biostudies-literatureMichael BDBrain Research UKMedical Research CouncilNational Institute for Health Research (NIHR)Wellcome TrustBiotechnology and Biological Sciences Research CouncilAcademy of Medical Sciences8487https://www.ebi.ac.uk/biostudies/studies/S-EPMC10746705biostudies-literatureUnknown14(1)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, UNature communicationsPara-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses.PMC10746705BB/R01390X/1ACF-2022-07-007ACF-2022-26-005AMS-CSF4-NewcombeACF-2020-07-003MR/V03605X/1ACF-2021-07-009CL-2017-01-005MR/V007181/1NIHR300669MR/T023791/1CL-2020-07-004MR/T028750/1ISSF201902/3CL-2018-17-004MC_PC_19059MR/S032304/1206330/Z/17/ZCO-CIN-01201819-20SGL020\1006NIHR302544Madarshahian DSancho-Shimizu VDigby RLeiner TMortimore KSmith CJMaclean ALittle JChristmas DVincent-Smith LRogers HCLillie PBradley JRHartley CKendall JFower AFinn AIrani SRFletcher TShaw VERambaut AYoung PCaruth VVenneri AKegg SLimb JWaddy SPapakonstantinou DJensen RLChechi KKiy RTDocherty ABMiller KSummers Cvan DJPooni JSHoward JMassey HTurtle LCPaddick SMBothma PSales DSpencer RGAndrikopoulos PKasipandian VHarrison PJGunatilake SSunderland GVincent RVuylsteke ATaylor JPIjaz SGarcia-Dorival IZhang JECollini PVincent ATakis PDrake TMHolland AERoberts SGunning PPhull MSaluja TSnelson CHormis AMills GArmstrong JAGrimbly VSharma AZambon MNewcombe VDavis CLiggi SKoch OSeed AWHusain MSharma PO'Malley RGreenhalf WMok QWiselka MSzemiel AHarrison NANelson MLett LLant SMcDonald SEArmour CAldera ELMacNaughton EZandi MSDunn CChukkambotla SBasu NWai AYThomson ECGriffiths MSwann OVAtkinson DHalpin SFlaherty LCutino-Moguel MTBasude SMurphy MParaiso HMurphy LDos Santos GSalman RASizer JHarris JDRuge BMatovu EGregory RSubramaniam KSGalea IAggleton JPMancini MPanchatsharam SPendered SKhoo SGriffiths FBulteel NMulla RCooper LTaggart AFernandes PMRota SWake RSawcer SJBaxter DPrince TLarkin SFox HWijesinghe MUpthegrove RKeller SLefteri DHiscox JNicholas NChinnery PFLim WSEgbe FNWrobel NLake AMcEvoy LEvangelou NStambach TDyer PRyan BDyer TChristmas DMDervisevic SLaha SChambler DTupper-Carey DAllen CMAsiimwe IGAdeniji KJones TRScott JTMcCafferty SFawkes AThomas JKnight SShankar-Hari MHafezi KBooth LCousins DNorris LSaviciute EHendry RCole SHetherington CMentzer AJDawson CFegan CBoardman SAGoldsmith AMitchell JColes AMerson LReynolds TShaw PJStewart JPSmall BReynolds WStewart RShaw VKingston NBullock KSingh BRen AFullerton DCox HCupitt JRoberts DSamuel MRoberts ADonnison PRoberts MCollie CBurtenshaw AWood NLaw ABaillie JKHavalda PMiddleton JSargent BLeibowitz MGodden JHodgson LTridente ABarlow GBlackledge BChild JWham MChand MElliott ADuRand IOpenshaw PJRussell CDPenrice-Randal RBreen GThwaites RSGamble CWinchester SBrennan BGarjani ASemple SDincarslan OUnderwood JHarrison EMVancheeswaran RLunn MPHarvey DMacMahon MYates BReschreiter HCarson ABarnass SShears RKHarrison NHardy ENorman LHarrison EMcLauchlan JMiah NSWalden ABarrett SVisuvanathan SMcIlwaine RMcIntosh AMSpittle NHarrison JMurphy EGBarrett NMenon DKLyttle MFinch LEllul MADushianthan ASmith JShawcross AAshworth MAlegria AShah ASmith SSmith RDonohue CAl-Chalabi AMulholland CThomas RHNair AWilliams MMeda MPatel ABach BThompson AARDrummond APatel BCarlucci NMaziere NDouthwaite SRae NBogaert DKlenerman PEaston AKaliappan APaxton WAJain SBreen DPHannah COrazulume OCosgrove CMankregod RBaker MRPost FCarson GMarsh LWilliams SWilliams RMonssen DAhmed KAChiollaz ACGeorge LNagarajan TDonnelly LGlen KDregan AClarke EAWootton DGKnight SRLatawiec DTatham KMcGlinchey ESemple MGLivoti LARidley PMPais MDonegan CSieradzki AHorby PWPintus SPius RFacer BNicholson THartshorn SMcCullough KTait SMclean KAThompson CTonder LVLaird SBeadsworth MPepperell JLinnett VCavanagh JMcDonald SDarby ATrochu EAgwuh KWilliams GBShaw CAMorris CMSriskandan SPeters MPollak TDunai CEvans AColes AJRousseau GEvans CGreen CAPlotkin DGupta RKCOVID-CNS ConsortiumKoukorava COtahal IBethlehem RMoon JLewis GMinton JPollakis GTedder RSMorris CCarracedo ADLeeming GCooke GSLahnsteiner EEziefula CTamborska ANeedham EJackson CFrancis RMeynert AMGrundmann AHolden KHeld MStaines NScott-Brown JFisher LWIrani SFairfield CJHampshire AHardwick MWood GKHartmann MJackson TJenkins TMde Silva TPapineni PAgranoff DChee NHotopf MOlanipekun MThompson RVallotton NPilgrim JZelaya FKerslake IPattison NHardwick HMoore SCGrammatikopoulos TMoore EMoses SOosthuyzen WTwagira MHamid SHTato ENoursadeghi MWilson LBassford CLeek CEbrahimi SCossette NHughes SMartin NBakshi SButler MKerrison CDavid ASPalmarini MRichardson NConnor MKoduri GOstermann MHawcutt DBDefres SGriffin JLNorton EWelters IOsagie AMurphy DSolomon TDavies NLilleker JBClark RBreuer JMpenge MClark TDalton JClohisey SBarlow SLPeacock SWorkman AWhittington AAmin JLee JHodel EMWhittaker PJacobs MPalmos AThomson EDunning JMacGillivray LPalmieri CColeman JRMohandas KBest NTanianis-Hughes JTaams LTakats ZBerridge JMacIver CLPrice NShanmuga PJones CBDodd KCBatra RSands CJHuang YMaslen LAllen SPrice DBurden TDumas MEBrittain-Long RKelsey MSzakmany TClark JJKoshy GKeating SVeenith TAshish AMorrice KJennings PCoutts AKhandaker SBullmore EChadwick DBroome MRAil DNagel MHolmes AGarg STaams LSHobrok MMcEwen RFoster Tda Silva AGarg ABari SKyaw SLewis MRGraham CBerry ABerry CRobertson DLBarclay WSSchmid MLMansoori PMcDonnell GStuart DSubudhi PSanchez JCBernatoniene JDuff ENeedham EJWong SHWolverson AWilcock EO'Shea MKProut RTharmaratnam KDark PSubramaniam KKing KGilchrist TJezzard PPlanche TBenjamin LCass EMetelmann SMasson HCatterall BWGkrania-Klotsas ELavelle-Langham LAlex BRose AMichael BDWhitehouse TGirvan MAngus BSigfrid LStirrups KISARIC4C InvestigatorsMorgan PfalsePara-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses.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, U2023-01-01T00:00:00Z2023 Dec2026-07-14T18:24:21.376Z2024-10-18T04:41:04.289ZS-EPMC107467053813568610.1038/s41467-023-42320-4