PB0054 - A role for Von Willebrand Factor-ADAMTS13 axis imbalance and abnormal angiogenesis in Long COVID syndrome

Sunday, July 10, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Helen Fogarty, MB BAO BCh MSc MRCPI

Haematology SpR and Wellcome Trust/HRB ICAT Fellow
Irish Centre for Vascular Biology, Royal College of Surgeons in Ireland, Dublin Ireland
Dublin, Dublin, Ireland

Co-Author(s)

SW

Soracha Ward

Postdoctoral
RCSI
Dublin, Dublin, Ireland
LT

Liam Townsend

Infectious Disease Specialist Registrar and Wellcome Trust ICAT Fellow
Department of Infectious Diseases, St James’s Hospital, Dublin, Ireland.
Dublin, Dublin, Ireland
EK

Ellie Karampini

Postdoctoral Researcher
2. Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
Dublin, Dublin, Ireland
SE

Stephanie Elliott

Research Assistant
Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin 2, Ireland
Dublin, Carlow, Ireland
MB

Mary Byrne

Coagulation Laboratory Chief
National Coagulation Centre, St James's Hospital, Dublin
Dublin, Dublin, Ireland
CB

Colm Bergin

Professor of Infectious Diseases
Department of Infectious Diseases, St James’s Hospital, Dublin, Ireland.
Dublin, Dublin, Ireland
JO

Jamie M. O’Sullivan, PhD

StAR Research Lecturer
Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland
Dublin, Dublin, Ireland
IM

Ignacio Martin-Loeches

Professor of Intensive Care Medicine
Department of Intensive Care Medicine, St James’s Hospital, Dublin, Ireland
Dublin, Dublin, Ireland
PN

Parthiban Nadarajan

Consultant in Respiratory Medicine
Department of Respiratory Medicine, St James’s Hospital, Dublin, Ireland.
Dublin, Dublin, Ireland
CB

Ciaran Bannon

Consultant in Infectious Diseases
Department of Infectious Diseases, St James’s Hospital, Dublin, Ireland.
Dublin, Dublin, Ireland
Roger J.S. Preston, PhD

Principal Investigator, Lecturer in Vascular Biology
Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons, Dublin 2, Ireland
Dublin, Dublin, Ireland
AR

Aisling M. M. Rehill

Postdoctoral researcher
Irish Centre for Vascular Biology, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons, Dublin 2, Ireland
Dublin, Dublin, Ireland
CN

Cliona Ni Cheallaigh

Consultant in Infectious Diseases
Department of Infectious Diseases, St James’s Hospital, Dublin, Ireland.
Dublin, Dublin, Ireland
JO

James S. O'Donnell, MB, PhD

Professor of Haematology
Irish Centre for Vascular Biology, Royal College of Surgeons in Ireland,Dublin, Ireland
Dublin, Dublin, Ireland

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.