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The Role of the VWF/ADAMTS13 Axis in the Thromboinflammatory Response in Ischemic Stroke After SARS-CoV2 Infection

Nadim Luka1,2, Kieron South1,2, Rachel Jones1,3,4

  • 1Geoffrey Jefferson Brain Research Centre, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.

Brain and Behavior
|February 20, 2025
PubMed
Abstract

Insights

SARS-CoV2 infection disrupts the Von Willebrand Factor (VWF)/ADAMTS13 balance, increasing stroke risk. This imbalance elevates tissue plasminogen activator (tPA) while reducing Factor IX (FIX), Matrix Metalloproteinase-2 (MMP-2), and soluble Intracellular Adhesion Molecule-1 (sICAM-1) post-stroke.

Area of Science:

  • Cardiovascular Science
  • Infectious Disease Immunology
  • Neurology

Background:

  • SARS-CoV2 infection is linked to increased ischemic stroke (IS) risk.
  • A potential mechanism involves a thromboinflammatory cascade driven by an imbalance in Von Willebrand Factor (VWF) and ADAMTS13.
  • The precise role of SARS-CoV2 in VWF/ADAMTS13 axis imbalance and post-stroke thromboinflammation is unclear.

Purpose of the Study:

  • To investigate the thromboinflammatory profile in patients with SARS-CoV2 infection and ischemic stroke.
  • To elucidate the impact of SARS-CoV2 on the VWF/ADAMTS13 axis.
  • To identify specific biomarkers associated with SARS-CoV2-related stroke.

Main Methods:

  • Plasma samples from three matched cohorts were analyzed: non-stroke controls, SARS-CoV2-negative IS, and SARS-CoV2-positive IS.
  • Detailed thromboinflammatory profiling was performed on all samples.
  • Patient cohorts were matched for age, sex, and stroke severity.

Main Results:

  • SARS-CoV2-positive IS patients exhibited increased VWF and ultra-large VWF (UL-VWF) with decreased ADAMTS13, indicating a VWF/ADAMTS13 axis imbalance.
  • Interleukin-6 (IL-6) correlated positively with VWF and negatively with ADAMTS13, suggesting IL-6 drives the imbalance.
  • Elevated tPA in SARS-CoV2-positive IS patients suggests intact fibrinolysis, while decreased FIX, MMP-2, and sICAM-1 were observed.

Conclusions:

  • SARS-CoV2 infection induces a VWF/ADAMTS13 axis imbalance post-stroke.
  • This imbalance is associated with increased tPA and decreased levels of FIX, MMP-2, and sICAM-1.
  • The findings highlight a specific thromboinflammatory signature in SARS-CoV2-related ischemic stroke.
Keywords:
ADAMTS13SARS‐CoV2VWFischemic stroke and thromboinflammation

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