Friday, October 30

What genetics can tell us about the severity of COVID-19

A fragment of DNA directly responsible for severe forms of COVID-19 that would come straight from Neanderthals. The information is enough to arouse questions, even fascination. How could a segment of a chromosome inherited from a species that has been extinct for thousands of years be so unfavorable to us today?

At the end of September, two genome researchers, Svante Pääbo (Max-Planck Institute for Evolutionary Anthropology, Leipzig) and Hugo Zeberg (Karolinska Institute, Stockholm), published a study in the journal Nature, in which they hypothesize that the severity of certain forms of COVID-19 is explained by being a carrier of a DNA fragment inherited from Neanderthals.

This is very well identified: it is a region of chromosome 3 comprising six genes. This group of genes is found, according to the researchers, in 16% of the European population, 50% of the Asian population, but hardly any in Africa. And it was therefore found by Pääbo and Zeberg in the genome of various Neanderthal fossils.

But before unraveling the mystery of this DNA fragment inherited from Neanderthals, let’s take the time to understand what its effect is on us today. Because before tracing this group of genes to Neanderthals, Svante Pääbo and Hugo Zeberg relied on two studies demonstrating that variants of this region of chromosomes were more present in severe patients with COVID-19. Be careful, being a carrier of this gene does not mean that by having the coronavirus, it will be fatal. Simply that it can be an aggravating factor of the disease.

One virus, different symptoms

What you should know is that genetics can lead to more or less sensitivity to a disease. Researchers know this and, in that sense, this study is further proof. What’s surprising here is mostly how quickly the researchers pinpointed this region of chromosomes.

Anyway, this study tells us that the same virus, or the same viral strain (in this case, SARS-CoV-2) can cause different symptoms in two people with different genetics. “The differences in the expression of an infection in different people can be explained by several factors: age, weight, severity of the virus, or comorbid factors. Once these factors are put aside, one of the hypotheses is that the genome of the infected person presents differences ”, indicates Vincent Pedergnana, CNRS researcher specializing in the genetics of infectious diseases, contacted by The HuffPost. In other words: genetics could explain why young, healthy individuals without any co-morbid factors are affected by severe forms of COVID-19 just like an elderly person, for example.

This is not the first time that scientists have linked part of the genome to the severity of a disease. “We know, for example, that mutations in certain antiviral molecules known as type 3 interferons are associated with a better capacity to eliminate the hepatitis C virus”, notes Lluis Quintana-Murci, professor at the college of France and at the Institut Pasteur.

Other genes involved

Another more recent example concerning the coronavirus. Two articles published in September in the journal Science report the involvement of certain genes in immunity against COVID-19. “These studies show that the deficiency of a certain type of molecules, type 1 interferons, can lead to the development of a more severe form of the infection. Your body has more difficulty managing the infection because the molecules supposed to attack the virus actually prevent the antiviral action of type 1 interferons, ”explains Vincent Pedergnana. But it is not yet clear exactly what causes this reaction.

We therefore understand why genetic research can be essential in the fight against an epidemic such as that of coronavirus. In terms of prevention, first of all. “Knowing that 13, 40 or 60% of the population can be carriers of a mutation responsible for severe forms of a disease makes it possible to set up a stratification of the population to prioritize support and care”, notes Lluis. Quintana-Murci.

But also, then, in terms of medication. “Finding which genetic fragments are linked to a disease allows us to understand how a pathology sets in. And therefore on which proteins we can act with drugs, ”emphasizes Vincent Pedergnana.

Natural selection

Still, a question still arises. How could a fragment of DNA as old as the world have survived the decades, despite natural selection, to be unfavorable to us in the face of an epidemic?

As intriguing as it may be, the link made by the authors of the study published in the journal Nature between our genome and that of the Neanderthals is not new. “About 2-3% of our genome comes from Neanderthals,” says Lluis Quintana-Murci. This means that when our ancestors left Africa, they met Neanderthals which bequeathed to them by hybridization part of their genome.

“We can provide two explanations for the survival of a gene carried by Neanderthals to us,” says Vincent Pedergnana. “The first is that it didn’t bother us, didn’t cause any disease. The second is that it gave us an advantage. ” In both cases, it is natural selection: a species evolves according to what gives it an advantage. To put it roughly, the genes that survive are propitious at some point in evolution. “We are the survivors of the great epidemics of the past, the result of natural selection from the past. Certain genes have, for example, enabled us to adapt to the cold, or to better survive certain viral infections ”, underlines Lluis Quintana-Murci.

“This is where it becomes counterintuitive: this DNA fragment, instead of helping us survive better, is in fact associated with an increased risk of developing a severe form of disease,” continues the researcher. This is the big mystery around this region of chromosomes 3, but more generally around this kind of groups of genes. They’ve probably given us an advantage so far. Or maybe they continue to give us an advantage. But which one?

That is the whole point. Upon discovering this fragment of DNA, scientists found a needle in a haystack. Not only may this be useful to us for something else entirely, but in addition, it is certainly not the only gene involved in COVID-19, as the study of Science. And as Lluis Quintana-Murci points out, the severity of COVID-19 is certainly “caused by lots of genes and not just one, each of them can increase our different susceptibilities”. The research is therefore only just beginning.

This text was originally published on the HuffPost France.

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