Persistent endotheliopathy in the pathogenesis of long COVID syndrome

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...

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Veröffentlicht in:Journal of thrombosis and haemostasis Jg. 19; H. 10; S. 2546 - 2553
Hauptverfasser: 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., O’Connell, Niamh, Ryan, Kevin, Kenny, Dermot, Fazavana, Judicael
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England Elsevier Limited 01.10.2021
John Wiley and Sons Inc
Schlagworte:
Aged
Autopsy
Biomarkers
Brief Report
Cell activation
Coagulation factors
convalescent COVID‐19
COVID-19
COVID-19 - complications
endothelial cell (EC) activation
Endothelial cells
Humans
Immunological tolerance
Long COVID
Microvasculature
Pathogenesis
Patients
Post-Acute COVID-19 Syndrome
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
Thrombin
THROMBOSIS
Von Willebrand factor
endothelial cell (EC) activation
long COVID
convalescent COVID-19
ISSN:1538-7933, 1538-7836, 1538-7836
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Zusammenfassung: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.
Bibliographie:section.
The members of Irish COVID‐19 Vasculopathy Study (iCVS) investigators are listed in the
Final decision: Flora Peyvandi, 09 August 2021
Manuscript Handled by: Flora Peyvandi
Appendix
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The members of Irish COVID‐19 Vasculopathy Study (iCVS) investigators are listed in the Appendix section.
ISSN:1538-7933
1538-7836
1538-7836
DOI:10.1111/jth.15490