Neurological manifestations of COVID-19: a clinical approach

  • Ni Made Susilawathi Department of Neurology, Faculty of Medicine, Universitas Udayana, Universitas Udayana Hospital, Bali, Indonesia
  • Kumara Tini Department of Neurology, Faculty of Medicine, Universitas Udayana, Universitas Udayana Hospital, Bali, Indonesia
  • Ida Ayu Sri Wijayanti Department of Neurology, Faculty of Medicine, Universitas Udayana, Universitas Udayana Hospital, Bali, Indonesia
  • Putu Lohita Rahmawati Department of Neurology, Faculty of Medicine, Universitas Udayana, Universitas Udayana Hospital, Bali, Indonesia
  • Dewa Putu Wisnu Wardhana Departement of Neurosurgery, Faculty of Medicine, Universitas Udayana, Universitas Udayana Hospital, Bali, Indonesia
  • Dewa Gde Purwa Samatra Department of Neurology, Faculty of Medicine, Universitas Udayana, Universitas Udayana Hospital, Bali, Indonesia
  • Anak Agung Raka Sudewi Department of Neurology, Faculty of Medicine, Universitas Udayana, Universitas Udayana Hospital, Bali, Indonesia
Keywords: COVID-19, neurological manifestations, SARS-CoV-2
Abstract viewed: 882 times
PDF downloaded: 389 times
HTML downloaded: 38 times
EPUB downloaded: 89 times

Abstract

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2 which attacks the respiratory tract and has been declared a global pandemic by the World Health Organization. The disease has a very wide clinical spectrum which can be manifested as asymptomatic to critical conditions. SARS-CoV-2 shows a neurotropism proven by its identification in the cerebrospinal fluid and brain vascular endothelial. The complete mechanism of how the virus invades the human nervous system is yet to be identified. Thus, every neurologist needs to follow the progressivity of COVID-19 symptoms involving the nervous system.

References

  1. World Health Organization (WHO). Coronavirus disease (COVID-19) pandemic. World Health Organization (WHO); 2020. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019.

  2. Docea AO, Tsatsakis A, Albulescu D, Cristea O, Zlatian O, Vinceti M, et al. A new threat from an old enemy: re-emergence of coronavirus (review). Int J Mol Med. 2020;45(6):1631-43. https://doi.org/10.3892/ijmm.2020.4555

  3. Kang S, Peng W, Zhu Y, Lu S, Zhou M, Lin W, et al. Recent progress in understanding 2019 novel coronavirus (SARS-CoV-2) associated with human respiratory disease: detection, mechanisms and treatment. Int J Antimicrob Agents. 2020;55(5):105950. https://doi.org/10.1016/j.ijantimicag.2020.105950

  4. Liu K, Fang YY, Deng Y, Liu W, Wang MF, Ma JP, et al. Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province. Chin Med J (Engl). 2020;133(9):1025-31. https://doi.org/10.1097/CM9.0000000000000744

  5. Wang HY, Li XL, Yan ZR, Sun XP, Han J, Zhang BW. Potential neurological symptoms of COVID-19. Ther Adv Neurol Disord. 2020;13. https://doi.org/10.1177/1756286420917830

  6. De Felice FG, Tovar-Moll F, Moll J, Munoz DP, Ferreira ST. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the central nervous system. Trends Neurosci. 2020;43(6):355-7. https://doi.org/10.1016/j.tins.2020.04.004

  7. Needham EJ, Chou SH, Coles AJ, Menon DK. Neurological implications of COVID-19 infections. Neurocrit Care. 2020;32(3):667-71. https://doi.org/10.1007/s12028-020-00978-4

  8. Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 2020;77(6):683-90. https://doi.org/10.1001/jamaneurol.2020.1127

  9. Zhai P, Ding Y, Wu X, Long J, Zhong Y, Li Y. The epidemiology, diagnosis and treatment of COVID-19. Int J Antimicrob Agents. 2020;55(5):105955. https://doi.org/10.1016/j.ijantimicag.2020.105955

  10. Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med. 2020;382(13):1199-207. https://doi.org/10.1056/NEJMoa2001316

  11. Guo YR, Cao QD, Hong ZS, Tan YY, Chen SD, Jin HJ, et al. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak - an update on the status. Mil Med Res. 2020;7(1):11. https://doi.org/10.1186/s40779-020-00240-0

  12. Chen T, Wu D, Chen H, Yan W, Yang D, Chen G, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ. 2020;368:m1091. https://doi.org/10.1136/bmj.m1091

  13. Wang W, Tang J, Wei F. Updated understanding of the outbreak of 2019 novel coronavirus (2019-nCoV) in Wuhan, China. J Med Virol. 2020;92(4):441-7. https://doi.org/10.1002/jmv.25689

  14. Wu Y, Xu X, Yang L, Liu C, Yang C. Nervous system damage after COVID-19 infection: presence or absence? Brain Behav Immun. 2020;87:55. https://doi.org/10.1016/j.bbi.2020.04.043

  15. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507-13. https://doi.org/10.1016/S0140-6736(20)30211-7

  16. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382:1708-20. https://doi.org/10.1056/NEJMoa2002032

  17. Rabi FA, Al Zoubi MS, Kasasbeh GA, Salameh DM, Al-Nasser AD. SARS-CoV-2 and coronavirus disease 2019: what we know so far. Pathogens. 2020;9(3):231. https://doi.org/10.3390/pathogens9030231

  18. Borges do Nascimento IJ, Cacic N, Abdulazeem HM, von Groote TC, Jayarajah U, Weerasekara I, et al. Novel coronavirus infection (COVID-19) in humans: a scoping review and meta-analysis. J Clin Med. 2020;9(4):941. https://doi.org/10.3390/jcm9040941

  19. Moriguchi T, Harii N, Goto J, Harada D, Sugawara H, Takamino J, et al. A first case of meningitis/encephalitis associated with SARS-coronavirus-2. Int J Infect Dis. 2020;94:55-8. https://doi.org/10.1016/j.ijid.2020.03.062

  20. Jin H, Hong C, Chen S, Zhou Y, Wang Y, Mao L, et al. Consensus for prevention and management of coronavirus disease 2019 (COVID-19) for neurologists. Stroke Vasc Neurol. 2020;5(2):146-51. https://doi.org/10.1136/svn-2020-000382

  21. Lechien JR, Chiesa-Estomba CM, Place S, Van Laethem Y, Cabaraux P, Mat Q, et al. Clinical and epidemiological characteristics of 1,420 European patients with mild-to-moderate coronavirus disease 2019. J Intern Med. 2020;288(3):335-44. https://doi.org/10.1111/joim.13089

  22. Helms J, Kremer S, Merdji H, Clere-Jehl R, Schenck M, Kummerlen C, et al. Neurologic features in severe SARS-CoV-2 infection. N Engl J Med. 2020;382(23):2268-70. https://doi.org/10.1056/NEJMc2008597

  23. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506. https://doi.org/10.1016/S0140-6736(20)30183-5

  24. Li Y, Li M, Wang M, Zhou Y, Chang J, Xian Y, et al. Acute cerebrovascular disease following COVID 19: a single center retrospective, observational study. Stroke Vasc Neurol. 2020;5(3):279-84. https://doi.org/10.1136/svn-2020-000431

  25. Craen A, Logan G, Ganti L. Novel coronavirus disease 2019 and subarachnoid hemorrhage: a case report. Cureus. 2020;12(4):e7846. https://doi.org/10.7759/cureus.7846

  26. Guidon AC, Amato AA. COVID-19 and neuromuscular disorders. Neurology. 2020;94(22):959-69. https://doi.org/10.1212/WNL.0000000000009566

  27. Jin X, Lian JS, Hu JH, Gao J, Zheng L, Zhang YM, et al. Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms. Gut. 2020;69(6):1002-9. https://doi.org/10.1136/gutjnl-2020-320926

  28. Lechien JR, Chiesa-Estomba CM, De Siati DR, Horoi M, Le Bon SD, Rodriguez A, et al. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. Eur Arch Otorhinolaryngol. 2020;277(8):2251-61. https://doi.org/10.1007/s00405-020-05965-1

  29. Giacomelli A, Pezzati L, Conti F, Bernacchia D, Siano M, Oreni L, et al. Self-reported olfactory and taste disorders in patients with severe acute respiratory coronavirus 2 infection: a cross-sectional study. Clin Infect Dis. 2020;71(15):889-90. https://doi.org/10.1093/cid/ciaa330

  30. Paniz-Mondolfi A, Bryce C, Grimes Z, Gordon RE, Reidy J, Lednicky J, et al. Central nervous system involvement by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). J Med Virol. 2020;92(7):699-702. https://doi.org/10.1002/jmv.25915

  31. Ye M, Ren Y, Lv T. Encephalitis as a clinical manifestation of COVID-19. Brain Behav Immun. 2020;88:945-6. https://doi.org/10.1016/j.bbi.2020.04.017

  32. Oxley TJ, Mocco J, Majidi S, Kellner CP, Shoirah H, Singh IP, et al. Large-vessel stroke as a presenting feature of covid-19 in the young. N Engl J Med. 2020;382(20):e60. https://doi.org/10.1056/NEJMc2009787

  33. Alberti P, Beretta S, Piatti M, Karantzoulis A, Piatti ML, Santoro P, et al. Guillain-Barré syndrome related to COVID-19 infection. Neurol Neuroimmunol Neuroinflamm. 2020;7(4):e741. https://doi.org/10.1212/NXI.0000000000000741

  34. Zhao H, Shen D, Zhou H, Liu J, Chen S. Guillain-Barré syndrome associated with SARS-CoV-2 infection: causality or coincidence? Lancet Neurol. 2020;19(5):383-4. https://doi.org/10.1016/S1474-4422(20)30109-5

  35. Toscano G, Palmerini F, Ravaglia S, Ruiz L, Invernizzi P, Cuzzoni MG, et al. Guillain-Barré syndrome associated with SARS-CoV-2. N Engl J Med. 2020:NEJMc2009191. https://doi.org/10.1056/NEJMc2009191

  36. Virani A, Rabold E, Hanson T, Haag A, Elrufay R, Cheema T, et al. Guillain-Barré syndrome associated with SARS-CoV-2 infection. IDCases. 2020;20:e00771. https://doi.org/10.1016/j.idcr.2020.e00771

  37. Gutiérrez-Ortiz C, Méndez-Guerrero A, Rodrigo-Rey S, Pedro-Murillo ES, Bermejo-Guerrero L, Gordo-Mañas R, et al. Miller Fisher syndrome and polyneuritis cranialis in COVID-19. Neurology. 2020;95(5). https://doi.org/10.1212/WNL.0000000000009619

  38. Barzegar M, Mirmosayyeb O, Nehzat N, Sarrafi R, Khorvash F, Maghzi AH, et al. COVID-19 infection in a patient with multiple sclerosis treated with fingolimod. Neurol Neuroimmunol Neuroinflamm. 2020;7(4). https://doi.org/10.1212/NXI.0000000000000753

  39. Delly F, Syed MJ, Lisak RP, Zutshi D. Myasthenic crisis in COVID-19. J Neurol Sci. 2020;414:116888. https://doi.org/10.1016/j.jns.2020.116888

  40. Su S, Wong G, Shi W, Liu J, Lai AC, Zhou J, et al. epidemiology, genetic recombination, and pathogenesis of coronaviruses. Trends Microbiol. 2016;24(6):490-502. https://doi.org/10.1016/j.tim.2016.03.003

  41. 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;11(7):995-8. https://doi.org/10.1021/acschemneuro.0c00122

  42. Hui DS, Azhar EI, Madani TA, Ntoumi F, Kock R, Dar O, et al. The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health - The latest 2019 novel coronavirus outbreak in Wuhan, China. Int J Infect Dis. 2020;91:264-6. https://doi.org/10.1016/j.ijid.2020.01.009

  43. Koyuncu OO, Hogue IB, Enquist LW. Virus infections in the nervous system. Cell Host Microbe. 2013;13(4):379-93. https://doi.org/10.1016/j.chom.2013.03.010

  44. 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;77(8):1018-27. https://doi.org/10.1001/jamaneurol.2020.2065

  45. Xia H, Lazartigues E. Angiotensin-converting enzyme 2 in the brain: properties and future directions. J Neurochem. 2008;107(6):1482-94. https://doi.org/10.1111/j.1471-4159.2008.05723.x

  46. Li YC, Bai WZ, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. J Med Virol. 2020;1-4. https://doi.org/10.1002/jmv.25728

  47. Marchioni E, Minoli L. Headache attributed to infections nosography and differential diagnosis. Handb Clin Neurol. 2010;97:601-26. https://doi.org/10.1016/S0072-9752(10)97052-8

  48. Zhou Z, Kang H, Li S, Zhao X. Understanding the neurotropic characteristics of SARS-CoV-2: from neurological manifestations of COVID-19 to potential neurotropic mechanisms. J Neurol. 2020:1-6. https://doi.org/10.1007/s00415-020-09929-7

  49. Gladstone J, Bigal ME. Headaches attributable to infectious diseases. Curr Pain Headache Rep. 2010;14(4):299-308. https://doi.org/10.1007/s11916-010-0125-7

  50. Li YC, Bai WZ, Hashikawa T. Response to commentary on "The neuroinvasive potential of SARS-CoV-2 may play a role in the respiratory failure of COVID-19 patients". J Med Virol. 2020;92(7):707-9. https://doi.org/10.1002/jmv.25824

  51. Tyler KL. Acute viral encephalitis. N Engl J Med. 2018;379(6):557-66. https://doi.org/10.1056/NEJMra1708714

  52. Ellul M, Solomon T. Acute encephalitis - diagnosis and management. Clin Med (Lond). 2018;18(2):155-9. https://doi.org/10.7861/clinmedicine.18-2-155

  53. Desforges M, Le Coupanec A, Dubeau P, Bourgouin A, Lajoie L, Dubé M, et al. Human coronaviruses and other respiratory viruses: underestimated opportunistic pathogens of the central nervous system? Viruses. 2019;12(1):14. https://doi.org/10.3390/v12010014

  54. Bookstaver PB, Mohorn PL, Shah A, Tesh LD, Quidley AM, Kothari R, et al. Management of viral central nervous system infections: a primer for clinicians. J Cent Nerv Syst Dis. 2017;9:1179573517703342. https://doi.org/10.1177/1179573517703342

  55. Wu Y, Xu X, Chen Z, Duan J, Hashimoto K, Yang L, et al. Nervous system involvement after infection with COVID-19 and other coronaviruses. Brain Behav Immun. 2020;87:18-22. https://doi.org/10.1016/j.bbi.2020.03.031

  56. Baig AM. Neurological manifestations in COVID-19 caused by SARS-CoV-2. CNS Neurosci Ther. 2020;26(5):499-501. https://doi.org/10.1111/cns.13372

  57. Li Z, Liu T, Yang N, Han D, Mi X, Li Y, et al. Neurological manifestations of patients with COVID-19: potential routes of SARS-CoV-2 neuroinvasion from the periphery to the brain. Front Med. 2020;14(5):533-41. https://doi.org/10.1007/s11684-020-0786-5

  58. Serrano-Castro PJ, Estivill-Torrús G, Cabezudo-García P, Reyes-Bueno JA, Ciano Petersen N, Aguilar-Castillo MJ, et al. Impact of SARS-CoV-2 infection on neurodegenerative and neuropsychiatric diseases: a delayed pandemic? Neurologia. 2020;35(4):245-51. https://doi.org/10.1016/j.nrl.2020.04.002

  59. Du W, Yu J, Wang H, Zhang X, Zhang S, Li Q, et al. Clinical characteristics of COVID-19 in children compared with adults in Shandong Province, China. Infection. 2020:1-8. https://doi.org/10.21203/rs.3.rs-17119/v1

  60. Swanson PA II, McGavern DB. Viral diseases of the central nervous system. Curr Opin Virol. 2015;11:44-54. https://doi.org/10.1016/j.coviro.2014.12.009

  61. Desforges M, Le Coupanec A, Stodola JK, Meessen-Pinard M, Talbot PJ. Human coronaviruses: viral and cellular factors involved in neuroinvasiveness and neuropathogenesis. Virus Res. 2014;194:145-58. https://doi.org/10.1016/j.virusres.2014.09.011

  62. Benameur K, Agarwal A, Auld SC, Butters MP, Webster AS, Ozturk T, et al. Encephalopathy and encephalitis associated with cerebrospinal fluid cytokine alterations and coronavirus disease, Atlanta, Georgia, USA, 2020. Emerg Infect Dis. 2020;26(9):2016-21. https://doi.org/10.3201/eid2609.202122

  63. Markus HS, Brainin M. COVID-19 and stroke-A global World Stroke Organization perspective. Int J Stroke. 2020;15(4):361-4. https://doi.org/10.1177/1747493020923472

  64. Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, et al. Dysregulation of immune response in patients with COVID-19 in Wuhan, China. Clin Infect Dis. 2020;71(15):762-8. https://doi.org/10.1093/cid/ciaa248

  65. McGonagle D, Sharif K, O'Regan A, Bridgewood C. The role of cytokines including interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease. Autoimmun Rev. 2020;19(6):102537. https://doi.org/10.1016/j.autrev.2020.102537

  66. Pérez CA. Looking ahead: the risk of neurologic complications due to COVID-19. Neurol Clin Pract. 2020;10(4):371-4. https://doi.org/10.1212/CPJ.0000000000000836

  67. Saavedra JM. COVID-19, angiotensin receptor blockers, and the brain. Cell Mol Neurobiol. 2020;40(5):667-74. https://doi.org/10.1007/s10571-020-00861-y

  68. Speth MM, Singer-Cornelius T, Obere M, Gengler I, Brockmeier SJ, Sedaghat AR. Olfactory dysfunction and sinonasal symptomatology in COVID-19: prevalence, severity, timing, and associated characteristics. Otolaryngol Head Neck Surg. 2020;163(1):114-20. https://doi.org/10.1177/0194599820929185

  69. Netland J, Meyerholz DK, Moore S, Cassell M, Perlman S. Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2. J Virol. 2008;82(15):7264-75. https://doi.org/10.1128/JVI.00737-08

  70. Bolay H, Gül A, Baykan B. COVID-19 is a real headache! Headache. 2020;60(7):1415-21. https://doi.org/10.1111/head.13856

  71. Wilson MP, Jack AS. Coronavirus disease 2019 (COVID-19) in neurology and neurosurgery: a scoping review of the early literature. Clin Neurol Neurosurg. 2020;193:105866. https://doi.org/10.1016/j.clineuro.2020.105866

  72. Federico A. Experiencing COVID19 pandemic and neurology: learning by the recent reports and by old literary or scientific descriptions. Neurol Sci. 2020;41(6):1323-7. https://doi.org/10.1007/s10072-020-04471-w

  73. Moazzami B, Razavi-Khorasani N, Dooghaie Moghadam A, Farokhi E, Rezaei N. COVID-19 and telemedicine: immediate action required for maintaining healthcare providers well-being. J Clin Virol. 2020;126:104345. https://doi.org/10.1016/j.jcv.2020.104345

  74. Al Hussona M, Maher M, Chan D, Micieli JA, Jain JD, Khosravani H, et al. the virtual neurologic exam: instructional videos and guidance for the COVID-19 era. Can J Neurol Sci. 2020;47(5):598-603. https://doi.org/10.1017/cjn.2020.96

  75. Pollett S, Rivers C. Social media and the new world of scientific communication during the COVID19 pandemic. Clin Infect Dis. 2020;71(16):2184-6. https://doi.org/10.1093/cid/ciaa553

  76. Orsucci D, Lenco EC, Nocita G, Napolitano A, Vista M. Neurological features of COVID-19 and their treatment: a review. Drugs Context. 2020;9:2020-5-1. https://doi.org/10.7573/dic.2020-5-1

Published
2021-05-03
How to Cite
1.
Susilawathi NM, Tini K, Wijayanti IAS, Rahmawati PL, Wardhana DPW, Samatra DGP, Sudewi AAR. Neurological manifestations of COVID-19: a clinical approach. Med J Indones [Internet]. 2021May3 [cited 2021Sep.28];30(2):157–65. Available from: https://mji.ui.ac.id/journal/index.php/mji/article/view/4821
Section
Review Article