Journal
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
Volume 19, Issue 10, Pages 2546-2553Publisher
WILEY
DOI: 10.1111/jth.15490
Keywords
convalescent COVID-19; endothelial cell (EC) activation; long COVID
Categories
Funding
- Health Research Board COVID-19 Rapid Response award [COV19-2020-086]
- 3 M Foundation
- Wellcome Trust [203930/B/16/Z]
- Health Research Board [203930/B/16/Z]
- Health Service Executive, National Doctors Training and Planning
- Health and Social Care, Research and Development Division, Northern Ireland
- National Children's Research Centre Project Award [C/18/1]
- German Research Foundation [A11/SFB 877, P6/KFO 306, B8/SFB 841]
- IReL
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The study found that endothelial cell activation may persist in convalescent COVID-19 patients and may contribute to the pathogenesis of long COVID. This sustained endotheliopathy was more common in older, comorbid patients, and those requiring hospitalization, indicating a potential link between endothelial dysfunction and long-term COVID symptoms.
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.
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