Brazil is generalizing its use, Donald Trump takes it every day: what do we know about the very controversial hydroxychloroquine – derived from the antimalarial chloroquine – currently tested in several countries against Covid-19?
What is that?
Chloroquine has been prescribed for several decades against malaria, a parasite carried by the mosquito. Its better tolerated derivative, hydroxychloroquine (HCQ), known in France as Plaquénil, is prescribed for lupus or rheumatoid arthritis.
Most often, the HCQ is tested against the Covid-19. Because chloroquine and hydroxychloroquine are well-known and inexpensive molecules, they have raised a lot of hope, especially in Africa. But they are far, far from being the only ones to be tested: more than 800 clinical trials seek to assess dozens of potential treatments, according to the medical journal The Lancet.
Hydroxychloroquine has known unprecedented fame since the end of February since Professor Didier Raoult, from the Institut hospitalo-universitaire (IHU) Méditerranée-Infection, relayed a small, little detailed Chinese study, claiming that chloroquine phosphate was showing signs efficacy in patients with SARS-CoV2.
The excitement around hydroxychloroquine then knew a revival when the American president Donald Trump made himself the apostle, to the point of taking it himself daily as a preventive measure, as he announced Tuesday . In Brazil, President Jair Bolsonaro is convinced of its effects, yet unproven, to the point that the Ministry of Health on Wednesday recommended its use for all patients slightly affected by the disease.
Going far beyond the political realm, hydroxychloroquine has become a subject of much publicized public and political debate, sparking heated discussions in the family and in the media, and fierce outbursts on social networks, particularly in France.
Does hydroxychloroquine work against Covid-19?
That’s the whole question. The hypothesis of an action of these molecules against the new coronavirus comes from the fact that their antiviral properties have shown in vitro or on animals and on different viruses, sometimes positive results. Studies have also shown in vitro effects on SARS-Cov2 but in many cases scientific results in vitro are not found in vivo in humans.
As for efficacy on humans against SARS-Cov2, there is no scientific consensus, due to the lack of sufficient experience and studies which are carried out according to the usual rules which must guarantee: randomization (patients chosen by lot), “control group” (patients receive treatment, others do not), “double-blind” (patients and doctors do not know who took the treatment and who received the placebo).
Most of these studies are, moreover, conducted with a limited number of patients. Finally, a study must be published in a scientific journal after critical review and validation by other scientists, independent of those who conducted the tests. To date, there are no studies that meet all of these criteria at the same time and many contain more or less significant methodological biases.
Professor Didier Raoult has released several studies, which he says show the efficacy of hydroxychloroquine in combination with the antibiotic azithromycin. For him, the health emergency justifies that we widely give this drug. He advocates the administration of this dual therapy at the first symptoms and states in his third study on more than 1,000 patients that after 10 days, more than nine in ten (91.7%) had no more viral load. But this figure, like that of the mortality of treated patients, is comparable to that observed in the event of natural progression of the disease.
Among the methodological biases of this study, pointed out by other scientists: no control group, which prevents demonstrating anything about the effectiveness of the HCQ. In addition, 95% of the treated patients showed no signs of severity. Like most patients, they could therefore have healed spontaneously, with or without treatment.
A study done in New York hospitals and published earlier this month in the American journal NEJM shows that hydroxychloroquine has not significantly improved or worsened the situation of patients in serious condition. Two studies, one Chinese and one French, published last week, find that the HCQ does not significantly reduce the risk of admission to intensive care or death in patients hospitalized with pneumonia caused by Covid-19.
The risks
Choloroquine in particular, but also hydroxychloroquine are drugs whose side effects can be significant, even serious. The French drug agency ANSM particularly warned of the cardiac risks linked to the combination of HCQ and azithromycin.
The Swedish Medicines Agency decided on April 2 to limit the prescription of chloroquine and hydroxychloroquine only to certain conditions, not Covid-19, given the lack of data on their safety for Covid patients.
Because knowledge is too limited, the European Medicines Agency, in particular, believes that these medicines should not “be used only for clinical trials or emergency programs“within the framework of strict protocols validated in each country.
Who uses it and in what context?
With the explosion of requests for chloroquine and hydroxycholoroquine over the past several weeks, it can be assumed that doctors around the world have prescribed it for Covid. In fact, these molecules – usually HCQ, more rarely chloroquine – are administered to Covid-19 patients in many countries. But the framework is often limited: clinical trials and in general in the hospital. Sometimes only for severe cases, sometimes for the least affected.
A notable exception since Wednesday: the Brazilian Ministry of Health therefore recommended the use of chloroquine and hydroxychloroquine for patients slightly affected by Covid-19. However, “as there are no comprehensive studies proving the benefits of these molecules for the treatment of Covid-19, (…) the decision to prescribe them rests with the doctor, with the patient’s agreement“, the ministry added. In the United States, the drug agency (FDA) authorized the use, only in the hospital” de suitably, when a clinical trial is not available or not feasible“.
Apart from clinical trials, France has restricted the use of hydroxychloroquine in hospitals only and only for serious cases on the collegial decision of doctors. In Senegal, many coronavirus patients have received hydroxychloroquine in hospitals. It is also used in Chad, Syria, Algeria, Morocco … In Russia, it is also distributed to hospitals to treat patients who test positive or suspected of being infected.
In terms of clinical trials: the CHUs of Angers and Bordeaux are testing hydroxychloroquine, while a study of 900 caregivers must assess whether hydroxychloroquine and azithromycin are effective in prevention. The European trial (Discovery) which tests four treatments including hydroxycholoroquine and which raised a lot of hope proves to be more complicated than expected, in particular for lack of patients. He will probably not deliver conclusions for several weeks.
In any case, despite the high hopes, we should not expect a “miracle molecule“(whatever it is), because otherwise, the researchers who started trials earlier, in China and Italy,”would have already found it“warned Professor Florence Ader, who heads the Discovery study, on May 7.
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