Molecular mechanism of SARS-CoV-2 components caused ARDS in murine model

  1. Tingxuan Gu
  2. Simin Zhao
  3. Guoguo Jin
  4. Mengqiu Song
  5. Yafei Zhi
  6. Ran Zhao
  7. Fayang Ma
  8. Yaqiu Zheng
  9. Keke Wang
  10. Hui Liu
  11. Mingxia Xin
  12. Wei Han
  13. Xiang Li
  14. Christopher D Dong
  15. Kangdong Liu
  16. Zigang Dong

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Abstract

COVID-19 has become a major challenge to global health, and until now, no efficient antiviral agents have been developed. The SARS-CoV-2 infection is characterized by pulmonary and systemic inflammation in severe patients, and acute respiratory distress syndrome (ARDS) caused respiratory failure contributes to most mortalities. There is an urgent need for developing effective drugs and vaccines against SARS-CoV-2 and COVID-19 caused ARDS. However, most researchers cannot perform SARS-CoV-2 related researches due to lacking P3 or P4 facility. We developed a non-infectious, highly safety, time-saving SARS-CoV-2 components induced murine model to study the SARS-CoV-2 caused ARDS and cytokine storm syndrome (CSS). We also investigated mAbs and inhibitors which potentially neutralize the pro-inflammatory phenotype of COVID-19, and found that anti-IL-1α, anti-IL-6, anti-TNFα, anti-GM-CSF mAbs, p38 inhibitor, and JAK inhibitor partially relieved CSS. Besides, anti-IL-6, anti-TNFα, anti-GM-CSF mAbs and inhibitors of p38, ERK, and MPO somewhat reduced neutrophilic alveolitis in the lung. In all, we established the murine model mimic of COVID-19, opening a biosafety and less time-consuming avenue for clarifying the mechanism of ARDS and CSS in COVID-19 and developing the therapeutic drugs.

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  1. Version published to 10.1101/2020.06.07.119032v4 on bioRxiv
  2. Version published to 10.1101/2020.06.07.119032v3 on bioRxiv
  3. ScreenIT

    SciScore for 10.1101/2020.06.07.119032: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: All experimental procedures involving animals were approved by the Ethics Review Commission of Zhengzhou University (following internationally established guidelines)
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Blocking and neutralizing antibodies anti-IL-1α (InVivoMab, BE0243)
    anti-IL-1α
    suggested: None
    BE0243
    suggested: (Bio X Cell Cat# BE0243, RRID:AB_2687724)
    Experimental Models: Cell Lines
    SentencesResources
    This method is similar to the treatment of RAW264.7.
    RAW264.7
    suggested: CLS Cat# 400319/p462_RAW-2647, RRID:CVCL_0493)
    Experimental Models: Organisms/Strains
    SentencesResources
    Experimental Animals: Male BALB/c mice (8-10 weeks) free of pathogens were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China).
    BALB/c
    suggested: None
    Software and Algorithms
    SentencesResources
    Next, concentrations of mice inflammatory related cytokines IL-1α, IL-1β, IL-6, IL-10, IL-12p70, IL-17A, IL-23, IL-27, MCP-1, IFN-β, IFN-γ, TNF-α, and GM-CSF were measured by LEGENDplex™ Mouse Inflammation Panel (13-plex, Biolegend), the datas were harvest by flow cytometry using FACSCalibur (BD).
    FACSCalibur
    suggested: None
    Samples were analyzed in the BD FACSCalibur (BD).
    BD FACSCalibur
    suggested: (BD FACSCalibur Flow Cytometry System, RRID:SCR_000401)
    Statistical Analysis: Statistical analysis was performed using GraphPad Prism 7.0 (GraphPad Software, United States).
    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: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04400929RecruitingUsing GM-CSF as a Host Directed Therapeutic Against COVID-19

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: Please consider improving the rainbow (“jet”) colormap(s) used on pages 24, 22 and 23. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.

    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.

  4. Version published to 10.1101/2020.06.07.119032v2 on bioRxiv
  5. Version published to 10.1101/2020.06.07.119032v1 on bioRxiv