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Exploratory neuroimmune profiling identifies CNS-specific alterations in COVID-19 patients with neurological involvement
One third of COVID-19 patients develop significant neurological symptoms, yet SARS-CoV-2 is rarely detected in central nervous system (CNS) tissue, suggesting a potential role for parainfectious processes, including neuroimmune responses. We therefore examined immune parameters in cerebrospinal flui...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491516/ https://www.ncbi.nlm.nih.gov/pubmed/32935102 http://dx.doi.org/10.1101/2020.09.11.293464 |
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author | Song, Eric Bartley, Christopher M. Chow, Ryan D. Ngo, Thomas T. Jiang, Ruoyi Zamecnik, Colin R. Dandekar, Ravi Loudermilk, Rita P. Dai, Yile Liu, Feimei Hawes, Isobel A. Alvarenga, Bonny D. Huynh, Trung McAlpine, Lindsay Rahman, Nur-Taz Geng, Bertie Chiarella, Jennifer Goldman-Israelow, Benjamin Vogels, Chantal B.F. Grubaugh, Nathan D. Casanovas-Massana, Arnau Phinney, Brett S. Salemi, Michelle Alexander, Jessa Gallego, Juan A. Lencz, Todd Walsh, Hannah Lucas, Carolina Klein, Jon Mao, Tianyang Oh, Jieun Ring, Aaron Spudich, Serena Ko, Albert I. Kleinstein, Steven H. DeRisi, Joseph L. Iwasaki, Akiko Pleasure, Samuel J. Wilson, Michael R. Farhadian, Shelli F. |
author_facet | Song, Eric Bartley, Christopher M. Chow, Ryan D. Ngo, Thomas T. Jiang, Ruoyi Zamecnik, Colin R. Dandekar, Ravi Loudermilk, Rita P. Dai, Yile Liu, Feimei Hawes, Isobel A. Alvarenga, Bonny D. Huynh, Trung McAlpine, Lindsay Rahman, Nur-Taz Geng, Bertie Chiarella, Jennifer Goldman-Israelow, Benjamin Vogels, Chantal B.F. Grubaugh, Nathan D. Casanovas-Massana, Arnau Phinney, Brett S. Salemi, Michelle Alexander, Jessa Gallego, Juan A. Lencz, Todd Walsh, Hannah Lucas, Carolina Klein, Jon Mao, Tianyang Oh, Jieun Ring, Aaron Spudich, Serena Ko, Albert I. Kleinstein, Steven H. DeRisi, Joseph L. Iwasaki, Akiko Pleasure, Samuel J. Wilson, Michael R. Farhadian, Shelli F. |
author_sort | Song, Eric |
collection | PubMed |
description | One third of COVID-19 patients develop significant neurological symptoms, yet SARS-CoV-2 is rarely detected in central nervous system (CNS) tissue, suggesting a potential role for parainfectious processes, including neuroimmune responses. We therefore examined immune parameters in cerebrospinal fluid (CSF) and blood samples from a cohort of patients with COVID-19 and significant neurological complications. We found divergent immunological responses in the CNS compartment, including increased levels of IL-12 and IL-12-associated innate and adaptive immune cell activation. Moreover, we found increased proportions of B cells in the CSF relative to the periphery and evidence of clonal expansion of CSF B cells, suggesting a divergent intrathecal humoral response to SARS-CoV-2. Indeed, all COVID-19 cases examined had anti-SARS-CoV-2 IgG antibodies in the CSF whose target epitopes diverged from serum antibodies. We directly examined whether CSF resident antibodies target self-antigens and found a significant burden of CNS autoimmunity, with the CSF from most patients recognizing neural self-antigens. Finally, we produced a panel of monoclonal antibodies from patients’ CSF and show that these target both anti-viral and anti-neural antigens—including one mAb specific for the spike protein that also recognizes neural tissue. This exploratory immune survey reveals evidence of a compartmentalized and self-reactive immune response in the CNS meriting a more systematic evaluation of neurologically impaired COVID-19 patients. |
format | Online Article Text |
id | pubmed-7491516 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-74915162020-09-16 Exploratory neuroimmune profiling identifies CNS-specific alterations in COVID-19 patients with neurological involvement Song, Eric Bartley, Christopher M. Chow, Ryan D. Ngo, Thomas T. Jiang, Ruoyi Zamecnik, Colin R. Dandekar, Ravi Loudermilk, Rita P. Dai, Yile Liu, Feimei Hawes, Isobel A. Alvarenga, Bonny D. Huynh, Trung McAlpine, Lindsay Rahman, Nur-Taz Geng, Bertie Chiarella, Jennifer Goldman-Israelow, Benjamin Vogels, Chantal B.F. Grubaugh, Nathan D. Casanovas-Massana, Arnau Phinney, Brett S. Salemi, Michelle Alexander, Jessa Gallego, Juan A. Lencz, Todd Walsh, Hannah Lucas, Carolina Klein, Jon Mao, Tianyang Oh, Jieun Ring, Aaron Spudich, Serena Ko, Albert I. Kleinstein, Steven H. DeRisi, Joseph L. Iwasaki, Akiko Pleasure, Samuel J. Wilson, Michael R. Farhadian, Shelli F. bioRxiv Article One third of COVID-19 patients develop significant neurological symptoms, yet SARS-CoV-2 is rarely detected in central nervous system (CNS) tissue, suggesting a potential role for parainfectious processes, including neuroimmune responses. We therefore examined immune parameters in cerebrospinal fluid (CSF) and blood samples from a cohort of patients with COVID-19 and significant neurological complications. We found divergent immunological responses in the CNS compartment, including increased levels of IL-12 and IL-12-associated innate and adaptive immune cell activation. Moreover, we found increased proportions of B cells in the CSF relative to the periphery and evidence of clonal expansion of CSF B cells, suggesting a divergent intrathecal humoral response to SARS-CoV-2. Indeed, all COVID-19 cases examined had anti-SARS-CoV-2 IgG antibodies in the CSF whose target epitopes diverged from serum antibodies. We directly examined whether CSF resident antibodies target self-antigens and found a significant burden of CNS autoimmunity, with the CSF from most patients recognizing neural self-antigens. Finally, we produced a panel of monoclonal antibodies from patients’ CSF and show that these target both anti-viral and anti-neural antigens—including one mAb specific for the spike protein that also recognizes neural tissue. This exploratory immune survey reveals evidence of a compartmentalized and self-reactive immune response in the CNS meriting a more systematic evaluation of neurologically impaired COVID-19 patients. Cold Spring Harbor Laboratory 2020-12-09 /pmc/articles/PMC7491516/ /pubmed/32935102 http://dx.doi.org/10.1101/2020.09.11.293464 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Article Song, Eric Bartley, Christopher M. Chow, Ryan D. Ngo, Thomas T. Jiang, Ruoyi Zamecnik, Colin R. Dandekar, Ravi Loudermilk, Rita P. Dai, Yile Liu, Feimei Hawes, Isobel A. Alvarenga, Bonny D. Huynh, Trung McAlpine, Lindsay Rahman, Nur-Taz Geng, Bertie Chiarella, Jennifer Goldman-Israelow, Benjamin Vogels, Chantal B.F. Grubaugh, Nathan D. Casanovas-Massana, Arnau Phinney, Brett S. Salemi, Michelle Alexander, Jessa Gallego, Juan A. Lencz, Todd Walsh, Hannah Lucas, Carolina Klein, Jon Mao, Tianyang Oh, Jieun Ring, Aaron Spudich, Serena Ko, Albert I. Kleinstein, Steven H. DeRisi, Joseph L. Iwasaki, Akiko Pleasure, Samuel J. Wilson, Michael R. Farhadian, Shelli F. Exploratory neuroimmune profiling identifies CNS-specific alterations in COVID-19 patients with neurological involvement |
title | Exploratory neuroimmune profiling identifies CNS-specific alterations in COVID-19 patients with neurological involvement |
title_full | Exploratory neuroimmune profiling identifies CNS-specific alterations in COVID-19 patients with neurological involvement |
title_fullStr | Exploratory neuroimmune profiling identifies CNS-specific alterations in COVID-19 patients with neurological involvement |
title_full_unstemmed | Exploratory neuroimmune profiling identifies CNS-specific alterations in COVID-19 patients with neurological involvement |
title_short | Exploratory neuroimmune profiling identifies CNS-specific alterations in COVID-19 patients with neurological involvement |
title_sort | exploratory neuroimmune profiling identifies cns-specific alterations in covid-19 patients with neurological involvement |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491516/ https://www.ncbi.nlm.nih.gov/pubmed/32935102 http://dx.doi.org/10.1101/2020.09.11.293464 |
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