Mecanismos fisiopatológicos asociados al daño neurológico por Covid-19

Pathophysiological mechanisms involved in neurological damage by Covid-19

Contenido principal del artículo

Jose Gaya
Odalys Puentes Corrales
Iliana Alonso Rodríguez
Liliam Leyva Medrano
Adonisbel Mario Valero Sanchez
Yoelvis Cesar Del Pozo Burgos

Resumen

Introducción: en diciembre 2019, se reportó en China la presencia de un nuevo coronavirus que, se clasificó y denominó como Síndrome Respiratorio Agudo Severo-Coronavirus 2 (SARS-CoV-2), causante de la enfermedad pandémica Covid-19. Este virus es capaz de producir daño adicional en el sistema nervioso y provocar síntomas y complicaciones neurológicas. Objetivo: describir los principales mecanismos fisiopatológicos que explican el daño neurológico reportado en la enfermedad Covid-19. Métodos: se realizó una selección de artículos científicos publicados entre 2019 y 2021, utilizando el repositorio electrónico de PubMed/ScienceDirect (y artículos de libre acceso en las Bases/Datos de Scopus, MedLine, Scielo y LILACs) según las recomendaciones del tesauro DeCS (Descriptores en Ciencias de la Salud) para operadores lógicos y descriptores sobre esta temática. Resultados: aunque, se considera una enfermedad típicamente respiratoria, se han descrito una serie de manifestaciones extra-pulmonares como posibles síntomas de presentación y/o complicaciones, en pacientes con Covid-19. El coronavirus SARS-CoV-2, tiene propiedades neuroinvasivas, neurotrópicas y pro-inflamatorias capaces de exacerbar el proceso neurodegenerativo que provoca la enfermedad. Se ha reportado que entre 30-80% de los pacientes con Covid-19 suelen presentar síntomas neurológicos. Conclusión: esta revisión describe los principales fundamentos fisiopatológicos invocados para intentan explicar los mecanismos que determinan la generación de enfermedad y complicaciones neurológicas en la infección por Covid-19. Las manifestaciones neurológicas reportadas en los pacientes infectados pueden deberse a invasión viral directa (propiedades neurotrópicas) o mecanismos indirectos (derivados del estado infeccioso post-inflamatorio, alteraciones metabólicas y desregulaciones de la respuesta inmune).

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Referencias (VER)

Cui J, Li F, Shi Z. Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol. 2019; 17(2): 181-92. doi: 10.1038/s41579-018-0118-9

Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020; 579(7798): 270–3. doi: 10.1038/s41586-020-2012-7

Zhong NS, Zheng BJ, Li YM, Poon LLM, ZH, Xie ZH, Chan KH, et al. Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People’s Republic of China. Lancet. 2003; 362 (8667):1353-8. doi: 10.1016/S0140-6736(03)14630-2

Zaki AM, Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA. Isolation of a novel coronavirus from man with pneumonia in Saudi Arabia. N Engl J Med. 2012; 367(7): 1814-20. doi: 10.1056/NEJMoa1211721

Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al (China Novel Coronavirus Investigating and Research Team). A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2019; 24(1): 1017-20. doi: 10.1056/NEJMoa2001017

Sohrabi C, Alsafi Z, O´Neill N, Khan M, Kerwan A, Al-Jabir A, et al. WHO declares global emergency: A review of 2019 novel coronavirus (COVID-19). Int J Surg. 2020; 76(1): 71-6. doi: 10.1016/j.ijsu.2020.02.034

Conferencia de Prensa del MINSAP: Actualización sobre la situación epidemiológica de la COVID-19 en Cuba (31.01.2020). Disponible en: http://www//CubaPorLaVida; www//COVID19.

Berger JR. COVID-19 and the nervous system. J Neurovirol. 2020; 26(2): 143-8. doi: 10.1007/s13365-020-00840-5

Butala N. Neurological aspects of Coronavirus Infectious Disease 2019 (COVID-19). Innov Clin Neurosci. 2020; 17(4-6): 13-15. Disponible en: PMID: 32802586

Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with COVID-19 in Wuhan, China. Lancet. 2020; 395 (10223): 497-506. doi: 10.1016/S0140-6736(20)30183-5

Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 2020; 77(6): 683-90. doi: 10.1016/j.clineuro.2020.105921

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. doi: 10.1016/j.clineuro.2020.105921

Niazkar HR, Zibaee B, Nasimi A, Bahri N. The neurological manifestations of COVID-19: a review article. Neurol Sci. 2020; 41(7): 1667-71. doi: 10.1007/s10072-020-04486-3

Paterson RW, Brown RL, Benjamin L, Nortley R, Wiethoff S, Bharucha T, et al. The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings. Brain. 2020; 143(10): 3104-20. doi: 10.1093/brain/awaa240

Wu Y, Xu X, Chen Z, Duan J, Hashimoto K, Yang L, et al. Nervous system involvement after infection with COVID-19 and other coronaviruses. Brain Behav Immun. 2020; 1(2): 357-63. doi: 10.1016/j.bbi.2020.03.031

Zhou M, Zhang X, Qu J. Coronavirus disease 2019 (COVID-19): A clinical update. Front Med. 2020; 127: 10436. doi: 10.1007/s11684-020-0767-8

Helms J, Kremer S, Merdji H, Clere-Jehl R, Schenck M, Kummerlen C, et al. Neurologic features in severe SARS-CoV-2 infection. N Engl J Med. 2020; 382(23): 2268-70. doi: 10.1056/NEJMc2008597

Liotta EM, Batra A, Clark JR, Shlobin NA, Hoffman SC, Orban ZS, et al. Frequent neurologic manifestations and encephalopathy-associated morbidity in COVID-19 patients. Ann Clin Transl Neurol. 2020; 7(11): 2221-30. doi: 10.1002/acn3.51210

Chen Y, Liu Q, Guo D. Emerging coronaviruses: genome structure, replication, and pathogenesis. J Med Virol. 2020; 92: 418-23. doi.org/10.1002/jmv.25681

Schoeman D, Fielding BC. Coronavirus envelope protein: current knowledge. Virol J. 2019; 16: 69 (1-22). doi: 10.1186/s12985-019-1182-0

Paules CI, Marston HD, Fauci AS. Coronavirus infections: more than just the common cold. J Am Med Assoc. 2020; 323(8): 707-8. doi: 10.1001/jama.2020.0757

Vabret N, Britton GJ, Gruber C, Hegde S, Kim J, Kuksin M, et al. Immunology of COVID-19: current state of the science. Immunity. 2020; 52: 910-41. doi: 10.1016/j.immuni.2020.05.002

Cascella M, Rajnik M, Aleem A, Dulebohn SC, Di Napoli R. Features, Evaluation and Treatment of Coronavirus (COVID-19). StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022. Disponible en: https://www.ncbi.nlm.nih.gov/books/NBK554776

Krett JD, Jewett GA, Elton-Lacasse C, Fonseca K, Hahn C, Au S, et al. Hemorrhagic encephalopathy associated with COVID-19. J Neuroimmunol. 2020; 577326 (1-4). doi: 10.1016/j.jneuroim.2020.577326

Verdecchia P, Cavallini C, Spanevello A, Angeli F. The pivotal link between ACE2 deficiency and SARS-CoV-2 infection. Eur J Intern Med. 2020; 20(2): 3151-5. doi: 10.1016/j.ejim.2020.04.037

Baig AM, 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): 995-8. doi: 10.1021/acschemneuro.0c00122

Bender del Busto J, León-Castellón R, Mendieta-Pedroso M, Rodríguez-Labrada R, Velázquez-Pérez L. Infección por el SARS-CoV-2: de los mecanismos neuroinvasivos a las manifestaciones neurológicas. Anales ACC. 2020; 10(2): e855. Disponible en: http://www.revistaccuba.cu/index.php/revacc/article/view/855

Machado C. Cómo el SARS-CoV-2 ataca al Sistema Nervioso?. Trabajo para optar por el Premio Anual de la Academia de Ciencias de Cuba. La Habana, 2020.

Machado C, DeFina P. Covid-19: Anosmia and Ageusia might be initial or unique symptoms. SF J Clin Neurol Brain. 2020; 1(1): 1002 (1-7). Disponible en: https://doi.org/10.20944/preprints202004.0272.v1

Weir EM, Reed DR, Pepino MY, Veldhuizen MG, Hayes JE. Massively collaborative crowdsourced research on COVID19 and the chemical senses: insights and outcomes. Food Quality & Preference. 2022; 97: 104483 (1-8). doi: 10.1016/j.foodqual.2021.104483

Zahra SA, Iddawela S, Pillai K, Choudhury RY, Harky A. Can symptoms of anosmia and dysgeusia be diagnostic for COVID‐19?. Brain Behav. 2020; 10(11): e011839. doi.org/10.1002/BRB3.1839

Van Doremalen N, Bushmaker T, Morris DH, Holbrook MG, Gamble A, Williamson BN, et al. Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1. N Engl J Med. 2020; 27(2): 1564-7. doi: 10.1056/NEJMc2004973

Tang A, Tong ZD, Wang HL, Dai YX, Li KF, Liu JN, et al. Detection of novel coronavirus by RT-PCR in stool specimen, China. Emerg Infect Dis. 2020; 26(6): 110-8. doi: 10.3201/eid2606.200301

Connors JM, Levy JH. COVID-19 and its implications for thrombosis and anticoagulation. Blood. 2020; 135(23): 2033-40. doi: 10.1182/blood.2020006000

Machado C. Silent or 'Happy' Hypoxemia: An urgent dilemma for COVID-19 patient care. MEDICC Rev. 2020; 22:85-86. doi: 10.37757/MR2020.V22.N4.9

Machado C. Severe COVID-19 cases: Is respiratory distress partially explained by CNS involvement?. MEDICC Rev. 2020; 22(2): 38-9. doi: 10.37757/MR2020.V22.N2.10

Orsini A, Corsi M, Santangelo A, Riva A, Peroni D, Foiadelli T, et al. Challenges and management of neurological and psychiatric manifestations in SARS-Cov-2 (COVID-19) patients. Neurol Sci. 2020; 41(9): 2353-40. doi: 10.1007/s10072-020-04544-w

Zou L, Dai L, Zhang Y, Fu W, Gao Y, Zhang Z, et al. Clinical characteristics and risk factors for disease severity and death in patients with COVID-19 in Wuhan, China. Front Med. 2020; 7(1): 532-41. doi: 10.3389/fmed.2020.00532

Michalicova A, Bhide K, Bhide M, Kovac A. How viruses infiltrate the central nervous system. Acta Virol. 2017; 61: 393-400. doi: 10.4149/av_2017_401

He Q, Liu H, Huang C, Wang R, Luo M, Lu W. Herpes simplex virus 1-induced Blood-Brain Barrier damage involves apoptosis associated with GM130-mediated Golgi stress. Front Mol Neurosci. 2020; 13: 2 (1-16). doi: 10.3389/fnmol.2020.00002

Tian J, Shi R, Liu T, She R, Wu Q, An J, et al. Brain infection by Hepatitis E virus probably via damage of the blood-brain barrier due to alteration of tight junction proteins. Front Cell Infect Microbiol. 2020; 9: 52. doi: 10.3389/fcimb.2019.00052

Padrón AA, González C, Dorta A. Empleo del Reibergrama en manifestaciones neurológicas del dengue. Rev Hab Cienc Med. 2017; 16(5): 711-9. Disponible en: http://scielo.sld.cu/scielo.php?script=sci_arttext&pid=S1729-519X2017000500005

Rodríguez JA, Pérez V, Mirabal A, Padrón AA, Castillo W, Gonzalez, et al. Epstein-Barr virus and Multiple Sclerosis. FASEB J. 2018; 32(1): 617-20. Disponible en: http://www.revibiomedica.sld.cu/index.php/ibi/article/view/868/892

Esposito G, Pesce M, Seguella L, Sanseverino W, Lu J, Sarnelli G. Can the enteric nervous system be an alternative entrance door in SARS-CoV-2 neuroinvasion?. Brain Behav Immum. 2020; 87(2): 93-4. doi: 10.1016/j.bbi.2020.04.060

Skinner D, Marro BS, Lane TE. Chemokine CXCL10 and coronavirus induced neurologic disease. Viral Inmunol. 2019; 32(1): 25-37. doi: 10.1089/vim.2018.0073

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(5): 383-4. doi: 10.1016/S1474-4422(20)30109-5

Céspedes HR, Rodríguez DJ, Céspedes HA, Céspedes RA. Mecanismos neuroinvasivos y daño neurológico en infecciones por coronavirus. Rev Cub Ped. 2020; 92 (Suppl.): e1203. Disponible en: http://www.revpediatria.sld.cu/index.php/ped/article/view/1203

Ellul MA, Benjamin L, Singh B, Lant S, Michael BD, Easton A, et al. Neurological associations of COVID-19. Lancet Neurol. 2020; 19(9): 767-83. doi: 10.1016/S1474-4422(20)30221-0

Cilia R, Bonvegna S, Straccia G, Andreasi NG, Elia AE, Romito LM, et al. Effects of COVID-19 on Parkinson's disease clinical features: a community-based case-control study. Mov Disord. 2020; 35(8): 1287-92. doi: 10.1002/mds.28170

Brown EG, Chahine LM, Goldman SM, Korell M, Mann E, Kinel DR, et al. The effect of the COVID-19 pandemic on people with Parkinson's disease. J Parkinson's Dis. 2020; 10(4): 1365-77. doi: 10.3233/JPD-202249

Berger JR, Brandstadter R, Bar-Or A. COVID-19 and MS disease-modifying therapies. Neurol Neuroimmunol Neuroinflamm. 2020; 7(4): e761 (1-8). doi: 10.1212/NXI.0000000000000761

COViMS Registry. The COViMS database public data update. Disponible en: https://www.COViMS.org

Padrón AA, Dorta A. Patogenia de las manifestaciones neurológicas asociadas al SARS-CoV-2. Rev Cub Inv Biomedicas. 2020; 39(3): e868. Disponible en: http://www.revibiomedica.sld.cu/index.php/ibi/article/view/868

Aschman T, Schneider J, Greuel S, Meinhardt J, Streit S, Goebel HH, et al. Association between SARS-CoV-2 infection and immune-mediated myopathy in patients who have died. JAMA Neurol. 2021;78(8): 948-60. doi: 10.1001/jamaneurol.2021.2004

Machado C, Brock B, Schift A. Reader Response: Skeletal Muscle and Peripheral Nerve Histopathology in COVID-19. Neurology. 2021; 97(18): 881-2. doi: 10.1212/WNL.0000000000012790

Mughal MS, Kaur IP, Alhashemi R, Rehman R, Du D. Acute viral myositis complicated by rhabdomyolysis: a sole manifestation of COVID-19 infection. J Community Hosp Intern Med Perspect. 2021; 11(2): 289-91. doi: 10.1080/20009666.2021.1878601

Paliwal VK, Garg RK, Gupta A, Tejan N. Neuromuscular presentations in patients with COVID-19. Neurol Sci. 2020; 41(11): 3039-56. doi: 10.1007/s10072-020-04708-8

Suh J, Mukerji SS, Collens SI, Padera RF, Pinkus GS, Amato AA, et al. Skeletal muscle and peripheral nerve histopathology in COVID-19. Neurology. 2021; 97(8): e849-e858. doi: 10.1212/WNL.0000000000012344

Carod-Artal FJ. Complicaciones neurológicas por coronavirus y COVID-19. Rev Neurol. 2020; 70(3): 311-22. doi: 10.33588/rn.7009.2020179

Cortés ME. Enfermedad por coronavirus 2019 (COVID-19): importancia de sus potenciales efectos neurológicos. Rev Ecuatoriana Neurol. 2020; 29(1): 16-7. Disponible en: http://revecuatneurol.com/wp-content/uploads/2020/05/2631-2581-rneuro-29-01-00016.pdf

Machado C, DeFina PA, Chinchilla M, Machado Y, Machado Y. Brainstem dysfunction in SARS-COV-2 infection can be a potential cause of respiratory distress. Neurol India. 2020; 68(5): 989-93. doi: 10.4103/0028-3886.299165

Casez O, Willaume G, Grand S, Nemoz B, Lupo J, Kahane P, et al. Teaching NeuroImages: SARS-CoV-2−Related Encephalitis: MRI pattern of olfactory tract involvement. Neurology. 2021; 96: e645-e646. doi: 10.1212/WNL.0000000000011150

Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, et al. Dysregulation of immune response in patients with COVID-19 in Wuhan, China. Clin Infect Dis. 2020; 71(15): 762-8. doi: 10.1093/cid/ciaa248

Helms J, Tacquard C, Severac F, Leonard-Lorant I, Ohana M, Delabranche X, et al. High risk of thrombosis in severe SARS-Cov-2 infection: a multicenter prospective cohort study. Intensive Care Med. 2020; 46(6): 1089-98. doi: 10.1007/s00134-020-06062-x

García-Azorín D, Martínez-Pías E, Trigo J, Hernandez-Perez I, Valle-Peñacoba G, Talavera B, et al. Neurological comorbidity is a predictor of death in COVID-19 disease: a cohort study on 576 patients. Front Neurol. 2020; 11 (3): 781 (1-8). doi.org/10.3389/fneur.2020.00781

Romagnolo A, Balestrino R, Imbalzano G, Ciccone G, Riccardini F, Artusi CA, et al. Neurological comorbidity and severity of COVID-19. J Neurol. 2021; 268(3): 762-9. doi: 10.1007/s00415-020-10123-y

World Health Organization. Tracking SARS-CoV-2 variants. World Health Organization, 2021. Disponible en: https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/

Papanikolaou V, Chrysovergis A, Ragos V, Tsiambas E, Katsinis S, Manoli A, et al. From delta to Omicron: S1- RBD/S2 mutation/deletion equilibrium in SARS-CoV-2 defined variants. Gene. 2022; 814: 146134 (1-5). doi: 10.1016/j.gene.2021.146134

Karim SSA, Karim QA. Omicron SARS-CoV-2 variant: a new chapter in the COVID-19 pandemic. Lancet. 2021; 398: 2126-8. doi: 10.1016/S0140-6736(21)02758-6

Abdullah F, Myers J, Basu D, Tintinger G, Ueckermann V, Mathebula M, et al. Decreased severity of disease during the first global omicron variant covid-19 outbreak in a large hospital in Tshwane, South Africa. Int J Infect Dis. 2021; 116(1): 38-42. doi: 10.1016/j.ijid.2021.12.357

Tureček P, Kleisner K. Symptomic mimicry between SARS-CoV-2 and the Common Cold Complex. Biosemiotics. 2022; 10(1): 1-6. doi: 10.1007/s12304-021-09472-6

Zhang L, Li Q, Liang Z, Li T, Liu S, Qiangian C, et al. The significant immune escape of pseudotyped SARS-CoV-2 variant Omicron. Emerg Microbes Infect. 2022; 11(1): 1-5. doi: 10.1080/22221751.2021.2017757

Borrelli M, Corcione A, Castellano F, Fiori Nastro F, Santamaria F. Coronavirus disease 2019 in children. Front Pediatr. 2021; 28(9): 668484. doi: 10.3389/fped.2021.668484

Castillo-Martínez M, Castillo M, Ferrer M, González-Peris S. Depresión infanto-juvenil y otros aspectos de salud mental durante el confinamiento y la pandemia por SARS-CoV-2/COVID-19: encuesta en contexto escolar. An Pediatr (Barc). 2022; 96(1): 61-4. doi: 10.1016/j.anpedi.2020.09.013

Golberstein E, Wen H, Miller BF. Coronavirus Disease 2019 (COVID19) and mental health for children and adolescents. JAMA Pediatr. 2020; 174(9): 819-20. doi: 10.1001/jamapediatrics.2020.1456

Lee PI, Hu YL, Chen PY, Huang YC, Hsueh PR. Are children less susceptible to COVID-19? J Microbiol Immunol Infect. 2020; 53(3): 371-2. doi: 10.1016/j.jmii.2020.02.011

Carsetti R, Quintarelli C, Quinti I, Mortari E, Zumla A, Ippolito G, et al. The immune system of children: the key to understanding SARS-CoV-2 susceptibility? Lancet Child Adolesc Health. 2020; 4(6): 414-6. doi: 10.1016/S2352-4642(20)30135-8

González P, Pérez-Moneo Agapito B, Albi MS, Aizpurúa P, Rodrigo MA, Fernández MM, et al (Grupo de Trabajo de Pediatría Basada en la Evidencia de la AEP y AEPap). COVID-19 en Pediatría: valoración crítica de la evidencia. An Pediatr (Barc). 2021; 95(3): e1-e13. doi:10.1016/j.anpedi.2021.05.019

Callard F, Perego E. How and Why patients made Long-Covid? Soc Sci Med. 2021; 268: 113426 (1-5). doi: 10.1016/j.socscimed.2020.113426

Iqbal FM, Lam K, Sounderajah V, Clarke JM, Ashrafian H, Darzi A. Characteristics and predictors of acute and chronic post-Covid syndrome: a systematic review and meta-analysis. EClinical Medicine. 2021; 36: 100899 (1-13). doi: 10.1016/j.eclinm.2021.100899

Liu YH, Chen Y, Wang QH, Wang LR, Jiang L, Yang Y, et al. One-Year trajectory of cognitive changes in older survivors of COVID-19 in Wuhan, China: A longitudinal cohort study. JAMA Neurol. 2022; e220461 (e1-e10). doi: 10.1001/jamaneurol.2022.0461

Douaud G, Lee S, Alfaro-Almagro F, Arthofer C, Wang C, McCarthy P, et al. SARS-CoV-2 is associated with changes in brain structure in UK Biobank. Nature. 2022; s41586. doi: 10.1038/s41586-022-04569-5

Taquet M, Geddes JR, Husain M, Luciano S, Harrison PJ. 6-month neurological and psychiatric outcomes in 236.379 survivors of COVID-19: a retrospective cohort study using electronic health records. Lancet Psychiatry. 2021; 8(5): 416-27. doi: https://doi.org/10.1101/2021.01.16.21249950

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