Long Covid: these hypotheses that could explain the persistence of symptoms over time

Chronic fatigue, shortness of breath, brain fog… Several months after their infection with Covid-19, millions of people suffer from a “long Covid”, without research having yet been able to precisely explain this phenomenon, even if several assumptions are on the table.

According to the Institute for Health Metrics and Evaluation, based in the United States, 145 million people worldwide suffered from a long Covid in 2020 and 2021. “At least 17 million Europeans”, according to a recent World Health Organization (WHO) estimate.

This would represent between 10 and 20% of people who have been infected with the virus. Fatigue, cough, shortness of breath, intermittent fever, loss of taste or smell, difficulty concentrating, depression… the long Covid is manifested by one or more symptoms from a long list, generally within three months after infection and persisting for at least two months. The syndrome affects twice as many women as men.

“There are no symptoms really specific to long Covid, but they still have certain characteristics: they are fluctuating with fatigue that remains in the background, they seem to be exacerbated after intellectual or physical effort and become rare during course of time”, summarizes Olivier Robineau, infectiologist at the Tourcoing hospital center (northern France) and coordinator on long Covid at the National Agency for Emerging Infectious Diseases.

Viral reservoirs

Many teams are working around the world to understand the causes of these symptoms. In France, for example, the Parisian hospital of the Hôtel-Dieu (AP-HP), the University of Paris and the public medical research institute Inserm launched a study at the end of 2020 on the long Covid within the cohort “ComPaRe” (https://compare.aphp.fr/covid-long/): “2,500 patients are monitored very regularly, which should allow us to understand the variations in the manifestations of the disease over time”, explains the Dr. Viet-Thi Tran, co-investigator of the cohort.

But the variability of symptoms and their non-specific nature makes research difficult. So far, several hypotheses are being studied by scientists.

One of them is the persistence of the virus in the organism in certain individuals. Thus, at the beginning of September, a study published in “Clinical infectious diseases” concluded that the Spike protein (the key allowing SARS-Cov 2 to enter cells, editor’s note) was present in patients with long Covid. This suggests viral replication or the persistence of viral remnants long after the initial infection.

A live virus or remnants of virus could maintain an inflammatory activity, perhaps at the origin of the symptoms. These results are however not found by other teams.

Other avenues exist. The virus would have disappeared after the infection but the initial inflammation, once triggered, would have caused a disruption of the immune system.

Multidisciplinary course

The so-called “tissue damage” hypothesis evokes the role of the initial infectious episode in the appearance of lasting lesions in certain organs.

Studies have further demonstrated damage to blood vessels as a result of the infection.

“For each of these hypotheses, the data is not yet very solid”, affirms Olivier Robineau, betting that “we are not going to find a single cause to explain the long Covid”. “The causes may not be exclusive, they could be associated, even succeed each other in the same individual and be different in different individuals,” he says.

It is therefore difficult to find a solution for these long Covid patients.

At the Hôtel-Dieu in Paris, a protocol known as “CASPER” has been offering patients a course of care for a half-day for a year: “They meet an infectiologist or an internist, a psychiatrist then a doctor specializing in sports rehabilitation” , explains Professor Brigitte Ranque, specialist in internal medicine, at the origin of this circuit.

“In the team’s experience, a majority of the symptoms can be attributed to + functional somatic disorders + (the symptoms result from an imbalance in the functioning of the central nervous system, editor’s note). As a result, a cognitive-behavioral treatment is often associated with supervised physical activity”.

“The patients are called back three months later: the majority of them are better, more than half say they are cured”, explains Professor Ranque. “But about 15% are not improved at all,” she admits.

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