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Outcomes of 3,737 COVID-19 patients treated with hydroxychloroquine/azithromycin and other regimens in Marseille, France: A retrospective analysis.
Travel Med Infect Dis. 2020 Jul - Aug; 36:101791.TM

Abstract

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.

Authors+Show Affiliations

IHU-Méditerranée Infection, Marseille, France; Aix Marseille University, IRD, AP-HM, MEPHI, Marseille, France.IHU-Méditerranée Infection, Marseille, France; Aix Marseille University, IRD, AP-HM, MEPHI, Marseille, France.IHU-Méditerranée Infection, Marseille, France; Aix Marseille University, IRD, AP-HM, SSA, VITROME, Marseille, France.IHU-Méditerranée Infection, Marseille, France; Aix Marseille University, IRD, AP-HM, MEPHI, Marseille, France.IHU-Méditerranée Infection, Marseille, France; Aix Marseille University, IRD, AP-HM, SSA, VITROME, Marseille, France.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.Aix Marseille University, Laboratoire de Pharmacie Clinique, Marseille, France; AP-HM, Hôpital Timone, Service Pharmacie, Marseille, France.Department of Radiology and Cardiovascular Imaging, Aix Marseille Univ, LIIE, Marseille, France.IHU-Méditerranée Infection, Marseille, France; Aix Marseille University, IRD, AP-HM, SSA, VITROME, Marseille, France.IHU-Méditerranée Infection, Marseille, France; Aix Marseille University, IRD, AP-HM, MEPHI, Marseille, France.IHU-Méditerranée Infection, Marseille, France; Aix Marseille University, IRD, AP-HM, MEPHI, Marseille, France.IHU-Méditerranée Infection, Marseille, France; Aix Marseille University, IRD, AP-HM, MEPHI, Marseille, France.AP-HM, Aix Marseille University, Hôpital Timone, Cardiologie, Rythmologie, Marseille, France.IHU-Méditerranée Infection, Marseille, France; Aix Marseille University, IRD, AP-HM, SSA, VITROME, Marseille, France.IHU-Méditerranée Infection, Marseille, France; Aix Marseille University, IRD, AP-HM, MEPHI, Marseille, France.IHU-Méditerranée Infection, Marseille, France.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.IHU-Méditerranée Infection, Marseille, France; Aix Marseille University, IRD, AP-HM, MEPHI, Marseille, France.IHU-Méditerranée Infection, Marseille, France; Aix Marseille University, IRD, AP-HM, MEPHI, Marseille, France.IHU-Méditerranée Infection, Marseille, France; Aix Marseille University, IRD, AP-HM, MEPHI, Marseille, France.IHU-Méditerranée Infection, Marseille, France; Aix Marseille University, IRD, AP-HM, SSA, VITROME, Marseille, France.IHU-Méditerranée Infection, Marseille, France; Aix Marseille University, IRD, AP-HM, MEPHI, Marseille, France. Electronic address: didier.raoult@gmail.com.No affiliation info available

Pub Type(s)

Evaluation Study
Journal Article

Language

eng

PubMed ID

32593867

Citation

Lagier, Jean-Christophe, et al. "Outcomes of 3,737 COVID-19 Patients Treated With Hydroxychloroquine/azithromycin and Other Regimens in Marseille, France: a Retrospective Analysis." Travel Medicine and Infectious Disease, vol. 36, 2020, p. 101791.
Lagier JC, Million M, Gautret P, et al. Outcomes of 3,737 COVID-19 patients treated with hydroxychloroquine/azithromycin and other regimens in Marseille, France: A retrospective analysis. Travel Med Infect Dis. 2020;36:101791.
Lagier, J. C., Million, M., Gautret, P., Colson, P., Cortaredona, S., Giraud-Gatineau, A., Honoré, S., Gaubert, J. Y., Fournier, P. E., Tissot-Dupont, H., Chabrière, E., Stein, A., Deharo, J. C., Fenollar, F., Rolain, J. M., Obadia, Y., Jacquier, A., La Scola, B., Brouqui, P., ... Raoult, D. (2020). Outcomes of 3,737 COVID-19 patients treated with hydroxychloroquine/azithromycin and other regimens in Marseille, France: A retrospective analysis. Travel Medicine and Infectious Disease, 36, 101791. https://doi.org/10.1016/j.tmaid.2020.101791
Lagier JC, et al. Outcomes of 3,737 COVID-19 Patients Treated With Hydroxychloroquine/azithromycin and Other Regimens in Marseille, France: a Retrospective Analysis. Travel Med Infect Dis. 2020 Jul - Aug;36:101791. PubMed PMID: 32593867.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Outcomes of 3,737 COVID-19 patients treated with hydroxychloroquine/azithromycin and other regimens in Marseille, France: A retrospective analysis. AU - Lagier,Jean-Christophe, AU - Million,Matthieu, AU - Gautret,Philippe, AU - Colson,Philippe, AU - Cortaredona,Sébastien, AU - Giraud-Gatineau,Audrey, AU - Honoré,Stéphane, AU - Gaubert,Jean-Yves, AU - Fournier,Pierre-Edouard, AU - Tissot-Dupont,Hervé, AU - Chabrière,Eric, AU - Stein,Andreas, AU - Deharo,Jean-Claude, AU - Fenollar,Florence, AU - Rolain,Jean-Marc, AU - Obadia,Yolande, AU - Jacquier,Alexis, AU - La Scola,Bernard, AU - Brouqui,Philippe, AU - Drancourt,Michel, AU - Parola,Philippe, AU - Raoult,Didier, AU - ,, Y1 - 2020/06/25/ PY - 2020/05/27/received PY - 2020/06/12/revised PY - 2020/06/14/accepted PY - 2020/7/1/pubmed PY - 2020/9/25/medline PY - 2020/6/29/entrez KW - Azithromycin KW - COVID-19 KW - Hydroxychloroquine KW - SARS-CoV-2 SP - 101791 EP - 101791 JF - Travel medicine and infectious disease JO - Travel Med Infect Dis VL - 36 N2 - 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. SN - 1873-0442 UR - https://www.unboundmedicine.com/medline/citation/32593867/Outcomes_of_3737_COVID_19_patients_treated_with_hydroxychloroquine/azithromycin_and_other_regimens_in_Marseille_France:_A_retrospective_analysis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1477-8939(20)30281-7 DB - PRIME DP - Unbound Medicine ER -