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Long COVID: a deregulated immune response (Inserm)

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Some people have persistent symptoms several months after infection with SARS-CoV-2. This phenomenon, called “post-Covid state” or “long Covid”, is still poorly understood.

Researchers from Inserm (University and University Hospital of Montpellier) have shed light on the possible role of the deregulation of part of the innate immune defence.

In particular, they suggest that the production of “neutrophil extracellular traps”, a first-line defense mechanism against pathogens, could have a role in the persistence of symptoms at six months, in patients who have developed a severe form of COVID-19. .

The results are published in October 2022 in the Journal of medical virology.

Neutrophils are the most abundant class of white blood cells and the first line of defense against viruses and bacteria. When activated, they are particularly capable of producing a defense mechanism called “extracellular traps”. (or NETs, ​​for neutrophil extracellular traps). Composed of DNA fibers, bactericidal enzymes and pro-inflammatory molecules, these extracellular traps contribute to the fight against pathogens, but they can also in some cases trigger excessive inflammation, which is harmful to the body.

In previous work, Alain Thierry and his colleagues had shown that part of the innate immune response is deregulated in people with severe forms of COVID-19. In the latter, the formation of NETs is amplified, which results in multi-organ lesions.

In their new study, the researchers analyzed the biological samples of more than 155 people with COVID-19 in the non-severe acute phase (hospitalized) and severe (placed in intensive care), and who had a post-acute infection assessment. more than six months after discharge from critical care. These samples were compared with those of 122 healthy people.

NETs and persistent autoantibodies in the body

Compared to healthy people, the production of NETs was higher in people infected with SARS-CoV-2 and a greater quantity of autoantibodies called “anti-cardiolipin autoantibodies” was observed. Produced by the immune system, these auto-antibodies are often associated with the abnormal formation of clots in the veins (phlebitis) and in the arteries (arterial thrombosis).

This dysregulated immune response is maintained in people who have long COVID symptoms, six months after hospitalization for a severe form. The amplified and uncontrolled production of NETs six months after infection as well as the persistent presence of auto-antibodies could partly explain the symptoms of long COVID, in particular via the formation of micro-thromboses.

Our results could indicate the persistence of a sustained imbalance of the innate immune response, and a potential prolonged pro-thrombotic activity that could explain the sequelae of acute post-infection or “long COVID”», concludes Alain Thierry. “It is necessary to continue research in order, on the one hand, to confirm this and, on the other hand, to better understand the nature of this phenomenon, which can be serious and long-lasting, in order to improve the therapeutic management of patients”.

Research work is already underway in certain laboratories around the world, to consolidate this data and to explore other avenues.

For more information, see the links below.

Psychomedia with sources: Inserm, Journal of medical virology.
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