Abstract: International Journal of Infectious Diseases 108 (2021) 370–376 Contents lists available at ScienceDirect International Journal of Infectious Diseases journal homepage: www.elsevier.com/locate/ijid Hydroxychloroquine as a primary prophylactic agent against SARS-CoV-2 infection: A cohort study Peter Kamstrupa,* , Pradeesh Sivapalana , Josefin Eklöfa , Nils Hoyera , Charlotte Suppli Ulrikb , Lars Pedersenc, Therese S. Lapperrec , Zitta Barrella Harboed,i , Uffe Bodtgere, Rasmus Dahlin Bojesenf , Kjell E.J. Håkanssonb , Casper Tidemandsenb , Karin Armbrustera , Andrea Browatzkid , Howraman Meterana , Christian Niels Meyerg, Kristoffer Grundtvig Skaaruph , Mats Christian Højbjerg Lassenh , Jens D. Lundgreni,j , Tor Biering-Sørensenh,i,k , Jens-Ulrik Jensena,i,j a Section of Respiratory Medicine, Department of Medicine, Copenhagen University Hospital Herlev and Gentofte Hospital, Hellerup, Denmark Department of Respiratory Medicine, Copenhagen University Hospital-Hvidovre, Hvidovre, Denmark Department of Respiratory Medicine, Copenhagen University Hospital-Bispebjerg, Copenhagen, Denmark d Department of Pulmonary and Infectious Diseases, Copenhagen University Hospital North Zealand, Hillerød, Denmark e Respiratory Research Unit, Department of Respiratory Medicine, Næstved, Slagelse and Ringsted Hospitals, Næstved, Denmark f Department of Surgery, Næstved, Slagelse and Ringsted Hospitals, Slagelse, Denmark g Department of Medicine, Zealand University Hospital, Roskilde, Denmark h Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte Hospital, Hellerup, Denmark i Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark j PERSIMUNE & CHIP: Department of Infectious Diseases, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark k Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark b c A R T I C L E I N F O A B S T R A C T Article history: Received 16 April 2021 Received in revised form 17 May 2021 Accepted 28 May 2021 Objective: Hydroxychloroquine has been proposed as a primary prophylactic agent against coronavirus disease 2019 (COVID-19). This study aimed to investigate if patients treated with hydroxychloroquine for a non-COVID-19 indication had a lower risk of verified infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) compared with matched controls. Methods: A cohort comprising all persons in Denmark collecting hydroxychloroquine prescriptions in 2020 and 2019 (i.e., both during and before SARS-CoV-2 was confirmed in Denmark), matched by age and sex with controls, was studied. Data were collected using the Danish national registries, which contain complete information on patient health data, prescriptions and microbiological test results. The main outcome was microbiologically verified SARS-CoV-2 infection. Results: In total, 5488 hydroxychloroquine users were matched with 54,486 non-users. At baseline, the groups differed in terms of diagnoses of pulmonary disease, cardiovascular disease, renal disease, gastrointestinal/metabolic disease and dementia, as well as treatment with antirheumatic drugs. The final model was adjusted for these potential confounders. Use of hydroxychloroquine for non-COVID-19 indications was not associated with any change in confirmed SARS-CoV-2 (hazard ratio 0.90, 95% confidence interval 0.76–1.07). This result was robust in..