Increased risk of acute stroke in patients with severe course of COVID-19: A multicenter study and meta-analysis

Introduction: Recent studies linked coronavirus disease 2019 (COVID-19) to thromboembolic complications likely mediated by increased blood coagulability and inflammatory endothelial impairment Objective: We aimed to assess the risk of acute stroke in patients with COVID-19 related to clinical severity of the disease Methods: We conducted an observational multicenter cohort study in four participating hospitals in Saxony, Germany to characterize consecutive patients with laboratory-confirmed COVID-19 who experienced acute stroke during hospitalization Furthermore, we performed a systematic review using PubMed/MEDLINE, EMBASE, Cochrane Library and bibliographies of identified articles following PRISMA guidelines including data from observational studies of acute stroke in COVID-19 patients Data was extracted by two independent reviewers and pooled with multicenter data to calculate risk ratios (RR) and 95% confidence intervals (95%CIs) for acute stroke related to COVID- 19 severity using random effects model Between-study heterogeneity was assessed using Cochran's Q and I -statistics PROSPERO identifier: CRD42020187194 Results: Of 165 patients hospitalized for COVID-19 (49 1% males, median age 67 [57-79], 72 1% severe or critical) included in the multicenter study, overall stroke rate was 4 2% (95%CI: 1 9-8 7) Systematic literature search identified two observational studies involving 576 patients that were StrokeJournal of the American Heart Association (JAHA)eligible for meta-analysis Among 741 pooled COVID-19 patients overall stroke rate was 2 9%(95%CI: 1 9-4 5) Risk of acute stroke was increased for patients with severe compared to non-severe COVID-19 (RR 4 12, 95%CI 1 7-10 25;p=0 002) with no evidence of heterogeneity (I=0%,p=0 82) Conclusions: Synthesized analysis of data from our multicenter study and previously publishedcohorts demonstrate that severity of COVID-19 is associated with an increased risk of acute stroke, underscoring the necessity of neurological monitoring in patients infected with SARS-CoV-2