Variation in Use of Anti-Viral and Anti-Inflammatory Medications in Patients Hospitalized with COVID-19: Results from the International Viral Infection and Respiratory Illness Universal Study (VIRUS)

RATIONALE: In the absence of effective therapies at the start of the Coronavirus disease of 2019 (COVID-19) pandemic, anti-viral and antiinflammatory medications were used for management of COVID-19 without robust evidence of their benefit. The patterns of use, implementation, and de-implementation of these medications is unclear. METHODS: We performed a retrospective, observational study on an international cohort of adult patients hospitalized from March 2020 to November 2020 with laboratory confirmed COVID-19 infection, receiving supplemental oxygen, and enrolled in the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) Registry. The primary outcome of interest was to describe the hospital-level variation in the most commonly used medications repurposed for empiric management of patients hospitalized with COVID-19 (hydroxychloroquine, remdesivir, corticosteroids, and anti-IL-6 therapies). Secondary outcomes included geographic and temporal variation in medication use. RESULTS: Among 6,621 patients with COVID-19 across 86 hospitals (predominantly USbased [88%]), 1,373 (20.7%, hospital usage rates range 0%-96.4%) received corticosteroids, 1,302 (19.7%, range 0%-100%) received hydroxychloroquine, 602 (9.1%, range: 0%-65.7%) received remdesivir, and 405 (6.1%, range 0%-87.5%) received an anti-IL6 medication. USbased hospitals vs non-US hospitals showed differences in medication use with 9.9% vs. 0.8% use of remdesivir, 19.5% vs 33.2% use of corticosteroids, 18.7% vs 29.6% use of hydroxychloroquine and 6.3% vs. 3.9% use of anti-IL6 medications. Comparing use prior to July 2020 with use after July 2020, prescription of remdesivir increased from 6.5% to 20.5%, corticosteroid use increased from 17.5% to 35.0%, hydroxychloroquine use decreased from 23.9% to 1.1% and anti-IL6 use decreased from 7.0% to 2.4%. CONCLUSIONS: Hospital-level variation and geographic variation in use of repurposed anti-viral and anti-inflammatory medications for the management of COVID-19 infection was large. Coinciding with accrual of scientific evidence, the use of remdesivir and corticosteroids increased over time, while the use of hydroxychloroquine and anti-IL6 medications decreased over time. Further studies are needed to evaluate the drivers of hospital variation and impact on clinical outcomes.