Posthospitalization COVID-19 cognitive deficits at 1 year are global and associated with elevated brain injury markers and gray matter volume reduction
Authors: Wood Greta K. , Sargent Brendan F. , Ahmad Zain-Ul-Abideen , Tharmaratnam Kukatharmini , Dunai Cordelia , Egbe Franklyn N. , Martin Naomi H. , Facer Bethany , Pendered Sophie L. , Rogers Henry C. , Hübel Christopher , van Wamelen Daniel J. , Bethlehem Richard A. I. , Giunchiglia Valentina , Hellyer Peter J. , Trender William , Kalsi Gursharan , Needham Edward , Easton Ava , Jackson Thomas A. , Cunningham Colm , Upthegrove Rachel , Pollak Thomas A. , Hotopf Matthew , Solomon Tom , Pett Sarah L. , Shaw Pamela J. , Wood Nicholas , Harrison Neil A. , Miller Karla L. , Jezzard Peter , Williams Guy , Duff Eugene P. , Williams Steven , Zelaya Fernando , Smith Stephen M. , Keller Simon , Broome Matthew , Kingston Nathalie , Husain Masud , Vincent Angela , Bradley John , Chinnery Patrick , Menon David K. , Aggleton John P. , Nicholson Timothy R. , Taylor John-Paul , David Anthony S. , Carson Alan , Bullmore Ed , Breen Gerome , Hampshire Adam ,   COVID-CNS Consortium, Alam Ali M. , Al-Chalabi Ammar , Allen Christopher M. , Amin Jay , Armour Cherie , Baker Mark R. , Barrett Suzanne , Basu Neil , Batra Rahul , Benjamin Laura , Berry Alex , Bethlehem Richard A. I. , Blackledge Bethan , Boardman Sarah A. , Bradley John , Breen David P. , Breuer Judith , Broome Matthew , Bullmore Ed , Butler Matthew , Castell Hannah , Cavanagh Jonathan , Christmas David , Christmas David M. , Coleman Jonathan R. I. , Coles Alaistair , Collie Ceryce , Cossette Nadine , Cousins David , Darby Alastair , Davies Nicholas , Defres Sylviane , Dodd Katherine C. , Dregan Alex , Duff Eugene , Ellul Mark A. , Evangelou Nikos , Fernandes Peter M. , Francis Richard , Galea Ian , Garjani Afagh , George Lily , Giunchiglia Valentina , Glen Kiran , Gregory Rebecca , Griffiths Michael , Grimbly Victoria , Grundmann Alexander , Gunatilake Savini , Hamid Shahd H. M. , Hardwick Marc , Harris Jade D. , Harrison Ewan , Harrison Paul J. , Hartmann Monika , Hetherington Claire , Hilton Orla , Hiscox Julian , Hodel Eva Maria , Holland Angela E. , Huang Yun , Hughes Stella , Irani Sarosh , Jenkins Thomas M. , Zvrskovec Johan Kallberg , Kyaw Sandar , Lewis Gabriella , Lilleker James B. , Lunn Michael P. , MacIver Claire L. , Madarshahian Daniel , Mansoori Parisa , Martin Naomi , McDonnell Gavin , McGlinchey Emily , McKeever Stephen , McIlwaine Ryan , McIntosh Andrew M. , Miller Karla L. , Monssen Dina , Morris Christopher M. , Mulholland Ciaran , Nair Akshay , Newcombe Virginia , Nicholas Nathalie , Nicholson Timothy R. , O’Malley Ronan , Orazulume Obioma , Ostermann Marlies , Palmos Alish , Patel Arvind , Peacock Sharon , Pendered Sophie L. , Pollak Thomas A. , Roberts Angela , Rota Silvia , Salman Rustam Al-Shahi , Samuel Merna , Sargent Brendan F. , Sawcer Stephen J. , Seed Adam W. , Semple Scott , Shil Rajish S. K. , Sieradzki Adam , Singh Bhagteshwar , Smith Craig J. , Smith Jacqueline , Smith Stephen M. , Taams Leonie , Tamborska Arina , Thomas Rhys H. , Thomson Emma , Trender William , Ahmad Zain-Ul-Abideen , Underwood Jonathan , Veenith Tonny , Venneri Annalena , van Wamelen Daniel J. , Williams Guy , Wong Sui Hsien , Zandi Michael S. , Michael Benedict D. , Paddick Stella-Maria , Leek E. Charles 
Published: September 2024

Abstract
The spectrum, pathophysiology and recovery trajectory of persistent post-COVID-19 cognitive deficits are unknown, limiting our ability to develop prevention and treatment strategies. We report the 1-year cognitive, serum biomarker and neuroimaging findings from a prospective, national study of cognition in 351 COVID-19 patients who required hospitalization, compared with 2,927 normative matched controls. Cognitive deficits were global, associated with elevated brain injury markers and reduced anterior cingulate cortex volume 1 year after COVID-19. Severity of the initial infective insult, postacute psychiatric symptoms and a history of encephalopathy were associated with the greatest deficits. There was strong concordance between subjective and objective cognitive deficits. Longitudinal follow-up in 106 patients demonstrated a trend toward recovery. Together, these findings support the hypothesis that brain injury in moderate to severe COVID-19 may be immune-mediated, and should guide the development of therapeutic strategies.