Risk of Ischemic Stroke in Patients With Coronavirus Disease 2019 (COVID-19) vs Patients With Influenza | Cerebrovascular Disease | JN Learning | AMA Ed Hub [Skip to Content]
[Skip to Content Landing]

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.

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.

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 CME Credit™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

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.

References
1.
World Health Organization. Coronavirus (COVID-2019) situation reports. Accessed June 15, 2020. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports/
2.
Zhang  Y , Xiao  M , Zhang  S ,  et al.  Coagulopathy and antiphospholipid antibodies in patients with COVID-19.   N Engl J Med. 2020;382(17):e38. doi:10.1056/NEJMc2007575PubMedGoogle Scholar
3.
Klok  FA , Kruip  MJHA , van der Meer  NJM ,  et al.  Incidence of thrombotic complications in critically ill ICU patients with COVID-19.   Thromb Res. 2020;191(191):145-147. doi:10.1016/j.thromres.2020.04.013PubMedGoogle ScholarCrossref
4.
Helms  J , Tacquard  C , Severac  F ,  et al; Clinical Research in Intensive Care and Sepsis Trial Group for Global Evaluation and Research in Sepsis.  High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study.   Intensive Care Med. 2020;46(6):1089-1098. doi:10.1007/s00134-020-06062-xPubMedGoogle ScholarCrossref
5.
Oxley  TJ , Mocco  J , Majidi  S ,  et al.  Large-vessel stroke as a presenting feature of COVID-19 in the young.   N Engl J Med. 2020;382(20):e60. doi:10.1056/NEJMc2009787PubMedGoogle Scholar
6.
Helms  J , Kremer  S , Merdji  H ,  et al.  Neurologic features in severe SARS-CoV-2 infection.   N Engl J Med. 2020;382(23):2268-2270. doi:10.1056/NEJMc2008597PubMedGoogle ScholarCrossref
7.
Mao  L , Jin  H , Wang  M ,  et al.  Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China.   JAMA Neurol. 2020;77:683-690. doi:10.1001/jamaneurol.2020.1127PubMedGoogle ScholarCrossref
8.
Yaghi  S , Ishida  K , Torres  J ,  et al.  SARS2-CoV-2 and stroke in a New York healthcare system.   Stroke. 2020;A120030335. doi:10.1161/STROKEAHA.120.030335PubMedGoogle Scholar
9.
Boehme  AK , Luna  J , Kulick  ER , Kamel  H , Elkind  MSV .  Influenza-like illness as a trigger for ischemic stroke.   Ann Clin Transl Neurol. 2018;5(4):456-463. doi:10.1002/acn3.545PubMedGoogle ScholarCrossref
10.
Elkind  MS , Carty  CL , O’Meara  ES ,  et al.  Hospitalization for infection and risk of acute ischemic stroke: the Cardiovascular Health Study.   Stroke. 2011;42(7):1851-1856. doi:10.1161/STROKEAHA.110.608588PubMedGoogle ScholarCrossref
11.
Centers for Disease Control and Prevention. How CDC classifies flu severity. Accessed May 1, 2020. https://www.cdc.gov/flu/about/classifies-flu-severity.htm
12.
Sholle  ET , Kabariti  J , Johnson  SB ,  et al.  Secondary Use of Patients’ Electronic Records (SUPER): an approach for meeting specific data needs of clinical and translational researchers.   AMIA Annu Symp Proc. 2018;2017:1581-1588.PubMedGoogle Scholar
13.
Sacco  RL , Kasner  SE , Broderick  JP ,  et al; American Heart Association Stroke Council, Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular and Stroke Nursing; Council on Epidemiology and Prevention; Council on Peripheral Vascular Disease; Council on Nutrition, Physical Activity and Metabolism.  An updated definition of stroke for the 21st century: a statement for healthcare professionals from the American Heart Association/American Stroke Association.   Stroke. 2013;44(7):2064-2089. doi:10.1161/STR.0b013e318296aecaPubMedGoogle ScholarCrossref
14.
Adams  HP  Jr , Bendixen  BH , Kappelle  LJ ,  et al.  Classification of subtype of acute ischemic stroke: definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment.   Stroke. 1993;24(1):35-41. doi:10.1161/01.STR.24.1.35PubMedGoogle ScholarCrossref
15.
Hart  RG , Diener  HC , Coutts  SB ,  et al; Cryptogenic Stroke/ESUS International Working Group.  Embolic strokes of undetermined source: the case for a new clinical construct.   Lancet Neurol. 2014;13(4):429-438. doi:10.1016/S1474-4422(13)70310-7PubMedGoogle ScholarCrossref
16.
Kamel  H , Navi  BB , Merkler  AE ,  et al.  Reclassification of ischemic stroke etiological subtypes on the basis of high-risk nonstenosing carotid plaque.   Stroke. 2020;51(2):504-510. doi:10.1161/STROKEAHA.119.027970PubMedGoogle ScholarCrossref
17.
Garg  S , Kim  L , Whitaker  M ,  et al.  Hospitalization rates and characteristics of patients hospitalized with laboratory-confirmed coronavirus disease 2019—COVID-NET, 14 states, March 1-30, 2020.   MMWR Morb Mortal Wkly Rep. 2020;69(15):458-464. doi:10.15585/mmwr.mm6915e3PubMedGoogle ScholarCrossref
18.
Kwong  JC , Schwartz  KL , Campitelli  MA .  Acute myocardial infarction after laboratory-confirmed influenza infection.   N Engl J Med. 2018;378(26):2540-2541. doi:10.1056/NEJMoa1702090PubMedGoogle Scholar
19.
Boehme  AK , Esenwa  C , Elkind  MS .  Stroke risk factors, genetics, and prevention.   Circ Res. 2017;120(3):472-495. doi:10.1161/CIRCRESAHA.116.308398PubMedGoogle ScholarCrossref
20.
Lindsberg  PJ , Grau  AJ .  Inflammation and infections as risk factors for ischemic stroke.   Stroke. 2003;34(10):2518-2532. doi:10.1161/01.STR.0000089015.51603.CCPubMedGoogle ScholarCrossref
21.
Spiezia  L , Boscolo  A , Poletto  F ,  et al.  COVID-19-related severe hypercoagulability in patients admitted to intensive care unit for acute respiratory failure.   Thromb Haemost. 2020;120(6):998-1000. doi:10.1055/s-0040-1710018PubMedGoogle ScholarCrossref
22.
Panigada  M , Bottino  N , Tagliabue  P ,  et al.  Hypercoagulability of COVID-19 patients in intensive care unit: a report of thromboelastography findings and other parameters of hemostasis.   J Thromb Haemost. 2020. doi:10.1111/jth.14850PubMedGoogle Scholar
23.
Goyal  P , Choi  JJ , Pinheiro  LC ,  et al.  Clinical characteristics of COVID-19 in New York City.   N Engl J Med. 2020;382(24):2372-2374. doi:10.1056/NEJMc2010419PubMedGoogle ScholarCrossref
24.
Shi  S , Qin  M , Shen  B ,  et al.  Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China.   JAMA Cardiol. 2020;e200950. doi:10.1001/jamacardio.2020.0950PubMedGoogle Scholar
25.
Guo  T , Fan  Y , Chen  M ,  et al.  Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19).   JAMA Cardiol. 2020;3201017. doi:10.1001/jamacardio.2020.1017PubMedGoogle Scholar
26.
Zhang  L , Feng  X , Zhang  D ,  et al.  Deep vein thrombosis in hospitalized patients with coronavirus disease 2019 (COVID-19) in Wuhan, China: prevalence, risk factors, and outcome.   Circulation. 2020. doi:10.1161/CIRCULATIONAHA.120.046702PubMedGoogle Scholar
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_LoginSubscribe_Purchase
Close
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_LoginSubscribe_Purchase
Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close

Name Your Search

Save Search
Close
With a personal account, you can:
  • Track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
jn-learning_Modal_SaveSearch_NoAccess_Purchase
Close

Lookup An Activity

or

Close

My Saved Searches

You currently have no searches saved.

Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close