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 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.
| Errataetall: |
UpdateIn: Cell Rep Med. 2021 May 18;2(5):100288. - PMID 33969321 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2020 |
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| Enthalten in: |
bioRxiv : the preprint server for biology - (2020) vom: 09. Dez. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Song, Eric [VerfasserIn] |
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| Links: |
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Date Revised 10.11.2023 published: Electronic UpdateIn: Cell Rep Med. 2021 May 18;2(5):100288. - PMID 33969321 Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1101/2020.09.11.293464 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM315069856 |
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| 245 | 1 | 0 | |a Exploratory neuroimmune profiling identifies CNS-specific alterations in COVID-19 patients with neurological involvement |
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| 500 | |a published: Electronic | ||
| 500 | |a UpdateIn: Cell Rep Med. 2021 May 18;2(5):100288. - PMID 33969321 | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a 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 | ||
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| 700 | 1 | |a Bartley, Christopher M |e verfasserin |4 aut | |
| 700 | 1 | |a Chow, Ryan D |e verfasserin |4 aut | |
| 700 | 1 | |a Ngo, Thomas T |e verfasserin |4 aut | |
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