Semin Neurol 2023; 43(02): 219-228
DOI: 10.1055/s-0043-1768475
Review Article

COVID-19 and Cerebrovascular Disease

Christina Catherine
1   Department of Neurology, UPMC Altoona Regional Hospital, Altoona, Pennsylvania
,
Julia Veitinger
2   Division of Neurocritical Care, The Ken and Ruth Davee Department of Neurology, Northwestern Feinberg School of Medicine, Chicago, Illinois
,
Sherry H-Y. Chou
2   Division of Neurocritical Care, The Ken and Ruth Davee Department of Neurology, Northwestern Feinberg School of Medicine, Chicago, Illinois
› Author Affiliations
Funding This study was supported by a grant from the National Institute of Health R21-NS113037.

Abstract

COVID-19 has been associated with numerous neurological complications, with acute cerebrovascular disease being one of the most devastating complications. Ischemic stroke is the most common cerebrovascular complication of COVID-19, affecting between 1 and 6% of all patients. Underlying mechanisms for COVID-related ischemic strokes are thought to be due to vasculopathy, endotheliopathy, direct invasion of the arterial wall, and platelet activation. Other COVID-19-associated cerebrovascular complications include hemorrhagic stroke, cerebral microbleeds, posterior reversible encephalopathy syndrome, reversible cerebral vasoconstriction syndrome, cerebral venous sinus thrombosis, and subarachnoid hemorrhage. This article discusses the incidence of these cerebrovascular complications, risk factors, management strategies, prognosis and future research directions, as well as considerations in pregnancy-related cerebrovascular events in the setting of COVID-19.



Publication History

Article published online:
22 May 2023

© 2023. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 
  • References

  • 1 Robinson CP, Busl KM. Neurologic manifestations of severe respiratory viral contagions. Crit Care Explor 2020; 2 (04) e0107
  • 2 Mao L, Jin H, Wang M. et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol 2020; 77 (06) 683-690
  • 3 Zakeri A, Jadhav AP, Sullenger BA, Nimjee SM. Ischemic stroke in COVID-19-positive patients: an overview of SARS-CoV-2 and thrombotic mechanisms for the neurointerventionalist. J Neurointerv Surg 2021; 13 (03) 202-206
  • 4 Li Y, Li M, Wang M. et al. Acute cerebrovascular disease following COVID-19: a single center, retrospective, observational study. Stroke Vasc Neurol 2020; 5 (03) 279-284
  • 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
  • 6 Xiong T-Y, Redwood S, Prendergast B, Chen M. Coronaviruses and the cardiovascular system: acute and long-term implications. Eur Heart J 2020; 41 (19) 1798-1800
  • 7 Vogrig A, Gigli GL, Bnà C, Morassi M. Stroke in patients with COVID-19: clinical and neuroimaging characteristics. Neurosci Lett 2021; 743: 135564
  • 8 Arandela K, Samudrala S, Abdalkader M. et al. Reversible cerebral vasoconstriction syndrome in patients with coronavirus disease: a multicenter case series. J Stroke Cerebrovasc Dis 2021; 30 (12) 106118
  • 9 Elkind MSV, Harrington RA, Benjamin IJ. The role of the American Heart Association in the global COVID-19 pandemic. Circulation 2020; 141 (15) e743-e745
  • 10 Kim YE, Huh K, Park YJ, Peck KR, Jung J. Association between vaccination and acute myocardial infarction and ischemic stroke after COVID-19 infection. JAMA 2022; 328 (09) 887-889
  • 11 Qureshi AI, Baskett WI, Huang W. et al. Acute ischemic stroke and COVID-19: an analysis of 27 676 patients. Stroke 2021; 52 (03) 905-912
  • 12 Srivastava PK, Zhang S, Xian Y. et al. Acute ischemic stroke in patients with COVID-19: an analysis from get with the guidelines-stroke. Stroke 2021; 52 (05) 1826-1829
  • 13 Siegler JE, Cardona P, Arenillas JF. et al. Cerebrovascular events and outcomes in hospitalized patients with COVID-19: The SVIN COVID-19 Multinational Registry. Int J Stroke 2021; 16 (04) 437-447
  • 14 Cervantes-Arslanian AM, Venkata C, Anand P. et al. Neurologic manifestations of severe acute respiratory syndrome coronavirus 2 infection in hospitalized patients during the first year of the COVID-19 pandemic. Crit Care Explor 2022; 4 (04) e0686
  • 15 Misra S, Kolappa K, Prasad M. et al. Frequency of neurologic manifestations in COVID-19: a systematic review and meta-analysis. Neurology 2021; 97 (23) e2269-e2281
  • 16 Chou SHY, Beghi E, Helbok R. et al; GCS-NeuroCOVID Consortium and ENERGY Consortium. Global incidence of neurological manifestations among patients hospitalized with COVID-19 - a report for the GCS-NeuroCOVID Consortium and the ENERGY Consortium. JAMA Netw Open 2021; 4 (05) e2112131
  • 17 Beghi E, Helbok R, Crean M. et al; EAN Neuro-COVID Task Force. The European Academy of Neurology COVID-19 registry (ENERGY): an international instrument for surveillance of neurological complications in patients with COVID-19. Eur J Neurol 2021; 28 (10) 3303-3323
  • 18 Merkler AE, Parikh NS, Mir S. et al. Risk of ischemic stroke in patients with coronavirus disease 2019 (COVID-19) vs patients with influenza. JAMA Neurol 2020; 77 (11) 1-7
  • 19 Simonetto M, Wechsler PM, Merkler AE. Stroke treatment in the era of COVID-19: a review. Curr Treat Options Neurol 2022; 24 (04) 155-171
  • 20 Katsoularis I, Fonseca-Rodríguez O, Farrington P, Lindmark K, 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
  • 21 Taquet M, Sillett R, Zhu L. et al. Neurological and psychiatric risk trajectories after SARS-CoV-2 infection: an analysis of 2-year retrospective cohort studies including 1 284 437 patients. Lancet Psychiatry 2022; 9 (10) 815-827
  • 22 Xie Y, Xu E, Bowe B, Al-Aly Z. Long-term cardiovascular outcomes of COVID-19. Nat Med 2022; 28 (03) 583-590
  • 23 Stefanou MI, Palaiodimou L, Aguiar de Sousa D. et al. Acute arterial ischemic stroke following COVID-19 vaccination: a systematic review and meta-analysis. Neurology 2022:10.1212/WNL.0000000000200996
  • 24 Dmytriw AA, Dibas M, Schirmer CM. et al; North American Neurovascular COVID-19 (NAN-C) Consortium. Age and acute ischemic stroke outcome in North American patients with COVID-19. J Am Heart Assoc 2021; 10 (14) e021046
  • 25 Seeliger B, Doebler M, Hofmaenner DA. et al. Intracranial hemorrhages on extracorporeal membrane oxygenation: differences between COVID-19 and other viral acute respiratory distress syndrome. Crit Care Med 2022; 50 (06) e526-e538
  • 26 Majidi S, Fifi JT, Ladner TR. et al. Emergent large vessel occlusion stroke during New York City's COVID-19 outbreak: clinical characteristics and paraclinical findings. Stroke 2020; 51 (09) 2656-2663
  • 27 Kihira S, Schefflein J, Mahmoudi K. et al. Association of coronavirus disease (COVID-19) with large vessel occlusion strokes: a case-control study. AJR Am J Roentgenol 2021; 216 (01) 150-156
  • 28 Rothstein A, Oldridge O, Schwennesen H, Do D, Cucchiara BL. Acute cerebrovascular events in hospitalized COVID-19 patients. Stroke 2020; 51 (09) e219-e222
  • 29 Jillella DV, Janocko NJ, Nahab F. et al. Ischemic stroke in COVID-19: an urgent need for early identification and management. PLoS One 2020; 15 (09) e0239443
  • 30 Dogra S, Jain R, Cao M. et al. Hemorrhagic stroke and anticoagulation in COVID-19. J Stroke Cerebrovasc Dis 2020; 29 (08) 104984
  • 31 Ramos-Araque ME, Siegler JE, Ribo M. et al; SVIN Multinational Registry and Task Force. Stroke etiologies in patients with COVID-19: the SVIN COVID-19 multinational registry. BMC Neurol 2021; 21 (01) 43
  • 32 Tan AT, Linster M, Tan CW. et al. Early induction of functional SARS-CoV-2-specific T cells associates with rapid viral clearance and mild disease in COVID-19 patients. Cell Rep 2021; 34 (06) 108728
  • 33 Nannoni S, de Groot R, Bell S, Markus HS. Stroke in COVID-19: a systematic review and meta-analysis. Int J Stroke 2021; 16 (02) 137-149
  • 34 Zureigat H, Alhusban M, Cobia M. Mechanical thrombectomy outcomes in COVID-19 patients with acute ischemic stroke: a narrative review. Neurologist 2021; 26 (06) 261-267
  • 35 John S, Kesav P, Mifsud VA. et al. Characteristics of large-vessel occlusion associated with COVID-19 and ischemic stroke. AJNR Am J Neuroradiol 2020; 41 (12) 2263-2268
  • 36 Dmytriw AA, Dibas M, Phan K. et al; North American Neurovascular COVID-19 (NAN-C) Consortium & Society of Vascular and Interventional Neurology (SVIN) Investigators. Acute ischaemic stroke associated with SARS-CoV-2 infection in North America. J Neurol Neurosurg Psychiatry 2022; 93 (04) 360-368
  • 37 Luo W, Liu X, Bao K, Huang C. Ischemic stroke associated with COVID-19: a systematic review and meta-analysis. J Neurol 2022; 269 (04) 1731-1740
  • 38 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
  • 39 Beyrouti R, Adams ME, Benjamin L. et al. Characteristics of ischaemic stroke associated with COVID-19. J Neurol Neurosurg Psychiatry 2020; 91 (08) 889-891
  • 40 Bowles L, Platton S, Yartey N. et al. Lupus anticoagulant and abnormal coagulation tests in patients with COVID-19. N Engl J Med 2020; 383 (03) 288-290
  • 41 Harzallah I, Debliquis A, Drénou B. Lupus anticoagulant is frequent in patients with COVID-19. J Thromb Haemost 2020; 18 (08) 2064-2065
  • 42 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
  • 43 Carneiro T, Dashkoff J, Leung LY. et al. Intravenous tPA for acute ischemic stroke in patients with COVID-19. J Stroke Cerebrovasc Dis 2020; 29 (11) 105201
  • 44 Powers WJ, Rabinstein AA, Ackerson T. et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2019; 50 (12) e344-e418
  • 45 Hsu PJ, Chen CH, Yeh SJ, Tsai LK, Tang SC, Jeng JS. High plasma D-dimer indicates unfavorable outcome of acute ischemic stroke patients receiving intravenous thrombolysis. Cerebrovasc Dis 2016; 42 (1-2): 117-121
  • 46 Strbian D, Piironen K, Meretoja A. et al; Helsinki Stroke Thrombolysis Registry Group. Intravenous thrombolysis for acute ischemic stroke patients presenting with mild symptoms. Int J Stroke 2013; 8 (05) 293-299
  • 47 Zakeri R, Bendayan R, Ashworth M. et al. A case-control and cohort study to determine the relationship between ethnic background and severe COVID-19. EClinicalMedicine 2020; 28: 100574
  • 48 Wang A, Mandigo GK, Yim PD, Meyers PM, Lavine SD. Stroke and mechanical thrombectomy in patients with COVID-19: technical observations and patient characteristics. J Neurointerv Surg 2020; 12 (07) 648-653
  • 49 Al-Smadi AS, Mach JC, Abrol S, Luqman A, Chamiraju P, Abujudeh H. Endovascular thrombectomy of COVID-19-related large vessel occlusion: a systematic review and summary of the literature. Curr Radiol Rep 2021; 9 (04) 4
  • 50 Lopes RD, de Barros E Silva PGM, Furtado RHM. et al; ACTION Coalition COVID-19 Brazil IV Investigators. Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial. Lancet 2021; 397 (10291): 2253-2263
  • 51 Goligher EC, Bradbury CA, McVerry BJ. et al; REMAP-CAP Investigators, ACTIV-4a Investigators, ATTACC Investigators. Therapeutic anticoagulation with heparin in critically ill patients with COVID-19. N Engl J Med 2021; 385 (09) 777-789
  • 52 Sadeghipour P, Talasaz AH, Rashidi F. et al; INSPIRATION Investigators. Effect of intermediate-dose vs standard-dose prophylactic anticoagulation on thrombotic events, extracorporeal membrane oxygenation treatment, or mortality among patients with COVID-19 admitted to the intensive care unit: the INSPIRATION Randomized Clinical Trial. JAMA 2021; 325 (16) 1620-1630
  • 53 Jurkevičienė J, Vaišvilas M, Masiliūnas R. et al. Reperfusion therapies for acute ischemic stroke in COVID-19 patients: a nationwide multi-center study. J Clin Med 2022; 11 (11) 11
  • 54 Harrison SL, Fazio-Eynullayeva E, Lane DA, Underhill P, Lip GYH. Higher mortality of ischaemic stroke patients hospitalized with COVID-19 compared to historical controls. Cerebrovasc Dis 2021; 50 (03) 326-331
  • 55 de Havenon A, Ney JP, Callaghan B. et al. Characteristics and outcomes among US patients hospitalized for ischemic stroke before vs during the COVID-19 pandemic. JAMA Netw Open 2021; 4 (05) e2110314
  • 56 Martí-Fàbregas J, Guisado-Alonso D, Delgado-Mederos R. et al; COVICTUS Collaborators. Impact of COVID-19 infection on the outcome of patients with ischemic stroke. Stroke 2021; 52 (12) 3908-3917
  • 57 Skow RJ, Nandadeva D, Grotle AK, Stephens BY, Wright AN, Fadel PJ. Impact of breakthrough COVID-19 cases during the omicron wave on vascular health and cardiac autonomic function in young adults. Am J Physiol Heart Circ Physiol 2022; 323 (01) H59-H64
  • 58 Lin E, Lantos JE, Strauss SB. et al. Brain imaging of patients with COVID-19: findings at an academic institution during the height of the outbreak in New York City. AJNR Am J Neuroradiol 2020; 41 (11) 2001-2008
  • 59 Shah S, Patel U, Mehta N, Shingru P. Posterior reversible encephalopathy syndrome (PRES) associated with COVID-19 infection—a case report and review. Journal of Stroke Medicine 2022; 5: 78-84
  • 60 Dakay K, Cooper J, Bloomfield J. et al. Cerebral venous sinus thrombosis in COVID-19 infection: a case series and review of the literature. J Stroke Cerebrovasc Dis 2021; 30 (01) 105434
  • 61 Mansoor T, Alsarah AA, Mousavi H, Khader Eliyas J, Girotra T, Hussein O. COVID-19 associated reversible cerebral vasoconstriction syndrome successfully treated with nimodipine and aspirin. J Stroke Cerebrovasc Dis 2021; 30 (07) 105822
  • 62 Leasure AC, Khan YM, Iyer R. et al. Intracerebral hemorrhage in patients with COVID-19: an analysis from the COVID-19 Cardiovascular Disease Registry. Stroke 2021; 52 (07) e321-e323
  • 63 Schmidbauer ML, Ferse C, Salih F. et al; On Behalf of the Ignite Study Group. COVID-19 and intracranial hemorrhage: a multicenter case series, systematic review and pooled analysis. J Clin Med 2022; 11 (03) 11
  • 64 Qureshi AI, Baskett WI, Huang W. et al. Subarachnoid hemorrhage and COVID-19: an analysis of 282,718 patients. World Neurosurg 2021; 151: e615-e620
  • 65 Hanafi R, Roger PA, Perin B. et al. COVID-19 neurologic complication with CNS vasculitis-like pattern. AJNR Am J Neuroradiol 2020; 41 (08) 1384-1387
  • 66 Harrogate S, Mortimer A, Burrows L, Fiddes B, Thomas I, Rice CM. Non-aneurysmal subarachnoid haemorrhage in COVID-19. Neuroradiology 2021; 63 (01) 149-152
  • 67 Agarwal S, Jain R, Dogra S. et al. Cerebral microbleeds and leukoencephalopathy in critically ill patients with COVID-19. Stroke 2020; 51 (09) 2649-2655
  • 68 Shoskes A, Huang M, Gedansky A. et al. MRI of cerebrovascular injury associated with COVID-19 and non-COVID-19 acute respiratory distress syndrome: a matched case-control study. Crit Care Med 2022; 50 (11) 1638-1643
  • 69 Thakur KT, Tamborska A, Wood GK. et al. Clinical review of cerebral venous thrombosis in the context of COVID-19 vaccinations: evaluation, management, and scientific questions. J Neurol Sci 2021; 427: 117532
  • 70 McCullough-Hicks ME, Halterman DJ, Anderson D, Cohen K, Lakshminarayan K. High incidence and unique features of cerebral venous sinus thrombosis in hospitalized patients with COVID-19 infection. Stroke 2022; 53 (09) e407-e410
  • 71 Bhola S, Trisal J, Thakur V. et al. Neurological toll of COVID-19. Neurol Sci 2022; 43 (04) 2171-2186
  • 72 Ostovan VR, Foroughi R, Rostami M. et al. Cerebral venous sinus thrombosis associated with COVID-19: a case series and literature review. J Neurol 2021; 268 (10) 3549-3560
  • 73 Baracy Jr M, Afzal F, Szpunar SM. et al. Coronavirus disease 2019 (COVID-19) and the risk of hypertensive disorders of pregnancy: a retrospective cohort study. Hypertens Pregnancy 2021; 40 (03) 226-235
  • 74 Metz TD, Clifton RG, Hughes BL. et al; National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (MFMU) Network. Association of SARS-CoV-2 infection with serious maternal morbidity and mortality from obstetric complications. JAMA 2022; 327 (08) 748-759
  • 75 Magalhães JE, Sampaio-Rocha-Filho PA. Pregnancy and neurologic complications of COVID-19: a scoping review. Acta Neurol Scand 2022; 146 (01) 6-23