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

H. Fogarty; S.E. Ward; L. Townsend; E. Karampini; S. Elliott; N. Conlon; J. Dunne; R. Kiersey; A. Naughton; M. Gardiner; M. Byrne; C. Bergin; J.M. O'Sullivan; I. Martin‐Loeches; P. Nadarajan; C. Bannan; P.W. Mallon; G.F. Curley; R.J.S. Preston; A.M. Rehill; R.I. Baker; C.N. Cheallaigh; J.S. O'Donnell; N. O’Connell; K. Ryan; D. Kenny; J. Fazavana

doi:10.1111/jth.15830

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

Journal article

Peer reviewed

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

H. Fogarty, S.E. Ward, L. Townsend, E. Karampini, S. Elliott, N. Conlon, J. Dunne, R. Kiersey, A. Naughton, M. Gardiner, …

Journal of Thrombosis and Haemostasis, Vol.20(10), pp.2429-2438

2022

DOI: https://doi.org/10.1111/jth.15830

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Abstract

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.

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Title: Sustained VWF‐ADAMTS‐13 axis imbalance and endotheliopathy in long COVID syndrome is related to immune dysfunction
Authors/Creators: H. Fogarty (Author/Creator) - Royal College of Surgeons in Ireland
S.E. Ward (Author/Creator) - Royal College of Surgeons in Ireland
L. Townsend (Author/Creator) - St. James's Hospital
E. Karampini (Author/Creator) - Royal College of Surgeons in Ireland
S. Elliott (Author/Creator) - Royal College of Surgeons in Ireland
N. Conlon (Author/Creator) - Trinity College Dublin
J. Dunne (Author/Creator) - St. James's Hospital
R. Kiersey (Author/Creator) - St. James's Hospital
A. Naughton (Author/Creator) - St. James's Hospital
M. Gardiner (Author/Creator) - St. James's Hospital
M. Byrne (Author/Creator) - St. James's Hospital
C. Bergin (Author/Creator) - St. James's Hospital
J.M. O'Sullivan (Author/Creator)
I. Martin‐Loeches (Author/Creator)
P. Nadarajan (Author/Creator) - St. James's Hospital
C. Bannan (Author/Creator) - St. James's Hospital
P.W. Mallon (Author/Creator) - University College Dublin
G.F. Curley (Author/Creator) - Royal College of Surgeons in Ireland
R.J.S. Preston (Author/Creator) - Royal College of Surgeons in Ireland
A.M. Rehill (Author/Creator) - Royal College of Surgeons in Ireland
R.I. Baker (Author/Creator) - Western Australia Centre for Thrombosis and Haemostasis, Perth Blood Institute Murdoch University Perth WA Australia
C.N. Cheallaigh (Author/Creator)
J.S. O'Donnell (Author/Creator)
N. O’Connell (Author/Creator)
K. Ryan (Author/Creator)
D. Kenny (Author/Creator)
J. Fazavana (Author/Creator)
Publication Details: Journal of Thrombosis and Haemostasis, Vol.20(10), pp.2429-2438
Publisher: Wiley-Blackwell
Identifiers: 991005542330307891
Copyright: © 2022 The Authors.
Murdoch Affiliation: Western Australian Centre for Thrombosis and Haemostasis
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.104 Virology - General; 1.104.1353 Coronavirus Research
Web Of Science research areas: Hematology; Peripheral Vascular Disease
ESI research areas: Clinical Medicine