Defining the Syrian hamster as a highly susceptible preclinical model for SARS-CoV-2 infection

  1. Kyle Rosenke
  2. Kimberly Meade-White
  3. Michael Letko
  4. Chad Clancy
  5. Frederick Hansen
  6. Yanan Liu
  7. Atsushi Okumura
  8. Tsing-Lee Tang-Huau
  9. Rong Li
  10. Greg Saturday
  11. Friederike Feldmann
  12. Dana Scott
  13. Zhongde Wang
  14. Vincent Munster
  15. Michael A. Jarvis
  16. Heinz Feldmann

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Abstract

Following emergence in late 2019, SARS-CoV-2 rapidly became pandemic and is presently responsible for millions of infections and hundreds of thousands of deaths worldwide. There is currently no approved vaccine to halt the spread of SARS-CoV-2 and only very few treatment options are available to manage COVID-19 patients. For development of preclinical countermeasures, reliable and well-characterized small animal disease models will be of paramount importance. Here we show that intranasal inoculation of SARS-CoV-2 into Syrian hamsters consistently caused moderate broncho-interstitial pneumonia, with high viral lung loads and extensive virus shedding, but animals only displayed transient mild disease. We determined the infectious dose 50 to be only five infectious particles, making the Syrian hamster a highly susceptible model for SARS-CoV-2 infection. Neither hamster age nor sex had any impact on the severity of disease or course of infection. Finally, prolonged viral persistence in interleukin 2 receptor gamma chain knockout hamsters revealed susceptibility of SARS-CoV-2 to adaptive immune control. In conclusion, the Syrian hamster is highly susceptible to SARS-CoV-2 making it a very suitable infection model for COVID-19 countermeasure development.

One Sentence Summary

The Syrian hamster is highly susceptible to SARS-CoV-2 making it an ideal infection model for COVID-19 countermeasure development.

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  1. ScreenIT

    SciScore for 10.1101/2020.09.25.314070: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIACUC: Biosafety and ethics: All work using live SARS-COV-2 was performed in BSL4 using standard operating protocols approved by the Rocky Mountain Laboratories Institutional Biosafety Committee.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableAnimal studies: Syrian hamsters (Mesocricetus auratus), 6-8-weeks-of-age and >27-weeks-of-age, males and females, were purchased from Envigo.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    The secondary antibody is an anti-rabbit IgG polymer from Vector Laboratories ImPress VR.
    anti-rabbit IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Cell entry assay: Vesicular stomatitis virus (VSV) particles were pseudotyped with different wildtype or chimeric spike proteins or no spike in 293T cells as previously described (18)
    293T
    suggested: NCBI_Iran Cat# C498, RRID:CVCL_0063)
    BHK cells were transfected in 96-well format with 100 ng of host receptor plasmid, or no receptor and subsequently infected with spike-pseudotyped VSV particles as previously described (18).
    BHK
    suggested: None
    Virus was quantified through end-point titrations performed in Vero E6 cells.
    Vero E6
    suggested: RRID:CVCL_XD71)
    Software and Algorithms
    SentencesResources
    Statistical analyses: Statistical analysis was performed in Prism 8 (GraphPad).
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Although, as with all animal models, there are some limitations exemplified by the lack of a systemic response to SARS-CoV-2 infection. The only mild disease manifestation and ability to quickly limit the infection make this model less suitable to study the mechanisms of severe COVID-19. However, the consistent and easily measured lung disease found in hamsters of all ages and sex make this a suitable infection model to evaluate SARS-CoV-2 countermeasure development.

    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. Version published to 10.1101/2020.09.25.314070v1 on bioRxiv
  3. Version published to 10.1080/22221751.2020.1858177