Neurological Manifestations of COVID-19
Abstract
The year 2020 started with the news of a novel coronavirus, severe acute respiratory syndrome corona virus 2
(SARS-CoV2), induced disease in China which was termed as coronavirus disease 2019 (COVID-19). This viral
infection soon became pandemic and affected millions of people all over the world. The virus preferentially
affects respiratory system causing dry cough and fever, but has the tendency to spread to different organs in the body leading to multiple organ failure. Recent evidences show that corona virus can invade nervous system and damage it. This review is based on different articles and case reports that provide an evidence of neuro-virulent nature of COVID-19 and its consequences. The neuro-invasive property of the virus is divided into three
categories i) Central Nervous System (CNS) manifestations, ii) Peripheral Nervous System (PNS) manifestations
and iii) Skeletal Muscle damage. Headache and dizziness were observed to be common symptoms for CNS,
whereas loss of smell and taste for PNS damage due to COVID-19. The aim of this review is, to develop an
understanding of the devastating effects of COVID-19 on nervous system for the early recognition of virusinduced damage. This information can be used for the development of better therapeutic strategies.
References
M u k h e r j e e S . E m e rg i n g i n fe c t i o u s d i s e a s e s : epidemiological perspective. Indian J Dermatol. 2017; 62: 459.
Yashavantha Rao H, Jayabaskaran C. The emergence of a novel coronavirus (SARS-CoV-2) disease and their
neuroinvasive propensity may affect in COVID-19 patients. J Med Virol. 2020; 92: 786-90.
Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020; 382:727-33.
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; 24: 91-8.
Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterisation and epidemiology of 2019 novel
coronavirus: implications for virus origins and receptor binding. The Lancet 2020; 395: 565-74.
Gorbalenya AE, Baker SC, Baric R, Groot RJd, Drosten C, Gulyaeva AA, et al. Severe acute respiratory syndromerelated coronavirus: The species and its viruses–a statement of the Coronavirus Study Group. 2020.
Dua Azim SN, Kumar S, Hussain A, Patel S. Neurological Consequences of 2019-nCoV Infection: A Comprehensive Literature Review. Cureus 2020; 12: e8790.
Cataldi M, Pignataro G, Taglialatela M. Neurobiology of coronaviruses: Potential relevance for COVID-19.
Neurobiology of Disease. 2020: 105007.
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; 92: 552-5.
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: 7264-75.
Hung EC, Chim SS, Chan PK, Tong YK, Ng EK, Chiu RW, et al. Detection of SARS coronavirus RNA in the cerebrospinal fluid of a patient with severe acute respiratory syndrome. Clin Chem. 2003; 49: 2108.
Zhou L, Zhang M, Wang J, Gao J. Sars-Cov-2: Underestimated damage to nervous system. Travel Med
Infect Dis. 2020: 101642.
Li MY, Li L, Zhang Y, Wang XS. Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues. Infect Dis Poverty. 2020; 9: 45.
Bernstein HG, Dobrowolny H, Keilhoff G, Steiner J. Dipeptidyl peptidase IV, which probably plays important
roles in Alzheimer disease (AD) pathology, is up regulated in AD brain neurons and associates with amyloid plaques. Neurochem Int. 2018; 114: 55-7.
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; 11: 995-8.
Brann D, Tsukahara T, Weinreb C, Logan DW, Datta SR. Nonneural expression of SARS-CoV-2 entry genes in the olfactory epithelium suggests mechanisms underlying anosmia in COVID-19 patients. BioRxiv 2020.
Buzhdygan TP, DeOre BJ, Baldwin-Leclair A, McGary H, Razmpour R, Galie PA, et al. The SARS-CoV-2 spike protein alters barrier function in 2D static and 3D microfluidic in vitro models of the human blood–brain barrier. bioRxiv 2020.
Bohmwald K, Galvez N, Ríos M, Kalergis AM. Neurologic alterations due to respiratory virus infections. Frontiers in cellular neuroscience. 2018; 12: 386.
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. 2020;
: 14.
Tu H, Tu S, Gao S, Shao A, Sheng J. Current epidemiological and clinical features of COVID-19; a global perspective from China. J Infect. 2020; 81: 1-9.
Jose RJ, Manuel A. COVID-19 cytokine storm: the interplay between inflammation and coagulation. The Lancet
Respiratory Medicine. 2020; 8: e46-7.
Coperchini F, Chiovato L, Croce L, Magri F, Rotondi M. The cytokine storm in COVID-19: an overview of the
involvement of the chemokine/chemokine-receptor system. Cytokine Growth Factor Rev. 2020; 53: 25-32.
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.
Nile SH, Nile A, Qiu J, Li L, Jia X, Kai G. COVID-19: Pathogenesis, cytokine storm and therapeutic potential of
interferons. Cytokine Growth Factor Rev. 2020; 53: 66-70.
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 neurology. 2020; 77: 683-90.
Helms J, Kremer S, Merdji H, Clere-Jehl R, Schenck M, Kummerlen C, et al. Neurologic features in severe SARSCoV- 2 infection. N Engl J Med. 2020; 382: 2268-70.
Yin R, Yang Z, Wei Y, Li Y, Chen H, Ma D, et al. Clinical characteristics of 106 patients with neurological diseases
and co-morbid coronavirus disease 2019: a retrospective study. medRxiv. 2020.
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: 889-90.
Bagheri SHR, Asghari AM, Farhadi M, Shamshiri AR, Kabir A, Kamrava SK, et al. Coincidence of COVID-19 epidemic and olfactory dysfunction outbreak. Medrxiv. 2020.
Yan CH, Faraji F, Prajapati DP, Boone CE, DeConde AS, editors. Association of chemosensory dysfunction and
Covid-19 in patients presenting with influenza-like symptoms. International forum of allergy and rhinology.
; 10: 806-13.
Xiang P, Xu X, Gao L, Wang H, Xiong H, Li R. First case of 2019 novel coronavirus disease with encephalitis. ChinaXiv. 2020; 202003: 00015.
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.
Ye M, Ren Y, Lv T. Encephalitis as a clinical manifestation of COVID-19. Brain Behav Immun. 2020.
Filatov A, Sharma P, Hindi F, Espinosa PS. Neurological complications of coronavirus disease (COVID-19):
encephalopathy. Cureus. 2020; 12: e7352.
Poyiadji N, Shahin G, Noujaim D, Stone M, Patel S, Griffith B. COVID-19–associated acute hemorrhagic necrotizing encephalopathy: CT and MRI features. Radiology. 2020: 201187.
Sharifi-Razavi A, Karimi N, Rouhani N. COVID-19 and intracerebral haemorrhage: causative or coincidental? New microbes and new infections. 2020; 35: 100669.
Zhao K, Huang J, Dai D, Feng Y, Liu L, Nie S. Acute myelitis after SARS-CoV-2 infection: a case report. MedRxiv. 2020.
Zanin L, Saraceno G, Panciani PP, Renisi G, Signorini L, Migliorati K, et al. SARS-CoV-2 can induce brain and spine demyelinating lesions. Acta Neurochir (Wien). 2020; 162: 1491-4.
Haldrup M, Johansen M, Fjaeldstad A. Anosmia and ageusia as primary symptoms of COVID-19. Ugeskr Laeger 2020;182: 32400371.
Hjelmesæth J, Skaare D. Loss of smell or taste as the only symptom of COVID-19. Tidsskrift for Den norske
legeforening. 2020.
Melley LE, Bress E, Polan E. Hypogeusia as the initial presenting symptom of COVID-19. BMJ Case Reports CP.
; 13: e236080.
Zhao H, Shen D, Zhou H, Liu J, Chen S. Guillain-Barré syndrome associated with SARS-CoV-2 infection: causality or coincidence? The Lancet Neurology. 2020; 19: 383-4.
Sedaghat Z, Karimi N. Guillain Barre syndrome associated with COVID-19 infection: a case report. Journal of Clinical Neuroscience. 2020.
Virani A, Rabold E, Hanson T, Haag A, Elrufay R, Cheema T, et al. Guillain-Barré syndrome associated with SARS-CoV-2 infection. ID Cases. 2020: e00771.
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; 382: 2574-6.
Gutiérrez-Ortiz C, Méndez A, Rodrigo-Rey S, San Pedro- Murillo E, Bermejo-Guerrero L, Gordo-Mañas R, et al. Miller Fisher Syndrome and polyneuritis cranialis in COVID-19. Neurology. 2020; 95: e601-5.
Cabello-Verrugio C, Morales MG, Rivera JC, Cabrera D, Simon F. Renin-angiotensin system: an old player with novel functions in skeletal muscle. Med Res Rev. 2015; 35: 437-63.
Yamamoto K, Takeshita H, Rakugi H. ACE2, angiotensin 1-7 and skeletal muscle: review in the era of COVID-19. Clinical Sci. 2020; 134: 3047-62.
