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

Abstract

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.

Laboratory Biomarkers for Diagnosis and Prognosis in COVID-19

“…In COVID-19 patients with altered NfL and GFAP, values of these markers had normalized in all individuals at 6-month follow-up, suggesting that post-COVID-19 neurological sequelae may be not accompanied by ongoing brain injury ( 91 ). Inflammatory and coagulatory markers like D-dimer, LDH, erythrocyte sedimentation rate (ESR), and CRP were independently associated with the occurrence of ischemic stroke in COVID-19 ( 92 , 93 ), while higher age, diabetes mellitus, and hypertension were found not to be significant predictors of stroke in this population, despite being known predictors of non-COVID-19 stroke ( 93 ). Levels of lymphocytes, procalcitonin, and creatinine were higher in COVID-19 stroke patients ( 94 ).…”

Cerebrovascular Complications of COVID-19 and COVID-19 Vaccination

“… 5 Patients with COVID-19 at the highest risk of ischemic stroke appear to be those with a history of ischemic stroke, 26 possibly a history of diabetes 4 and other traditional stroke risk factors, 27 and higher serum d -dimer levels. 28 , 29 …”

“…5 Patients with COVID-19 at the highest risk of ischemic stroke appear to be those with a history of ischemic stroke, 26 possibly a history of diabetes 4 and other traditional stroke risk factors, 27 and higher serum d-dimer levels. 28,29 Outcomes in strokes occurring in patients with COVID-19 also appear worse, in terms of initial stroke severity (compared with historical controls), 30 functional outcome at discharge (compared with contemporary and historical controls), 30,31 discharge destination (compared with historical controls), 32 and inpatient mortality (compared with both contemporary and historical controls). 4,[30][31][32][33] With regard to etiologic classification, patients with COVID-19-associated ischemic strokes have been shown to present with more embolic-appearing findings on neuroimaging.…”

Neutrophil–Lymphocyte ratio is associated with poor clinical outcome after mechanical thrombectomy in stroke in patients with COVID-19

“…al demonstrated that higher admission NLR values are independent predictors of symptomatic intracranial hemorrhage and 3-month mortality in LVO patients treated with mechanical thrombectomy. 27 – 29 In an observational study of 60 patients with acute ischemic stroke, Lin et. al showed that patients with the SARS-Cov-2 virus had a higher NLR compared to those without infection.…”