Objective To investigate the use of repurposed and adjuvant drugs in patients admitted to hospital with covid-19 across three continents. Design Multinational network cohort study. Setting Hospital electronic health records from the United States, Spain, and China, and nationwide claims data from South Korea. Participants 303 264 patients admitted to hospital with covid-19 from January 2020 to December 2020. Main outcome measures Prescriptions or dispensations of any drug on or 30 days after the date of hospital admission for covid-19. Results Of the 303 264 patients included, 290 131 were from the US, 7599 from South Korea, 5230 from Spain, and 304 from China. 3455 drugs were identified. Common repurposed drugs were hydroxychloroquine (used in from <5 (<2%) patients in China to 2165 (85.1%) in Spain), azithromycin (from 15 (4.9%) in China to 1473 (57.9%) in Spain), combined lopinavir and ritonavir (from 156 (<2%) in the VA-OMOP US to 2,652 (34.9%) in South Korea and 1285 (50.5%) in Spain), and umifenovir (0% in the US, South Korea, and Spain and 238 (78.3%) in China). Use of adjunctive drugs varied greatly, with the five most used treatments being enoxaparin, fluoroquinolones, ceftriaxone, vitamin D, and corticosteroids. Hydroxychloroquine use increased rapidly from March to April 2020 but declined steeply in May to June and remained low for the rest of the year. The use of dexamethasone and corticosteroids increased steadily during 2020. Conclusions Multiple drugs were used in the first few months of the covid-19 pandemic, with substantial geographical and temporal variation. Hydroxychloroquine, azithromycin, lopinavir-ritonavir, and umifenovir (in China only) were the most prescribed repurposed drugs. Antithrombotics, antibiotics, H2 receptor antagonists, and corticosteroids were often used as adjunctive treatments. Research is needed on the comparative risk and benefit of these treatments in the management of covid-19.
Bibliographical noteFunding: The European Health Data and Evidence Network has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 806968. This initiative receives support from the European Union’s Horizon 2020 research and innovation programme and the European Federation of Pharmaceutical Industries and Associations (EFPIA). This research received partial support from the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, US National Institutes of Health (R01 LM00691), US Department of Veterans Affairs, Janssen Research and Development, and IQVIA. This work was also supported by the Bio Industrial Strategic Technology Development programme (20001234) funded by the Ministry of Trade, Industry, and Energy (MOTIE, Korea) and a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (grant No HI16C0992). This study was supported by the National Key Research and Development programme of China (project No 2018YFC0116901). Personal funding included Versus Arthritis (21605), Medical Research Council Doctoral Training Partnership (MRC-DTP) (MR/K501256/1) (JL); MRC-DTP (MR/K501256/1, MR/N013468/1) and Fundación Alfonso Martín Escudero (FAME) (APU); Innovation Fund Denmark (5153-00002B) and the Novo Nordisk Foundation (NNF14CC0001) (BSKH); VINCI (VA HSR RES 13-457) (SLD, MEM, KEL); and NIHR senior research fellowship (SRF-2018-11-ST2-004, DPA). The University of Oxford received funding related to this work from the Bill and Melinda Gates Foundation (investment ID INV-016201 and INV-019257). No funders had a direct role in this study. The views and opinions expressed are those of the authors and do not necessarily reflect those of the Clinician Scientist Award programme, NIHR, Department of Veterans Affairs or the US government, the Ministry of Science and Technology of China, and the UK National Health Service or Department of Health, England. The funders had no role in considering the study design or in the collection, analysis, interpretation of data, writing of the report, or decision to submit the article for publication.
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