Abstract
Early reduction of SARS-CoV-2 viral replication emerges as a new strategy to reduce COVID-related morbidity and mortality.1 Notably, early observations2 and models3 have revealed an association between high SARS-CoV-2 nasopharyngeal RNA levels and high risk of hospitalization or death. How much this relationship relies on confounding is unknown. For example, age influences both viral clearance and the risk of adverse outcomes.3 In clinical trials, testing the potential antiviral effect using SARS-CoV-2 RNA reduction endpoint appears as a logical first step, but pivotal trials must demonstrate an effect on a clinically meaningful aspect of the disease4—that is, a patient-oriented endpoint.5 To date, there is no established predictive relationship between the magnitude and timing of viral load reductions and the extent of clinical benefit. Nevertheless, Mitjà and collaborators6 recommended 7 days as the optimal time for measurement and 0.5 log10 decrease or greater as the minimal threshold for significant reduction between arms.
Funding Information
  • Université Caen Normandie
  • Amsterdam UMC