2023-05-03 12:44:06
Several months following infection with SARS-CoV-2, some patients still show symptoms. This phenomenon is commonly referred to as “long Covid”. In new work, research teams from Inserm and Université Paris Cité1 in collaboration with theuniversity from Minho to Braga (Portugal), showed that it might be explained biologically by anomalies of the immune system associated with the persistent presence of the virus in the mucous membranes of the body. These results published in the journal Nature Communication might in the longer term pave the way for a diagnostic tool for long-term Covid as explained below, by press release, Inserm…
According to various studies, long Covid affects between 10 and 30% of people infected with SARS-CoV-2, but this condition is still difficult to diagnose and treat. The team of Inserm researcher Jérôme Estaquier, in collaboration with that of Ricardo Silvestre at the University of Minho in Portugal, is carrying out work to explain this phenomenon from a biological point of view. At present, few biological criteria, apart from the persistence of symptoms beyond three months following the acute infection, make it possible to diagnose it. As soon as a patient is not fully recovered following this period, he is classified in the long Covid category. Without a more reliable means of diagnosis, it is difficult to offer appropriate care.
To better understand the long Covid and find diagnostic markers, the researchers studied the immune system of 164 people six months following their infection. They analyzed the blood samples of 127 people, half of whom had a long Covid (fatigue, shortness of breath, cough, muscle or chest pain, anxiety, etc.) and 37 control people who had not been infected. The authors were particularly interested in specific immune cells: T lymphocytes (including CD8 cells) involved in the elimination of the virus and antibodies directed once morest SARS-CoV-2. In addition, they had blood samples taken during the acute phase of the disease from 72 of these patients, which allowed them to retrospectively compare the level of inflammation in the early stage in people who subsequently developed Covid. long or not.
Several immune markers identified
The researchers thus identified a number of blood markers present six months following infection in 70 to 80% of people with long Covid, while these same blood markers were rare in subjects who had not developed a long form. The teams have shown in particular that a CD8 cell subtype expressing granzyme A, an inflammatory protein, is in excess, while another CD8 subtype expressing the b7 integrin is in low quantity. This last subpopulation is however essential to control the viruses in the mucous membranes. In addition, virus-specific IgA antibodies are also in excess, whereas they should be quickly eliminated if the virus is absent. These observations suggest the persistence of the virus in the body and in particular in the mucous membranes.
« The researchers’ hypothesis is that SARS-CoV-2 might hide at the level of the intestinal mucosa because it is more “permissive” on the immune level than the rest of the body, insofar as it must tolerate the bacterial flora. Other viruses like HIV use this escape strategy. Initially present in the lung mucous membranes, SARS-Cov-2 might therefore descend to the intestinal level and persist there without the immune system being able to eliminate it altogether.« .
In the last stage of the study, by evaluating the initial level of inflammation during the acute phase, the scientists observed an association between an inflammatory response characterized in particular by very high levels of interferon IP-10 or interleukin IL-6 and the risk of having a long Covid followingwards.
« This confirms clinical observations according to which the initial severity of Covid is associated with a higher risk of developing a long Covid”, specify the researchers. “One of the hypotheses is that people who present with a more exacerbated immunodeficiency early on develop more serious initial forms of Covid-19 and do not manage to effectively eliminate the virus which passes into the intestinal mucous membranes, where it settles durably. The immune system somehow ends up tolerating it at the cost of persistence of symptoms of varying intensity and nature.“, explains Jérôme Estaquier.
The objective now is to validate these results in new cohorts in order to determine whether some of these markers might serve as a diagnostic tool.
« If an IgA assay remote from the acute phase and possibly CD8 b7 cells made it possible to diagnose a long Covid, doctors might make an objective diagnosis. In a second step, we will be able to think regarding therapeutic targets on the basis of this work.“, concludes Jérôme Estaquier.
1- This work in France was supported by the Foundation for Medical Research, the National Research Agency (ANR) and the ANRS | Emerging infectious diseases.
Photo caption – This transmission electron microscope image shows SARS-CoV-2, isolated from a patient in the United States, emerging from the surface of cells cultured in the laboratory. © National Institute of Allergy and Infectious Diseases-Rocky Mountain Laboratories, NIH. Public domain
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