Crossroads of Neurology and Virology: The Neurological Manifestations of COVID-19
DOI:
https://doi.org/10.25305/unj.310374Keywords:
Neuro-COVID, SARS-CoV-2, Neurological manifestations, Long COVID, NeuroinvasionAbstract
Introduction: The COVID-19 pandemic, caused by SARS-CoV-2, has led to an unprecedented global health crisis. While primarily recognized for its respiratory implications, the virus has shown a significant affinity for the nervous system, resulting in a wide spectrum of neurological manifestations. This literature review explores the intersection of neurology and virology, focusing on the acute and long-term neurological effects of COVID-19.
Methods: A comprehensive review of current literature was conducted using databases such as PubMed, Scopus, and Web of Science. Relevant studies were selected based on their focus on the pathophysiology, clinical presentations, and long-term neurological outcomes of COVID-19. Special attention was given to peer-reviewed articles, meta-analyses, and clinical case reports published between 2019 and 2024.
Results: The review identifies multiple mechanisms by which SARS-CoV-2 invades the nervous system, including direct viral entry and systemic inflammation. Acute neurological manifestations include encephalitis, stroke, and Guillain-Barré syndrome, while long-term sequelae encompass cognitive impairment, neurodegeneration, and psychiatric disorders. The findings underscore the complexity of COVID-19’s impact on the nervous system, with both immediate and enduring effects.
Conclusion: Neuro-COVID represents a significant and evolving challenge in the context of the pandemic. Understanding the neurological implications of COVID-19 is crucial for improving patient outcomes and guiding future research. This review underscores the need for heightened clinical awareness and a multidisciplinary approach to effectively address the complex neuro-COVID spectrum.
References
1. Yu H, Sun T, Feng J. Complications and Pathophysiology of COVID-19 in the Nervous System. Front Neurol. 2020 Dec 4;11:573421. [CrossRef] [PubMed] [PubMed Central]
2. Oxley TJ, Mocco J, Majidi S, Kellner CP, Shoirah H, Singh IP, De Leacy RA, Shigematsu T, Ladner TR, Yaeger KA, Skliut M, Weinberger J, Dangayach NS, Bederson JB, Tuhrim S, Fifi JT. Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young. N Engl J Med. 2020 May 14;382(20):e60. [CrossRef] [PubMed] [PubMed Central]
3. Varatharaj A, Thomas N, Ellul MA, Davies NWS, Pollak TA, Tenorio EL, Sultan M, Easton A, Breen G, Zandi M, Coles JP, Manji H, Al-Shahi Salman R, Menon DK, Nicholson TR, Benjamin LA, Carson A, Smith C, Turner MR, Solomon T, Kneen R, Pett SL, Galea I, Thomas RH, Michael BD; CoroNerve Study Group. Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study. Lancet Psychiatry. 2020 Oct;7(10):875-882. [CrossRef] [PubMed] [PubMed Central]
4. Meinhardt J, Radke J, Dittmayer C, Franz J, Thomas C, Mothes R, Laue M, Schneider J, Brünink S, Greuel S, Lehmann M, Hassan O, Aschman T, Schumann E, Chua RL, Conrad C, Eils R, Stenzel W, Windgassen M, Rößler L, Goebel HH, Gelderblom HR, Martin H, Nitsche A, Schulz-Schaeffer WJ, Hakroush S, Winkler MS, Tampe B, Scheibe F, Körtvélyessy P, Reinhold D, Siegmund B, Kühl AA, Elezkurtaj S, Horst D, Oesterhelweg L, Tsokos M, Ingold-Heppner B, Stadelmann C, Drosten C, Corman VM, Radbruch H, Heppner FL. Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19. Nat Neurosci. 2021 Feb;24(2):168-175. [CrossRef] [PubMed]
5. Paniz-Mondolfi A, Bryce C, Grimes Z, Gordon RE, Reidy J, Lednicky J, Sordillo EM, Fowkes M. Central nervous system involvement by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). J Med Virol. 2020 Jul;92(7):699-702. [CrossRef] [PubMed] [PubMed Central]
6. Kabbani N, Olds JL. Does COVID19 Infect the Brain? If So, Smokers Might Be at a Higher Risk. Mol Pharmacol. 2020 May;97(5):351-353. [CrossRef] [PubMed] [PubMed Central]
7. Nath A. Neurologic complications of coronavirus infections. Neurology. 2020 May 12;94(19):809-810. [CrossRef] [PubMed]
8. Baig AM. Chronic COVID syndrome: Need for an appropriate medical terminology for long-COVID and COVID long-haulers. J Med Virol. 2021 May;93(5):2555-2556. [CrossRef] [PubMed]
9. Li Y, Li M, Wang M, Zhou Y, Chang J, Xian Y, Wang D, Mao L, Jin H, Hu B. Acute cerebrovascular disease following COVID-19: a single center, retrospective, observational study. Stroke Vasc Neurol. 2020 Sep;5(3):279-284. [CrossRef] [PubMed] [PubMed Central]
10. Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, Chang J, Hong C, Zhou Y, Wang D, Miao X, Li Y, Hu B. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol. 2020 Jun 1;77(6):683-690. [CrossRef] [PubMed] [PubMed Central]
11. Paterson RW, Brown RL, Benjamin L, Nortley R, Wiethoff S, Bharucha T, Jayaseelan DL, Kumar G, Raftopoulos RE, Zambreanu L, Vivekanandam V, Khoo A, Geraldes R, Chinthapalli K, Boyd E, Tuzlali H, Price G, Christofi G, Morrow J, McNamara P, McLoughlin B, Lim ST, Mehta PR, Levee V, Keddie S, Yong W, Trip SA, Foulkes AJM, Hotton G, Miller TD, Everitt AD, Carswell C, Davies NWS, Yoong M, Attwell D, Sreedharan J, Silber E, Schott JM, Chandratheva A, Perry RJ, Simister R, Checkley A, Longley N, Farmer SF, Carletti F, Houlihan C, Thom M, Lunn MP, Spillane J, Howard R, Vincent A, Werring DJ, Hoskote C, Jäger HR, Manji H, Zandi MS. The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings. Brain. 2020 Oct 1;143(10):3104-3120. [CrossRef] [PubMed] [PubMed Central]
12. Caress JB, Castoro RJ, Simmons Z, Scelsa SN, Lewis RA, Ahlawat A, Narayanaswami P. COVID-19-associated Guillain-Barré syndrome: The early pandemic experience. Muscle Nerve. 2020 Oct;62(4):485-491. [CrossRef] [PubMed] [PubMed Central]
13. Keddie S, Pakpoor J, Mousele C, Pipis M, Machado PM, Foster M, Record CJ, Keh RYS, Fehmi J, Paterson RW, Bharambe V, Clayton LM, Allen C, Price O, Wall J, Kiss-Csenki A, Rathnasabapathi DP, Geraldes R, Yermakova T, King-Robson J, Zosmer M, Rajakulendran S, Sumaria S, Farmer SF, Nortley R, Marshall CR, Newman EJ, Nirmalananthan N, Kumar G, Pinto AA, Holt J, Lavin TM, Brennan KM, Zandi MS, Jayaseelan DL, Pritchard J, Hadden RDM, Manji H, Willison HJ, Rinaldi S, Carr AS, Lunn MP. Epidemiological and cohort study finds no association between COVID-19 and Guillain-Barré syndrome. Brain. 2021 Mar 3;144(2):682-693. [CrossRef] [PubMed] [PubMed Central]
14. Giacomelli A, Pezzati L, Conti F, Bernacchia D, Siano M, Oreni L, Rusconi S, Gervasoni C, Ridolfo AL, Rizzardini G, Antinori S, Galli M. Self-reported Olfactory and Taste Disorders in Patients With Severe Acute Respiratory Coronavirus 2 Infection: A Cross-sectional Study. Clin Infect Dis. 2020 Jul 28;71(15):889-890. [CrossRef] [PubMed] [PubMed Central]
15. NIH study identifies features of Long COVID neurological symptoms. National Institutes of Health (NIH). 2023, May 5. https://www.nih.gov/news-events/news-releases/nih-study-identifies-features-long-covid-neurological-symptoms#:~:text=People%20with%20post%2Dacute%20sequelae,SARS%2DCoV%2D2%20infection
16. Zubair AS, McAlpine LS, Gardin T, Farhadian S, Kuruvilla DE, Spudich S. Neuropathogenesis and Neurologic Manifestations of the Coronaviruses in the Age of Coronavirus Disease 2019: A Review. JAMA Neurol. 2020 Aug 1;77(8):1018-1027. [CrossRef] [PubMed] [PubMed Central]
17. Sudre CH, Murray B, Varsavsky T, Graham MS, Penfold RS, Bowyer RC, Pujol JC, Klaser K, Antonelli M, Canas LS, Molteni E, Modat M, Jorge Cardoso M, May A, Ganesh S, Davies R, Nguyen LH, Drew DA, Astley CM, Joshi AD, Merino J, Tsereteli N, Fall T, Gomez MF, Duncan EL, Menni C, Williams FMK, Franks PW, Chan AT, Wolf J, Ourselin S, Spector T, Steves CJ. Attributes and predictors of long COVID. Nat Med. 2021 Apr;27(4):626-631. [CrossRef] [PubMed] [PubMed Central]
18. Heneka MT, Golenbock D, Latz E, Morgan D, Brown R. Immediate and long-term consequences of COVID-19 infections for the development of neurological disease. Alzheimers Res Ther. 2020 Jun 4;12(1):69. [CrossRef] [PubMed] [PubMed Central]
19. Taquet M, Geddes JR, Husain M, Luciano S, Harrison PJ. 6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records. Lancet Psychiatry. 2021 May;8(5):416-427. [CrossRef] [PubMed] [PubMed Central]
20. Holder K, Reddy PH. The COVID-19 Effect on the Immune System and Mitochondrial Dynamics in Diabetes, Obesity, and Dementia. Neuroscientist. 2021 Aug;27(4):331-339. [CrossRef] [PubMed]
21. Schreiner P, Harrer T, Scheibenbogen C, Lamer S, Schlosser A, Naviaux RK, Prusty BK. Human Herpesvirus-6 Reactivation, Mitochondrial Fragmentation, and the Coordination of Antiviral and Metabolic Phenotypes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Immunohorizons. 2020 Apr 23;4(4):201-215. [CrossRef] [PubMed]
22. Roep BO. Molecular mimicry in autoimmune neurological disease after viral infection. Curr Med Chem. 2003 Oct;10(19):1939-43. [PubMed]
23. Baig AM, Khaleeq A, Ali U, Syeda H. Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host-Virus Interaction, and Proposed Neurotropic Mechanisms. ACS Chem Neurosci. 2020 Apr 1;11(7):995-998. [CrossRef] [PubMed]
24. Wang Y, Liu S, Liu H, Li W, Lin F, Jiang L, Li X, Xu P, Zhang L, Zhao L, Cao Y, Kang J, Yang J, Li L, Liu X, Li Y, Nie R, Mu J, Lu F, Zhao S, Lu J, Zhao J. SARS-CoV-2 infection of the liver directly contributes to hepatic impairment in patients with COVID-19. J Hepatol. 2020 Oct;73(4):807-816. [CrossRef] [PubMed] [PubMed Central]
25. Santos MO, Gonçalves LC, Silva PAN, Moreira ALE, Ito CRM, Peixoto FAO, Wastowski IJ, Carneiro LC, Avelino MAG. Multisystem inflammatory syndrome (MIS-C): a systematic review and meta-analysis of clinical characteristics, treatment, and outcomes. J Pediatr (Rio J). 2022 Jul-Aug;98(4):338-349. [CrossRef] [PubMed] [PubMed Central]
26. LaRovere KL, Riggs BJ, Poussaint TY, Young CC, Newhams MM, Maamari M, Walker TC, Singh AR, Dapul H, Hobbs CV, McLaughlin GE, Son MBF, Maddux AB, Clouser KN, Rowan CM, McGuire JK, Fitzgerald JC, Gertz SJ, Shein SL, Munoz AC, Thomas NJ, Irby K, Levy ER, Staat MA, Tenforde MW, Feldstein LR, Halasa NB, Giuliano JS Jr, Hall MW, Kong M, Carroll CL, Schuster JE, Doymaz S, Loftis LL, Tarquinio KM, Babbitt CJ, Nofziger RA, Kleinman LC, Keenaghan MA, Cvijanovich NZ, Spinella PC, Hume JR, Wellnitz K, Mack EH, Michelson KN, Flori HR, Patel MM, Randolph AG; Overcoming COVID-19 Investigators. Neurologic Involvement in Children and Adolescents Hospitalized in the United States for COVID-19 or Multisystem Inflammatory Syndrome. JAMA Neurol. 2021 May 1;78(5):536-547. [CrossRef] [PubMed] [PubMed Central]
27. Morand, A.; Urbina, D.; Fabre, A. COVID-19 and Kawasaki Like Disease: The Known-Known, the Unknown-Known and the Unknown-Unknown. Preprints 2020, 2020050160. [CrossRef]
28. Nalbandian A, Sehgal K, Gupta A, Madhavan MV, McGroder C, Stevens JS, Cook JR, Nordvig AS, Shalev D, Sehrawat TS, Ahluwalia N, Bikdeli B, Dietz D, Der-Nigoghossian C, Liyanage-Don N, Rosner GF, Bernstein EJ, Mohan S, Beckley AA, Seres DS, Choueiri TK, Uriel N, Ausiello JC, Accili D, Freedberg DE, Baldwin M, Schwartz A, Brodie D, Garcia CK, Elkind MSV, Connors JM, Bilezikian JP, Landry DW, Wan EY. Post-acute COVID-19 syndrome. Nat Med. 2021 Apr;27(4):601-615. [CrossRef] [PubMed] [PubMed Central]
29. Avittan H, Kustovs D. Cognition and Mental Health in Pediatric Patients Following COVID-19. Int J Environ Res Public Health. 2023 Mar 13;20(6):5061. [CrossRef] [PubMed] [PubMed Central]
30. Sharma VK, Singh TG, Mehta V, Mannan A. Biomarkers: Role and Scope in Neurological Disorders. Neurochem Res. 2023 Jul;48(7):2029-2058. [CrossRef] [PubMed]
31. Kanberg N, Simrén J, Edén A, Andersson LM, Nilsson S, Ashton NJ, Sundvall PD, Nellgård B, Blennow K, Zetterberg H, Gisslén M. Neurochemical signs of astrocytic and neuronal injury in acute COVID-19 normalizes during long-term follow-up. EBioMedicine. 2021 Aug;70:103512. [CrossRef] [PubMed] [PubMed Central]
32. Paterson RW, Benjamin LA, Mehta PR, Brown RL, Athauda D, Ashton NJ, Leckey CA, Ziff OJ, Heaney J, Heslegrave AJ, Benedet AL, Blennow K, Checkley AM, Houlihan CF, Mummery CJ, Lunn MP, Manji H, Zandi MS, Keddie S, Chou M, Vinayan Changaradil D, Solomon T, Keshavan A, Barker S, Jäger HR, Carletti F, Simister R, Werring DJ, Spyer MJ, Nastouli E, Gauthier S, Rosa-Neto P; UCLH Queen Square COVID-19 Biomarker Study Group; Zetterberg H, Schott JM. Serum and cerebrospinal fluid biomarker profiles in acute SARS-CoV-2-associated neurological syndromes. Brain Commun. 2021 May 12;3(3):fcab099. [CrossRef] [PubMed] [PubMed Central]
33. Barbosa-Silva MC, Lima MN, Battaglini D, Robba C, Pelosi P, Rocco PRM, Maron-Gutierrez T. Infectious disease-associated encephalopathies. Crit Care. 2021 Jul 6;25(1):236. [CrossRef] [PubMed] [PubMed Central]
34. Kiani L. Preventing COVID-19 neurological complications. Nat Rev Neurol. 2022 Dec;18(12):699. [CrossRef] [PubMed] [PubMed Central]
35. Rolin S, Chakales A, Verduzco-Gutierrez M. Rehabilitation Strategies for Cognitive and Neuropsychiatric Manifestations of COVID-19. Curr Phys Med Rehabil Rep. 2022;10(3):182-187. [CrossRef] [PubMed] [PubMed Central]
36. Fotuhi M, Mian A, Meysami S, Raji CA. Neurobiology of COVID-19. J Alzheimers Dis. 2020;76(1):3-19. [CrossRef] [PubMed] [PubMed Central]
37. Thankachen SS, Devasenapathy N, Bassi A, Ghosh A, Arfin S, Gummidi B, Basheer A, Bangi A, Sahu D, Bhalla A, Blesson M, Jain M, Jha V. Colchicine to reduce coronavirus disease-19-related inflammation and cardiovascular complications in high-risk patients post-acute infection with SARS-COV-2-a study protocol for a randomized controlled trial. Trials. 2024 Jun 12;25(1):378. [CrossRef] [PubMed] [PubMed Central]
38. Daniels K, Mourad J, Bonnechère B. Exploring the Use of Mobile Health for the Rehabilitation of Long COVID Patients: A Scoping Review. Healthcare (Basel). 2024 Feb 10;12(4):451. [CrossRef] [PubMed] [PubMed Central]
39. D'Arcy RCN, Sandhu JK, Marshall S, Besemann M. Mitigating Long-Term COVID-19 Consequences on Brain Health. Front Neurol. 2021 Sep 27;12:630986. [CrossRef] [PubMed] [PubMed Central]
40. Frank MG, Ball JB, Hopkins S, Kelley T, Kuzma AJ, Thompson RS, Fleshner M, Maier SF. SARS-CoV-2 S1 subunit produces a protracted priming of the neuroinflammatory, physiological, and behavioral responses to a remote immune challenge: A role for corticosteroids. Brain Behav Immun. 2024 Oct;121:87-103. [CrossRef] [PubMed]
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Kirolos Eskandar
This work is licensed under a Creative Commons Attribution 4.0 International License.
Ukrainian Neurosurgical Journal abides by the CREATIVE COMMONS copyright rights and permissions for open access journals.
Authors, who are published in this Journal, agree to the following conditions:
1. The authors reserve the right to authorship of the work and pass the first publication right of this work to the Journal under the terms of Creative Commons Attribution License, which allows others to freely distribute the published research with the obligatory reference to the authors of the original work and the first publication of the work in this Journal.
2. The authors have the right to conclude separate supplement agreements that relate to non-exclusive work distribution in the form of which it has been published by the Journal (for example, to upload the work to the online storage of the Journal or publish it as part of a monograph), provided that the reference to the first publication of the work in this Journal is included.