Brain injury in COVID-19 is associated with dysregulated innate and adaptive immune responses
© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain..
COVID-19 is associated with neurological complications including stroke, delirium and encephalitis. Furthermore, a post-viral syndrome dominated by neuropsychiatric symptoms is common, and is seemingly unrelated to COVID-19 severity. The true frequency and underlying mechanisms of neurological injury are unknown, but exaggerated host inflammatory responses appear to be a key driver of COVID-19 severity. We investigated the dynamics of, and relationship between, serum markers of brain injury [neurofilament light (NfL), glial fibrillary acidic protein (GFAP) and total tau] and markers of dysregulated host response (autoantibody production and cytokine profiles) in 175 patients admitted with COVID-19 and 45 patients with influenza. During hospitalization, sera from patients with COVID-19 demonstrated elevations of NfL and GFAP in a severity-dependent manner, with evidence of ongoing active brain injury at follow-up 4 months later. These biomarkers were associated with elevations of pro-inflammatory cytokines and the presence of autoantibodies to a large number of different antigens. Autoantibodies were commonly seen against lung surfactant proteins but also brain proteins such as myelin associated glycoprotein. Commensurate findings were seen in the influenza cohort. A distinct process characterized by elevation of serum total tau was seen in patients at follow-up, which appeared to be independent of initial disease severity and was not associated with dysregulated immune responses unlike NfL and GFAP. These results demonstrate that brain injury is a common consequence of both COVID-19 and influenza, and is therefore likely to be a feature of severe viral infection more broadly. The brain injury occurs in the context of dysregulation of both innate and adaptive immune responses, with no single pathogenic mechanism clearly responsible.
| Errataetall: | |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:145 |
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| Enthalten in: |
Brain : a journal of neurology - 145(2022), 11 vom: 21. Nov., Seite 4097-4107 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Needham, Edward J [VerfasserIn] |
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| Links: |
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| Themen: |
Autoantibodies |
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| Anmerkungen: |
Date Completed 23.11.2022 Date Revised 20.03.2024 published: Print CommentIn: Brain. 2022 Oct 06;:. - PMID 36200409 Citation Status MEDLINE |
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| doi: |
10.1093/brain/awac321 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 500 | |a published: Print | ||
| 500 | |a CommentIn: Brain. 2022 Oct 06;:. - PMID 36200409 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. | ||
| 520 | |a COVID-19 is associated with neurological complications including stroke, delirium and encephalitis. Furthermore, a post-viral syndrome dominated by neuropsychiatric symptoms is common, and is seemingly unrelated to COVID-19 severity. The true frequency and underlying mechanisms of neurological injury are unknown, but exaggerated host inflammatory responses appear to be a key driver of COVID-19 severity. We investigated the dynamics of, and relationship between, serum markers of brain injury [neurofilament light (NfL), glial fibrillary acidic protein (GFAP) and total tau] and markers of dysregulated host response (autoantibody production and cytokine profiles) in 175 patients admitted with COVID-19 and 45 patients with influenza. During hospitalization, sera from patients with COVID-19 demonstrated elevations of NfL and GFAP in a severity-dependent manner, with evidence of ongoing active brain injury at follow-up 4 months later. These biomarkers were associated with elevations of pro-inflammatory cytokines and the presence of autoantibodies to a large number of different antigens. Autoantibodies were commonly seen against lung surfactant proteins but also brain proteins such as myelin associated glycoprotein. Commensurate findings were seen in the influenza cohort. A distinct process characterized by elevation of serum total tau was seen in patients at follow-up, which appeared to be independent of initial disease severity and was not associated with dysregulated immune responses unlike NfL and GFAP. These results demonstrate that brain injury is a common consequence of both COVID-19 and influenza, and is therefore likely to be a feature of severe viral infection more broadly. The brain injury occurs in the context of dysregulation of both innate and adaptive immune responses, with no single pathogenic mechanism clearly responsible | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a autoantibodies | |
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