Hydroxychloroquine as a primary prophylactic agent against SARS-CoV-2 infection: A cohort study
Peter Kamstrup, Pradeesh Sivapalan, Josefin Eklöf, Nils Hoyer, Charlotte Suppli Ulrik, Lars Pedersen, Therese S Lapperre, Zitta Barrella Harboe, Uffe Bodtger, Rasmus Dahlin Bojesen, Kjell E J Håkansson, Casper Tidemandsen, Karin Armbruster, Andrea Browatzki, Howraman Meteran, Christian Niels Meyer, Kristoffer Grundtvig Skaarup, Mats Christian Højbjerg Lassen, Jens D Lundgren, Tor Biering-Sørensen, Jens-Ulrik Jensen
International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.05.076
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 the propensity-score-matched sensitivity analysis.
Conclusion: This study, which is the largest to date to investigate the primary prophylactic effect of hydroxychloroquine against SARS-CoV-2, does not support any prophylactic benefit of hydroxychloroquine in the prevention of infection with SARS-CoV-2.
Conflict of interest PS reports personal fees from Boehringer Ingelheim outside the submitted work. CT reports personal fees from TEVA outside the submitted work. KEJH reports personal fees from AstraZeneca, personal fees from TEVA and personal fees from Chiesi outside the submitted work. CSU reports personal fees from AstraZeneca; personal fees and non-financial support from GSK; personal fees from Chiesi; personal fees from TEVA; grants and personal fees from Sanofi Genzyme; personal fees from Orion Pharma; personal fees from Actelion; grants and personal fees from Boehringer-Ingelheim; grants and personal fees from Mundipharma; and grants, personal fees and non-financial support from Novartis outside the submitted work. TBS reports personal fees from Amgen, grants from Sanofi Pasteur, grants from GE Healthcare, personal fees from Sanofi Pasteur, and personal fees from Novartis outside the submitted work. All other authors declare no competing interests.
Data sharing Statistical source code used for generation of the results can be obtained via the corresponding author. Source data collected for this study will not be made available to others due to Danish legislation regarding data sharing on population data. However, Danish citizens who have a legitimate reason can apply for access to the data via the Danish National Health Authority (https:// sundhedsdatastyrelsen.dk/da/forskerservice/ansog-om-data). The study protocol is available at http://coptrin.dk/wp-content/..
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