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A role for Von Willebrand Factor-ADAMTS13 axis imbalance and abnormal angiogenesis in long COVID syndrome
Research and Practice in Thrombosis and Haemostasis Conference ; 6(Supplement 1), 2022.
Article in English | EMBASE | ID: covidwho-2128157
ABSTRACT

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. Aim(s) 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. Method(s) 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 VWFAg and ADAMTS13 levels were measured by ELISA, and angiogenesis markers assessed by membrane-based antibody array. Result(s) Plasma VWFAg levels were significantly elevated in convalescent COVID-19 patients compared to controls (1.1 vs. 0.84 IU/ml;p = 0.004), with 30% (15/50) having VWFAg levels above the upper limit of normal. In contrast, plasma ADAMTS13 was significantly reduced in convalescent COVID-19 (median 467 ng/ml vs. 636 ng/ 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 454 ng/ml vs. 513 ng/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 >=430 m or <430 m 1.8 vs. 2.4, p = 0.02). In total, 15 angiogenesis markers were elevated in convalescent COVID-19 compared to controls. An additional 17 angiogenesis (Figure Presented) 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.
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Full text: Available Collection: Databases of international organizations Database: EMBASE Topics: Long Covid Language: English Journal: Research and Practice in Thrombosis and Haemostasis Conference Year: 2022 Document Type: Article

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Full text: Available Collection: Databases of international organizations Database: EMBASE Topics: Long Covid Language: English Journal: Research and Practice in Thrombosis and Haemostasis Conference Year: 2022 Document Type: Article