Ammad Mahmood, MBChB
McAlpine LS, Zubair AS, Maran I, Chojecka P, Lleva P, Jasne AS, Navaratnam D, Matouk C, Schindler J, Sheth KN, et al. Ischemic Stroke, Inflammation, and Endotheliopathy in COVID-19 Patients. Stroke. 2021.
Ischemic stroke occurring during COVID-19 infection has been the subject of significant interest, though exact mechanisms linking infection to stroke risk are not yet understood and, as such, management of this increased risk is still debated.1 This retrospective observational cohort study compares 2 cohorts of patients with ischemic stroke, one with COVID-19 infection (n=21) and one without (n=168). As well as gathering data on clinical characteristics and etiology, serial laboratory markers of inflammation were examined to ascertain what role inflammation and endothelial damage and activation may play in the pathogenesis of ischemic stroke in COVID-19.
Traditional risk factors between groups were similar with a similar rate of LVO, though COVID-19 patients were less likely to receive intravenous thrombolysis. A correlation between onset of stroke and peak levels of CRP, ferritin and D-dimer was found. An association was found between elevated interleukin-6 and soluble interleukin-2 receptor levels at stroke onset and cases of embolic stroke of undetermined source (ESUS), though the ESUS criteria used is not mentioned. A subset ofD, Matouk C, Schind 8 patients had markers of endotheliopathy measured (von Willebrand factor activity and antigen, Factor VIII), and these were found to be elevated compared with a similar cohort of non-COVID-19 patients.
The authors hypothesize that ischemic stroke in COVID-19 is caused by underlying endotheliopathy and thrombosis that is distinct to disseminated intravascular coagulation or antiphospholipid antibody syndrome. COVID-19 patients had traditional stroke risk factors suggesting pre-existing endothelial damage. A suggested mechanism involves COVID-19 infection triggering a systemic inflammatory response resulting in endothelial damage, activation and hypercoagulability leading to thrombosis. The authors acknowledge the small number of participants with COVID-19 and relevant full laboratory panels in this study were limited. Patients with and without COVID-19 in this study had traditional risk factors for stroke; other cohort studies have not found an additional risk posed by COVID-19 above usual risk factors.2 Antithrombotic therapy has been initiated in selected COVID-19 patients to prevent thrombotic events since the beginning of the pandemic,3 and further research into underlying mechanisms may help to guide this therapy in ischemic stroke patients. Further larger studies of relevant markers of inflammation and endotheliopathy in ischemic stroke patients may be warranted.
- Zakeri A, Jadhav AP, Sullenger BA, et al. Ischemic stroke in COVID-19-positive patients: an overview of SARS-CoV-2 and thrombotic mechanisms for the neurointerventionalist. Journal of NeuroInterventional Surgery. 2021;13:202-206.
- Qureshi AI, Baskett WI, Huang W, Shyu D, Myers D, Raju M, Lobanova I, Suri MFK, Naqvi SH, French BR, Siddiq F, Gomez CR, Shyu CR. Acute Ischemic Stroke and COVID-19: An Analysis of 27 676 Patients. Stroke. 2021 Mar;52(3):905-912
- Rentsch C T, Beckman J A, Tomlinson L, Gellad W F, Alcorn C, Kidwai-Khan F, et al. Early initiation of prophylactic anticoagulation for prevention of coronavirus disease 2019 mortality in patients admitted to hospital in the United States: cohort study. BMJ. 2021;372:n311.