Early combination therapy with hydroxychloroquine and azithromycin reduces mortality in 10,429 COVID-19 outpatients.

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.

Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial.

BACKGROUND: Chloroquine and hydroxychloroquine have been found to be efficient on SARS-CoV-2, and reported to be efficient in Chinese COV-19 patients. We evaluate the effect of hydroxychloroquine on respiratory viral loads. PATIENTS AND METHODS: French Confirmed COVID-19 patients were included in a single arm protocol from early March to March 16th, to receive 600mg of hydroxychloroquine daily and their viral load in nasopharyngeal swabs was tested daily in a hospital setting. Depending on their clinical presentation, azithromycin was added to the treatment. Untreated patients from another center and cases refusing the protocol were included as negative controls. Presence and absence of virus at Day6-post inclusion was considered the end point. RESULTS: Six patients were asymptomatic, 22 had upper respiratory tract infection symptoms and eight had lower respiratory tract infection symptoms. Twenty cases were treated in this study and showed a significant reduction of the viral carriage at D6-post inclusion compared to controls, and much lower average carrying duration than reported in the litterature for untreated patients. Azithromycin added to hydroxychloroquine was significantly more efficient for virus elimination. CONCLUSION: Despite its small sample size, our survey shows that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin.

Early treatment of COVID-19 patients with hydroxychloroquine and azithromycin: A retrospective analysis of 1061 cases in Marseille, France.

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.

Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study.

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.

Rapid viral diagnosis and ambulatory management of suspected COVID-19 cases presenting at the infectious diseases referral hospital in Marseille, France, - January 31st to March 1st, 2020: A respiratory virus snapshot.

BACKGROUND: Rapid virological diagnosis is needed to limit the length of isolation for suspected COVID-19 cases. METHOD: We managed the first 280 patients suspected to have COVID-19 through a rapid care circuit and virological diagnosis in our infectious disease reference hospital in Marseille, France. Rapid viral detection was performed on sputum and nasopharyngeal samples. RESULTS: Over our study period, no SARS-CoV-2 was detected. Results were obtained within approximately 3 h of the arrival of patient samples at the laboratory. Other viral infections were identified in 49% of the patients, with most common pathogens being influenza A and B viruses, rhinovirus, metapneumovirus and common coronaviruses, notably HKU1 and NL63. CONCLUSION: Early recognition of COVID-19 is critical to isolate confirmed cases and prevent further transmission. Early rule-out of COVID-19 allows public health containment measures to be adjusted by reducing the time spent in isolation.

Testing the repatriated for SARS-Cov2: Should laboratory-based quarantine replace traditional quarantine?

BACKGROUND: An ongoing epidemic of respiratory diseases caused by a novel coronavirus (COVID 2019, SARS-CoV2) started in Wuhan, Hubei, in China at the end of December 2019. The French government decided to repatriate the 337 French nationals living in Wuhan and place them in quarantine in their home country. We decided to test them all for SARS-Cov2 twice in order to reduce anxiety among the population and decision-makers. METHODS: We investigated the presence of SARS-CoV-19 in asymptomatic carriers by testing all repatriated patients within the first 24 h of their arrival in France and at day 5. Viral RNA was extracted from pooled nasal and oropharyngeal swab fluids or sputum in the absence of nasal/oropharyngeal swabs. Detection of SARS-CoV-2 RNA was then carried out using several real-time reverse transcription (RT)-PCR assays. RESULTS: We tested 337 passengers at day 0 and day 5. All the tests for SARS-CoV2 were negative. By optimising the sampling process, sending samples sequentially and reducing the time-scale for biological analysis, we were able to test the samples within 5 h (including sampling, shipment and biological tests). CONCLUSION: Optimising our procedures reduces anxiety and reassures the population and decision makers.