Understanding the interplay between the virus and the host remains paramount in the battle against COVID-19. A recent systematic review titled “Genetic and Epigenetic Determinants of COVID-19 Susceptibility” (Gasmi et al., 2024), conducted by international researchers, sheds light on the complex genetic and epigenetic factors influencing susceptibility to COVID-19 and its severity.

Researchers affiliated with various institutions and universities in France, Kazakhstan, Luxembourg, Pakistan, Iran, Ukraine, Egypt, Italy, and Norway analyzed data from December 2019 to June 2023. Their study, under the guidance of Dr. Geir Bjørklund from the Council for Nutritional and Environmental Medicine, delved into gender-specific differences in COVID-19 susceptibility and severity.

One significant finding highlighted the critical role of the host’s HLA genotype in regulating immune responses to viral protein antigens, which is pivotal for effective immune surveillance against COVID-19. The review also suggests that genes located on the X chromosome, responsible for immune regulation in females, may contribute to a more robust defense against viral load and inflammation than males. Additionally, individuals with blood type A may exhibit heightened susceptibility to COVID-19 and an increased risk of disease-related mortality.

The study underscores how SARS-CoV-2 can hinder antiviral interferon responses, leading to uncontrolled viral replication and exacerbating disease severity. These findings emphasize the importance of further investigation, particularly regarding gender-related vulnerabilities to infection, and considering comorbidities and immune status in assessing COVID-19 risk.

Dr. Bjørklund remarked, “We anticipate our findings will deepen the understanding of the genetic and epigenetic determinants influencing COVID-19 susceptibility.”

The publication of this systematic review in Current Medicinal Chemistry signifies an advancement in the global fight against COVID-19. It elucidates genetic and epigenetic factors underlying susceptibility to the virus.

While the epidemiology and clinical features of COVID-19 have been widely reported, few studies have explored the role of genetics and epigenetics in its prevalence and severity. The review concludes that while many individuals may be infected with the virus and remain asymptomatic, they can still be carriers. However, the proportion of individuals requiring hospitalization increases with age and comorbidities associated with genetic and epigenetic factors. Factors such as HLA type, AB0 blood group, ACE2 receptor, and interferons were identified as prime factors increasing the disease risk. However, comprehensive studies on the sex-linked affinity of infection are still lacking. A significant proportion of people infected or experiencing severe complications were already immunosuppressed, marking them as a high-risk group.

Prompt and early recognition followed by isolation are crucial measures to decrease cross-infections in high-risk groups and avoid complications. Epigenetic profiling of host tissue may permit the discovery of age- and sex-related potential risk factors for COVID-19, which is critical for developing treatments and vaccines.

Vital Press

Reference

Gasmi A, Kassym L, Menzel A, Anzar W, Dadar M, Semenova Y, Arshad M, Bihunyak T, Meguid NA, Peana M, Bekbergenova Z, Bjørklund G. Genetic and epigenetic determinants of COVID-19 susceptibility: A systematic review. Curr Med Chem 2024. doi: 10.2174/0109298673267890231221100659.