The Role of Genes in the Severity of COVID-19

The Role of Genes in the Severity of COVID-19 Symptoms

The new strain of coronavirus known as SARS-CoV-2 or COVID-19 is a highly contagious yet highly selective respiratory virus that continues to puzzle researchers and medical professionals. At first, it seemed as though only the elderly and those with underlying health conditions were at risk of developing severe symptoms and dying from the virus — but more recent events have proved otherwise. We are hearing more cases every day of young and healthy individuals falling seriously ill and passing away due to COVID-19.

Why is there so much variation in peoples’ immune response to this pathogen? This mystery has spurred researchers into action. Scientists all over the world are teaming up to share their data and search the genomes of the infected for variant DNA that could provide insight into COVID-19 risk. This article outlines findings from this early research and what it could mean for the future.

Past Viruses Have Set a Precedent for Genetic Susceptibility Studies

We’re fortunate to live in a time in which we have data from prior outbreaks to set a precedent for COVID-19 research. Recently, for example, a research team from the Medical University of Wroclaw in Poland found that their theory of genetic susceptibility to COVID-19 is consistent with findings from past studies on the connection of genes to other viruses.

In this team’s prior gene association analysis research, they found a clear-cut relationship between genetic variation and infection risk with viruses like dengue, HIV, HCV, HBV, and more. Specifically, in a gene study on HIV, they found that mutations in a gene responsible for encoding the CCR5 receptor protein on the surface of white blood cells can make people less likely to contract HIV in the first place.

Another researcher — a doctor from the Medical University of Bialystok — also discovered variations in the angiotensin-converting enzyme 2 (ACE2) gene, which made people more susceptible to the last coronavirus outbreak (SARS-CoV) in 2002.

Possible Culprits for Genetic Susceptibility to COVID-19

Ongoing research projects across the world are comparing the DNA of patients with severe cases of novel coronavirus to the DNA of those with mild and asymptomatic cases. A couple of theories have arisen from the results of this research, and they agree that the answer may be found in the aforementioned gene that instructs our bodies to create the ACE2 receptor that COVID-19 needs to enter our cells. Another theory originating from China says that our blood type may protect us from this virus or increase our risk. These suspicions are explained in greater detail below.

ACE2 Gene

The ACE2 gene may be able to explain why young and healthy people can become so sick from a virus that only causes mild symptoms in others. This gene codes for the ACE2 protein that resides on the outside surface of cells and determines how easily the virus can enter target cells in the lungs, small intestines, and more. This is why many believe the ACE2 gene could make a person more susceptible to the virus and increase a person’s risk of severe COVID-19 symptoms.

Perhaps this theory is widely accepted because, in the past, studies confirmed that mutations of CCR5, a different protein on our cell surfaces, behave similarly to ACE2 mutations and reduce a person’s chances of contracting HIV. SARS-CoV and other activated virus proteins have behaved like this in the past as well, binding to the receptor encoded by the ACE2 gene and causing infection. Down the road, we could potentially see angiotensin receptor blockers as a possible treatment for COVID-19 if this theory holds.

Leukocyte Antigen Gene Variants

In response to a finding in China suggesting that those with type-O blood may be immune to COVID-19, researchers have also been exploring the variants in peoples’ leukocyte antigen genes to see if variants in these immune-supporting genes have an effect on the severity of coronavirus symptoms.

The China-based researchers who conducted the original studies tested the blood of 2,173 infected patients in three different hospitals in Shenzhen and Wuhan — the origin of the novel coronavirus outbreak. They noticed that those who had more severe symptoms had lower white blood cell counts and acknowledged that lymphocyte presence could be a major contributor to COVID-19 susceptibility.

The same study also showed that those with type-O blood had a consistently lower risk of serious coronavirus infection, while those with type-A blood had much higher infection rates and more severe symptoms.

Areas for Further Research

The genes involved in our immune system response are some of the most diverse in our genome, pointing to our evolutionary advantage of a varied immune response to a huge range of pathogens. We still have much to learn about the newest strain of coronavirus, and with COVID-19 research being still in its infancy, along with so many viable possibilities, it is difficult to conclude whether we could predict someone’s chances of having severe coronavirus symptoms based on their genes. There could be hundreds of genes involved in the immune response, or could be that just the genes responsible for the construction of our respiratory tract or lung function make us more susceptible to the symptoms.

In order to get the conclusive answers about the genes that increase a person’s risk, DNA sequencing is our best bet. Those confirmed with coronavirus must have their genomes sequenced and compared to others. After obtaining only a few thousand genomes from those with both severe and mild symptoms, we could compare them and quickly discover the extent to which our genes are responsible for our immune response to COVID-19.

Geneticists including Alessandra Renieri from the University of Siena share the belief that genetic variation of coronavirus hosts are a major contributor to our susceptibility to severe acute pneumonia. That’s why they are calling for more hospitals to approve DNA sample collections from volunteer patients.

What COVID-19 DNA Sequencing Could Mean for the Future

Armed with such data, geneticists could make more accurate predictions about who is the most at risk, and physicians could then advise high-risk individuals on the best ways to protect themselves. In the race for a COVID-19 cure, this simple genetic knowledge could potentially help the healthcare industry save many lives during this pandemic — even before a vaccine exists.

Join a united effort by teaming up with Psomagen today to work with leading industry experts on your COVID-19 DNA sequencing studies.