Coronavirus

Chloroquine and Covid-19: what to think about it?

Chloroquine, this malaria treatment, triggers a lot of discussion in social networks, even among scientists. What should we think of this substance in the fight against Covid-19?

The following article does not assess local medical practice in times of health crisis. You need to be aware of the difficulty and need to be pragmatic about it epidemic. Likewise, the measures taken when navigating the unknown in an unprecedented situation are necessarily unprecedented. BUT. Because yes, there is a “but”.

To present the goal of this article, we quote Gandhi: Mistakes do not become truth because they spread and multiply. Truth does not become a mistake because nobody sees it. “” If this famous and elegant speech can be used to justify everything and its opposite, we will try to honor it here.

The goal will then be to identify and evaluate the evidence we have at the time of writing to know if chloroquine is present (or not) you need to know how to put your hope aside) appropriate treatment ( ie with a specific effect of more than one) placebo and a positive benefit-risk ratio) the new Covid 19 disease induced by SARS-CoV-2 infection.

Short feedback on chloroquine

Chloroquine is a preventive antimalarial and healing. It is also used against Autoimmune diseases like lupus. Most often its chemical derivative is prescribed: hydroxychloroquine (ie with a group) alcohol OH more on the molecule). As for the drug, it is door the trade name of Plaquenil for hydroxychloroquine and Nivaquine for chloroquine.

After the media outbreak regarding this molecule, which we’ll talk about below, a comment was published in the scientific literature by two researchers (Franck Touret and Xavier de Lamballerie)Emerging Virus Unit from the University of Aix-Marseille. Here’s what we can learn about chloroquine and its history in treating respiratory viral diseases:

  • experience in vitro (on cells therefore suggest that chloroquine inhibits Replication of SARS-CoV-2.
  • Chloroquine has shown its potential in the past in vitro against many virus different, but has always failed in testing in vivo (hence on living organisms) on animal models.
  • Chloroquine has often been suggested in the treatment of viral diseases of the human respiratory system. Without success.
  • The Chinese consensusWhat confirms its effectiveness does not mention raw data. However, the peer review process, independent assessments of the method and results, and replication of studies are essential to assess the potential benefits (but also the risks) for patients.

Here is a measured, nuanced comment that is up to date with the data currently known. Unfortunately, not all researchers are so careful.

Media excitement

In such cases, the media have a great time. At these moments one can only regret the general ignorance of the scientific method. However, you are not alone. As a matter of fact, Didier raoultThe infectiologist and professor of microbiology at the Institut-hospitalo-universitaire (IHU) Méditerranée at the Timone Hospital in Marseille is currently talking a lot about him. This great teacher (whom we won’t try in this article, we don’t judge the man or his great career, but lots of data) seems to be the source of this excitement a published video February 25, 2020, initially titled “” Corona virus : The end of the game! “” (based on the consensus of Chinese experts already quoted) renamed some time later “Corona virus: on the way out of the crisis? “” Since then he has intervened a lot in the media to talk about chloroquine with little care. He is particularly active on the video platform YouTube also, which is quite curious for a scientist, especially when it comes to presenting works that his colleagues have not read.

If it is not a question of assessing a doctor on site, especially in times of crisis, one can ask where the caution in communicating the results, the essential quality of the scientist, has gone? Before treatment accepted and approved It usually takes a long time. A time that we do not necessarily have in medical practice at the moment. Either. This is easy to understand. However, this also requires accuracy. This rigor is important if we want to learn something. Otherwise we don’t learn stricto sensuNothing.

The role of the science journalist has not changed. To use the words of a colleague, Florian Gouthière – who just wrote a very insightful article on this topic – on his Blog curiologie.frthe role of a science journalist would be more ” to inform about the uncertain in an uncertain world. To do this, we need to make the public understand that uncertainty does not go hand in hand with the advancement of scientific knowledge, and that public announcement, as exciting as it is, must still stand the test of time. “”

Therefore, we understand that going through the media can be harmful. Be careful when you go to the hospital, trust your doctor.

Simply, like the science that the scientific journalist reports, he informs about the description. The normative then belongs to everyone. The information about the description then, as originally stated, amounts to confiscating the large amount of available evidence and more or less likely to judge a given hypothesis or claim. It can change over time and prove us right or wrong. Whatever happens, an honest science journalist will stand up for hard data. But before time goes by and clinical studies Quality is made, impossible to know. Neither we nor major teachers have the ability to predict the future.

Authority is not an argument

In this story, it is important to come back to this basic principle of the skeptical approach. A person’s authority, diploma, or fame are not arguments. Naturally our assessment heuristic Let us believe our doctor when he talks to us about medicine. And it is legitimate. Nevertheless, our doctor remains a biased person Who can make mistakes, especially if they get carried away, as was the case with Professor Raoult when he titled his video? ” Corona virus: end of game! “” on the sole basis of a consensus of experts without raw data. Unfortunately, the game is far from over. You just have to look at the curves of contamination electricity their development is exponential. The number of deceased is also increasing (fortunately also that of the healed people).

In addition, this professor is illustrated by his numerous publications, which gives him even more confidence in his subject. However, if you dig lightly, you’ll find that a certain number (not all, of course) are published in newspapers, where the editors are sometimes part of the research team. Some are also accepted with insane speed that leaves no time for the peer review process. It is neither more nor less Short circuit sporadically the scientific approach.

Unfortunately, this type of exercise more frequently and can be partially explained by the climate in which develops the world of science and research currently. The goal is to talk about it, publish a lot of innovative research results and make a name for yourself. All this to get funding that is painfully lacking. Sometimes it goes through one amputation free from the rules of scientific art.

Professor Raoult’s study: a nest of “bias”

Much is required to scientifically validate a hypothesis strict studies, Similarly reproduced around the world and independently. Studies are underway to assess what we are talking about today, namely: ” Chloroquine is effective in the treatment of Covid-19 ? “” Professor Raoult’s study has just been broadcast, accepted and released in record time (which is not a good sign). What can we conclude from this study to validate or invalidate the original hypothesis? Not much! Let’s list the methodological biases of this paper point by point (you can consult for more details the page PubPeer dedicated to this study, in which criticism and questions come from the scientific community).

  • The study is being conducted in Open label, that is, without a blindness procedure (the patient and the doctor know who is in which group, which is subject to strong bias) and without randomization (which means that the potential confounding factors are not likely to be excluded).
  • The goals of the study are much more moderate than Professor Raoult’s media interventions. We can then read there “We are investigating the role of hydroxychloroquine Viral loads Respiratory tract “, the goal is to lower them. However an article appeared in the newspaper nature in terms of examining respiratory diseases as they go through SARS-CoV-1 Where MERS-CoV concluded in 2016 that the most serious forms were associated with a decrease in Viraemia. This forces us to be extra careful when we hear Professor Raoult cry out YouTube “” If you no longer have the virus, you are saved, “ although, as we will see below, the clinical condition of the patients is not described in his review.
  • The team had bet as a secondary goal Monitor changes in parameters such as apyrexia, normalization of frequency Respiratory system that Duration mean hospitalization and mortality. This ghost data is completely missing from the paper.
  • The patients were treated either with hydroxychloroquine alone or with a antibiotic (Azithromycin) with hydroxychloroquine or they were not treated (control group). Hence no placebo treatment. From the beginning we know that from this experience only a comparison between two treatments and a non-treatment can be learned, not between a treatment and a deception, which is essential for the knowledge of the effect. clean of what you think is a “medicine”. In addition, the control group was not in the same place as the treated group.
  • The sample is initially small with 26 patients (only 20 at the end of the study), which is too small to produce robust results contrary to Professor Raoult’s claims. The laws of probability do not change either in times of pandemic.
  • Neither the clinical status nor the initial viral load of the patient is known. The clinical condition is also unknown at the end of the study. In addition, viral load tests deliver different results depending on the day (a positive stroke, a negative stroke and then positive again). We can therefore rightly question the current reliability of these tests.
  • The follow-up should take 14 days, but the results presented only go to 6e Day, which is clearly not normal.
  • Certain exclusion criteria (e.g. not including children under the age of 12) are not met.
  • Some patients were considered “lost to aftercare”. This usually happens, but here the authors have decided to exclude them. We then discover that all of these patients were part of the chloroquine group. Three were transferred to the intensive care unit, one died, one patient may not have been ill, and one patient wanted to discontinue treatment because of the side effects. It is surprising that the three intensive care patients were not followed up.
  • His contribution does not respect the ethical basis of a scientific publication. The study is published in a newspaper in which the editor-in-chief works for the same institute on behalf of Professor Raoult. Also note that the document was received on March 16, adopted on March 17, and published on March 20.

The Zhejiang University School of Medicine (China) has also just released a Covid-19 prevention and treatment manual where to read on page 40 that chloroquine data are insufficient to treat it and where the combination of hydroxychloroquine and azithromycin is strongly recommended. The World Health Organization (WHO) also spoke yesterday and indicate this “Small, non-randomized observational studies don’t give us the answers we need. Using an untested pill without the right evidence could raise false hopes, do more harm than good, and lead to a lack of the pill needed to treat other diseases. “.

Finally the Minister of Health, Olivier Véran, answered questions on chloroquine and Professor Raoult’s study, which is not lacking in moderation in the results obtained.

The importance of informing with nuances

This article not only wants to inform you about the currently known (or not interested) interest of chloroquine in the treatment of Covid-19, but also to inform you about the importance of nuanced information. The media outbreak serves no legitimate reason if it does not at best reassure the population for reasons that prove to be good, or at worst raise false hopes that do not completely discredit you. If this treatment is effective, we have certainly lost a little time to save lives. However, if it turns out that it doesn’t work or worsens the situation, we have saved it. Treatment is not always better than doing nothing. For example, in those early days thehomeopathy ((It is nothing but a placebo) was more beneficial for patients than bloodshed. Doing nothing was the best way to save lives. You have to remember that.

In addition, the consequences of this type of communication are difficult to predict, except perhaps for those who know human behavior well. On the other side of the Atlantic, Donald Trump recorded these results with the same enthusiasm as Professor Raoult. He is doing print on the Food and drug administration ((FDA) so that chloroquine is expressly approved. We currently have pharmacies at the door an unusual request of chloroquine. Note that Professor Raoult has never spoken or advised about self-medication.

Any argument other than strict and documented data is not an argument. They can “serve” on a media or political level, but trying to make a fact understandable to an audience or a readership (and not to force it on) necessarily means going through an argument concrete. However, we have seen a range of evidence to support the claim at the moment. ” Chloroquine is effective in the treatment of Covid-19 “ is too thin to judge it as likely. There is a difference between what doctors do in a crisis situation and what doctors do construction and the broadcast of what we generally call A friend.

Doctors are currently struggling to save lives. Chloroquine is part of the latest therapeutic arsenal (due to its low level of evidence) recommended by various learned societies (two molecules, remdesivir and the combination lopinavir / ritonavir, are offered first) in the treatment of intensive care patients who are infected with SARS-CoV-2. The defamatory speeches, which assume that you do not treat in hospitals because you do not give chloroquine, are a lie and a lack of respect for the medical teams.

The health minister said that studies are underway on a larger scale. Large clinical trials have just started to evaluate several possible treatments (including hydroxychloroquine), the French part of which is being carried out by the National Institute for Science and Medical Research (Inserm). We have to wait for the results of these experiments to update our comments. Finally, like everyone else, we sincerely hope that time will demonstrate our epistemological caution in dealing with this new disease.

Consequences already visible

Two days after writing this article, this media excitement is already showing its harmful consequences. After this Banner health hospital In the United States, a 60-year-old man (and his wife is worried) died after overdosing on chloroquine phosphate. According to an article in the Parisians and lupus patients who need treatment find it difficult to find. The Sanofi Group, a key player in the pharmaceutical industry, ensures that the shares are received.

Please note:

The editors will advise you to complete this article the excellent and short analysis of Nicolas Martin on France culture about chloroquine and the very complete article by Florian Gouthière on the same subject: Covid-19 & Chloroquin: on a very fragile study and dangerous media and political excitement “”

What you should remember

  • Chloroquine has shown effects in vitro however, in the past it has always failed to offer therapeutic benefits in animal models and in humans for respiratory viral infections.
  • Professor Raoult’s latest study is full of bias. It doesn’t teach us much. We hope that further studies with a better methodology will be carried out. They allow us to decide on the effectiveness (or ineffectiveness) of chloroquine in the treatment of Covid-19.
  • It is very important to combat the media hype and its consequences. It is an essential topic to inform people with nuances and to make the scientific method understandable for the population.
  • And don’t forget: stay at home!

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