PB0051 - Persistent elevation of ɣ’ fibrinogen in acute and convalescent COVID-19

Sunday, June 25, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

Helen Fogarty, MD PhD

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)

GG

Grace Gilmore

Senior Research Scientist
Health Futures Institute, Murdoch University, Perth, Australia
Perth, Western Australia, Australia
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
DF

David H. Farrell

Founder and Chief Scientific Officer Gamma Diagnostics Inc.
Oregon Health and Science University, Portland, OR, United States of America
Portland, Oregon, United States
JT

Jim Tiao

Senior Research Scientist
Health Futures Institute, Murdoch University, Perth, Australia
Perth, Western Australia, Australia
Ross Baker, MD

Professor of Haematology
Health Futures Institute, Murdoch University, Perth, Australia
Perth, Western Australia, Australia

Background: COVID-19 is associated with an increased risk of arterial and venous thrombosis, persisting for months following acute SARS-CoV-2 infection. ɣ’ Fibrinogen (GPF) is an alternatively spliced fibrinogen variant that binds to thrombin with high affinity, modulates clot structure and is resistant to fibrinolysis. Increased levels of GPF are associated with arterial disease, but it is uncertain if this is causal or reactive to inflammation.

Aims: To evaluate plasma GPF levels in acute and convalescent COVID-19 and compare with other coagulation and endotheliopathy markers.

Methods: Following ethical approval by the local Research Ethics Committee and written informed consent, patients attending Beaumont and St James’s Hospitals were recruited, including 47 acute hospitalized COVID-19 patients (n=30 severe/ICU, n=17 moderate/ward), 50 convalescent COVID-19 patients at least six weeks post-illness and 28 asymptomatic controls. The ELISA assay (Gamma Diagnostics) measured GPF with a normal range of 8.9-55.1 mg/dl. Additionally, clinical characteristics and plasma D-dimer, fibrinogen, VWF, factor VIII, CRP, IL-6, and IL-8 levels were evaluated.

Results: GPF is markedly elevated in acute COVID-19, proportional to the clinical severity and persisted across a 3-week ICU admission in severe cases. Furthermore, GPF remains raised six weeks post-illness (See Figure). The majority of convalescent COVID-19 patients (35/50, 70%) had persistently elevated GPF above the normal range. Conversely, elevated FVIII, VWF and D-dimer, were observed in 29%, 26% and 23% in convalescence, respectively. GPF correlated with fibrinogen (r=0.45, p=0.0001) but not age, gender, BMI, co-morbidities, CRP, VWF, FVIII, D-dimer, IL-6 or IL-8 levels, suggesting elevated GPF is distinct from endothelial cell activation.

Conclusion(s): In most COVID-19 cases, GPF is markedly elevated, dependent on illness severity, and remains abnormal at least six weeks post-COVID-19. Raised GPF is independent of other coagulation or endothelial markers. GPF may be a marker of persistent vasculopathy associated with COVID-19.