Sustained VWF-ADAMTS13 axis imbalance and endotheliopathy in Long COVID syndrome is related to immune dysfunction, 2022, Fogarty et al

Abstract

Background
Prolonged recovery is common after SARs-CoV-2 infection, however the pathophysiological mechanisms underpinning Long COVID syndrome remain unknown. VWF-ADAMTS13 imbalance, dysregulated angiogenesis and immuno-thrombosis are hallmarks of acute COVID-19. We hypothesized that VWF-ADAMTS13 imbalance persists in convalescence together with EC activation and angiogenic disturbance. Additionally, we postulate that ongoing immune cell dysfunction may be linked to sustained EC and coagulation activation.

Patients and Methods
Fifty patients were reviewed at a minimum of 6 weeks following acute COVID-19. ADAMTS13, WPB proteins and angiogenesis-related proteins were assessed and clinical evaluation and immunophenotyping performed. Comparisons were made with healthy controls (n=20) and acute COVID-19 patients (n=36).

Results
ADAMTS13 levels were reduced (p=0.009) and the VWF/ADAMTS13 ratio was increased in convalescence (p=0.0004). Levels of Platelet Factor 4 (PF4), a putative protector of VWF, were also elevated (p=0.0001). A non-significant increase in WPB proteins Angiopoietin-2 (Ang-2) and Osteoprotegerin (OPG) was observed in convalescent patients and WPB markers correlated with EC parameters. Enhanced expression of 21 angiogenesis-related proteins was observed in convalescent COVID-19. Finally, immunophenotyping revealed significantly elevated intermediate monocytes and activated CD4+ and CD8+ T cells in convalescence, which correlated with thrombin generation and endotheliopathy markers, respectively.

Conclusion
Our data provide insights into sustained EC activation, dysregulated angiogenesis and VWF/ADAMTS13 axis imbalance in convalescent COVID-19. In keeping with the pivotal role of immuno-thrombosis in acute COVID-19, our findings support the hypothesis that abnormal T cell and monocyte populations may be important in the context of persistent EC activation and hemostatic dysfunction during convalescence.

Paywall, https://onlinelibrary.wiley.com/doi/10.1111/jth.15830

 

See also this preprint (2020, doesn't appear to have been accepted)
Severity-stratified and longitudinal analysis of VWF/ADAMTS13 imbalance, altered fibrin crosslinking and inhibition of fibrinolysis as contributors to COVID-19 coagulopathy