Disruption of Adaptive Immunity Enhances Disease in SARS-CoV-2-Infected Syrian Hamsters

  1. Rebecca L. Brocato
  2. Lucia M. Principe
  3. Robert K. Kim
  4. Xiankun Zeng
  5. Janice A. Williams
  6. Yanan Liu
  7. Rong Li
  8. Jeffrey M. Smith
  9. Joseph W. Golden
  10. Dave Gangemi
  11. Sawsan Youssef
  12. Zhongde Wang
  13. Jacob Glanville
  14. Jay W. Hooper

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Abstract

Syrian hamsters are in use as a model of disease caused by SARS-CoV-2. Pathology is pronounced in the upper and lower respiratory tract, and disease signs and endpoints include weight loss and viral RNA and/or infectious virus in swabs and organs (e.g., lungs). However, a high dose of virus is needed to produce disease, and the disease resolves rapidly. Here, we demonstrate that immunosuppressed hamsters are susceptible to low doses of virus and develop more severe and prolonged disease. We demonstrate the efficacy of a novel neutralizing monoclonal antibody using the cyclophosphamide transient suppression model. Furthermore, we demonstrate that RAG2 knockout hamsters develop severe/fatal disease when exposed to SARS-CoV-2. These immunosuppressed hamster models provide researchers with new tools for evaluating therapies and vaccines and understanding COVID-19 pathogenesis.

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  1. ScreenIT

    SciScore for 10.1101/2020.06.19.161612: (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.
    • No funding statement was detected.
    • 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 10.1128/jvi.01683-20
  3. Version published to 10.21203/rs.3.rs-43931/v1 on Research Square
  4. ScreenIT

    SciScore for 10.1101/2020.06.19.161612: (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

    Antibodies
    SentencesResources
    Protective efficacy of anti-SARS-CoV-2 mAb A human monoclonal antibody ( mAb ) targeting the spike protein of SARS-CoV-2 was evaluated in a passive transfer experiment using immunosuppressed hamster .
    anti-SARS-CoV-2
    suggested: None
    Several groups have reported in vitro characterization of anti-SARS-CoV-2 neutralizing mAbs and a number of antibodies have been shown to protect in small animal models , including Syrian hamsters ( 22 , 23) .
    anti-SARS-CoV-2 neutralizing mAbs
    suggested: None
    F ) SARS-CoV-2 genomic RNA was frequently detected in alveolar pneumocytes , alveolar infiltrates , and bronchiolar epithelial cells from RAG2 KO hamsters by ISH . ( G-I ) Immunofluorescence assays demonstrate SARS-CoV-2 antigens ( S or NP , green ) were detected in brochiolar epithelium labelled anti-pan-cytokeratin antibody ( red , G ) club ( clara ) cells labelled by anti-CC10 antibody ( red , H ) and alveolar epithelial cells labelled by anti E-cadherin antibody ( red , I ) in RAG2 KO hamsters .
    NP
    suggested: None
          <div style="margin-bottom:8px">
        <div><b>anti-pan-cytokeratin</b></div>
        <div>suggested: None</div>
      </div>
    
      <div style="margin-bottom:8px">
        <div><b>anti-CC10</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;text-align:center; padding-top:4px;" colspan="2"><b>Software and Algorithms</b></td></tr><tr><td style="min-width:100px;text=align:center"><i>Sentences</i></td><td style="min-width:100px;text-align:center"><i>Resources</i></td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">Clin Infect Dis , ( 2020) . T . F . Rodgers , Zhao , F . , Huang , D . , Beutler , N . , Abbott , R . K . , Callaghan , S. , Garcia , E . , He , W . , Hurtado , J . , Limbo , O .</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>Abbott</b></div>
        <div>suggested: (Abbott, <a href="https://scicrunch.org/resources/Any/search?q=SCR_010477">SCR_010477</a>)</div>
      </div>
    </td></tr></table>

    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 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.

  5. Version published to 10.1101/2020.06.19.161612v1 on bioRxiv