Success of prophylactic antiviral therapy for SARS-CoV-2: Predicted critical efficacies and impact of different drug-specific mechanisms of action

  1. Peter Czuppon
  2. Florence Débarre
  3. Antonio Gonçalves
  4. Olivier Tenaillon
  5. Alan S. Perelson
  6. Jérémie Guedj
  7. François Blanquart

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Abstract

Repurposed drugs that are safe and immediately available constitute a first line of defense against new viral infections. Despite limited antiviral activity against SARS-CoV-2, several drugs are being tested as medication or as prophylaxis to prevent infection. Using a stochastic model of early phase infection, we evaluate the success of prophylactic treatment with different drug types to prevent viral infection. We find that there exists a critical efficacy that a treatment must reach in order to block viral establishment. Treatment by a combination of drugs reduces the critical efficacy, most effectively by the combination of a drug blocking viral entry into cells and a drug increasing viral clearance. Below the critical efficacy, the risk of infection can nonetheless be reduced. Drugs blocking viral entry into cells or enhancing viral clearance reduce the risk of infection more than drugs that reduce viral production in infected cells. The larger the initial inoculum of infectious virus, the less likely is prevention of an infection. In our model, we find that as long as the viral inoculum is smaller than 10 infectious virus particles, viral infection can be prevented almost certainly with drugs of 90% efficacy (or more). Even when a viral infection cannot be prevented, antivirals delay the time to detectable viral loads. The largest delay of viral infection is achieved by drugs reducing viral production in infected cells. A delay of virus infection flattens the within-host viral dynamic curve, possibly reducing transmission and symptom severity. Thus, antiviral prophylaxis, even with reduced efficacy, could be efficiently used to prevent or alleviate infection in people at high risk.

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  1. Version published to 10.1371/journal.pcbi.1008752
  2. Rapid Reviews Infectious Diseases

    Anna Bershteyn

    Review 1: "Predicted success of prophylactic antiviral therapy to block or delay SARS-CoV-2 infection depends on the drug’s mechanism of action"

    Authors claim that stochastic modeling can be used to predict the efficacy of repurposed drugs to prevent or treat SARS-CoV-2 infections. Readers and decision makers should assess results with some caution.

  3. Rapid Reviews Infectious Diseases

    Praveen P Nekkar Rao

    Review 2: "Predicted success of prophylactic antiviral therapy to block or delay SARS-CoV-2 infection depends on the drug's mechanism of action"

    Authors claim that stochastic modeling can be used to predict the efficacy of repurposed drugs to prevent or treat SARS-CoV-2 infections. Readers and decision makers should assess these results with caution -- reviews of the paper are mixed.

  5. Version published to 10.1101/2020.05.07.20092965v3 on medRxiv
  6. Version published to 10.1101/2020.05.07.20092965v2 on medRxiv
  7. ScreenIT

    SciScore for 10.1101/2020.05.07.20092965: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: Thank you for sharing your code and data.

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04497987RecruitingA Study of LY3819253 (LY-CoV555) and LY3832479 (LY-CoV016) i…

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  8. Version published to 10.1101/2020.05.07.20092965v1 on medRxiv