Effect of remdesivir on viral dynamics in COVID-19 hospitalized patients: a modelling analysis of the randomized, controlled, open-label DisCoVeRy trial

J Antimicrob Chemother. 2022 Apr 27;77(5):1404-1412. doi: 10.1093/jac/dkac048.

Abstract

Background: The antiviral efficacy of remdesivir in COVID-19 hospitalized patients remains controversial.

Objectives: To estimate the effect of remdesivir in blocking viral replication.

Methods: We analysed nasopharyngeal normalized viral loads from 665 hospitalized patients included in the DisCoVeRy trial (NCT04315948; EudraCT 2020-000936-23), randomized to either standard of care (SoC) or SoC + remdesivir. We used a mathematical model to reconstruct viral kinetic profiles and estimate the antiviral efficacy of remdesivir in blocking viral replication. Additional analyses were conducted stratified on time of treatment initiation (≤7 or >7 days since symptom onset) or viral load at randomization (< or ≥3.5 log10 copies/104 cells).

Results: In our model, remdesivir reduced viral production by infected cells by 2-fold on average (95% CI: 1.5-3.2-fold). Model-based simulations predict that remdesivir reduced time to viral clearance by 0.7 days compared with SoC, with large inter-individual variabilities (IQR: 0.0-1.3 days). Remdesivir had a larger impact in patients with high viral load at randomization, reducing viral production by 5-fold on average (95% CI: 2.8-25-fold) and the median time to viral clearance by 2.4 days (IQR: 0.9-4.5 days).

Conclusions: Remdesivir halved viral production, leading to a median reduction of 0.7 days in the time to viral clearance compared with SoC. The efficacy was larger in patients with high viral load at randomization.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Monophosphate / analogs & derivatives
  • Alanine / analogs & derivatives
  • Alanine / therapeutic use
  • Antiviral Agents / therapeutic use
  • COVID-19 Drug Treatment*
  • Humans
  • SARS-CoV-2

Substances

  • Antiviral Agents
  • remdesivir
  • Adenosine Monophosphate
  • Alanine

Associated data

  • ClinicalTrials.gov/NCT04315948