Incidence of Stroke in Randomized Trials of COVID-19 Therapeutics: A Systematic Review and Meta-Analysis

Abstract

Background: COVID-19 has been frequently associated with an increased risk of thrombotic complications. There have also been reports of an increased likelihood of stroke, although its true incidence in patients with COVID-19 is currently unknown. Methods: Electronic databases PubMed and Scopus were searched from inception up to July 30, 2021 to identify randomized controlled studies in patients with confirmed COVID-19 undergoing one or more interventions. Studies were screened for eligibility using a predefined inclusion criterion and selected using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A random-effects model meta-analysis was conducted, and heterogeneity was assessed using I-squared test. Results: Out of 3960 potentially eligible articles, 77 randomized studies (38 732 patients) were included. Mean age of the study population was 55±9.3 years. Females constituted 38% of the study population and mean duration of follow-up after study enrollment was 23±12.9 days. Cumulative incidence of stroke in the overall study population was 0.001 (95% CI, 0.001–0.002) with a total of 65 events in 38 732 patients, corresponding to an absolute incidence of 0.168%. Incidence of stroke in the inpatient population was 0.001 (95% CI, 0.001–0.002; 65 events in 37 069 patients), corresponding to an absolute incidence of 0.175%. No strokes were observed in the outpatient setting. Conclusions: The overall incidence of stroke in patients with COVID-19 appears to be lower than that reported in previous observational reports.

Prevalence and Mortality Risk of Neurological Disorders during the COVID-19 Pandemic: An Umbrella Review of the Current Evidence

“…Considering the methodological quality of AMSTAR-2 tool items, 15 [6,8,[14][15][16][17][18][19][20][21][22][23][24][25][26] and 1 [27] studies were rated as being of high and moderate quality, respectively. Overall, 16 [7,24,[28][29][30][31][32][33][34][35][36][37][38][39][40][41] and 12 [5,[42][43][44][45][46][47][48][49][50][51][52] studies were rated as being of low and critically low quality (online suppl. Material S3 Table 1).…”

Pathophysiology, diagnosis, and management of neuroinflammation in covid-19

“…Acute stroke has been commonly reported as a neurological complication, but the overall frequency in the covid-19 population is low (1.4%; 95% confidence interval 1.0 to 1.9) 111. A meta-analysis suggested that the absolute incidence of stroke was 0.168%, lower than previously estimated 112. The most common manifestation was acute ischemic stroke (87.4%); intracerebral hemorrhage was less common (11.6%) 111.…”

COVID-19 and Acute Ischemic Stroke Mortality and Clinical Outcomes among Hospitalized Patients in the United States: Insight from National Inpatient Sample

“…The prevalence of AIS with COVID-19 was reported as 0.2–2.7% in previous publications, which is consistent with our prevalence data of 0.4% [ 3 , 8 , 9 , 17 ]. A recent systematic review and meta-analysis by Nagraj et al reviewed the incidence of stroke in randomized trials for COVID-19 therapeutics and included studies until 30 July 2021 [ 18 ]. This systematic review included 38,732 patients from inpatient and outpatient settings (65 patients with stroke) from 77 randomized studies, and all reported stroke events happened in the inpatient setting with an overall incidence of 0.18%.…”

“…They also concluded that there is a possibility of an association between the severity of the COVID-19 infection with the occurrence of stroke. Compared to prior studies, which have included smaller sample sizes [ 6 , 18 ], our study compares AIS outcomes in COVID-19 patients based on one of the largest cohorts of COVID-19 patients hospitalized in the United States in 2020. To our knowledge, our study is the largest study looking at the inpatient outcomes of patients hospitalized with AIS and COVID-19.…”