Neurological manifestations of COVID-19 and other coronavirus infections: A systematic review

V Montalvan, J Lee, T Bueso, J De Toledo, K Rivas, V Montalvan, J Lee, T Bueso, J De Toledo, K Rivas

Abstract

Background: Increasing research reports neurological manifestations of COVID-19 patients. SARS-CoV-2 shares homology with other human coronaviruses that have also had nervous system involvement.

Objective: To review the neurological aspects of SARS-cov2 and other coronavirus, including transmission pathways, mechanisms of invasion into the nervous system, and mechanisms of neurological disease.

Methods: We conducted a systematic review of articles in PubMed, SCOPUS and EMBASE data bases. Reviewed evidence is presented in sections of this manuscript which includes pathogenesis, neuro-invasion, encephalitis, Guillain-Barré, ADEM, multiple sclerosis, polyneuropathy, and cerebrovascular disease.

Results: A total 67 studies were included in the final analysis of experimental studies, case reports, series of cases, cohort studies, and systematic reviews related to neurological manifestations of SARS- CoV-2 and other human coronavirus infections. The SARS-CoV-2 receptor is expressed in the nervous system. Common reported symptoms included hyposmia, headaches, weakness, altered consciousness. Encephalitis, demyelination, neuropathy, and stroke have been associated with COVID-19. Infection through the cribriform plate and olfactory bulb and dissemination through trans-synaptic transfer are some of the mechanisms proposed. Invasion of the medullary cardiorespiratory center by SARS-CoV-2 may contribute to the refractory respiratory failure observed in critically-ill COVID-19 patients.

Conclusion: An increasing number of reports of COVID-19 patients with neurological disorders add to emergent experimental models with neuro-invasion as a reasonable concern that SARS-CoV-2 is a new neuropathogen. How it may cause acute and chronic neurologic disorders needs to be clarified in future research.

Keywords: COVID-19; Coronavirus; Encephalitis; Neurological manifestations; SARS-CoV-2.

Copyright © 2020 Elsevier B.V. All rights reserved.

Figures

Fig. 1
Fig. 1
MRI sequence of images from a patient with suspected COVID-19 associated acute necrotizing hemorrhagic encephalopathy. A. T2 FLAIR image with bilateral thalamic hyperintensity and surrounding edema. B. T2 image revealing bilateral thalamic hyperintensity. C. SWI reveals evidence of bilateral thalamic hemorrhage. D. T2 image with post contrast ring enhancement lesions in bilateral thalami. 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. doi:https://doi.org/10.1148/radiol.2020201187. Copyright Radiological Society of North America 2020.

References

    1. Cucinotta D., Vanelli M. WHO declares COVID-19 a pandemic. Acta Biomed. 2020;91(1):157–160.
    1. Velavan T.P., Meyer C.G. The COVID-19 epidemic. Trop. Med. Int. Health. 2020;25(3):278–280.
    1. Dong E., Du H., Gardner L. An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect. Dis. 2020
    1. Li Y.C., Bai W.Z., 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. Wang D. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020
    1. Mao L. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 2020
    1. Baig A.M. Evidence of the COVID-19 virus targeting the CNS: tissue distribution, host-virus interaction, and proposed neurotropic mechanisms. ACS Chem. Neurosci. 2020;11(7):995–998.
    1. Netland J. 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.
    1. Ding Y. 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(2):622–630.
    1. Li K. 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(5):712–722.
    1. Walls A.C. Structure, function, and Antigenicity of the SARS-CoV-2 spike glycoprotein. Cell. 2020
    1. Rothan H.A., Byrareddy S.N. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J. Autoimmun. 2020:102433.
    1. Wan Y. Receptor recognition by the novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS coronavirus. J. Virol. 2020;94(7):e00127–20.
    1. Doobay M.F. Differential expression of neuronal ACE2 in transgenic mice with overexpression of the brain renin-angiotensin system. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2007;292(1):R373–81.
    1. Palasca O. 2018. TISSUES 2.0: An Integrative Web Resource on Mammalian Tissue Expression. Database (Oxford) 2018.
    1. McCray P.B., Jr. Lethal infection of K18-hACE2 mice infected with severe acute respiratory syndrome coronavirus. J. Virol. 2007;81(2):813–821.
    1. Huang C. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506.
    1. Chen N. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507–513.
    1. Xu X.W. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series. BMJ. 2020;368:m606.
    1. Sun N. Activation of astrocytes in the spinal cord of mice chronically infected with a neurotropic coronavirus. Virology. 1995;213(2):482–493.
    1. Houtman J.J., Hinze H.C., Fleming J.O. Demyelination induced by murine coronavirus JHM infection of congenitally immunodeficient mice. In: Talbot P.J., Levy G.A., editors. Corona- and Related Viruses: Current Concepts in Molecular Biology and Pathogenesis. Springer US; Boston, MA: 1995. pp. 159–163.
    1. Wege H. Immunopathological aspects of coronavirus infections. Semin. Immunopathol. 1995;17(2–3):133–148.
    1. Arbour N. Persistent infection of human oligodendrocytic and neuroglial cell lines by human coronavirus 229E. J. Virol. 1999;73(4):3326–3337.
    1. Duffy L., O’Reilly S.C. Toll-like receptors in the pathogenesis of autoimmune diseases: recent and emerging translational developments. Immunotargets Ther. 2016;5:69–80.
    1. Arbour N. Neuroinvasion by human respiratory coronaviruses. J. Virol. 2000;74(19):8913–8921.
    1. Murray R.S. Detection of coronavirus RNA and antigen in multiple sclerosis brain. Ann. Neurol. 1992;31(5):525–533.
    1. Stewart J.N., Mounir S., Talbot P.J. Human coronavirus gene expression in the brains of multiple sclerosis patients. Virology. 1992;191(1):502–505.
    1. Gerna G. Human respiratory coronavirus HKU1 versus other coronavirus infections in Italian hospitalised patients. J. Clin. Virol. 2007;38(3):244–250.
    1. Libbey J.E., Lane T.E., Fujinami R.S. Axonal pathology and demyelination in viral models of multiple sclerosis. Discov. Med. 2014;18(97):79–89.
    1. Boucher A. Long-term human coronavirus-myelin cross-reactive T-cell clones derived from multiple sclerosis patients. Clin. Immunol. 2007;123(3):258–267.
    1. Wu G.F., Perlman S. Macrophage infiltration, but not apoptosis, is correlated with immune-mediated demyelination following murine infection with a neurotropic coronavirus. J. Virol. 1999;73(10):8771–8780.
    1. Savarin C. Memory CD4+ T-cell-mediated protection from lethal coronavirus encephalomyelitis. J. Virol. 2008;82(24):12432–12440.
    1. Fehr A.R., Perlman S. Coronaviruses: an overview of their replication and pathogenesis. Methods Mol. Biol. 2015;1282:1–23.
    1. Yeh E.A. Detection of coronavirus in the central nervous system of a child with acute disseminated encephalomyelitis. Pediatrics. 2004;113(1 Pt 1):e73–6.
    1. 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.
    1. Kim J.E. Neurological complications during treatment of middle east respiratory syndrome. J. Clin. Neurol. 2017;13(3):227–233.
    1. Tsai L.K., Hsieh S.T., Chang Y.C. Neurological manifestations in severe acute respiratory syndrome. Acta Neurol. Taiwan. 2005;14(3):113–119.
    1. Tsai L.K. Neuromuscular disorders in severe acute respiratory syndrome. Arch. Neurol. 2004;61(11):1669–1673.
    1. Camdessanche J.P. COVID-19 may induce Guillain-Barre syndrome. Rev Neurol (Paris) 2020
    1. Turgay C. A rare cause of acute flaccid paralysis: human coronaviruses. J. Pediatr. Neurosci. 2015;10(3):280–281.
    1. Sedaghat Z., Karimi N. Guillain Barre syndrome associated with COVID-19 infection: a case report. J. Clin. Neurosci. 2020
    1. El Otmani H. Covid-19 and Guillain-Barre syndrome: more than a coincidence! Rev Neurol (Paris) 2020
    1. Zhao H. Guillain-Barre syndrome associated with SARS-CoV-2 infection: causality or coincidence? Lancet Neurol. 2020;19(5):383–384.
    1. Toscano G. Guillain-barre syndrome associated with SARS-CoV-2. N. Engl. J. Med. 2020
    1. Padroni M. Guillain-Barre syndrome following COVID-19: new infection, old complication? J. Neurol. 2020
    1. Alberti P. Guillain-Barre syndrome related to COVID-19 infection. Neurol. Neuroimmunol. Neuroinflamm. 2020;7(4)
    1. Virani A. Guillain-Barre Syndrome associated with SARS-CoV-2 infection. IDCases. 2020:e00771.
    1. Jacomy H. Human coronavirus OC43 infection induces chronic encephalitis leading to disabilities in BALB/C mice. Virology. 2006;349(2):335–346.
    1. Morfopoulou S. Human coronavirus OC43 associated with fatal encephalitis. N. Engl. J. Med. 2016;375(5):497–498.
    1. Poyiadji N. COVID-19-associated acute hemorrhagic necrotizing encephalopathy: CT and MRI features. Radiology. 2020:201187.
    1. Moriguchi T. A first case of Meningitis/Encephalitis associated with SARS-Coronavirus-2. Int. J. Infect. Dis. 2020
    1. Umapathi T. Large artery ischaemic stroke in severe acute respiratory syndrome (SARS) J. Neurol. 2004;251(10):1227–1231.
    1. Lew T.W. Acute respiratory distress syndrome in critically ill patients with severe acute respiratory syndrome. JAMA. 2003;290(3):374–380.
    1. Avula A. COVID-19 presenting as stroke. Brain Behav. Immun. 2020
    1. Guo J. Coronavirus disease 2019 (COVID-19) and cardiovascular disease: a viewpoint on the potential influence of angiotensin-converting enzyme Inhibitors/Angiotensin receptor blockers on onset and severity of severe acute respiratory syndrome coronavirus 2 infection. J. Am. Heart Assoc. 2020;9(7):e016219.
    1. Panigada M. Hypercoagulability of COVID-19 patients in intensive care unit. A report of thromboelastography findings and other parameters of hemostasis. J. Thromb. Haemost. 2020
    1. Yang J. Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19) infection: a systematic review and meta-analysis. Int. J. Infect. Dis. 2020
    1. Zhou F. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054–1062.
    1. Oxley T.J. Large-vessel stroke as a presenting feature of Covid-19 in the young. N. Engl. J. Med. 2020:e60.
    1. Powers W.J. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2019;50(12):e344–e418.
    1. Stainsby B., Howitt S., Porr J. Neuromusculoskeletal disorders following SARS: a case series. J. Can. Chiropr. Assoc. 2011;55(1):32–39.
    1. Lau K.K. Possible central nervous system infection by SARS coronavirus. Emerg Infect Dis. 2004;10(2):342–344.
    1. Arabi Y.M. Severe neurologic syndrome associated with Middle East respiratory syndrome corona virus (MERS-CoV) Infection. 2015;43(4):495–501.
    1. Lachance C. Involvement of aminopeptidase N (CD13) in infection of human neural cells by human coronavirus 229E. J. Virol. 1998;72(8):6511–6519.
    1. Niu J. Non-invasive bioluminescence imaging of HCoV-OC43 infection and therapy in the central nervous system of live mice. Antiviral Res. 2020;173:104646.
    1. Nilsson A. Fatal encephalitis associated with coronavirus OC43 in an immunocompromised child. Infect Dis (Lond) 2020:1–4.
    1. Dube M. Axonal transport enables neuron-to-neuron propagation of human coronavirus OC43. J. Virol. 2018;92(17)
    1. Xu J. Detection of severe acute respiratory syndrome coronavirus in the brain: potential role of the chemokine mig in pathogenesis. Clin. Infect. Dis. 2005;41(8):1089–1096.
    1. Gu J. Multiple organ infection and the pathogenesis of SARS. J. Exp. Med. 2005;202(3):415–424.
    1. Alsaad K.O. Histopathology of Middle East respiratory syndrome coronovirus (MERS-CoV) infection - clinicopathological and ultrastructural study. Histopathology. 2018;72(3):516–524.

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