Brain injury in COVID-19 is associated with dysregulated innate and adaptive immune responses
Brain injury in COVID-19 is associated with dysregulated innate and adaptive immune responses
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.
4097-4107
Needham, Edward J.
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Ren, Alexander L.
11b83c14-2873-4b2c-a509-8decfc2ad618
Digby, Richard J.
df28689d-d249-45f1-9faa-7138a9d6e6e9
Norton, Emma
76746af3-fcfc-40cb-aa84-c8da09c830db
2 November 2022
Needham, Edward J.
07742423-ce99-44b3-a8a8-6f0a88e7b0cf
Ren, Alexander L.
11b83c14-2873-4b2c-a509-8decfc2ad618
Digby, Richard J.
df28689d-d249-45f1-9faa-7138a9d6e6e9
Norton, Emma
76746af3-fcfc-40cb-aa84-c8da09c830db
Needham, Edward J., Ren, Alexander L. and Digby, Richard J.
,
et al.
(2022)
Brain injury in COVID-19 is associated with dysregulated innate and adaptive immune responses.
Brain, 147 (2), .
(doi:10.1093/brain/awac321).
Abstract
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.
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awac321
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Accepted/In Press date: 1 August 2022
e-pub ahead of print date: 6 September 2022
Published date: 2 November 2022
Additional Information:
A correction to this research output can be found at: https://doi.org/10.1093/brain/awad371
Identifiers
Local EPrints ID: 498901
URI: http://eprints.soton.ac.uk/id/eprint/498901
ISSN: 0006-8950
PURE UUID: 7f3b7215-f0e1-49a9-a6cc-b7a1706cea05
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Date deposited: 04 Mar 2025 17:53
Last modified: 22 Aug 2025 02:44
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Author:
Edward J. Needham
Author:
Alexander L. Ren
Author:
Richard J. Digby
Author:
Emma Norton
Corporate Author: et al.
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