Increased expression of ACE2, the SARS-CoV-2 entry receptor, in alveolar and bronchial epithelium of smokers and COPD subjects

  1. Merel Jacobs
  2. Hannelore P. Van Eeckhoutte
  3. Sara R.A. Wijnant
  4. Wim Janssens
  5. Guy F. Joos
  6. Guy G. Brusselle
  7. Ken R. Bracke

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Abstract

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  1. Version published to 10.1183/13993003.02378-2020
  2. ScreenIT

    SciScore for 10.1101/2020.05.27.20114298: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: Written informed consent was obtained from all subjects.
    IRB: This study was approved by the medical ethical committees of the Ghent University Hospital (2011/0114; 2016/0132; 2019/0537) and the University Hospital Gasthuisberg Leuven (S51577)
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    After antigen retrieval with citrate buffer (Scytek), the slides were incubated with anti-ACE2 antibody (polyclonal rabbit-anti-human, Abcam ab15248).
    anti-ACE2
    suggested: None
    rabbit-anti-human,
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical analysis: Statistical analysis was performed with Sigma Stat software (SPSS 26.0, Chicago, IL, USA) and R3.5.1, using Student’s t-test, Kruskal-Wallis and Mann-Whitney U test, Fisher’s exact test, Spearman’s Rank correlations, and multivariate linear regression analyses.
    Sigma Stat
    suggested: None
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    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:
    We measured mRNA expression of ACE2 and TMPRSS2 in lung tissue samples from 120 never smokers and smokers with and without airflow limitation and demonstrate higher ACE2 mRNA levels in current smokers and patients with moderate (GOLD II) and severe to very severe COPD (GOLD III-IV). Importantly, ACE2 mRNA expression shows an inverse correlation with physiological parameters of airway obstruction and emphysema. Linear regression analysis confirms that smoking and COPD are associated with increased ACE2 mRNA expression, independent of covariables such as age, gender, comorbidities, and medication use. The association between COPD and ACE2 mRNA seems to be partly driven by smoking as the effect size of the association between COPD and ACE2 mRNA decreased after adjusting for smoking. The remaining statistically significant association between COPD and ACE2 mRNA might be explained by other factors such as aggravated pulmonary and systemic inflammation, previous exacerbations or genetic predisposition. Interestingly, a recent large meta-analysis of transcriptomic data confirms the increased ACE2 mRNA expression in lung tissue of smokers and patients with COPD [28]. TMPRSS2 mRNA expression is only significantly higher in patients with (very) severe COPD. However, there is a significant correlation between TMPRSS mRNA and ACE2 mRNA expression levels, even in sensitivity analyses omitting (very) severe COPD patients from the analysis. Our data suggest that both ACE2 and TMPRSS2 are ex...

    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

    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.

  3. Version published to 10.1101/2020.05.27.20114298v1 on medRxiv