Low-Dose Lung Radiation Therapy for COVID-19 Lung Disease: A Preclinical Efficacy Study in a Bleomycin Model of Pneumonitis

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 10.1101/2021.03.03.433704: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    BlindingLung histology: Serial 4 μm sections of the left lobe were cut and stained with haematoxylin and eosin (H&E) and Masson’s trichrome and evaluated independently by a veterinary pathologist and a pulmonary immunologist both of whom were blinded to the experimental treatment.
    Power Analysisnot detected.
    Sex as a biological variableFemale, 11-13 week old C57BL/6 mice (Charles River Laboratories) were administered one intranasal 40 μL dose of bleomycin sulphate (7.5 or 11.25 units/kg) or phosphate buffered saline (PBS) vehicle control under light isoflurane anaesthesia.

    Table 2: Resources

    Experimental Models: Organisms/Strains
    SentencesResources
    Female, 11-13 week old C57BL/6 mice (Charles River Laboratories) were administered one intranasal 40 μL dose of bleomycin sulphate (7.5 or 11.25 units/kg) or phosphate buffered saline (PBS) vehicle control under light isoflurane anaesthesia.
    C57BL/6
    suggested: None
    Software and Algorithms
    SentencesResources
    Flow cytometry data were acquired on a BD Fortessa and analysed using FlowJo (version10, BD Biosciences).
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)

    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:
    However we recognise its limitations: immune responses to bleomycin and SARS-CoV-2 are not identical, neither within the lungs nor systemically. Furthermore, our experiments were conducted exclusively in female mice aged 11-13 weeks. There is some evidence that young mice are less responsive to bleomycin than older mice (36) and it is possible that male mice would respond differently to bleomycin, LDLR or both. Furthermore, it is well established that the risk of severe COVID-19 lung disease is much greater in older patients (37), and that males are at higher risk of poor outcomes (38). Having identified bodyweight as a clinically relevant primary endpoint that correlates with the severity of bleomycin-induced pneumonitis and the associated systemic inflammatory response (39), we observed wide variation between mice in terms of rapidity and severity of weight loss, and subsequent recovery. Despite the challenges posed by this variability, our findings support the hypothesis that LDLR, delivered at a time when early histological and immunological features of lung inflammation are apparent, increases the likelihood of recovery in a subset of mice (approximately 25%). Subsequent analyses indicated that mice with moderate lung disease (measured either by lower rates of weight loss or by less marked imaging changes on CT scans) were more likely to respond to LDLR than those with severe pneumonitis. These bodyweight data are supported by histological, radiological and immunological...

    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.