Geographic and Temporal Variations Observed With Repurposed and Adjuvant Drug Use During COVID-19 Pandemic

Researchers assessed the use of repurposed and adjuvant drugs in hospitalized patients with COVID-19 across 3 continents.

The use of repurposed and adjuvant drugs during the COVID-19 pandemic varied geographically and temporally, based on the emergence of safety and efficacy data, according to findings from a multinational cohort study published in BMJ.

The urgency during the COVID-19 pandemic led to the rapid use of repurposed drugs and adjunctive treatments, without evidence of their effectiveness.

The current study was aimed to evaluate the use of repurposed and adjuvant drugs in hospitalized patients with COVID-19 across locations and time.

Data from electronic health records (EHRs) and insurance claims in the US, Spain, South Korea, and China were analyzed. Study participants included patients admitted to the hospital with a diagnosis of COVID-19 or a positive COVID-19 test between January and December 2020. Drugs included in the analysis were those with at least 2 randomized controlled trials, as listed in the COVID-19 Clinical Trial Tracker, which were then validated by drug development and research stakeholders.

From the 11 databases, 303,264 patients were included in the study (96% from the United States, 2.5% from South Korea, 1.7% from Spain, and 0.1% from China). In the month following hospital admission, 3455 different drugs were administered to patients with COVID-19. Some of the common repurposed drugs were:

  • Hydroxychloroquine (from <2% of patients in China to 85.1% in Spain)
  • Azithromycin (from 4.9% of patients in China to 57.9% in Spain)
  • Combined lopinavir and ritonavir (from <2% of patients in the Veterans Affairs Observational Medical Outcomes Partnership US to 34.9% in South Korea and 50.5% in Spain)
  • Umifenovir (used only in China in 78.3% of patients)

Other repurposed drugs that were commonly observed in the 11 databases were remdesivir, oseltamivir, ivermectin, pegylated interferon alfa-2a, chloroquine, ribavirin, and itraconazole. The 5 most used adjunctive treatments were enoxaparin, fluoroquinolones, ceftriaxone, vitamin D, and corticosteroids.

During the study period, hydroxychloroquine use peaked in March and April 2020 after initial (but flawed) studies were highly publicized, then declined rapidly following reports of safety concerns. However, the use of dexamethasone was initially low, but then increased in June when clinical trial data were released showing its effectiveness in reducing death rates among patients admitted to the hospital with severe respiratory disease.

Limitations of the study included the potential for misclassification of disease and treatments, inability to differentiate between when a drug was prescribed in relation to disease progression, and the lack of information on the dose and duration of the treatments.

Researchers concluded, “Great interest has been shown in the safety and efficacy of drugs used to treat [COVID-19], but little evidence exists on the prescribing patterns for repurposed and adjuvant drugs in routine clinical practice. Our study shows how unproven drug treatments were used during the first months of the pandemic, with great heterogeneity between [centers], and that they were quickly replaced by proven treatments.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Prats-Uribe A, Sena AG, Lai LYH, et al. Use of repurposed and adjuvant drugs in hospital patients COVID-19: multinational network cohort study. BMJ. Published online May 11, 2021. doi:10.1136/bmj.n1038