Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial
Authors: Morgane Mailhe
Philippe Gautret
St√©phane Honor√©
Philippe Parola
Jean-Christophe Lagier
Vera Esteves Vieira
Eric Chabri√®re
Van Thuan Hoang
Jean-Marc Rolain
Herv√© Tissot Dupont
Philippe Colson
Barbara Doudier
Val√©rie Giordanengo
Johan Courjon
Line Meddeb
Didier Raoult
Philippe Brouqui
Bernard La Scola
Journal: International Journal of Antimicrobial Agents (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: 2019-nCoV; Azithromycin; COVID-19; Clinical trial; Hydroxychloroquine
Affiliations: IHU-M√©diterran√©e Infection, Marseille, France; Aix Marseille Univ, IRD, AP-HM, SSA, VITROME, Marseille, France., IHU-M√©diterran√©e Infection, Marseille, France; Aix Marseille Univ, IRD, APHM, MEPHI, Marseille, France., IHU-M√©diterran√©e Infection, Marseille, France; Aix Marseille Univ, IRD, AP-HM, SSA, VITROME, Marseille, France; Thai Binh University of Medicine and Pharmacy, Thai Binh, Viet Nam., IHU-M√©diterran√©e Infection, Marseille, France., Infectiologie, H√¥pital de l'Archet, Centre Hospitalier Universitaire de Nice, Nice, France; Universit√© C√¥te d'Azur, Nice, France; U1065, Centre M√©diterran√©en de M√©decine Mol√©culaire, C3M, Virulence Microbienne et Signalisation Inflammatoire, INSERM, Nice, France., Department of Virology, Biological and Pathological Center, Centre Hospitalier Universitaire de Nice, 06200 Nice, France., Service Pharmacie, H√¥pital Timone, AP-HM, Marseille, France; Laboratoire de Pharmacie Clinique, Aix Marseille Universit√©, Marseille, France., IHU-M√©diterran√©e Infection, Marseille, France; Aix Marseille Univ, IRD, APHM, MEPHI, Marseille, France. Electronic address: .

Abstract:  Background: Chloroquine and hydroxychloroquine have been found to be efficient on SARS-CoV-2, and reported to be efficient in Chinese COV-19 patients. We evaluate the effect of hydroxychloroquine on respiratory viral loads. Patients and methods: French Confirmed COVID-19 patients were included in a single arm protocol from early March to March 16th, to receive 600mg of hydroxychloroquine daily and their viral load in nasopharyngeal swabs was tested daily in a hospital setting. Depending on their clinical presentation, azithromycin was added to the treatment. Untreated patients from another center and cases refusing the protocol were included as negative controls. Presence and absence of virus at Day6-post inclusion was considered the end point. Results: Six patients were asymptomatic, 22 had upper respiratory tract infection symptoms and eight had lower respiratory tract infection symptoms. Twenty cases were treated in this study and showed a significant reduction of the viral carriage at D6-post inclusion compared to controls, and much lower average carrying duration than reported in the litterature for untreated patients. Azithromycin added to hydroxychloroquine was significantly more efficient for virus elimination. Conclusion: Despite its small sample size, our survey shows that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin. 

Retracted: No

PubPeer comments:
 https: www.isac.world news-and-publications official-isac-statement *Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial (Gautret P et al. PMID 32205204)* ISAC shares the concerns regarding the above article published recently in the International Journal of Antimicrobial Agents (IJAA). The ISAC Board believes the article does not meet the Societyu2019s expected standard, especially relating to the lack of better explanations of the inclusion criteria and the triage of patients to ensure patient safety. Despite some suggestions online as to the reliability of the article s peer review process, the process did adhere to the industry s peer review rules. Given his role as Editor in Chief of this journal, Jean-Marc Rolain had no involvement in the peer review of the manuscript and has no access to information regarding its peer review. Full responsibility for the manuscript s peer review process was delegated to an Associate Editor. Although ISAC recognises it is important to help the scientific community by publishing new data fast, this cannot be at the cost of reducing scientific scrutiny and best practices. Both Editors in Chief of our journals (IJAA and Journal of Global Antimicrobial Resistance) are in full agreement. Andreas Voss ISAC President April 3rd-2020 , 
 It would be great if the ISAC Society and or the Journal would give some openness about the peer review process. Since the peer review took place within 24h, there are still serious doubts about the rigor of this process, even if the the peer review was handled by a different editor. Of note, an associate editor might push for a light peer review since one of the authors is their boss in the editorial team. With almost no changes between preprint and peer-reviewed versions (except for some ND PCRs that were changed to an outcome), a very short time between submission and acceptance, a conflict of interest in the handling of this manuscript, there are many concerns left about the peer review process, even if the paper was not handled by one of the authors himself. With the whole world implementing new policies and treatment plans based on this sub-standard scientific paper, the world deserves to have a better insight in the peer-review process of this paper and to see the full peer review reports. , 
 The world also deserves a full report with an analysis using all the cases, an intent-to-treat analysis, without excluding the inconvenient cases as was done in the originally published analysis. , 
 See also the many comments on the preprint, both on PubPeer: https: pubpeer.com publications B4044A446F35DF81789F6F20F8E0EE And on the preprint server (some duplicates): https: www.medrxiv.org content 10.1101 2020.03.16.20037135v1 ,