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

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.

Keywords: Azithromycin; COVID-19; Hydroxychloroquine; SARS-CoV-2.

Fig. 1

Flowchart summarizing our study design.

Fig. 2

Multiple correspondence analysis (MCA) including all the clinical and biological radiological data and the outcomes. Each dot represents a patient with good clinical outcome in green or poor clinical outcome in red (HCQ-AZ: hydroxychloroquine and azithromycin; ICU = intensive care unit). Unsupervised approaches (such as multiple correspondence analysis for qualitative variables) allow graphical representation without a priori that takes together the variables and observations (biplot). Observations (individuals) can be identified and analysed according to an additional variable (such as their good or poor clinical course). Red ellipse: 90% confidence ellipse for patients with poor clinical outcome “Death/ICU/Hospitalization=>10 days”. Green ellipse: 90% confidence ellipse for patients with good clinical outcome. Dotted ellipses were added to the MCA to better figure the 2 main clinical presentations and the severe evolutionary stage of the disease. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 3

Kaplan-Meier curve of clinical outcomes/viral shedding clearance according to treatment groups (n = 3,737). HCQ: hydroxychloroquine, AZ: azithromycin, ICU: Intensive care unit, PCR: polymerase chain reaction. a: For time to negative PCR, event was defined as first negative PCR during follow-up. Accordingly, patients were still considered positive at each time point if previous sample was positive.

Fig. 4

Evolutionary stages of SARS-CoV-2 infection, including major clinical and biological features and possible therapies.