Nervous system involvement after infection with COVID-19 and other coronaviruses

Yeshun Wu, Xiaolin Xu, Zijun Chen, Jiahao Duan, Kenji Hashimoto, Ling Yang, Cunming Liu, Chun Yang, Yeshun Wu, Xiaolin Xu, Zijun Chen, Jiahao Duan, Kenji Hashimoto, Ling Yang, Cunming Liu, Chun Yang

Abstract

Viral infections have detrimental impacts on neurological functions, and even to cause severe neurological damage. Very recently, coronaviruses (CoV), especially severe acute respiratory syndrome CoV 2 (SARS-CoV-2), exhibit neurotropic properties and may also cause neurological diseases. It is reported that CoV can be found in the brain or cerebrospinal fluid. The pathobiology of these neuroinvasive viruses is still incompletely known, and it is therefore important to explore the impact of CoV infections on the nervous system. Here, we review the research into neurological complications in CoV infections and the possible mechanisms of damage to the nervous system.

Keywords: COVID-19; Coronaviruses infection; Mechanisms; Nervous system.

Copyright © 2020 Elsevier Inc. All rights reserved.

Figures

Fig. 1
Fig. 1
The mechanisms of coronaviruses infections and neurological damage caused by coronaviruses. The coronaviruses can cause nerve damage through direct infection pathways (blood circulation pathways and neuronal pathways), hypoxia, immune injury, ACE2, and other mechanisms. Meanwhile, the coronaviruses have detrimental effects to attack the lung tissue, and causes a series of lung lesions such as hypoxia. Furthermore, the coronaviruses can enter the nervous system directly through the olfactory nerve, and also enter the nervous system through blood circulation and neuronal pathways, resulting in neurological disorders. Ab: antibody; ACE2: angiotensin-converting enzyme 2; CSF: cerebrospinal fluid; ER: endoplasmic reticulum; TNF: tumor necrosis factor.
Fig. 2
Fig. 2
Pathogenesis of nervous system injury caused by coronaviruses. ACE2: angiotensin-converting enzyme 2; BBB: blood brain barrier; IL: interleukin; MHC: major histocompatibility complexes; SIRS: systemic inflammatory response syndrome.

References

    1. Abdennour L., Zeghal C., Deme M., Puybasset L. Interaction brain-lungs. Ann. Fr. Anesth. Reanim. 2012;31(6):e101–107.
    1. Al-Obaidi M.M.J., Bahadoran A., Wang S.M., Manikam R., Raju C.S., Sekaran S.D. Disruption of the blood brain barrier is vital property of neurotropic viral infection of the central nervous system. Acta Virol. 2018;62(1):16–27.
    1. Baig A.M., 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 Chem. Neurosci. 2020;11(7):995–998.
    1. Bohmwald K., Galvez N.M.S., Rios M., Kalergis A.M. Neurologic alterations due to respiratory virus infections. Front Cell Neurosci. 2018;12:386.
    1. Chen C., Zhang X.R., Ju Z.Y., He W.F. Advances in the research of cytokine storm mechanism induced by Corona Virus Disease 2019 and the corresponding immunotherapies. Zhonghua Shao Shang Za Zhi. 2020;36:E005.
    1. Corman V.M., Lienau J., Witzenrath M. Coronaviruses as the cause of respiratory infections. Internist (Berl) 2019;60(11):1136–1145.
    1. Desforges M., Le Coupanec A., Dubeau P., Bourgouin A., Lajoie L., Dube M. Human coronaviruses and other respiratory viruses: underestimated opportunistic pathogens of the central nervous system? Viruses. 2019;12(1)
    1. Dobbs M.R. Toxic encephalopathy. Semin. Neurol. 2011;31(2):184–193.
    1. Elkind M.S. Why now? Moving from stroke risk factors to stroke triggers. Curr. Opin. Neurol. 2007;20(1):51–57.
    1. Ellul M., Solomon T. Acute encephalitis - diagnosis and management. Clin. Med. (Lond) 2018;18(2):155–159.
    1. Fu, Y., Cheng, Y., Wu, Y., 2020. Understanding SARS-CoV-2-Mediated Inflammatory Responses: From Mechanisms to Potential Therapeutic Tools [published online ahead of print, 2020 Mar 3]. Virologica Sinica.
    1. Giacomelli, A., Pezzati, L., Conti, F., Bernacchia, D., Siano, M., Oreni, L., et al., 2020. Self-reported olfactory and taste disorders in SARS-CoV-2 patients: a cross-sectional study [published online ahead of print, 2020 Mar 26]. Clin Infect Dis ciaa330.
    1. Gu J., Gong E., Zhang B., Zheng J., Gao Z., Zhong Y. Multiple organ infection and the pathogenesis of SARS. J. Exp. Med. 2005;202(3):415–424.
    1. Guo Y.R., Cao Q.D., Hong Z.S., Tan Y.Y., Chen S.D., Jin H.J. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak - an update on the status. Mil. Med. Res. 2020;7(1):11.
    1. Hopkins, C., Kumar, N., 2020. Loss of sense of smell as marker of COVID-19 infection. Retrieved from .
    1. Kim J.E., Heo J.H., Kim H.O., Song S.H., Park S.S., Park T.H. Neurological complications during treatment of middle east respiratory syndrome. J. Clin. Neurol. 2017;13(3):227–233.
    1. Klein R.S., Garber C., Howard N. Infectious immunity in the central nervous system and brain function. Nat. Immunol. 2017;18(2):132–141.
    1. Koyuncu O.O., Hogue I.B., Enquist L.W. Virus infections in the nervous system. Cell Host Microbe. 2013;13(4):379–393.
    1. Lai K.N., Tsang K.W., Seto W.H., Ooi C.G. Clinical, Laboratory, and Radiologic Manifestation of SARS. Curr. Infect Dis. Rep. 2004;6(3):213–219.
    1. Leber A.L., Everhart K., Balada-Llasat J.M., Cullison J., Daly J., Holt S. Multicenter evaluation of biofire filmarray meningitis/encephalitis panel for detection of bacteria, viruses, and yeast in cerebrospinal fluid specimens. J. Clin. Microbiol. 2016;54(9):2251–2261.
    1. Li Y., Fu L., Gonzales D.M., Lavi E. Coronavirus neurovirulence correlates with the ability of the virus to induce proinflammatory cytokine signals from astrocytes and microglia. J. Virol. 2004;78(7):3398–3406.
    1. Mao L., Wang M.D., Chen S.H., He Q.W., Chang J., Hong C.D., et al., 2020. Neurological manifestations of hospitalized patients with COVID-19 in Wuhan, China: a retrospective case series study. MedRxiv 2020.02.22.20026500.
    1. Mehta P, McAuley D.F., Brown M., Sanchez E., Tattersall R.S., Manson J.J., 2020. COVID-19: consider cytokine storm syndromes and immunosuppression [published online ahead of print, 2020 Mar 16]. Lancet S0140-6736(20)30628-0.
    1. Michalicova A., Bhide K., Bhide M., Kovac A. How viruses infiltrate the central nervous system. Acta Virol. 2017;61(4):393–400.
    1. Miller A.J., Arnold A.C. The renin-angiotensin system in cardiovascular autonomic control: recent developments and clinical implications. Clin. Auton. Res. 2019;29(2):231–243.
    1. Mizuguchi M., Yamanouchi H., Ichiyama T., Shiomi M. Acute encephalopathy associated with influenza and other viral infections. Acta Neurol. Scand. Suppl. 2007;186:45–56.
    1. Mori I. Transolfactory neuroinvasion by viruses threatens the human brain. Acta Virol. 2015;59(4):338–349.
    1. Muhammad S., Haasbach E., Kotchourko M., Strigli A., Krenz A., Ridder D.A. Influenza virus infection aggravates stroke outcome. Stroke. 2011;42(3):783–791.
    1. Reinhold A.K., Rittner H.L. Barrier function in the peripheral and central nervous system-a review. Pflugers. Arch. 2017;469(1):123–134.
    1. Ryan W.M., 2020. There's a new symptom of coronavirus, doctors say: Sudden loss of smell or taste. Retrieved from .
    1. Saad M., Omrani A.S., Baig K., Bahloul A., Elzein F., Matin M.A. Clinical aspects and outcomes of 70 patients with Middle East respiratory syndrome coronavirus infection: a single-center experience in Saudi Arabia. Int. J. Infect. Dis. 2014;29:301–306.
    1. Schoeman D., Fielding B.C. Coronavirus envelope protein: current knowledge. Virol J. 2019;16(1):69.
    1. Soung A., Klein R.S. Viral encephalitis and neurologic diseases: focus on astrocytes. Trends Mol. Med. 2018;24(11):950–962.
    1. Swanson P.A., 2nd, McGavern D.B. Viral diseases of the central nervous system. Curr. Opin. Virol. 2015;11:44–54.
    1. Tauber S.C., Eiffert H., Bruck W., Nau R. Septic encephalopathy and septic encephalitis. Expert Rev. Anti. Infect. Ther. 2017;15(2):121–132.
    1. Thompson R. Pandemic potential of 2019-nCoV. Lancet. Infect. Dis. 2020;20(3):280.
    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. Turner A.J., Hiscox J.A., Hooper N.M. ACE2: from vasopeptidase to SARS virus receptor. Trends Pharmacol. Sci. 2004;25(6):291–294.
    1. Unni S.K., Ruzek D., Chhatbar C., Mishra R., Johri M.K., Singh S.K. Japanese encephalitis virus: from genome to infectome. Microbes Infect. 2011;13(4):312–321.
    1. Wan S.X., Yi Q.J., Fan S.B., Lv J.L., Zhang X.X., Guo L., et al., 2020. Characteristics of lymphocyte subsets and cytokines inperipheral blood of 123 hospitalized patients with 2019 novel coronavirus pneumonia (NCP). MedRxiv 2020.02.10.20021832.
    1. Wang, Y., Wang, Y., Chen, Y., Qin, Q., 2020. Unique epidemiological and clinical features of the emerging 2019 novel coronavirus pneumonia (COVID-19) implicate special control measures [published online ahead of print, 2020 Mar 5]. J Med Virol.
    1. Warren-Gash C., Blackburn R., Whitaker H., McMenamin J., Hayward A.C. Laboratory-confirmed respiratory infections as triggers for acute myocardial infarction and stroke: a self-controlled case series analysis of national linked datasets from Scotland. Eur. Respir. J. 2018;51(3)
    1. WHO MERS-Cov Research, G., 2013. State of Knowledge and Data Gaps of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Humans. PLoS Curr 5.
    1. Wrapp D., Wang N., Corbett K.S., Goldsmith J.A., Hsieh C.L., Abiona O. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020;367(6483):1260–1263.
    1. Wright, E.J., Brew, B.J., Wesselingh, S.L., 2008. Pathogenesis and diagnosis of viral infections of the nervous system. Neurol Clin 26 (3), 617-633, vii.
    1. Wu A., Peng Y., Huang B., Ding X., Wang X., Niu P. Genome composition and divergence of the novel coronavirus (2019-nCoV) originating in China. Cell Host Microbe. 2020;27(3):325–328.
    1. Wuthrich C., Batson S., Koralnik I.J. Lack of Major Histocompatibility complex class I upregulation and restrictive infection by JC virus hamper detection of neurons by T lymphocytes in the central nervous system. J. Neuropathol. Exp. Neurol. 2015;74(8):791–803.
    1. Xiang P., Xu X.M., Gao L.L., Wang H.Z., Xiong H.F., Li R.H. First case of 2019 novel coronavirus disease with Encephalitis. ChinaXiv. 2020;T202003:00015.
    1. Xu, Z., Shi, L., Wang, Y., Zhang, J., Huang, L., Zhang, C., et al., 2020. Pathological findings of COVID-19 associated with acute respiratory distress syndrome [published online ahead of print, 2020 Feb 18]. Lancet Respir Med.
    1. Yang P., Gu H., Zhao Z., Wang W., Cao B., Lai C. Angiotensin-converting enzyme 2 (ACE2) mediates influenza H7N9 virus-induced acute lung injury. Sci. Rep. 2014;4:7027.
    1. Yin, C.H., Wang, C., Tang, Z., Wen, Y., Zhang, S.W., Wang, B.E., 2004. [Clinical analysis of multiple organ dysfunction syndrome in patients suffering from SARS]. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 16 (11), 646-650.
    1. Young G.B. Encephalopathy of infection and systemic inflammation. J. Clin. Neurophysiol. 2013;30(5):454–461.
    1. Zhang, Q.L., Ding, Y.Q., Hou, J.L., He, L., Huang, Z.X., Wang, H.J., et al., 2003. [Detection of severe acute respiratory syndrome (SARS)-associated coronavirus RNA in autopsy tissues with in situ hybridization]. Di Yi Jun Yi Da Xue Xue Bao 23 (11), 1125-1127.

Source: PubMed

赞助者和合作者

医疗条件

药物干预

3
订阅