Covid-19: An immunodeficiency deficiency will explain about a quarter of the extremely rare severe forms of the vaccine. Newsroom

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Electron microscopy of a cell infected by SARS-CoV-2 © Philippe Roingeard, Anne Bull-Maurer, Sonia Georgeault, Inserm unit U1259 MAVIVH & University of Tours, France.

All scientific studies have shown that vaccination against Kovid-19 is effective in preventing severe forms of the disease. However, in very rare cases, patients vaccinated with two doses after SARS CoV-2 infection have been hospitalized. To better understand why, lecturers-researchers at the University of Paris City between Insaram, AP-HP and the Institute Has conceived Some of these patients have done things that highlight the immunological deficiencies. Scientists show that 24% of these individuals contain auto-antibodies that neutralize the action of type 1 interferon, the protein that forms the first immunological barrier against the virus. These results are published In the newspaper Science Immunology.

Since the onset of the Covid-19 epidemic, many researchers have been interested in an important question: How can it be explained that some patients infected with SARS-CoV-2 show no symptoms while others develop pneumonia that can lead to death?

This question has been the subject of rigorous research in an international collaborative framework led by teams from Insarm, the University of Paris site and AP-HP in the laboratory of human genetics for infectious diseases, in two branches: at the Institute. Has conceivedNecker-Enfants Malades Hospital is located at AP-HP and Rockefeller University in New York.

The work that led to the publication specifically shows that severe pneumonia after infection by SARS-CoV-2 is explained by genetic (5% of cases) and immunological (about 14% of cases) that weaken immunity to type I interferon. By

Type 1 interferon

Type 1 interferon (IFN 1) is a group of 17 proteins that are normally produced rapidly by the body’s cells in response to a viral infection and whose main effect is to inhibit virus replication in infected cells. There are different types, divided into different families: Alphas, Beta, Omega, Kappa and Epsilon.

In addition, we are talking about automated antibodies when antibodies attack a person’s own cells in the body.

In some patients with severe forms of Covid-19, autoantibodies directed against type 1 interferon have been found. By neutralizing the action of IFN 1, these automated antibodies therefore prevent the body from better protecting against the virus.

The mRNA vaccines against Covid-19 have been shown to be very effective in preventing serious diseases, especially in reducing the risk of pneumonia, as has been shown in numerous studies. However, it can happen that in very rare cases, some vaccinated people become infected with SARS-CoV-2 and develop a severe form of the disease, which requires hospitalization.

Research teams led by Pr জিনn-Laurent Casanova, co-director of human genetics at the Infectious Diseases Laboratory, and Dr. Laurent Abel, try to better understand this phenomenon, in light of the knowledge gained about the immunological deficiencies associated with the increased risk of severe Covid-19.

IFN-1 autoantibody

In their study, the researchers recruited 48 patients between the ages of 20 and 80 who, despite having a full immunization schedule with an mRNA vaccine, became more severe after delta variant infection.

The first step was to verify whether the vaccine was actually effective in these participants, meaning that the body responded by producing a good level of SARS-CoV-2 antibodies. The idea was thus to exclude and identify other causes, discarding the critical forms that could develop after immunization failure. For various reasons (HIV infection, presence of lymphoma, taking immunosuppressive treatment, etc.), six patients had a defective vaccine response and were therefore excluded from the study.

The scientists then built on their previous work and looked for the presence of anti-interferon type 1 (IFN-1) autoantibodies in the remaining 42 patients. Various tests were performed to measure the levels of anti-IFN-1 autoantibodies and their neutral character.

Analysis of the collected data indicated that 24% of the 42 patients presented were presented with antibodies that were able to neutralize type 1 interferon. In addition to these specialties, these patients had no other immunological deficiencies and no history of serious viral infections.

Interestingly, although these patients developed a severe form of Covid-19, none of them died. However, in the immunized population, 20% of those who die contain type 1 anti-interferon autoantibodies. So we can assume that the vaccine did not succeed in preventing the development of the disease but it did have an effect. Illness.

Examine patients to identify risks

In order to understand the underlying biological processes, deeper molecular studies have finally allowed researchers to identify the subtypes of the corresponding autoantibodies, showing that they are essentially autoantibodies. Anti-alpha 2 and / or anti-omega.

These results, therefore, make it possible to explain why some vaccinated individuals present high levels of antibodies against SARS-CoV-2, even though they may be serious. Although the phenomenon remains very rare, it is important to gain a solid knowledge of the subject in order to adapt to prevention and patient management strategies.

The study authors also recommended testing for the presence of anti-IFN-1 autoantibodies in hospitalized vaccine patients after SARS-CoV-2 infection. They will continue to work on their own to better understand why these anti-IFN-1 autoantibodies are made in specific patients, especially focusing on genetic factors.

Strict communication in the service of science

If this study raises concerns about very rare forms of severe Covid-19 occurring in vaccinated people and therefore only concerns a small number of patients, it seems important to relay these results rigorously and transparently, in favor of the Insaram method. Reliable scientific information so that these results are not misinterpreted or manipulated.

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