{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T05:13:10Z","timestamp":1784783590359,"version":"3.55.0"},"reference-count":47,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T00:00:00Z","timestamp":1739923200000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["FS\/4yPhD\/F\/20\/34131"],"award-info":[{"award-number":["FS\/4yPhD\/F\/20\/34131"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>SARS\u2010CoV2 infections increase the risk of ischemic 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\u2010large VWF (UL\u2010VWF). However, the SARS\u2010CoV2 infection's contribution to any VWF\/ADAMTS13 axis imbalance and the subsequent thromboinflammatory response post\u2010stroke remain poorly understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a detailed thromboinflammatory profile of the plasma samples from three experimental cohorts matched by age, sex, and stroke severity: non\u2010stroke controls (<jats:italic>n<\/jats:italic> = 23), SARS\u2010CoV2 negative IS (<jats:italic>n<\/jats:italic> = 22), and SARS\u2010CoV2 positive IS (<jats:italic>n<\/jats:italic> = 24). SARS\u2010CoV2 positive IS patients presented varying degrees of infection severity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We observed an increase in VWF and UL\u2010VWF and a decrease in ADAMTS13 in the SARS\u2010CoV2 positive IS cohort, suggesting a VWF\/ADAMTS13 axis imbalance. Interleukin\u20106 (IL\u20106) levels were positively correlated with VWF and negatively correlated with ADAMTS13, suggesting that IL\u20106 may drive this imbalance. Fibrinogen and D\u2010Dimers were elevated in SARS\u2010CoV2 negative IS cohort and SARS\u2010CoV2 positive IS cohort, but D\u2010Dimers were within the normal range, indicating no disseminated intravascular coagulation. Factor IX (FIX) was elevated in the SARS\u2010CoV2 negative IS cohort. Tissue plasminogen activator (tPA) was elevated in the SARS\u2010CoV2 positive IS cohort, suggesting no fibrinolysis defects. Matrix Metalloproteinase\u20102 (MMP\u20102) and soluble Intracellular Adhesion Molecule\u20101 (sICAM\u20101) were elevated in the SARS\u2010CoV2 negative IS cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We show that SARS\u2010CoV2 infections drive a VWF\/ADAMTS13 axis imbalance, inducing an increase in tPA while decreasing FIX, MMP\u20102, and sICAM\u20101 post\u2010stroke.<\/jats:p><\/jats:sec>","DOI":"10.1002\/brb3.70348","type":"journal-article","created":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T01:04:43Z","timestamp":1740013483000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Role of the VWF\/ADAMTS13 Axis in the Thromboinflammatory Response in Ischemic Stroke After SARS\u2010CoV2 Infection"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7912-835X","authenticated-orcid":false,"given":"Nadim","family":"Luka","sequence":"first","affiliation":[{"name":"Geoffrey Jefferson Brain Research Centre, School of Biological Sciences, Faculty of Biology, Medicine and Health The University of Manchester  Manchester UK"},{"name":"Division of Neuroscience The University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kieron","family":"South","sequence":"additional","affiliation":[{"name":"Geoffrey Jefferson Brain Research Centre, School of Biological Sciences, Faculty of Biology, Medicine and Health The University of Manchester  Manchester UK"},{"name":"Division of Neuroscience The University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Jones","sequence":"additional","affiliation":[{"name":"Geoffrey Jefferson Brain Research Centre, School of Biological Sciences, Faculty of Biology, Medicine and Health The University of Manchester  Manchester UK"},{"name":"Division of Cardiovascular Sciences The University of Manchester  Manchester UK"},{"name":"Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health Manchester Academic Health Science Centre, The University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda J.","family":"Unsworth","sequence":"additional","affiliation":[{"name":"Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine University of Leeds  Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham","family":"Coutts","sequence":"additional","affiliation":[{"name":"Geoffrey Jefferson Brain Research Centre, School of Biological Sciences, Faculty of Biology, Medicine and Health The University of Manchester  Manchester 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