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. 2020 Jul 2;77(11):1-7.
doi: 10.1001/jamaneurol.2020.2730. Online ahead of print.

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

Alexander E Merkler  1 , Neal S Parikh  1 , Saad Mir  1 , Ajay Gupta  1   2 , Hooman Kamel  1   3 , Eaton Lin  2 , Joshua Lantos  2 , Edward J Schenck  4 , Parag Goyal  5 , Samuel S Bruce  1 , Joshua Kahan  1 , Kelsey N Lansdale  1 , Natalie M LeMoss  1 , Santosh B Murthy  1 , Philip E Stieg  6 , Matthew E Fink  1 , Costantino Iadecola  1 , Alan Z Segal  1 , Marika Cusick  7 , Thomas R Campion Jr  7 , Ivan Diaz  7 , Cenai Zhang  1 , Babak B Navi  1
Affiliations

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

Alexander E Merkler et al. JAMA Neurol. .

Abstract

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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Conflict of interest statement

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.

Figures

Figure.
Figure.. Timeline in Days From Coronavirus Disease 2019 (COVID-19) Symptom Onset to Acute Ischemic Stroke Diagnosis
Horizontal lines represent individual patients with a hospitalization or emergency department (ED) visit for COVID-19 infection who had acute ischemic stroke. A white square indicates the day of hospitalization, a gray diamond indicates the day of intensive care unit (ICU) admission, if applicable, and an orange circle indicates the day of acute ischemic stroke diagnosis. For patients who did not have preceding typical COVID-19 symptoms, the day of their stroke was considered the day of COVID-19 symptom onset. For patients with typical symptoms of COVID-19 but without a clear onset date, the date of hospital presentation was considered the day of onset.
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