Genetic and Epigenetic Determinants of COVID-19 Susceptibility: A Systematic Review

Gasmi A. Kassym L. Menzel A. Anzar W. Dadar M. Semenova Y. Arshad M. Bihunyak T. Abdel Meguid N. Peana M. Bekbergenova Z. Bjørklund G.
2025 Bentham Science Publishers

Current Medicinal Chemistry
2025 #32 Issue 4 753 - 770 pp.

Background: The molecular mechanisms regulating coronavirus pathogenesis are complex, including virus-host interactions associated with replication and innate immune control. However, some genetic and epigenetic conditions associated with comorbidities increase the risk of hospitalization and can prove fatal in infected patients. This systematic review will provide insight into host genetic and epigenetic factors that interfere with COVID-19 expression in light of available evidence. Methods: This study conducted a systematic review to examine the genetic and epigenetic susceptibility to COVID-19 using a comprehensive approach. Through systematic searches and applying relevant keywords across prominent online databases, including Scopus, PubMed, Web of Science, and Science Direct, we compiled all pertinent papers and reports published in English between December 2019 and June 2023. Results: The findings reveal that the hosts HLA genotype plays a substantial role in determining how viral protein antigens are showcased and the subsequent immune system reaction to these antigens. Within females, genes responsible for immune system regulation are found on the X chromosome, resulting in reduced viral load and inflammation levels when contrasted with males. Possessing blood group A may contribute to an increased susceptibility to contracting COVID-19 as well as a heightened risk of mortality associated with the disease. The capacity of SARS-CoV-2 involves inhibiting the antiviral interferon (IFN) reactions, resulting in uncontrolled viral multiplication. Conclusion: There is a notable absence of research into the gender-related predisposition to infection, necessitating a thorough examination. According to the available literature, a significant portion of individuals affected by the ailment or displaying severe ramifications already had suppressed immune systems, categorizing them as a group with elevated risk.

comorbidities , COVID-19 , epigenetic , genetic , molecular mechanisms , Novel coronavirus

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Department of Research, Société Francophone de Nutrithérapie et de Nutrigénétique Appliquée, Villeurbanne, France
Department of Research, Astana Medical University, Astana, Kazakhstan
Department of Research, Laboratoires Réunis, Junglinster, Luxembourg
Department of Research, Dow University of Health Sciences, Karachi, Pakistan
Department of Research, CONEM Iran Microbiology Research Group, Tehran, Iran
Department of Research, Nazarbayev University School of Medicine, Astana, Kazakhstan
Department of Research, National University of Sciences and Technology, Islamabad, Pakistan
Department of Research, I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine
Research on Children with Special Needs Department, National Research Centre, Giza, Egypt
CONEM Egypt Child Brain Research Group, National Research Center, Giza, Egypt
Department of Chemical, Physical, Mathematical and Natural Sciences, University of Sassari, Sassari, Italy
Department of Research, Council for Nutritional and Environmental Medicine (CONEM), Mo i Rana, Norway

Department of Research
Department of Research
Department of Research
Department of Research
Department of Research
Department of Research
Department of Research
Department of Research
Research on Children with Special Needs Department
CONEM Egypt Child Brain Research Group
Department of Chemical
Department of Research

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