Single‐cell RNA analysis on ACE2 expression provides insights into SARS‐CoV‐2 potential entry into the bloodstream and heart injury

  1. Jieyu Guo
  2. Xiangxiang Wei
  3. Qinhan Li
  4. Liliang Li
  5. Zhaohua Yang
  6. Yu Shi
  7. Yue Qin
  8. Xinyue Zhang
  9. Xinhong Wang
  10. Xiuling Zhi
  11. Dan Meng

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Abstract

Coronavirus disease‐2019 (COVID‐19) is a global pandemic with high infectivity and pathogenicity, accounting for tens of thousands of deaths worldwide. Recent studies have found that the pathogen of COVID‐19, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), shares the same cell receptor angiotensin converting enzyme II (ACE2) as SARS‐CoV. The pathological investigation of COVID‐19 deaths showed that the lungs had characteristics of pulmonary fibrosis. However, how SARS‐CoV‐2 spreads from the lungs to other organs has not yet been determined. Here, we performed an unbiased evaluation of cell‐type‐specific expression of ACE2 in healthy and fibrotic lungs, as well as in normal and failed adult human hearts, using published single‐cell RNA‐seq data. We found that ACE2 expression in fibrotic lungs mainly locates in arterial vascular cells, which might provide a route for bloodstream spreading of SARS‐CoV‐2. Failed human hearts have a higher percentage of ACE2‐expressing cardiomyocytes, and SARS‐CoV‐2 might attack cardiomyocytes through the bloodstream in patients with heart failure. Moreover, ACE2 was highly expressed in cells infected by respiratory syncytial virus or Middle East respiratory syndrome coronavirus and in mice treated by lipopolysaccharide. Our findings indicate that patients with pulmonary fibrosis, heart failure, and virus infection have a higher risk and are more susceptible to SARS‐CoV‐2 infection. The SARS‐CoV‐2 might attack other organs by getting into the bloodstream. This study provides new insights into SARS‐CoV‐2 blood entry and heart injury and might propose a therapeutic strategy to prevent patients from developing severe complications.

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  1. Version published to 10.1002/jcp.29802
  2. ScreenIT

    SciScore for 10.1101/2020.03.31.20047621: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: Reviewing patients’ charts were exempted from informed consent by the Ethics Committee Board at the School of Basic Medical Sciences, Fudan University.
    IRB: Reviewing patients’ charts were exempted from informed consent by the Ethics Committee Board at the School of Basic Medical Sciences, Fudan University.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Gene ontology (GO) and Kyoto encyclopedia of genes, genomes (KEGG) pathway analysis were performed with marker genes on DAVID website (https://david.ncifcrf.gov/).
    KEGG
    suggested: (KEGG, RRID:SCR_012773)
    DAVID
    suggested: (DAVID, RRID:SCR_001881)
    Statistical analyses were conducted with GraphPad prism 7.
    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: No clinical trial numbers were referenced.

    Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    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

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  3. Version published to 10.1101/2020.03.31.20047621v1 on medRxiv