Early postmortem mapping of SARS-CoV-2 RNA in patients with COVID-19 and the correlation with tissue damage

  1. Stefanie Deinhardt-Emmer
  2. Daniel Wittschieber
  3. Juliane Sanft
  4. Sandra Kleemann
  5. Stefan Elschner
  6. Karoline Frieda Haupt
  7. Vanessa Vau
  8. Clio Häring
  9. Jürgen Rödel
  10. Andreas Henke
  11. Christina Ehrhardt
  12. Michael Bauer
  13. Mike Philipp
  14. Nikolaus Gaßler
  15. Sandor Nietzsche
  16. Bettina Löffler
  17. Gita Mall

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Abstract

Clinical observations indicate that COVID-19 is a systemic disease. An investigation of the viral distribution within the human body and its correlation with tissue damage can aid in understanding the pathophysiology of SARS-CoV-2 infection. We present a detailed mapping of the viral RNA in 61 tissues and organs of 11 deceased patients with COVID-19. The autopsies were performed within the early postmortem interval (between 1.5 and 15 hr, mean: 5.6 hr) to minimize the bias due to viral RNA and tissue degradation. Very high viral loads (>10 4 copies/ml) were detected in most patients' lungs, and the presence of intact viral particles in the lung tissue could be verified by transmission electron microscopy. Interestingly, viral RNA was detected throughout various extrapulmonary tissues and organs without visible tissue damage. The dissemination of SARS-CoV-2-RNA throughout the body supports the hypothesis that there is a maladaptive host response with viremia and multiorgan dysfunction.

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  1. Version published to 10.7554/elife.60361 on eLife
  2. ScreenIT

    SciScore for 10.1101/2020.07.01.182550: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: As soon as possible after death the closest relatives were contacted and gave their informed consent.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    For immunohistochemistry the antibodies detailed in follow were used: AE1/3 (Dako/IR053), TTF-1 (Dako/IR056), CK7 (Dako/IR619), CK5/6 (Dako/IR780), p40 (Zytomed/MSK097), Ki67 (Dako/IR626), CD68 (Dako/M0876), CD61 (Dako/M0753), CD31 (Dako/IR610), CD34 (Dako/IR623), ASMA
    TTF-1
    suggested: (Agilent Cat# IR056, RRID:AB_2755006)
    CK7
    suggested: None
    p40
    suggested: (Zytomed Systems Cat# MSG097, RRID:AB_2864460)
    Ki67
    suggested: None
    CD68
    suggested: (Agilent Cat# M0876, RRID:AB_2074844)
    CD61
    suggested: (Agilent Cat# M0753, RRID:AB_2128777)
    CD31
    suggested: None
    CD34
    suggested: None

    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 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. ScreenIT

    SciScore for 10.1101/2020.07.01.182550: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementAs soon as possible after death the closest relatives were contacted and gave 113 their informed consent.Randomizationnot detected.Blindingnot detected.Power Analysisnot detected.Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    For 156 immunohistochemistry the antibodies detailed in follow were used: AE1/3 (Dako/IR053), TTF-1 157 (Dako/IR056), CK7 (Dako/IR619), CK5/6 (Dako/IR780), p40 (Zytomed/MSK097), Ki67 (Dako/IR626), 158 CD68 (Dako/M0876), CD61 (Dako/M0753), CD31 (Dako/IR610), CD34 (Dako/IR623), ASMA 159 (Dako/IR611), 160 (Dako/M0785), Tenascin (Chemicon/MAB19101).
    TTF-1
    suggested: (Agilent Cat# IR056, AB_2755006)
          <div style="margin-bottom:8px">
        <div><b>CK7</b></div>
        <div>suggested: None</div>
      </div>
    
      <div style="margin-bottom:8px">
        <div><b>p40</b></div>
        <div>suggested: None</div>
      </div>
    
      <div style="margin-bottom:8px">
        <div><b>Ki67</b></div>
        <div>suggested: None</div>
      </div>
    
      <div style="margin-bottom:8px">
        <div><b>CD61</b></div>
        <div>suggested: (Agilent Cat# M0753, <a href="https://scicrunch.org/resources/Any/search?q=AB_2128777">AB_2128777</a>)</div>
      </div>
    
      <div style="margin-bottom:8px">
        <div><b>CD31</b></div>
        <div>suggested: None</div>
      </div>
    
      <div style="margin-bottom:8px">
        <div><b>CD34</b></div>
        <div>suggested: None</div>
      </div>
    
      <div style="margin-bottom:8px">
        <div><b>Tenascin</b></div>
        <div>suggested: (Millipore Cat# MAB19101, <a href="https://scicrunch.org/resources/Any/search?q=AB_94402">AB_94402</a>)</div>
      </div>
    </td></tr><tr><td style="min-width:100px;text-align:center; padding-top:4px;" colspan="2"><b>Software and Algorithms</b></td></tr><tr><td style="min-width:100px;text=align:center"><i>Sentences</i></td><td style="min-width:100px;text-align:center"><i>Resources</i></td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">The samples from bioRxiv preprint doi: https://doi.org/10.1101/2020.07.01.182550. this version posted July 2, 2020.</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>bioRxiv</b></div>
        <div>suggested: (bioRxiv, <a href="https://scicrunch.org/resources/Any/search?q=SCR_003933">SCR_003933</a>)</div>
      </div>
    </td></tr></table>

    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 OddPub: We did not find a statement about open data. We also did not find a statement about open code. Researchers are encouraged to share open data when possible (see Nature blog).

    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 is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.

  4. Version published to 10.1101/2020.07.01.182550v1 on bioRxiv