CC BY-NC-ND 4.0 · J Neuroanaesth Crit Care 2020; 07(02): 062-066
DOI: 10.1055/s-0040-1713017
Review Article

Spectrum of Neurologic Complications in COVID-19: An Evidence-Based Review

Soumya Sarkar
1   Department of Anaesthesia, Pain Medicine and Critical Care, All India Institute of Medical Sciences, New Delhi, India
,
Puneet Khanna
1   Department of Anaesthesia, Pain Medicine and Critical Care, All India Institute of Medical Sciences, New Delhi, India
,
Surya K. Dube
2   Department of Neuroanaesthesiology, All India Institute of Medical Sciences, New Delhi, India
› Author Affiliations

Abstract

The world is facing an unprecedented crisis due to the pandemic of current coronavirus disease 2019 (COVID-19). Coronavirus (CoVs) infections not only are always involving the respiratory tract but also possess significant neuroinvasive potential. The literature regarding neuropathogenic potential of human CoVs is sparse. Thus, the number of COVID-19–related neurologic complications is likely to be underestimated. Awareness regarding the possible spectrum of neurologic complications is essential for therapeutic decision-making and individualized treatment and thereby limiting the COVID-19–related morbidity and mortality. The aim of this review is to address the neurologic manifestations of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).



Publication History

Article published online:
11 June 2020

© .

Thieme Medical and Scientific Publishers Private Ltd.
A-12, Second Floor, Sector -2, NOIDA -201301, India

 
  • References

  • 1 Lu R, Zhao X, Li J. et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 2020; 395 (10224) 565-574
  • 2 Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The species severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol 2020; 5 (04) 536-544
  • 3 Rothan HA, Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun 2020; 109 (February) 102433
  • 4 Pan Y, Zhang D, Yang P, Poon LL, Wang Q. Viral load of SARS-CoV-2 in clinical samples. Lancet Infect Dis 2020; 20 (04) 411-412
  • 5 Zou L, Ruan F, Huang M. et al. SARS-CoV-2 viral load in upper respiratory specimens of infected patients. N Engl J Med 2020; 382 (12) 1177-1179
  • 6 Bai Y, Yao L, Wei T. et al. Presumed asymptomatic carrier transmission of COVID-19. JAMA 2020; 323 (14) 1406-1407
  • 7 Li Q, Guan X, Wu P. et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med 2020; 382 (13) 1199-1207
  • 8 Tsai LK, Hsieh ST, Chao CC. et al. Neuromuscular disorders in severe acute respiratory syndrome. Arch Neurol 2004; 61 (11) 1669-1673
  • 9 Zochodne DW. SARS, SIRS, and neurological disease. Arch Neurol 2004; 61 (11) 1647-1648
  • 10 Donoghue M, Hsieh F, Baronas E. et al. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ Res 2000; 87 (05) E1-E9
  • 11 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
  • 12 Xia H, Lazartigues E. Angiotensin-converting enzyme 2 in the brain: properties and future directions. J Neurochem 2008; 107 (06) 1482-1494
  • 13 Hamming I, Timens W, Bulthuis ML. Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol 2004; 203 (02) 631-637
  • 14 Ou X, Liu Y, Lei X. et al. Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat Commun 2020; 11 (01) 1620
  • 15 Podvin S, Wojnicz A, Hook V. Human brain gene expression profiles of the cathepsin V and cathepsin L cysteine proteases, with the PC1/3 and PC2 serine proteases, involved in neuropeptide production. Heliyon 2018; 4 (07) e00673
  • 16 Wang K, Chen W, Zhou Y-S. SARSCoV-2 invades host cells via a novel route: CD147-spike protein. bioRxiv 2020; DOI: 10.1101/2020.03.14.988345.
  • 17 Catepsin L. The Human Protein Atlas. Available at: https://www.proteinatlas.org/ENSG00000172270-BSG/brain. Accessed May 20, 2020
  • 18 Ding Y, He L, Zhang Q. et al. Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways. J Pathol 2004; 203 (02) 622-630
  • 19 Gu J, Gong E, Zhang B. et al. Multiple organ infection and the pathogenesis of SARS. J Exp Med 2005; 202 (03) 415-424
  • 20 Xu J, Zhong S, Liu J. et al. Detection of severe acute respiratory syndrome coronavirus in the brain: potential role of the chemokine mig in pathogenesis. Clin Infect Dis 2005; 41 (08) 1089-1096
  • 21 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) 7264-7275
  • 22 Li K, Wohlford-Lenane C, Perlman S. et al. Middle East respiratory syndrome coronavirus causes multiple organ damage and lethal disease in mice transgenic for human dipeptidyl peptidase 4. J Infect Dis 2016; 213 (05) 712-722
  • 23 Li YC, Bai WZ, Hirano N, Hayashida T, Hashikawa T. Coronavirus infection of rat dorsal root ganglia: ultrastructural characterization of viral replication, transfer, and the early response of satellite cells. Virus Res 2012; 163 (02) 628-635
  • 24 Li YC, Bai WZ, Hirano N. et al. Neurotropic virus tracing suggests a membranous-coating-mediated mechanism for transsynaptic communication. J Comp Neurol 2013; 521 (01) 203-212
  • 25 Andries K, Pensaert MB. Immunofluorescence studies on the pathogenesis of hemagglutinating encephalomyelitis virus infection in pigs after oronasal inoculation. Am J Vet Res 1980; 41 (09) 1372-1378
  • 26 Matsuda K, Park CH, Sunden Y. et al. The vagus nerve is one route of transneural invasion for intranasally inoculated influenza a virus in mice. Vet Pathol 2004; 41 (02) 101-107
  • 27 Hadziefendic S, Haxhiu MA. CNS innervation of vagal preganglionic neurons controlling peripheral airways: a transneuronal labeling study using pseudorabies virus. J Auton Nerv Syst 1999; 76 (2-3) 135-145
  • 28 Dubé M, Le Coupanec A, Wong AHM, Rini JM, Desforges M, Talbot PJ. Axonal transport enables neuron-to-neuron propagation of human coronavirus OC43. J Virol 2018; 92 (17) e00404-e00418
  • 29 Wong SH, Lui RN, Sung JJ. Covid-19 and the digestive system. J Gastroenterol Hepatol 2020; DOI: 10.1111/jgh.15047.
  • 30 Boehme KW, Lai CM, Dermody TS. Mechanisms of reovirus bloodstream dissemination. Adv Virus Res 2013; 87: 1-35
  • 31 Alenquer M, Amorim MJ. Exosome biogenesis, regulation, and function in viral infection. Viruses 2015; 7 (09) 5066-5083
  • 32 Perlman S, Dandekar AA. Immunopathogenesis of coronavirus infections: implications for SARS. Nat Rev Immunol 2005; 5 (12) 917-927
  • 33 Louveau A, Herz J, Alme MN. et al. CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature. Nat Neurosci 2018; 21 (10) 1380-1391
  • 34 Glass WG, Subbarao K, Murphy B, Murphy PM. Mechanisms of host defense following severe acute respiratory syndrome-coronavirus (SARS-CoV) pulmonary infection of mice. J Immunol 2004; 173 (06) 4030-4039
  • 35 Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA 2020; 323 (13) 1239-1242
  • 36 Chen N, Zhou M, Dong X. et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020; 395 (10223) 507-513
  • 37 Helms J, Kremer S, Merdji H. et al. Neurologic features in severe SARS-CoV-2 infection. N Engl J Med 2020; DOI: 10.1056/NEJMc2008597.
  • 38 Mao L, Jin H, Wang M. et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol 2020; DOI: 10.1001/jamaneurol.2020.1127.
  • 39 Baig AM, Khaleeq A, Ali U, Syeda H. et al. Evidence of the COVID-19 virus targeting the CNS: tissue distribution, host-virus interaction, and proposed neurotropic mechanisms. ACS Chem Neurosci 2020; 11 (07) 995-998
  • 40 Zhou F, Yu T, Du R. et al. Articles Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020; 6736 (20) 1-9
  • 41 Desforges M, Le Coupanec A, Dubeau P. et al. Human coronaviruses and other respiratory viruses: underestimated opportunistic pathogens of the central nervous system?. Viruses 2019; 12 (01) 14
  • 42 Nikolich-Zugich J, Knox KS, Rios CT, Natt B, Bhattacharya D, Fain MJ. SARS-CoV-2 and COVID-19 in older adults: what we may expect regarding pathogenesis, immune responses, and outcomes. Geroscience 2020; DOI: 10.1007/s11357-020-00186-0.
  • 43 Erta M, Quintana A, Hidalgo J. Interleukin-6, a major cytokine in the central nervous system. Int J Biol Sci 2012; 8 (09) 1254-1266
  • 44 Siami S, Annane D, Sharshar T. The encephalopathy in sepsis. Crit Care Clin 2008; 24 (01) 67-82
  • 45 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; DOI: 10.1148/radiol.2020201187.
  • 46 Giacomelli A, Pezzati L, Conti F. et al. Self-reported olfactory and taste disorders in SARS-CoV-2 patients: a cross-sectional study. Clin Infect Dis 2020; DOI: 10.1093/cid/ciaa330.
  • 47 Fazzini E, Fleming J, Fahn S. Cerebrospinal fluid antibodies to coronavirus in patients with Parkinson’s disease. Mov Disord 1992; 7 (02) 153-158
  • 48 Yeh EA, Collins A, Cohen ME, Duffner PK, Faden H. Detection of coronavirus in the central nervous system of a child with acute disseminated encephalomyelitis. Pediatrics 2004; 113 (1 Pt 1) e73-e76
  • 49 Murray RS, Brown B, Brian D, Cabirac GF. Detection of coronavirus RNA and antigen in multiple sclerosis brain. Ann Neurol 1992; 31 (05) 525-533
  • 50 Stewart JN, Mounir S, Talbot PJ. Human coronavirus gene expression in the brains of multiple sclerosis patients. Virology 1992; 191 (01) 502-505
  • 51 Yeh EA, Collins A, Cohen ME, Duffner PK, Faden H. Detection of coronavirus in the central nervous system of a child with acute disseminated encephalomyelitis. Pediatrics 2004; 113 (1 Pt 1) e73-e76
  • 52 Cristallo A, Gambaro F, Biamonti G, Ferrante P, Battaglia M, Cereda PM. Human coronavirus polyadenylated RNA sequences in cerebrospinal fluid from multiple sclerosis patients. New Microbiol 1997; 20 (02) 105-114
  • 53 Algahtani H, Subahi A, Shirah B. Neurological complications of Middle East respiratory syndrome coronavirus: a report of two cases and review of the literature. Case Rep Neurol Med 2016; 2016: 3502683
  • 54 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 (05) 383-384
  • 55 Chew FT, Ong SY, Hew CL. Severe acute respiratory syndrome coronavirus and viral mimicry. Lancet 2003; 361 (9374) 2081
  • 56 Galougahi MK, Ghorbani J, Bakhshayeshkaram M, Naeini AS, Haseli S. Olfactory bulb magnetic resonance imaging in SARS-CoV-2-induced anosmia: the first report. Acad Radiol 2020; DOI: 10.1016/j.acra.2020.04.002.
  • 57 Liverpool COVID-19 Interactions [Internet]. Covid19-druginteractions.org. 2020 [cited 15 May 2020]. Available at: http://www.covid19-druginteractions.org/. Accessed May 20, 2020
  • 58 Shen C, Wang Z, Zhao F. et al. Treatment of 5 critically ill patients with COVID-19 with convalescent plasma. JAMA 2020; 323 (16) 1582-1589
  • 59 Chinese Clinical Trial Registry. A multicenter, randomized controlled trial for the efficacy and safety of tocilizumab in the treatment of new coronavirus pneumonia (COVID-19). Available at: http://www.chictr.org.cn/showprojen.aspx?proj=49409. Accessed May 20. 2020
  • 60 National Multiple Sclerosis Society. Disease Modifying Treatment Guidelines for Coronavirus (COVID-19). National Multiple Sclerosis Society. Available at: https://www.nationalmssociety.org/What-you-need-to-know-about-Coronavirus-(COVID-19)/DMT-Guidelines-for-Coronavirus-(COVID-19)-and. Published 2020. Accessed April 15, 2020
  • 61 Association of British Neurologists. Association of British Neurologists Guidance on COVID-19 for people with neurological conditions, their doctors and carers. 2020. Available at: https://cdn.ymaws.com/www.theabn.org/resource/collection/6750BAE6-4CBC-4DDB-A684-116E03BFE634/ABN_Neurology_COVID-19_Guidance_22.3.20.pdf. Accessed May 20, 2020