The medical and scientific community has worked tirelessly since the commencement of the COVID-19 pandemic to unravel the mysteries of this virus and the human body’s reaction to it. The spectrum of presentation is wide and highly variable ranging from asymptomatic to having symptoms of the common cold to more severe indications such as bronchitis, severe acute respiratory distress syndrome (ARDS), multi-organ failure, and even death. One piece of the puzzle that is still being explored is the relationship between COVID-19 and genetics.

It is understood that individuals with higher risk factors or comorbidities are more likely to be on the severe end of the spectrum and that younger individuals with no known underlying conditions are more likely to be on the milder end or the asymptomatic end of the spectrum. Despite this intel, the harsh reality is that we are unable to predict how an individual’s body will react to this virus and what their symptoms will be.

While we are far from solving this puzzle, some light has been shed on the undeniable role played by genetics in the interaction and response of the human body to the COVID-19 virus or any infection for this matter. The observed variability, such as individuals with no known comorbidities having a severe presentation to COVID-19, is potentially owed, at least in part, to the knowns and unknowns of genetics.

Genetic Factors of COVID-19

A multitude of factors play a role in how a person’s body contracts the COVID-19 virus and responds to it. Multifactorial inheritance – the interplay of environment and genetics in the presentation of disease – is very complex and the role of genetics is significant because it defines the foundation of each bodily function and in turn contributes to every physical interaction and reaction.

Let us start with some examples of factors affecting susceptibility. Patients with COPD have been found to have a 4 times higher risk of contracting COVID-19 compared to individuals without COPD. A study identified the angiotensin‐converting enzyme 2 (ACE2) as the receptor for the SARS-CoV-2 virus and that having a higher ACE2 level is associated with being more susceptible to getting infected. Men (compared to women) and individuals of Asian ancestry (compared to those of Caucasian and African ancestries) were found to have higher ACE2 levels and these groups, particularly Asian males, were concluded as being more susceptible to getting infected.

Numerous factors further shape the body’s response to this infection including our immune system, any underlying comorbidity, and other miscellaneous factors.

COVID-19 Immune Response

A maladapted immune response profile has been associated with severe COVID-19 and poor clinical outcomes. There are numerous genetic conditions, called the inborn errors in immunity, that predispose individuals to infections, some of them causing susceptibility to all pathogens. There are also single gene mutations that have been associated with susceptibility to a single pathogen and this would not come to light until and unless the person is exposed to this particular pathogen and has the appropriate genetic testing. A recent study has identified loss of function variants in the TLR7 gene in 4 young male patients, with no history of major chronic disease, with severe COVID-19.

Individuals with an underlying condition such as diabetes, hypertension, heart disease, increased age, an underlying lung disease, etc. are more likely to develop a more severe course and progression of the disease. Majority of these involved factors others mentioned previously such as the immune response, COPD, etc. are complex in their etiologies and present as a culmination of genes and the environment.

A great example of other miscellaneous factors contributing to disease severity is one’s blood group – it has been seen that people with blood group A have a significantly higher risk of SARS‐CoV‐2 infection, whereas people with blood group O have a significantly lower risk of SARS‐CoV‐2 infection.


How Genetics Can Help in the Fight Against COVID-19

Genetics is not black and white but 50,000 shades of grey in between. While some underlying genetic risk factors are more obvious and can be traced to a single mutation, such as having Alpha-1 Antitrypsin Deficiency in which individuals have a lung disease or severe combined immunodeficiency (SCID) which causes a defect in the immune system, most are not so apparent. . The genetic contribution is often spread across the genome in the form of single nucleotide polymorphisms (SNPs). Hence, genetics frequently plays a more subtle role in terms of predisposing individuals to different factors and in turn predisposing them to a COVID-19 infection – but the factors involved are so many that the cumulative contribution of genetics cannot be ignored. More large-scale studies such as the COVID Human Genetic Effort are needed to understand the influence of genetics in infectious diseases.

As the understanding of genetics progresses, the understanding of the human response to infections will be better understood, possibly accompanied by far reaching implications.

Genetic counselors play a pivotal role in bridging the gap between the scientific community and the layman. As the role of genetics becomes better understood, it can be anticipated that genetic counselors will become a more crucial part of patient care for infectious diseases.


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