Abstract: ORIGINAL RESEARCH Annals of Internal Medicine Evaluation of the Effects of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19 A Randomized Trial Andreas Barratt-Due, PhD; Inge Christoffer Olsen, PhD; Katerina Nezvalova-Henriksen, PhD; Trine Kåsine, MD; Fridtjof Lund-Johansen, PhD; Hedda Hoel, PhD; Aleksander Rygh Holten, PhD; Anders Tveita, PhD; Alexander Mathiessen, PhD; Mette Haugli, MD; Ragnhild Eiken, MD; Anders Benjamin Kildal, PhD; Åse Berg, PhD; Asgeir Johannessen, PhD; Lars Heggelund, PhD; Tuva Børresdatter Dahl, PhD; Karoline Hansen Skåra, MSc; Pawel Mielnik, MD; Lan Ai Kieu Le, MD; Lars Thoresen, MD; Gernot Ernst, MD; Dag Arne Lihaug Hoff, PhD; Hilde Skudal, MD; Bård Reiakvam Kittang, PhD; Roy Bjørkholt Olsen, PhD; Birgitte Tholin, MD; Carl Magnus Ystrøm, MD; Nina Vibeche Skei, MD; Trung Tran, PhD; Susanne Dudman, PhD; Jan Terje Andersen, PhD; Raisa Hannula, MD; Olav Dalgard, PhD; Ane-Kristine Finbråten, PhD; Kristian Tonby, PhD; Bjorn Blomberg, PhD; Saad Aballi, MD; Cathrine Fladeby, PhD; Anne Steffensen, MSc; Fredrik Müller, PhD; Anne Ma Dyrhol-Riise, PhD; Marius Trøseid, PhD; and Pål Aukrust, PhD; for the NOR-Solidarity trial* Background: New treatment modalities are urgently needed for patients with COVID-19. The World Health Organization (WHO) Solidarity trial showed no effect of remdesivir or hydroxychloroquine (HCQ) on mortality, but the antiviral effects of these drugs are not known. Objective: To evaluate the effects of remdesivir and HCQ on all-cause, in-hospital mortality; the degree of respiratory failure and inflammation; and viral clearance in the oropharynx. Design: NOR-Solidarity is an independent, add-on, randomized controlled trial to the WHO Solidarity trial that included biobanking and 3 months of clinical follow-up (ClinicalTrials. gov: NCT04321616) Setting: 23 hospitals in Norway. Patients: Eligible patients were adults hospitalized with confirmed SARS-CoV-2 infection. Intervention: Between 28 March and 4 October 2020, a total of 185 patients were randomly assigned and 181 were included in the full analysis set. Patients received remdesivir (n = 42), HCQ (n = 52), or standard of care (SoC) (n = 87). Measurements: In addition to the primary end point of WHO Solidarity, study-specific outcomes were viral clearance I n February 2020, a World Health Organization (WHO) expert group recommended that 4 drugs approved for other indications—hydroxychloroquine (HCQ), remdesivir, ritonavir-boosted lopinavir, and interferon-b 1a—should be evaluated in an international, adaptive, open-label, randomized clinical trial and compared with standard of care (SoC) in the treatment of hospitalized patients with SARS-CoV-2 infection. This initiative resulted in initiation of the WHO Solidarity trial (1). The HCQ and lopinavir groups of this trial were subsequently stopped because of reported lack of effect based on emerging external evidence from the RECOVERY (Randomised Evaluation of COVID-19 Therapy) trial, as well as internal evidence from interim analyses (2). In October 2020, the WHO Solidarity trial consortium published interim results, reporting that all of the repurposed drugs evaluated showed little or no effect on inhospital mortality and did not reduce the need for mechanical in oropharyngeal specimens, the degree of respiratory failure, and inflammatory variables. Results: No significant differences were seen between treatment groups in mortality during hospitalization. There was a..