COVID 19 and hydroxychloroquine meta-analysis: Put your face down!

The COVID 19 epidemic began in early 2020. Professor Raoult quickly proposed an effective treatment, combining hydroxychloroquine (an antimalarial) and azithromycin (an antibiotic), on the basis of Chinese studies and studies taking place at the IHU in Marseille. It was only the beginning of a controversy, a real ” Dreyfus affair », Of unprecedented violence in the history of medicine, opposing the supporters of the treatment and their detractors.

In August 2020 appeared in the scientific journal ” Clinical Microbiology and Infection »A meta-analysis supposed to take stock of everything that had been published in the scientific journals indexed concerning the effectiveness of the treatment combining hydroxychloroquine and azithromycin.

This meta-analysis (including 17 articles out of 839), concluded, contrary to what many doctors observe in their practice, in the ineffectiveness of this treatment. We are going to explain to you why this partisan meta-analysis, emanating from physicians fiercely opposed to this treatment, presents such biases (or errors) that it does not provide any element allowing such a conclusion.

We have published a response to this meta-analysis which will appear in the journal “Clinical Microbiology and Infection”, the main points of which are explained below.

This treatment, we have been reiterating it for many months, must be prescribed early, (before the inflammatory cascade leading to pulmonary lesions where it is, at this advanced stage, ineffective). However, the “meta-analysis” (except for one study) only focused on hospitalized patients, that is to say with pulmonary symptoms, and therefore treated too late! The only out-patient article included patients whose diagnosis was uncertain, as only 34% of them had PCR positive for coronavirus. These elements are enough to totally discredit this meta-analysis.

In addition, the authors did what is known in science as “cherry picking” or “cherry picking”! Cherry picking consists of only taking into account the data that is favorable to what you want to demonstrate. Thus, the authors excluded numerous studies grouping together thousands of patients and demonstrating a drastic decrease in mortality with the treatment combining hydroxychloroquine and azithromycin. We have cited three, the Garch study in which Christian Perronne (1), an Italian study (3451 patients, 30% decrease in mortality!) (2) and a Belgian study (8,075 patients, 17.7 versus 27.1% mortality respectively with and without hydroxychloroquine) (3).

L’American Journal of Medicine is about to publish an article explaining the mechanisms of action of hydroxychloroquine and azithromycin and recommends the implementation of the treatment as soon as possible, in combination with zinc (4).

We add that it is not serious to claim that hydroxychloroquine, a drug known for decades, is toxic, including in association with azithromycin, a fortiori in a hospital environment where the patients treated benefit from electrocardiograms and monitoring of potassium levels. Such ridiculous reasoning would lead, if it extended to all medicine, to the withdrawal of all the drugs referenced in the Vidal. Note that the authors cite the Recovery study giving patients toxic doses of hydroxychloroquine (2400 mg the first day, then 9 days at 800 mg, while Professor Raoult uses 600 mg per day)! Giving such doses also testifies to a great misunderstanding of the mechanism of this molecule, which has the property of being concentrated more than 1000 times in certain places of the cell (the phagolysosome).

What are the reasons for these young scientists to strive to discredit this treatment, by including in their analyzes patients who are already too sick for it to be effective and by hiding all the articles that do not go in their direction?

These young scientists also have links of interest, show partisanism against dual therapy and are fervent detractors of Professors Perronne and Raoult with the support of Inserm and SPILF. We can underline the virulence of their comments on social networks. Nathan Peiffer-Smadja, one of the authors of the article, has just finished his internship, in the infectious diseases department, at the Bichat university hospital in Paris, under the supervision of Professor Yazdanpanah. The latter is also a member of the scientific committee, set up for the management of the epidemic in France, whose role has greatly contributed to the prohibition of the use of this therapy from the start of the COVID-19 epidemic. . Although Nathan Peiffer-Smadja, is subordinate to Professor Yazdanpanah, this link of interest was not brought to the attention of readers of the article. Nathan Peiffer-Smadja is also doing research at Imperial College London. Recall that the vastly overestimated estimates from Imperial College were used by the scientific committee and the government to decide on containment.

We seem to be living in a time when values ​​are reversed, where a young intern puts his dignity at risk by passing judgment on Professor Raoult and not hesitating to relay the words of doctors treating him with ” charlatan »On social networks… We recall that before the epidemic, Professor Raoult was widely regarded as a world-class scientist, spearhead of research in microbiology.

There was a time when Tradition wanted the values ​​and roles to be reversed once a year: the king became a beggar, the beggar king, the teacher the apprentice, the apprentice the teacher… and a mask was then worn. ! This secular Tradition was called “Carnival”. It is clear that the Carnival now takes place every day, and that the voice of young students and laymen or inexperienced doctors covers that of a world-renowned teacher.

Take off the masks! No, scientific controversy should not be ” cherry picking », Neither dogmatic, nor appealing to sarcasm, but must be articulated around a respectful, honest and reasoned discussion. Links of interest must be mentioned.

History will condemn critics of a simple, well-tolerated and inexpensive treatment that could have saved tens of thousands of patients if it had been prescribed early.

1. Davido B, et al. Impact of medical care including anti-infective agents use on the prognosis of COVID-19 hospitalized patients over time. Int J Antimicrob Agents. 2020;106129. doi:10.1016/j.ijantimicag.2020.106129
2. Castelnuovo AD, et al. Use of hydroxychloroquine in hospitalised COVID-19 patients is associated with reduced mortality: Findings from the observational multicentre Italian CORIST study [published online ahead of print, 2020 Aug 25]. Eur J Intern Med. 2020;S0953-6205(20)30335-6. doi:10.1016/j.ejim.2020.08.019
3. Catteau L et al. Low-dose Hydroxychloroquine Therapy and Mortality in Hospitalized Patients with COVID-19: A Nationwide Observational Study of 8075 Participants [published online ahead of print, 2020 Aug 24]. Int J Antimicrob Agents. 2020;106144. doi:10.1016/j.ijantimicag.2020.106144
4. Mc Cullough et al, Pathophysiological Basis and Rationale for Early Outpatient Treatment of SARS-CoV-2 (COVID-19) Infection. The American Journal of Medicine, (in press)

Dr Alexis Lacout Medical Radiologist

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