Biomarkers of Coagulation and Inflammation in COVID-19-Associated Ischemic Stroke

Charles Esenwa, Natalie T. Cheng, Jorge Luna, Joshua Willey, Amelia K. Boehme, Kathryn Kirchoff-Torres, Daniel Labovitz, Ava L. Liberman, Peter Mabie, Khadean Moncrieffe, Ainie Soetanto, Andrea Lendaris, Johanna Seiden, Inessa Goldman, David Altschul, Ryan Holland, Joshua Benton, Joseph Dardick, Jenelys Fernandez-Torres, David FlomenbaumJenny Lu, Avinash Malaviya, Nikunj Patel, Aureliana Toma, Aaron Lord, Koto Ishida, Jose Torres, Thomas Snyder, Jennifer Frontera, Shadi Yaghi

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Background and Purpose: We sought to determine if biomarkers of inflammation and coagulation can help define coronavirus disease 2019 (COVID-19)-associated ischemic stroke as a novel acute ischemic stroke (AIS) subtype. Methods: We performed a machine learning cluster analysis of common biomarkers in patients admitted with severe acute respiratory syndrome coronavirus 2 to determine if any were associated with AIS. Findings were validated using aggregate data from 3 large healthcare systems. Results: Clustering grouped 2908 unique patient encounters into 4 unique biomarker phenotypes based on levels of c-reactive protein, D-dimer, lactate dehydrogenase, white blood cell count, and partial thromboplastin time. The most severe cluster phenotype had the highest prevalence of AIS (3.6%, P<0.001), in-hospital AIS (53%, P<0.002), severe AIS (31%, P=0.004), and cryptogenic AIS (73%, P<0.001). D-dimer was the only biomarker independently associated with prevalent AIS with quartile 4 having an 8-fold higher risk of AIS compared to quartile 1 (P=0.005), a finding that was further corroborated in a separate cohort of 157 patients hospitalized with COVID-19 and AIS. Conclusions: COVID-19-associated ischemic stroke may be related to COVID-19 illness severity and associated coagulopathy as defined by increasing D-dimer burden.

Original languageEnglish
Pages (from-to)E706-E709
Issue number11
StatePublished - 1 Nov 2021
Externally publishedYes


  • COVID-19
  • biomarker
  • inflammation
  • ischemic stroke
  • mortality


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