https://www.sciencedirect.com/science/article/pii/S1477893920302817"Outcomes of 3,737 COVID-19 patients treated with hydroxychloroquine/azithromycin and other regimens in Marseille, France: A retrospective analysisAbstract
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."
"Indeed, among the candidate treatments,
only three main drugs (remdesivir, lopinavir-ritonavir and HCQ) have been tested in large comparative studies [[11], [12], [13]].
Lopinavir-ritonavir and remdesivir have not clearly demonstrated efficacy but are associated with many adverse events [11,12,14].
HCQ has demonstrated its efficacy in reducing viral shedding persistence [6] and improving clinical status in observational or randomized clinical trials [13,15,16]. In addition, we performed
a recent meta-analysis of 20 available reports, including 105,040 patients demonstrating that, in clinical studies, chloroquine and its derivatives improve clinical and biological outcomes and reduce mortality by a factor 3 in coronavirus disease 2019 (COVID-19) patients [10]. In addition, we recently reported a very low mortality rate in a retrospective analysis of more than 1,000 patients early treated with a combination of HCQ-AZ, with a very low mild adverse event rate (2.3%) [8]. Conversely, in a recent observational study, patients treated with HCQ showed no difference regarding risk of death or intubation compared with patients under other treatments [17]. However, the patients included in the group receiving HCQ had more severe disease and had more comorbidities than those who did not receive the drug [17]."
