CSF Biomarkers in COVID-19 Associated Encephalopathy and Encephalitis Predict Long-Term Outcome

Patients with coronavirus disease 2019 (COVID-19) frequently develop acute encephalopathy and encephalitis, but whether these complications are the result from viral-induced cytokine storm syndrome or anti-neural autoimmunity is still unclear. In this study, we aimed to evaluate the diagnostic and p...

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Autores: Guasp, Mar, Muñoz Sánchez, Guillermo, Martínez Hernández, Eugenia, Santana Moreno, Daniel, Carbayo, Álvaro, Naranjo, Laura, Bolós, Uma, Framil, Mario, Saiz Hinarejos, Albert, Balasa, Mircea, Ruiz García, Raquel, Sánchez Valle, Raquel, Barcelona Neuro-COVID Study Group
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/185909
Acceso en línea:https://hdl.handle.net/2445/185909
Access Level:acceso abierto
Palabra clave:COVID-19
Encefalitis
Encephalitis
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spelling CSF Biomarkers in COVID-19 Associated Encephalopathy and Encephalitis Predict Long-Term OutcomeGuasp, MarMuñoz Sánchez, GuillermoMartínez Hernández, EugeniaSantana Moreno, DanielCarbayo, ÁlvaroNaranjo, LauraBolós, UmaFramil, MarioSaiz Hinarejos, AlbertBalasa, MirceaRuiz García, RaquelSánchez Valle, RaquelBarcelona Neuro-COVID Study GroupCOVID-19EncefalitisCOVID-19EncephalitisPatients with coronavirus disease 2019 (COVID-19) frequently develop acute encephalopathy and encephalitis, but whether these complications are the result from viral-induced cytokine storm syndrome or anti-neural autoimmunity is still unclear. In this study, we aimed to evaluate the diagnostic and prognostic role of CSF and serum biomarkers of inflammation (a wide array of cytokines, antibodies against neural antigens, and IgG oligoclonal bands), and neuroaxonal damage (14-3-3 protein and neurofilament light [NfL]) in patients with acute COVID-19 and associated neurologic manifestations (neuro-COVID). We prospectively included 60 hospitalized neuro-COVID patients, 25 (42%) of them with encephalopathy and 14 (23%) with encephalitis, and followed them for 18 months. We found that, compared to healthy controls (HC), neuro-COVID patients presented elevated levels of IL-18, IL-6, and IL-8 in both serum and CSF. MCP1 was elevated only in CSF, while IL-10, IL-1RA, IP-10, MIG and NfL were increased only in serum. Patients with COVID-associated encephalitis or encephalopathy had distinct serum and CSF cytokine profiles compared with HC, but no differences were found when both clinical groups were compared to each other. Antibodies against neural antigens were negative in both groups. While the levels of neuroaxonal damage markers, 14-3-3 and NfL, and the proinflammatory cytokines IL-18, IL-1RA and IL-8 significantly associated with acute COVID-19 severity, only the levels of 14-3-3 and NfL in CSF significantly correlated with the degree of neurologic disability in the daily activities at 18 months follow-up. Thus, the inflammatory process promoted by SARS-CoV-2 infection might include blood-brain barrier disruption in patients with neurological involvement. In conclusion, the fact that the levels of pro-inflammatory cytokines do not predict the long-term functional outcome suggests that the prognosis is more related to neuronal damage than to the acute neuroinflammatory process.Frontiers Media2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/185909Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.3389/fimmu.2022.866153Frontiers in Immunology, 2022, vol. 13https://doi.org/10.3389/fimmu.2022.866153cc by (c) Guasp, Mar et al, 2022http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1859092026-05-27T06:46:51Z
dc.title.none.fl_str_mv CSF Biomarkers in COVID-19 Associated Encephalopathy and Encephalitis Predict Long-Term Outcome
title CSF Biomarkers in COVID-19 Associated Encephalopathy and Encephalitis Predict Long-Term Outcome
spellingShingle CSF Biomarkers in COVID-19 Associated Encephalopathy and Encephalitis Predict Long-Term Outcome
Guasp, Mar
COVID-19
Encefalitis
COVID-19
Encephalitis
title_short CSF Biomarkers in COVID-19 Associated Encephalopathy and Encephalitis Predict Long-Term Outcome
title_full CSF Biomarkers in COVID-19 Associated Encephalopathy and Encephalitis Predict Long-Term Outcome
title_fullStr CSF Biomarkers in COVID-19 Associated Encephalopathy and Encephalitis Predict Long-Term Outcome
title_full_unstemmed CSF Biomarkers in COVID-19 Associated Encephalopathy and Encephalitis Predict Long-Term Outcome
title_sort CSF Biomarkers in COVID-19 Associated Encephalopathy and Encephalitis Predict Long-Term Outcome
dc.creator.none.fl_str_mv Guasp, Mar
Muñoz Sánchez, Guillermo
Martínez Hernández, Eugenia
Santana Moreno, Daniel
Carbayo, Álvaro
Naranjo, Laura
Bolós, Uma
Framil, Mario
Saiz Hinarejos, Albert
Balasa, Mircea
Ruiz García, Raquel
Sánchez Valle, Raquel
Barcelona Neuro-COVID Study Group
author Guasp, Mar
author_facet Guasp, Mar
Muñoz Sánchez, Guillermo
Martínez Hernández, Eugenia
Santana Moreno, Daniel
Carbayo, Álvaro
Naranjo, Laura
Bolós, Uma
Framil, Mario
Saiz Hinarejos, Albert
Balasa, Mircea
Ruiz García, Raquel
Sánchez Valle, Raquel
Barcelona Neuro-COVID Study Group
author_role author
author2 Muñoz Sánchez, Guillermo
Martínez Hernández, Eugenia
Santana Moreno, Daniel
Carbayo, Álvaro
Naranjo, Laura
Bolós, Uma
Framil, Mario
Saiz Hinarejos, Albert
Balasa, Mircea
Ruiz García, Raquel
Sánchez Valle, Raquel
Barcelona Neuro-COVID Study Group
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv COVID-19
Encefalitis
COVID-19
Encephalitis
topic COVID-19
Encefalitis
COVID-19
Encephalitis
description Patients with coronavirus disease 2019 (COVID-19) frequently develop acute encephalopathy and encephalitis, but whether these complications are the result from viral-induced cytokine storm syndrome or anti-neural autoimmunity is still unclear. In this study, we aimed to evaluate the diagnostic and prognostic role of CSF and serum biomarkers of inflammation (a wide array of cytokines, antibodies against neural antigens, and IgG oligoclonal bands), and neuroaxonal damage (14-3-3 protein and neurofilament light [NfL]) in patients with acute COVID-19 and associated neurologic manifestations (neuro-COVID). We prospectively included 60 hospitalized neuro-COVID patients, 25 (42%) of them with encephalopathy and 14 (23%) with encephalitis, and followed them for 18 months. We found that, compared to healthy controls (HC), neuro-COVID patients presented elevated levels of IL-18, IL-6, and IL-8 in both serum and CSF. MCP1 was elevated only in CSF, while IL-10, IL-1RA, IP-10, MIG and NfL were increased only in serum. Patients with COVID-associated encephalitis or encephalopathy had distinct serum and CSF cytokine profiles compared with HC, but no differences were found when both clinical groups were compared to each other. Antibodies against neural antigens were negative in both groups. While the levels of neuroaxonal damage markers, 14-3-3 and NfL, and the proinflammatory cytokines IL-18, IL-1RA and IL-8 significantly associated with acute COVID-19 severity, only the levels of 14-3-3 and NfL in CSF significantly correlated with the degree of neurologic disability in the daily activities at 18 months follow-up. Thus, the inflammatory process promoted by SARS-CoV-2 infection might include blood-brain barrier disruption in patients with neurological involvement. In conclusion, the fact that the levels of pro-inflammatory cytokines do not predict the long-term functional outcome suggests that the prognosis is more related to neuronal damage than to the acute neuroinflammatory process.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/185909
url https://hdl.handle.net/2445/185909
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3389/fimmu.2022.866153
Frontiers in Immunology, 2022, vol. 13
https://doi.org/10.3389/fimmu.2022.866153
dc.rights.none.fl_str_mv cc by (c) Guasp, Mar et al, 2022
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Guasp, Mar et al, 2022
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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