This living review in the Annals of Internal Medicine is updated every 2 months with the latest evidence on the use of remdesivir for the treatment of adults with severe coronavirus disease 2019 (COVID-19). The review provides extensive details on the trials and the different comparisons. The following are key points to remember:

1. Remdesivir is a nucleotide analogue prodrug administered intravenously that inhibits viral RNA polymerases. It was initially developed for the treatment of Ebola and other viral infections but has shown in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has received emergency use authorization by the Food and Drug Administration (FDA) in May of 2020 for the treatment of hospitalized patients with severe COVID-19. Remdesivir still does not have FDA approval for use in COVID-19.
2. There are four randomized trials studying the use of remdesivir in COVID-19. Two trials compared remdesivir to placebo (ACTT-1 and Wang et al.), and two assessed 5- versus 10-day courses of remdesivir (SIMPLE-1 and SIMPLE-2).
3. ACTT-1 is a multinational double-blind randomized trial, which had enrolled 1,063 at the time of publication of preliminary results. SIMPLE-1 and SIMPLE-2 were open-label multinational studies and had enrolled 397 and 582, respectively. Wang et al. enrolled 237 in China, and was stopped early.
4. The dose of remdesivir in the trials was 200 mg on day 1, then 100 mg on subsequent days. Most patients were white, men, and >50 years old. Three of the trials included patients on mechanical ventilation.
5. Primary outcomes were recovery or clinical improvement defined according to an ordinal scale that included death and worsening respiratory failure. The exact definition differed across studies.
6. Compared to placebo, remdesivir shortened time to recovery (absolute risk difference, 7%-10%), and reduced adverse events (-8% to -6%) without impacting length of hospitalization. The risk reduction in mortality (-4% to 1%) was not statistically significant in either trials. A 10-day course did not confer any benefits compared to a 5-day course of remdesivir and was instead associated with higher risk of serious adverse events.
7. Remdesivir should not be used in patients with estimated glomerular filtration rate <30 ml/min/1.73 m², and should be withdrawn if alanine aminotransferase levels increase 5 times above the upper limits of normal. It should not be co-administered with hydroxychloroquine because of the latter’s potential to reduce antiviral activity.
8. Patients with severe COVID-19 on mechanical ventilation or extracorporeal membrane oxygenation did not show significant improvement on remdesivir. Otherwise, recovery due to remdesivir did vary by patient age, sex, race, or time from symptom onset.
9. ACTT-1, SIMPLE-1, and SIMPLE-2 trials continue to enroll patients. Additional large randomized trials are evaluating the effectiveness of remdesivir alone or in combination with other agents or potentially active comparators, including baricitinib, interferon-β1a, tocilizumab, lopinavir with ritonavir, and hydroxychloroquine.
10. An inhaled nebulized version of remdesivir is being evaluated for use in the outpatient setting.

Clinical Topics: COVID-19 Hub, Prevention, Novel Agents, Statins

Keywords: Alanine Transaminase, Coronavirus, COVID-19, Ebolavirus, Extracorporeal Membrane Oxygenation, Hydroxychloroquine, Interferons, Lopinavir, Outpatients, Primary Prevention, Prodrugs, remdesivir, Respiration, Artificial, Ritonavir, severe acute respiratory syndrome coronavirus 2

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