Neurological Consequences of 2019-nCoV Infection: A Comprehensive Literature Review

Dua Azim, Sundus Nasim, Sohail Kumar, Azhar Hussain, Sundip Patel, Dua Azim, Sundus Nasim, Sohail Kumar, Azhar Hussain, Sundip Patel

Abstract

First identified in November 2019 in Hubei Province, the coronavirus disease of 2019 (COVID-19) caused by SARS-CoV-2 soon spread worldwide to become a global health pandemic. The COVID-19 preferentially damages the respiratory system that produces symptoms such as fever, cough, and shortness of breath. However, the infection often tends to disseminate to involve various organ systems. Recent evidence indicates that SARS-CoV-2 can cause significant neurological damage and resultant neurological symptoms and complications. Here, we provide a comprehensive and thorough review of original articles, case reports, and case series to delineate the possible mechanisms of nervous system invasion and damage by SARS-CoV-2 and subsequent consequences. We divided the neurological manifestations into three categories: (1) Central Nervous System involvement, (2) Peripheral Nervous System manifestations, and (3) Skeletal Muscle Injury. Headache and dizziness were found to be the most prevalent symptoms followed by impaired consciousness. Among the symptoms indicating peripheral nervous system invasion, anosmia and dysgeusia were commonly reported. Skeletal muscle injury predominantly presents as myalgia. In addition, encephalitis, myelitis, cerebrovascular disease, Guillain-Barre syndrome, and Miller Fischer syndrome were among the commonly noted complications. We also emphasized the association of pre-existing comorbidities with neurological manifestations. The aim of this review is to provide a deeper understanding of the potential neurological implications to help neurologists have a high index of clinical suspicion allowing them to manage the patient appropriately.

Keywords: cerebrovascular injury; covid-19; hypoxic injury; immune-mediated injury; sars-cov-2.

Conflict of interest statement

The authors have declared that no competing interests exist.

Copyright © 2020, Azim et al.

Figures

Figure 1. Major modes of nervous system…
Figure 1. Major modes of nervous system invasion and damage by SARS-CoV-2.
Figure 2. Categorization of neurological manifestations and…
Figure 2. Categorization of neurological manifestations and most reported symptoms.
Figure 3. Central nervous system manifestations of…
Figure 3. Central nervous system manifestations of COVID-19.
Figure 4. Peripheral nervous system manifestations of…
Figure 4. Peripheral nervous system manifestations of COVID-19.
Figure 5. Skeletal muscle injury complications associated…
Figure 5. Skeletal muscle injury complications associated with COVID-19.

References

    1. Human coronaviruses: what do they cause? van der Hoek L. Antivir Ther. 2007;12:651–658.
    1. COVID-19 infection: origin, transmission, and characteristics of human coronaviruses. Shereen MA, Khan S, Kazmi A, Bashir N, Siddique R. J Adv Res. 2020;24:91–98.
    1. World Health Organization. Pneumonia of unknown cause - China. [May;2020 ]; 2020
    1. Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov (PREPRINT) Zhao Y, Zhao Z, Wang Y, Zhou Y, Ma Y, Zuo W. BioRxiv. 2020
    1. WHO Director-General's opening remarks at the media briefing on COVID-19 - 11 March 2020. [May;2020 ]; 2020
    1. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. Mao L, Jin H, Wang M, et al. JAMA Neurol. 2020;77:683–690.
    1. Neurologic features in severe SARS-CoV-2 infection. Helms J, Kremer S, Merdji H, et al. N Engl J Med. 2020;382:2268–2270.
    1. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Li W, Moore MJ, Vasilieva N, et al. Nature. 2003;426:450–454.
    1. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. J Pathol. 2004;203:631–637.
    1. Human coronaviruses and other respiratory viruses: underestimated opportunistic pathogens of the central nervous system? Desforges M, Le Coupanec A, Dubeau P, Bourgouin A, Lajoie L, Dubé M, Talbot PJ. Viruses. 2020;12:14.
    1. Evidence of the COVID-19 virus targeting the CNS: tissue distribution, host-virus Interaction, and proposed neurotropic mechanisms. Baig AM, Khaleeq A, Ali U, Syeda H. ACS Chem Neurosci. 2020;11:995–998.
    1. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study (Epub ahead of print) Lechien JR, Chiesa-Estomba CM, De Siati DR, et al. Eur Arch Otorhinolaryngol. 2020
    1. Non-neural expression of SARS-CoV-2 entry genes in the olfactory epithelium suggests mechanisms underlying anosmia in COVID-19 patients (PREPRINT) Brann DH, Tsukahara T, Weinreb C, et al. BioRxiv. 2020
    1. Current epidemiological and clinical features of COVID-19; a global perspective from China. Tu H, Tu S, Gao S, Shao A, Sheng J. J Infect. 2020;81:1–9.
    1. COVID-19: consider cytokine storm syndromes and immunosuppression. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ; HLH Across Speciality Collaboration, UK UK. Lancet. 2020;395:1033–1034.
    1. The cytokine storm in COVID- 19: an overview of the involvement of the chemokine/chemokine-receptor system. Coperchini F, Chiovato L, Croce L, Magri F, Rotondi M. Cytokine Growth Factor Rev. 2020;53:25–32.
    1. Nervous system involvement after infection with COVID-19 and other coronaviruses. Wu Y, Xu X, Chen Z, et al. Brain Behav Immun. 2020;87:18–22.
    1. COVID-19: pathogenesis, cytokine storm and therapeutic potential of interferons. Nile SH, Nile A, Qiu J, Li L, Jia X, Kai G. Cytokine Growth Factor Rev. 2020;53:66–70.
    1. Self-reported olfactory and taste disorders in patients with severe acute respiratory coronavirus 2 infection: a cross-sectional study (Epub ahead of print) Giacomelli A, Pezzati L, Conti F, et al. Clin Infect Dis. 2020
    1. Coincidence of COVID-19 epidemic and olfactory dysfunction outbreak (IN PRESS) Bagheri SH, Asghari AM, Farhadi M, et al. MedRxiv. 2020
    1. Loss of sense of smell as marker of COVID-19 infection. [May;2020 ];Hopkins C, Kumar N. 2020
    1. Clinical characteristics of 106 patients with neurological diseases and co-morbid coronavirus disease 2019: a retrospective study (PREPRINT) Yin R, Yang Z, Wei Y, et al. MedRxiv. 2020
    1. The olfactory nerve: a shortcut for influenza and other viral diseases into the central nervous system. van Riel D, Verdijk R, Kuiken T. J Pathol. 2015;235:277–287.
    1. Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2. Netland J, Meyerholz DK, Moore S, Cassell M, Perlman S. J Virol. 2008;82:7264–7275.
    1. Association of chemosensory dysfunction and Covid-19 in patients presenting with influenza-like symptoms (Epub ahead of print) Yan CH, Faraji F, Prajapati DP, Boone CE, DeConde AS. Int Forum Allergy Rhinol. 2020
    1. First case of 2019 novel coronavirus disease with encephalitis (IN PRESS) Xiang P, Xu XM, Gao LL, Wang HZ, Xiong HF, Li RH. ChinaXiv. 2020;202003:15.
    1. A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. Moriguchi T, Harii N, Goto J, et al. Int J Infect Dis. 2020;94:55–58.
    1. Encephalitis as a clinical manifestation of COVID-19 (Epub ahead of print) Ye M, Ren Y, Lv T. Brain Behav Immun. 2020
    1. Neurological complications of coronavirus disease (COVID-19): encephalopathy. Filatov A, Sharma P, Hindi F, Espinosa PS. Cureus. 2020;12:0.
    1. COVID-19-associated acute hemorrhagic necrotizing encephalopathy: CT and MRI features (Epub ahead of print) Poyiadji N, Shahin G, Noujaim D, Stone M, Patel S, Griffith B. Radiology. 2020
    1. Laboratory-confirmed respiratory infections as triggers for acute myocardial infarction and stroke: a self-controlled case series analysis of national linked datasets from Scotland. Warren-Gash C, Blackburn R, Whitaker H, McMenamin J, Hayward AC. Eur Respir J. 2018;51:1701794.
    1. COVID-19 and intracerebral haemorrhage: causative or coincidental? Sharifi-Razavi A, Karimi N, Rouhani N. New Microbes New Infect. 2020;35:100669.
    1. Acute myelitis after SARS-CoV-2 infection: a case report (PREPRINT) Zhao K, Huang J, Dai D, Feng Y, Liu L, Nie S. MedRxiv. 2020
    1. SARS-CoV-2 can induce brain and spine demyelinating lesions. Zanin L, Saraceno G, Panciani PP, Renisi G, Signorini L, Migliorati K, Fontanella MM. Acta Neurochir (Wien) 2020;162:1491–1494.
    1. Loss of smell or taste as the only symptom of COVID-19 (Article in English, Norwegian) Hjelmesæth J, Skaare D. Tidsskr Nor Laegeforen. 2020;140
    1. Hypogeusia as the initial presenting symptom of COVID-19. Melley LE, Bress E, Polan E. BMJ Case Rep. 2020;13:0.
    1. Anosmia and ageusia as primary symptoms of COVID-19 (Article in Danish) Haldrup M, Johansen MI, Fjaeldstad AW. Ugeskr Laeger. 2020;182:0.
    1. Population incidence of Guillain-Barré syndrome: a systematic review and meta-analysis. Sejvar JJ, Baughman AL, Wise M, Morgan OW. Neuroepidemiology. 2011;36:123–133.
    1. Guillain-Barré syndrome associated with SARS-CoV-2 infection: causality or coincidence? Zhao H, Shen D, Zhou H, Liu J, Chen S. Lancet Neurol. 2020;19:383–384.
    1. Guillain Barre syndrome associated with COVID-19 infection: a case report. Sedaghat Z, Karimi N. J Clin Neurosci. 2020;76:233–235.
    1. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Huang C, Wang Y, Li X, et al. Lancet. 2020;395:497–506.
    1. Guillain-Barré syndrome associated with SARS-CoV-2 (Epub ahead of print) Toscano G, Palmerini F, Ravaglia S, et al. N Engl J Med. 2020
    1. Guillain-Barré syndrome associated with SARS-CoV-2 infection. Virani A, Rabold E, Hanson T, et al. IDCases. 2020;20:0.
    1. Antecedent infections in Fisher syndrome: sources of variation in clinical characteristics. Koga M, Kishi M, Fukusako T, Ikuta N, Kato M, Kanda T. J Neurol. 2019;266:1655–1662.
    1. Miller Fisher syndrome and polyneuritis cranialis in COVID-19 (Epub ahead of print) Gutiérrez-Ortiz C, Méndez A, Rodrigo-Rey S, et al. Neurology. 2020
    1. Clinical characteristics of coronavirus disease 2019 in China. Guan WJ, Ni ZY, Hu Y, et al. N Engl J Med. 2020;382:1708–1720.
    1. Renin-angiotensin system: an old player with novel functions in skeletal muscle. Cabello-Verrugio C, Morales MG, Rivera JC, Cabrera D, Simon F. Med Res Rev. 2015;35:437–463.
    1. Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. Yang J, Zheng Y, Gou X, et al. Int J Infect Dis. 2020;94:91–95.

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