Direct and indirect neurological manifestations of COVID-19

Gromova O.A.; Torshin I.Yu.; Semenov V.A.; Putilina M.V.; Chuchalin A.G.

doi:https://doi.org/10.17116/jnevro202012011111

Close metadata

OBJECTIVE

To systemize the neurological manifestations of COVID-19.

MATERIALS AND METHODS

A systematic computer analysis of all currently available publications on the neurological manifestations of COVID-19 (2374 publications in PUBMED) using algorithms of topological data analysis was performed.

RESULTS

A complex of interactions between SARS-CoV-2 infection, metabolic disorders of neurotransmitters (acetylcholine, dopamine, serotonin and GABA), enkephalins and neurotrophins, micronutrients, chronic and acute inflammation, encephalopathy, cerebral ischemia and neurodegeneration, including demyelination, was described. The most common neurological manifestation of COVID-19 is anosmia/ageusia arising as a result of ischemia, neurodegeneration, and/or systemic elevation of proinflammatory cytokine levels. COVID-19 provokes ischemic stroke, Guillain—Barré syndrome, polyneuropathy, encephalitis, meningitis and parkinsonism. Coronavirus infection significantly aggravates the course of multiple sclerosis and myopathies. Possible roles of the human virome in the neuropathophysiology of COVID-19 are considered. A case of clinical management of a patient with neurological complications of COVID-19 is described.

CONCLUSION

In the long term, COVID-19 stimulates neurodegenerative changes, which require specific programs of neurological rehabilitation. It is advisable to use choline drugs and antihypoxants that are compatible with COVID-19 therapy.

Keywords:

COVID-19

neurological symptoms

complications

choline drugs

Authors:

Gromova O.A.

Federal Research Center «Computer Science and Control»

ORCID: 0000-0002-7663-710X

Torshin I.Yu.

Federal Research Center «Computer Science and Control»

ORCID: 0000-0002-2659-7998

Semenov V.A.

Kemerovo State Medical University

Putilina M.V.

Pirogov Russian National Research Medical University

ORCID: 0000-0002-8655-8501

Chuchalin A.G.

Pirogov Russian National Research Medical University

Received:

17.09.2020

Accepted:

22.09.2020

Close metadata

References:

Koralnik IJ, Tyler KL. COVID-19: A Global Threat to the Nervous System. Ann Neurol. 2020;88(1):1-11. https://doi.org/10.1002/ana.25807
Carod-Artal FJ. Neurological complications of coronavirus and COVID-19. Rev Neurol. 2020;70(9):311-322. https://doi.org/10.33588/rn.7009.2020179
Wu Y, Xu X, Chen Z, Duan J, Hashimoto K, Yang L, Liu C, Yang C. Nervous system involvement after infection with COVID-19 and other coronaviruses. Brain Behav Immun. 2020;87:18-22. https://doi.org/10.1016/j.bbi.2020.03.031
Manto M, Dupre N, Hadjivassiliou M, Louis ED, Mitoma H, Molinari M, Shaikh AG, Soong BW, Strupp M, Van Overwalle F, Schmahmann JD. Medical and Paramedical Care of Patients With Cerebellar Ataxia During the COVID-19 Outbreak: Seven Practical Recommendations of the COVID 19 Cerebellum Task Force. Front Neurol. 2020;11:516. https://doi.org/10.3389/fneur.2020.00516
Munhoz RP, Pedroso JL, Nascimento FA, Almeida SM, Barsottini OGP, Cardoso FEC, Teive HAG. Neurological complications in patients with SARS-CoV-2 infection: a systematic review. Arq Neuropsiquiatr. 2020;78(5):290-300. https://doi.org/10.1590/0004-282x20200051
Ahmad I, Rathore FA. Neurological manifestations and complications of COVID-19: A literature review. J Clin Neurosci. 2020;77:8-12. https://doi.org/10.1016/j.jocn.2020.05.017
Butler MJ, Barrientos RM. The impact of nutrition on COVID-19 susceptibility and long-term consequences. Brain Behav Immun. 2020;87:53-54. https://doi.org/10.1016/j.bbi.2020.04.040
Torshin IYu, Gromova OA; Chuchalina AG. red. Mikronutrienty protiv koronavirusov. Moscow, GEOTAR-Media, 2020.
Torshin IY, Rudakov KV. Combinatorial analysis of the solvability properties of the problems of recognition and completeness of algorithmic models. Part 1: Factorization approach. Pattern Recognit. Image Anal. 2017; 27: 16-28. https://doi.org/10.1134/S1054661817010151
Torshin IY, Rudakov KV. Combinatorial analysis of the solvability properties of the problems of recognition and completeness of algorithmic models. Part 2: Metric approach within the framework of the theory of classification of feature values. Pattern Recognit. Image Anal. 2017; 27: 184-199. https://doi.org/10.1134/S1054661817020110
Torshin IY, Rudakov KV. On metric spaces arising during formalization of recognition and classification problems. Part 1: Properties of compactness. Pattern Recognit. Image Anal. 2016; 26: 274-284. https://doi.org/10.1134/S1054661816020255
Torshin IY, Rudakov KV. On the Procedures of Generation of Numerical Features over Partitions of Sets of Objects in the Problem of Predicting Numerical Target Variables. Pattern Recognit. Image Anal. 2019; 29: 654-667. https://doi.org/10.1134/S1054661819040175
Mi H, Huang X, Muruganujan A, Tang H, Mills C, Kang D, Thomas PD. PANTHER version 14: more genomes, a new PANTHER GO-slim and improvements in enrichment analysis tools. Nucleic Acids Res. 2019;47(D1):D419-D426. https://doi.org/10.1093/nar/gky1038
Putilina MV. Combined therapy of cerebrovascular disorders with neuroprotectors. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova. 2016;116(11):58-63. (In Russ.). https://doi.org/10.17116/jnevro201611611158-63
Fan S, Xiao M, Han F, Xia P, Bai X, Chen H, Zhang H, Ding X, Zhao H, Zhao J, Sun X, Jiang W, Wang C, Cao W, Guo F, Tian R, Gao P, Wu W, Ma J, Wu D, Liu Z, Zhou X, Wang J, Guan T, Qin Y, Li T, Xu Y, Zhang D, Chen Y, Xie J, Li Y, Yan X, Zhu Y, Peng B, Cui L, Zhang S, Guan H. Neurological Manifestations in Critically Ill Patients With COVID-19: A Retrospective Study. Front Neurol. 2020;11:806. https://doi.org/10.3389/fneur.2020.00806
Poyiadji N, Shahin G, Noujaim D, Stone M, Patel S, Griffith B. COVID-19-associated Acute Hemorrhagic Necrotizing Encephalopathy: Imaging Features. Radiology. 2020;296(2):E119-E120. https://doi.org/10.1148/radiol.2020201187
Niazkar HR, Zibaee B, Nasimi A, Bahri N. The neurological manifestations of COVID-19: a review article. Neurol Sci. 2020;41(7):1667-1671. https://doi.org/10.1007/s10072-020-04486-3
Montalvan V, Lee J, Bueso T, De Toledo J, Rivas K. Neurological manifestations of COVID-19 and other coronavirus infections: A systematic review. Clin Neurol Neurosurg. 2020;194:105921. https://doi.org/10.1016/j.clineuro.2020.105921
Correia AO, Feitosa PWG, Moreira JLS, Nogueira SÁR, Fonseca RB, Nobre MEP. Neurological manifestations of COVID-19 and other coronaviruses: A systematic review. Neurol Psychiatry Brain Res. 2020;37:27-32. https://doi.org/10.1016/j.npbr.2020.05.008
Petrescu AM, Taussig D, Bouilleret V. Electroencephalogram (EEG) in COVID-19: A systematic retrospective study. Neurophysiol Clin. 2020;50(3):155-165. https://doi.org/10.1016/j.neucli.2020.06.001
Jain R, Young M, Dogra S, Kennedy H, Nguyen V, Jones S, Bilaloglu S, Hochman K, Raz E, Galetta S, Horwtiz L. COVID-19 related neuroimaging findings: A signal of thromboembolic complications and a strong prognostic marker of poor patient outcome. J Neurol Sci. 2020;414:116923. https://doi.org/10.1016/j.jns.2020.116923
Li Z, Liu T, Yang N, Han D, Mi X, Li Y, Liu K, Vuylsteke A, Xiang H, Guo X. Neurological manifestations of patients with COVID-19: potential routes of SARS-CoV-2 neuroinvasion from the periphery to the brain. Front Med. 2020;14(5):533-541. https://doi.org/10.1007/s11684-020-0786-5
Heneka MT, Golenbock D, Latz E, Morgan D, Brown R. Immediate and long-term consequences of COVID-19 infections for the development of neurological disease. Alzheimers Res Ther. 2020;12(1):69. https://doi.org/10.1186/s13195-020-00640-3
Farsalinos K, Niaura R, Le Houezec J, Barbouni A, Tsatsakis A, Kouretas D, Vantarakis A, Poulas K. Nicotine and SARS-CoV-2: COVID-19 may be a disease of the nicotinic cholinergic system. Toxicology Reports. 2020;7:658-663 https://doi.org/10.1016/j.toxrep.2020.04.012
Pérez Álvarez ÁI, Suárez Cuervo C, Fernández Menéndez S. SARS-CoV-2 infection associated with diplopia and anti-acetylcholine receptor antibodies. Neurologia. 2020;35(4):264-265. https://doi.org/10.1016/j.nrl.2020.04.003
Al Saiegh F, Ghosh R, Leibold A, Avery MB, Schmidt RF, Theofanis T, Mouchtouris N, Philipp L, Peiper SC, Wang ZX, Rincon F, Tjoumakaris SI, Jabbour P, Rosenwasser RH, Gooch MR. Status of SARS-CoV-2 in cerebrospinal fluid of patients with COVID-19 and stroke. J Neurol Neurosurg Psychiatry. 2020;91(8):846-848. https://doi.org/10.1136/jnnp-2020-323522
Bellon M, Schweblin C, Lambeng N, Cherpillod P, Vazquez J, Lalive PH, Schibler M, Deffert C. Cerebrospinal fluid features in SARS-CoV-2 RT-PCR positive patients. Clin Infect Dis. 2020;ciaa1165. https://doi.org/10.1093/cid/ciaa1165
Caress JB, Castoro RJ, Simmons Z, Scelsa SN, Lewis RA, Ahlawat A, Narayanaswami P. COVID-19-associated Guillain-Barré syndrome: The early pandemic experience. Muscle Nerve. 2020;62(4):485-491. https://doi.org/10.1002/mus.27024
Lechien JR, Chiesa-Estomba CM, De Siati DR, Horoi M, Le Bon SD, Rodriguez A, Dequanter D, Blecic S, El Afia F, Distinguin L, Chekkoury-Idrissi Y, Hans S, Delgado IL. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. Eur Arch Otorhinolaryngol. 2020;277(8):2251-2261. https://doi.org/10.1007/s00405-020-05965-1
Han AY, Mukdad L, Long JL, Lopez IA. Anosmia in COVID-19: Mechanisms and Significance. Chem Senses. 2020;bjaa040. https://doi.org/10.1093/chemse/bjaa040
Yazdanpanah N, Saghazadeh A, Rezaei N. Anosmia: a missing link in the neuroimmunology of coronavirus disease 2019 (COVID-19). Rev Neurosci. 2020;31(7):691-701. https://doi.org/10.1515/revneuro-2020-0039
Zhang AJ, Lee AC, Chu H, Chan JF, Fan Z, Li C, Liu F, Chen Y, Yuan S, Poon VK, Chan CC, Cai JP, Wu KL, Sridhar S, Chan YS, Yuen KY. SARS-CoV-2 infects and damages the mature and immature olfactory sensory neurons of hamsters. Clin Infect Dis. 2020;ciaa995. https://doi.org/10.1093/cid/ciaa995
Cazzolla AP, Lovero R, Lo Muzio L, Testa NF, Schirinzi A, Palmieri G, Pozzessere P, Procacci V, Di Comite M, Ciavarella D, Pepe M, De Ruvo C, Crincoli V, Di Serio F, Santacroce L. Taste and Smell Disorders in COVID-19 Patients: Role of Interleukin-6. ACS Chem Neurosci. 2020;11(17):2774-2781. https://doi.org/10.1021/acschemneuro.0c00447
Li Y, Li M, Wang M, Zhou Y, Chang J, Xian Y, Wang D, Mao L, Jin H, Hu B. Acute cerebrovascular disease following COVID-19: a single center, retrospective, observational study. Stroke Vasc Neurol. 2020;5(3):279-284. https://doi.org/10.1136/svn-2020-000431
Lodigiani C, Iapichino G, Carenzo L, Cecconi M, Ferrazzi P, Sebastian T, Kucher N, Studt JD, Sacco C, Alexia B, Sandri MT, Barco S. Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. Thromb Res. 2020;191:9-14. https://doi.org/10.1016/j.thromres.2020.04.024
Tan YK, Goh C, Leow AST, Tambyah PA, Ang A, Yap ES, Tu TM, Sharma VK, Yeo LLL, Chan BPL, Tan BYQ. COVID-19 and ischemic stroke: a systematic review and meta-summary of the literature. J Thromb Thrombolysis. 2020;50(3):587-595. https://doi.org/10.1007/s11239-020-02228-y
Belani P, Schefflein J, Kihira S, Rigney B, Delman BN, Mahmoudi K, Mocco J, Majidi S, Yeckley J, Aggarwal A, Lefton D, Doshi AH. COVID-19 Is an Independent Risk Factor for Acute Ischemic Stroke. AJNR Am J Neuroradiol. 2020;41(8):1361-1364. https://doi.org/10.3174/ajnr.A6650
Gusev EI, Martynov MY, Boyko AN, Voznyuk IA, Latsh NY, Sivertseva SA, Spirin NN, Shamalov NA. Novel coronavirus infection (COVID-19) and nervous system involvement: pathogenesis, clinical manifestations, organization of neurological care. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2020;120(6):7-16. (In Russ.). https://doi.org/10.17116/jnevro20201200617 PMID:32678542
Cao X, Yin R, Albrecht H, Fan D, Tan W. Cholesterol: A new game player accelerating vasculopathy caused by SARS-CoV-2? Am J Physiol Endocrinol Metab. 2020;319(1):E197-E202. https://doi.org/10.1152/ajpendo.00255.2020
Bodro M, Compta Y, Llansó L, Esteller D, Doncel-Moriano A, Mesa A, Rodríguez A, Sarto J, Martínez-Hernandez E, Vlagea A, Egri N, Filella X, Morales-Ruiz M, Yagüe J, Soriano Á, Graus F, García F. Increased CSF levels of IL-1β, IL-6, and ACE in SARS-CoV-2-associated encephalitis. Neurol Neuroimmunol Neuroinflamm. 2020;7(5):e821. https://doi.org/10.1212/NXI.0000000000000821
Benameur K, Agarwal A, Auld SC, Butters MP, Webster AS, Ozturk T, Howell JC, Bassit LC, Velasquez A, Schinazi RF, Mullins ME, Hu WT. Encephalopathy and Encephalitis Associated with Cerebrospinal Fluid Cytokine Alterations and Coronavirus Disease, Atlanta, Georgia, USA, 2020. Emerg Infect Dis. 2020;26(9):2016-2021. https://doi.org/10.3201/eid2609.202122
Taha MK, Deghmane AE. Impact of COVID-19 pandemic and the lockdown on invasive meningococcal disease. BMC Res Notes. 2020;13(1):399. https://doi.org/10.1186/s13104-020-05241-9
Guidon AC, Amato AA. COVID-19 and neuromuscular disorders. Neurology. 2020;94(22):959-969. https://doi.org/10.1212/WNL.0000000000009566
Haji Akhoundi F, Sahraian MA, Naser Moghadasi A. Neuropsychiatric and cognitive effects of the COVID-19 outbreak on multiple sclerosis patients. Mult Scler Relat Disord. 2020;41:102164. https://doi.org/10.1016/j.msard.2020.102164
Veerapandiyan A, Wagner KR, Apkon S, McDonald CM, Mathews KD, Parsons JA, Wong BL, Eichinger K, Shieh PB, Butterfield RJ, Rao VK, Smith EC, Proud CM, Connolly AM, Ciafaloni E. The care of patients with Duchenne, Becker, and other muscular dystrophies in the COVID-19 pandemic. Muscle Nerve. 2020;62(1):41-45. https://doi.org/10.1002/mus.26902
Benny R, Khadilkar SV. COVID 19: Neuromuscular Manifestations. Ann Indian Acad Neurol. 2020;23(Suppl 1):S40-S42. https://doi.org/10.4103/aian.AIAN_309_20
Putilina MV. Modern ideas about the treatment of anxiety and depressive disorders in chronic brain ischemia. RMJ. 2011;19(9):569-573. (In Russ.).
Eldeeb MA, Hussain FS, Siddiqi ZA. COVID-19 infection may increase the risk of parkinsonism — Remember the Spanish flu? Cytokine Growth Factor Rev. 2020;54:6-7. https://doi.org/10.1016/j.cytogfr.2020.06.009
Bracaglia M, Naldi I, Govoni A, Brillanti Ventura D, De Massis P. Acute inflammatory demyelinating polyneuritis in association with an asymptomatic infection by SARS-CoV-2. J Neurol. 2020;267(11):3166-3168. https://doi.org/10.1007/s00415-020-10014-2
Pinto AA, Carroll LS, Nar V, Varatharaj A, Galea I. CNS inflammatory vasculopathy with antimyelin oligodendrocyte glycoprotein antibodies in COVID-19. Neurol Neuroimmunol Neuroinflamm. 2020;7(5):e813. https://doi.org/10.1212/NXI.0000000000000813
Kanberg N, Ashton NJ, Andersson LM, Yilmaz A, Lindh M, Nilsson S, Price RW, Blennow K, Zetterberg H, Gisslén M. Neurochemical evidence of astrocytic and neuronal injury commonly found in COVID-19. Neurology. 2020;95(12):e1754-e1759. https://doi.org/10.1212/WNL.0000000000010111
Torshin IYu, Gromova OA, Zakharova IN, Maksimov VA. Chemomicrobiome analysis of Lactitol. Experimental and clinical gastroenterology. 2019;164(4):111-121. (In Russ.). https://doi.org/10.31146/1682-8658-ecg-164-4-111-121
Kachuri L, Francis SS, Morrison M, Wendt GA, Bossé Y, Cavazos TB, Rashkin SR, Ziv E, Witte JS. The landscape of host genetic factors involved in infection to common viruses and SARS-CoV-2. medRxiv. 2020. Accessed Nov 23, 2020. https://doi.org/10.1101/2020.05.01.20088054
Kumata R, Ito J, Takahashi K, Suzuki T, Sato K. A tissue level atlas of the healthy human virome. BMC Biol. 2020;18(1):55. https://doi.org/10.1186/s12915-020-00785-5
Zhang Z, Ye S, Wu A, Jiang T, Peng Y. Prediction of the Receptorome for the Human-Infecting Virome. Virol Sin. 2020. Accessed Nov 23, 2020. https://doi.org/10.1007/s12250-020-00259-6
Focosi D, Antonelli G, Pistello M, Maggi F. Torquetenovirus: the human virome from bench to bedside. Clin Microbiol Infect. 2016;22(7):589-593. https://doi.org/10.1016/j.cmi.2016.04.007
Maggi F, Bendinelli M. Human anelloviruses and the central nervous system. Rev Med Virol. 2010;20(6):392-407. https://doi.org/10.1002/rmv.668
Vremennye metodicheskie rekomendatsii «Profilaktika, diagnostika i lechenie novoi koronavirusnoi infektsii (COVID-19)». Versiya 9 (26.10.2020). (utv. Minzdravom Rossii). Accessed Nov 23, 2020. (In Russ.). https://www.consultant.ru/law/hotdocs/65400.html
Gromova OA, Torshin IYu, Putilina MV, Semenov VA, Rudakov KV. Choice of neuroprotective therapy regimens in patients with chronic cerebral ischemia, taking into account the synergy of drug interactions. Zhurnal nevrologiii psikhiatrii imeni S.S. Korsakova. 2020;120(8):42-50. (In Russ.). https://doi.org/10.17116/jnevro202012008142