Are You Genetically Susceptible To COVID-19?

Image source: bioworld.com
Image source: bioworld.com

Despite the availability of surmountable amount of knowledge and techniques we, the Homo sapiens are evidently ill-equipped to combat the natural forces of massive destruction such as, one viral pandemic that continues to wreak havoc around the globe, unhindered.

As the SARS-CoV-2 continues to take innumerable lives, medical community worldwide are putting up a brave fight. While the doctors have managed to save millions of lives there is still an increasing number of young and seemingly healthy individuals that have unexpectedly, succumbed to the viral attack. The evident difference in the severity of attack and complications among varied population groups and communities has raised many questions. Researchers now claim that all answers lie within the realm of genetics. Scientists have found a link between the genetic variations of two important human genes, those that play host factors for COVD-19 and vulnerability to the infection.

The Genetic Link

KNOW YOUR VOCAB...

Before we jump headfirst into the sea of genetic research let us all first take a pause and jolt our memory of a certain genetic jargon:

Genetic polymorphism-a gene is said to be polymorphic if there is a presence of variants of the gene, other than those we inherit from our parents, at a defined location on the chromosome

A research conducted by a group of scientists from Lerner Research Institute, USA has found that human genetic factors play a substantial role in contributing to an extremely high rate of transmission of SARS-CoV-2 in specific population groups. These findings can help explains why some regions of the world have brought the attack under control, while others are still struggling with a large number of COVID-19 related deaths. The variation in death and infectivity rate world over is indisputable.

SARS-CoV-2 infection depends majorly upon two host cell factors,

  • Angiotensin-converting enzyme 2 (ACE2) that serves as its entry point and
  • The host transmembrane serine protease TMPRSS2 that is accountable for SARS-CoV-2 spike protein’s conformational changes, which is essential for its entry into human cell.

The research that was published in BMC Medicine investigated genetic susceptibility to COVID-19 by examining DNA polymorphisms in ACE2 and TMPRSS2 genes from three genomic databases with a collective contribution of approximately 81,000 human genomes. They identified “63 potentially deleterious variants in ACE2 and 68 deleterious variants in TMPRSS2”.

The authors found that the frequency of distribution of these variants differed among 9 diverse ethnic population groups, “It was noted that about 39% of variants occurred in African/African-American population and about 54% of them were seen in Non-Finnish European (EUR) populations. Similarly, 35% of deleterious variants in TMPRSS2 coding regions are carried by the AFR and 59% by EUR populations”, they stated.

Applicability of the Study

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The researchers have resolved the mystery shrouding the significant difference in incidence and mortality rates between male and female COVID-19 patients. ACE2 is an X-linked gene, with a strong variant that shows an inclination for X-linked dominant inheritance, specifically in severely affected patients. It might be an answer to the higher prevalence and severity of COVID-19 in men than in women.

Interestingly, they also noted that because TMPRSS2 is located on the 21st chromosome, we could speculate that individuals with Down syndrome would be at high risk for COVID-19 infection.

Finally, the group of researchers have found, “unique but prevalent polymorphisms in TMPRSS2 that offer potential explanations for differential genetic susceptibility to COVID-19 as well as for risk factors” they concluded.

This study has implicated that polymorphism associated with ACE-2 and TMPRSS2 genes are likely associated with genetic vulnerability to COVID-19. Understanding each individual’s genetic makeup is henceforth fundamental to determine the susceptibility and severity of clinical outcomes in the case of COVID-19. This horizon if further explored, could guide personalised and targeted treatment strategies in the face of pandemic and even explain current epidemiologic observations.

The research also calls for a human genetics initiative for fighting the COVID-19 pandemic and come up with a more effective and efficient protocol to determine prognostic and preventive procedures.

We must apprehend that it is an all hands on deck situation to recognize the virus’s structure, its mode of action and its target, in a bid to win this war and minimise the casualty index.

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Author:

Dr. Vidushi Khanna

Dental Intern

Student Coordinator, IACDG

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