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Thursday, May 28, 2020

Chloroquine, hydroxychloroquine and Covid-19: where are we?

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Paris (AFP)

Studies, tests, uses: what do we know about chloroquine and its derivative hydroxychloroquine, currently being tested in several countries, alongside other molecules, against Covid-19?

What is that?

It is a synthetic derivative of quinine prescribed for several decades against malaria, a parasite carried by the mosquito.

Chloroquine is marketed under several names depending on the country and the laboratories: Nivaquine or Resochin for example.

There is a derivative, hydroxychloroquine, better tolerated, known in France under the name of Plaquénil, used against lupus or rheumatoid arthritis.

Why do they spark hope?

Pending a hypothetical vaccine, probably not available for at least a year, scientists are testing existing drugs and their combination to find a treatment as quickly as possible.

Compared to other molecules, chloroquine and hydroxychloroquine have the advantage of being already available, inexpensive and well known.

Even before the SARS-CoV-2 pandemic, their antiviral properties were the subject of numerous studies, in vitro or on animals and on various viruses.

“It has long been known that chloroquine (C) and its derivative hydroxychloroquine (HC) inhibit the replication in vitro” of certain viruses, recalls Marc Lecuit, researcher in infection biology at the Pasteur Institute.

“As expected”, tests have recently confirmed that they do have “antiviral activity on SARS-CoV-2 in vitro” he continues.

But “this does not necessarily imply that these drugs have antiviral activity in vivo in humans”, he notes, citing “many disappointing tests” on the dengue virus (no benefit) or chikungunya (the molecule “helps” the virus to develop).

Scientific controversy

Several publications, Chinese and French, report positive results on patients with Covid-19.

In France, Professor Didier Raoult and his team at the Institut Hospitalo-Universitaire (IHU) Méditerranée infection concluded, in two publications (on twenty patients then 80), that “the effectiveness of hydroxychloroquine associated with l azithromycin in the treatment of Covid-19 “.

But many scientists and the World Health Organization point out the limits of these studies, because they were not conducted according to standard scientific protocols: lot of patients, doctors and patients not knowing who receives the treatment, published results in an independent peer-reviewed scientific journal, etc.

Proof of the complexity of the subject, two Chinese clinical studies (one at the beginning of March and one on Tuesday) come to different conclusions: no particular efficacy for the first, while the second affirms that hydroxychloroquine does indeed have “potential” in Covid processing.

“These questions absolutely do not mean that HC has no interest in the treatment of Covid” but “to find out, it must be evaluated scientifically by following the methodology of clinical trials”, underlines Marc Lecuit.

The European Medicines Agency said on Wednesday that the effectiveness of chloroquine and hydroxycholoroquine “remains to be demonstrated in studies”.

The risks

Part of the scientific community and health authorities warn of a hasty craze for these substances.

“One of the unexpected consequences may be a shortage of chloroquine for people who need it for their rheumatoid arthritis for example,” said Peter Pitts, a former official of the US drug agency FDA.

After having observed “difficulties of access” to hydroxychloroquine for the chronically ill, the French authorities even had to regulate by decree its sale and its use.

In addition, the side effects are numerous: nausea, vomiting, skin rashes but also dermatological, ophthalmological, cardiac, psychiatric attacks … An overdose can be dangerous, even fatal.

However, the advertising of the substance may encourage self-medication if people bought it with “convenience” orders or if they had chloroquine or hydroxychloroquine drugs at the back of their medicine cabinet.

Cases of emergency hospitalization after the absorption of too large doses have also been reported for example in Nigeria and, in the United States, a man died after having ingested a form of chloroquine intended for aquariums.

In France, the Medicines Agency (ANSM) warned on Monday that the treatments tested against Covid-19 could cause serious adverse effects and should “in no case” be used for self-medication, whether it be hydroxychloroquine or Kaletra (an antiretroviral combining lopinavir / ritonavir).

The ANSM has listed around thirty “serious adverse effects, most of which occurred in hospital, including” three suspected deaths “following the use of one of these treatments.

The organization also warned “in particular” against “the combination of hydroxychloroquine with azithromycin to treat Covid-19 disease, which to date has not been proven to be effective and exposes to increased risk of abnormality in the heart’s electrical system. “

Who is using it against the Covid-19?

Given the explosion in demand for chloroquine and hydroxycholoroquine over the past several weeks, it can be assumed that doctors around the world have prescribed it against Covid.

In fact, they are administered to Covid-19 patients in several countries around the world, generally in hospitals, in different ways.

But they should “only be used for clinical trials or emergency programs” under strict protocols validated in each country, according to the European Medicines Agency on Wednesday.

In the United States, where President Donald Trump, very enthusiastic, spoke of a “donation from heaven”, the FDA has authorized the use, only in the hospital, of chloroquine and hydroxychloroquine against Covid -19, “suitably, when a clinical trial is not available or not feasible”.

In Senegal, half of the identified coronavirus patients, or around fifty patients, have been prescribed hydroxychloroquine in hospitals, while Greece has revived its production and Morocco wishes to use it for “confirmed cases”, Algeria for “acute cases”.

In France, Professor Raoult has publicly promised to distribute a combination of hydroxycholoroquine and azythromicin to “all infected patients” and certain doctors and politicians call for the drug to be widely administered in the name of health emergencies.

However, French health authorities have restricted the use of hydroxychloroquine (but also the antiviral drugs lopinavir / ritonavir) in hospitals only and only for severe cases.

At the same time, clinical trials are launched to test its effectiveness according to a protocol respecting strict scientific orthodoxy.

The Angers CHU in France will thus launch a study on 1,300 patients (Hycovid), conducted with 32 other national hospitals.

A European trial called “Discovery” has been launched in several countries to test four treatments, including hydroxycholoroquine, on 3,200 patients including 800 serious cases in France. Initial assessments are expected this weekend.

WHO is also to launch a large international clinical trial.


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