A light, at the end of the interminable tunnel crossed by the patients most affected by the Covid-19? Dexamethasone, a powerful steroid, is now acclaimed by the WHO, which requests that its production be increased, in order to provide it widely and on a global scale, to the most critical patients. British researchers have been able to prove that this inexpensive drug helps reduce their mortality, making dexamethasone the first treatment to show a marked improvement in the survival of Covid-19 patients, in the midst of a battle of clinical trials .
This hormone, from the steroid and corticosteroid family, was already used upstream of the epidemic, in order to treat several pathologies due to its anti-inflammatory effects and its power against the weakening of the immune system, details with the Parisian Professor Jean-Daniel Lelièvre, head of the infectious diseases department of Mondor hospital, in Créteil. He himself decided to use this molecule to treat patients with Covid-19.
Dexamethasone, which can be taken orally or intravenously, is also widely used in palliative care, especially to relieve pain, or reduce fatigue and nausea. It has several notable advantages: inexpensive, the molecule is already marketed by many manufacturers around the world, so it is quickly and easily available, especially for countries such as Brazil, the United States, Russia or India , who are experiencing an outbreak of severe cases.
A drop in mortality of up to 30%
It is by examining the effects of this molecule that the scientists of the Recovery trial were able to highlight its benefits, compared to more conventional treatments. In their conclusions, a summary of which was published in the journal Nature last week, they report having opposed two categories of populations: on the one hand 2,100 British patients, seriously affected by Covid-19, who received 6 mg of dexamethasone daily for 10 days and on the other 4321 also very ill patients, who did not receive this treatment, but usual care. Among ventilated patients, mortality without dexamethasone reached 41%. The treatment made it possible to lower it by a third. Dexamethasone also reduced the mortality rate for patients on oxygen by 20% (25% without treatment). By cons, "no benefit is seen in patients who do not require respiratory assistance," note the researchers.
"Not revolutionary, but its effects are interesting"
Because of these qualities and long before the Recovery study welcomed its effects, dexamethasone, like other synthetic corticosteroids aimed like it at reducing inflammation of the lungs, were quickly used in hospital patients, recalls the infectious disease specialist Jean-Daniel Lelièvre. Like him, doctors from Parisian, Breton and Grand Est establishments also report using it. Professor Lelièvre sums up: “It is a drug that we know well, that we are used to using. We know that it is not revolutionary, but its effects are interesting. "We used this corticosteroid previously to treat acute respiratory distress syndrome, but the Covid had an identical picture," he says. We also know that in the most severe forms, it can be useful in influencing the immune response. "
Doctor François Goehringer, infectious disease specialist at Nancy's CHRU also used this medication from the end of March, when the first wave of patients had already largely fallen on the Grand Est. Studies are underway in France to compare this use over the past few months with treated patients and control patients from around fifty hospitals. Pending the first conclusions, the specialist remains very careful about its benefits. "It has been used for patients with large, oxygen-dependent inflammations, and some have survived, but others have died. Was it the right strategy? We cannot yet say whether the patient's condition has improved thanks to this, ”he wonders.
"We used empirical criteria"
First, the uses were not all similar. If in Rennes, dexamethasone was rather used for patients already admitted to intensive care, in Nancy, it is the patients who required more than 3 liters of oxygen, much more than those already intubated and ventilated, who mainly benefited from the drug . "We decided on a discussion between heads of unit," recalls Dr. Goehringer. The idea was to prevent the condition of certain patients from getting too carried away and our patients from going to intensive care. We used empirical criteria. "
Each time, however, only the most serious patients were targeted by prescriptions. Indeed, as Tedros Adhanom Ghebreyesus hammered on Monday, the Director General of WHO "Dexamethasone should only be used for patients with Covid-19 in serious or critical condition, under close clinical supervision". "There is no evidence that this drug works for patients with a mild condition or as a preventative, and it could cause harm," he said.
Professor Jean-Daniel Lelièvre abounds: “It should not be used right away, because, at the beginning, we do not know how the patients evolve and the consumption of an anti-inflammatory drug in a person at the initial stage of Covid can prevent let there be a response to the virus. "Unlike antivirals, dexamethasone or other synthetic corticosteroids are therefore reserved for severe cases, not for all patients," insists the specialist.
Adverse effects
Like him, many doctors therefore "played on two counts", with patients, according to their condition during the epidemic. For the patients who were at the initial stage, it was a question of treating them with antiviral treatments, sometimes in the form of clinical trials, such as, the much contested hydroxychloroquine - antimalarial molecule whose antiviral properties were ultimately not proven against coronavirus - or remdesivir. But if the latter drug has shown a certain effectiveness to accelerate the recovery of hospitalized patients, its effect on mortality has not been established. This is where dexamethasone, used by many doctors when patients' conditions deteriorate, comes in to "play on immunosuppression", explains Professor Lelièvre.
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Like many treatments, however, this steroid has unwanted effects and should be administered with caution. In particular, it can facilitate the occurrence of other antibacterial or nosocomial infections. "The latter are the fear of resuscitators, because patients are often intubated and can catch them more easily," said the infectious disease specialist.
