Royal College of Surgeons in Ireland
Browse
Persistent endotheliopathy in the pathogenesis of long COVID syndrome.pdf (873.75 kB)
Download file

Persistent endotheliopathy in the pathogenesis of long COVID syndrome

Download (873.75 kB)
journal contribution
posted on 2021-09-29, 16:26 authored by Helen FogartyHelen Fogarty, Liam Townsend, Hannah Morrin, Azaz Ahmad, Claire ComerfordClaire Comerford, Ellie KarampiniEllie Karampini, Hanna Englert, Mary Byrne, Colm Bergin, Jamie O'SullivanJamie O'Sullivan, Ignacio Martin-Loeches, Parthiban Nadarajan, Ciaran Bannan, Patrick W Mallon, Gerard CurleyGerard Curley, Roger PrestonRoger Preston, Aisling Rehill, Dennis McGonagle, Cliona Ni Cheallaigh, Ross I Baker, Thomas Renné, Soracha Enright Ward, James O'DonnellJames O'Donnell, Irish COVID-19 Vasculopathy Study (iCVS) investigators

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.

Funding

Health Research Board COVID-19 Rapid Response award, Grant/Award Number: COV19-2020-086

National Children’s Research Centre, Grant/Award Number: C/18/1

Wellcome Trust

3M Foundation

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

German Research Foundation (grants A11/SFB 877, P6/KFO 306 and B8/SFB 841)

IReL (open access funding)

History

Comments

The original article is available at https://onlinelibrary.wiley.com

Published Citation

Fogarty H. et al. Persistent endotheliopathy in the pathogenesis of long COVID syndrome. J Thromb Haemost. 2021 Oct;19(10):2546-2553.

Publication Date

10 August 2021

PubMed ID

34375505

Department/Unit

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

Research Area

  • Vascular Biology

Publisher

Wiley

Version

  • Published Version (Version of Record)