Posthospitalization COVID-19 cognitive deficits at 1 year are global and associated with elevated brain injury markers and gray matter volume reduction

Cunningham, Colm

doi:http://dx.doi.org/10.1038/s41591-024-03309-8

Posthospitalization COVID-19 cognitive deficits at 1 year are global and associated with elevated brain injury markers and gray matter volume reduction

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s41591-024-03309-8.pdf (4.47 MB)

Date

2025

Authors

Cunningham, Colm

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openAccess

Citation

Wood, Greta K. and Sargent, Brendan F. and Ahmad, Zain-Ul-Abideen and Tharmaratnam, Kukatharmini and Dunai, Cordelia and Egbe, Franklyn N. and Martin, Naomi H. and Facer, Bethany and Pendered, Sophie L. and Rogers, Henry C. and Hÿbel, Christopher and van Wamelen, Daniel J. and Bethlehem, Richard A. I. and Giunchiglia, Valentina and Hellyer, Peter J. and Trender, William and Kalsi, Gursharan and Needham, Edward and Easton, Ava and Jackson, Thomas A. and Cunningham, Colm and Upthegrove, Rachel and Pollak, Thomas A. and Hotopf, Matthew and Solomon, Tom and Pett, Sarah L. and Shaw, Pamela J. and Wood, Nicholas and Harrison, Neil A. and Miller, Karla L. and Jezzard, Peter and Williams, Guy and Duff, Eugene P. and Williams, Steven and Zelaya, Fernando and Smith, Stephen M. and Keller, Simon and Broome, Matthew and Kingston, Nathalie and Husain, Masud and Vincent, Angela and Bradley, John and Chinnery, Patrick and Menon, David K. and Aggleton, John P. and Nicholson, Timothy R. and Taylor, John-Paul and David, Anthony S. and Carson, Alan and Bullmore, Ed and Breen, Gerome and Hampshire, Adam and Zandi, Michael S. and Wong, Sui Hsien and Venneri, Annalena and Veenith, Tonny and Underwood, Jonathan and Thomson, Emma and Thomas, Rhys H. and Tamborska, Arina and Taams, Leonie and Smith, Jacqueline and Smith, Craig J. and Singh, Bhagteshwar and Sieradzki, Adam and Shil, Rajish S. K. and Semple, Scott and Seed, Adam W. and Sawcer, Stephen J. and Samuel, Merna and Salman, Rustam Al-Shahi and Rota, Silvia and Roberts, Angela and Peacock, Sharon and Patel, Arvind and Palmos, Alish and Ostermann, Marlies and Orazulume, Obioma and O’Malley, Ronan and Nicholas, Nathalie and Newcombe, Virginia and Nair, Akshay and Mulholland, Ciaran and Morris, Christopher M. and Monssen, Dina and McIntosh, Andrew M. and McIlwaine, Ryan and McKeever, Stephen and McGlinchey, Emily and McDonnell, Gavin and Mansoori, Parisa and Madarshahian, Daniel and MacIver, Claire L. and Lunn, Michael P. and Lilleker, James B. and Lewis, Gabriella and Kyaw, Sandar and Zvrskovec, Johan Kallberg and Jenkins, Thomas M. and Irani, Sarosh and Hughes, Stella and Huang, Yun and Holland, Angela E. and Hodel, Eva Maria and Hiscox, Julian and Hilton, Orla and Hetherington, Claire and Hartmann, Monika and Harrison, Paul J. and Harrison, Ewan and Harris, Jade D. and Hardwick, Marc and Hamid, Shahd H. M. and Gunatilake, Savini and Grundmann, Alexander and Grimbly, Victoria and Griffiths, Michael and Gregory, Rebecca and Glen, Kiran and George, Lily and Garjani, Afagh and Galea, Ian and Francis, Richard and Fernandes, Peter M. and Evangelou, Nikos and Ellul, Mark A. and Dregan, Alex and Dodd, Katherine C. and Defres, Sylviane and Davies, Nicholas and Darby, Alastair and Cousins, David and Cossette, Nadine and Collie, Ceryce and Coles, Alaistair and Coleman, Jonathan R. I. and Christmas, David and Cavanagh, Jonathan and Castell, Hannah and Butler, Matthew and Breuer, Judith and Breen, David P. and Boardman, Sarah A. and Blackledge, Bethan and Berry, Alex and Benjamin, Laura and Batra, Rahul and Basu, Neil and Barrett, Suzanne and Baker, Mark R. and Armour, Cherie and Amin, Jay and Allen, Christopher M. and Al-Chalabi, Ammar and Alam, Ali M. and Michael, Benedict D. and Paddick, Stella-Maria and Leek, E. C, Posthospitalization COVID-19 cognitive deficits at 1 year are global and associated with elevated brain injury markers and gray matter volume reduction, Nature Medicine, 31, 1, 2025, 245 – 257

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.