Understanding the Biological Explanation for Long Covid: Abnormalities of the Immune System and the Persistence of SARS-CoV-2 in Mucous Membranes

According to different studies, the long Covid would affect between 10 and 30% of people infected with SARS-CoV-2. However, the diagnosis and treatment of this condition remain complex. The team of Inserm researcher Jérôme Estaquier, in collaboration with that of Ricardo Silvestre from the University of Minho in Portugal, is currently looking into a biological explanation for this phenomenon.

Today, it is difficult to diagnose long Covid, because there are few biological criteria to identify it apart from the persistence of symptoms beyond three months after the acute infection. In the absence of a more reliable means of diagnosis, it is difficult to offer appropriate care.

In order to better understand the long Covid and to identify diagnostic markers, the researchers studied the immune systems of 164 people six months after their infection. They analyzed the blood samples of 127 people, half of whom suffered from long Covid (fatigue, shortness of breath, cough, muscle or chest pain, anxiety, etc.) and 37 people who had not been infected (control group).

The authors were particularly interested in specific immune cells: T lymphocytes (including CD8 cells) which play a role in the elimination of the virus, and antibodies directed against SARS-CoV-2. In addition, they were able to compare the level of inflammation at the early stage in patients who subsequently developed long-term Covid or not, thanks to blood samples taken during the acute phase of the disease in 72 of these patients.

Researchers have discovered several immune markers that can help diagnose long Covid. These markers were found in the blood of 70-80% of people with long Covid, while they were rare in people who did not develop this prolonged form of the disease.

In particular, the teams noted an excess of CD8 cells expressing the inflammatory protein granzyme A, while another subpopulation of CD8 essential for controlling viruses in the mucous membranes, expressing the integrin b7, was in low quantity. In addition, the virus-specific IgA antibodies were in excess, suggesting the persistence of the virus in the organism and in particular in the mucous membranes.

The virus SARS-CoV-2 would remain in the mucous membranes in the intestinal mucosa

Scientists hypothesize that SARS-CoV-2 could hide in the intestinal mucosa due to its immune permeability and persist there without being totally eliminated by the immune system. Other viruses, such as HIV, use this same strategy.

Finally, by assessing the initial level of inflammation during the acute phase, the researchers discovered a association between an inflammatory response and the risk of developing a long Covid. Very high levels of interferon IP-10 or interleukin IL-6 can indeed promote the appearance of long Covid.

« This confirms clinical observations that the initial severity of Covid is associated with a higher risk of developing long Covid. “, explain 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 fail to effectively eliminate the virus which passes into the intestinal mucous membranes, where it settles permanently. The immune system somehow ends up tolerating it at the cost of persistence of symptoms of varying intensity and nature. says Jérôme Estaquier.

The goal now is to confirm these results in new studies to determine if some of these markers could be used as a diagnostic tool for long Covid.

« If an IgA assay remote from the acute phase and possibly CD8 b7 cells made it possible to diagnose a long Covid, doctors could make an objective diagnosis. In a second step, we will be able to think about therapeutic targets on the basis of this work. concludes Jérôme Estaquier.