Professor Raoult Comments on COVID-19 Treatments Researched Around the World

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Professor Didier Raoult commented on the various COVID-19 treatments currently researched, by various teams around the world, using hydroxychloroquine and other molecules, on the website of the institute Méditerranée Infection. The brief review is co-authored with the institute’s communication officer Yanis Roussel.

Remember, Professor Raoult and his team conducted several studies about the use of hydroxychloroquine, alone or in combination with azithromycin, and concluded that their treatment was effective, including in the context of their most recent study encompassing 1061 patients.

It should be stressed here that not all hydroxychloroquine-based treatments are the same. For example, there was renewed bad publicity in the media for the treatment, but it referred to adverse effects in a clinical trial in Brazil, where half of the patients were administered 600mg twice daily for 10 days or total dose 12g, which is double the dose used by Professor Raoult for his recommended treatment. 

https://www.medrxiv.org/content/10.1101/2020.04.07.20056424v1

Note that in Brazil, there are very good stories about hydroxychloroquine-based treatments, as reported by CNN-Brazil.

Key Excerpts

Here are key excerpts of the review. See below the complete text, provided in English on the Méditerranée Infection institute website.

“5 therapeutic pathways are emerging to fight against the coronavirus epidemic and are the subject of clinical trials worldwide: chloroquine / hydroxychloroquine, hydroxychloroquine combined with azithromycin, lopinavir / ritonavir (kaletra), remdesivir and the use of plasma from patients with COVID-19 infection.”

“Concerning chloroquine/hydroxychloroquine alone, the results of three studies have been published: one in France involving 24 patients and concluding to the effectiveness of the treatment, and two in China, the first not concluding to be effective following the experiment on 15 patients with control group, the second having concluded that hydroxychloroquine is effective.”

“Regarding the use of the hydroxychloroquine + azithromycin combination, our team published observational studies, the first relating to 80 patients (6), the second relating to 1061 patients. Both conclude that this treatment is effective …”

“Regarding kaletra, a comparative study with two arms concluded that it was ineffective. Its effectiveness in vitro remains to be demonstrated.”

“Regarding remdesivir, an interesting study … only allows concluding that the remdesivir is extremely toxic to the patients to whom it was administered (60% of serious side effects).”

Regarding the use of plasma, it’s seen as “a theoretically interesting idea” but “this solution poses a problem because the use of plasma is difficult to envisage in non-serious forms of the disease. In severe forms, the problem is not virological but immune.”

Read the complete article below.

See also this just published explosive interview of Professor Raoult, in French.

NEWS ABOUT TREATMENT

The fight against the COVID-19 epidemic has involved the exploration of numerous therapeutic pathways, which have given rise to research in vitro and in vivo. However, practitioners around the world did not wait for the results of this research to use what appeared to them to be the most adequate treatment (1). This implicates the need of being quick in carrying out research and then disseminating the results to doctors confronted with the epidemic in the field, to guide their therapeutic management of patients.

The use of potential treatments on patients makes it possible to produce data, which can then be used in research. In the scientific community, conducting randomized double-blind clinical trials has become the gold standard for validating the effectiveness of a treatment. However, when the urgency is to treat life-threatened patients, it is unethical to give them a placebo when the state of the art gives the doctor the intimate conviction that the risk-benefit balance is in favor of the administration of the treatment that he wishes to experience. We must therefore not forget that single-arm studies, without randomization, can be just as convincing as randomized studies.

Two elements appear crucial to us for a study carried out without randomization to be significant. First, it must study clearly identified endpoints. For COVID19, we identify three: mortality, transition to intensive care, and viral load. It must also be comparative. The study needs to compare the results following the use of a treatment to a series of historical results, or to a series of results in other health care centers.

Today, 5 therapeutic pathways are emerging to fight against the coronavirus epidemic and are the subject of clinical trials worldwide: chloroquine / hydroxychloroquine, hydroxychloroquine combined with azithromycin, lopinavir / ritonavir (kaletra), remdesivir and the use of plasma from patients with COVID-19 infection. We propose to review the results published on the subject of these 5 therapeutic pathways.

Concerning chloroquine/hydroxychloroquine alone, the results of three studies have been published: one in France involving 24 patients and concluding to the effectiveness of the treatment (2), and two in China, the first not concluding to be effective following the experiment on 15 patients with control group (3), the second having concluded that hydroxychloroquine is effective following an experiment on 31 patients with control group (4). Two limits in these studies limit knowledge today. First, these studies report neither the same duration of treatment, nor the same dosage. Then, the two Chinese studies do not give details concerning the other treatments used within the framework of the protocol. The in vitro results show an effectiveness of chloroquine and hydroxychloroquine (5).

Regarding the use of the hydroxychloroquine + azithromycin combination, our team published observational studies, the first relating to 80 patients (6), the second relating to 1061 patients (7). Both conclude that this treatment is effective for the three endpoints defined above. Our points of comparison are, concerning the duration of viral carriage, Chinese studies on the natural history of the disease (8), and concerning the clinical aspects, studies carried out in Marseille in services not using this prescription.

Regarding kaletra, a comparative study with two arms concluded that it was ineffective (9). Its effectiveness in vitro remains to be demonstrated.

Regarding remdesivir, an interesting study funded by Gilead was published in the New England Journal of Medicine (10). It only allows concluding that the remdesivir is extremely toxic to the patients to whom it was administered (60% of serious side effects). While it is encouraging to see that serious teams, like the one who wrote this article, understand that it is unethical to give a placebo to a life-threatening patient, it should not imply that to forget that a study that includes neither end-point nor comparison, cannot allow to conclude anything.

The use of plasma is a theoretically interesting idea. However, only two studies without end point or comparison have been published to date (11-12). Scientifically, this solution poses a problem because the use of plasma is difficult to envisage in non-serious forms of the disease. In severe forms, the problem is not virological but immune.

In view of these data from the literature, IHU doctors have made the decision to continue the treatment of patients with COVID19 with a hydroxychloroquine+azithromycin protocol.

Yanis Roussel, Didier Raoult

  1. Sermo (2020) Sermo COVID-19 Real Time Barometer. https://app.sermo.com/covid19- 442 barometer?utm_campaign=wwwsermo_covid19
  2. Gautret P, Lagier J-C, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents 2020;105949.
  3. Wang M, Cao R, Zhang L, Yang X, Liu J et al (2020) Remdesivir and chloroquine 427 effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell 428 Res 30:269-271.
  4. Chen J, Liu D, Liu L, et al. A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19) J Zhejiang Univ (Med Sci) 2020, 49 (1): 0-0.   DOI: 10.3785/j.issn.1008-9292.2020.03.03
  5. Chen Z, Hu J, Zhang Z, et al. Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial [Internet]. Epidemiology; 2020 [cited 2020 Apr 1]. Available from: http://medrxiv.org/lookup/doi/10.1101/2020.03.22.20040758
  6. Gautret P, Lagier J-C, Parola P, Hoang VT. Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a siw-day follow up : an observational study. Preprint.
  7. Million M, Lagier J-C, Gautret P, COLSON P, Parola P, RAOULT D. Early treatment of 1061 COVID-19 patients with hydroxychloroquine and azithromycin, Marseille, France. 2020
  8. Zhou F, Yu T, Du R, Fan G, Liu Y et al (2020) Clinical course and risk factors for 395 mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort 396 study. Lancet 395:1054-1062
  9. Cao B, Wang Y, Wen D, et al. A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med 2020;NEJMoa2001282.
  10. Grein J, Ohmagari N, Shin D, et al. Compassionate Use of Remdesivir for Patients with Severe Covid-19. N Engl J Med 2020;NEJMoa2007016.
  11. Duan K, Liu B, Li C, et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci USA 2020;202004168.
  12. Shen C, Wang Z, Zhao F, et al. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA [Internet] 2020 [cited 2020 Mar 29];Available from: https://jamanetwork.com/journals/jama/fullarticle/2763983

Source: https://www.mediterranee-infection.com/actualite-du-traitement/