Top

Published in:

01-06-2020 | Coronavirus | Review

COVID-19 virus may have neuroinvasive potential and cause neurological complications: a perspective review

Authors: Ali Sepehrinezhad, Ali Shahbazi, Sajad Sahab Negah

Published in: Journal of NeuroVirology | Issue 3/2020

Abstract

Coronavirus disease 2019 (COVID-19) was reported at the end of 2019 in China for the first time and has rapidly spread throughout the world as a pandemic. Since COVID-19 causes mild to severe acute respiratory syndrome, most studies in this field have only focused on different aspects of pathogenesis in the respiratory system. However, evidence suggests that COVID-19 may affect the central nervous system (CNS). Given the outbreak of COVID-19, it seems necessary to perform investigations on the possible neurological complications in patients who suffered from COVID-19. Here, we reviewed the evidence of the neuroinvasive potential of coronaviruses and discussed the possible pathogenic processes in CNS infection by COVID-19 to provide a precise insight for future studies.

Algahtani H, Subahi A, Shirah B (2016) Neurological complications of Middle East respiratory syndrome coronavirus: a report of two cases and review of the literature. Case Rep Neurol Med 2016:3502683–3502686. https://doi.org/10.1155/2016/3502683 CrossRefPubMedPubMedCentral

Arbour N, Ekandé S, Côté G, Lachance C, Chagnon F, Tardieu M et al (1999) Persistent infection of human oligodendrocytic and neuroglial cell lines by human coronavirus 229E. J Virol 73(4):3326–3337CrossRefPubMedPubMedCentral

Arbour N, Day R, Newcombe J, Talbot PJ (2000) Neuroinvasion by human respiratory coronaviruses. J Virol 74(19):8913–8921. https://doi.org/10.1128/jvi.74.19.8913-8921.2000 CrossRefPubMedPubMedCentral

Baig AM, Khaleeq A, Ali U, Syeda H (2020) Evidence of the COVID-19 virus targeting the CNS: tissue distribution, host-virus interaction, and proposed neurotropic mechanisms. ACS chemical neuroscience

Bonavia A, Arbour N, Yong VW, Talbot PJ (1997) Infection of primary cultures of human neural cells by human coronaviruses 229E and OC43. J Virol 71(1):800–806CrossRefPubMedPubMedCentral

Butler N, Pewe L, Trandem K, Perlman S (2006) Murine encephalitis caused by HCoV-OC43, a human coronavirus with broad species specificity, is partly immune-mediated. Virology 347(2):410–421. https://doi.org/10.1016/j.virol.2005.11.044 CrossRefPubMed

Cabirac GF, Soike KF, Zhang JY, Hoel K, Butunoi C, Cai GY, Johnson S, Murray RS (1994) Entry of coronavirus into primate CNS following peripheral infection. Microb Pathog 16(5):349–357. https://doi.org/10.1006/mpat.1994.1035 CrossRefPubMedPubMedCentral

Cavanagh D (2005) Coronaviruses in poultry and other birds. Avian Pathol 34(6):439–448CrossRefPubMed

Chan JF, Chan KH, Choi GK, To KK, Tse H, Cai JP et al (2013) Differential cell line susceptibility to the emerging novel human betacoronavirus 2c EMC/2012: implications for disease pathogenesis and clinical manifestation. J Infect Dis 207(11):1743–1752. https://doi.org/10.1093/infdis/jit123 CrossRefPubMed

Chan-Yeung M, Xu RH (2003) SARS: epidemiology. Respirology 8(Suppl):S9–S14. https://doi.org/10.1046/j.1440-1843.2003.00518.x CrossRefPubMedPubMedCentral

Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J', Yu T, Zhang X, Zhang L (2020) Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 395(10223):507–513. https://doi.org/10.1016/S0140-6736(20)30211-7 CrossRefPubMedPubMedCentral

Collins AR (2002) In vitro detection of apoptosis in monocytes/macrophages infected with human coronavirus. Clin Diagn Lab Immunol 9(6):1392–1395. https://doi.org/10.1128/cdli.9.6.1392-1395.2002 CrossRefPubMedPubMedCentral

Desforges M, Miletti TC, Gagnon M, Talbot PJ (2007) Activation of human monocytes after infection by human coronavirus 229E. Virus Res 130(1–2):228–240. https://doi.org/10.1016/j.virusres.2007.06.016 CrossRefPubMedPubMedCentral

Desforges M, Favreau DJ, Brison É, Desjardins J, Meessen-Pinard M, Jacomy H, Talbot PJ (2013) Human coronaviruses: respiratory pathogens revisited as infectious neuroinvasive, neurotropic, and neurovirulent agents neuroviral infections (pp. 112-141): CRC press

Desforges M, Le Coupanec A, Brison E, Meessen-Pinard M, Talbot PJ (2014) Neuroinvasive and neurotropic human respiratory coronaviruses: potential neurovirulent agents in humans. Adv Exp Med Biol 807:75–96. https://doi.org/10.1007/978-81-322-1777-0_6 CrossRefPubMedPubMedCentral

Edwards JA, Denis F, Talbot PJ (2000) Activation of glial cells by human coronavirus OC43 infection. J Neuroimmunol 108(1):73–81. https://doi.org/10.1016/S0165-5728(00)00266-6 CrossRefPubMedPubMedCentral

Filatov A, Sharma P, Hindi F, Espinosa PS (2020) Neurological complications of coronavirus disease (covid-19): encephalopathy. Cureus 12(3):e7352PubMedPubMedCentral

Gu J, Gong E, Zhang B, Zheng J, Gao Z, Zhong Y, Zou W, Zhan J, Wang S, Xie Z, Zhuang H, Wu B, Zhong H, Shao H, Fang W, Gao D, Pei F, Li X, He Z, Xu D, Shi X, Anderson VM, Leong AS (2005) Multiple organ infection and the pathogenesis of SARS. J Exp Med 202(3):415–424. https://doi.org/10.1084/jem.20050828 CrossRefPubMedPubMedCentral

Guan W-j, Ni Z-y, Hu Y, Liang W-h, Ou C-q, He J-x et al (2020) Clinical characteristics of 2019 novel coronavirus infection in China. medRxiv, 2020.2002.2006.20020974. https://doi.org/10.1101/2020.02.06.20020974

Guo Y, Korteweg C, McNutt MA, Gu J (2008) Pathogenetic mechanisms of severe acute respiratory syndrome. Virus Res 133(1):4–12. https://doi.org/10.1016/j.virusres.2007.01.022 CrossRefPubMed

Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B (2020) Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395(10223):497–506. https://doi.org/10.1016/S0140-6736(20)30183-5 CrossRefPubMedPubMedCentral

Huaxia (2020) Beijing hospital confirms nervous system infections by novel coronavirus. Available via DIALOG.http://www.xinhuanet.com/english/2020-03/05/c_138846529.htm. Accessed 5 Mar 2020

Jacomy H, Talbot PJ (2003) Vacuolating encephalitis in mice infected by human coronavirus OC43. Virology 315(1):20–33. https://doi.org/10.1016/s0042-6822(03)00323-4 CrossRefPubMed

Jacomy H, Fragoso G, Almazan G, Mushynski WE, Talbot PJ (2006) Human coronavirus OC43 infection induces chronic encephalitis leading to disabilities in BALB/C mice. Virology 349(2):335–346. https://doi.org/10.1016/j.virol.2006.01.049 CrossRefPubMed

Jevšnik M, Steyer A, Pokorn M, Mrvič T, Grosek Š, Strle F, Lusa L, Petrovec M (2016) The role of human coronaviruses in children hospitalized for acute bronchiolitis, acute gastroenteritis, and febrile seizures: a 2-year prospective study. PLoS One 11(5):e0155555. https://doi.org/10.1371/journal.pone.0155555 CrossRefPubMedPubMedCentral

Jiang F, Deng L, Zhang L, Cai Y, Cheung CW, Xia Z (2020) Review of the clinical characteristics of coronavirus disease 2019 (COVID-19). J Gen Intern Med. https://doi.org/10.1007/s11606-020-05762-w

Kim JE, Heo JH, Kim HO, Song SH, Park SS, Park TH, Ahn JY, Kim MK, Choi JP (2017) Neurological complications during treatment of Middle East respiratory syndrome. J Clin Neurol 13(3):227–233. https://doi.org/10.3988/jcn.2017.13.3.227 CrossRefPubMedPubMedCentral

Lachance C, Arbour N, Cashman NR, Talbot PJ (1998) Involvement of aminopeptidase N (CD13) in infection of human neural cells by human coronavirus 229E. J Virol 72(8):6511–6519CrossRefPubMedPubMedCentral

Lam TT-Y, Shum MH-H, Zhu H-C, Tong Y-G, Ni X-B, Liao Y-S et al (2020) Identification of 2019-nCoV related coronaviruses in Malayan pangolins in southern China. bioRxiv, 2020.2002.2013.945485. https://doi.org/10.1101/2020.02.13.945485

Lanese N (2020) Woman with COVID-19 developed a rare brain condition. Doctors suspect a link. Available via DIALOG. https://www.livescience.com/woman-with-covid19-coronavirus-had-rare-brain-disease.html. Accessed 1 Apr 2020

Lau KK, Yu WC, Chu CM, Lau ST, Sheng B, Yuen KY (2004) Possible central nervous system infection by SARS coronavirus. Emerg Infect Dis 10(2):342–344. https://doi.org/10.3201/eid1002.030638 CrossRefPubMedPubMedCentral

Leung WK, To K-F, Chan PKS, Chan HLY, Wu AKL, Lee N, Yuen KY, Sung JJY (2003) Enteric involvement of severe acute respiratory syndrome-associated coronavirus infection1 1The authors thank Man-yee Yung, Sara Fung, Dr. Bonnie Kwan, and Dr. Thomas Li for their help in retrieving patient information. Gastroenterology 125(4):1011–1017. https://doi.org/10.1016/j.gastro.2003.08.001 CrossRefPubMed

Li J, Gao J, Xu YP, Zhou TL, Jin YY, Lou JN (2007) Expression of severe acute respiratory syndrome coronavirus receptors, ACE2 and CD209L in different organ derived microvascular endothelial cells. Zhonghua Yi Xue Za Zhi 87(12):833–837PubMed

Li Y-C, Bai W-Z, Hirano N, Hayashida T, Taniguchi T, Sugita Y, Tohyama K, Hashikawa T (2013) Neurotropic virus tracing suggests a membranous-coating-mediated mechanism for transsynaptic communication. J Comp Neurol 521(1):203–212. https://doi.org/10.1002/cne.23171 CrossRefPubMed

Li K, Wohlford-Lenane C, Perlman S, Zhao J, Jewell AK, Reznikov LR, Gibson-Corley KN, Meyerholz DK, McCray PB Jr (2016a) Middle East respiratory syndrome coronavirus causes multiple organ damage and lethal disease in mice transgenic for human dipeptidyl peptidase 4. J Infect Dis 213(5):712–722. https://doi.org/10.1093/infdis/jiv499 CrossRefPubMed

Li Y, Li H, Fan R, Wen B, Zhang J, Cao X, Wang C, Song Z, Li S, Li X, Lv X, Qu X, Huang R, Liu W (2016b) Coronavirus infections in the central nervous system and respiratory tract show distinct features in hospitalized children. Intervirology 59(3):163–169. https://doi.org/10.1159/000453066 CrossRefPubMed

Li YC, Bai WZ, Hashikawa T (2020) The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. J Med Virol 92:552–555. https://doi.org/10.1002/jmv.25728 CrossRefPubMed

Liang B, Zhao Y-X, Zhang X-X, Lu J, Gu N (2020) Clinical characteristics of 457 cases with coronavirus disease 2019. Available at SSRN 3543581

Liu Z, Xiao X, Wei X, Li J, Yang J, Tan H et al (2020) Composition and divergence of coronavirus spike proteins and host ACE2 receptors predict potential intermediate hosts of SARS-CoV-2. J Med Virol n/a(n/a). https://doi.org/10.1002/jmv.25726

Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, Chang J, Hong C, Zhou Y, Wang D, Miao X, Li Y, Hu B (2020a) Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. https://doi.org/10.1001/jamaneurol.2020.1127

Mao L, Wang M, Chen S, He Q, Chang J, Hong C et al (2020b) Neurological manifestations of hospitalized patients with COVID-19 in Wuhan, China: a retrospective case series study. medRxiv, 2020.2002.2022.20026500. https://doi.org/10.1101/2020.02.22.20026500

Matoba Y, Abiko C, Ikeda T, Aoki Y, Suzuki Y, Yahagi K, Matsuzaki Y, Itagaki T, Katsushima F, Katsushima Y, Mizuta K (2015) Detection of the human coronavirus 229E, HKU1, NL63, and OC43 between 2010 and 2013 in Yamagata, Japan. Jpn J Infect Dis 68(2):138–141. https://doi.org/10.7883/yoken.JJID.2014.266 CrossRefPubMed

McCray PB, Pewe L, Wohlford-Lenane C, Hickey M, Manzel L, Shi L et al (2007) Lethal infection of K18-<em>hACE2</em> mice infected with severe acute respiratory syndrome coronavirus. J Virol 81(2):813–821. https://doi.org/10.1128/jvi.02012-06 CrossRefPubMed

Myint, S. H. (1995). Human coronavirus infections The Coronaviridae (pp. 389-401): springer

Netland J, Meyerholz DK, Moore S, Cassell M, Perlman S (2008) Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2. J Virol 82(15):7264–7275. https://doi.org/10.1128/jvi.00737-08 CrossRefPubMedPubMedCentral

Niu J, Shen L, Huang B, Ye F, Zhao L, Wang H, Deng Y, Tan W (2020) Non-invasive bioluminescence imaging of HCoV-OC43 infection and therapy in the central nervous system of live mice. Antivir Res 173:104646. https://doi.org/10.1016/j.antiviral.2019.104646 CrossRefPubMed

Pearson J, Mims CA (1985) Differential susceptibility of cultured neural cells to the human coronavirus OC43. J Virol 53(3):1016–1019CrossRefPubMedPubMedCentral

Peiris JS, Lai ST, Poon LL, Guan Y, Yam LY, Lim W et al (2003) Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet 361(9366):1319–1325. https://doi.org/10.1016/s0140-6736(03)13077-2 CrossRefPubMedPubMedCentral

Poyiadji N, Shahin G, Noujaim D, Stone M, Patel S, Griffith B (2020) COVID-19-associated acute hemorrhagic necrotizing encephalopathy: CT and MRI features. Radiology. https://doi.org/10.1148/radiol.2020201187

Rahhal N (2020) Coronavirus may cause brain damage by triggering dangerous inflammation that can cause bleeds and cell death. Available via DIALOG. https://www.dailymail.co.uk/health/article-8181257/Coronavirus-damage-brains-patients-reports-suggests.html. Accessed 3 Apr 2020

St-Jean JR, Jacomy H, Desforges M, Vabret A, Freymuth F, Talbot PJ (2004) Human respiratory coronavirus OC43: genetic stability and neuroinvasion. J Virol 78(16):8824–8834. https://doi.org/10.1128/jvi.78.16.8824-8834.2004 CrossRefPubMedPubMedCentral

Stodola JK, Dubois G, Le Coupanec A, Desforges M, Talbot PJ (2018) The OC43 human coronavirus envelope protein is critical for infectious virus production and propagation in neuronal cells and is a determinant of neurovirulence and CNS pathology. Virology 515:134–149. https://doi.org/10.1016/j.virol.2017.12.023 CrossRefPubMed

Talbot PJ, Desforges M, Brison E, Jacomy H, Tkachev S (2011) Coronaviruses as encephalitis-inducing infectious agents. Non-flavirus Encephalitis In-Tech, 185–202

Vabret A, Mourez T, Gouarin S, Petitjean J, Freymuth F (2003) An outbreak of coronavirus OC43 respiratory infection in Normandy, France. Clin Infect Dis 36(8):985–989. https://doi.org/10.1086/374222 CrossRefPubMed

Vu HT, Leitmeyer KC, Le DH, Miller MJ, Nguyen QH, Uyeki TM et al (2004) Clinical description of a completed outbreak of SARS in Vietnam, February-May 2003. Emerg Infect Dis 10(2):334–338. https://doi.org/10.3201/eid1002.030761 CrossRefPubMedPubMedCentral

Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z (2020) Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China. JAMA 323(11):1061–1069. https://doi.org/10.1001/jama.2020.1585 CrossRefPubMedPubMedCentral

Woelfel R, Corman VM, Guggemos W, Seilmaier M, Zange S, Mueller MA, . . . Wendtner C (2020) Clinical presentation and virological assessment of hospitalized cases of coronavirus disease 2019 in a travel-associated transmission cluster. medRxiv, 2020.2003.2005.20030502. doi:https://doi.org/10.1101/2020.03.05.20030502

Wu C, Chen X, Cai Y, Xia J a, Zhou X, Xu S et al (2020) Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Int Med. https://doi.org/10.1001/jamainternmed.2020.0994

Xu J, Zhong S, Liu J, Li L, Li Y, Wu X, Li Z, Deng P, Zhang J, Zhong N, Ding Y, Jiang Y (2005) Detection of severe acute respiratory syndrome coronavirus in the brain: potential role of the chemokine mig in pathogenesis. Clin Infect Dis 41(8):1089–1096. https://doi.org/10.1086/444461 CrossRefPubMed

Xu X-W, Wu X-X, Jiang X-G, Xu K-J, Ying L-J, Ma C-L, Li SB, Wang HY, Zhang S, Gao HN, Sheng JF, Cai HL, Qiu YQ, Li L-J (2020) Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series. BMJ 368:m606. https://doi.org/10.1136/bmj.m606 CrossRefPubMedPubMedCentral

Yang W, Cao Q, Qin L, Wang X, Cheng Z, Pan A, Dai J, Sun Q, Zhao F, Qu J, Yan F (2020) Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19):a multi-center study in Wenzhou city, Zhejiang, China. J Infect 80(4):388–393. https://doi.org/10.1016/j.jinf.2020.02.016 CrossRefPubMedPubMedCentral

Yeh EA, Collins A, Cohen ME, Duffner PK, Faden H (2004) Detection of coronavirus in the central nervous system of a child with acute disseminated encephalomyelitis. Pediatrics 113(1 Pt 1):e73–e76. https://doi.org/10.1542/peds.113.1.e73 CrossRefPubMed

Yuan Y, Cao D, Zhang Y, Ma J, Qi J, Wang Q, Lu G, Wu Y, Yan J, Shi Y, Zhang X, Gao GF (2017) Cryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains. Nat Commun 8:15092. https://doi.org/10.1038/ncomms15092 CrossRefPubMedPubMedCentral

Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA (2012) Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med 367(19):1814–1820. https://doi.org/10.1056/NEJMoa1211721 CrossRefPubMed

Zhang C, Shi L, Wang F-S (2020) Liver injury in COVID-19: management and challenges. Lancet Gastroenterol Hepatol. https://doi.org/10.1016/S2468-1253(20)30057-1

Title: COVID-19 virus may have neuroinvasive potential and cause neurological complications: a perspective review
Authors: Ali Sepehrinezhad
Ali Shahbazi
Sajad Sahab Negah
Publication date: 01-06-2020
Publisher: Springer International Publishing
Keywords: Coronavirus
Severe Acute Respiratory Syndrome Coronavirus
Middle Eastern Respiratory Syndrome
COVID-19
Published in: Journal of NeuroVirology / Issue 3/2020
Print ISSN: 1355-0284
Electronic ISSN: 1538-2443
DOI: https://doi.org/10.1007/s13365-020-00851-2

At a glance: The STEP trials

Springer Medicine

COVID-19 virus may have neuroinvasive potential and cause neurological complications: a perspective review

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2020

The “Three Italy” of the COVID-19 epidemic and the possible involvement of SARS-CoV-2 in triggering complications other than pneumonia

Epilepsia partialis continua revealing idelalisib-associated PML-IRIS: clinical and pathological features

Blood-based inflammation biomarkers of neurocognitive impairment in people living with HIV

A special symptom of olfactory dysfunction in coronavirus disease 2019: report of three cases

Human encephalitis caused by pseudorabies virus infection: a case report

Zika virus infection in chemosensory cells