Timing of Antiviral Treatment Initiation is Critical to Reduce SARS-CoV-2 Viral Load

Antonio Gonçalves, Julie Bertrand, Ruian Ke, Emmanuelle Comets, Xavier de Lamballerie, Denis Malvy, Andrés Pizzorno, Olivier Terrier, Manuel Rosa Calatrava, France Mentré, Patrick Smith, Alan S Perelson, Jérémie Guedj, Antonio Gonçalves, Julie Bertrand, Ruian Ke, Emmanuelle Comets, Xavier de Lamballerie, Denis Malvy, Andrés Pizzorno, Olivier Terrier, Manuel Rosa Calatrava, France Mentré, Patrick Smith, Alan S Perelson, Jérémie Guedj

Abstract

We modeled the viral dynamics of 13 untreated patients infected with severe acute respiratory syndrome-coronavirus 2 to infer viral growth parameters and predict the effects of antiviral treatments. In order to reduce peak viral load by more than two logs, drug efficacy needs to be > 90% if treatment is administered after symptom onset; an efficacy of 60% could be sufficient if treatment is initiated before symptom onset. Given their pharmacokinetic/pharmacodynamic properties, current investigated drugs may be in a range of 6-87% efficacy. They may help control virus if administered very early, but may not have a major effect in severely ill patients.

Conflict of interest statement

J.G. has consulted for F. Hoffman‐La Roche. All other authors declared no competing interests for this work.

© 2020 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.

Figures

Figure 1
Figure 1
Individual predictions of severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) of 13 untreated patients from Young et al. 3
Figure 2
Figure 2
Reduction in viral load at day 5 post‐symptom onset according to the level of antiviral effectiveness of a treatment blocking the viral production and the timing of treatment initiation (a) at time of infection; (b) at time of symptom onset; (c) 3days after symptom onset). We assumed an incubation period of 5 days.

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