Outcomes of 3,737 COVID-19 patients treated with hydroxychloroquine/azithromycin and other regimens in Marseille, France: A retrospective analysis.


Journal

Travel medicine and infectious disease
ISSN: 1873-0442
Titre abrégé: Travel Med Infect Dis
Pays: Netherlands
ID NLM: 101230758

Informations de publication

Date de publication:
Historique:
received: 27 05 2020
revised: 12 06 2020
accepted: 14 06 2020
pubmed: 1 7 2020
medline: 25 9 2020
entrez: 29 6 2020
Statut: ppublish

Résumé

In our institute in Marseille, France, we initiated early and massive screening for coronavirus disease 2019 (COVID-19). Hospitalization and early treatment with hydroxychloroquine and azithromycin (HCQ-AZ) was proposed for the positive cases. We retrospectively report the clinical management of 3,737 screened patients, including 3,119 (83.5%) treated with HCQ-AZ (200 mg of oral HCQ, three times daily for ten days and 500 mg of oral AZ on day 1 followed by 250 mg daily for the next four days, respectively) for at least three days and 618 (16.5%) patients treated with other regimen ("others"). Outcomes were death, transfer to the intensive care unit (ICU), ≥10 days of hospitalization and viral shedding. The patients' mean age was 45 (sd 17) years, 45% were male, and the case fatality rate was 0.9%. We performed 2,065 low-dose computed tomography (CT) scans highlighting lung lesions in 592 of the 991 (59.7%) patients with minimal clinical symptoms (NEWS score = 0). A discrepancy between spontaneous dyspnoea, hypoxemia and lung lesions was observed. Clinical factors (age, comorbidities, NEWS-2 score), biological factors (lymphocytopenia; eosinopenia; decrease in blood zinc; and increase in D-dimers, lactate dehydrogenase, creatinine phosphokinase, troponin and C-reactive protein) and moderate and severe lesions detected in low-dose CT scans were associated with poor clinical outcome. Treatment with HCQ-AZ was associated with a decreased risk of transfer to ICU or death (Hazard ratio (HR) 0.18 0.11-0.27), decreased risk of hospitalization ≥10 days (odds ratios 95% CI 0.38 0.27-0.54) and shorter duration of viral shedding (time to negative PCR: HR 1.29 1.17-1.42). QTc prolongation (>60 ms) was observed in 25 patients (0.67%) leading to the cessation of treatment in 12 cases including 3 cases with QTc> 500 ms. No cases of torsade de pointe or sudden death were observed. Although this is a retrospective analysis, results suggest that early diagnosis, early isolation and early treatment of COVID-19 patients, with at least 3 days of HCQ-AZ lead to a significantly better clinical outcome and a faster viral load reduction than other treatments.

Sections du résumé

BACKGROUND
In our institute in Marseille, France, we initiated early and massive screening for coronavirus disease 2019 (COVID-19). Hospitalization and early treatment with hydroxychloroquine and azithromycin (HCQ-AZ) was proposed for the positive cases.
METHODS
We retrospectively report the clinical management of 3,737 screened patients, including 3,119 (83.5%) treated with HCQ-AZ (200 mg of oral HCQ, three times daily for ten days and 500 mg of oral AZ on day 1 followed by 250 mg daily for the next four days, respectively) for at least three days and 618 (16.5%) patients treated with other regimen ("others"). Outcomes were death, transfer to the intensive care unit (ICU), ≥10 days of hospitalization and viral shedding.
RESULTS
The patients' mean age was 45 (sd 17) years, 45% were male, and the case fatality rate was 0.9%. We performed 2,065 low-dose computed tomography (CT) scans highlighting lung lesions in 592 of the 991 (59.7%) patients with minimal clinical symptoms (NEWS score = 0). A discrepancy between spontaneous dyspnoea, hypoxemia and lung lesions was observed. Clinical factors (age, comorbidities, NEWS-2 score), biological factors (lymphocytopenia; eosinopenia; decrease in blood zinc; and increase in D-dimers, lactate dehydrogenase, creatinine phosphokinase, troponin and C-reactive protein) and moderate and severe lesions detected in low-dose CT scans were associated with poor clinical outcome. Treatment with HCQ-AZ was associated with a decreased risk of transfer to ICU or death (Hazard ratio (HR) 0.18 0.11-0.27), decreased risk of hospitalization ≥10 days (odds ratios 95% CI 0.38 0.27-0.54) and shorter duration of viral shedding (time to negative PCR: HR 1.29 1.17-1.42). QTc prolongation (>60 ms) was observed in 25 patients (0.67%) leading to the cessation of treatment in 12 cases including 3 cases with QTc> 500 ms. No cases of torsade de pointe or sudden death were observed.
CONCLUSION
Although this is a retrospective analysis, results suggest that early diagnosis, early isolation and early treatment of COVID-19 patients, with at least 3 days of HCQ-AZ lead to a significantly better clinical outcome and a faster viral load reduction than other treatments.

Identifiants

pubmed: 32593867
pii: S1477-8939(20)30281-7
doi: 10.1016/j.tmaid.2020.101791
pmc: PMC7315163
pii:
doi:

Substances chimiques

Antiviral Agents 0
Hydroxychloroquine 4QWG6N8QKH
Azithromycin 83905-01-5

Types de publication

Evaluation Study Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

101791

Investigateurs

Sophie Amrane (S)
Camille Aubry (C)
Matthieu Bardou (M)
Cyril Berenger (C)
Laurence Camoin-Jau (L)
Nadim Cassir (N)
Claire Decoster (C)
Catherine Dhiver (C)
Barbara Doudier (B)
Sophie Edouard (S)
Stéphanie Gentile (S)
Katell Guillon-Lorvellec (K)
Marie Hocquart (M)
Anthony Levasseur (A)
Morgane Mailhe (M)
Isabelle Ravaux (I)
Magali Richez (M)
Yanis Roussel (Y)
Piseth Seng (P)
Christelle Tomei (C)
Christine Zandotti (C)

Informations de copyright

Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.

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Auteurs

Jean-Christophe Lagier (JC)

IHU-Méditerranée Infection, Marseille, France; Aix Marseille University, IRD, AP-HM, MEPHI, Marseille, France.

Matthieu Million (M)

IHU-Méditerranée Infection, Marseille, France; Aix Marseille University, IRD, AP-HM, MEPHI, Marseille, France.

Philippe Gautret (P)

IHU-Méditerranée Infection, Marseille, France; Aix Marseille University, IRD, AP-HM, SSA, VITROME, Marseille, France.

Philippe Colson (P)

IHU-Méditerranée Infection, Marseille, France; Aix Marseille University, IRD, AP-HM, MEPHI, Marseille, France.

Sébastien Cortaredona (S)

IHU-Méditerranée Infection, Marseille, France; Aix Marseille University, IRD, AP-HM, SSA, VITROME, Marseille, France.

Audrey Giraud-Gatineau (A)

IHU-Méditerranée Infection, Marseille, France; Aix Marseille University, IRD, AP-HM, SSA, VITROME, Marseille, France; Centre d'Epidémiologie et de Santé Publique des Armées (CESPA), Marseille, France; AP-HM, Marseille, France.

Stéphane Honoré (S)

Aix Marseille University, Laboratoire de Pharmacie Clinique, Marseille, France; AP-HM, Hôpital Timone, Service Pharmacie, Marseille, France.

Jean-Yves Gaubert (JY)

Department of Radiology and Cardiovascular Imaging, Aix Marseille Univ, LIIE, Marseille, France.

Pierre-Edouard Fournier (PE)

IHU-Méditerranée Infection, Marseille, France; Aix Marseille University, IRD, AP-HM, SSA, VITROME, Marseille, France.

Hervé Tissot-Dupont (H)

IHU-Méditerranée Infection, Marseille, France; Aix Marseille University, IRD, AP-HM, MEPHI, Marseille, France.

Eric Chabrière (E)

IHU-Méditerranée Infection, Marseille, France; Aix Marseille University, IRD, AP-HM, MEPHI, Marseille, France.

Andreas Stein (A)

IHU-Méditerranée Infection, Marseille, France; Aix Marseille University, IRD, AP-HM, MEPHI, Marseille, France.

Jean-Claude Deharo (JC)

AP-HM, Aix Marseille University, Hôpital Timone, Cardiologie, Rythmologie, Marseille, France.

Florence Fenollar (F)

IHU-Méditerranée Infection, Marseille, France; Aix Marseille University, IRD, AP-HM, SSA, VITROME, Marseille, France.

Jean-Marc Rolain (JM)

IHU-Méditerranée Infection, Marseille, France; Aix Marseille University, IRD, AP-HM, MEPHI, Marseille, France.

Yolande Obadia (Y)

IHU-Méditerranée Infection, Marseille, France.

Alexis Jacquier (A)

Department of Radiology and Cardiovascular Imaging, Aix-Marseille Univ., UMR 7339, CNRS, CRMBM-CEMEREM (Centre de Résonance Magnétique Biologique et Médicale-Centre d'Exploration Métaboliques Par Résonance Magnétique), Marseille, France.

Bernard La Scola (B)

IHU-Méditerranée Infection, Marseille, France; Aix Marseille University, IRD, AP-HM, MEPHI, Marseille, France.

Philippe Brouqui (P)

IHU-Méditerranée Infection, Marseille, France; Aix Marseille University, IRD, AP-HM, MEPHI, Marseille, France.

Michel Drancourt (M)

IHU-Méditerranée Infection, Marseille, France; Aix Marseille University, IRD, AP-HM, MEPHI, Marseille, France.

Philippe Parola (P)

IHU-Méditerranée Infection, Marseille, France; Aix Marseille University, IRD, AP-HM, SSA, VITROME, Marseille, France.

Didier Raoult (D)

IHU-Méditerranée Infection, Marseille, France; Aix Marseille University, IRD, AP-HM, MEPHI, Marseille, France. Electronic address: didier.raoult@gmail.com.

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