What have we learned about long-lasting COVID?

While the contagious Omicron variant has already infected millions of people, many fear an increase in cases of long-lasting COVID, this condition with various extremely disabling symptoms which persist for months after the acute infection.

Discouraged by the little or no improvement in their state of health more than 14 months after their infection, people with this post-COVID-19 syndrome oscillate between the despair of seeing themselves disabled for the rest of their days and the hope that the research suggests. This has indeed progressed and various hypotheses have been proposed to explain this disease which affects 10 to 20% of people who are infected with SARS-CoV-2, including children.

Sixteen months after contracting COVID-19, Violaine Cousineau is still severely disabled. She still has great difficulty climbing stairs and performing cognitive tasks, such as reading a book. However, she claims to be able to speak more easily than when our report from April 17, but the improvements occur “so slowly that they are barely perceptible”. Her participation in the TELEPORT research project in rehabilitation, led by scientist Simon Décary, allowed her to recover part of her respiratory capacity and helped her regulate her activities in order to avoid relapses.

For her part, Sophie Alix has not seen any significant improvements since her initial infection in March 2020. But she was struck down by the Omicron variant in January: her chronic leg pain was exacerbated, her lack of physical strength now bedridden, her shortness of breath makes her unable to take steps. His great fatigue prevents him from carrying out any activity requiring a certain concentration.

Family doctor Anne Bhéreur, who contracted COVID-19 in December 2020, has seen some of her symptoms improve since last year. An ENT specialist diagnosed him with spasmodic abductor dysphonia, which prevented him from speaking normally. She is now being injected with botox into her vocal cords to prevent the spasm that leaves her vocal cords open when they should be closed. Her concentration has also improved, but she has to perform all tasks, cognitive or physical, in small doses. “I learned above all that I must not exceed my threshold [d’énergie]otherwise I relapse and my symptoms reappear”, specifies the DD Bhéreur, who is involved in four research projects, including the SCOPIMED project of Dr Alain Moreau, from CHU Sainte-Justine, which aims to screen for post-exercise discomfort in people with long-term COVID.

Mme Bhéreur also follows physiotherapy adapted to post-exercise discomfort, which results in a relapse a few hours to 72 hours after an activity that has exceeded the person’s energy capacities, as part of the TELEPORT project.

She also enlisted in the IMPACT COVID project of the DD Thao Huynh, cardiologist at the Research Institute of the MUHC, who is interested in the cardiovascular sequelae of COVID-19. A magnetic resonance imaging of the heart of the DD Bhéreur then discovered that she still had heart inflammation nine months after her infection with COVID-19. “All the electrocardiograms, blood tests and cardiac ultrasounds that I had had so far had however turned out to be normal. This shows that we are not looking with the right means, ”points out the DD Bhéreur who, since this diagnosis, has been treated with colchicine, which has greatly reduced his chest pain and shortness of breath on exertion.

Hidden viruses and microclots

Currently, various hypotheses are put forward to explain the mechanisms behind the symptoms of long-lasting COVID. According to a first hypothesis, COVID-19 viruses persist in hidden sites of the body and promote generalized inflammation. In support of this hypothesis, publications have reported the presence of viruses or virus particles in various tissues of patients with long-lasting COVID, including fatty tissue, intestine, lymph nodes and brain. Researchers have also noted in these people elevated amounts of certain proteins and cells of the immune system that are normally present only during a viral infection, acute or chronic.

This hypothesis would explain why some patients see their condition improve following their vaccination, which would help to eliminate these hidden viruses.

According to a second hypothesis, patients would develop autoimmunity, that is to say that their immune system would react to their own cells or to certain proteins that their body manufactures. Yale University immunologist Akiko Iwasaki’s team had already noticed the presence of autoantibodies during the acute phase of COVID-19 in some patients. She is now applying herself to verifying whether these autoantibodies have persisted in these same patients who have developed long-lasting COVID. These autoantibodies can appear because of a molecular resemblance between the spike protein of the virus and a protein in the patient’s body, or simply because the antibodies directed against the virus are mistaken in their target and attack a molecule of the self, explains M.me Awasaki.

Another possibility is that acute COVID-19 induces an immune disruption that contributes to the reactivation of another pathogen that has remained latent in the person. In the magazine Cellresearcher Yapeng Su rightly mentions the presence of the Epstein-Barr virus, which causes mononucleosis, in the blood of patients among the factors that would predispose to long-term COVID.

Scientist Resia Pretorius, from Stellenbosch University in South Africa, has detected microclots in the blood of patients suffering from long-lasting COVID. These microclots, which are difficult to detect with the methods used in the clinic, would be present in the small vessels where they could compromise the oxygenation of certain organs and tissues.

The DD Emilia Liana Falcone, who directs the Post-COVID-19 Research Clinic at the Montreal Clinical Research Institute (IRCM), is exploring the hypothesis that people who have contracted SARS-CoV-2 have a disturbance of the microbiota of their intestine which would decrease the tightness of the intestinal barrier. “If we find that patients who present with exuberant inflammation associated with covid symptoms also have an abnormal microbiota, we could rectify their microbiota, and thus improve or decrease the state of inflammation”, she specifies.

These different mechanisms are not exclusive, they can occur concomitantly or in sequence, during different stages of the disease, says M.me Awasaki.

Although long-lasting COVID occurs more frequently in people who have had a severe infection, it can also develop in individuals who have had a moderate to mild infection that did not require hospitalization. Because of this, scientists believe that while the Omicron variant causes less severe infections on average, it too could cause long-lasting COVIDs. But the fact that a good part of the population has been vaccinated could mitigate their number, since a few studies published recently suggest that two doses of the vaccine decrease the risk of developing this post-COVID syndrome.

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