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

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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.

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  1. SciScore for 10.1101/2020.04.04.20047886: (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: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).


    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Related to this question, our study had some limitations. Our calculations relied on blood or plasma drug concentrations. Except for hydroxychloroquine, for which the ratio of lung to plasma concentration is known to be high23,24, the lung exposure of the other drugs that we considered is unknown, and their effect on viral load in the lower respiratory tract, as measured from broncho-alveolar aspirates for instance, may differ. In addition, the drug EC50 that we used were determined on Vero E6 cells, an in vitro system that may not reflect the in vivo EC50. For instance, we found in another study that hydroxychloroquine had no antiviral activity in a more physiological model of reconstituted human airway epithelium, and this may explain the absence of antiviral of activity of HCQ in vivo against SARS-CoV-224,25. Finally we focused solely on the antiviral effects of these drugs, and did not consider other potential effects of these drugs, such as their immunomodulatory effects. Such effects have been suggested for drugs that are not purely antivirals, such as hydroxychloroquine and IFN-β-1a26,27. Another implicit implication of our work is the benefit of drugs used for prophylaxis, i.e., before exposure to the virus. In that case the objective of the treatment may be to “flatten the peak viral load” (by analogy with the now popular terminology of epidemiological models) but also to prevent infection. Our deterministic, ODE-based model, cannot reproduce virus extinction, but th...

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

    IdentifierStatusTitle
    NCT04315948Active, not recruitingTrial of Treatments for COVID-19 in Hospitalized Adults


    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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