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

Abstract

Background and purpose 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 Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines including data from observational studies of acute stroke in COVID‐19 patients. Data were extracted by two independent reviewers and pooled with multicenter data to calculate risk ratios (RRs) and 95% confidence intervals (95% CIs) for acute stroke related to COVID‐19 severity using a random‐effects model. Between‐study heterogeneity was assessed using Cochran’s Q and I2 statistics. International Prospective Register of Systematic Reviews registration number: CRD42020187194. Results Of 165 patients hospitalized for COVID‐19 (49.1% males, median age = 67 years [57–79 years], 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. Amongst 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 indicates that severity of COVID‐19 is associated with an increased risk of acute stroke.

Risk, clinical course and outcome of ischemic stroke in patients hospitalized with COVID-19: a multicenter cohort study

“…The overall incidence of ischemic stroke of 1.8% in hospitalized patients with COVID-19 is in line with previously published hospital-based COVID-19 cohorts, which reported cumulative incidences ranging between 1.0% and 2.4%. [3][4][5] Lower stroke rates have been found in studies that reported on a combination of hospitalized and non-hospitalized patients. 6,23 Higher rates of up to 6.9% have been reported in populations consisting of ICU patients alone or in other selected patient populations.…”

“…First, most studies were performed in Asia and North America, with only a few European cohorts. [3][4][5]7 Geographical variation may explain some of the heterogeneity, with a higher incidence reported in Asia than in North America and Europe. 3 In addition, regional differences in COVID-19 surges may have resulted in a higher threshold for seeking medical attention in some pandemic areas, especially for patients with mild symptoms of stroke.…”

“…The occurrence of ischemic stroke varied greatly, ranging from 0.01% to 6.9%. [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] This may be explained in part by differences in study design, size, case-findings methods, and settings.…”

“…2 Several studies have found that patients with COVID-19 who had acute ischemic stroke were more likely to die. [3][4][5] It remains unclear whether this association with an increased mortality is driven by disease severity and the prothrombotic state triggered by COVID-19. Alternatively, other confounding factors, such as impeded functional recovery due to fever and infection and withdrawal of care in patients with COVID-19 and ischemic stroke, may also play a role.…”

COVID-19: Intensivmedizinische Aspekte und Langzeitfolgen

“…Pathophysiologisch könnte dies auf direkte negative Auswirkungen der Immunreaktion, die Beschleunigung oder Aggravation bereits bestehender kognitiver Defizite oder sogarwie von einigen Forschern vermutetauf die De-novo-Entstehung einer neurodegenerativen Erkrankung zurückzuführen sein [37]. Auch akute zerebrale Ischämien finden sich bei COVID-19-Patienten häufiger [38].…”