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.
Data sharing statement: Analyses were performed locally in compliance with all applicable data privacy laws. Although the underlying data is not readily available to be shared, authors contributing to this paper have direct access to the data sources used in this study. All results (e.g. aggregate statistics, not presented at a patient-level with redactions for minimum cell count) are available for public inquiry. These results are inclusive of site-identifiers by contributing data sources to enable interrogation of each contributing site. All analytic code and result sets are made available at: https://github.com/ohdsi-studies/Covid19CharacterizationCharybdis
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