• Jean-Christophe Lagier, Matthieu Million, Philippe Gautret, Philippe Colson, Sébastien Cortaredona, Audrey Giraud-Gatineau, Stéphane Honoré, Jean-Yves Gaubert, Pierre-Edouard Fournier, Hervé Tissot-Dupont, Eric Chabrière, Andreas Stein, Jean-Claude Deharo, Florence Fenollar, Jean-Marc Rolain, Yolande Obadia, Alexis Jacquier, Bernard La Scola, Philippe Brouqui, Michel Drancourt, Philippe Parola, Didier Raoult, and IHU COVID-19 Task force.
• IHU-Méditerranée Infection, Marseille, France; Aix Marseille University, IRD, AP-HM, MEPHI, Marseille, France.
• Travel Med Infect Dis. 2020 Jul 1; 36: 101791.

BackgroundIn 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.MethodsWe 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.ResultsThe 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.ConclusionAlthough 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.Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.

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