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Lookup NU author(s): Dr Christopher Morris, Dr David Cousins, Professor John-Paul TaylorORCiD, Professor Mark BakerORCiD, Dr Stella Paddick
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© 2023, The Author(s).To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely.
Author(s): Michael BD, Needham EJ, Tharmaratnam K, Williams R, Huang Y, Boardman SA, Clark JJ, Sharma P, Subramaniam K, Wood GK, Collie C, Digby R, Ren A, Norton E, Leibowitz M, Ebrahimi S, Fower A, Fox H, Tato E, Ellul MA, Sunderland G, Held M, Hetherington C, Egbe FN, Stirrups K, Grundmann A, Chiollaz A-C, Sanchez J-C, Stewart JP, Griffiths M, Solomon T, Breen G, Coles AJ, Kingston N, Bradley JR, Chinnery PF, Cavanagh J, Irani SR, Vincent A, Baillie JK, Openshaw PJ, Semple MG, Baillie JK, Openshaw PJ, Semple MG, Alex B, Andrikopoulos P, Bach B, Barclay WS, Bogaert D, Chand M, Chechi K, Cooke GS, da Silva A, de Silva T, Docherty AB, dos Santos G, Dumas M-E, Dunning J, Fletcher T, Green CA, Greenhalf W, Griffin JL, Gupta RK, Harrison EM, Wai AY, Holden K, Horby PW, Ijaz S, Khoo S, Klenerman P, Law A, Lewis MR, Liggi S, Lim WS, Maslen L, Mentzer AJ, Merson L, Meynert AM, Moore SC, Noursadeghi M, Olanipekun M, Osagie A, Palmarini M, Palmieri C, Paxton WA, Pollakis G, Price N, Rambaut A, Robertson DL, Russell CD, Sancho-Shimizu V, Sands CJ, Scott JT, Sigfrid L, Solomon T, Sriskandan S, Stuart D, Summers C, Swann OV, Takats Z, Takis P, Tedder RS, Thompson AAR, Thomson EC, Thwaites RS, Turtle LC, Zambon M, Drake TM, Fairfield CJ, Knight SR, Mclean KA, Murphy D, Norman L, Pius R, Shaw CA, Connor M, Dalton J, Gamble C, Girvan M, Halpin S, Harrison J, Jackson C, Lee J, Marsh L, Plotkin D, Roberts S, Saviciute E, Clohisey S, Hendry R, Knight S, Lahnsteiner E, Leeming G, Norris L, Scott-Brown J, Tait S, Wham M, Clark R, Coutts A, Donnelly L, Fawkes A, Gilchrist T, Hafezi K, MacGillivray L, Maclean A, McCafferty S, Morrice K, Murphy L, Wrobel N, Carson G, Adeniji K, Agranoff D, Agwuh K, Ail D, Aldera EL, Alegria A, Allen S, Angus B, Ashish A, Atkinson D, Bari S, Barlow G, Barnass S, Barrett N, Bassford C, Basude S, Baxter D, Beadsworth M, Bernatoniene J, Berridge J, Berry C, Best N, Bothma P, Brittain-Long R, Bulteel N, Burden T, Burtenshaw A, Caruth V, Chadwick D, Chambler D, Chee N, Child J, Chukkambotla S, Clark T, Collini P, Cosgrove C, Cupitt J, Cutino-Moguel M-T, Dark P, Dawson C, Dervisevic S, Donnison P, Douthwaite S, Drummond A, DuRand I, Dushianthan A, Dyer T, Evans C, Eziefula C, Fegan C, Finn A, Fullerton D, Garg S, Garg A, Gkrania-Klotsas E, Godden J, Goldsmith A, Graham C, Grammatikopoulos T, Hardy E, Hartshorn S, Harvey D, Havalda P, Hawcutt DB, Hobrok M, Hodgson L, Hormis A, Howard J, Jacobs M, Jain S, Jennings P, Kaliappan A, Kasipandian V, Kegg S, Kelsey M, Kendall J, Kerrison C, Kerslake I, Koch O, Koduri G, Koshy G, Laha S, Laird S, Larkin S, Leiner T, Lillie P, Limb J, Linnett V, Little J, Lyttle M, MacMahon M, MacNaughton E, Mankregod R, Masson H, Matovu E, McCullough K, McEwen R, Meda M, Mills G, Minton J, Mohandas K, Mok Q, Moon J, Moore E, Morgan P, Morris C, Mortimore K, Moses S, Mpenge M, Mulla R, Murphy M, Nagarajan T, Nagel M, Nelson M, Norris L, O'Shea MK, Ostermann M, Otahal I, Pais M, Panchatsharam S, Papakonstantinou D, Papineni P, Paraiso H, Patel B, Pattison N, Pepperell J, Peters M, Phull M, Pintus S, Planche T, Post F, Price D, Prout R, Rae N, Reschreiter H, Reynolds T, Richardson N, Roberts M, Roberts D, Rose A, Rousseau G, Ruge B, Ryan B, Saluja T, Schmid ML, Shah A, Shankar-Hari M, Shanmuga P, Sharma A, Shawcross A, Pooni JS, Sizer J, Smith R, Snelson C, Spittle N, Staines N, Stambach T, Stewart R, Subudhi P, Szakmany T, Tatham K, Thomas J, Thompson C, Thompson R, Tridente A, Tupper-Carey D, Twagira M, Vallotton N, Vancheeswaran R, Vincent R, Vincent-Smith L, Visuvanathan S, Vuylsteke A, Waddy S, Wake R, Walden A, Welters I, Whitehouse T, Whittaker P, Whittington A, Wijesinghe M, Williams M, Wilson L, Winchester S, Wiselka M, Wolverson A, Wootton DG, Workman A, Yates B, Young P, McDonald SE, Shaw V, Ahmed KA, Armstrong JA, Ashworth M, Asiimwe IG, Bakshi S, Barlow SL, Booth L, Brennan B, Bullock K, Carlucci N, Cass E, Catterall BW, Clark JJ, Clarke EA, Cole S, Cooper L, Cox H, Davis C, 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Singh B, Sargent B, Collie C, Leek C, Armour C, Morris CM, Allen CM, Mulholland C, MacIver CL, Dunai C, Dunai C, Smith CJ, van DJ, Madarshahian D, Christmas D, Cousins D, Menon DK, Christmas DM, Breen DP, Monssen D, Bullmore E, Needham E, McGlinchey E, Thomson E, Duff E, Hodel EM, Harrison E, Zelaya F, Lewis G, McDonnell G, Breen G, Wood GK, Williams GB, Hannah C, Rogers HC, Smith J, Harris JD, Lilleker JB, Amin J, Aggleton JP, Bradley JR, Taylor J-P, Cavanagh J, Coleman JR, Underwood J, Breuer J, Hiscox J, Miller K, Dodd KC, Glen K, Benjamin L, Taams L, George L, Hardwick M, Baker MR, Husain M, Butler M, Hotopf M, Broome MR, Samuel M, Griffiths M, Lunn MP, Zandi MS, Hartmann M, Cossette N, Martin N, Nicholas N, Harrison NA, Basu N, Harrison N, Davies N, Wood N, Evangelou N, Shaw PJ, Mansoori P, Harrison PJ, Jezzard P, Fernandes PM, Upthegrove R, Batra R, Gregory R, Thomas RH, Bethlehem R, Francis R, O'Malley R, Salman RA, McIlwaine R, Kyaw S, Irani S, Gunatilake S, Semple S, Hamid SH, Peacock S, Rota S, Keller S, Pendered S, Barrett S, Hughes S, Paddick S-M, Sawcer SJ, Smith S, Williams S, Wong SH, Defres S, Jackson T, Jenkins TM, Pollak T, Nicholson T, Veenith T, Grimbly V, Newcombe V, Taams LS, Menon DK
Publication type: Article
Publication status: Published
Journal: Nature Communications
Year: 2023
Volume: 14
Issue: 1
Online publication date: 22/12/2023
Acceptance date: 06/10/2023
ISSN (electronic): 2041-1723
Publisher: Nature Research
URL: https://doi.org/10.1038/s41467-023-42320-4
DOI: 10.1038/s41467-023-42320-4
PubMed id: 38135686
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