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Early Treatment with Hydroxychloroquine and Azithromycin in 10,429 COVID-19 Outpatients: A Monocentric Retrospective Cohort Study

Million et al., Reviews in Cardiovascular Medicine, doi:10.31083/j.rcm2203116 (date from preprint)
May 2021  
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Mortality 83% Improvement Relative Risk ICU admission 44% Hospitalization 4% HCQ for COVID-19  Million et al.  EARLY TREATMENT Is early treatment with HCQ + AZ beneficial for COVID-19? Retrospective 10,429 patients in France Lower mortality with HCQ + AZ (p=0.0007) Million et al., Reviews in Cardiovascu.., May 2021 FavorsHCQ Favorscontrol 0 0.5 1 1.5 2+
HCQ for COVID-19
1st treatment shown to reduce risk in March 2020
*, now with p < 0.00000000001 from 411 studies, recognized in 46 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,300+ studies for 75 treatments.
Retrospective 10,429 outpatients in France, 8,315 treated with HCQ+AZ a median of 4 days from symptom onset, showing significantly lower mortality with treatment.
risk of death, 83.0% lower, HR 0.17, p < 0.001, treatment 5 of 8,315 (0.1%), control 11 of 2,114 (0.5%), NNT 217, adjusted per study.
risk of ICU admission, 44.0% lower, HR 0.56, p = 0.18, treatment 17 of 8,315 (0.2%), control 7 of 2,114 (0.3%), NNT 789, adjusted per study.
risk of hospitalization, 4.0% lower, HR 0.96, p = 0.77, treatment 214 of 8,315 (2.6%), control 64 of 2,114 (3.0%), adjusted per study.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Million et al., 27 May 2021, retrospective, France, peer-reviewed, 39 authors, average treatment delay 4.0 days, dosage 200mg tid days 1-10, this trial uses multiple treatments in the treatment arm (combined with AZ) - results of individual treatments may vary.
This PaperHCQAll
Early combination therapy with hydroxychloroquine and azithromycin reduces mortality in 10,429 COVID-19 outpatients
Matthieu Million, Jean-Christophe Lagier, Hervé Tissot-Dupont, Isabelle Ravaux, Catherine Dhiver, Christelle Tomei, Nadim Cassir, Léa Delorme, Sébastien Cortaredona, Sophie Amrane, Camille Aubry, Karim Bendamardji, Cyril Berenger, Barbara Doudier, Sophie Edouard, Marie Hocquart, Morgane Mailhe, Coralie Porcheto, Piseth Seng, Catherine Triquet, Stéphanie Gentile, Elisabeth Jouve, Audrey Giraud-Gatineau, Herve Chaudet, Laurence Camoin-Jau, Philippe Colson, Philippe Gautret, Pierre-Edouard Fournier, Baptiste Maille, Jean-Claude Deharo, Paul Habert, Jean-Yves Gaubert, Alexis Jacquier, Stéphane Honore, Katell Guillon-Lorvellec, Yolande Obadia, Philippe Parola, Philippe Brouqui, Didier Raoult
Reviews in Cardiovascular Medicine, doi:10.31083/j.rcm2203116
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. Metaanalysis evidenced consistency with 4 previous outpatient studies (32,124 patients-Odds ratio 0.31 [0.20-0.47], I 2 = 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.
Abbreviations HCQ, hydroxychloroquine; AZ, azithromycin; IFR, infection fatality rate. Author contributions MMillion designed and supervised the study, conducted the investigation, formal analysis and wrote the first draft of the manuscript, JCL participated in the study design, investigation and critical review, all authors (HTD, IR, CD, CT, NC, SA, CA, KB, BD, SE, MH, MMailhe, CP, PS, CT, SG, EJ, AGG, HC, LCJ, PC, PG, PEF, BM, JCD, PH, JYG, AJ, SH, KGL, YO, PP, PB) participated in the investigation and provided constructive criticism and comments, LD, CB and SC conducted the formal analysis and meta-analysis, DR designed and supervised the study, and final proofreading with key finalization of the text. Ethics approval and consent to participate Data presented herein were collected retrospectively from the routine care setting using the electronic health recording system of the hospital. The retrospective nature of the study was approved by our institutional review board committee (Méditerranée Infection N • : 2021-007). As previously reported [15] , for all patients, the prescription of HCQ+AZ was made during day hospital attendance by one of the physicians, after a collegial decision based on the most recent scientific data available and after assessment of the benefit/harm ratio of the treatment. According to European General Data Protection Regulation No 2016/679, patients were informed of the potential use of their medical data and that they could refuse the use..
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