Genetic gateways to COVID-19 infection: Implications for risk, severity, and outcomes
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 authorMoinak Banerjee
Human Molecular Genetics Laboratory, Rajiv Gandhi Centre for Biotechnology, Thiruvanathapuram, India
Search for more papers by this authorMichael 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 authorCorresponding 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 authorMoinak Banerjee
Human Molecular Genetics Laboratory, Rajiv Gandhi Centre for Biotechnology, Thiruvanathapuram, India
Search for more papers by this authorMichael 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 authorAbstract
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.
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