Do Genes Contribute to Susceptibility to COVID-19? | HBKU
Hamad Bin Khalifa University

Opinion editorial Do Genes Contribute to Susceptibility to COVID-19?

By Omar Albagha

With almost 1 million confirmed cases, COVID-19 has now spread to almost every corner of the world. This infectious disease is caused by a new coronavirus strain known as SARS-CoV-2, which affects the respiratory system leading to severe acute respiratory syndrome (SARS). Common symptoms include a dry cough, sore throat, fever and difficulty breathing. Symptoms vary from person to person, with some showing no or very mild signs of infection whereas others require medical attention. According to the World Health Organization (WHO), approximately 80% of cases are mild, 15% of patients require hospitalization, and 5% need intensive care.  

Data from China and Europe indicates that the most severe cases of COVID-19 occur among patients aged 60 years and older, as well as individuals with underlying medical conditions that reduce their ability to fight the virus. These include diabetes, as well as heart, lung and kidney problems. More recent reports nevertheless point to a growing number of critical cases among younger and relatively healthy patients. 
The reasons why some people develop a more severe form of COVID-19 while others present little-to-no symptoms are still unknown. One answer might lie in our genes. Individuals with certain genetic variations in their DNA might be better protected whereas others succumb to more harmful effects. Indeed, scientists have identified multiple genetic variations associated with the severity of many viral infections, such as influenza, AIDS and the SARS outbreak that originated in China back in 2002.    

It is worth mentioning that viruses are not living organisms but are instead made of a small amount of genetic material (DNA or RNA) protected by a protein coat. These must penetrate living cells to replicate and cause infection to the host organism. Viruses are also selective and usually target certain types of cells. This selectivity in turn depends on their protein coat, which also acts as a key to unlocking specific receptors present on host cells. Once inside, the virus hijacks the normal cell machinery and uses it to make thousands of copies of itself resulting in cell death. The newly formed viruses will then invade more healthy cells and the cycle continues. The extent of damage caused is determined by how efficient our immune system is in fighting and clearing the virus. 

The SARS-CoV-2 virus specifically targets the cells in our lungs, and this selectivity comes from protein spikes on its surface that recognize specific receptors (known as ACE2) present on lung cells. One way our genes contribute to the variability in disease severity is through genetic variations in our DNA. For example, genetic variations can cause changes in the ACE2 receptor making it more difficult for the virus to penetrate cells leading to a mild disease.  However, if changes in the ACE2 receptor allow more viruses to enter the lung cells, it can lead to more severe symptoms. 

Another way our genes can determine the severity of COVID-19 is by controlling how our immune system fights the virus. Many genes are associated with immune response to infection. Variations in these genes can either enhance or reduce our ability to fight viruses. Examples of these genes include the HLA gene complex which are responsible for regulating our immune system. 

As COVID-19 is caused by a newly emerged virus, studies are urgently needed to identify the exact genetic variations that determine clinical outcome. These studies should be conducted on an appropriate number of patients to allow conclusive findings since preliminary data is based on a small number of patients and requires additional confirmation. Additionally, genetic variations are known to vary from one population to another. For example, findings from studies performed in East Asians may not be applicable to European or Middle Eastern populations. Accordingly, there is a need to conduct studies among all population ethnic groups. To address this need, a collaborative study is underway in Qatar that involves researchers from Hamad Bin Khalifa University and Qatar University using infrastructure and genomic data provided by Qatar Genome Project. 

Identification of genetic variations associated with COVID-19 severity could have important clinical applications. They could be used to identify those who might be protected or expected to develop a mild illness from those at risk of developing serious symptoms. Doing so can greatly improve the efficiency of healthcare facilities. Moreover, these findings could facilitate the discovery of treatments by advancing our understanding of how this virus infects our cells and identifying targets for designing new drugs. 

Omar Albagha is a Professor of Genomic and Precision Medicine at the College of Health and Life Sciences (CHLS) at Hamad Bin Khalifa University (HBKU). 

This article is submitted on behalf of the author by the HBKU Communications Directorate. The views expressed are the author’s own and do not necessarily reflect the University’s official stance.

Hamad Bin Khalifa University

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