Long Covid: “Something seems to happen in the very first moments of infection”

Long Covid Something seems to happen in the very first

He is one of the rare French specialists in long Covid. Suffice it to say, a lover of scientific and medical enigmas and mysteries. While a study published on August 31 in Nature revived hopes diagnosis and treatmentOlivier Robineau, infectious disease specialist at the Tourcoing Hospital Center and coordinator of a study on persistent forms of Covid-19, provides an updated overview of what we know about this disease, which is still largely misunderstood.

L’Express: In Nature, researchers led by Maxime Taquet, psychiatrist at Oxford, have discovered predictive biomarkers for long Covid. Some saw it as a giant step in the wilderness of research on Covid-19. What does this work bring?

Olivier Robineau: The aim of this study was to clarify the origin of the persistence of symptoms of long Covid, in particular neurological disorders, this sort of “cognitive fog” in which many patients are immersed, and which sometimes greatly handicaps them in thinking. Neurological disorders are among the most commonly reported symptoms along with severe fatigue and shortness of breath. The researchers showed the presence at the beginning of the disease of two molecules at levels abnormally high in patients with long Covid. This is a very interesting result.

What molecules did they find?

Fragments of fibrin, a protein involved in healing, and fibrinogen, another protein, produced in the liver, which makes it possible to produce fibrin. These two elements are what are called “biological markers” of inflammation. In other words, they are found in common inflammatory reactions in the body.

Will these markers make it possible to produce a test to identify long Covid?

Alas, not really. This would be a major breakthrough, because today, we still do not have a positive diagnosis of long Covid. We must proceed by elimination. This slows down research because it is more difficult to ensure in trials that people are indeed suffering from long-term Covid and not another chronic illness. But unfortunately, the biological markers found are not specific to long Covid.

Why is the study still important?

It confirms that people who have a very strong initial inflammatory reaction are more likely to develop persistent symptoms and in particular neurological symptoms. We already had avenues and elements in favor of this mechanism. With my team, we had, for example, demonstrated that the persistence of symptoms was linked to the clinical state of the patient in the acute phase, in other words, the strength of their illness at the start. The worse off you are at the start of the illness, the more risk there is. to develop persistent symptoms.

The study clarifies the phenomenon, from a biological point of view, and supports the hypothesis that inflammation plays a role, and not just the virus itself. When you are sick, the body turns into a battlefield. The virus attacks, the body leads a counter-offensive. The damage, the injuries therefore, can come from both camps. Scientists, including myself, will now try to understand what exactly the markers identified do in the body. This could ultimately allow us to move forward towards better prevention and management of long Covid.

If the study finds markers, does that mean that all long-term Covid patients could have these proteins in abnormal proportions?

No, we do not know if these results apply to all long Covid cases. The study concerns people who have been hospitalized, that is to say people who had a very strong inflammatory reaction and required hospital treatment. We are not certain of finding exactly the same biological markers in those who contracted the disease, but whose state of health did not trigger a hospital stay. It is possible that the mechanisms at play are slightly different, because these people do not have such extreme inflammatory reactions.

This question of knowing whether the research results apply to all long-term Covid patients is recurrent, it is one of the main problems that we encounter with this pathology. There is very little data on patients who have not been hospitalized. However, this is the vast majority of cases. Most only did a PCR test, whereas in the hospital, a blood test is frequently carried out, which notably allowed the authors of the study to Nature to know precisely the different levels of molecules in the blood of patients, as soon as they are hospitalized.

Can these results accelerate the search for a cure?

The study can pave the way for progress. But these would above all be treatments to be administered during the acute phase of Covid-19, for prevention, to avoid an overly intense inflammatory reaction. A randomized trial whose results were published in The Lancet Infectious Disease in June 2023 has already shown that metformin, normally used against diabetes, can also reduce the risk of developing persistent symptoms if administered early in the disease. This molecule has immunomodulatory activity, that is to say it modifies the immune reaction, but we do not know exactly how it acts.

What is interesting is the convergence of the avenues: a strong inflammatory reaction, a potential drug to be taken early… Something seems to happen in the very first moments of the infection. Which indicates that management of the initial phase of Covid is very important. Especially since we also see that people who have received certain antiviral drugs develop long Covid less frequently. Prevention is also crucial: we are starting to show that vaccination can reduce the risk of persistent symptoms.

Do you think that one day a drug will be able to cure long Covid?

We are not giving up on the idea. But pills for chronic illnesses are rare. In essence, these are conditions with multiple causes and consequences, which may not disappear with a single molecule. Rehabilitation matters a lot. A molecule will not regenerate the loss of mobility, autonomy, endurance, muscle tissue caused by the symptoms, for example.

I believe that it is still possible to find treatments that will improve the condition of patients. In the meantime, based on our experience in the field, we have the impression that the earlier we treat patients, in a care pathway, the quicker they recover. Through respiratory rehabilitation, for example. To do before exercise rehabilitation! Otherwise, the patient risks being discouraged, hampered by shortness of breath or discomfort. It is important that general practitioners know that these methods exist, to prevent patients from leaving the care pathway, and delaying their treatment, and their chance to get better as quickly as possible.