Pneumonia appears to be the most common manifestation of coronavirus disease 2019 (COVID-19), but some extrapulmonary involvement, such as gastrointestinal, cardiac and renal, has been reported. The limited clinical data about the virus's behavior to date, especially extrapulmonary symptoms, suggest that we should be aware of the possibility of initial cerebrovascular manifestations of COVID-19.

Objectives:To investigate the hypothesis that strokes occurring in patients with COVID-19 have distinctive features, we investigated stroke risk, clinical phenotypes, and outcomes in this population.Methods:We performed a systematic search resulting in 10 studies reporting stroke frequency among COVID-19 patients, which were pooled with one unpublished series from Canada. We applied random-effects meta-analyses to estimate the proportion of stroke among COVID-19. We performed an additional systematic search for cases series of stroke in COVID-19 patients (n=125) and we pooled these data with 35 unpublished cases from Canada, USA, and Iran. We analyzed clinical characteristics and in-hospital mortality stratified into age groups (<50, 50-70, >70 years). We applied cluster analyses to identify specific clinical phenotypes and their relationship with death.Results:The proportion of COVID-19 patients with stroke (1.8%, 95%CI 0.9-3.7%) and in-hospital mortality (34.4%, 95%CI 27.2-42.4%) were exceedingly high. Mortality was 67% lower in patients <50 years-old relative to those >70 years-old (OR 0.33, 95%CI 0.12-0.94, P=0.039). Large vessel occlusion was twice as frequent (46.9%) as previously reported and was high across all age groups, even in the absence of risk factors or comorbidities. A clinical phenotype characterized by older age, a higher burden of comorbidities, and severe COVID-19 respiratory symptoms, was associated with the highest in-hospital mortality (58.6%) and a 3x higher risk of death than the rest of the cohort (OR 3.52, 95%CI 1.53-8.09, P=0.003).Conclusions:Stroke is relatively frequent among COVID-19 patients and has devastating consequences across all ages. The interplay of older age, comorbidities, and severity of COVID-19 respiratory symptoms is associated with an extremely elevated mortality.