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February 22, 2022; 98 (8) Editorial

Risk of Acute Ischemic Stroke in Patients 65 and Older Is Early After COVID-19 Diagnosis

Alexis N. Simpkins, Alain Lekoubou
First published February 3, 2022, DOI: https://doi.org/10.1212/WNL.0000000000013182
Alexis N. Simpkins
From the Department of Neurology (A.N.S.), University of Florida, Gainesville; and Departments of Neurology and Public Health Sciences (A.L.), Penn State University, Hershey Medical Center, PA.
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Alain Lekoubou
From the Department of Neurology (A.N.S.), University of Florida, Gainesville; and Departments of Neurology and Public Health Sciences (A.L.), Penn State University, Hershey Medical Center, PA.
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Risk of Acute Ischemic Stroke in Patients 65 and Older Is Early After COVID-19 Diagnosis
Alexis N. Simpkins, Alain Lekoubou
Neurology Feb 2022, 98 (8) 301-302; DOI: 10.1212/WNL.0000000000013182

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Associated acute and long-term medical complications of COVID-19 beyond respiratory illness include acute ischemic stroke (AIS).1,-,5 Hypercoagulability, inflammation, cardiac dysfunction, and endothelial inflammation that occur during the infectious phase can lead to thrombotic events and thus cerebral ischemia.6 Reported risks of stroke in COVID-19 have varied substantially across studies.7 Most studies have focused on AIS incidence in patients diagnosed during or upon hospitalization. Unlike any other infectious disease in modern times and as a result of the need to trace and monitor for outbreaks to prevent the spread of COVID-19, a very large number of patients have been screened for COVID-19 at the time of hospital admission. This screening has identified both asymptomatic and symptomatic individuals with COVID-19, thus making it more difficult to determine whether and in whom COVID-19 may increase the risk of AIS and whether the association is true or incidental. In this issue of Neurology®, Yang et al.8 evaluated the estimated incidence rate ratio of AIS after COVID-19 infection in a known high-risk group—patients older than 65—and determined the time frame of highest risk of AIS associated with COVID-19 within this population.8

The authors used inpatient and outpatient fee-for-service Medicare claims to identify 37,379 patients with COVID-19 and AIS between January 2019 and February 2021.8 A pre-COVID diagnosis phase was used to account for unknown possible inoculation times and the time frame from COVID-19 billing diagnosis to stroke billing diagnosis code of up to 28 days was evaluated.8 Applying the self-controlled case series method, the authors found that the incidence rate ratios (IRRs) were highest within 3 days of diagnosis of COVID-19, with an odds ratio of 10.3 (95% confidence interval 9.86–10.8), and that the estimated IRR was higher in those between ages 65 and 74 without a prior history of stroke.8 By contrast, the association between stroke and COVID-19 was weaker 15–28 days after the initial diagnosis, suggesting that AIS rarely manifests as a long-term COVID-19 sequela in elderly patients.8 Major strengths of the study are the inclusion of COVID-19 cases diagnosed both in outpatient and inpatient settings, the inclusion of a large number of patients from minority groups, and the use of robust statistical methods, such as the self-case-controlled case study, which has the advantage of implicit control for all fixed confounding effects. The authors made a great effort to verify that all assumptions were not violated, albeit with some modifications. They solidified the findings of their study by performing a number of sensitivity analyses.

Interpretation of the study results should consider potential limitations, which were described by Yang et al.8 These limitations stem primarily from the retrospective nature of the analysis and the use of administrative claims to identify cases of COVID-19 and AIS. As the Medicare data are updated monthly, cases of COVID-19 and deaths could have been missed. Also, rapid changes in the entire health care system during the COVID-19 pandemic, including access to preventative care, patient presentation to health care facilities for evaluation of stroke-like symptoms, availability of testing and procedures, and acute stroke care, could have affected the results and the applicability of the self-controlled case study.9

The study has important clinical implications. The authors identified both a group of patients (65–74 years without a prior history of stroke) and a critical period (first 3 days) for which the risk of AIS after COVID-19 diagnosis is highest. These raise important questions: Should patients aged 65–74 years be treated more preemptively and aggressively to prevent ischemic stroke? What would be the ideal duration of such specific interventions? Well-designed clinical trials are needed to answer these questions.

Study Funding

The authors report no targeted funding.

Disclosure

The authors report no disclosures. Go to Neurology.org/N for full disclosures.

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the editorial.

  • See page 305

  • © 2022 American Academy of Neurology

References

  1. 1.↵
    1. Groff D,
    2. Sun A,
    3. Ssentongo AE, et al
    . Short-term and long-term rates of postacute sequelae of SARS-CoV-2 infection: a systematic review. JAMA Netw Open. 2021;4(10):e2128568.
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    1. Katsanos AH,
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    . The impact of SARS-CoV-2 on stroke epidemiology and care: a meta-analysis. Ann Neurol. 2021;89(2):380-388.
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    1. Merkler AE,
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    . Risk of ischemic stroke in patients with coronavirus disease 2019 (COVID-19) vs patients with influenza. JAMA Neurol. 2020;77(11):1-7.
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    1. Modin D,
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    . Acute COVID-19 and the incidence of ischemic stroke and acute myocardial infarction. Circulation. 2020;142(21):2080-2082.
    OpenUrlPubMed
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    1. Katsoularis I,
    2. Fonseca-Rodríguez O,
    3. Farrington P,
    4. Lindmark K,
    5. Fors Connolly AM
    . Risk of acute myocardial infarction and ischaemic stroke following COVID-19 in Sweden: a self-controlled case series and matched cohort study. Lancet. 2021;398(10300):599-607.
    OpenUrlCrossRefPubMed
  6. 6.↵
    1. Elfasi A,
    2. Echevarria FD,
    3. Rodriguez R, et al
    . Impact of COVID-19 on future ischemic stroke incidence. eNeurologicalSci. 2021;22:100325.
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  7. 7.↵
    1. Nannoni S,
    2. de Groot R,
    3. Bell S,
    4. Markus HS
    . Stroke in COVID-19: a systematic review and meta-analysis. Int J Stroke. 2021;16(2):137-149.
    OpenUrlCrossRefPubMed
  8. 8.↵
    1. Yang Q,
    2. Tong X,
    3. George MG,
    4. Chang A,
    5. Merritt RK
    . COVID-19 and risk of acute ischemic stroke among Medicare beneficiaries aged 65 years or older: self-controlled case series study. Neurology. 2022;98(8):e778-e789.
    OpenUrlAbstract/FREE Full Text
  9. 9.↵
    1. Leira EC,
    2. Russman AN,
    3. Biller J, et al
    . Preserving stroke care during the COVID-19 pandemic: potential issues and solutions. Neurology. 2020;95(3):124-133.
    OpenUrlAbstract/FREE Full Text

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