Royal College of Surgeons in Ireland
J of Thrombosis Haemost - 2022 - Fogarty - Sustained VWF‐ADAMTS‐13 axis imbalance and endotheliopathy in long COVID.pdf (6.98 MB)

Sustained VWF-ADAMTS-13 axis imbalance and endotheliopathy in long COVID syndrome is related to immune dysfunction

Download (6.98 MB)
journal contribution
posted on 2022-09-29, 12:56 authored by Helen FogartyHelen Fogarty, Soracha E Ward, Liam Townsend, Ellie KarampiniEllie Karampini, Stephanie Elliott, Niall Conlon, Jean Dunne, Rachel Kiersey, Aifric Naughton, Mary Gardiner, Mary Byrne, Colm Bergin, Jamie O'SullivanJamie O'Sullivan, Ignacio Martín-Loeches, Parthiban Nadarajan, Ciaran Bannan, Patrick W Mallon, Gerard CurleyGerard Curley, Roger PrestonRoger Preston, Aisling Rehill, Ross I Baker, Cliona Ni Cheallaigh, James O'DonnellJames O'Donnell, Irish COVID-19 Vasculopathy Study (iCVS) Investigators

Background: Prolonged recovery is common after acute SARS-CoV-2 infection; however, the pathophysiological mechanisms underpinning Long COVID syndrome remain unknown. VWF/ADAMTS-13 imbalance, dysregulated angiogenesis, and immunothrombosis are hallmarks of acute COVID-19. We hypothesized that VWF/ADAMTS-13 imbalance persists in convalescence together with endothelial cell (EC) activation and angiogenic disturbance. Additionally, we postulate that ongoing immune cell dysfunction may be linked to sustained EC and coagulation activation.

Patients and methods: Fifty patients were reviewed at a minimum of 6 weeks following acute COVID-19. ADAMTS-13, Weibel Palade Body (WPB) proteins, and angiogenesis-related proteins were assessed and clinical evaluation and immunophenotyping performed. Comparisons were made with healthy controls (n = 20) and acute COVID-19 patients (n = 36).

Results: ADAMTS-13 levels were reduced (p = 0.009) and the VWF-ADAMTS-13 ratio was increased in convalescence (p = 0.0004). Levels of platelet factor 4 (PF4), a putative protector of VWF, were also elevated (p = 0.0001). A non-significant increase in WPB proteins Angiopoietin-2 (Ang-2) and Osteoprotegerin (OPG) was observed in convalescent patients and WPB markers correlated with EC parameters. Enhanced expression of 21 angiogenesis-related proteins was observed in convalescent COVID-19. Finally, immunophenotyping revealed significantly elevated intermediate monocytes and activated CD4+ and CD8+ T cells in convalescence, which correlated with thrombin generation and endotheliopathy markers, respectively.

Conclusion: Our data provide insights into sustained EC activation, dysregulated angiogenesis, and VWF/ADAMTS-13 axis imbalance in convalescent COVID-19. In keeping with the pivotal role of immunothrombosis in acute COVID-19, our findings support the hypothesis that abnormal T cell and monocyte populations may be important in the context of persistent EC activation and hemostatic dysfunction during convalescence.


Health Research Board COVID-19 Rapid Response award (COV19- 2020-086)

3M Foundation philanthropic grant to RCSI University of Medicine and Health Sciences in support of COVID-19 research

Science Foundation Ireland Strategic Parternship Programme (Grant Code 20/SPP/3685)

Irish Clinical Academic Training (ICAT) Programme

Wellcome Trust and the Health Research Board (Grant Number 203930/B/16/Z),

Health Service Executive, National Doctors Training and Planning and the Health and Social Care, Research and Development Division, Northern Ireland

National Children's Research Centre Project Award (C/18/1)

Open access funding provided by IReL



The original article is available at

Published Citation

Fogarty H, et al. Sustained VWF-ADAMTS-13 axis imbalance and endotheliopathy in long COVID syndrome is related to immune dysfunction. J Thromb Haemost. 2022;20(10):2429-2438.

Publication Date

25 July 2022

PubMed ID



  • Irish Centre for Vascular Biology
  • School of Pharmacy and Biomolecular Sciences
  • Anaesthetics and Critical Care


John Wiley & Sons, Inc.


  • Published Version (Version of Record)