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

Million, Matthieu; Lagier, Jean-Christophe; Tissot-Dupont, Hervé; Ravaux, Isabelle; Dhiver, Catherine; Tomei, Christelle; Cassir, Nadim; Delorme, Léa; Cortaredona, Sébastien; Amrane, Sophie; Aubry, Camille; Bendamardji, Karim; Berenger, Cyril; Doudier, Barbara; Edouard, Sophie; Hocquart, Marie; Mailhe, Morgane; Porcheto, Coralie; Seng, Piseth; Triquet, Catherine; Gentile, Stéphanie; Jouve, Elisabeth; Giraud-Gatineau, Audrey; Chaudet, Herve; Camoin-Jau, Laurence; Colson, Philippe; Gautret, Philippe; Fournier, Pierre-Edouard; Maille, Baptiste; Deharo, Jean-Claude; Habert, Paul; Gaubert, Jean-Yves; Jacquier, Alexis; Honore, Stéphane; Guillon-Lorvellec, Katell; Obadia, Yolande; Parola, Philippe; Brouqui, Philippe; Raoult, Didier

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.