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Persistent Endotheliopathy in the Pathogenesis of Long COVID Syndrome

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Persistent Endotheliopathy in the Pathogenesis of Long COVID Syndrome. / Fogarty, Helen; Townsend, Liam; Morrin, Hannah; Ahmad, Azaz; Comerford, Claire; Karampini, Ellie; Englert, Hanna; Byrne, Mary; Bergin, Colm; O'Sullivan, Jamie M; Martin-Loeches, Ignacio; Nadarajan, Parthiban; Bannan, Ciaran; Mallon, Patrick W; Curley, Gerard F; Preston, Roger J S; Rehill, Aisling M; McGonagle, Dennis; Ni Cheallaigh, Cliona; Baker, Ross I; Renné, Thomas; Ward, Soracha E; O' Donnell, James S; Irish COVID-19 Vasculopathy Study (iCVS) investigators.

in: J THROMB HAEMOST, Jahrgang 19, Nr. 10, 10.2021, S. 2546-2553.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Fogarty, H, Townsend, L, Morrin, H, Ahmad, A, Comerford, C, Karampini, E, Englert, H, Byrne, M, Bergin, C, O'Sullivan, JM, Martin-Loeches, I, Nadarajan, P, Bannan, C, Mallon, PW, Curley, GF, Preston, RJS, Rehill, AM, McGonagle, D, Ni Cheallaigh, C, Baker, RI, Renné, T, Ward, SE, O' Donnell, JS & Irish COVID-19 Vasculopathy Study (iCVS) investigators 2021, 'Persistent Endotheliopathy in the Pathogenesis of Long COVID Syndrome', J THROMB HAEMOST, Jg. 19, Nr. 10, S. 2546-2553. https://doi.org/10.1111/jth.15490

APA

Fogarty, H., Townsend, L., Morrin, H., Ahmad, A., Comerford, C., Karampini, E., Englert, H., Byrne, M., Bergin, C., O'Sullivan, J. M., Martin-Loeches, I., Nadarajan, P., Bannan, C., Mallon, P. W., Curley, G. F., Preston, R. J. S., Rehill, A. M., McGonagle, D., Ni Cheallaigh, C., ... Irish COVID-19 Vasculopathy Study (iCVS) investigators (2021). Persistent Endotheliopathy in the Pathogenesis of Long COVID Syndrome. J THROMB HAEMOST, 19(10), 2546-2553. https://doi.org/10.1111/jth.15490

Vancouver

Fogarty H, Townsend L, Morrin H, Ahmad A, Comerford C, Karampini E et al. Persistent Endotheliopathy in the Pathogenesis of Long COVID Syndrome. J THROMB HAEMOST. 2021 Okt;19(10):2546-2553. https://doi.org/10.1111/jth.15490

Bibtex

@article{fedbc892281349ea99510849d8fa7c5a,
title = "Persistent Endotheliopathy in the Pathogenesis of Long COVID Syndrome",
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.",
author = "Helen Fogarty and Liam Townsend and Hannah Morrin and Azaz Ahmad and Claire Comerford and Ellie Karampini and Hanna Englert and Mary Byrne and Colm Bergin and O'Sullivan, {Jamie M} and Ignacio Martin-Loeches and Parthiban Nadarajan and Ciaran Bannan and Mallon, {Patrick W} and Curley, {Gerard F} and Preston, {Roger J S} and Rehill, {Aisling M} and Dennis McGonagle and {Ni Cheallaigh}, Cliona and Baker, {Ross I} and Thomas Renn{\'e} and Ward, {Soracha E} and {O' Donnell}, {James S} and {Irish COVID-19 Vasculopathy Study (iCVS) investigators}",
note = "This article is protected by copyright. All rights reserved.",
year = "2021",
month = oct,
doi = "10.1111/jth.15490",
language = "English",
volume = "19",
pages = "2546--2553",
journal = "J THROMB HAEMOST",
issn = "1538-7933",
publisher = "Wiley-Blackwell",
number = "10",

}

RIS

TY - JOUR

T1 - Persistent Endotheliopathy in the Pathogenesis of Long COVID Syndrome

AU - Fogarty, Helen

AU - Townsend, Liam

AU - Morrin, Hannah

AU - Ahmad, Azaz

AU - Comerford, Claire

AU - Karampini, Ellie

AU - Englert, Hanna

AU - Byrne, Mary

AU - Bergin, Colm

AU - O'Sullivan, Jamie M

AU - Martin-Loeches, Ignacio

AU - Nadarajan, Parthiban

AU - Bannan, Ciaran

AU - Mallon, Patrick W

AU - Curley, Gerard F

AU - Preston, Roger J S

AU - Rehill, Aisling M

AU - McGonagle, Dennis

AU - Ni Cheallaigh, Cliona

AU - Baker, Ross I

AU - Renné, Thomas

AU - Ward, Soracha E

AU - O' Donnell, James S

AU - Irish COVID-19 Vasculopathy Study (iCVS) investigators

N1 - This article is protected by copyright. All rights reserved.

PY - 2021/10

Y1 - 2021/10

N2 - 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.

AB - 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.

U2 - 10.1111/jth.15490

DO - 10.1111/jth.15490

M3 - SCORING: Journal article

C2 - 34375505

VL - 19

SP - 2546

EP - 2553

JO - J THROMB HAEMOST

JF - J THROMB HAEMOST

SN - 1538-7933

IS - 10

ER -