Persistent endotheliopathy in the pathogenesis of long COVID syndrome

H. Fogarty; L. Townsend; H. Morrin; A. Ahmad; C. Comerford; E. Karampini; H. Englert; 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; D. McGonagle; C. Ni Cheallaigh; R.I. Baker; T. Renné; S.E. Ward; J.S. O’Donnell; N. O’Connell; K. Ryan; D. Kenny; J. Fazavana

doi:10.1111/jth.15490

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Persistent endotheliopathy in the pathogenesis of long COVID syndrome

Journal article

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Peer reviewed

Persistent endotheliopathy in the pathogenesis of long COVID syndrome

H. Fogarty, L. Townsend, H. Morrin, A. Ahmad, C. Comerford, E. Karampini, H. Englert, M. Byrne, C. Bergin, J.M. O’Sullivan, …

Journal of Thrombosis and Haemostasis

2021

DOI: https://doi.org/10.1111/jth.15490

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Abstract

Background Persistent symptoms including breathlessness, fatigue, and decreased exercise tolerance have been reported in patients after acute SARS-CoV-2 infection. The biological mechanisms underlying this “long COVID” syndrome remain unknown. However, autopsy studies have highlighted the key roles played by pulmonary endotheliopathy and microvascular immunothrombosis in acute COVID-19. Objectives To assess whether endothelial cell activation may be sustained in convalescent COVID-19 patients and contribute to long COVID pathogenesis. Patients and Methods Fifty patients were reviewed at a median of 68 days following SARS-CoV-2 infection. In addition to clinical workup, acute phase markers, endothelial cell (EC) activation and NETosis parameters and thrombin generation were assessed. Results Thrombin generation assays revealed significantly shorter lag times (p < .0001, 95% CI −2.57 to −1.02 min), increased endogenous thrombin potential (p = .04, 95% CI 15–416 nM/min), and peak thrombin (p < .0001, 95% CI 39–93 nM) in convalescent COVID-19 patients. These prothrombotic changes were independent of ongoing acute phase response or active NETosis. Importantly, EC biomarkers including von Willebrand factor antigen (VWF:Ag), VWF propeptide (VWFpp), and factor VIII were significantly elevated in convalescent COVID-19 compared with controls (p = .004, 95% CI 0.09–0.57 IU/ml; p = .009, 95% CI 0.06–0.5 IU/ml; p = .04, 95% CI 0.03–0.44 IU/ml, respectively). In addition, plasma soluble thrombomodulin levels were significantly elevated in convalescent COVID-19 (p = .02, 95% CI 0.01–2.7 ng/ml). Sustained endotheliopathy was more frequent in older, comorbid patients, and those requiring hospitalization. Finally, both plasma VWF:Ag and VWFpp levels correlated inversely with 6-min walk tests. Conclusions Collectively, our findings demonstrate that sustained endotheliopathy is common in convalescent COVID-19 and raise the intriguing possibility that this may contribute to long COVID pathogenesis.

Details

Title: Persistent endotheliopathy in the pathogenesis of long COVID syndrome
Authors/Creators: H. Fogarty (Author/Creator) - Royal College of Surgeons in Ireland
L. Townsend (Author/Creator) - Trinity College Dublin
H. Morrin (Author/Creator) - Royal College of Surgeons in Ireland
A. Ahmad (Author/Creator) - Royal College of Surgeons in Ireland
C. Comerford (Author/Creator) - Royal College of Surgeons in Ireland
E. Karampini (Author/Creator) - Royal College of Surgeons in Ireland
H. Englert (Author/Creator) - University Medical Center Hamburg-Eppendorf
M. Byrne (Author/Creator) - St. James's Hospital
C. Bergin (Author/Creator) - Trinity College Dublin
J.M. O’Sullivan (Author/Creator) - Royal College of Surgeons in Ireland
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
D. McGonagle (Author/Creator) - University of Leeds
C. Ni Cheallaigh (Author/Creator) - Trinity College Dublin
R.I. Baker (Author/Creator) - Western Australia Centre for Thrombosis and Haemostasis Perth Blood Institute Murdoch University Perth WA Australia
T. Renné (Author/Creator) - University Medical Center of the Johannes Gutenberg University Mainz
S.E. Ward (Author/Creator) - Royal College of Surgeons in Ireland
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
Publisher: Wiley-Blackwell
Identifiers: 991005543476507891
Copyright: © 2021 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