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Risk of Ischemic Stroke in Patients With Coronavirus Disease 2019 (COVID-19) vs Patients With Influenza

Educational Objective
To understand the risk of ischemic stroke in patients with COVID-19 vs patients with influenza
1 Credit CME
Key Points

Question  How does the risk of acute ischemic stroke compare between patients with coronavirus disease 2019 (COVID-19) and patients with influenza, a respiratory virus previously associated with stroke?

Findings  In this cohort study, 1916 patients with emergency department visits or hospitalizations with COVID-19 had an elevated risk of ischemic stroke compared with 1486 patients with emergency department visits or hospitalizations with influenza.

Meaning  Patients with COVID-19 appear to have a heightened risk of acute ischemic stroke compared with patients with influenza.


Importance  It is uncertain whether coronavirus disease 2019 (COVID-19) is associated with a higher risk of ischemic stroke than would be expected from a viral respiratory infection.

Objective  To compare the rate of ischemic stroke between patients with COVID-19 and patients with influenza, a respiratory viral illness previously associated with stroke.

Design, Setting, and Participants  This retrospective cohort study was conducted at 2 academic hospitals in New York City, New York, and included adult patients with emergency department visits or hospitalizations with COVID-19 from March 4, 2020, through May 2, 2020. The comparison cohort included adults with emergency department visits or hospitalizations with influenza A/B from January 1, 2016, through May 31, 2018 (spanning moderate and severe influenza seasons).

Exposures  COVID-19 infection confirmed by evidence of severe acute respiratory syndrome coronavirus 2 in the nasopharynx by polymerase chain reaction and laboratory-confirmed influenza A/B.

Main Outcomes and Measures  A panel of neurologists adjudicated the primary outcome of acute ischemic stroke and its clinical characteristics, mechanisms, and outcomes. We used logistic regression to compare the proportion of patients with COVID-19 with ischemic stroke vs the proportion among patients with influenza.

Results  Among 1916 patients with emergency department visits or hospitalizations with COVID-19, 31 (1.6%; 95% CI, 1.1%-2.3%) had an acute ischemic stroke. The median age of patients with stroke was 69 years (interquartile range, 66-78 years); 18 (58%) were men. Stroke was the reason for hospital presentation in 8 cases (26%). In comparison, 3 of 1486 patients with influenza (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 higher with COVID-19 infection than with influenza infection (odds ratio, 7.6; 95% CI, 2.3-25.2). The association persisted across sensitivity analyses adjusting for vascular risk factors, viral symptomatology, and intensive care unit admission.

Conclusions and Relevance  In this retrospective cohort study from 2 New York City academic hospitals, approximately 1.6% of adults with COVID-19 who visited the emergency department or were hospitalized experienced ischemic stroke, a higher rate of stroke compared with a cohort of patients with influenza. Additional studies are needed to confirm these findings and to investigate possible thrombotic mechanisms associated with COVID-19.

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Article Information

Accepted for Publication: June 18, 2020.

Corresponding Author: Babak B. Navi, MD, MS, Department of Neurology, Weill Cornell Medicine, 420 E 70th St, Room 411, New York, NY 10021 (ban9003@med.cornell.edu).

Published Online: July 2, 2020. doi:10.1001/jamaneurol.2020.2730

Author Contributions: Dr Navi had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Merkler and Parikh are co–first authors.

Concept and design: Merkler, Parikh, Mir, Gupta, Kamel, Murthy, Stieg, Fink, Iadecola, Navi.

Acquisition, analysis, or interpretation of data: Merkler, Parikh, Mir, Gupta, Kamel, Lin, Lantos, Schenck, Goyal, Bruce, Kahan, Lansdale, LeMoss, Fink, Segal, Campion, Diaz, Zhang, Navi.

Drafting of the manuscript: Merkler, Parikh, Mir, Lantos, Lansdale, Stieg, Iadecola, Campion, Navi.

Critical revision of the manuscript for important intellectual content: Merkler, Parikh, Mir, Gupta, Kamel, Lin, Lantos, Schenck, Goyal, Bruce, Kahan, LeMoss, Murthy, Fink, Iadecola, Segal, Diaz, Zhang, Navi.

Statistical analysis: Stieg, Diaz, Zhang.

Obtained funding: Gupta, Fink, Iadecola, Navi.

Administrative, technical, or material support: Gupta, Lin, Goyal, Lansdale, LeMoss, Fink, Iadecola, Campion, Navi.

Supervision: Gupta, Lantos, Fink, Iadecola, Segal, Navi.

Conflict of Interest Disclosures: Dr Merkler has received personal fees for medicolegal consulting on stroke. Dr Kamel serves as co–principal investigator for the National Institutes of Health (NIH)–funded ARCADIA trial, for which receives in-kind study drugs from the BMS-Pfizer Alliance and in-kind study assays from Roche Diagnostics, serves as a deputy editor for JAMA Neurology, serves as a steering committee member of Medtronic’s Stroke AF trial (uncompensated), serves on an end point adjudication committee for a trial of empagliflozin for Boehringer-Ingelheim, and has served on an advisory board for Roivant Sciences associated with Factor XI inhibition. Dr Fink serves as the editor-in-chief of Neurology Alert, Relias LLC. Dr Segal has received personal fees for medicolegal consulting on stroke. Dr Navi serves as a data and safety monitoring board member for the Patient-Centered Outcomes Research Institute–funded TRAVERSE trial and has received personal fees for medicolegal consulting on stroke. No other disclosures were reported.

Funding/Support: This study was supported by the NIH grants K23NS091395, R01HL144541, and UL1TR000457 as well as support from NewYork-Presbyterian Hospital and Weill Cornell Medical College, including their Clinical and Translational Science Center and Joint Clinical Trials Office.

Role of the Funder/Sponsor: The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: Dr Kamel is a deputy editor of JAMA Neurology, but he was not involved in any of the decisions regarding review of the manuscript or its acceptance.

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AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

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