Neurological Manifestations of Covid-19: A Comprehensive Review
DOI:
https://doi.org/10.21276/f24m5j86Keywords:
Neurological complications, SARS-Cov-2, Neurological signs, Neurological symptoms, Covid-19, Novel CoronavirusAbstract
The COVID-19 pandemic causing virus, SARS-CoV-2 emerged in the year 2019 from China. Since
then, it has inflicted millions of people globally. Common presentations include cough, fever, body
ache, fatigue, and shortness of breath, whereas few people might not develop any symptom. The
main target of this virus is respiratory system; precisely it attacks the ACE-2 receptors of alveolar
cells of lungs. ACE-2 receptors are also found in heart, gastrointestinal tract, kidneys, testis, and
brain; hence involvement of these organs is also seen with this disease. An emerging discovery of
invasion of nervous system by this virus has impelled researchers to investigate and understand the
neurological mechanisms and features of COVID-19. The virus can affect Central as well as
Peripheral Nervous System. Peripheral nervous system implications are not critical and include
hypersomnia, ageusia, Guillain barre syndrome, paresthesia, skeletal muscle injury and cranial nerve
involvement, whereas in central nervous system, dizziness, headache, acute cerebrovascular
disease, altered level of consciousness, transverse myelitis, acute hemorrhagic necrotizing
encephalopathy, encephalopathy, encephalitis, epilepsy and ataxia can develop. Neurological
manifestations are particularly seen with severely ill COVID patients.
In this article, we present a comprehensive review of prevalence of various CNS and PNS symptoms
in COVID-19, risk factors, investigations, management, and prognosis related to these. This will aid
the physicians and neurologists in better understanding the course of this illness and the current
statistics of neurological presentations, crucial for handling the disease.
Downloads
References
P. A novel coronavirus from patients with pneumonia in China ,2019. New England Journal of medicine.2020 Jan 24.
Green A. Li wenliang. The Lancet.2020 Feb 29;395(10225):682.
World Health Organization. Pneumonia of unknown cause- China. Disease outbreak news.5 January 2020 available at https://www.who.int/csr/don/05-january-2020-pneumonia-of-unknown-cause-china/en/.
WHO Director-General's opening remarks at the media briefing on Covid-19-11 March 2020. Available at https://www.who.int/dg/speeches/detail/Who-director-general-s-opening -remarks-at-the-media-briefing-on-covid-19-11-march-2020.
WHO Covid-19 Dashboard. Geneva: World Health Organization,2020. Available online: https://covid-19.who.int/(last cited: [27 April 2021] ).
Niazkar M, Niazkar HR. Covid-19 outbreak: Application of multi-gene genetic programming to country -based prediction models. Electronic Journal of General Medicine.2020 Sep 1;17 (5).
MW ML. Neurological manifestations of Hospitalized Patients with Covid-19 in Wuhan. China: a retrospective case series.2020.
Helms J, Kremer S, Merdji H, Clere-Jehl R, Schenck M, Kummerlen C, Collange O, Boulay C, FafiKremmer S, Ohana M, Anheim M. Neurologic features in severe SARS-COV-2 infection. New England Journal of Medicine. 2020 Jun 4;382(23):2268-70.
Jiang F, Deng L, Zhang L, Cai Y, Cheung CW, Xia Z. Review of the clinical characteristics of coronavirus disease 2019(COVID-19). Journal of general internal medicine.2020 May;35(5):1545-9.
Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, Chang J, Hong C, Zhou Y, Wang D, Miao X. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA neurology,2020 Jun 1;77(6):683-90.
Shereen MA, Khan S, Kazmi A, Bashir N, Siddique R. Covid-19 infection: Origin, transmission and characteristics of human coronaviruses. Journal of advanced research. 2020 Jul; 24:91-8.
Verdecchia P, Cavallini C, Spanevello A, Angeli F. The pivotal link between ACE2 deficiency and SARS-COV-2 infection. European journal of internal medicine 2020 Apr 20.
Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DS, Du B. Clinical characteristics of coronavirus disease 2019 in China. New England journal of medicine 2020 Apr 30;382(18):1708-20.
Hang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z. Clinical features of patients infected with 2019 novel coronavirus in Wuhan China. The lancet,2020 Feb 15;395(10223):497-506.
Meunier N, Briand L, Jacquin-Piques A, Brondel L, Pènicaud L. Covid-19 induced smell and taste impairments: putative impact on physiology. Frontiers in Physiology,2021 Jan 26;11:1882.
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. Journal of neurology.2020 Aug;267:2179-84.
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 chemical neuroscience.2020 Mar 13;11(7):995-8.
Bourgonje AR, Abdulle AF, Timens W, Hillebrands JL, Navis GJ, Gordijn SJ, Bolling MC, Dijkstra G, Voors AA, Osterhaus AD, van Der Voort PH. Angiotensin-converting enzyme 2(ACE2), SARS-CoV-2 and the pathophysiology of coronavirus disease 2019 (COVID-19). The Journal of pathology.2020 Jul;251(3):228-48.
Labò N, Ohnuki H, Tosato G. Vasculopathy and coagulopathy associated with SARS-CoV-2 infection. Cells .2020 Jul;9(7):1583.
Koralnik IJ, Tyler KL. COVID-19: a global threat to the nervous system. Annals of neurology.2020 Jul;88(1):1-1.
y Galàn JT. Stroke as a complication and prognostic factor of COVID-1. Neurologia (English Edition).2020 May 29.
McFayden JD, Stevens H, Peter K. The emerging threat of (micro)thrombosis in COVID-19 and its therapeutic implications. Circulation research.2020 Jul 31;127(4):571-87.
Acarli AN, Samanci B, Ekizoģlu E, Çakar A, Şirin NG, Gündüz T, Parman Y, Baykan B. Coronavirus disease 2019 (COVID-19) from the point of view of neurologists: observation of neurological findings and symptoms during the combat against a pandemic. Archives of Neuropsychiatry.2020 Jun;57(2):154.
Bobker SM, Robbins MS. COVID-19 and headache: A primer for Trainees. Headache : The journal of Head and Face pain. 2020 Sep: 60(8):1806-11.
Chan JL, Murphy KA, Sarna JR. Myoclonus and cerebellar ataxia associated with COVID-19 : a case report and systematic review. Journal of neurology .2021 Feb:22:1-32.
Sedaghat Z, Karimi N, Gullian Barre syndrome associated with COVID-19 infection: a case report. Journal of Clinical Neuroscience. 2020 Jun 1; 76:233-5.
Liguori C, Pierantozzi M, Spanetta M, Sarmati L, Cesta N, Iannetta M, Ora J, Mina GG, Puxeddu E, Balbi O, Pezzuto G. Subjective neurological symptoms frequently occur in patients with SARS-COV-2 infection. Brain, behavior, and immunity .2020 Aug 1;88:11-6.
Paliwal VK, Garg RK, Gupta A, Tejan N. Neuromuscular presentations in patients with COVID-19. Neurological sciences .2020 Sep 15:1-8.
Klopfenstein T, Kadiane-Oussou NJ, Toko L, Royer PY, Lepiller Q, Gendrin V, Zayet S. Features of anosmia in COVID-19. Medicine ey Maladies infection .2020 Aug 1;50(5):436-9.
Lechien JR, Chiesa-Estomba CM, De Siati DR, Horoi M, Le Bon SD, Rodriguez A, Dequanter D, Blecic S, El Afia F, Distinguin L, Chekkoury-Idrissi Y. Olfactory and gustatory dysfunction as a clincial presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. European Archives of Oto-Rhino-Laryngology. 2020 Aug:277(8):225-61.
Kim GU, Kim MJ, Ra SH, Lee J, Bae S, Jung J, Kim SH. Clinical characteristics of asymptomatic and symptomatic patients with mild COVID-19. Clinical microbiology and infection. 2020 Jul 1;26(7):948-e1.
Kacem I, Gharbi A, Harizi C, Souissi E, Safer M, Nasri A, Letaief H, Akkari M, Hechaichi A, Mrabet S, Dhaouadi S. Characteristics, onset and evolution of neurological symptoms in patients with COVID-19. Neurological Sciences .2021 Jan;42(1):39-46.
Patel A, Charani E, Ariyanayagam D, Abdulaal A, Denny SJ, Mughal N, Moore LS. New-onset anosmia and ageusia in adult patients diagnosed with SARS-COV-2 infection. Clinical Microbiology and Infection.2020 Sep 1;26(9):1236-41.
Romero-Sànchez CM, Diaz-Maroto I, Fernàndez-Diaz E, Sànchez-Larsen À, Layos-Romero A, Garcia-Garcia J, Gonzàlez E, Redondo-Peñas I, Perona- Moratalla AB, Del Valle-Pèrez JA, Gracia-Gil J. Neurologic manifestations in hospitalized patients with COVID-19: the ALBACOVID registry. Neurology .2020 Aug 25;95(8): e1060-70.
Rahimi K. Guillain-Barre syndrome during COVID-19 pandemic: an overview of the reports. Neurological Sciences. 2020 Sep 2:1-8.
Gòmez-Belda AB, Fernåndez-Garcès M, Mateo-Sanchis E, Madrazo M, Carmona M, Piles-Roger L, Artero A. COVID-19 in older adults: What are the differences with younger patients? Geriatrics &gerontology international. 2021 Jan;21(1):60-5.
Iltaf Sr S, Fatima M, Salman Sr S, Salam JU, Abbas S. Frequency of neurological presentations of coronavirus disease in patients presenting to a tertiary care hospital during the 2019 coronavirus disease pandemic. Cureus. 2020 Aug;12(8).
Bureau BL, Obeidat A, Dhariwal MS, Jha P. Peripheral Neuropathy as a Complication of SARS-COV-2. Cureus.2020 Nov;12(11).
Andalib S, Biller J, Di Napoli M, Moghini N, McCullough LD,Rubinos CA, Nobleza CO, Azarpazhooh MR, Catanese L, Elicer I, Jafari M. Peripheral nervous system manifestations associated with COVID-19. Current neurology and neuroscience reports.2021 Mar;21(3):1-4.
Kilic O, Kalcioglu MT, Cag Y, Tuysuz O, Pektas E, Caskurlu H, Cetin F. Could sudden sensorineural hearing loss be the sole manifestation of COVID-19? An investigation into SARS-COV-2 in the etiology of sudden sensorineural hearing loss. International Journal of Infectious Diseases.2020 Aug 1;97:208-11.
Jacob J, Flannery W, Mostert C. Novel ENT triad of anosmia, ageusia and hearing impairment in COVID-19. Internal Medicine Journal 2020 Sep 1.
Chern A, Famuyide AO, Moonis G, Lalwani AK. Bilateral Sudden Sensorineural Hearing Loss and Intralabyrinthine Hemorrhage in a Patient with COVID-19. Otology & Neurology. 2021 Jan; 42(1): e10.
De Luca P, Cassandro E, Scarpa A, Cassandro C, Ralli M, Gioacchini FM, Re M, Chiarella G. Sudden sensorineural hearing loss and COVID-19 (commentary on “Could sudden sensorineural hearing loss be the sole manifestation of COVID-19? An investigation into SARS-COV-2 in the etiology of sudden sensorineural hearing loss” by Osman Kilic, MahmutTayyarKalcioglu, Yasemin Cag, Ozan Tuysuz, EmelPektas, HulyaCaskurlu, and Ferihan Cetin). International Journal of Infectious Diseases.2020 Dec 1;101:201-2.
Luigetti M, Iorio R, Bentivoglio AR, Tricoli L, Riso V, Marotta J, Piano C, Primiano G, Zileri Del Verme L, Lo Monaco MR, Calabresi P. Assessment of neurological manifestations in hospitalized patients with COVID-19. European journal of neurology. 2020 Nov;27(11):2322-8.
Fiani B, Covarrubias C, Desai A, Sekhon M, Jarrah R. A contemporary review of neurological sequelae of COVID-19. Frontiers in Neurology.2020;11:640.
Ponset-Megemont L, Paris P, Tronchere A, Salazard JP, Pereira B, Dallel R, Aumeran C, Beytout J, Jacomet C, Laurichesse H, Lesens O. High prevalence of headache during COVID-19 infection: a retrospective cohort study. Headache: The journal of Head and Face Pain. 2020 Nov;60(10):2578-82.
Graham EL, Clark JR, Orban ZS, Lim PH, Szymanski AL, Taylor C, DiBiase RM, Jia DT, Balabanov R, Ho SU, Batra A. Persistent neurologic symptoms and cognitive dysfunction in non-hospitalized COVID-19 “Long hauler". Annals of clinical and translational neurology. 2021 May;8(5):1073-85.
Huang C, Huang L, Wang Y, Li X, Ren L, Guo L, Liu M, Zhou X, Luo J. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. The Lancet. 2021.
Abu-Rumeileh S, Abdelhak A, Foschi M, Tumani H, Otto M. Guillain-Barrė syndrome spectrum associated with COVID-19: an up-to-date systematic review of 73 cases. Journal of neurology.2020 Aug 25:1-38.
Ahmad I, Rathore FA. Neurological manifestations and complications of COVID-19: A literature review. Journal of Clinical Neuroscience. 2020 May 6.
Flores-Silva FD, García-Grimshaw M, Valdès-Ferrer SI, Vigueras-Hernàndez AP, Domínguez-Moreno R, Tristàn-Samaniego DP,Michel-Chàvez A, Gonzàlez-Duarte A, Vega Boada FA, Reyes-Melo I, Jimènez-Ruiz A. Neurologic manifestations in hospitalized patients with COVID-19 in Mexico city. Plos one. 2021 Apr 8;16(4): e0247433.
Uygun Ö, Ertaş M, Ekizoğlu E, Bolay H, Özge A, Orhan EK, Çağatay AA, Baykan B. Headache characteristics in COVID-19 pandemic-a survey study. The journal of headache and pain.2020 Dec;21(1):1-0.
Sampaio Racho-Filho PA, Magalhães JE. Headache associated with COVID-19: Frequency, characteristics and association with anosmia and ageusia. Cephalalgia. 2020 Nov;40(13):1443-51.
Kong Z, Wang J, Li T, Zhang Z, Jian J. 2019 novel coronavirus pneumonia with onset of dizziness: a case report. Annals of translational medicine.2020 Apr;8(7).
Saniasiaya J, Kulasegarah J. Dizziness and COVID-19. Ear, Nose & Throat Journal.2021 Jan;100(1):29-30.
Malayala SV, Raza A. A case of COVID-19-induced vestibular neuritis. Cureus.2020 Jun;12(6).
Kotfis K, Roberson SW, Wilson JE, Pun BT, Ely EW, Jeźowska I, Jezierska M, Dabrowski W. COVID-19: What do we need to know about ICU delirium during the SARS-COV-2 pandemic? Anaesthesiology intensive therapy. 2020;52(2):132.
Guan WJ, Liang WH, Zhao Y, Liang HR, Chen ZS, Li YM, Liu XQ, Chen RC, Tang CL, Wang T, Ou CQ. Comorbidity and its impact on 1590 patients with COVID-19 in China: a nationwide analysis. European Respiratory Journal .2020 May1;55(5).
Vogrig A, Gigli GL, BnàC, Morassi M. unStroke in patients with COVID-19: Clinical and neuroimaging characteristics. Neuroscience letters.2020 Dec 19:135564.
Hernàndez-Fernàndez F, Sandoval Valencia H, Barbella-Aponte RA, Collado-Jimènez R, Ayo-Martin Ò, Barrena C, Molina-Neuvo JD, García-García J, Lozano-Setíen E, Alcahut-Rodriguez C, Martínez-Martín À. Cerebrovascular disease in patients with COVID-19: neuroimaging, histological and clinical description. Brain.2020 Oct;143(10):3089-103.
Zhang JJ, Dong X, Cao YY, Yuan YD, Yang YB, Yan YQ, Akdis CA, Gao YD. Clinical characteristics of 140 patients infected with SARS-COV-2 in Wuhan, China. Allergy.2020.Jul;75(7):1730-41.
Aggarwal G, Lippi G, Michael Henry B. Cerebrovascular disease is associated with coronavirus disease 2019 (COVID-19): a pooled analysis of published literature. International Journal of Stroke.2020 Jun;15(4):385-9.
Oxley TJ, Mocco J, Majidi S, Kellner CP, Shoirah H, Singh IP, De Leacy RA, Shigemastu T, Ladner TR, Yaeger KA, Skliut M. Large-vessel stroke as a presenting feature of Covid-19 in the young. New England Journal of Medicine.2020 May 14;382(20): e60.
Karimi N, Sharifi Razavi A, Rouhani N. Frequent convulsive seizures in an adult patient with COVID-19: a case report. Iranian Red Crescent Medical Journal. 2020 Mar 31;22(3).
Lu L, Xiong W, Liu D, Liu J, Yang D, Li N, Mu J, Guo J, Li W, Wang G, Gao H. New onset acute symptomatic seizure and risk factors in coronavirus disease 2019: a retrospective multicenter study. Epilepsia.2020 Jun;61(6): e49 -53.
Diezma-Martin AM, Morales-Casado MI, Alvarado NG, Bermejo-AV. Lopèz-Ariztegui N, Berrocal MS. Tremor and ataxia in COVID-19. Neurologia (English Edition). 2020 Jul;35(6):409.
Meppiel E, Peiffer-Smadja N, Maury A, Bekri I, Delorme C, Desestret V, Gorza L, Hautecloque-Raysz G, Landre S, Lannuzel A, Moulin S. Neurologic manifestations associated with COVID-19: a multicenter registry. Clinical Microbiology and Infection.2021 Mar 1;27(3):458-66.
Scullen T, Keen J, Mathkour M, Dumont AS, Kahn L. Coronavirus 2019 (COVID-19)-associated encephalopathies and cerebrovascular disease: the New Orleans experience. World neurosurgery .2020 Sep 1;141: e437-46.
Varatharaj A, Thomas N, Ellul M, Davies NW, Pollak T, Tenorio EL, Sultan M, Easton A, Breen G, Zandi M, Coles JP. UK-wide surveillance of neurological and neuropsychiatric complications of COVID-19: the first 153 patients.
Durrani M, Kucharski K, Smith Z, Fien S. Acute transverse myelitis secondary to severe acute respiratory syndrome coronavirus 2 (SARS-COV-2): a case report. Clinical practice and cases in emergency medicine. 2020 Aug;4(3):344.
Poyiadji N, Shahin G, Noujaim D, Stone M, Patel S, Griffith B. COVID-19-associated acute hemorrhagic necrotizing encephalopathy: imaging features. Radiology.2020 Aug;296(2); E119-20.
Downloads
Published
Issue
Section
License
Copyright (c) 2024 International Archives of BioMedical and Clinical Research (IABCR)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors are required to sign and submit the completed “Copyright transfer Form” upon acceptance of publication of the paper. This is determined by a publishing agreement between the author and International Archives of Biomedical and Clinical Research. These rights might include the right to publish, communicate and distribute online. Author(s) retain the copyright of their work. International Archives of Biomedical and Clinical Research supports the need for authors to share, disseminate and maximize the impact of their research.
