Volume 34, Issue 7 p. 8787-8795
HYPOTHESIS
Free to Read

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

Monojit Debnath

Corresponding Author

Monojit Debnath

Department of Human Genetics, National Institute of Mental Health and Neurosciences, Bangalore, India

Correspondence

Monojit Debnath, Department of Human Genetics, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bangalore 560029, India.

Email: [email protected]

Search for more papers by this author
Moinak Banerjee

Moinak Banerjee

Human Molecular Genetics Laboratory, Rajiv Gandhi Centre for Biotechnology, Thiruvanathapuram, India

Search for more papers by this author
Michael Berk

Michael Berk

IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Deakin University, Geelong, VIC, Australia

Florey Institute for Neuroscience and Mental Health, Department of Psychiatry and Orygen, The National Centre of Excellence in Youth Mental Health, The University of Melbourne, Melbourne, VIC, Australia

Search for more papers by this author
First published: 11 June 2020
Citations: 77
This article was fast-tracked under a recently instituted interim policy in which editors may, at their discretion, accept coronavirus-related manuscripts submitted for the Review, Perspectives, and Hypotheses categories without additional review.

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.

CONFLICT OF INTEREST

The authors have no conflicts to declare.