Post-acute COVID-19 neuropsychiatric symptoms are not associated with ongoing nervous system injury
Authors: Taquet Maxime , Skorniewska Zuzanna , Zetterberg Henrik , Geddes John R , Mummery Catherine J , Chalmers James D , Ho Ling-Pei , Horsley Alex , Marks Michael , Poinasamy Krisnah , Raman Betty , Leavy Olivia C , Richardson Matthew , Elneima Omer , McAuley Hamish J C , Shikotra Aarti , Singapuri Amisha , Sereno Marco , Saunders Ruth M , Harris Victoria Claire , Houchen-Wolloff Linzy , Mansoori Parisa , Greening Neil J , Harrison Ewen M , Docherty Annemarie B , Lone Nazir I , Quint Jennifer , Greenhalf William , Wain Louise V , Brightling Christopher E , Evans Rachael E , Harrison Paul J , Koychev Ivan ,   PHOSP-COVID Study Collaborative Group, Brightling C E , Evans R A , Wain L V , Chalmers J D , Harris V C , Ho L P , Horsley A , Marks M , Poinasamy K , Raman B , Shikotra A , Singapuri A , Brightling C E , Evans R A , Wain L V , Dowling R , Edwardson C , Elneima O , Finney S , Greening N J , Hargadon B , Harris V , Houchen--Wolloff L , Leavy O C , McAuley H J C , Overton C , Plekhanova T , Saunders R M , Sereno M , Singapuri A , Shikotra A , Taylor C , Terry S , Tong C , Zhao B , Lomas D , Sapey E , Berry C , Bolton C E , Brunskill N , Chilvers E R , Djukanovic R , Ellis Y , Forton D , French N , George J , Hanley N A , Hart N , McGarvey L , Maskell N , McShane H , Parkes M , Peckham D , Pfeffer P , Sayer A , Sheikh A , Thompson A A R , Williams N , Brightling C E , Greenhalf W , Semple M G , Ashworth M , Hardwick H E , Lavelle-Langham L , Reynolds W , Sereno M , Saunders R M , Singapuri A , Shaw V , Shikotra A , Venson B , Wain L V , Docherty A B , Harrison E M , Sheikh A , Baillie J K , Brightling C E , Daines L , Free R , Evans R A , Kerr S , Leavy O C , Lone N I , McAuley H J C , Pius R , Quint J , Richardson M , Sereno M , Thorpe M , Wain L V , Halling-Brown M , Gleeson F , Jacob J , Neubauer S , Raman B , Siddiqui S , Wild J M , Aslani S , Jezzard P , Lamlum H , Lilaonitkul W , Tunnicliffe E , Willoughby J , Wain L V , Baillie J K , Baxendale H , Brightling C E , Brown M , Chalmers J D , Evans R A , Gooptu B , Greenhalf W , Hardwick H E , Jenkins R G , Jones D , Koychev I , Langenberg C , Lawrie A , Molyneaux P L , Shikotra A , Pearl J , Ralser M , Sattar N , Saunders R M , Scott J T , Shaw T , Thomas D , Wilkinson D , Heaney L G , De Soyza A , Adeloye D , Brightling C E , Brown J S , Busby J , Chalmers J D , Echevarria C , Daines L , Elneima O , Evans R A , Hurst J , Novotny P , Pfeffer P , Poinasamy K , Quint J , Rudan I , Sapey E , Shankar-Hari M , Sheikh A , Siddiqui S , Walker S , Zheng B , Geddes J R , Hotopf M , Abel K , Ahmed R , Allan L , Armour C , Baguley D , Baldwin D , Ballard C , Bhui K , Breen G , Broome M , Brugha T , Bullmore E , Burn D , Callard F , Cavanagh J , Chalder T , Clark D , David A , Deakin B , Dobson H , Elliott B , Evans J , Francis R , Guthrie E , Harrison P , Henderson M , Hosseini A , Huneke N , Husain M , Jackson T , Jones I , Kabir T , Kitterick P , Korszun A , Koychev I , Kwan J , Lingford-Hughes A , Mansoori P , McAllister-Williams H , McIvor K , Milligan L , Morriss R , Mukaetova-Ladinska E , Munro K , Nevado-Holgado A , Nicholson T , Paddick S , Pariante C , Pimm J , Saunders K , Sharpe M , Simons G , Upthegrove R , Wessely S , McCann G P , Amoils S , Antoniades C , Banerjee A , Bell R , Bularga A , Berry C , Chowienczyk P , Greenwood J P , Hughes A D , Khunti K , Kingham L , Lawson C , Mangion K , Mills N L , Moss A J , Neubauer S , Raman B , Sattar A N , Sudlow C L , Toshner M , Openshaw P J M , Altmann D , Baillie J K , Batterham R , Baxendale H , Bishop N , Brightling C E , Calder P C , Evans R A , Heeney J L , Hussell T , Klenerman P , Lord J M , Moss P , Rowland-Jones S L , Schwaeble W , Semple M G , Thwaites R S , Turtle L , Wain L V , Walmsley S , Wraith D , Rowland M J , Rostron A , Baillie J K , Connolly B , Docherty A B , Lone N I , McAuley D F , Parekh D , Rostron A , Simpson J , Summers C , Jenkins R G , Porter J , Allen R J , Aul R , Baillie J K 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A R , Wild J M , Wilkins M , Singh S J , Man W D-C , Lord J M , Greening N J , Chalder T , Scott J T , Armstrong N , Baldry E , Baldwin M , Basu N , Beadsworth M , Bishop L , Bolton C E , Briggs A , Buch M , Carson G , Cavanagh J , Chinoy H , Daynes E , Defres S , Evans R A , Greenhaff P , Greenwood S , Harvie M , Husain M , MacDonald S , McArdle A , McAuley H J C , McMahon A , McNarry M , Nolan C , O'Donnell K , Parekh D , Pimm J , Sargent J , Sigfrid L , Steiner M , Stensel D , Tan A L , Whitney J , Wilkinson D , Wilson D , Witham M , Wootton D G , Yates T , Thomas D , Brunskill N , Francis S , Greenwood S , Laing C , Bramham K , Chowdhury P , Frankel A , Lightstone L , McAdoo S , McCafferty K , Ostermann M , Selby N , Sharpe C , Willicombe M , Shaw A , Armstrong L , Hairsine B , Henson H , Kurasz C , Shenton L , Fairbairn S , Dell A , Hawkings N , Haworth J , Hoare M , Lucey A , Lewis V , Mallison G , Nassa H , Pennington C , Price A , Price C , Storrie A , Willis G , Young S , Pfeffer P , Chong-James K , David C , James W Y , Martineau A , Zongo O , Sanderson A , Heaney L G , Armour C , Brown V , Craig T , Drain S , King B , Magee N , McAulay D , Major E , McGarvey L , McGinness J , Stone R , Haggar A , Bolger A , Davies F , Lewis J , Lloyd A , Manley R , McIvor E , Menzies D , Roberts K , Saxon W , Southern D , Subbe C , Whitehead V , El-Taweel H , Dawson J , Robinson L , Saralaya D , Brear L , Regan K , Storton K , Fuld J , Bermperi A , Cruz I , Dempsey K , Elmer A , Jones H , Jose S , Marciniak S , Parkes M , Ribeiro C , Taylor J , Toshner M , Watson L , Worsley J , Sabit R , Broad L , Buttress A , Evans T , Haynes M , Jones L , Knibbs L , McQueen A , Oliver C , Paradowski K , Williams J , Harris E , Sampson C , Lynch C , Davies E , Evenden C , Hancock A , Hancock K , Rees M , Roche L , Stroud N , Thomas-Woods T , Babores M , Bradley-Potts J , Holland M , Keenan N , Shashaa S , Wassall H , Beranova E , Weston H , Cosier T , Austin L , Deery J , Hazelton T , Price C , Ramos H , Solly R , Turney S , Pearce L , McCormack W , Pugmire S , Stoker W , Wilson A , Hart N , Aguilar Jimenez L A , Arbane G , Betts S , Bisnauthsing K , Dewar A , Chowdhury P , Dewar A , Kaltsakas G , Kerslake H , Magtoto M M , Marino P , Martinez L M , Ostermann M , Rossdale J , Solano T S , Wynn E , Williams N , Storrar W , Corral M Alvarez , Arias A , Bevan E , Griffin D , Martin J , Owen J , Payne S , Prabhu A , Reed A , Brown C Wrey , Lawson C , Burdett T , Featherstone J , Layton A , Mills C , Stephenson L , Easom N , Atkin P , Brindle K , Crooks M G , Drury K , Flockton R , Holdsworth L , Richards A , Sykes D L , Thackray-Nocera S , Wright C , Lewis K E , Mohamed A , Ross G , Coetzee S , Davies K , Hughes R , Loosley R , O'Brien L , Omar Z , McGuinness H , Perkins E , Phipps J , Taylor A , Tench H , Wolf-Roberts R , Howard L S , Kon O , Thomas D C , Anifowose S , Burden L , Calvelo E , Card B , Carr C , Chilvers E R , Copeland D , Cullinan P , Daly P , Evison L , Fayzan T , Gordon H , Haq S , Jenkins R G , King C , March K , Mariveles M , McLeavey L , Mohamed N , Moriera S , Munawar U , Nunag J , Nwanguma U , Orriss-Dib L , Ross A , Roy M , Russell E , Samuel K , Schronce J , Simpson N , Tarusan L , Wood C , Yasmin N , Reddy R , Guerdette A-M , Hewitt M , Warwick K , White S , Shah A M , Jolley C J , Adeyemi O , Adrego R , Assefa-Kebede H , Breeze J , Brown M , Byrne S , Chalder T , Dulawan P , Hart N , Hayday A , Hoare A , Knighton A , Malim M , Patale S , Peralta I , Powell N , Ramos A , Shevket K , Speranza F , Te A , Beirne P , Ashworth A , Clarke J , Coupland C , Dalton M , Wade E , Favager C , Greenwood J , Glossop J , Hall L , Hardy T , Humphries A , Murira J , Peckham D , Plein S , Rangeley J , Saalmink G , Tan A L , Whittam B , Window N , Woods J , Coakley G , Wootton D G , Turtle L , Allerton L , All A M , Beadsworth M , Berridge A , Brown J , Cooper S , Cross A , Defres S , Dobson S L , Earley J , French N , Greenhalf W , Hardwick H E , Hainey K , Hawkes J , Highett V , Kaprowska S , Key A L , Lavelle-Langham L , Lewis-Burke N , Madzamba G , Malein F , Marsh S , Mears C , Melling L , Noonan M J , Poll L , Pratt J , Richardson E , Rowe A , Semple M G , Shaw V , Tripp K A , Wajero L O , Williams-Howard S A , Wyles J , Diwanji S N , Papineni P , Gurram S , Quaid S , Tiongson G F , Watson E , Al-Sheklly B , Horsley A , Avram C , Blaikely J , Buch M , Choudhury N , Faluyi D , Felton T , Gorsuch T , Hanley N A , Hussell T , Kausar Z , Odell N , Osbourne R , Hanley K Piper , Radhakrishnan K , Stockdale S , De Soyza A , Echevarria C , Ayoub A , Brown J , Burns G , Davies G , Fisher H , Francis C , Greenhalgh A , Hogarth P , Hughes J , Jiwa K , Jones G , MacGowan G , Price D , Sayer A , Simpson J , Tedd H , Thomas S , West S , Witham M , Wright S , Young A , McMahon M J , Neill P , Anderson D , Bayes H , Berry C , Grieve D , McInnes I B , Basu N , Brown A , Dougherty A , Fallon K , Gilmour L , Mangion K , Morrow A , Scott K , Sykes R , Sage E K , Barrett F , Donaldson A , Patel M , Bell D , Brown A , Brown M , Hamil R , Leitch K , Macliver L , Quigley J , Smith A , Welsh B , Choudhury G , Baillie J K , Clohisey S , Deans A , Docherty A B , Furniss J , Harrison E M , Kelly S , Lone N I , Sheikh A , Chalmers J D , Connell D , Elliott A , Deas C , George J , Mohammed S , Rowland J , Solstice A R , Sutherland D , Tee C J , Jayaraman B , Light T , Bolton C E , Almeida P , Bonnington J , Chrystal M , Dupont C , Greenhaff P , Gupta A , Howard L , Jang W , Linford S , Matthews L , Needham R , Nikolaidis A , Prosper S , Shaw K , Thomas A K , Ho L P , Rahman N M , Ainsworth M , Alamoudi A , Bates A , Bloss A , Burns A , Carter P , Chen J , Conneh F , Dong T , Evans R I , Fraser E , Fu X , Geddes J R , Gleeson F , Harrison P , Havinden-Williams M , Jezzard P , Kanellakis N , Koychev I , Kurupati P , Li X , McShane H , Megson C , Motohashi K , Neubauer S , Nicoll D , Ogg G , Pacpaco E , Pavlides M , Peng Y , 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S , Davies G A , Connor L , Cook A , Rees T , Thaivalappil F , Thomas C , Butt A , Coulding M , Jones H , Kilroy S , McCormick J , McIntosh J , Savill H , Turner V , Vere J , Fraile E , Ugoji J , Kon S S , Lota H , Landers G , Nasseri M , Portukhay S , Hormis A , Daniels A , Ingham J , Zeidan L , Chablani M , Osborne L , Marks M , Brown J S , Ahwireng N , Bang B , Basire D , Chambers R C , Checkley A , Evans R , Heightman M , Hillman T , Hurst J , Jacob J , Janes S , Jastrub R , Lipman M , Logan S , Lomas D , Morillas M Merida , Plant H , Porter J C , Roy K , Wall E , Parekh D , Haider N Ahmad , Atkin C , Baggott R , Bates M , Botkai A , Casey A , Cooper B , Dasgin J , Draxlbauer K , Gautam N , Hazeldine J , Hiwot T , Holden S , Isaacs K , Jackson T , Johnson S , Kamwa V , Lewis D , Lord J M , Madathil S , McGhee C , Mcgee K , Neal A , Cox A Newton , Nyaboko J , Parekh D , Peterkin Z , Qureshi H , Ratcliffe L , Sapey E , Short J , Soulsby T , Stockley J , Suleiman Z , Thompson T , 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Wheeler H , Dharmagunawardena R , Bright E , Crisp P , Stern M , Wight A , Bailey L , Reddington A , Ashish A , Cooper J , Robinson E , Broadley A , Howard K , Barman L , Brookes C , Elliott K , Griffiths L , Guy Z , Ionita D , Redfearn H , Sarginson C , Turnbull A , Ellis Y , Marks M , Briggs A , Holmes K , UK Asthma , Lung British , Poinasamy K , Walker S , Halling-Brown M , Breen G , Hotopf M , Lewis K , Williams N 
Published: December 2023

Abstract
A proportion of patients infected with severe acute respiratory syndrome coronavirus 2 experience a range of neuropsychiatric symptoms months after infection, including cognitive deficits, depression and anxiety. The mechanisms underpinning such symptoms remain elusive. Recent research has demonstrated that nervous system injury can occur during COVID-19. Whether ongoing neural injury in the months after COVID-19 accounts for the ongoing or emergent neuropsychiatric symptoms is unclear. Within a large prospective cohort study of adult survivors who were hospitalized for severe acute respiratory syndrome coronavirus 2 infection, we analysed plasma markers of nervous system injury and astrocytic activation, measured 6 months post-infection: neurofilament light, glial fibrillary acidic protein and total tau protein. We assessed whether these markers were associated with the severity of the acute COVID-19 illness and with post-acute neuropsychiatric symptoms (as measured by the Patient Health Questionnaire for depression, the General Anxiety Disorder assessment for anxiety, the Montreal Cognitive Assessment for objective cognitive deficit and the cognitive items of the Patient Symptom Questionnaire for subjective cognitive deficit) at 6 months and 1 year post-hospital discharge from COVID-19. No robust associations were found between markers of nervous system injury and severity of acute COVID-19 (except for an association of small effect size between duration of admission and neurofilament light) nor with post-acute neuropsychiatric symptoms. These results suggest that ongoing neuropsychiatric symptoms are not due to ongoing neural injury.