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@article{Needham:2022:brain/awac321,
author = {Needham, EJ and Ren, AL and Digby, RJ and Norton, EJ and Ebrahimi, S and Outtrim, JG and Chatfield, DA and Manktelow, AE and Leibowitz, MM and Newcombe, VFJ and Doffinger, R and Barcenas-Morales, G and Fonseca, C and Taussig, MJ and Burnstein, RM and Samanta, RJ and Dunai, C and Sithole, N and Ashton, NJ and Zetterberg, H and Gisslén, M and Edén, A and Marklund, E and Openshaw, PJM and Dunning, J and Griffiths, MJ and Cavanagh, J and Breen, G and Irani, SR and Elmer, A and Kingston, N and Summers, C and Bradley, JR and Taams, LS and Michael, BD and Bullmore, ET and Smith, KGC and Lyons, PA and Coles, AJ and Menon, DK and Cambridge, NeuroCOVID Group the CITIID-NIHR COVID-19 BioResource Collaboration and Cambridge NIHR Clinical Research Facility},
doi = {brain/awac321},
journal = {Brain: a journal of neurology},
pages = {4097--4107},
title = {Brain injury in COVID-19 is associated with dysregulated innate and adaptive immune responses},
url = {http://dx.doi.org/10.1093/brain/awac321},
volume = {145},
year = {2022}
}

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TY  - JOUR
AB  - 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 hospitalisation, 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 characterised 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.
AU  - Needham,EJ
AU  - Ren,AL
AU  - Digby,RJ
AU  - Norton,EJ
AU  - Ebrahimi,S
AU  - Outtrim,JG
AU  - Chatfield,DA
AU  - Manktelow,AE
AU  - Leibowitz,MM
AU  - Newcombe,VFJ
AU  - Doffinger,R
AU  - Barcenas-Morales,G
AU  - Fonseca,C
AU  - Taussig,MJ
AU  - Burnstein,RM
AU  - Samanta,RJ
AU  - Dunai,C
AU  - Sithole,N
AU  - Ashton,NJ
AU  - Zetterberg,H
AU  - Gisslén,M
AU  - Edén,A
AU  - Marklund,E
AU  - Openshaw,PJM
AU  - Dunning,J
AU  - Griffiths,MJ
AU  - Cavanagh,J
AU  - Breen,G
AU  - Irani,SR
AU  - Elmer,A
AU  - Kingston,N
AU  - Summers,C
AU  - Bradley,JR
AU  - Taams,LS
AU  - Michael,BD
AU  - Bullmore,ET
AU  - Smith,KGC
AU  - Lyons,PA
AU  - Coles,AJ
AU  - Menon,DK
AU  - Cambridge,NeuroCOVID Group the CITIID-NIHR COVID-19 BioResource Collaboration and Cambridge NIHR Clinical Research Facility
DO  - brain/awac321
EP  - 4107
PY  - 2022///
SN  - 0006-8950
SP  - 4097
TI  - Brain injury in COVID-19 is associated with dysregulated innate and adaptive immune responses
T2  - Brain: a journal of neurology
UR  - http://dx.doi.org/10.1093/brain/awac321
UR  - https://www.ncbi.nlm.nih.gov/pubmed/36065116
UR  - https://academic.oup.com/brain/article/145/11/4097/6692467
UR  - http://hdl.handle.net/10044/1/99518
VL  - 145
ER  -

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