Hydroxychloroquine Proves Ineffective in Hamsters and Macaques Infected with SARS-CoV-2

  1. Kyle Rosenke
  2. Michael A. Jarvis
  3. Friederike Feldmann
  4. Benjamin Schwarz
  5. Atsushi Okumura
  6. Jamie Lovaglio
  7. Greg Saturday
  8. Patrick W. Hanley
  9. Kimberly Meade-White
  10. Brandi N. Williamson
  11. Frederick Hansen
  12. Lizette Perez-Perez
  13. Shanna Leventhal
  14. Tsing-Lee Tang-Huau
  15. Martha Nason
  16. Julie Callison
  17. Elaine Haddock
  18. Dana Scott
  19. Graham Sewell
  20. Catharine M. Bosio
  21. David Hawman
  22. Emmie de Wit
  23. Heinz Feldmann

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Abstract

We remain largely without effective prophylactic/therapeutic interventions for COVID-19. Although many human clinical trials are ongoing, there remains a deficiency of supportive preclinical drug efficacy studies. Here we assessed the prophylactic/therapeutic efficacy of hydroxychloroquine (HCQ), a drug of interest for COVID-19 management, in two animal models. When used for prophylaxis or treatment neither the standard human malaria dose (6.5 mg/kg) nor a high dose (50 mg/kg) of HCQ had any beneficial effect on clinical disease or SARS-CoV-2 kinetics (replication/shedding) in the Syrian hamster disease model. Similarly, HCQ prophylaxis/treatment (6.5 mg/kg) did not significantly benefit clinical outcome nor reduce SARS-CoV-2 replication/shedding in the upper and lower respiratory tract in the rhesus macaque disease model. In conclusion, our preclinical animal studies do not support the use of HCQ in prophylaxis/treatment of COVID-19.

Hydroxychloroquine prophylaxis/treatment showed no beneficial effect in SARS-CoV-2 hamster and macaque disease models.

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  1. ScreenIT

    SciScore for 10.1101/2020.06.10.145144: (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: 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: No clinical trial numbers were referenced.

    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

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. ScreenIT

    SciScore for 10.1101/2020.06.10.145144: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.RandomizationFor the prophylactic arm , 10 healthy rhesus macaques were randomly divided into vehicle control and HCQ prophylaxis groups ( n=5 per group) .Blindingnot detected.Power Analysisnot detected.Sex as a biological variablenot detected.Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    First, we confirmed the in vitro inhibitory effect of HCQ on SARS-CoV-2 replication in Vero E6 cells.
    Vero E6
    suggested: CVCL_XD71
    Software and Algorithms
    SentencesResources
    These in vitro studies , which we confirmed herein , identified HCQ ( and other 4aminoquinolines ) as potent inhibitors of coronaviruses , including SARS-CoV-2 , with low EC50 values within the range of antivirals such as remdesivir ( 6); a drug that is now approved for COVID-19 cases by the FDA .
    SARS-CoV-2
    suggested: (Sino Biological Cat# 40143-R019, AB_2827973)

    Results from OddPub: We did not find a statement about open data. We also did not find a statement about open code. Researchers are encouraged to share open data when possible (see Nature blog).

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2020.06.10.145144v1 on bioRxiv