Early alveolar epithelial cell necrosis is a potential driver of COVID-19-induced acute respiratory distress syndrome

  1. Kentaro Tojo
  2. Natsuhiro Yamamoto
  3. Nao Tamada
  4. Takahiro Mihara
  5. Miyo Abe
  6. Mototsugu Nishii
  7. Ichiro Takeuchi
  8. Takahisa Goto

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Abstract

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  1. Version published to 10.1016/j.isci.2022.105748
  2. Version published to 10.1101/2022.01.23.22269723v3 on medRxiv
  3. Version published to 10.1101/2022.01.23.22269723v2 on medRxiv
  4. ScreenIT

    SciScore for 10.1101/2022.01.23.22269723: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The study protocol was approved by the Yokohama City University Hospital institutional review board (B200700100).
    Consent: The requirement for informed consent was waived due to the observational nature of the study.
    IACUC: Animal experiments: All animal experimental protocols were approved by Yokohama City University Animal Research Committee.
    Sex as a biological variableMale specific-pathogen-free C57/BL6J mice aged 8–10 weeks were used.
    RandomizationTwelve animals were randomly allocated to one of the following three groups (n = 4 per group): control, mild COVID-19, and severe COVID-19.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    To evaluate effects of anti-HMGB-1 neutralizing antibodies in severe COVID-19 animal model, six animals were randomly placed in either anti-HMGB-1 antibody or isotype control groups (n = 3 for each).
    anti-HMGB-1 neutralizing
    suggested: None
    anti-HMGB-1
    suggested: None
    Then, 100 μg anti-HMGB-1 neutralizing or isotype control antibodies dissolved in 100 μL PBS were intravenously administered via the tail vein 4 h after intratracheal instillation.
    isotype control antibodies dissolved in 100 μL PBS
    suggested: None
    Lung tissue sections were stained with anti-phospho-MLKL and anti- GSDMD n-terminal antibodies.
    anti-phospho-MLKL
    suggested: None
    anti- GSDMD
    suggested: None
    Experimental Models: Organisms/Strains
    SentencesResources
    Male specific-pathogen-free C57/BL6J mice aged 8–10 weeks were used.
    C57/BL6J
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical analyses: Statistical analyses were performed using Prism 9 (GraphPad Software, La Jolla, CA).
    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: We detected the following sentences addressing limitations in the study:
    This study has some limitations. First, only patients admitted to a single center were included in the analysis due to the limited availability of clinical samples. Further studies that use samples from multiple centers several countries are warranted. Second, our animal model was created by exposing mice to components of SARS-CoV-2, and not an infectious strain of SARS-CoV-2. Despite this, the observation of a COVID-19- like pathology supports the use of our animal model. Importantly, use of a non- infectious model is convenient for laboratories that do not specialize in infectious disease research. Third, the efficacy of inhibiting a single DAMP, HMGB-1, was evaluated. Several DAMPs are released from necrotic cells; therefore, future studies that investigate whether other DAMP are promising therapeutic targets for COVID-19 are warranted.

    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.

    Results from scite Reference Check: We found no unreliable references.

    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.

  5. Version published to 10.1101/2022.01.23.22269723v1 on medRxiv