Geneticists are trying to draw a map to determine who is most likely to suffer from a severe Covid infection. They have already reached some interesting conclusions.

Covid-19 does not affect men in the same way as it does women, it is suspected that it doesn’t have the same impact on Asians as it does Europeans, and statistics point to differences according to blood group. Geneticist Luis Izquierdo, head of the medical team at Veritas Intercontinental and a genetics consultant for several hospitals, is convinced that hereditary factors are key in understanding why some people go through the disease without symptoms and others end up dying, regardless of age and prior conditions.

QUESTION. Much has been theorised in recent months about genetic risk factors. The same infection that has no symptoms for many people ends up killing others. Has any definite conclusion been reached?

ANSWER. Several studies are being done comparing asymptomatic and severe patients. Obviously, everything in science has to be proven, but in principle there are three types of studies that are trying to determine how a person’s genetics influence their reaction to the coronavirus infection. Firstly, we are detecting predispositions to latent diseases that can be triggered by Covid-19. Secondly, genetic variables that directly intervene in our body’s response to the virus. And thirdly, associations that appear clear in the statistics for now, but we are still unaware of their pathophysiological basis. Broadly speaking, we are making progress in these three fields.

Q: Let’s start with the first group. It is, I believe, about the genetic predisposition to develop a disease that subsequently triggers or accelerates Covid. Is this correct?

A: That’s it, yes. For example, during the first wave we saw that thrombosis episodes were one of the most severe side effects of the infection. We now know that this is because of how the virus infects the blood vessel wall, the endothelium. We also know that 8% of the general population has a series of genetic variants that are predisposed to developing these thromboses.

“We are detecting predispositions to certain effects that can be triggered by Covid and genetic variables involved in the response”

They are at higher risk of getting infected. In this population group, we see how thrombosis is becoming much more aggressive than among those who do not have these genetic factors. All hospitalised Covid patients are anticoagulated, but at the beginning of the infection, this wasn’t being done.

Q: I understand that this can be useful, especially for risk prevention.

A: That’s right. And it can even be used to decide which drugs to administer. I’ll use the example of hydroxychloroquine. It became so famous that Trump was taking it all day. Well, we know that it causes heart rhythm disturbance in some people. If you do not know that a patient has this genetic predisposition and you give them hydroxychloroquine, this can lead to sudden death.

Q: What is the second group of studies?

A: It is based on something we already knew about other viruses: there are genetic variants that make you resistant to the plague, to malaria, even to AIDS. There are genetic variants that are directly related to our body’s response to infection.

In the case of the coronavirus, for example, recent articles have been published on interferon, which, as we understand, is like a medicine generated by the body itself to fight the virus. The information for our body to form this protein is encoded in the genes. And it seems that there are genetic variants that do not produce an efficient interferon to fight this virus, making those people more susceptible to the disease it causes.

Covid-19 – mild or severe? The key is in the genetic inheritance of Neanderthals

Berta Tena

The study, published in ‘Nature’, compares the genetic profiles of approximately 3,200 hospitalised coronavirus patients and almost 900,000 people from the general population. Studies have analysed the reaction of young people with severe disease and it has been proven that in many cases there were a series of genetic variables that determine the::production of interferon.

Q: And the third study group?

A: Well, for example, blood groups. We only have statistical associations, but we do not yet know what determines them. Why are there blood groups that respond worse to the disease? Or regarding biological sex. Why do women suffer less from this disease than men? We are looking for the reasons from a genetic point of view, but there are no firm conclusions.

The main difference between men and women is that women carry reinforced genes because they have a double copy, located on the X chromosome.  The question is whether there is a defect in the response to the virus related to males having only one X chromosome. For example, the ACE protein is on the X chromosome, but there is also no obvious association. In other words, even if the response to Covid depended on the X chromosome, which is something we do not know, it would not be a sufficient explanation to understand why women are less affected than men.

Q: This has to do with how Covid enters our cells, doesn’t it?

A: This is where the ACE protein comes into play. As always, the virus has to bind to receptors on our cells in order to enter cells. And those receptors are genetically determined. If you have fewer or more receptors, you make it harder or easier for the virus cells to enter. That is why it is important.

Q: Iceland has genetic information on its entire population. Are they not using this to combat the virus? Does it make sense to do so?

A: There are still no recommendations regarding this subject. Keep in mind that, within these genetic associations that are being made, populations also come into the picture. Just like a person’s blood group or sex … populations are also relevant. There are populations that are responding worse than others to Covid-19. For example, one study linked certain regions of chromosome three, which are very well preserved from the Neanderthal population, that were mainly in Europe, and these could be the regions that condition the worst response to the coronavirus. Those populations that have most maintained the gene we have in common with Neanderthals may be an additional factor. Ancestral study has been based on this. It seems clear that there are differences between populations, but we do not yet know why.

Q: The virus has also hit Latin America very hard.

A: It has hit them hard in terms of infection, but the mortality rate has not been as high as in Spain or Italy. I have spent a lot of time checking up on them because we have partnerships with several hospitals there. And the fatality rate was much lower than in Europe. It is very difficult to evaluate it because so many things come into play: measures, health systems, etc. But the feeling is that it is hitting Europe harder.

“There are populations that are responding worse than others to Covid-19. It is being studied , but we do not know why yet”

Perhaps those who are dying in Latin America are of Spanish descent. In any case, Europe is the continent most affected and yes, perhaps the reason lies in our genes.

Q: You mentioned before that there are people immune to infectious diseases such as malaria. What other proven examples are there of viral diseases that depend on genetic markers?

A: The plague is a well-studied case . For example, the plague was rampant in the Middle East and most of those who did not have a genetic variant that made them resistant, died. The same has happened with malaria in sub-Saharan Africa, where more people survive because they have a variant in their genes that determines the shape of their more resistant red blood cells. They live longer, have more children and that is why this genetic trait is more widespread there than in other populations where there is no malaria. It has a selective effect . And something similar happens with AIDS: a percentage of the population is resistant because they have a variant in a receptor that prevents HIV from entering their cells. It is no more than 2-3% of the population.

Q: Science fiction plays around a lot with the figure of the immune system and with getting cures or vaccines by studying the body. One of the most successful video games of recent years comes to mind, ‘Last of Us’, whose plot is peppered with that idea. Does it have any scientific basis or is it just fiction?

A: It’s not science fiction. For example, we can create drug as a result of knowledge concerning the genetic variables that make someone resistant to AIDS. You cannot change people’s genes, but you can, for example, administer the protein that those genes encode and that can be an effective treatment.

Q: I suppose the pandemic is to medical science the equivalent of a world war for engineering. So a lot of research and effort is concentrated into such a short space time that there will inevitably be unexpected results, advances that will help us to alleviate or stop the virus, among other things.

A: Without a doubt, a lot is being invested into discovering new drugs, studying immunity, into vaccines … It is a time of need and society has been turned upside down, but there will be rewards. This will not only benefit us in finding a response against Covid-19 but also in fighting other infectious diseases, in the field of vaccines, in genetics, etc. One could, for example, sequence the genomes of thousands of asymptomatic and people with severe cases. As always, every cloud has a silver lining.