Abstract Number: PB0054
Meeting: ISTH 2022 Congress
Theme: COVID and Coagulation » COVID and Coagulation, Clinical
Background: Acute COVID-19 is associated with marked endotheliopathy, VWF-ADAMTS13 axis imbalance and abnormal pulmonary angiogenesis. Persistent endotheliopathy and elevated VWF levels have also been reported in convalescent COVID-19 patients.
Aims: We investigated the hypothesis that altered pulmonary microvascular architecture may persist in COVID-19 convalescence, resulting in ongoing endothelial cell (EC) activation and VWF-ADAMTS13 axis imbalance, possibly contributing to Long COVID pathogenesis.
Methods: 50 patients (median age 50 years, 60% male, median 68 days post acute COVID-19) were reviewed. Six-minute-walk tests (6MWT) were performed (median 6MWT distance 430m) and plasma samples collected. Plasma VWF:Ag and ADAMTS13 levels were measured by ELISA, and angiogenesis markers assessed by membrane-based antibody array.
Results: Plasma VWF:Ag levels were significantly elevated in convalescent COVID-19 patients compared to controls (1.1 versus 0.84 IU/ml; p=0.004), with 30% (15/50) having VWF:Ag levels above the upper limit of normal. In contrast, plasma ADAMTS13 was significantly reduced in convalescent COVID-19 (median 467ng/ml vs 636ng/ml p < 0.001). ADAMTS13 levels were significantly lower in those who required hospitalization for acute COVID-19 compared with those managed as outpatients (median 454ng/ml v 513ng/ml, p=0.04). Overall, the VWF/ADAMTS13 ratio was significantly elevated in convalescent COVID-19 compared with controls (2.1 vs 1.1 p=0.0002) and interestingly was elevated in patients with reduced 6MWT distance (distance ≥430m or < 430m: 1.8 v 2.4, p=0.02). In total, 15 angiogenesis markers were elevated in convalescent COVID-19 compared to controls. An additional 17 angiogenesis markers were unique to convalescent COVID-19 and were not found in control plasma (Table 1).
Conclusion(s): Collectively, these novel findings demonstrate that endotheliopathy is sustained for months following acute COVID-19 in some patients. As a result, plasma VWF levels are significantly increased; ADAMTS13 levels reduced, and there is ongoing dysregulation of angiogenesis. Further studies will be required to define whether these alterations play a role in Long COVID pathogenesis.
Table 1
Table 1: Heatmap visualization indicating angiogenesis marker levels detected in convalescent COVID-19 compared to controls in each subject -columns- for each protein -rows-. Protein levels were measured via membrane-based antibody array and data are represented by mean pixel intensity with red indicating higher and green indicating lower levels of the protein of interest.
To cite this abstract in AMA style:
Fogarty H, Ward S, Townsend L, Karampini E, Elliott S, Byrne M, Bergin C, O'Sullivan J, Martin-Loeches I, Nadarajan P, Bannon C, Preston R, Rehill A, Ni Cheallaigh C, O'Donnell J. A role for Von Willebrand Factor-ADAMTS13 axis imbalance and abnormal angiogenesis in Long COVID syndrome [abstract]. https://abstracts.isth.org/abstract/a-role-for-von-willebrand-factor-adamts13-axis-imbalance-and-abnormal-angiogenesis-in-long-covid-syndrome/. Accessed September 24, 2023.« Back to ISTH 2022 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/a-role-for-von-willebrand-factor-adamts13-axis-imbalance-and-abnormal-angiogenesis-in-long-covid-syndrome/