Encephalitis and encephalopathy in patients affected by COVID-19
DOI:
https://doi.org/10.33448/rsd-v10i12.20764Keywords:
Neuropathy; SARS-CoV-2; Central Nervous System.Abstract
Not only the respiratory tract being the main one affected by COVID-19, but also neurological involvement is not uncommon in hospitalized patients and can result in serious complications. Encephalopathy and encephalitis are serious and devastating complications of the Central Nervous System (CNS) that have been associated with COVID-19. This systematic review gathers existing data in the literature regarding the development of different types of encephalitis and encephalopathies in patients with COVID-19. A search was performed in the PubMed, Scopus and Web of Science databases, resulting in 231 articles. There were 25 works left to compose this systematic review. Among them, 2 were retrospective studies and 23 are case reports. 12 studies presented cases with data consistent with encephalitis and 14 with encephalopathies. Among them, some cases with more specific types were observed more than once in our research: 3 meningoencephalitis, 3 Acute Necrotizing Encephalopathy (ANE), 2 Posterior Reversible Encephalopathy Syndrome (PRES), 2 Acute Disseminated Encephalomyelitis (ADEM). Findings of white matter, cortical or subcortical hyperintensities were common. Hypodensity and hypoattenuation of deep white matter structures and focal hypodensity of deep structures, as well as multiple lesions involving hippocampus, basal ganglia, medulla, brainstem, thalamus, among other regions. Postmortem studies have already demonstrated the presence of SARS-CoV-2 viral particles in brain tissue. This CNS involvement associated with COVID-19 is considered an indicator of poor prognosis, which can lead to rapid clinical deterioration of patients.
References
Ahmad, I., & Rathore, F. A. (2020). Neurological manifestations and complications of COVID-19: a literature review. Journal of Clinical Neuroscience, 77, 8-12.
Al-Olama, M., Rashid, A., & Garozzo, D. (2020). COVID-19-associated meningoencephalitis complicated with intracranial hemorrhage: a case report. Acta neurochirurgica, 162(7), 1495-1499.
Beach, S. R., Praschan, N. C., Hogan, C., Dotson, S., Merideth, F., Kontos, N., ... & Smith, F. A. (2020). Delirium in COVID-19: a case series and exploration of potential mechanisms for central nervous system involvement. General Hospital Psychiatry, 65, 47-53.
Benameur, K., Agarwal, A., Auld, S. C., Butters, M. P., Webster, A. S., Ozturk, T., ... & Hu, W. T. (2020). Encephalopathy and encephalitis associated with cerebrospinal fluid cytokine alterations and coronavirus disease, Atlanta, Georgia, USA, 2020. Emerging infectious diseases, 26(9), 2016.
Bernard‐Valnet, R., Pizzarotti, B., Anichini, A., Demars, Y., Russo, E., Schmidhauser, M., ... & Du Pasquier, R. (2020). Two patients with acute meningoencephalitis concomitant with SARS‐CoV‐2 infection. European journal of neurology., 0-1.
Bonzano, C., Borroni, D., Lancia, A., & Bonzano, E. (2020). Doxycycline: from ocular rosacea to COVID-19 anosmia. New insight into the coronavirus outbreak. Frontiers in medicine, 7, 200.
Bridwell, R., Long, B., & Gottlieb, M. (2020). Neurologic complications of COVID-19. The American journal of emergency medicine, 38(7), 1549-e3.
Byrnes, S., Bisen, M., Syed, B., Huda, S., Siddique, Z., Sampat, P., ... & Dargon, I. (2020). COVID‐19 encephalopathy masquerading as substance withdrawal. Journal of medical virology, 6–8.
Carod-Artal, F. J. (2020). Complicaciones neurológicas por coronavirus y COVID-19. Rev Neurol, 70(9), 311-322.
Condie, L. O. (2020). Neurotropic mechanisms in COVID-19 and their potential influence on neuropsychological outcomes in children. Child Neuropsychology, 26(5), 577-596.
Danser, A. J., Epstein, M., & Batlle, D. (2020). Renin-angiotensin system blockers and the COVID-19 pandemic: at present there is no evidence to abandon renin-angiotensin system blockers. Hypertension, 75(6), 1382-1385.
Das, G., Mukherjee, N., & Ghosh, S. (2020). Neurological insights of COVID-19 pandemic. ACS chemical neuroscience, 11(9), 1206-1209.
Deliwala, S., Abdulhamid, S., Abusalih, M. F., Al-Qasmi, M. M., & Bachuwa, G. (2020). Encephalopathy as the sentinel sign of a cortical stroke in a patient infected with coronavirus disease-19 (COVID-19). Cureus, 12(5).
Deshmane, S. L., Kremlev, S., Amini, S., & Sawaya, B. E. (2009). Monocyte chemoattractant protein-1 (MCP-1): an overview. Journal of interferon & cytokine research, 29(6), 313-326.
Dixon, L., Varley, J., Gontsarova, A., Mallon, D., Tona, F., Muir, D., ... & Everitt, A. (2020). COVID-19-related acute necrotizing encephalopathy with brain stem involvement in a patient with aplastic anemia. Neurology-Neuroimmunology Neuroinflammation, 7(5), 1–8.
Dogan, L., Kaya, D., Sarikaya, T., Zengin, R., Dincer, A., Akinci, I. O., & Afsar, N. (2020). Plasmapheresis treatment in COVID-19–related autoimmune meningoencephalitis: case series. Brain, behavior, and immunity, 87, 155-158.
Durjoy, L., & Alfredo, A. (2020). COVID-19 Pandemic: A Neurological Perspective. Cureus, 12(4).
Efe, I. E., Aydin, O. U., Alabulut, A., Celik, O., & Aydin, K. (2020). COVID-19− associated encephalitis mimicking glial tumor. World neurosurgery, 140, 46-48.
Filatov, A., Sharma, P., Hindi, F., & Espinosa, P. S. (2020). Neurological complications of coronavirus disease (COVID-19): encephalopathy. Cureus, 12(3).
Franceschi, A. M., Ahmed, O., Giliberto, L., & Castillo, M. (2020). Hemorrhagic posterior reversible encephalopathy syndrome as a manifestation of COVID-19 infection. American Journal of Neuroradiology, 41(7), 1173-1176.
Garg, R. K., Paliwal, V. K., & Gupta, A. (2021). Encephalopathy in patients with COVID‐19: a review. Journal of Medical Virology, 93(1), 206-222.
Hayashi, M., Sahashi, Y., Baba, Y., Okura, H., & Shimohata, T. (2020). COVID-19-associated mild encephalitis/encephalopathy with a reversible splenial lesion. Journal of the neurological sciences, 415, 116941.
Hepburn, M., Mullaguri, N., George, P., Hantus, S., Punia, V., Bhimraj, A., & Newey, C. R. (2021). Acute symptomatic seizures in critically ill patients with COVID-19: is there an association?. Neurocritical care, 34, 139-143.
Huang, Y. H., Jiang, D., & Huang, J. T. (2020). SARS-CoV-2 detected in cerebrospinal fluid by PCR in a case of COVID-19 encephalitis. Brain, behavior, and immunity, 87, 149.
Hung, E. C., Chim, S. S., Chan, P. K., Tong, Y. K., Ng, E. K., Chiu, R. W., ... & Lo, Y. D. (2003). Detection of SARS coronavirus RNA in the cerebrospinal fluid of a patient with severe acute respiratory syndrome. Clinical Chemistry, 49(12), 2108.
Karimi, N., Razavi, A. S., & Rouhani, N. (2020). Frequent convulsive seizures in an adult patient with COVID-19: a case report. Iranian Red Crescent Medical Journal, 22(3).
Kaya, Y., Kara, S., Akinci, C., & Kocaman, A. S. (2020). Transient cortical blindness in COVID-19 pneumonia; a PRES-like syndrome: case report. Journal of the neurological sciences, 413, 116858.
Kishfy, L., Casasola, M., Banankhah, P., Parvez, A., Jan, Y. J., Shenoy, A. M., ... & AbdelRazek, M. A. (2020). Posterior reversible encephalopathy syndrome (PRES) as a neurological association in severe Covid-19. Journal of the neurological sciences, 414, 116943.
Klok, F. A., Kruip, M. J. H. A., Van der Meer, N. J. M., Arbous, M. S., Gommers, D. A. M. P. J., Kant, K. M., ... & Endeman, H. (2020). Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thrombosis research, 191, 145-147.
Kotfis, K., Roberson, S. W., Wilson, J. E., Dabrowski, W., Pun, B. T., & Ely, E. W. (2020). COVID-19: ICU delirium management during SARS-CoV-2 pandemic. Critical care, 24(1), 1-9.
Li, H., Xue, Q., & Xu, X. (2020). Involvement of the nervous system in SARS-CoV-2 infection. Neurotoxicity research, 1.
Li, Y. C., Bai, W. Z., & Hashikawa, T. (2020). The neuroinvasive potential of SARS‐CoV2 may play a role in the respiratory failure of COVID‐19 patients. Journal of medical virology, 92(6), 552-555.
Li, Y., Li, H., Fan, R., Wen, B., Zhang, J., Cao, X., ... & Liu, W. (2017). Coronavirus infections in the central nervous system and respiratory tract show distinct features in hospitalized children. Intervirology, 59(3), 163-169.
Linares-Espinós, E., Hernández, V., Domínguez-Escrig, J. L., Fernández-Pello, S., Hevia, V., Mayor, J.,... & Ribal, M. J. (2018). Methodology of a systematic review. Metodología de una revisión sistemática. Actas urologicas espanolas, 42(8), 499–506.
Lu, R., Zhao, X., Li, J., Niu, P., Yang, B., Wu, H., ... & Tan, W. (2020). Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. The lancet, 395(10224), 565-574.
Mao, L., Wang, M., Chen, S., He, Q., Chang, J., Hong, C., ... & Hu, B. (2020). Neurological manifestations of hospitalized patients with COVID-19 in Wuhan, China: a retrospective case series study. MedRxiv.
Mehta, P., McAuley, D. F., Brown, M., Sanchez, E., Tattersall, R. S., & Manson, J. J. (2020). COVID-19: consider cytokine storm syndromes and immunosuppression. The lancet, 395(10229), 1033-1034.
Mizuguchi, M., Yamanouchi, H., Ichiyama, T., & Shiomi, M. (2007). Acute encephalopathy associated with influenza and other viral infections. Acta Neurologica Scandinavica, 115, 45-56.
Moriguchi, T., Harii, N., Goto, J., Harada, D., Sugawara, H., Takamino, J., ... & Shimada, S. (2020). A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. International journal of infectious diseases, 94, 55-58.
Munhoz, R. P., Pedroso, J. L., Nascimento, F. A., Almeida, S. M. D., Barsottini, O. G. P., Cardoso, F. E. C., & Teive, H. A. G. (2020). Neurological complications in patients with SARS-CoV-2 infection: a systematic review. Arquivos de Neuro-Psiquiatria, 78, 290-300.
Netland, J., Meyerholz, D. K., 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. Journal of virology, 82(15), 7264-7275.
Paniz‐Mondolfi, A., Bryce, C., Grimes, Z., Gordon, R. E., Reidy, J., Lednicky, J., ... & Fowkes, M. (2020). Central nervous system involvement by severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2). Journal of medical virology, 92(7), 699-702.
Parsons, T., Banks, S., Bae, C., Gelber, J., Alahmadi, H., & Tichauer, M. (2020). COVID-19-associated acute disseminated encephalomyelitis (ADEM). Journal of neurology, 267, 2799-2802.
Pilotto, A., Odolini, S., Masciocchi, S., Comelli, A., Volonghi, I., Gazzina, S., ... & Padovani, A. (2020). Steroid‐responsive encephalitis in coronavirus disease 2019. Annals of neurology, 88(2), 423-427.
Poyiadji, N., Shahin, G., Noujaim, D., Stone, M., Patel, S., & Griffith, B. (2020). COVID-19–associated acute hemorrhagic necrotizing encephalopathy: imaging features. Radiology, 296(2), E119-E120.
Radmanesh, A., Derman, A., Lui, Y. W., Raz, E., Loh, J. P., Hagiwara, M., ... & Fatterpekar, G. M. (2020). COVID-19–associated diffuse leukoencephalopathy and microhemorrhages. Radiology, 297(1), E223-E227.
Romero-Sánchez, C. M., Díaz-Maroto, I., Fernández-Díaz, E., Sánchez-Larsen, Á., Layos-Romero, A., García-García, J., ... & Segura, T. (2020). Neurologic manifestations in hospitalized patients with COVID-19: the ALBACOVID registry. Neurology, 95(8), e1060-e1070.
Rossi, A. (2008). Imaging of acute disseminated encephalomyelitis. Neuroimaging clinics of North America, 18(1), 149-161.
Scullen, T., Keen, J., Mathkour, M., Dumont, A. S., & Kahn, L. (2020). Coronavirus 2019 (COVID-19)–associated encephalopathies and cerebrovascular disease: the New Orleans experience. World neurosurgery, 141, e437-e446.
Sepehrinezhad, A., Shahbazi, A., & Negah, S. S. (2020). COVID-19 virus may have neuroinvasive potential and cause neurological complications: a perspective review. Journal of neurovirology, 1.
Sheraton, M., Deo, N., Kashyap, R., & Surani, S. (2020). A review of neurological complications of COVID-19. Cureus, 12(5).
Sohal, S., & Mansur, M. (2020). COVID-19 presenting with seizures. IDCases, 20, e00782.
Steardo, L., Steardo Jr, L., Zorec, R., & Verkhratsky, A. (2020). Neuroinfection may contribute to pathophysiology and clinical manifestations of COVID‐19. Acta Physiologica (Oxford, England), 229, 10–3.
Tassorelli, C., Mojoli, F., Baldanti, F., Bruno, R., & Benazzo, M. (2020). COVID‐19: what if the brain had a role in causing the deaths?. European journal of neurology.
Toljan, K. (2020). Letter to the editor regarding the viewpoint “evidence of the COVID-19 virus targeting the CNS: tissue distribution, host–virus interaction, and proposed neurotropic mechanism”. ACS chemical neuroscience, 11(8), 1192-1194.
Werner, C., Scullen, T., Mathkour, M., Zeoli, T., Beighley, A., Kilgore, M. D., ... & Keen, J. R. (2020). Neurological impact of coronavirus disease of 2019: practical considerations for the neuroscience community. World neurosurgery, 139, 344-354.
Wong, P. F., Craik, S., Newman, P., Makan, A., Srinivasan, K., Crawford, E., ... & Ahmad, N. (2020). Lessons of the month 1: a case of rhombencephalitis as a rare complication of acute COVID-19 infection. Clinical Medicine, 20(3), 293-294.
Xu, J., Zhong, S., Liu, J., Li, L., Li, Y., Wu, X., ... & Jiang, Y. (2005). Detection of severe acute respiratory syndrome coronavirus in the brain: potential role of the chemokine mig in pathogenesis. Clinical infectious diseases, 41(8), 1089-1096.
Xu, Z., Shi, L., Wang, Y., Zhang, J., Huang, L., Zhang, C., ... & Wang, F. S. (2020). Pathological findings of COVID-19 associated with acute respiratory distress syndrome. The Lancet respiratory medicine, 8(4), 420-422.
Ye, M., Ren, Y., & Lv, T. (2020). Encephalitis as a clinical manifestation of COVID-19. Brain, behavior, and immunity, 88, 945-946.
Zayet, S., Royer, P. Y., Toko-Tchiundzie, L., Gendrin, V., & Klopfenstein, T. (2020). Encephalopathy in patients with COVID-19:'Causality or coincidence?'. Journal of medical virology, 1–3.
Zubair, A. S., McAlpine, L. S., Gardin, T., Farhadian, S., Kuruvilla, D. E., & Spudich, S. (2020). Neuropathogenesis and neurologic manifestations of the coronaviruses in the age of coronavirus disease 2019: a review. JAMA neurology, 77(8), 1018-1027.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2021 Daniele Alcoforado Costa; Brenda Nascimento Dias; Bruna Maria de Carvalho Pereira; Francisco Alex da Rocha Coelho; Grazielle Araújo dos Santos; Joana Darc Viana Silva; Maria Rikelly Frota Aguiar; Thayaná Fernandes; Eduardo de Melo Prado; Rubens Renato de Sousa Carmo; Antônio Thomaz Oliveira
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
1) Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
2) Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
3) Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.
