Increased risk of acute stroke among patients with severe COVID-19: a multicenter study and meta-analysis.

BACKGROUND: Recent observations linked coronavirus disease 2019 (COVID-19) to thromboembolic complications possibly mediated by increased blood coagulability and inflammatory endothelial impairment. We aimed to define the risk of acute stroke in patients with severe and non-severe COVID-19. METHODS: We performed 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 conducted a systematic review using PubMed/MEDLINE, EMBASE, Cochrane Library and bibliographies of identified papers 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 I2 -statistics. PROSPERO registration number: 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 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 4.18, 95%CI 1.7-10.25; p=0.002) with no evidence of heterogeneity (I2 =0%, p=0.82). CONCLUSIONS: Synthesized analysis of data from our multicenter study and previously published cohorts indicate that severity of COVID-19 is associated with an increased risk of acute stroke.