Angiopoietin 2 Is Associated with Vascular Necroptosis Induction in Coronavirus Disease 2019 Acute Respiratory Distress Syndrome

This article has been Reviewed by the following groups

Read the full article See related articles

Abstract

No abstract available

Article activity feed

  1. SciScore for 10.1101/2021.05.20.21257542: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Study Approval: The study was approved by the institutional review board (IRB) at WCM (20-05022072, 20-0302168, 20-03021681, and 1811019771).
    Consent: Written informed consent was received from all participants prior to inclusion in the study.
    Sex as a biological variablenot detected.
    RandomizationQuantification of ANGPT2 and CD61 was performed on four random 20X images selected using a random overlay of points and excluding fields with large vessels or airway.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Recombinant DNA
    SentencesResources
    Immunohistochemistry was carried out for angiopoietin-2 (sc-74403, Santa Cruz, TX, 1:100), CD-61 (CD61 clone 2F2, Leica Biosystems, IL) and phosphorylated mixed lineage kinase domain-like (pMLKL, MAB91871, NOVUS Biologicals, CO, 1:750 with casein for background reduction).
    pMLKL
    suggested: None
    Software and Algorithms
    SentencesResources
    All twenty autopsies were analyzed using Immunohistochemistry profiler (63) as a plugin for Image J (National Institutes of Health, USA).
    Image J
    suggested: (ImageJ, RRID:SCR_003070)

    Results from OddPub: Thank you for sharing your code and data.


    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Consistently low circulating angiogenic (low PDGFA and PDGFB) and barrier protein (low ANGPT1) in our higher vascular injury and low platelet subjects imply limitations in these essential reparative processes. The validation of our vascular phenotype across diverse causes of ARDS broadens the relevance of our findings. In linking low platelets, vascular function, and mortality in COVID-19, bacterial sepsis, and influenza ARDS, we hint at a common final pathway of vascular injury that is more disease- (ARDS) than cause- (COVID-19) specific. Of note is that this vascular injury pattern may be related to a reduced baseline vascular resilience in our high vascular injury subjects. Consistently, our high vascular injury subjects are older (41), have worse baseline renal function (42, 43), and are more likely to have cancer (44) (Supplementary Table 2), all variables know to be associated with vascular disease. The identification of this severe vascular phenotype across infectious causes of ARDS also presents an opportunity for targeted vascular therapies in ARDS, including those that have shown promise in COVID-19 (45), ARDS generally (46), and in exciting preclinical (47, 48) and early human experimental therapies, including ANGPT1 supplementation trial currently underway in COVID-19 subjects (49). And while a ANGPT2 neutralizing antibody study in hospitalized patient with COVID-19 was stopped for futility in October 2020 (50), our data could improve patient selection for similar...

    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.