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

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

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.