• Volodymyr Lychko Department of Neurosurgery and Neurology, Sumy State University, Sumy, Ukraine https://orcid.org/0000-0001-5518-5274
  • Mykola Burtyka Medical Institute of Sumy State University, Sumy, Ukraine
Keywords: ischemic stroke, coagulopathy, immune storm, COVID 19, hospitalization, symptom


The systematic online search of articles utilizing the search terms ”Coronavirus, SARS-COV-2 and Neurological complications”, published between January 2019 and September 2021, was performed.

Neurological manifestations are prevalent during infection with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There is a clear association between cerebrovascular disease and coronavirus disease 2019 (COVID-19). But today, whether this association is causal or incidental is still unknown. This systemic review presents the possible pathophysiological mechanisms linking COVID-19 and cerebrovascular disease, describes the most often neurological complications and their prognosis, discusses several clinical and laboratory characteristics.

A systematic literature search was conducted, and relevant information was abstracted. Angiotensin-converting enzyme-2 receptor dysregulation, uncontrollable immune storm with inflammation, coagulopathy, complications due to critical illness and prolonged hospitalization can all contribute as potential etiological and pathogenic mechanisms leading to diverse cerebrovascular clinical manifestations.

Acute ischemic stroke, intracerebral haemorrhage, and cerebral venous sinus thrombosis have been described in case reports and cohorts of COVID-19 patients, with a prevalence ranging between 0.5 % and 5.0 %. SARS-CoV-2-positive stroke patients have higher mortality rates, worse functional outcomes at discharge and longer duration of hospitalization as compared with SARS-CoV-2-negative stroke patients. Understanding of the specific demographic, clinical, laboratory and radiological characteristics may be used as ‘red flags’ in recognizing COVID-19-related acute neurological complications.

Author Biographies

Volodymyr Lychko, Department of Neurosurgery and Neurology, Sumy State University, Sumy, Ukraine

Department of Neurosurgery and Neurology, Sumy State University, Sumy, Ukraine

e-mail: volodlychko@gmail.com; tel.: +380662550120

Mykola Burtyka, Medical Institute of Sumy State University, Sumy, Ukraine

5th-year student, Medical Institute, Sumy State University, Sumy, Ukraine


1. COVID-19 Map. Available online: https://coronavirus.jhu.edu/map.html (accessed on 05 September 2021).
2. Oran DP, Topol EJ. Prevalence of Asymptomatic SARS-CoV-2 Infection. Annals of Internal Medicine. 2020; 173 (5): 362–367. Available from: doi:10.7326/m20-3012.
3. Mao L, Jin H, Wang M, et al. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurology. 2020; 77 (6): 683–691. Available from: doi:10.1001/jamaneurol.2020.1127.
4. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet. 2020; 395 (10223): 497–506. Available from: doi:10.1016/s0140-6736(20)30183-5.
5. Li H, Liu L, Zhang D, et al. SARS-CoV-2 and viral sepsis: observations and hypotheses. The Lancet. 2020; 395 (10235): 1517–1520. Available from: doi:10.1016/s0140-6736(20)30920-x.
6. Cheng Q, Yang Y, Gao J. Infectivity of human coronavirus in the brain. EBioMedicine. 2020; 56: 102799. Available from: doi:10.1016/j.ebiom.2020.102799.
7. Xia H, Lazartigues E. Angiotensin-converting enzyme 2 in the brain: properties and future directions. Journal of Neurochemistry. 2008; 107 (6): 1482–1494. Available from: doi:10.1111/j.1471-4159.2008.05723.x.
8. Paniz‐Mondolfi A, Bryce C, Grimes Z, et al. Central nervous system involvement by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Journal of Medical Virology. 2020; 92 (7): 699–702. Available from: doi:10.1002/jmv.25915.
9. Neumann B, Schmidbauer ML, Dimitriadis K, et al. Cerebrospinal fluid findings in COVID-19 patients with neurological symptoms. Journal of the Neurological Sciences. 2020; 418: 117090. Available from: doi:10.1016/j.jns.2020.117090.
10. Paterson RW, Brown RL, Benjamin L. et al. The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings. Brain. 2020; 143 (10): 3104–3120. Available from: doi:10.1093/brain/awaa240.
11. Solomon IH, Normandin E, Bhattacharyya S, et al. Neuropathological Features of COVID-19. New England Journal of Medicine. 2020; 383 (10): 989–992. Available from: doi:10.1056/nejmc2019373.
12. Mehta P, Mcauley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. The Lancet. 2020; 395 (10229): 1033–1034. Available from: doi:10.1016/s0140-6736(20)30628-0.
13. Poyiadji N, Shahin G, Noujaim D, et al. COVID-19-associated Acute Hemorrhagic Necrotizing Encephalopathy: Imaging Features. Radiology. 2020; 296 (2): E119–E120. Available from: doi:10.1148/radiol.2020201187.
14. Belvis R. Headaches During COVID‐19: My Clinical Case and Review of the Literature. Headache: The Journal of Head and Face Pain. 2020; 60 (7): 1422–1426. Available from: doi:10.1111/head.13841.
15. Finsterer J, Scorza FA, Ghosh R. COVID‐19 polyradiculitis in 24 patients without SARS‐CoV‐2 in the cerebro‐spinal fluid. Journal of Medical Virology. 2021; 93 (1): 66–68. Available from: doi:10.1002/jmv.26121.
16. Assini A, Benedetti L, Di Maio S, et al. New clinical manifestation of COVID-19 related Guillain-Barrè syndrome highly responsive to intravenous immunoglobulins: two Italian cases. Neurological Sciences. 2020; 41 (7): 1657–1658. Available from: doi:10.1007/s10072-020-04484-5.
17. Gutiérrez-Ortiz C, Méndez-Guerrero A, Rodrigo-Rey S, et al. Miller Fisher syndrome and polyneuritis cranialis in COVID-19. Neurology. 2020; 95 (5): e601–e605. Available from: doi:10.1212/wnl.0000000000009619.
18. Hernández-Fernández F, Sandoval Valencia H, Barbella-Aponte RA, et al. Cerebrovascular disease in patients with COVID-19: neuroimaging, histological and clinical description. Brain. 2020; 143 (10): 3089–3103. Available from: doi:10.1093/brain/awaa239.
19. Vaschetto R, Cena T, Sainaghi PP, et al. Cerebral nervous system vasculitis in a COVID-19 patient with pneumonia. Journal of Clinical Neuroscience. 2020; 79: 71–73. Available from: doi:10.1016/j.jocn.2020.07.032.
20. Princiotta Cariddi L, Tabaee Damavandi P, Carimati F, et al. Reversible Encephalopathy Syndrome (PRES) in a COVID-19 patient. Journal of Neurology. 2020; 267 (11): 3157–3160. Available from: doi:10.1007/s00415-020-10001-7.
21. Swanson PA, Mcgavern DB. Viral diseases of the central nervous system. Current Opinion in Virology. 2015; 11: 44–54. Available from: doi:10.1016/j.coviro.2014.12.009.
22. Koyuncu O, Orkide, Hogue B, et al. Virus Infections in the Nervous System. Cell Host & Microbe. 2013; 13 (4): 379–393. Available from: doi:10.1016/j.chom.2013.03.010.
23. Ann Yeh E, Collins A, Cohen ME, et al. Detection of Coronavirus in the Central Nervous System of a Child With Acute Disseminated Encephalomyelitis. Pediatrics. 2004; 113 (1): e73–e76. Available from: doi:10.1542/peds.113.1.e73.
24. Jacomy H, Fragoso G, Almazan G, et al. Human coronavirus OC43 infection induces chronic encephalitis leading to disabilities in BALB/C mice. Virology. 2006; 349 (2): 335–346. Available from: doi:10.1016/j.virol.2006.01.049.
25. Lucchese G, Flöel A. SARS-CoV-2 and Guillain-Barré syndrome: molecular mimicry with human heat shock proteins as potential pathogenic mechanism. Cell Stress and Chaperones. 2020; 25 (5): 731–735. Available from: doi:10.1007/s12192-020-01145-6.
26. Rojas M, Restrepo-Jiménez P, Monsalve DM, et al. Molecular mimicry and autoimmunity. Journal of Autoimmunity. 2018; 95: 100–123. Available from: doi:10.1016/j.jaut.2018.10.012.
27. Romi F, Helgeland G, Gilhus NE. Heat-Shock Proteins in Clinical Neurology. European Neurology. 2011; 66 (2): 65–69. Available from: doi:10.1159/000329373.
28. Franke C, Ferse C, Kreye J, et al. High frequency of cerebrospinal fluid autoantibodies in COVID-19 patients with neurological symptoms. Brain, Behavior, and Immunity. 2021; 93: 415–419. Available from: doi:10.1016/j.bbi.2020.12.022.
29. Lewis JF, Placantonakis DG, Lighter J, et al. Cerebrospinal fluid in COVID-19: A systematic review of the literature. J Neurol Sci. 2021; 421 (117316): 1–24. Available from: doi:10.1016/j.jns.2021.117316.
30. Tandon M, Kataria S, Patel J, et al. A Comprehensive Systematic Review of CSF analysis that defines Neurological Manifestations of COVID-19. International Journal of Infectious Diseases. 2021; 104: 390–397. Available from: doi:10.1016/j.ijid.2021.01.002.
31. Duong L, Xu P, Liu A. Meningoencephalitis without respiratory failure in a young female patient with COVID-19 infection in Downtown Los Angeles, early April 2020. Brain, Behavior, and Immunity. 2020; 87: 33–43. Available from: doi:10.1016/j.bbi.2020.04.024.
32. Song E, Bartley CM, Chow RD, et al. Exploratory neuroimmune profiling identifies CNS-specific alterations in COVID-19 patients with neurological involvement. Book Exploratory neuroimmune profiling identifies CNS-specific alterations in COVID-19 patients with neurological involvement / EditorCold Spring Harbor Laboratory, 2020.
33. Schiaffino MT, Di Natale M, García-Martínez E, et al. Immunoserologic Detection and Diagnostic Relevance of Cross-Reactive Autoantibodies in Coronavirus Disease 2019 Patients. The Journal of Infectious Diseases. 2020; 222 (9): 1439–1443. Available from: doi:10.1093/infdis/jiaa485.
34. Mohkhedkar M, Venigalla SS, Janakiraman V. Autoantigens That May Explain Postinfection Autoimmune Manifestations in Patients With Coronavirus Disease 2019 Displaying Neurological Conditions. The Journal of Infectious Diseases. 2021; 223 (3): 536–537. Available from: doi:10.1093/infdis/jiaa703.
35. Levi M, Thachil J, Iba T, Levy JH. Coagulation abnormalities and thrombosis in patients with COVID-19. The Lancet Haematology. 2020; 7 (6): e438–e440. Available from: doi:10.1016/s2352-3026(20)30145-9.
36. Lippi G, South AM, Henry BM. Electrolyte imbalances in patients with severe coronavirus disease 2019 (COVID-19). Annals of Clinical Biochemistry: International Journal of Laboratory Medicine. 2020; 57 (3): 262–265. Available from: doi:10.1177/0004563220922255.
37. Kashani KB. Hypoxia in COVID-19: Sign of Severity or Cause for Poor Outcomes. Mayo Clinic Proceedings. 2020; 95 (6): 1094–1096. Available from: doi:10.1016/j.mayocp.2020.04.021.
38. Parry AH, Wani AH, Yaseen M. Neurological Dysfunction in Coronavirus Disease-19 (COVID-19). Academic Radiology. 2020; 27 (9): 1329–1330. Available from: doi:10.1016/j.acra.2020.05.024.
39. Von Weyhern CH, Kaufmann I, Neff F, Kremer M. Early evidence of pronounced brain involvement in fatal COVID-19 outcomes. The Lancet. 2020; 395 (10241): e109–е118. Available from: doi:10.1016/s0140-6736(20)31282-4.
40. Reichard RR, Kashani KB, Boire NA, et al. Neuropathology of COVID-19: a spectrum of vascular and acute disseminated encephalomyelitis (ADEM)-like pathology. Acta Neuropathologica. 2020; 140 (1): 1–6. Available from: doi:10.1007/s00401-020-02166-2.
41. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. The Lancet. 2020; 395 (10223): 507–513. Available from: doi:10.1016/s0140-6736(20)30211-7.
42. Wang L, Shen Y, Li M, et al. Clinical manifestations and evidence of neurological involvement in 2019 novel coronavirus SARS-CoV-2: a systematic review and meta-analysis. Journal of Neurology. 2020; 267 (10): 2777–2789. Available from: doi:10.1007/s00415-020-09974-2.
43. Lechien JR, Chiesa-Estomba CM, De Siati DR, at al. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. European Archives of Oto-Rhino-Laryngology. 2020; 277 (8): 2251–2261. Available from: doi:10.1007/s00405-020-05965-1.
44. Lechien JR, Chiesa‐Estomba CM, Place S, et al. Clinical and epidemiological characteristics of 1420 European patients with mild‐to‐moderate coronavirus disease 2019. Journal of Internal Medicine. 2020; 288 (3): 335–344. Available from: doi:10.1111/joim.13089.
45. Toptan T, Aktan Ç, Başarı A, Bolay H. Case Series of Headache Characteristics in COVID‐19: Headache Can Be an Isolated Symptom. Headache: The Journal of Head and Face Pain. 2020; 60 (8): 1788–1792. Available from: doi:10.1111/head.13940.
46. Trigo J, García-Azorín D, Planchuelo-Gómez Á, et al. Factors associated with the presence of headache in hospitalized COVID-19 patients and impact on prognosis: a retrospective cohort study. The Journal of Headache and Pain. 2020; 21 (1): 157–166. Available from: doi:10.1186/s10194-020-01165-8.
47. Oxley TJ, Mocco J, Majidi S, et al. Large-Vessel Stroke as a Presenting Feature of COVID-19 in the Young. New England Journal of Medicine. 2020; 382 (20): e60–е74. Available from: doi:10.1056/nejmc2009787.
48. Beyrouti R, Adams ME, Benjamin L, et al. Characteristics of ischaemic stroke associated with COVID-19. Journal of Neurology, Neurosurgery & Psychiatry. 2020; 91 (8): 889–891. Available from: doi:10.1136/jnnp-2020-323586.
49. Li Y, Li M, Wang M, et al. Acute cerebrovascular disease following COVID-19: a single center, retrospective, observational study. Stroke and Vascular Neurology. 2020; 5 (3): 279–284. Available from: doi:10.1136/svn-2020-000431.
50. Lodigiani C, Iapichino G, Carenzo L, et al. Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. Thrombosis Research. 2020; 191: 9–14. Available from: doi:10.1016/j.thromres.2020.04.024.
51. Ntaios G, Michel P, Georgiopoulos G, et al. Characteristics and Outcomes in Patients With COVID-19 and Acute Ischemic Stroke. Stroke. 2020; 51 (9): 144–171. Available from: doi:10.1161/strokeaha.120.031208.
52. Liu Y, Du X, Chen J, et al. Neutrophil-to-lymphocyte ratio as an independent risk factor for mortality in hospitalized patients with COVID-19. Journal of Infection. 2020; 81 (1): e6–e12. Available from: doi:10.1016/j.jinf.2020.04.002.
53. Liu J, Li S, Liu J, et al. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. EBioMedicine. 2020; 55 (102763): 188–197. Available from: doi:10.1016/j.ebiom.2020.102763.
54. Medcalf RL, Keragala CB, Myles PS. Fibrinolysis and COVID‐19: A plasmin paradox. Journal of Thrombosis and Haemostasis. 2020; 18 (9): 2118–2122. Available from: doi:10.1111/jth.14960.
55. Åkerström S, Gunalan V, Keng CT, et al. Dual effect of nitric oxide on SARS-CoV replication: Viral RNA production and palmitoylation of the S protein are affected. Virology. 2009; 395 (1): 1–9. Available from: doi:10.1016/j.virol.2009.09.007.
56. Tsivgoulis G, Katsanos AH, Ornello R, Sacco S. Ischemic Stroke Epidemiology During the COVID-19 Pandemic. Stroke. 2020; 51 (7): 1924–1926. Available from: doi:10.1161/strokeaha.120.030791.
57. Agarwal S, Jain R, Dogra S, et al. Cerebral Microbleeds and Leukoencephalopathy in Critically Ill Patients With COVID-19. Stroke. 2020; 51 (9): 2649–2655. Available from: doi:10.1161/strokeaha.120.030940.
58. Llitjos JF, Leclerc M, Chochois C, et al. High incidence of venous thromboembolic events in anticoagulated severe COVID‐19 patients. Journal of Thrombosis and Haemostasis. 2020; 18 (7): 1743–1746. Available from: doi:10.1111/jth.14869.
59. Escalard S, Maïer B, Redjem H, Dat al. Treatment of Acute Ischemic Stroke due to Large Vessel Occlusion With COVID-19. Stroke. 2020; 51 (8): 2540–2543. Available from: doi:10.1161/strokeaha.120.030574.
60. Pereira MD, Lima EG, Serrano Junior CV. Viral infections and atherothrombosis: Another caution in the wake of COVID-19? Revista da Associação Médica Brasileira. 2020; 66 (3): 366–369. Available from: doi:10.1590/1806-9282.66.3.366.
61. Munakomi S, Bharati K. Letter to the Editor Regarding “Acute Hemorrhage After Intracerebral Biopsy in COVID-19 Patients: A Report of 3 Cases”. World Neurosurgery. 2020; 141: 558–570. Available from: doi:10.1016/j.wneu.2020.06.128.
62. Sharifian-Dorche M, Huot P, Osherov M, et al. Neurological complications of coronavirus infection; a comparative review and lessons learned during the COVID-19 pandemic. Journal of the Neurological Sciences. 2020; 417 (117085): 241–255. Available from: doi:10.1016/j.jns.2020.117085.
How to Cite
Volodymyr Lychko, & Mykola Burtyka. (2021). CEREBROVASCULAR COMPLICATIONS OF COVID-19. Eastern Ukrainian Medical Journal, 9(3), 219-227. https://doi.org/10.21272/eumj.2021;9(3):219-227