Erythrocytes identify complement activation in patients with COVID-19

  1. L. K. Metthew Lam
  2. John P. Reilly
  3. Ann H. Rux
  4. Sophia J. Murphy
  5. Leticia Kuri-Cervantes
  6. Ariel R. Weisman
  7. Caroline A. G. Ittner
  8. M. Betina Pampena
  9. Michael R. Betts
  10. E. John Wherry
  11. Wen-Chao Song
  12. John D. Lambris
  13. Nuala J. Meyer
  14. Douglas B. Cines
  15. Nilam S. Mangalmurti

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Abstract

COVID-19, the disease caused by the SARS-CoV-2 virus, can progress to multisystem organ failure and viral sepsis characterized by respiratory failure, arrhythmias, thromboembolic complications, and shock with high mortality. Autopsy and preclinical evidence implicate aberrant complement activation in endothelial injury and organ failure. Erythrocytes express complement receptors and are capable of binding immune complexes; therefore, we investigated complement activation in patients with COVID-19 using erythrocytes as a tool to diagnose complement activation. We discovered enhanced C3b and C4d deposition on erythrocytes in COVID-19 sepsis patients and non-COVID sepsis patients compared with healthy controls, supporting the role of complement in sepsis-associated organ injury. Our data suggest that erythrocytes may contribute to a precision medicine approach to sepsis and have diagnostic value in monitoring complement dysregulation in COVID-19-sepsis and non-COVID sepsis and identifying patients who may benefit from complement targeted therapies.

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  1. Version published to 10.1152/ajplung.00231.2021
  2. ScreenIT

    SciScore for 10.1101/2020.05.20.20104398: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Studies involving human subjects were approved by the University of Pennsylvania Institutional Review Board.
    Consent: Subjects were screened and approached for informed consent during the first 3 days of hospitalization.
    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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  3. Version published to 10.1101/2020.05.20.20104398v1 on medRxiv