Achados neuropatológicos da Covid-19: uma revisão sistemática
DOI:
https://doi.org/10.34024/rnc.2021.v29.11842Palavras-chave:
Covid-19, Coronavírus, Neuroinflamação, Acidente Vascular CerebralResumo
Introdução. A doença causada pelo Sars-Cov-2, Covid-19, foi identificada pela primeira vez na China e apresentou rápida expansão mundial, sendo reconhecida como pandemia em março de 2020. Apesar de causar uma infecção de vias aéreas, descobertas clínicas recentes e estudos com animais sugerem que o vírus também promove vias neuronais notáveis e comprometimentos do sistema circulatório, levando a lesões no sistema nervoso central. Objetivo. Coletar e analisar os dados publicados entre 2019 e 2020 a respeito de lesões encontradas no sistema nervoso a partir de estudos de necrópsia e de imagem realizados em seres humanos. Método. Uma busca sistemática foi feita nas bases de dados PubMed e Science Direct utilizando os descritores “COVID-19” OU “SARS-CoV-2” OU “Coronavirus” AND “Central Nervous System” OU “Brain” AND “Autopsy” OR “RMI”. Foram incluídos estudos originais primários, publicados entre 2019 e 2020. Foram excluídos estudos realizados em animais, casos não comprovados de contaminação por COVID-19 e estudos in vitro. Resultados. Os principais achados desta revisão sistemática apontam para causas imunológicas, inflamatórias e infecciosas. Hemorragia intracranial e intracerebral e Acidente Vascular Cerebral (AVC) isquêmico foram os principais eventos relatados, sendo que o AVC relacionado a Covid-19 tende a ser mais grave do que outras causas. Conclusão. Embora os dados científicos ainda sejam escassos para explicar as vias de dano do SARS-CoV-2 no sistema nervoso central, as evidências disponíveis sugerem uma correlação entre COVID-19 e complicações neurológicas em alguns pacientes.
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Ludwig S, Zarbock A. Coronaviruses and SARS-CoV-2: A Brief Overview. Anesth Analg 2020;131:93-6. http://dx.doi.org/10.1213/ANE.0000000000004845
Coronavirus disease (COVID-19). World Health Organization (endereço na Internet). Acessado em 12/2020). Disponível em: https://www.who.int/emergencies/diseases/novel-coronavirus-2019?gclid=CjwKCAjwrKr8BRB_EiwA7eFapjv8OZ_u6sHDmH9GDT30e5uo1lyInyKfUpJ0q5oQagPAVuYYojb4PxoC8RAQAvD_BwE
Jin Y, Yang H, Ji W, Wu W, Chen S, Zhang W, et al. Virology, Epidemiology, Pathogenesis, and Control of COVID-19. Viruses 2020;12:372. http://dx.doi.org/10.3390/v12040372
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;77:683-90. http://dx.doi.org/10.1001/jamaneurol.2020.1127
Al-Dalahmah O, Thakur KT, Nordvig AS, Prust ML, Roth W, Lignelli A, et al. Neuronophagia and microglial nodules in a SARS-CoV-2 patient with cerebellar hemorrhage. Acta Neuropathol Commun 2020;8:1-7. https://doi.org/10.1186/s40478-020-01024-2
Schurink B, Roos E, Radonic T, Barbe E, Bouman CSC, de Boer HH, et al. Viral presence and immunopathology in patients with lethal COVID-19: a prospective autopsy cohort study. Lancet Microbe 2020;1:e290-9. http://dx.doi.org/10.1016/S2666-5247(20)30144-0
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;143:3104-20. http://dx.doi.org/10.1093/brain/awaa240
Dalakas MC. Guillain-Barré syndrome: The first documented COVID-19–triggered autoimmune neurologic disease. Neurol Neuroimmunol Neuroinflamm 2020;7:e781. http://dx.doi.org/10.1212/nxi.0000000000000781
Bellon M, Schweblin C, Lambeng N, Cherpillod P, Vazquez J, Lalive PH, et al. Cerebrospinal Fluid Features in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Reverse Transcription Polymerase Chain Reaction (RT-PCR) Positive Patients. Clin Infect Dis 2020:ciaa1165. http://dx.doi.org/10.1093/cid/ciaa1165
Hanley B, Naresh KN, Roufosse C, Nicholson AG, Weir J, Cooke GS, et al. Histopathological findings and viral tropism in UK patients with severe fatal COVID-19: a post-mortem study. Lancet Microbe 2020;1:e245-53. http://dx.doi.org/10.1016/S2666-5247(20)30115-4
Remmelink M, De Mendonça R, D’Haene N, De Clercq S, Verocq C, Lebrun L, et al. Unspecific post-mortem findings despite multiorgan viral spread in COVID-19 patients. Crit Care 2020;24:495. http://dx.doi.org/10.1186/s13054-020-03218-5
Kantonen J, Mahzabin S, Mäyränpää MI, Tynninen O, Paetau A, Andersson N, et al. Neuropathologic features of four autopsied COVID-19 patients. Brain Pathol 2020;30:1012-6. http://dx.doi.org/10.1111/bpa.12889
Reichard RR, Kashani KB, Boire NA, Constantopoulos E, Guo Y, Lucchinetti CF. Neuropathology of COVID-19: a spectrum of vascular and acute disseminated encephalomyelitis (ADEM)-like pathology. Acta Neuropathol 2020;140:1-6. http://dx.doi.org/10.1007/s00401-020-02166-2
Matschke J, Lütgehetmann M, Hagel C, Sperhake JP, Schröder AS, Edler C, et al. Neuropathology of patients with COVID-19 in Germany: a post-mortem case series. Lancet Neurol 2020;19:919-29. http://dx.doi.org/10.1016/S1474-4422(20)30308-2
Fabbri VP, Foschini MP, Lazzarotto T, Gabrielli L, Cenacchi G, Gallo C, et al. Brain ischemic injury in COVID-19-infected patients: a series of 10 post-mortem cases. Brain Pathol 2020;e12901. http://dx.doi.org/10.1111/bpa.12901
Jensen MP, Le Quesne J, Officer-Jones L, Teodòsio A, Thaventhiran J, Ficken C, et al. Neuropathological findings in two patients with fatal COVID-19. Neuropathol Appl Neurobiol 2020;47:17-25. http://dx.doi.org/10.1111/nan.12662
Kirschenbaum D, Imbach LL, Rushing EJ, Frauenknecht KBM, Gascho D, Ineichen BV, et al. Intracerebral endotheliitis and microbleeds are neuropathological features of COVID‐19. Neuropathol Appl Neurobiol 2021;47:454-9. http://dx.doi.org/10.1111/nan.12677
Kandemirli SG, Dogan L, Sarikaya ZT, Kara S, Akinci C, Kaya D, et al. Brain MRI Findings in Patients in the Intensive Care Unit with COVID-19 Infection. Radiology 2020;201697. http://dx.doi.org/10.1148/radiol.2020201697
Kremer S, Lersy F, de Sèze J, Ferré J-C, Maamar A, Carsin-Nicol B, et al. Brain MRI Findings in Severe COVID-19: A Retrospective Observational Study. Radiology 2020;202222. http://dx.doi.org/10.1148/radiol.2020202222
Moriguchi T, Harii N, Goto J, Harada D, Sugawara H, Takamino J, et al. A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. Int J Infect Dis 2020;94:55-8. http://dx.doi.org/10.1016/j.ijid.2020.03.062
Romero-Sánchez CM, Díaz-Maroto I, Fernández-Díaz E, Sánchez-Larsen Á, Layos-Romero A, García-García J, et al. Neurologic manifestations in hospitalized patients with COVID-19: The ALBACOVID registry. Neurology 2020;95:e1060-70. http://dx.doi.org/10.1212/WNL.0000000000009937
Radmanesh A, Raz E, Zan E, Derman A, Kaminetzky M. Brain Imaging Use and Findings in COVID-19: A Single Academic Center Experience in the Epicenter of Disease in the United States. Am J Neuroradiol 2020;41:1179-83. http://dx.doi.org/10.3174/ajnr.A6610
Radmanesh A, Derman A, Lui YW, Raz E, Loh JP, Hagiwara M, et al. COVID-19-associated Diffuse Leukoencephalopathy and Microhemorrhages. Radiology 2020;297:E223-7. http://dx.doi.org/10.1148/radiol.2020202040
Morassi M, Bagatto D, Cobelli M, D’Agostini S, Gigli GL, Bnà C, et al. Stroke in patients with SARS-CoV-2 infection: case series. J Neurol 2020;267:2185-92. http://dx.doi.org/10.1007/s00415-020-09885-2
Zoghi A, Ramezani M, Roozbeh M, Darazam IA, Sahraian MA. A case of possible atypical demyelinating event of the central nervous system following COVID-19. Mult Scler Relat Disord 2020;44:102324. http://dx.doi.org/10.1016/j.msard.2020.102324
Klironomos S, Tzortzakakis A, Kits A, Öhberg C, Kollia E, Ahoromazdae A, et al. Nervous System Involvement in Coronavirus Disease 2019: Results from a Retrospective Consecutive Neuroimaging Cohort. Radiology 2020;297:E324-34. http://dx.doi.org/10.1148/radiol.2020202791
Anzalone N, Castellano A, Scotti R, Scandroglio AM, Filippi M, Ciceri F, et al. Multifocal laminar cortical brain lesions: a consistent MRI finding in neuro-COVID-19 patients. J Neurol 2020;267:2806-9. http://dx.doi.org/10.1007/s00415-020-09966-2
Efe IE, Aydin OU, Alabulut A, Celik O, Aydin K. COVID-19−Associated Encephalitis Mimicking Glial Tumor. World Neurosurger 2020;140:46-8. http://dx.doi.org/10.1016/j.wneu.2020.05.194
Sirous R, Taghvaei R, Hellinger JC, Krauthamer AV, Mirfendereski S. COVID-19-associated encephalopathy with fulminant cerebral vasoconstriction: CT and MRI findings. Radiol Case Rep 2020;15:2208-12. http://dx.doi.org/10.1016/j.radcr.2020.08.024
AlKetbi R, AlNuaimi D, AlMulla M, AlTalai N, Samir M, Kumar N, et al. Acute myelitis as a neurological complication of Covid-19: A case report and MRI findings. Radiol Case Rep 2020;15:1591-5. http://dx.doi.org/10.1016/j.radcr.2020.06.001
TunÇ A, ÜnlÜbaŞ Y, Alemdar M, AkyÜz E. Coexistence of COVID-19 and acute ischemic stroke report of four cases. J Clin Neurosci 2020;77:227-9. http://dx.doi.org/10.1016/j.jocn.2020.05.018
Afshar H, Yassin Z, Kalantari S, Aloosh O, Lotfi T, Moghaddasi M, et al. Evolution and resolution of brain involvement associated with SARS- CoV2 infection: A close Clinical – Paraclinical follow up study of a case. Mult Scler Relat Disord 2020;43:102216. http://dx.doi.org/10.1016/j.msard.2020.102216
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;296:E119-20. http://dx.doi.org/10.1148/radiol.2020201187
Politi LS, Salsano E, Grimaldi M. Magnetic Resonance Imaging Alteration of the Brain in a Patient With Coronavirus Disease 2019 (COVID-19) and Anosmia. JAMA Neurol 2020;77:1028. http://dx.doi.org/10.1001/jamaneurol.2020.2125
Virhammar J, Kumlien E, Fällmar D, Frithiof R, Jackmann S, Sköld MK, et al. Acute necrotizing encephalopathy with SARS-CoV-2 RNA confirmed in cerebrospinal fluid. Neurology 2020;95:445-9. http://dx.doi.org/10.1212/WNL.0000000000010250
Guennec LL, Le Guennec L, Devianne J, Jalin L, Cao A, Galanaud D, et al. Orbitofrontal involvement in a neuroCOVID‐19 patient. Epilepsia 2020;61:e90-4. http://dx.doi.org/10.1111/epi.16612
Palao M, Fernández-Díaz E, Gracia-Gil J, Romero-Sánchez CM, Díaz-Maroto I, Segura T. Multiple sclerosis following SARS-CoV-2 infection. Mult Scler Relat Disord 2020;45:102377. http://dx.doi.org/10.1016/j.msard.2020.102377
Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell 2020;181:271-80. http://dx.doi.org/10.1016/j.cell.2020.02.052
Al-Olama M, Rashid A, Garozzo D. COVID-19-associated meningoencephalitis complicated with intracranial hemorrhage: a case report. Acta Neurochir 2020;162:1495-9. http://dx.doi.org/10.1007/s00701-020-04402-w
Yang L, Han Y, Nilsson-Payant BE, Gupta V, Wang P, Duan X, et al. A Human Pluripotent Stem Cell-based Platform to Study SARS-CoV-2 Tropism and Model Virus Infection in Human Cells and Organoids. Cell Stem Cell 2020;27:125-36.e7. http://dx.doi.org/10.1016/j.stem.2020.06.015
Kirschenbaum D, Imbach LL, Rushing EJ, Frauenknecht KBM, Gascho D, Ineichen BV, et al. Intracerebral endotheliitis and microbleeds are neuropathological features of COVID‐19. Neuropathol Appl Neurobiol 2020;47:454-9. http://dx.doi.org/10.1111/nan.12677
Conklin J, Frosch MP, Mukerji S, Rapalino O, Maher M, Schaefer PW, et al. Cerebral Microvascular Injury in Severe COVID-19. medRxiv 2020.07.21.20159376. http://dx.doi.org/10.1101/2020.07.21.20159376
Roy D, Hollingworth M, Kumaria A. A case of malignant cerebral infarction associated with COVID-19 infection. Br J Neurosurg 2020;1-4. http://dx.doi.org/10.1080/02688697.2020.1779180
He J, Cheng G, Xu W, Zhang L, Zeng Z. [Diagnosis and treatment of an elderly patient with secondary cerebral infarction caused by COVID-19]. Nan Fang Yi Ke Da Xue Xue Bao 2020;40:351-2. http://dx.doi.org/10.12122/j.issn.1673-4254.2020.03.10
Zhang L, Yan X, Fan Q, Liu H, Liu X, Liu Z, et al. D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19. J Thromb Haemost 2020;18:1324-9. http://dx.doi.org/10.1111/jth.14859
Ntaios G, Michel P, Georgiopoulos G, Guo Y, Li W, Xiong J, et al. Characteristics and Outcomes in Patients With COVID-19 and Acute Ischemic Stroke: The Global COVID-19 Stroke Registry. Stroke 2020;51:e254-8. http://dx.doi.org/10.1161/STROKEAHA.120.031208
Pinna P, Grewal P, Hall JP, Tavarez T, Dafer RM, Garg R, et al. Neurological manifestations and COVID-19: Experiences from a tertiary care center at the Frontline. J Neurol Sci 2020;415:116969. http://dx.doi.org/10.1016/j.jns.2020.116969
Lu L, Xiong W, Liu D, Liu J, Yang D, Li N, et al. New onset acute symptomatic seizure and risk factors in coronavirus disease 2019: A retrospective multicenter study. Epilepsia 2020;61:e49-53. http://dx.doi.org/10.1111/epi.16524
Vaira LA, Deiana G, Fois AG, Pirina P, Madeddu G, De Vito A, et al. Objective evaluation of anosmia and ageusia in COVID-19 patients: Single-center experience on 72 cases. Head Neck 2020;42:1252-8. http://dx.doi.org/10.1002/hed.26204
Kandemirli SG, Dogan L, Sarikaya ZT, Kara S, Akinci C, Kaya D, et al. Brain MRI Findings in Patients in the Intensive Care Unit with COVID-19 Infection. Radiology 2020;297:E232-5. http://dx.doi.org/10.1148/radiol.2020201697
Kremer S, Lersy F, Anheim M, Merdji H, Schenck M, Oesterlé H, et al. Neurologic and neuroimaging findings in patients with COVID-19: A retrospective multicenter study. Neurology 2020;95:e1868-82. http://dx.doi.org/10.1212/WNL.0000000000010112
Lavi E, Cong L. Type I astrocytes and microglia induce a cytokine response in an encephalitic murine coronavirus infection. Exp Mol Pathol 2020;115:104474. http://dx.doi.org/10.1016/j.yexmp.2020.104474
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Copyright (c) 2021 Qesya Rodrigues Ferreira, Bruna Teixeira da Costa, Marcelle Machado Mendes, Vinicius Nogueira Cavalcanti, Alberto Christian Luz Santos, David Manoel Pereira Araújo, Patrícia da Silva Oliveira
Este trabalho está licenciado sob uma licença Creative Commons Attribution 4.0 International License.
Aceito: 2021-09-13
Publicado: 2021-10-06
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