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1.
Rev Cardiovasc Med ; 22(3): 1063-1072, 2021 09 24.
Article in English | MEDLINE | ID: covidwho-1439023

ABSTRACT

We evaluated the age-specific mortality of unselected adult outpatients infected with SARS-CoV-2 treated early in a dedicated COVID-19 day hospital and we assessed whether the use of hydroxychloroquine (HCQ) + azithromycin (AZ) was associated with improved survival in this cohort. A retrospective monocentric cohort study was conducted in the day hospital of our center from March to December 2020 in adults with PCR-proven infection who were treated as outpatients with a standardized protocol. The primary endpoint was 6-week mortality, and secondary endpoints were transfer to the intensive care unit and hospitalization rate. Among 10,429 patients (median age, 45 [IQR 32-57] years; 5597 [53.7%] women), 16 died (0.15%). The infection fatality rate was 0.06% among the 8315 patients treated with HCQ+AZ. No deaths occurred among the 8414 patients younger than 60 years. Older age and male sex were associated with a higher risk of death, ICU transfer, and hospitalization. Treatment with HCQ+AZ (0.17 [0.06-0.48]) was associated with a lower risk of death, independently of age, sex and epidemic period. Meta-analysis evidenced consistency with 4 previous outpatient studies (32,124 patients-Odds ratio 0.31 [0.20-0.47], I2 = 0%). Early ambulatory treatment of COVID-19 with HCQ+AZ as a standard of care is associated with very low mortality, and HCQ+AZ improve COVID-19 survival compared to other regimens.


Subject(s)
Ambulatory Care , Antiviral Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19/drug therapy , Early Medical Intervention , Hydroxychloroquine/therapeutic use , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Antiviral Agents/adverse effects , Azithromycin/adverse effects , COVID-19/diagnosis , COVID-19/mortality , Drug Therapy, Combination , Female , France , Hospitalization , Humans , Hydroxychloroquine/adverse effects , Male , Middle Aged , Outpatients , Retrospective Studies , Risk Assessment , Risk Factors , Sex Factors , Time Factors , Treatment Outcome , Young Adult
2.
Microb Drug Resist ; 27(3): 281-290, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1137930

ABSTRACT

The coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2, has recently emerged worldwide. In this context, there is an urgent need to identify safe and effective therapeutic strategies for treatment of such highly contagious disease. We recently reported promising results of combining hydroxychloroquine and azithromycin as an early treatment option. Although ongoing clinical trials are challenging the efficacy of this combination, many clinicians claim the authorization to or have already begun to use it to treat COVID-19 patients worldwide. The aim of this article is to share pharmacology considerations contributing to the rationale of this combination, and to provide safety information to prevent toxicity and drug-drug interactions, based on available evidence.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Antiviral Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19/drug therapy , Hydroxychloroquine/therapeutic use , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/pharmacology , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , Antiviral Agents/pharmacology , Azithromycin/administration & dosage , Azithromycin/adverse effects , Azithromycin/pharmacology , Dose-Response Relationship, Drug , Drug Interactions , Drug Therapy, Combination , Humans , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/adverse effects , Hydroxychloroquine/pharmacology , SARS-CoV-2
3.
Int J Cardiol ; 331: 333-339, 2021 05 15.
Article in English | MEDLINE | ID: covidwho-1056682

ABSTRACT

BACKGROUND: QTc interval monitoring, for the prevention of drug-induced arrhythmias is necessary, especially in the context of coronavirus disease 2019 (COVID-19). For the provision of widespread use, surrogates for 12­lead ECG QTc assessment may be useful. This prospective observational study compared QTc duration assessed by artificial intelligence (AI-QTc) (Cardiologs®, Paris, France) on smartwatch single­lead electrocardiograms (SW-ECGs) with those measured on 12­lead ECGs, in patients with early stage COVID-19 treated with a hydroxychloroquine-azithromycin regimen. METHODS: Consecutive patients with COVID-19 who needed hydroxychloroquine-azithromycin therapy, received a smartwatch (Withings Move ECG®, Withings, France). At baseline, day-6 and day-10, a 12­lead ECG was recorded, and a SW-ECG was transmitted thereafter. Throughout the drug regimen, a SW-ECG was transmitted every morning at rest. Agreement between manual QTc measurement on a 12­lead ECG and AI-QTc on the corresponding SW-ECG was assessed by the Bland-Altman method. RESULTS: 85 patients (30 men, mean age 38.3 ± 12.2 years) were included in the study. Fair agreement between manual and AI-QTc values was observed, particularly at day-10, where the delay between the 12­lead ECG and the SW-ECG was the shortest (-2.6 ± 64.7 min): 407 ± 26 ms on the 12­lead ECG vs 407 ± 22 ms on SW-ECG, bias -1 ms, limits of agreement -46 ms to +45 ms; the difference between the two measures was <50 ms in 98.2% of patients. CONCLUSION: In real-world epidemic conditions, AI-QTc duration measured by SW-ECG is in fair agreement with manual measurements on 12­lead ECGs. Following further validation, AI-assisted SW-ECGs may be suitable for QTc interval monitoring. REGISTRATION: ClinicalTrial.govNCT04371744.


Subject(s)
Arrhythmias, Cardiac/diagnosis , Artificial Intelligence , COVID-19/drug therapy , Electrocardiography , Long QT Syndrome , Adult , Arrhythmias, Cardiac/chemically induced , Azithromycin/adverse effects , Azithromycin/therapeutic use , Female , Humans , Hydroxychloroquine/adverse effects , Hydroxychloroquine/therapeutic use , Long QT Syndrome/epidemiology , Male , Middle Aged , Pandemics
5.
Travel Med Infect Dis ; 36: 101791, 2020.
Article in English | MEDLINE | ID: covidwho-613565

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.


Subject(s)
Antiviral Agents/therapeutic use , Azithromycin/therapeutic use , Betacoronavirus , Coronavirus Infections/drug therapy , Hydroxychloroquine/therapeutic use , Pneumonia, Viral/drug therapy , Adult , COVID-19 , Coronavirus Infections/mortality , Coronavirus Infections/virology , Female , France/epidemiology , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Retrospective Studies , SARS-CoV-2 , Treatment Outcome
6.
Travel Med Infect Dis ; 35: 101738, 2020.
Article in English | MEDLINE | ID: covidwho-398900

ABSTRACT

BACKGROUND: In France, the combination hydroxychloroquine (HCQ) and azithromycin (AZ) is used in the treatment of COVID-19. METHODS: We retrospectively report on 1061 SARS-CoV-2 positive tested patients treated for at least three days with the following regimen: HCQ (200 mg three times daily for ten days) + AZ (500 mg on day 1 followed by 250 mg daily for the next four days). Outcomes were death, clinical worsening (transfer to ICU, and >10 day hospitalization) and viral shedding persistence (>10 days). RESULTS: A total of 1061 patients were included in this analysis (46.4% male, mean age 43.6 years - range 14-95 years). Good clinical outcome and virological cure were obtained in 973 patients within 10 days (91.7%). Prolonged viral carriage was observed in 47 patients (4.4%) and was associated to a higher viral load at diagnosis (p < .001) but viral culture was negative at day 10. All but one, were PCR-cleared at day 15. A poor clinical outcome (PClinO) was observed for 46 patients (4.3%) and 8 died (0.75%) (74-95 years old). All deaths resulted from respiratory failure and not from cardiac toxicity. Five patients are still hospitalized (98.7% of patients cured so far). PClinO was associated with older age (OR 1.11), severity of illness at admission (OR 10.05) and low HCQ serum concentration. PClinO was independently associated with the use of selective beta-blocking agents and angiotensin II receptor blockers (p < .05). A total of 2.3% of patients reported mild adverse events (gastrointestinal or skin symptoms, headache, insomnia and transient blurred vision). CONCLUSION: Administration of the HCQ+AZ combination before COVID-19 complications occur is safe and associated with a very low fatality rate in patients.


Subject(s)
Antiviral Agents/therapeutic use , Azithromycin/therapeutic use , Betacoronavirus/genetics , Coronavirus Infections/drug therapy , Hydroxychloroquine/therapeutic use , Pneumonia, Viral/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , Azithromycin/administration & dosage , Azithromycin/adverse effects , COVID-19 , Coronavirus Infections/mortality , Coronavirus Infections/virology , Drug Therapy, Combination , Female , Follow-Up Studies , France , Humans , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/adverse effects , Male , Middle Aged , Pandemics , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Polymerase Chain Reaction , Retrospective Studies , SARS-CoV-2 , Time Factors , Treatment Outcome , Viral Load , Young Adult
8.
Travel Med Infect Dis ; 34: 101663, 2020.
Article in English | MEDLINE | ID: covidwho-47331

ABSTRACT

BACKGROUND: We need an effective treatment to cure COVID-19 patients and to decrease virus carriage duration. METHODS: We conducted an uncontrolled, non-comparative, observational study in a cohort of 80 relatively mildly infected inpatients treated with a combination of hydroxychloroquine and azithromycin over a period of at least three days, with three main measurements: clinical outcome, contagiousness as assessed by PCR and culture, and length of stay in infectious disease unit (IDU). RESULTS: All patients improved clinically except one 86 year-old patient who died, and one 74 year-old patient still in intensive care. A rapid fall of nasopharyngeal viral load was noted, with 83% negative at Day7, and 93% at Day8. Virus cultures from patient respiratory samples were negative in 97.5% of patients at Day5. Consequently patients were able to be rapidly discharged from IDU with a mean length of stay of five days. CONCLUSION: We believe there is urgency to evaluate the effectiveness of this potentially-life saving therapeutic strategy at a larger scale, both to treat and cure patients at an early stage before irreversible severe respiratory complications take hold and to decrease duration of carriage and avoid the spread of the disease. Furthermore, the cost of treatment is negligible.


Subject(s)
Azithromycin/therapeutic use , Coronavirus Infections/drug therapy , Hydroxychloroquine/therapeutic use , Pneumonia, Viral/drug therapy , Adult , Aged , Aged, 80 and over , Betacoronavirus/drug effects , COVID-19 , Drug Therapy, Combination , Female , France , Humans , Male , Middle Aged , Nasopharynx/virology , Pandemics , Pilot Projects , SARS-CoV-2 , Viral Load , Young Adult
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