COVID-19 induces a hyperactive phenotype in circulating platelets

  1. Shane P. Comer
  2. Sarah Cullivan
  3. Paulina B. Szklanna
  4. Luisa Weiss
  5. Steven Cullen
  6. Sarah Kelliher
  7. Albert Smolenski
  8. Claire Murphy
  9. Haidar Altaie
  10. John Curran
  11. Katherine O’Reilly
  12. Aoife G. Cotter
  13. Brian Marsh
  14. Sean Gaine
  15. Patrick Mallon
  16. Brian McCullagh
  17. Niamh Moran
  18. Fionnuala Ní Áinle
  19. Barry Kevane
  20. Patricia B. Maguire
  21. On behalf of the COCOON Study investigators

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Abstract

Coronavirus Disease 2019 (COVID-19), caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has affected over 30 million globally to date. Although high rates of venous thromboembolism and evidence of COVID-19-induced endothelial dysfunction have been reported, the precise aetiology of the increased thrombotic risk associated with COVID-19 infection remains to be fully elucidated. Therefore, we assessed clinical platelet parameters and circulating platelet activity in patients with severe and nonsevere COVID-19. An assessment of clinical blood parameters in patients with severe COVID-19 disease (requiring intensive care), patients with nonsevere disease (not requiring intensive care), general medical in-patients without COVID-19, and healthy donors was undertaken. Platelet function and activity were also assessed by secretion and specific marker analysis. We demonstrated that routine clinical blood parameters including increased mean platelet volume (MPV) and decreased platelet:neutrophil ratio are associated with disease severity in COVID-19 upon hospitalisation and intensive care unit (ICU) admission. Strikingly, agonist-induced ADP release was 30- to 90-fold higher in COVID-19 patients compared with hospitalised controls and circulating levels of platelet factor 4 (PF4), soluble P-selectin (sP-selectin), and thrombopoietin (TPO) were also significantly elevated in COVID-19. This study shows that distinct differences exist in routine full blood count and other clinical laboratory parameters between patients with severe and nonsevere COVID-19. Moreover, we have determined all COVID-19 patients possess hyperactive circulating platelets. These data suggest abnormal platelet reactivity may contribute to hypercoagulability in COVID-19 and confirms the role that platelets/clotting has in determining the severity of the disease and the complexity of the recovery path.

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  1. ScreenIT

    SciScore for 10.1101/2020.07.24.20156240: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Patient recruitment and blood collection: Ethical approval to proceed with this study (1/378/2077) was granted by the Institutional Review Board of the Mater Misericordiae University
    Consent: Informed consent was sought prior to obtaining additional blood samples for analysis from a sub-group of patients with severe COVID-19, non-severe COVID-19 and hospitalised patients without COVID-19, with patients matched for age, body mass index (BMI) & gender.
    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: We detected the following sentences addressing limitations in the study:
    This study has a number of limitations. Firstly, our cohort of patients is relatively small, a factor which (at least in part) is likely to be related to the success of the Irish healthcare system in suppressing transmission of the virus during the early stages of the pandemic. Additionally, given the public health restrictions that were in place during the period of this study, recruitment of healthy controls was substantially impeded and consequently the available healthy controls were not appropriately matched for age relative to our COVID-19 group and hospitalised control group. Due to the small sample size, adjustment for confounding factors was not possible. In conclusion, it has been apparent since the early stages of the COVID-19 pandemic that derangements of haemostasis represent a hallmark of this disease and appear to be associated with significant morbidity (12, 69). Several investigators have reported data suggesting that rates of venous thromboembolism are high in this population and that these thrombotic complications appear to occur despite compliance with standard VTE prevention protocols (5, 7). Reports of unusual and devastating cases of arterial thrombosis are also emerging (18, 22-24). The safety and efficacy of conventional anti-platelet and anti-coagulant treatment strategies in the management of this thrombotic risk is becoming a major focus of translational and clinical interest. The aetiology of hypercoagulability in COVID-19 is likely multi-factoria...

    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.

  2. Version published to 10.1371/journal.pbio.3001109
  3. Version published to 10.1101/2020.07.24.20156240v2 on medRxiv
  4. ScreenIT

    SciScore for 10.1101/2020.07.24.20156240: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementMethods: Patient recruitment and blood collection Ethical approval to proceed with this study (1/378/2077) was granted by the Institutional Review Board of the Mater Misericordiae University Hospital.Randomizationnot detected.Blindingnot detected.Power Analysisnot detected.Sex as a biological variablenot detected.

    Table 2: Resources

    Data from additional tools added to each annotation on a weekly basis.

    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.

  5. Version published to 10.1101/2020.07.24.20156240v1 on medRxiv