SARS-CoV-2 infection in the Syrian hamster model causes inflammation as well as type I interferon dysregulation in both respiratory and non-respiratory tissues including the heart and kidney

  1. Magen Ellen Francis
  2. Una Goncin
  3. Andrea Kroeker
  4. Cynthia Swan
  5. Robyn Ralph
  6. Yao Lu
  7. Athema Louise Etzioni
  8. Darryl Falzarano
  9. Volker Gerdts
  10. Steven Machtaler
  11. Jason Kindrachuk
  12. Alyson Ann Kelvin

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Abstract

COVID-19 (coronavirus disease 2019) caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection is a disease affecting several organ systems. A model that captures all clinical symptoms of COVID-19 as well as long-haulers disease is needed. We investigated the host responses associated with infection in several major organ systems including the respiratory tract, the heart, and the kidneys after SARS-CoV-2 infection in Syrian hamsters. We found significant increases in inflammatory cytokines (IL-6, IL-1beta, and TNF) and type II interferons whereas type I interferons were inhibited. Examination of extrapulmonary tissue indicated inflammation in the kidney, liver, and heart which also lacked type I interferon upregulation. Histologically, the heart had evidence of myocarditis and microthrombi while the kidney had tubular inflammation. These results give insight into the multiorgan disease experienced by people with COVID-19 and possibly the prolonged disease in people with post-acute sequelae of SARS-CoV-2 (PASC).

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  1. Version published to 10.1371/journal.ppat.1009705
  2. ScreenIT

    SciScore for 10.1101/2021.04.07.438843: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIACUC: Ethics Statement: All work was conducted in accordance with the Canadian Council of Animal Care (CCAC) guidelines, AUP number 20200016 by the University Animal Care Committee (
    IRB: UACC) Animal Research Ethics Board at the University of Saskatchewan.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableThe rotor was loaded in the VetScan VS2 Analyzer and analyzed as plasma samples from male hamsters.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Rat anti-CD3 clone CD3-12, P. Moore, UC-Davis, Davis, CA) and CD20 (Rabbit anti-CD20, Thermo Fisher Scientific, Waltham, MA) primary antibodies were applied for 30 m at 1:25 and 1:400 dilutions, respectively.
    anti-CD3
    suggested: (RayBiotech Cat# DS-MB-02991, RRID:AB_1544189)
    CD20
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    (Wisent Bioproducts (Cat # 319-005-CL)), 2% fetal calf serum (Wisent Bioproducts (Cat # 090-150)), 5 mL 100x penicillin (10,000 U/mL)/streptomycin (10,000 μg/mL), and 2 μg/mL TPCK-trypsin) on Vero-76 cells.
    Vero-76
    suggested: IZSLER Cat# BS CL 101, RRID:CVCL_0603)
    Software and Algorithms
    SentencesResources
    Statistical Analysis: Unpaired, unequal variance, two-tail Student’s t-test or one-way ANOVAs were conducted using GraphPad Prism8 (San Diego, USA).
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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

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  3. Version published to 10.1101/2021.04.07.438843 on bioRxiv