Abstract: ARTICLE https://doi.org/10.1038/s41467-020-19056-6 OPEN A pragmatic randomized controlled trial reports lack of efficacy of hydroxychloroquine on coronavirus disease 2019 viral kinetics 1234567890():,; Magnus Nakrem Lyngbakken 1,2, Jan-Erik Berdal2,3, Arne Eskesen3, Dag Kvale 2,4, Inge Christoffer Olsen5, Corina Silvia Rueegg 5,6, Anbjørg Rangberg7, Christine Monceyron Jonassen7, Torbjørn Omland1,2, Helge Røsjø 2,8 ✉ & Olav Dalgard2,3 Here, we randomized 53 patients hospitalized with coronavirus disease 2019 (COVID-19) to hydroxychloroquine therapy (at a dose of 400 mg twice daily for seven days) in addition to standard care or standard care alone (ClinicalTrials.gov Identifier, NCT04316377). All severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive patients 18 years of age or older were eligible for study inclusion if they had moderately severe COVID-19 at admission. Treatment with hydroxychloroquine did not result in a significantly greater rate of decline in SARS-CoV-2 oropharyngeal viral load compared to standard care alone during the first five days. Our results suggest no important antiviral effect of hydroxychloroquine in humans infected with SARS-CoV-2. 1 Division of Medicine, Akershus University Hospital, Lørenskog, Norway. 2 Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. 3 Department of Infectious Diseases, Division of Medicine, Akershus University Hospital, Lørenskog, Norway. 4 Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway. 5 Department of Research Support for Clinical Trials, Oslo University Hospital, Oslo, Norway. 6 Oslo Centre for Biostatistics and Epidemiology, Oslo University Hospital, Oslo, Norway. 7 Center for Laboratory Medicine, Østfold Hospital Trust, Grålum, Norway. 8 Division of Research and Innovation, Akershus University Hospital, Lørenskog, Norway. ✉email: helge.rosjo@medisin.uio.no NATURE COMMUNICATIONS | (2020)11:5284 | https://doi.org/10.1038/s41467-020-19056-6 | www.nature.com/naturecommunications 1 ARTICLE NATURE COMMUNICATIONS | https://doi.org/10.1038/s41467-020-19056-6 H ydroxychloroquine is a registered therapeutic against malaria and several autoimmune conditions, and has in vitro inhibitory effects on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in nontoxic concentrations1. In a recent report, hydroxychloroquine given more than 2 weeks after first symptoms had no effect on the clearance of SARS-CoV-2 in various respiratory tract specimens of afebrile patients hospitalized with coronavirus 2019 (COVID-19) partly pretreated with antiviral drugs2. Viral clearance is however an incomplete characterization of viral kinetics, and the impact of hydroxychloroquine therapy on SARS-CoV-2 viral kinetics in subjects hospitalized with COVID-19 remains to be elucidated. Hydroxychloroquine is postulated to affect viral replication, and it is reasonable to assume that an effective antiviral drug will affect respiratory tract viral titers and thereby improve the symptoms and host inflammatory responses, including the cytokine and chemokine expression that is likely responsible for many of the clinical symptoms of COVID-193. Here we report findings from a two-arm, open label, pragmatic randomized controlled trial, the Norwegian Coronavirus Disease 2019 (NO COVID-19) Study (NCT04316377), that assessed the efficacy and safety of hydroxychloroquine therapy on SARS-CoV-2 oropharyngeal viral kinetics in patients..