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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Vydáno v:	Journal of thrombosis and haemostasis Ročník 19; číslo 10; s. 2546 - 2553
Hlavní autoři:	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
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	England Elsevier Limited 01.10.2021 John Wiley and Sons Inc
Témata:	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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Shrnutí:	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.
Bibliografie:	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 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 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