway. Host-pathogen interaction is a complex event and some additional genes might also contribute to the dynamics of COVID-19. Overall, these three genetic gateways proposed here might be the critical host determinants governing the risk, severity, and outcome of COVID-19. Genetic variations within these gateways could be key in influencing geographical discrepancies of COVID-19.

Keywords: ACE; COVID-19; HLA; SARS-CoV-2; cytokine storm; genetics; immunity.

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Conflict of interest statement

The authors have no conflicts to declare.

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