Stroke Risk, phenotypes, and death in COVID-19: Systematic review and newly reported cases.

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search resulting in 10 studies reporting stroke frequency among COVID-19 patients, which were pooled with one unpublished series from Canada.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additional systematic search for cases series of stroke in COVID-19 patients (n=125) and we pooled these data with 35 unpublished cases from Canada, USA, and Iran.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 ( 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 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.