IMR Press / RCM / Volume 22 / Issue 3 / DOI: 10.31083/j.rcm2203116
Open Access Original Research
Early combination therapy with hydroxychloroquine and azithromycin reduces mortality in 10,429 COVID-19 outpatients
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1 IHU-Méditerranée Infection, Aix Marseille Univ, Assistance Publique Hôpitaux de Marseille (AP-HM), Institut de recherche pour le développement (IRD), Unité Microbes Evolution Phylogénie et Infections (MEPHI),13005 Marseille, France
2 IHU-Méditerranée Infection, Aix Marseille Univ, Assistance Publique Hôpitaux de Marseille (AP-HM), Institut de recherche pour le développement (IRD), Unité Vecteurs – Infections Tropicales et Méditerranéennes (VITROME), Service de santé des armées (SSA), 13005 Marseille, France
3 EA 3279: CEReSS - Health Service Research and Quality of Life Center, Service d’Evaluation Médicale, Aix Marseille Univ, Assistance Publique Hôpitaux de Marseille, 13005 Marseille, France
4 Laboratoire D’Hématologie, Hôpital de La Timone, Assistance Publique Hôpitaux de Marseille, 13005 Marseille, France
5 Service de Cardiologie, Centre Hospitalier Universitaire La Timone, Assistance Publique Hôpitaux de Marseille, Aix Marseille Univ, C2VN, 13005 Marseille, France
6 Radiology Department, La Timone Hospital, Assistance Publique Des Hôpitaux de Marseille, Aix Marseille Univ, LIIE, CERIMED, 13005 Marseille, France
7 Service de Pharmacie, Hôpital Timone, Laboratoire de Pharmacie Clinique, Aix Marseille Université AP-HM, 13005 Marseille, France
*Correspondence: matthieu.million@gmail.com (Matthieu MILLION)
Academic Editor: Peter A. McCullough
Rev. Cardiovasc. Med. 2021, 22(3), 1063–1072; https://doi.org/10.31083/j.rcm2203116
Submitted: 10 August 2021 | Revised: 27 August 2021 | Accepted: 30 August 2021 | Published: 24 September 2021
(This article belongs to the Special Issue Utilizing Technology in the COVID 19 era)
Copyright: © 2021 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).
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.

Keywords
SARS-CoV-2
COVID-19
Hydroxychloroquine
Azithromycin
Ambulatory
Outpatients
Treatment
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