Compassionate Use of Remdesivir for Patients with Severe Covid-19

Grein J, Ohmagari N, Shin D, et al. N Engl J Med. 2020 Apr 10. [Epub ahead of print] [CrossRef] [PubMed]

Remdesivir, a nucleotide analogue prodrug that inhibits viral RNA polymerases, has shown in vitro activity against SARS-CoV-2. In article that is already being heavily criticized, the authors provided remdesivir on a compassionate-use basis to patients hospitalized with Covid-19, the illness caused by infection with SARS-CoV-2. Patients were those with confirmed SARS-CoV-2 infection who had an oxygen saturation of 94% or less while they were breathing ambient air or who were receiving oxygen support. Patients received a 10-day course of remdesivir, consisting of 200 mg administered intravenously on day 1, followed by 100 mg daily for the remaining 9 days of treatment. Of the 61 patients who received at least one dose of remdesivir, data from 8 could not be analyzed. Of the 53 patients, 30 patients (57%) were receiving mechanical ventilation and 4 (8%) were receiving extracorporeal membrane oxygenation. During a median follow-up of 18 days, 36 patients (68%) had an improvement in oxygen-support class, including 17 of 30 patients (57%) receiving mechanical ventilation who were extubated. A total of 25 patients (47%) were discharged, and 7 patients (13%) died; mortality was 18% (6 of 34) among patients receiving invasive ventilation and 5% (1 of 19) among those not receiving invasive ventilation. The authors suggest that measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesivir therapy. The  paper has been criticized by a number of scientists but probably none as severe as Josh Farkas in his Pulmcrit blog. He was particularly critical of the lack of a control group and the lack of endpoints for the trial.