key: cord-0831538-9b3d33ih authors: Charlier, P; Donell, S; Lippi, D; Nerlich, A; Asensi, V; Perciaccante, A; Appenzeller, O; Bianucci, R title: L’hydroxy-chloroquine pour traiter les patients infectés du COVID-19: quelques leçons d'an-thropologie médicale et d'histoire de la médecine date: 2020-08-27 journal: Ethics Med Public Health DOI: 10.1016/j.jemep.2020.100587 sha: 3fd90b72e94154dae1981bc25a61068cf94a703e doc_id: 831538 cord_uid: 9b3d33ih Il est certainement trop tôt pour faire le point sur les intuitions du professeur Raoult, et ce n'est d'ailleurs pas le but de ce court article. Néanmoins, l'expérience a montré qu'en période de crise sanitaire sans précédent, les prescriptions se révèlent souvent aventureuses, surtout lorsqu'il s'agit d'un nouveau virus. L'imagination collective autour d'un remède se substitue souvent à une garantie ou, au contraire, à une sauvegarde. Ici, les auteurs s'interrogent sur la mise en œuvre du traitement à l'hydroxychloroquine dans le contexte de la pandémie de Covid-19. Comment sa prescription a-t-elle été discutée dans ce contexte de crise? Quelle leçon pouvons-nous tirer de l'anthropologie médicale et de l'histoire de la médecine, en étant témoins d'autres épidémies et de substances ou comportements atypiques ou non conventionnels des praticiens? It is certainly too early to take stock of Professor Raoult's intuitions, and moreover, that is not the aim of this short article. Nevertheless, experience has shown that in times of unprecedented health crises, prescriptions often turn out to be adventurous, especially when it comes to a new virus. The collective imagination around a remedy often takes the place of a guarantee or, on the contrary, a safeguard. Here, the authors question the implementation of hydroxychloroquine treatment in the context of the Covid-19 pandemic. How was his prescription discussed in this context of crisis? What lesson can we learn from medical anthropology and the history of medicine, by witnessing other epidemics and atypical or unconventional substances or behaviors of practitioners? Here, the authors question the implementation of hydroxychloroquine treatment in the context of the Covid-19 pandemic. How was his prescription discussed in this context of crisis? What lesson can we learn from medical anthropology and the history of medicine, by witnessing other epidemics and atypical or unconventional substances or behaviors of practitioners? Keywords : Biomedical ethics; History of diseases; History of medicine; Medical anthropology; Medical controversy; Unconventional treatment. Il est certainement trop tôt pour faire le point sur les intuitions du professeur Raoult, et ce n'est d'ailleurs pas le but de ce court article. Néanmoins, l'expérience a montré qu'en période de crise sanitaire sans précédent, les prescriptions se révèlent souvent aventureuses, surtout lorsqu'il s'agit d'un nouveau virus. L'imagination collective autour d'un remède se substitue souvent à une garantie ou, au contraire, à une sauvegarde. Ici, les auteurs s'interrogent sur la mise en oeuvre du traitement à l'hydroxychloroquine dans le contexte de la pandémie de Covid-19. Comment sa prescription a-t-elle été discutée dans ce contexte de crise ? Quelle leçon pouvons-nous tirer de l'anthropologie médicale et de l'histoire de la médecine, en étant témoins d'autres épidémies et de substances ou comportements atypiques ou non conventionnels des praticiens ? Mots clés : Éthique biomédicale ; Histoire des maladies ; Histoire de la médecine ; Anthropologie médicale ; Controverse médicale ; Traitement non conventionnel. When faced with a ward full of very sick patients with oxygen saturations in the low 60s dying from a novel virus with no known therapy, what do you do? As Hippocrates taught; "For extreme diseases, extreme methods of cure, as to restriction, are most suitable" [1] . The antimalarial drug chloroquine and its safer derivative hydroxy-chloroquine (C18H26ClN3O) have been used since the 1940s to treat chronic inflammatory diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and Sjögren syndrome [2] . Chloroquine and hydroxy-chloroquine appear to block viral entry into cells by inhibiting glycosylation of host receptors, proteolytic processing, and endosomal acidification. These agents also have immunomodulatory effects through attenuation of cytokine production and inhibition of autophagy and lysosomal activity in host cells [3] [4] [5] [6] . The use of chloroquine and of hydroxy-chloroquine-related compounds in the treatment of COVID-19 infection and post-infection has not come out of the blue [7] but goes back to the 2002-2003 SARS epidemic in Asia. This treatment showed antiviral activity (in vitro) against SARS coronavirus [8] . Recently chloroquine [9] and hydroxyl-chloroquine [10] have also been found to have antiviral effects on COVID-19 in vitro, including inhibition of the viral entry and post-entry stages of infection. So far, there are very limited data from controlled human trials of hydroxyl-chloroquine treatment for SARS-1 or COVID-19. Gautret et al. [11] treated 26 patients infected with SARS-CoV-2 with hydroxy-chloroquine and showed a decreased viral load in nasopharyngeal swabs; however, this study was limited by the small patient numbers and high dropout rate. The COVID-19 pandemic put the Frenchman Didier Raoult on the front page of all Western journals. Since the start of the epidemics and then the pandemic, Professor Raoult has been in favour of using a drug combination (hydroxy-chloroquine +/ azithromycine) that shows a good in vitro antiviral effect against COVID-19 but without "robust" human clinical trials behind it [12, 13] . Trials have not been carried out according to the current standards of biomedical research with a double-blind randomised hand-washing following autopsies of obstetric patients to limit the risk of puerperal infection. He was mocked , criticised and hated, causing metal distress before subsequently being rehabilitated [19] . It is obvious that certain drugs, currently frequently used, would never be put on the market today if they passed modern quality controls, and yet, we could not do without them. Examples are paracetamol, aspirin, sulphamides (derived from aniline, a popular dye), and even hydroxychloroquine (because of the heart decompensation risk). Unfortunately some deaths of patients infected with Covid-19 have been reported to be due to misuse of hydroxy-chloroquine, or even chloroquine (although this drug is not part of the therapeutic arsenal proposed). Some patients had self-medicated, or cardiac contraindications had not been taken into account, causing paroxysmal rhythm disturbances and sudden deaths [20] . These complications are reminiscent of those observed during the Spanish flu (pandemic of 1918), where many deaths in the United States (at least 3%) were attributed, not to the direct action of the virus, but to an overdose of aspirin; official dosage recommendations are clearly excessive [21] . Amantadine was originally introduced as an antiviral drug to treat influenza A. Some patients noticed relief in their Parkinson disease symptoms after taking amantadine for influenza. This clinical observation sparked an initial interest, and promoted several important studies that eventually led to a new indication of this drug . Interestingly amantadine is discarded as influenza medication nowadays for lack of efficacy [22] . Shakespeare is worth reading again, since COVID-19 can be considered our plague [23] . In King Lear, the tragedian teaches us that the truth sometimes comes from the mouths of the Fool, the only character in the play to speak with sincerity to the sovereign, without twisted speech, but with coldness and righteousness. 7 For many clinicians, when facing a similar emergency with a great number of deaths, history has showed to us that it may be ethically and legally correct to act without confirmed robust clinical trials. Anything is worth trying to save even a low number of human lives and bringing some hope to mankind; at least as long as trials disproved positive therapeutic effects or a more efficient therapy is available. Returning to the discussion on hydroxy-chloroquine the look into the history of medicine offers one strong argument for the application as a potential treatment due to the lack of proven effective therapies for Covid-19 [24] . The second argument comes from already existing observations on hydroxyl-chloroquine from invitro experiments and clinical observations from previous other viral infections. Currently, resuscitation services are overwhelmed in many countries; containment procedures have only a partial effect in reducing the incidence of the disease, but without preventing its spread or the congestion of hospital services. If at the pandemic's start, the main goal was to avoid the saturation of the intensive care units, now the main goal is to reduce the number of patients developing severe acute respiratory syndrome. So it needs to plan a treatment in early stage of disease. It is to save time, but not to eradicate the disease, especially since the second wave of the pandemic has begun in Asia, and will soon hit Europe again, and the rest of the world; as has been shown in the evolution of the ancient epidemics in the past (plague, yellow fever, cholera). Other comparisons would have been possible (one thinks of the introduction into clinical practice of "discussed" molecules such as cinchona, antimony, or arsphenamine), other authors could have been called upon in medical anthropology (like Byron J. Good, from Harvard Medical School, and his work in the field of professional and individual acceptance and dissemination of treatment for mental illness), but this article is intended as a first approach, a first look, a strong introduction. 8 So certainly, in the context of hydroxy-chloroquine and Covid-19 pandemic, there are rules to follow, those of statistics and randomised controlled trials, but do we have the time? This is the key pointthe major question. We just ask the question. History has the answer. 10 13. Colson P, Rolain J-M, Lagier J-C, Brouqui P, Raoult D. Effects of chloroquine on viral infections: an old drug against today's diseases? Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19) A Review COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression New against coronavirus: what to expect for COVID-19? Excitement around hydroxychloroquine for treating COVID-19 causes challenges for rheumatology. The Lancet Hydroxychloroquine use during the COVID-19 pandemic 2020 Chloroquine is a potent inhibitor of SARS coronavirus infection and spread Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Hydroxychloroquine and azithromycin as a treatment of COVID-19: Results of an open-label non-randomised clinical trial Recycling of chloroquine and its hydroxyl analogue to face bacterial, fungal and viral infections in the 21st century Tratamientos disponsibles para el manejo de la infección respiratoria por SARS-CoV-2 (Treatments available for the management of respiratory infection by SARS-CoV-2) Agencia Espaňola de Medicaments y Productos Sanitaros EUA Hydroxychloriquine sulfate Health Care Provider Fact Sheet version date Containing an inquiry into the nature, causes and cure, of that disease. Together with a critical and chronological view of what has been published on the subject La vie et l'oeuvre de Philippe Ignace Semmelweis Husband and wife poison themselves trying to self-medicate with chloroquine. Live Science Salicylates and pandemic influenza mortality, 1918-1919 pharmacology, pathology, and historic evidence Amantadine: The Journey From Fighting Flu to Treating Parkinson Disease King Lear under Covid-19 lockdown Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19). A Review