Abstract: International Journal of Antimicrobial Agents 56 (2020) 106214 Contents lists available at ScienceDirect International Journal of Antimicrobial Agents journal homepage: www.elsevier.com/locate/ijantimicag COVID-19 outpatients: early risk-stratified treatment with zinc plus low-dose hydroxychloroquine and azithromycin: a retrospective case series study Roland Derwand a,1, Martin Scholz b,1,∗, Vladimir Zelenko c a b c Alexion Pharma Germany GmbH, 80687, Munich, Germany Heinrich-Heine-University, Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Germany Medical Group Practice, Monroe, NY, 10950, USA a r t i c l e Keywords: SARS-CoV-2 COVID-19 Outpatients Zinc Hydroxychloroquine Azithromycin i n f o a b s t r a c t The aim of this study was to describe the outcomes of patients with coronavirus disease 2019 (COVID-19) in the outpatient setting after early treatment with zinc, low-dose hydroxychloroquine and azithromycin (triple therapy) dependent on risk stratification. This was a retrospective case series study in the general practice setting. A total of 141 COVID-19 patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the year 2020 were included. The main outcome measures were risk-stratified treatment decision and rates of hospitalisation and all-cause death. A median of 4 days [interquartile range (IQR) 3–6 days; available for n = 66/141 patients] after the onset of symptoms, 141 patients (median age 58 years, IQR 40–67 years; 73.0% male) received a prescription for triple therapy for 5 days. Independent public reference data from 377 confirmed COVID-19 patients in the same community were used as untreated controls. Of 141 treated patients, 4 (2.8%) were hospitalised, which was significantly fewer (P < 0.001) compared with 58 (15.4%) of 377 untreated patients [odds ratio (OR) = 0.16, 95% confidence interval (CI) 0.06–0.5]. One patient (0.7%) in the treatment group died versus 13 patients (3.4%) in the untreated group (OR = 0.2, 95% CI 0.03–1.5; P = 0.12). No cardiac side effects were observed. Risk stratification-based treatment of COVID-19 outpatients as early as possible after symptom onset using triple therapy, including the combination of zinc with low-dose hydroxychloroquine, was associated with significantly fewer hospitalisations. © 2020 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)