Circulating markers of angiogenesis and endotheliopathy in COVID‐19

  1. Alexander B. Pine
  2. Matthew L. Meizlish
  3. George Goshua
  4. C‐Hong Chang
  5. Hanming Zhang
  6. Jason Bishai
  7. Parveen Bahel
  8. Amisha Patel
  9. Rana Gbyli
  10. Jennifer M. Kwan
  11. Christine H. Won
  12. Christina Price
  13. Charles S. Dela Cruz
  14. Stephanie Halene
  15. David van Dijk
  16. John Hwa
  17. Alfred I. Lee
  18. Hyung J. Chun

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Abstract

Increase in thrombotic and microvascular complications is emerging to be a key feature of patients with critical illness associated with COVID‐19 infection. While endotheliopathy is thought to be a key factor of COVID‐19‐associated coagulopathy, markers indicative of this process that are prognostic of disease severity have not been well‐established in this patient population. Using plasma profiling of patients with COVID‐19, we identified circulating markers that segregated with disease severity: markers of angiogenesis (VEGF‐A, PDGF‐AA and PDGF‐AB/BB) were elevated in hospitalized patients with non‐critical COVID‐19 infection, while markers of endothelial injury (angiopoietin‐2, FLT‐3L, PAI‐1) were elevated in patients with critical COVID‐19 infection. In survival analysis, elevated markers of endothelial injury (angiopoietin‐2, follistatin, PAI‐1) were strongly predictive of in‐hospital mortality. Our findings demonstrate that non‐critical and critical phases of COVID‐19 disease may be driven by distinct mechanisms involving key aspects of endothelial cell function, and identify drivers of COVID‐19 pathogenesis and potential targets for future therapies.

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  1. ScreenIT

    SciScore for 10.1101/2020.06.29.20140376: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    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

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  2. Version published to 10.1177/2045894020966547
  3. Version published to 10.1101/2020.06.29.20140376 on medRxiv