The role of the VWF/ADAMTS13 axis in the thromboinflammatory response in ischaemic stroke after SARS-CoV2 infection

Background
SARS-CoV2 infections increase the risk of ischaemic stroke (IS), potentially through a thromboinflammatory cascade driven by an imbalance in the ratio of Von Willebrand Factor (VWF) and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), leading to the formation of ultra-large VWF (UL-VWF). However, the SARS-CoV2 infection’s contribution to any VWF/ADAMTS13 axis imbalance and the subsequent thromboinflammatory response post-stroke remains poorly understood.
Methods
We performed a detailed thromboinflammatory profile of the plasma samples from three experimental cohorts matched by age, sex and stroke severity: non-stroke controls (n=23), SARS-CoV2 negative IS (n=22) and SARS-CoV2 positive IS (n=24). SARS-CoV2 positive IS patients presented varying degree of infection severity.
Results
We observed an increase in VWF and UL-VWF and a decrease in ADAMTS13 in the SARS-CoV2 positive IS cohort, suggesting a VWF/ADAMTS13 axis imbalance. Interleukin-6 (IL-6) levels were positively correlated with VWF and negatively correlated with ADAMTS13 suggesting that IL-6 may drive this imbalance. Fibrinogen and D-Dimers were elevated in SARS-CoV2 negative IS cohort and SARS-CoV2 positive IS cohort, but D-Dimers were within normal range, indicating no disseminated intravascular coagulation. Factor IX (FIX) was elevated in the SARS-CoV2 negative IS cohort. Tissue plasminogen activator (tPA) was elevated in the SARS-CoV2 positive IS cohort, suggesting no fibrinolysis defects. Matrix Metalloproteinase-2 (MMP-2) and soluble Intracellular Adhesion Molecule-1 (sICAM-1) were elevated in the SARS-CoV2 negative IS cohort.
Conclusions
We show that SARS-CoV2 infections drive a VWF/ADAMTS13 axis imbalance, inducing an increase in tPA, while decreasing FIX, MMP-2 and sICAM-1 post-stroke.