Covid-19: a quarter of severe forms due to a genetic or immune problem

In the fall of 2020, one in seven patients in intensive care for Covid-19 had developed a severe form due to a poor specific immune response.

After months of in-depth work, this share has been revised upwards: the problem is actually at the origin of a quarter of the number of patients with the coronavirus in intensive care, according to two studies published on Thursday, August 19 in Science Immunology.

A deficit of interferons for the immune response

We have had the time to develop a little more sophisticated methods, with more sensitive tests. “, Recognizes Doctor Laurent Abel, of the” human genetics of infectious diseases “team at the Imagine Institute and co-author of the studies. Of the 25% of serious forms concerned, 5% would be due to genetic defects, and the rest to a particular autoimmune reaction, where antibodies produced by the body “attack” proteins of the immune system, type interferons. I.

When a person is infected with Covid-19, or another virus, their cells produce interferons, proteins that act as early “whistleblowers”. They signal the mobilization of the immune system to defend itself against the arrival of the virus and alert neighboring cells. But in one in four patients in intensive care, these interferons are insufficient, whether they are produced little for genetic reasons or else neutralized by the autoimmune reaction. The resistance is organized less well, if at all.

Problems of genetic origin

A new gene involved in the production of interferons has been identified on the X chromosome, begins Laurent Abel. In some men, mutations in this gene cause loss of function. And since men only have one X chromosome, there is no redundancy to compensate for this loss. Which would partly explain why more men than women do severe forms.

Genetics could also explain the origin of the autoantibodies that attack interferons, although researchers have no conclusive evidence yet. ” Many autoimmune diseases have a genetic origin, but here the presence of these autoantibodies increases with age. », Observes the specialist. According to their study, only 0.3% of people under 65 have these autoantibodies, against 4% of over 70s, and up to 7% of over 80s. ” This increase with age, which also corresponds to the increased risk of severe forms of Covid-19, may perhaps point to genetic abnormalities that occur throughout life. All this remains to be proven », Recognizes Laurent Abel.

Tests to identify people at risk

In all cases, predisposition tests can be considered, to find out if a person has autoantibodies against interferons and is therefore at risk of a severe form of Covid-19, particularly after 65 years. The researchers have also entered into a partnership with the specialist Cerba HealthCare to develop these tests in the coming months.

→ ANALYSIS. Covid-19: monoclonal antibodies authorized for the immunocompromised

In addition to an essential vaccination in these people, the idea would then be to monitor them to act very quickly in case of infection by Sras-CoV-2, by injecting them with another type of interferons that would help the immune response. . Such treatment must take place within two days after infection at most to be useful, which is not without raising issues of logistics and management.


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