Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Guasp, Mar, Muñoz-Sánchez, Guillermo, Martínez-Hernández, Eugenia, Santana, Daniel, Carbayo, Álvaro, Naranjo, Laura, Bolós, Uma, Framil, Mario, Saiz, Albert, Balasa, Mircea, Ruiz-García, Raquel, Sánchez-Valle, Raquel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9035899/
https://www.ncbi.nlm.nih.gov/pubmed/35479062
http://dx.doi.org/10.3389/fimmu.2022.866153
_version_ 1784693401950617600
author Guasp, Mar
Muñoz-Sánchez, Guillermo
Martínez-Hernández, Eugenia
Santana, Daniel
Carbayo, Álvaro
Naranjo, Laura
Bolós, Uma
Framil, Mario
Saiz, Albert
Balasa, Mircea
Ruiz-García, Raquel
Sánchez-Valle, Raquel
author_facet Guasp, Mar
Muñoz-Sánchez, Guillermo
Martínez-Hernández, Eugenia
Santana, Daniel
Carbayo, Álvaro
Naranjo, Laura
Bolós, Uma
Framil, Mario
Saiz, Albert
Balasa, Mircea
Ruiz-García, Raquel
Sánchez-Valle, Raquel
author_sort Guasp, Mar
collection PubMed
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.
format Online
Article
Text
id pubmed-9035899
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-90358992022-04-26 CSF Biomarkers in COVID-19 Associated Encephalopathy and Encephalitis Predict Long-Term Outcome Guasp, Mar Muñoz-Sánchez, Guillermo Martínez-Hernández, Eugenia Santana, Daniel Carbayo, Álvaro Naranjo, Laura Bolós, Uma Framil, Mario Saiz, Albert Balasa, Mircea Ruiz-García, Raquel Sánchez-Valle, Raquel Front Immunol Immunology 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. Frontiers Media S.A. 2022-04-11 /pmc/articles/PMC9035899/ /pubmed/35479062 http://dx.doi.org/10.3389/fimmu.2022.866153 Text en Copyright © 2022 Guasp, Muñoz-Sánchez, Martínez-Hernández, Santana, Carbayo, Naranjo, Bolós, Framil, Saiz, Balasa, Ruiz-García, Sánchez-Valle and The Barcelona Neuro-COVID Study Group https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Guasp, Mar
Muñoz-Sánchez, Guillermo
Martínez-Hernández, Eugenia
Santana, Daniel
Carbayo, Álvaro
Naranjo, Laura
Bolós, Uma
Framil, Mario
Saiz, Albert
Balasa, Mircea
Ruiz-García, Raquel
Sánchez-Valle, Raquel
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
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_short 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
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9035899/
https://www.ncbi.nlm.nih.gov/pubmed/35479062
http://dx.doi.org/10.3389/fimmu.2022.866153
work_keys_str_mv AT guaspmar csfbiomarkersincovid19associatedencephalopathyandencephalitispredictlongtermoutcome
AT munozsanchezguillermo csfbiomarkersincovid19associatedencephalopathyandencephalitispredictlongtermoutcome
AT martinezhernandezeugenia csfbiomarkersincovid19associatedencephalopathyandencephalitispredictlongtermoutcome
AT santanadaniel csfbiomarkersincovid19associatedencephalopathyandencephalitispredictlongtermoutcome
AT carbayoalvaro csfbiomarkersincovid19associatedencephalopathyandencephalitispredictlongtermoutcome
AT naranjolaura csfbiomarkersincovid19associatedencephalopathyandencephalitispredictlongtermoutcome
AT bolosuma csfbiomarkersincovid19associatedencephalopathyandencephalitispredictlongtermoutcome
AT framilmario csfbiomarkersincovid19associatedencephalopathyandencephalitispredictlongtermoutcome
AT saizalbert csfbiomarkersincovid19associatedencephalopathyandencephalitispredictlongtermoutcome
AT balasamircea csfbiomarkersincovid19associatedencephalopathyandencephalitispredictlongtermoutcome
AT ruizgarciaraquel csfbiomarkersincovid19associatedencephalopathyandencephalitispredictlongtermoutcome
AT sanchezvalleraquel csfbiomarkersincovid19associatedencephalopathyandencephalitispredictlongtermoutcome
AT csfbiomarkersincovid19associatedencephalopathyandencephalitispredictlongtermoutcome