ABSTRACT
BACKGROUND: Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been shown to be efficacious. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. RESULTS: A total of 1062 patients underwent randomization (with 541 assigned to remdesivir and 521 to placebo). Those who received remdesivir had a median recovery time of 10 days (95% confidence interval [CI], 9 to 11), as compared with 15 days (95% CI, 13 to 18) among those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P<0.001, by a log-rank test). In an analysis that used a proportional-odds model with an eight-category ordinal scale, the patients who received remdesivir were found to be more likely than those who received placebo to have clinical improvement at day 15 (odds ratio, 1.5; 95% CI, 1.2 to 1.9, after adjustment for actual disease severity). The Kaplan-Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 and 11.4% with remdesivir and 15.2% with placebo by day 29 (hazard ratio, 0.73; 95% CI, 0.52 to 1.03). Serious adverse events were reported in 131 of the 532 patients who received remdesivir (24.6%) and in 163 of the 516 patients who received placebo (31.6%). CONCLUSIONS: Our data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.).
Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adenosine Monophosphate/administration & dosage , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/therapeutic use , Administration, Intravenous , Adult , Aged , Alanine/administration & dosage , Alanine/adverse effects , Alanine/therapeutic use , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , Betacoronavirus , COVID-19 , Coronavirus Infections/mortality , Coronavirus Infections/therapy , Double-Blind Method , Extracorporeal Membrane Oxygenation , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Oxygen Inhalation Therapy , Pandemics , Pneumonia, Viral/mortality , Pneumonia, Viral/therapy , Respiration, Artificial , SARS-CoV-2 , Time Factors , Young Adult , COVID-19 Drug TreatmentABSTRACT
The widespread use of facemasks has been a crucial element in the control of the SARS-CoV-2 pandemic. With mounting evidence for mask efficacy against respiratory infectious diseases and greater acceptability of this intervention, it is proposed that masking should continue after the pandemic has abated to protect some of our most vulnerable patients, recipients of stem cell and solid organ transplants. This may involve not only masking these high-risk patients, but possibly their close contacts and the healthcare workers involved in their care. We review the evidence for mask efficacy in prevention of respiratory viruses other than SARS-CoV-2 and address the burden of disease in transplant recipients. Although we acknowledge that there are limited data on masking to prevent infection in transplant recipients, we propose a framework for the study and implementation of routine masking as a part of infection prevention interventions after transplantation.