Do Genetics play a role in COVID-19 pandemic?

There are some COVID-19 cases where some patients are asymptomatic with others experiencing mild symptoms, similar to the common cold, whereas there is another group of patients, who may even have to fight for their lives.

By now, it is well known that patients with significant comorbidities, are more susceptible to the virus, and may develop much more serious symptoms. Hypertension, diabetes, other cardiovascular risk factors, along with lower respiratory syndromes increase the chances of life- threatening infection. As expected, increasing age increases the probability of the case becoming severe.

Furthermore, it has been observed that there are more deadly cases involving men than women. As a rule of thumb there are twice as many male deaths reported in USA, Western Europe & China vs female deaths. Could this be the first piece of evidence that there are underlying genetic factors triggering differences in response to the virus?

In general, we know that the immune response of women is more effective & aggressive than the respective of men, from infections to building immunity from vaccines. The main reason is that women have two copies of the X chromosomes, while men have one copy. As far as corona viruses are concerned this is quite important. The protein responsible for identifying the virus is encoded on the X chromosome. Therefore, the expression of this protein is doubled in women vs men’s immune cells, thus the response is more rapid and effective in women.

A fundamental law of biology is that genotype x environment = phenotype (G X E= P). Therefore, it could be that some environmental / behavioural choices might affect the results of more men dying from the virus than women. For example, there are more male than female smokers. According to data in China 50%of men are smokers, vs only 5% of women. Smoking can lead to cardiovascular diseases, cancer and other lower respiratory diseases like Chronic Obstructive Pulmonary Disease (COPD). The underlying diseases are found co-responsible inleading COVID-19 infected patients to the ICU, and some of course to eventually succumb.

But let’s focus back on the genetics of COVID-19 patients. Simply enough, some people’s genes make them more susceptible to viral infections, whereas other people’s genes make the individual more resistant. For instance, mutation of the CCR5 gene makes carriers resistant to HIV. In COVID-19’s case, the receptor the virus uses to fuse into the cell is ACE-2. There are a number of mutations of this receptor found in humans, which could play a role in severity of infection. However, there could be an underlying pharmacogenetic component in the above finding as different drugs or doses could be needed to compliment different genotypes.

In addition, it has been observed that some patients, who have chronic inflammatory diseases, show an over drive in their immune response to the pathogen, and release cytokine storms, a deadly immune system inflammatory response. We know that genetics plays a vital role in the development of a person’s immune system. But there is a hereditary component also in hypertension, diabetes, cancer, COPD, & obesity and other diseases associated with COVID-19 severe cases. All these diseases, even obesity, show greater inflammation levels. On the other hand, children have less developed immune systems than adults, where this kind of immune response is rarer, therefore lower mortality rates observed among them.

But apart from the genetics of the patient, what about the genetics of the virus? COVID-19 is part of the Corona Virus family, including well known members like SARS-CoV and MERS-CoV. All three viruses share common ancestry, and have mutated to the point where they are considered as different viruses. However, COVID-19 is a virus infecting millions of people around the globe. The more host cells it infects the higher the probability of it mutating, creating intra-viral mutated strains. Some strains are more deadly than others. This could be a reason of different responses from patients.

To conclude, at the moment we don’t know very much about the virus, the role of genetics, the level of its involvement, and why there is diversity in patient immune responses. It’s a numbers game, and data have to be accumulated in order to better understand the involved mechanisms. Current treatments involve non-patient specific responses in terms of types drugs and doses. Getting down to the molecular level would give us a much better understanding and a bigger variety of treatment alternatives. A whole new chapter has been opened in genetic research.