Brain injury in COVID-19 is associated with dysregulated innate and adaptive immune responses.
COVID-19
autoantibodies
brain injury
neuroinflammation
Journal
Brain : a journal of neurology
ISSN: 1460-2156
Titre abrégé: Brain
Pays: England
ID NLM: 0372537
Informations de publication
Date de publication:
21 11 2022
21 11 2022
Historique:
received:
16
03
2022
revised:
24
06
2022
accepted:
01
08
2022
pubmed:
7
9
2022
medline:
24
11
2022
entrez:
6
9
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 36065116
pii: 6692467
doi: 10.1093/brain/awac321
pmc: PMC9494359
doi:
Substances chimiques
Neurofilament Proteins
0
Biomarkers
0
Autoantibodies
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4097-4107Subventions
Organisme : Medical Research Council
ID : MR/T028750/1
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/V007173/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_G0802534
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/V03605X/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/V007181/1
Pays : United Kingdom
Investigateurs
Fahim Anwar
(F)
Kieren Allinson
(K)
Junaid Bhatti
(J)
Edward T Bullmore
(ET)
Dorothy A Chatfield
(DA)
David Christmas
(D)
Alasdair J Coles
(AJ)
Jonathan P Coles
(JP)
Marta Correia
(M)
Tilak Das
(T)
Paul C Fletcher
(PC)
Alasdair W Jubb
(AW)
Victoria C Lupson
(VC)
Anne E Manktelow
(AE)
David K Menon
(DK)
Andrew Michell
(A)
Edward J Needham
(EJ)
Virginia F J Newcombe
(VFJ)
Joanne G Outtrim
(JG)
Linda Pointon
(L)
Christopher T Rodgers
(CT)
James B Rowe
(JB)
Catarina Rua
(C)
Nyarie Sithole
(N)
Lennart R B Spindler
(LRB)
Emmanuel A Stamatakis
(EA)
Jonathan Taylor
(J)
Fernanda Valerio
(F)
Barry Widmer
(B)
Guy B Williams
(GB)
Patrick F Chinnery
(PF)
John Allison
(J)
Gisele Alvio
(G)
Ali Ansaripour
(A)
Sharon Baker
(S)
Stephen Baker
(S)
Laura Bergamaschi
(L)
Areti Bermperi
(A)
Ariana Betancourt
(A)
Heather Biggs
(H)
Sze-How Bong
(SH)
Georgie Bower
(G)
John R Bradley
(JR)
Karen Brookes
(K)
Ashlea Bucke
(A)
Ben Bullman
(B)
Katherine Bunclark
(K)
Helen Butcher
(H)
Sarah Caddy
(S)
Jo Calder
(J)
Laura Caller
(L)
Laura Canna
(L)
Daniela Caputo
(D)
Matt Chandler
(M)
Yasmin Chaudhry
(Y)
Patrick Chinnery
(P)
Debbie Clapham-Riley
(D)
Daniel Cooper
(D)
Chiara Cossetti
(C)
Cherry Crucusio
(C)
Isabel Cruz
(I)
Martin Curran
(M)
Jerome D Coudert
(JD)
Eckart M D D De Bie
(EMDD)
Rnalie De Jesus
(R)
Aloka De Sa
(A)
Anne-Maree Dean
(AM)
Katie Dempsey
(K)
Eleanor Dewhurst
(E)
Giovanni di Stefano
(GD)
Jason Domingo
(J)
Gordon Dougan
(G)
Benjamin J Dunmore
(BJ)
Anne Elmer
(A)
Madeline Epping
(M)
Codie Fahey
(C)
Stuart Fawke
(S)
Theresa Feltwell
(T)
Christian Fernandez
(C)
Stewart Fuller
(S)
Anita Furlong
(A)
Iliana Georgana
(I)
Anne George
(A)
Nick Gleadall
(N)
Ian G Goodfellow
(IG)
Stefan Gräf
(S)
Barbara Graves
(B)
Jennifer Gray
(J)
Richard Grenfell
(R)
Ravindra K Gupta
(RK)
Grant Hall
(G)
William Hamilton
(W)
Julie Harris
(J)
Sabine Hein
(S)
Christoph Hess
(C)
Sarah Hewitt
(S)
Andrew Hinch
(A)
Josh Hodgson
(J)
Myra Hosmillo
(M)
Elaine Holmes
(E)
Charlotte Houldcroft
(C)
Christopher Huang
(C)
Oisín Huhn
(O)
Kelvin Hunter
(K)
Tasmin Ivers
(T)
Aminu Jahun
(A)
Sarah Jackson
(S)
Isobel Jarvis
(I)
Emma Jones
(E)
Heather Jones
(H)
Sherly Jose
(S)
Maša Josipović
(M)
Mary Kasanicki
(M)
Jane Kennet
(J)
Fahad Khokhar
(F)
Yvonne King
(Y)
Nathalie Kingston
(N)
Jenny Kourampa
(J)
Emma Le Gresley
(EL)
Elisa Laurenti
(E)
Ekaterina Legchenko
(E)
Paul J Lehner
(PJ)
Daniel Lewis
(D)
Emily Li
(E)
Rachel Linger
(R)
Paul A Lyons
(PA)
Michael Mackay
(M)
John C Marioni
(JC)
Jimmy Marsden
(J)
Jennifer Martin
(J)
Cecilia Matara
(C)
Nicholas J Matheson
(NJ)
Caroline McMahon
(C)
Anne Meadows
(A)
Sarah Meloy
(S)
Vivien Mendoza
(V)
Luke Meredith
(L)
Nicole Mende
(N)
Federica Mescia
(F)
Alice Michael
(A)
Alexei Moulton
(A)
Rachel Michel
(R)
Lucy Mwaura
(L)
Francesca Muldoon
(F)
Francesca Nice
(F)
Criona O'Brien
(C)
Charmain Ocaya
(C)
Ciara O'Donnell
(C)
Georgina Okecha
(G)
Ommar Omarjee
(O)
Nigel Ovington
(N)
Willem H Owehand
(WH)
Sofia Papadia
(S)
Roxana Paraschiv
(R)
Surendra Parmar
(S)
Ciro Pascuale
(C)
Caroline Patterson
(C)
Christopher Penkett
(C)
Marlyn Perales
(M)
Marianne Perera
(M)
Isabel Phelan
(I)
Malte Pinckert
(M)
Linda Pointon
(L)
Petra Polgarova
(P)
Gary Polwarth
(G)
Nicole Pond
(N)
Jane Price
(J)
Venkatesh Ranganath
(V)
Cherry Publico
(C)
Rebecca Rastall
(R)
Carla Ribeiro
(C)
Nathan Richoz
(N)
Veronika Romashova
(V)
Sabrina Rossi
(S)
Jane Rowlands
(J)
Valentina Ruffolo
(V)
Jennifer Sambrook
(J)
Caroline Saunders
(C)
Natalia Savinykh Yarkoni
(NS)
Katherine Schon
(K)
Mayurun Selvan
(M)
Rahul Sharma
(R)
Joy Shih
(J)
Kenneth G C Smith
(KGC)
Sarah Spencer
(S)
Luca Stefanucci
(L)
Hannah Stark
(H)
Jonathan Stephens
(J)
Kathleen E Stirrups
(KE)
Mateusz Strezlecki
(M)
Charlotte Summers
(C)
Rachel Sutcliffe
(R)
James E D Thaventhiran
(JED)
Tobias Tilly
(T)
Zhen Tong
(Z)
Hugo Tordesillas
(H)
Carmen Treacy
(C)
Mark Toshner
(M)
Paul Townsend
(P)
Carmen Treacy
(C)
Lori Turner
(L)
Phoebe Vargas
(P)
Bensi Vergese
(B)
Julie von Ziegenweidt
(JV)
Neil Walker
(N)
Laura Watson
(L)
Jennifer Webster
(J)
Michael P Weekes
(MP)
Nicola K Wilson
(NK)
Jennifer Wood
(J)
Jieniean Worsley
(J)
Marta Wylot
(M)
Anna Yakovleva
(A)
Cissy Yong And Julie-Anne Zerrudo
(CYAJ)
Caroline Saunders
(C)
Anne Elmer
(A)
Commentaires et corrections
Type : CommentIn
Type : ErratumIn
Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.
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