Risk of Ischemic Stroke in Patients with Covid-19 versus Patients with Influenza

Merkler, Alexander E.; Parikh, Neal S.; Mir, Saad; Gupta, Ajay; Kamel, Hooman; Lin, Eaton; Lantos, Joshua; Schenck, Edward J.; Goyal, Parag; Bruce, Samuel S.; Kahan, Joshua; Lansdale, Kelsey N.; LeMoss, Natalie M.; Murthy, Santosh B.; Stieg, Philip E.; Fink, Matthew E.; Iadecola, Costantino; Segal, Alan Z.; Campion, Thomas R.; Diaz, Ivan; Zhang, Cenai; Navi, Babak B.

IMPORTANCE: Case series without control groups suggest that Covid-19 may cause ischemic stroke, but whether Covid-19 is associated with a higher risk of ischemic stroke than would be expected from a viral respiratory infection is uncertain. OBJECTIVE: To compare the rate of ischemic stroke between patients with Covid-19 and patients with influenza, a respiratory viral illness previously linked to stroke. DESIGN: A retrospective cohort study. SETTING: Two academic hospitals in New York City. PARTICIPANTS: We included adult patients with emergency department visits or hospitalizations with Covid-19 from March 4, 2020 through May 2, 2020. Our comparison cohort included adult patients with emergency department visits or hospitalizations with influenza A or B from January 1, 2016 through May 31, 2018 (calendar years spanning moderate and severe influenza seasons). EXPOSURES: Covid-19 infection confirmed by evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the nasopharynx by polymerase chain reaction, and laboratory-confirmed influenza A or B. MAIN OUTCOMES AND MEASURES: A panel of neurologists adjudicated the primary outcome of acute ischemic stroke and its clinical characteristics, etiological mechanisms, and outcomes. We used logistic regression to compare the proportion of Covid-19 patients with ischemic stroke versus the proportion among patients with influenza. RESULTS: Among 2,132 patients with emergency department visits or hospitalizations with Covid-19, 31 patients (1.5%; 95% confidence interval [CI], 1.0%-2.1%) had an acute ischemic stroke. The median age of patients with stroke was 69 years (interquartile range, 66-78) and 58% were men. Stroke was the reason for hospital presentation in 8 (26%) cases. For our comparison cohort, we identified 1,516 patients with influenza, of whom 0.2% (95% CI, 0.0-0.6%) had an acute ischemic stroke. After adjustment for age, sex, and race, the likelihood of stroke was significantly higher with Covid-19 than with influenza infection (odds ratio, 7.5; 95% CI, 2.3-24.9). CONCLUSIONS AND RELEVANCE: Approximately 1.5% of patients with emergency department visits or hospitalizations with Covid-19 experienced ischemic stroke, a rate 7.5-fold higher than in patients with influenza. Future studies should investigate the thrombotic mechanisms in Covid-19 in order to determine optimal strategies to prevent disabling complications like ischemic stroke.