Risk, Clinical Course, and Outcome of Ischemic Stroke in Patients Hospitalized With COVID-19: A Multicenter Cohort Study

  1. Wouter M. Sluis
  2. Marijke Linschoten
  3. Julie E. Buijs
  4. J. Matthijs Biesbroek
  5. Heleen M. den Hertog
  6. Tessa Ribbers
  7. Dennis J. Nieuwkamp
  8. Reinier C. van Houwelingen
  9. Andreas Dias
  10. Ingeborg W.M. van Uden
  11. Joost P. Kerklaan
  12. H. Paul Bienfait
  13. Sarah E. Vermeer
  14. Sonja W. de Jong
  15. Mariam Ali
  16. Marieke J.H. Wermer
  17. Marieke T. de Graaf
  18. Paul J.A.M. Brouwers
  19. Folkert W. Asselbergs
  20. L. Jaap Kappelle
  21. H. Bart van der Worp
  22. Annemijn M. Algra
  23. Richard C.J.M. Donders
  24. D. Martijn O. Pruissen
  25. Aaf F.M. Kuijper
  26. Clara E.E. van Ofwegen-Hanekamp
  27. Rik S. Hermanides
  28. Hortence E. Haerkens-Arends
  29. Rutger L. Anthonio
  30. Mireille E. Emans
  31. René A. Tio
  32. Jur M. ten Berg
  33. Björn E. Groenemeijer
  34. Ron Pisters
  35. P. Marc van der Zee
  36. Hans-Marc J. Siebelink
  37. Derk O. Verschure
  38. Matthijs F.L. Meijs
  39. Astrid Schut
  40. Robert G. Tieleman
  41. Wanda Hermans-van Ast
  42. Jeroen Schaap
  43. Lucia S. Jewbali
  44. Peter C. Smits
  45. Pim van der Harst
  46. Maarten van Smeden
  47. Wiek H. van Gilst

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Abstract

The frequency of ischemic stroke in patients with coronavirus disease 2019 (COVID-19) varies in the current literature, and risk factors are unknown. We assessed the incidence, risk factors, and outcomes of acute ischemic stroke in hospitalized patients with COVID-19.

Methods:

We included patients with a laboratory-confirmed SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) infection admitted in 16 Dutch hospitals participating in the international CAPACITY-COVID registry between March 1 and August 1, 2020. Patients were screened for the occurrence of acute ischemic stroke. We calculated the cumulative incidence of ischemic stroke and compared risk factors, cardiovascular complications, and in-hospital mortality in patients with and without ischemic stroke.

Results:

We included 2147 patients with COVID-19, of whom 586 (27.3%) needed treatment at an intensive care unit. Thirty-eight patients (1.8%) had an ischemic stroke. Patients with stroke were older but did not differ in sex or cardiovascular risk factors. Median time between the onset of COVID-19 symptoms and diagnosis of stroke was 2 weeks. The incidence of ischemic stroke was higher among patients who were treated at an intensive care unit (16/586; 2.7% versus nonintensive care unit, 22/1561; 1.4%; P =0.039). Pulmonary embolism was more common in patients with (8/38; 21.1%) than in those without stroke (160/2109; 7.6%; adjusted risk ratio, 2.08 [95% CI, 1.52–2.84]). Twenty-seven patients with ischemic stroke (71.1%) died during admission or were functionally dependent at discharge. Patients with ischemic stroke were at a higher risk of in-hospital mortality (adjusted risk ratio, 1.56 [95% CI, 1.13–2.15]) than patients without stroke.

Conclusions:

In this multicenter cohort study, the cumulative incidence of acute ischemic stroke in hospitalized patients with COVID-19 was ≈2%, with a higher risk in patients treated at an intensive care unit. The majority of stroke patients had a poor outcome. The association between ischemic stroke and pulmonary embolism warrants further investigation.

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  1. Version published to 10.1161/strokeaha.121.034787
  2. ScreenIT

    SciScore for 10.1101/2021.03.11.21253189: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementConsent: Ethical approval was obtained in all participating hospitals and the necessity of a consent procedure was determined conform local regulations.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableThe median age was 70.0 years (IQR: 59.0-77.0), about one-third of the patients was female (769; 35.8%) and cardiovascular risk factors and comorbidities were common.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Our study has some limitations. First, different forms of bias should be considered in observational research. Hospitalized patients with COVID-19, and in particular those requiring treatment at an ICU, represent a selected group. Numerous factors may have influenced whether patients sought emergency care, were admitted to a hospital and received intensive treatment. Some patients with COVID-19 and ischemic stroke may have died before reaching the hospital, but alternatively milder affected patients or those with treatment restrictions may have stayed at home.35 This may have underestimated the overall rate of ischemic stroke in patients hospitalized with COVID-19. The high caseload of COVID-19 patients in some hospitals, in combination with contagion containment and sedation on an ICU, may have impeded imaging investigations to diagnose ischemic strokes, especially among moribund patients. This may have resulted in an overestimation of the percentage of strokes with undetermined etiology in our study and others. Among patients with pulmonary embolism and ischemic stroke, the diagnostic work-up to rule out a patent foramen ovale was often not performed. In contrast, the relatively large proportion of patients with a cardioembolic atiology may reflect the accessibility of telemetry and ECG. Second, we were unable to adjust for changes in admission and treatment strategies that occurred during the first wave of the pandemic. This may have affected the rate of ischemic stroke an...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04325412RecruitingCardiac complicAtions in Patients With SARS Corona vIrus 2 (…
    NCT04325412RecruitingCardiac complicAtions in Patients With SARS Corona vIrus 2 (…

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  3. Version published to 10.1101/2021.03.11.21253189v1 on medRxiv