Covid: research progresses, we now know why patients vaccinated with two doses have developed severe forms of the disease

Since the start of the Covid-19 pandemic, many researchers have been interested in a crucial question: how to explain that some patients infected with SARS-CoV-2 have no symptoms while others develop pneumonia that can lead to death? In a new study, Inserm analyzed the rare severe forms observed in those vaccinated, another important issue in the pandemic.

While all scientific studies have shown that vaccination against Covid-19 was effective in preventing severe forms of the disease, the fact is that not all people actually reacted in the same way. Because some vaccinated people infected with SARS-CoV-2 have developed severe forms of the disease, requiring hospitalization.

What are type 1 interferons?

Type 1 interferons (IFN 1) are a group of 17 proteins that are usually produced rapidly by cells in the body in response to a viral infection and whose main effect is to inhibit the replication of the virus in infected cells. There are several types, divided into several families: alphas, beta, omega, kappa and epsilon.

In some patients with severe forms of Covid-19, autoantibodies directed against type 1 interferons have been found. By neutralizing the action of IFN 1, these autoantibodies prevent the body from defending itself well against the virus.

The cases are very rare but are subject to very specific monitoring by the Inserm (National Institute of Health and Medical Research). The challenge is to understand why patients vaccinated with two doses were hospitalized after SARS CoV-2 infection.

A fundamental issue in understanding the vaccination process on which researchers from Inserm, AP-HP and teacher-researchers from the University of the Cité de Paris within the Imagine Institute have carried out work that reveals an immunological deficit in some of the these patients.

Research teams led by Pr Jean-Laurent Casanova and Dr. Laurent Abel, co-directors of the Human Genetics of Infectious Diseases Laboratory, have sought to better understand this phenomenon. In their study, they recruited 48 patients aged 20 to 80 years who had severe to critical illness after delta variant infection, despite a full vaccination schedule with an mRNA vaccine.

In the end, the scientists show that 24% of the individuals followed in this study have autoantibodies that neutralize the action of type 1 interferons., proteins that constitute the first immunological barrier against viruses. These results are published in the journal Science Immunology.

It is therefore an immunological deficiency in some of these patients that would explain the appearance of severe forms even after two doses of the vaccine, according to the Inserm press release.

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