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

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.

Metadata

Item Type:	Article
Authors/Creators:	Wood, G.K. https://orcid.org/0000-0001-6098-2331 Sargent, B.F. https://orcid.org/0000-0003-2262-7755 Ahmad, Z.-U.-A. https://orcid.org/0000-0002-6940-8851 Tharmaratnam, K. https://orcid.org/0000-0002-8255-9822 Dunai, C. Egbe, F.N. https://orcid.org/0000-0002-9547-4609 Martin, N.H. Facer, B. Pendered, S.L. Rogers, H.C. Hübel, C. van Wamelen, D.J. https://orcid.org/0000-0003-0921-5158 Bethlehem, R.A.I. Giunchiglia, V. Hellyer, P.J. Trender, W. https://orcid.org/0000-0003-3947-5532 Kalsi, G. Needham, E. https://orcid.org/0000-0001-7042-7462 Easton, A. https://orcid.org/0000-0002-1739-2915 Jackson, T.A. Cunningham, C. https://orcid.org/0000-0003-1423-5209 Upthegrove, R. https://orcid.org/0000-0001-8204-5103 Pollak, T.A. https://orcid.org/0000-0002-6171-0810 Hotopf, M. Solomon, T. https://orcid.org/0000-0001-7266-6547 Pett, S.L. Shaw, P.J. https://orcid.org/0000-0002-8925-2567 Wood, N. https://orcid.org/0000-0002-9500-3348 Harrison, N.A. https://orcid.org/0000-0002-9584-3769 Miller, K.L. Jezzard, P. https://orcid.org/0000-0001-7912-2251 Williams, G. https://orcid.org/0000-0001-5223-6654 Duff, E.P. Williams, S. https://orcid.org/0000-0003-4299-1941 Zelaya, F. https://orcid.org/0000-0002-9525-1560 Smith, S.M. https://orcid.org/0000-0001-8166-069X Keller, S. Broome, M. https://orcid.org/0000-0002-6963-8884 Kingston, N. https://orcid.org/0000-0002-9190-2231 Husain, M. https://orcid.org/0000-0002-6850-9255 Vincent, A. https://orcid.org/0000-0003-2395-8695 Bradley, J. https://orcid.org/0000-0002-7774-8805 Chinnery, P. Menon, D.K. https://orcid.org/0000-0002-3228-9692 Aggleton, J.P. Nicholson, T.R. Taylor, J.-P. David, A.S. https://orcid.org/0000-0003-0967-774X Carson, A. Bullmore, E. Breen, G. https://orcid.org/0000-0003-2053-1792 Hampshire, A. Alam, A.M. Al-Chalabi, A. Allen, C.M. Amin, J. Armour, C. Baker, M.R. Barrett, S. Basu, N. Batra, R. Benjamin, L. Berry, A. Bethlehem, R.A.I. Blackledge, B. Boardman, S.A. Bradley, J. Breen, D.P. Breuer, J. Broome, M. Bullmore, E. Butler, M. Castell, H. Cavanagh, J. Christmas, D. Christmas, D.M. Coleman, J.R.I. Coles, A. Collie, C. Cossette, N. Cousins, D. Darby, A. Davies, N. Defres, S. Dodd, K.C. Dregan, A. Duff, E. Ellul, M.A. Evangelou, N. Fernandes, P.M. Francis, R. Galea, I. Garjani, A. George, L. Giunchiglia, V. Glen, K. Gregory, R. Griffiths, M. Grimbly, V. Grundmann, A. Gunatilake, S. Hamid, S.H.M. Hardwick, M. Harris, J.D. Harrison, E. Harrison, P.J. Hartmann, M. Hetherington, C. Hilton, O. Hiscox, J. Hodel, E.M. Holland, A.E. Huang, Y. Hughes, S. Irani, S. Jenkins, T.M. Zvrskovec, J.K. Kyaw, S. Lewis, G. Lilleker, J.B. Lunn, M.P. MacIver, C.L. Madarshahian, D. Mansoori, P. Martin, N. McDonnell, G. McGlinchey, E. McKeever, S. McIlwaine, R. McIntosh, A.M. Miller, K.L. Monssen, D. Morris, C.M. Mulholland, C. Nair, A. Newcombe, V. Nicholas, N. Nicholson, T.R. O’Malley, R. Orazulume, O. Ostermann, M. Palmos, A. Patel, A. Peacock, S. Pendered, S.L. Pollak, T.A. Roberts, A. Rota, S. Salman, R.A.-S. Samuel, M. Sargent, B.F. Sawcer, S.J. Seed, A.W. Semple, S. Shil, R.S.K. Sieradzki, A. Singh, B. Smith, C.J. Smith, J. Smith, S.M. Taams, L. Tamborska, A. Thomas, R.H. Thomson, E. Trender, W. Ahmad, Z.-U.-A. Underwood, J. Veenith, T. Venneri, A. van Wamelen, D.J. Williams, G. Wong, S.H. Zandi, M.S. Michael, B.D. https://orcid.org/0000-0002-8693-8926 Paddick, S.-M. Leek, E.C.
Copyright, Publisher and Additional Information:	© 2024 The Authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords:	COVID-CNS Consortium
Dates:	Published: January 2025 Published (online): 23 September 2024 Accepted: 18 September 2024
Institution:	The University of Sheffield
Academic Units:	The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine and Population Health
Depositing User:	Symplectic Sheffield
Date Deposited:	27 Jan 2025 10:58
Last Modified:	27 Jan 2025 10:58
Published Version:	https://doi.org/10.1038/s41591-024-03309-8
Status:	Published
Publisher:	Springer Science and Business Media LLC
Refereed:	Yes
Identification Number:	10.1038/s41591-024-03309-8
Related URLs:	PubMed URL Dataset
Sustainable Development Goals:
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:222360