"This is a major step forward , " promise the promoters of the British Recovery trial. "As a doctor, I like having published results ..." , nuance immediately to Le Figaro, Professor Yves Le Tulzo, head of the department of intensive medicine and resuscitation at the University Hospital of Rennes. After so many others, the very serious researchers at the University of Oxford therefore use, in their turn, a recipe that has only been used too much since the beginning of the Covid-19 epidemic: thundering announcements , but partial, and the promise of the forthcoming publication of complete data in a peer-reviewed journal.
Let's start with the results released on Tuesday. "Dexamethasone is the first drug which has been observed to improve survival in cases of Covid-19," said a press release. Some 2,104 hospital patients received a low dose (6 mg) of this corticosteroid for ten days. Their fate was then compared to that of 4,321 patients receiving usual care. The molecule would have reduced mortality by a third in intubated patients and a fifth in those simply placed on oxygen therapy. "According to these results, one death is avoided every 8 ventilated patients treated, and 1 every 25 patients treated with oxygen. Good news, it seems, moreover with an inexpensive and available drug.
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Many questions remain unanswered, however. First, the mortality in the control group is very high: 41% in intubated patients, 25% in those on oxygen. "In what structures were they broken down, and were they in the same groups as the group treated?" wonders Yves Le Tulzo. Before concluding, it will be necessary to verify that the patients were comparable in terms of severity and care received ... " The effectiveness of a drug is more" visible "when the basic mortality is high, and " in most trials positive, there is a very high overall mortality compared to what clinicians know in their service ” , notes Pr François Stephan, of the adult resuscitation service at Marie-Lannelongue hospital (Paris-Saint-Joseph group).
Beware of self-medication
The concept remains nevertheless "interesting" , judges Professor Stephan, who himself launched a study with this same drug (currently stalled for lack of a sufficient number of patients, the epidemic is regressing). "Corticosteroids have two types of properties ," explains Professor Nicolas Picard, pharmacologist at the University of Limoges. On the one hand, they are anti-inflammatory drugs ” ; this is the effect sought in this context, serious patients suffering from very significant inflammation of the lungs. "Besides, in high doses they are immunosuppressive." A risk when the patient still has a strong viral load, but not at the very low doses used in the Recovery trial, judges the pharmacologist.
The use of corticosteroids in acute respiratory distress syndromes (ARDS) is not new. In a notice of March 23, the High Council for Public Health mentioned the possibility of “corticotherapy with methylprednisolone or dexamethasone to be discussed on a case-by-case basis” in Covid-19 patients with “secondary aggravation and absence of viral excretion” . "We have been trying to modulate the inflammatory response with corticosteroids in ARDS for over 40 years , " says Professor Stephan. Since then, studies have followed one another and are… inconclusive; some have even observed an increase in mortality. A recently published article in the Lancet Respiratory Medicinein a study conducted in Spain with 277 patients suffering from ARDS (including 139 treated with dexamethasone) found a decrease in mortality (-15.3%) and a decrease in the number of days on a ventilator (-4.8 days ) in the treated group, at higher doses than in the Recovery trial. The study, however, suffered from several weaknesses and did not call for "a change in routine clinical practices , " said the authors of an editorial accompanying the publication.
Conclusion of Pr Yves Le Tulzo: "There may be a window of opportunity for dexamethasone for some patients, when the viral load is low and the inflammation persists." We will have to wait for the publication of the detailed results to really judge. In the meantime, one certainty: beware of self-medication with these very easy-to-access molecules. There is no reason to hope that it will be effective in preventing or following a non-serious infection; and their immunosuppressive properties may even make them the worst enemies of patients, preventing their body from fighting the growth of the virus…
