Is there sufficient evidence of antiviral medication effectiveness to prescribe one of these drugs for prevention or treatment of COVID-19?
Several antiviral agents, alone or in combination, have been used in patients with COVID-19. Many of the reports to date – usually small studies lacking a contemporaneous control group and often reported rapidly without the benefit of peer review – have suggested some benefit. Studies incorporating remdesivir have been the most frequently reported. This phosphorylated nucleoside analog interferes with viral RNA transcription and is rapidly taken up by cells. Based in part on data described below, the U.S. FDA approved an emergency use authorization (EUA – see ACMT webinar from April 22, 2020) for remdesivir use in hospitalized patients with severe COVID-19 on May 1, 2020. As with other EUAs, FDA is requiring health care providers to report all medication errors and serious adverse events potentially related to remdesivir use via the MedWatch program.
One report (NEJM 2020) of open-label administration of remdesivir (200mg followed by 100mg daily for up to an additional 9 days; completed in 75%) in 53 of 61 hospitalized COVID-19 patients demonstrating room air O2sat <94%, followed to outcome as of 28 days demonstrated improvement in 84% of patients, while 13% had died. The patient group had a median age of 62 (range 23-82yrs), 68% with co-existing conditions. Mechanical ventilation was performed in 57%, and 8% were on ECMO (extra-corporeal membrane oxygenation) for a median of 2 days before treatment begun (IQR: 1-8days). More than ½ of the intubated patients were extubated successfully and 3 of the 4 patients were able to come off ECMO. This multi-national study suggests that remdesivir was well-tolerated and associated with improvement, although data on 8 patients was not available. These results stand in contrast to reported randomized, controlled trials during the Ebola epidemics, where increased mortality in the remdesivir led to discontinuation of that arm. Late administration and potentially sicker patients are a possible explanation, with concern that inhibiting viral replication once that had already peaked would be of limited efficacy.
A recent interim analysis of a randomized controlled study of 1,063 patients did report a more rapid recovery from COVID-19 in those patients receiving remdesivir compared to placebo (median 11 days vs 15 days) and a borderline statistically nonsignificant improvement in mortality (8% vs 11.6%; p=0.059). The interim evaluation by an independent data and safety monitoring board of this NIAID (NIH/National Institute of Allergy and Infectious Diseases)-sponsored study at the University of Nebraska Medical Center did not include details regarding baseline or illness severity characteristics of the participants.
Grein J, Ohmagari N, Shin D, Diaz G, Asperges E, et al. Compassionate use of remdesivir for patients with severe Covid-19. NEJM 2020; published online April 20, 2020. Accessed May 12, 2020 at: https://www.nejm.org/doi/pdf/10.1056/NEJMoa2007016?articleTools=true
NIH/NIAID. NIH clinical trial shows remdesivir accelerates recovery from advanced COVID-19. April 29, 2020. Accessed May 12, 2020 at: https://www.niaid.nih.gov/news-events/nih-clinical-trial-shows-remdesivir-accelerates-recovery-advanced-covid-19
Tchesnokov EP, Feng JY, Porter DP, Götte M. Mechanism of inhibition of Ebola Virus RNA-dependent RNA polymerase by remdesivir. Viruses 2019;11, 326. Accessed May 12, 2020 at:
U.S. Food and Drug Administration. Fact Sheet for health care providers emergency use authorization (EUA) of remdesivir (GS-5734™). Accesssed May 12, 2020 at: https://www.fda.gov/media/137566/download