Clinical characteristics and outcomes of acute ischemic stroke in patients with COVID-19: A systematic review and meta-analysis of global data

¹ Department of Neurology of Drum Tower Hospital, Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210008, China

² Department of Neurology, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China

³ Nanjing Neurology Clinic Medical Center, Nanjing 210008, China

⁴ Institute of Brain Science, Nanjing University, Nanjing 210008, China

⁵ Medical Statistics and Analysis Center, Nanjing Drum Tower Hospital, Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, China

⁶ St George’s University Hospital NHS Foundation Trust, London, Blackshaw Rd, London SW17 0QT, United Kingdom

Advanced Neurology 2022, 1(1), 28 https://doi.org/10.36922/an.v1i1.28

Submitted: 8 December 2021 | Accepted: 2 March 2022 | Published: 24 March 2022

© 2022 by the Authors. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )

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Abstract

Objective. There is increased concern regarding acute ischemic stroke (AIS) in patients with coronavirus disease 2019 (COVID-19). The aim of this study was to depict the manifestations and outcomes of COVID-19-associated AIS.

Methods. We systematically searched for eligible studies describing AIS in patients with COVID-19 using PubMed, Embase, and Web of Science up to November 29, 2021. We complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and used the Newcastle–Ottawa Scale to assess data quality. The data were pooled using fixed- and random-effects models.

Results. Thirty-eight eligible studies involving 76,894 participants were included in this meta-analysis. Compared with AIS patients who did not have COVID-19, patients with COVID-19 were more likely to have anterior circulation stroke (odds ratio [OR]: 2.29, 95% confidence interval [CI]: 1.03 – 5.10; I2: 37%), particularly involving the internal carotid artery (OR: 1.85, 95% CI: 1.19 – 2.88; I2: 0); more severe neurological deficit (National Institutes of Health Stroke Scale [NIHSS]) (weighted mean difference [WMD]: 3.21, 95% CI: 2.13 – 4.29; I2: 64%); higher proportion of cryptogenic stroke (OR: 1.83, 95% CI: 1.24 – 2.70; I2: 62%), large vessel occlusion (OR: 1.68, 95% CI: 1.10 – 2.57; I2: 75%), and multi-territory involvement (OR: 2.64, 95% CI: 1.62 – 4.29; I2: 0%); higher C-reactive protein levels (WMD: 55.90, 95% CI: 33.32 – 78.49; I2: 67%), and D-dimer levels (standardized mean difference: 0.81, 95% CI: 0.52 – 1.10; I2: 59%). The proportion of poor outcomes were higher among patients with COVID-19, including increased risk of in-hospital death (OR: 3.70, 95% CI: 2.73 – 5.02; I2: 64%) and lower possibility of favorable discharge (OR: 0.49, 95% CI: 0.39 – 0.61; I2: 0). However, COVID-19 did not increase the risk of hemorrhagic transformation (OR: 1.34, 95% CI: 0.91 – 1.98; I2: 39%) and symptomatic intracerebral hemorrhage (OR: 1.46, 95% CI: 0.81 – 2.62; I2: 0).

Conclusion. AIS patients with COVID-19 seem to display a pattern of large vessel occlusion and multi-territory infarcts. These patients have high inflammatory marker levels and increased D-dimer levels, which implies that thrombosis and/or thromboembolism might be the underlying mechanism. These patients tend to have worse prognosis regardless of whether they receive reperfusion treatment.

Keywords

Acute ischemic stroke

COVID-19

Clinical characteristics and outcomes

Funding

National Natural Science Foundation of China

References

[1]

World Health Organization. WHO Coronavirus (COVID-19) Dashboard WHO Coronavirus (COVID-19) Dashboard with Vaccination Data. Geneva: World Health Organization; 2021.

[2]

Benussi A, Pilotto A, Premi E, et al., 2002, Clinical characteristics and outcomes of inpatients with neurologic disease and COVID-19 in Brescia, Lombardy, Italy. Neurology, 95(7): e910–e920. https://doi.org/10.1212/WNL.0000000000009848

[3]

Lodigiani C, Iapichino G, Carenzo L, et al., 2020, Venous and arterial thromboembolic complications in COVID-19 paients admitted to an academic hospital in Milan, Italy. Thromb Res, 191: 9–14. https://doi.org/10.1016/j.thromres.2020.04.024

[4]

Li Y, Li M, Wang M, et al., 2020, Acute cerebrovascular disease following COVID-19: A single center, retrospective, observational study. Stroke Vasc Neurol, 5(3): 279–284. https://doi.org/10.1136/svn-2020-000431

[5]

Ntaios, G., Michel P, Georgiopoulos G, et al., 2020, Characteristics and outcomes in patients with COVID-19 and acute ischemic stroke: The global COVID-19 stroke registry. Stroke, 51(9): e254–e258. https://doi.org/10.1161/STROKEAHA.120.031208

[6]

Sasanejad, P., Afshar Hezarkhani L, Arsang-Jang S, et al., 2021, Safety and outcomes of intravenous thrombolytic therapy in ischemic stroke patients with COVID-19: CASCADE initiative. J Stroke Cerebrovasc Dis, 30(12): 106121. https://doi.org/10.1016/j.jstrokecerebrovasdis.2021.106121

[7]

Siow, I., Lee KS, Zhang JJ, et al., 2021, Stroke as a neurological complication of COVID-19: A systematic review and meta-analysis of incidence, outcomes and predictors. J Stroke Cerebrovasc Dis, 30(3): 105549. https://doi.org/10.1016/j.jstrokecerebrovasdis.2020.105549

[8]

Nannoni S, de Groot R, Bell S, et al., 2021, Stroke in COVID-19: A systematic review and meta-analysis. Int J Stroke, 16(2): 137–149.

[9]

Panic N, Leoncini E, de Belvis G, et al., 2013, Evaluation of the endorsement of the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement on the quality of published systematic review and meta-analyses. PLoS One, 8(12): e83138.

[10]

Emergency Use ICD Codes for COVID-19 Disease Outbreak; 2021.

[11]

Adams HJ Jr., Bendixen BH, Kappelle LJ, et al., 1993, 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, 24(1): 35-41. https://doi.org/10.1161/01.str.24.1.35

[12]

Luchini C, Stubbs B, Solmi M, et al., 2017. Assessing the quality of studies in meta-analyses: Advantages and limitations of the Newcastle Ottawa Scale. World J Meta- Anal, 5(4):80–84. https://doi.org/10.13105/wjma.v5.i4.80.

[13]

Friedrich JO, Adhikari NK, Beyene J, 2007, Inclusion of zero total event trials in meta-analyses maintains analytic consistency and incorporates all available data. BMC Med Res Methodol, 7: 5. https://doi.org/10.1186/1471-2288-7-5

[14]

Hozo SP, Djulbegovic B, Hozo I, 2005, Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol, 5: 13.

[15]

Higgins JP, Thompson SG, 2002, Quantifying heterogeneity in a meta-analysis. Stat Med, 21(11): 1539–1558. https://doi.org/10.1002/sim.1186

[16]

Sobolewski P, Antecki J, Brola W, et al., 2022, Systemic thrombolysis in ischaemic stroke patients with COVID-19. Acta Neurol Scand, 145(1): 47–52. https://doi.org/10.1111/ane.13520

[17]

de Havenon A, Yaghi S, Mistry EA, et al., 2020, Endovascular thrombectomy in acute ischemic stroke patients with COVID-19: Prevalence, demographics, and outcomes. J Neurointerv Surg, 12(11): 1045–1048.

[18]

Al Kasab S, Almallouhi E, Alawieh A, et al., 2020, International experience of mechanical thrombectomy during the COVID-19 pandemic: Insights from STAR and ENRG. J Neurointerv Surg, 12(11): 1039–1044. http://dx.doi. org/10.1136/neurintsurg-2020-016671

[19]

Escalard S, Chalumeau V, Escalard C, et al., 2020, Early brain imaging shows increased severity of acute ischemic strokes with large vessel occlusion in COVID-19 patients. Stroke, 51(11): 3366–3370.

[20]

Pezzini A, Grassi M, Silvestrelli G, et al., 2021, Impact of SARS-CoV-2 on reperfusion therapies for acute ischemic stroke in Lombardy, Italy: The STROKOVID network. J Neurol, 268(10): 3561–3568. https://doi.org/10.1007/s00415-021-10497-7

[21]

Qureshi AI, Baskett WI, Huang W, et al., 2021, Utilization and outcomes of acute revascularization treatment in ischemic stroke patients with SARS-CoV-2 infection. J Stroke Cerebrovasc Dis, 31(1): 106157. https://doi.org/10.1016/j.jstrokecerebrovasdis.2021.106157

[22]

Requena M, Olivé-Gadea M, Muchada M, et al., 2020, COVID-19 and stroke: Incidence and etiological description in a high-volume center. J Stroke Cerebrovasc Dis, 29(11): 105225. https://doi.org/10.1016/j.jstrokecerebrovasdis.2020.105225

[23]

Akhtar N, Ben Abid F, Kamran S, et al., 2021, Characteristics and comparison of 32 COVID-19 and Non-COVID-19 Ischemic strokes and historical stroke patients. J Stroke Cerebrovasc Dis, 30(1): 105435. https://doi.org/10.1016/j.jstrokecerebrovasdis.2020.105435

[24]

Altschul DJ, Esenwa C, Haranhalli N, et al., 2020, Predictors of mortality for patients with COVID-19 and large vessel occlusion. Interv Neuroradiol, 26(5): 623-628.

[25]

Benny R, Singh RK, Venkitachalam A, et al., 2021, Characteristics and outcomes of 100 consecutive patients with acute stroke and COVID-19. J Neurol Sci, 423: 117348. https://doi.org/10.1016/j.jns.2021.117348

[26]

Calmettes J, Peres R, Goncalves B, et al., 2021, Clinical outcome of acute ischemic strokes in patients with COVID- 19. Cerebrovasc Dis, 50(4): 412-419.

[27]

Escalard S, Maïer B, Redjem H, et al., 2020, Treatment of acute ischemic stroke due to large vessel occlusion with COVID-19: Experience from Paris. Stroke, 51(8): 2540–2543. https://doi.org/10.1161/STROKEAHA.120.030574

[28]

Hernandez-Fernandez F, Valencia HS, Barbella-Aponte RA, et al., 2020, Cerebrovascular disease in patients with COVID- 19: neuroimaging, histological and clinical description. Brain, 143(10): 3089–3103. https://doi.org/10.1093/brain/awaa239

[29]

John S, Hussain SI, Piechowski-Jozwiak B, et al., 2020, Clinical characteristics and admission patterns of stroke patients during the COVID 19 pandemic: A single center retrospective, observational study from the Abu Dhabi, United Arab Emirates. Clin Neurol Neurosurg, 199: 106227. https://doi.org/10.1016/j.clineuro.2020.106227

[30]

Yaghi S, Ishida K, Torres J, et al., 2020, SARS-CoV-2 and stroke in a New York healthcare system. Stroke, 51(7): 2002–2011. https://doi.org/10.1161/STROKEAHA.120.030335

[31]

Srivastava PK, Zhang S, Xian Y, et al., 2021, Acute ischemic stroke in patients with COVID-19: An analysis from get with the guidelines-stroke. Stroke, 52(5): 1826–1829. https://doi.org/10.1161/STROKEAHA.121.034301

[32]

Dhamoon MS, Thaler A, Gururangan K, et al., 2021, Acute cerebrovascular events with COVID-19 Infection. Stroke, 52(1): 48–56. https://doi.org/10.1161/STROKEAHA.120.031668

[33]

Mathew T, John SK, Sarma G, et al., 2021, COVID-19- related strokes are associated with increased mortality and morbidity: A multicenter comparative study from Bengaluru, South India. Int J Stroke, 16(4): 429–436. https://doi.org/10.1177/1747493020968236

[34]

Ramos AD, Koyfman F, Byrns K, et al., 2021, Characterization of hemorrhagic and ischemic stroke in a diverse cohort of COVID-19 patients. Neurohospitalist, 11(4): 295–302. https://doi.org/10.1177/1941874421990545

[35]

Marti-Fabregas J, Guisado-Alonso D, Delgado-Mederos R, et al., 2021, Impact of COVID-19 infection on the outcome of patients with ischemic stroke. Stroke, 52(12): 3908–3917. https://doi.org/10.1161/STROKEAHA.121.034883

[36]

Sluis WM, Linschoten M, Buijs JE, et al., 2021, Risk, clinical course, and outcome of ischemic stroke in patients hospitalized with COVID-19: A multicenter cohort study. Stroke, 52(12): 3978–3986. https://doi.org/10.1161/STROKEAHA.121.034787

[37]

Majidi S, Fifi JT, Ladner TR, et al., 2020, Emergent large vessel occlusion stroke during New York city’s COVID-19 outbreak: Clinical characteristics and paraclinical findings. Stroke, 51(9): 2656–2663. https://doi.org/10.1161/STROKEAHA.120.030397

[38]

Ramos-Araque ME, Siegler JE, Ribo M, et al., 2021, Stroke etiologies in patients with COVID-19: The SVIN COVID- 19 multinational registry. BMC Neurol, 2021. 21(1): 43. https://doi.org/10.1186/s12883-021-02075-1

[39]

Merkler AE, Parikh NS, Mir S, et al., 2020, Risk of ischemic stroke in patients with coronavirus disease 2019 (COVID- 19) vs patients with influenza. JAMA Neurol, 77(11): 1–7. https://doi.org/10.1001/jamaneurol.2020.2730

[40]

Rothstein A, Oldridge O, Schwennesen H, et al., 2020, Acute cerebrovascular events in hospitalized COVID-19 patients. Stroke, 51(9): e219–e222. https://doi.org/10.1161/STROKEAHA.120.030995

[41]

Kremer S, Lersy F, Anheim M, et al., 2020, Neurologic and neuroimaging findings in patients with COVID-19: A retrospective multicenter study. Neurology, 95(13): e1868–e1882.

[42]

Shahjouei S, Naderi S, Li J, et al., 2020, Risk of stroke in hospitalized SARS-CoV-2 infected patients: A multinational study. EBioMedicine, 59: 102939. https://doi.org/10.1016/j.ebiom.2020.102939

[43]

Peng TJ, Jasne AS, Simonov M, et al., 2021, Prior stroke and age predict acute ischemic stroke among hospitalized COVID-19 patients: A derivation and validation study. Front Neurol, 12: 741044. https://doi.org/10.3389/fneur.2021.741044

[44]

Qureshi AI, Baskett WI, Huang W, et al., 2021, Acute ischemic stroke and COVID-19: An analysis of 27 676 patients. Stroke, 52(3): 905–912. https://doi.org/10.1161/STROKEAHA.120.031786

[45]

Bach I, Surathi P, Montealegre N, et al., 2020, Stroke in COVID-19: A single-centre initial experience in a hotspot of the pandemic. Stroke Vasc Neurol, 5(4): 331-336. https://doi.org/10.1136/svn-2020-000525

[46]

Topcuoglu MA, Pektezel MY, Oge DD, et al., 2021, Stroke mechanism in COVID-19 infection: A prospective case-control study. J Stroke Cerebrovasc Dis, 30(8): 105919. https://doi.org/10.1016/j.jstrokecerebrovasdis.2021.105919

[47]

Perry RJ, Smith CJ, Roffe C, et al., 2021, Characteristics and outcomes of COVID-19 associated stroke: A UK multicentre case-control study. J Neurol Neurosurg Psychiatry, 92(3): 242–248. https://doi.org/10.1136/jnnp-2020-324927

[48]

Bekelis K, Missios S, Ahmad J, et al., 2020, Ischemic stroke occurs less frequently in patients with COVID- 19: A multicenter cross-sectional study. Stroke, 51(12): 3570–3576. https://doi.org/10.1161/STROKEAHA.120.031217

[49]

Naval-Baudin P, Caamaño IR, Rubio-Maicas C, et al., 2021, COVID-19 and ischemic stroke: Clinical and neuroimaging findings. J Neuroimaging, 31(1): 62–66. https://doi.org/10.1111/jon.12790

[50]

Lin C, Arevalo YA, Nanavati HD, et al., 2020, Racial differences and an increased systemic inflammatory response are seen in patients with COVID-19 and ischemic stroke. Brain Behav Immun Health, 8: 100137. https://doi.org/10.1016/j.bbih.2020.100137

[51]

Khandelwal P, Al-Mufti F, Tiwari A, et al., 2021, Incidence, characteristics and outcomes of large vessel stroke in COVID-19 cohort: An international multicenter study. Neurosurgery, 89(1): E35-E41. https://doi.org/10.1093/neuros/nyab111

[52]

Avula A, Nalleballe K, Narula N, et al., 2020, COVID-19 presenting as stroke. Brain Behav Immun, 87: 115–119. https://doi.org/10.1016/j.bbi.2020.04.077

[53]

Di Napoli M, Papa F, Bocola V, 2001, Prognostic influence of increased C-reactive protein and fibrinogen levels in ischemic stroke. Stroke, 32(1): 133–138. https://doi.org/10.1161/01.str.32.1.133

[54]

Mobarra N, Morovatdar N, Di Napoli M, et al., 2019, The association between inflammatory markers in the acute phase of stroke and long-term stroke outcomes: Evidence from a population-based study of stroke. Neuroepidemiology, 53(1-2): 20–26. https://doi.org/10.1159/000494685

[55]

Luan YY, Yin CH, Yao YM, 2021, Update advances on C-reactive protein in COVID-19 and other viral infections. Front Immunol, 12: 720363. https://doi.org/10.3389/fimmu.2021.720363

[56]

Snell J, 2021, SARS-CoV-2 infection and its association with thrombosis and ischemic stroke: A review. Am J Emerg Med, 40: 188–192. https://doi.org/10.1016/j.ajem.2020.09.072

[57]

Patone M, Mei XW, Handunnetthi L, et al., 2022, Risks of myocarditis, pericarditis, and cardiac arrhythmias associated with COVID-19 vaccination or SARS-CoV-2 infection. Nat Med, 28(2): 410–422. https://doi.org/10.1038/s41591-021-01630-0

[58]

Zhang L, Yan X, Fan Q, et al., 2020, D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19. J Thromb Haemost, 18(6): 1324–1329. https://doi.org/10.1111/jth.14859

[59]

Lapergue B, Lyoubi A, Meseguer E, et al., 2020, Large vessel stroke in six patients following SARS-CoV-2 infection: A retrospective case study series of acute thrombotic complications on stable underlying atherosclerotic disease. Eur J Neurol, 27(11): 2308–2311. https://doi.org/10.1111/ene.14466

[60]

Wang A, Mandigo GK, Yim PD, et al., 2020, Stroke and mechanical thrombectomy in patients with COVID- 19: technical observations and patient characteristics. J Neurointerv Surg, 12(7): 648–653. https://doi.org/10.1136/neurintsurg-2020-016220

[61]

Li G, Han C, Xia X, et al., 2021, Relationship of uric acid, C-reactive protein, and N-terminal pro-B-type natriuretic peptide with acute cerebral infarction. Rev Assoc Med Bras, (1992), 67(11): 1639–1643. https://doi.org/10.1590/1806-9282.20210693

[62]

Zi WJ, Shuai J, 2014, Plasma D-dimer levels are associated with stroke subtypes and infarction volume in patients with acute ischemic stroke. PLoS One, 9(1): e86465. https://doi.org/10.1371/journal.pone.0086465

[63]

Bikdeli B, Madhavan MV, Jimenez D, et al., 2020, COVID- 19 and thrombotic or thromboembolic disease: Implications for prevention, antithrombotic therapy, and follow-up: JACC State-of-the-art review. J Am Coll Cardiol, 75(23): 2950–2973. https://doi.org/10.1016/j.jacc.2020.04.031

[64]

Mijajlovic MD, Pavlović A, Brainin M, et al., 2017, Post-stroke dementia a comprehensive review. BMC Med, 15(1): 11.

[65]

Parsay S, Vosoughi A, Khabbaz A, et al., 2021, The incidence and mortality ratio of ischemic cerebrovascular accidents in COVID-19 cases: A systematic review and meta-analysis. J Stroke Cerebrovasc Dis, 30(3): 105552. https://doi.org/10.1016/j.jstrokecerebrovasdis.2020.105552

[66]

Strambo D, De Marchis GM, Bonati LH, et al., 2021, Ischemic stroke in COVID-19 patients: Mechanisms, treatment and outcomes in a consecutive Swiss Stroke Registry analysis. Eur J Neurol, 29(3): 732–743. https://doi.org/10.1111/ene.15199

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The authors declare that they have no conflicts of interest.

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