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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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.
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COVID-19 is very rarely neuroinvasive, but its impact on the brain might be immune-mediated and cause glial neuroinflammation.
“Indeed, while COVID-19 is very rarely neuroinvasive [127], its impact on the brain might be immune-mediated [126] and cause glial neuroinflammation [128,129,130].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [126]
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- Authors
- Wood, G. K., Sargent, B. F., Ahmad, Z.-U.-A., Tharmaratnam, K., Dunai, C., Egbe, F. N., Martin, N. H., Facer, B., Pendered, S. L., Rogers, H. C., Hübel, C., van Wamelen, D. J., Bethlehem, R. A. I., Giunchiglia, V., Hellyer, P. J., Trender, W., Kalsi, G., Needham, E., Easton, A., Jackson, T. A., Cunningham, C., Upthegrove, R., Pollak, T. A., Hotopf, M., Solomon, T., Pett, S. L., Shaw, P. J., Wood, N., Harrison, N. A., Miller, K. L., Jezzard, P., Williams, G., Duff, E. P., Williams, S., Zelaya, F., Smith, S. M., Keller, S., Broome, M., Kingston, N., Husain, M., Vincent, A., Bradley, J., Chinnery, P., Menon, D. K., Aggleton, J. P., Nicholson, T. R., Taylor, J.-P., David, A. S., Carson, A., Bullmore, E., Breen, G., Hampshire, A., COVID-CNS Consortium, 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., Paddick, S.-M., & Leek, E. C.
- Affiliations
- University of Liverpool (GB)
- King's College London (GB)
- University of Cambridge (GB)
- University of Birmingham (GB)
- Trinity College Dublin (IE)
- MRC Clinical Trials Unit at UCL (GB)
- NIHR Sheffield Biomedical Research Centre (GB)
- UCL Queen Square Institute of Neurology (GB)
- Cardiff University (GB)
- University of Oxford (GB)
- UK Dementia Research Institute (GB)
- John Radcliffe Hospital (GB)
- Cumbria Northumberland Tyne and Wear NHS Foundation Trust (GB)
- University College London (GB)
- University of Edinburgh (GB)
- University of Nottingham (GB)
- University of Southampton (GB)
- Newcastle University (GB)
- Northern Health and Social Care Trust (GB)
- University of Glasgow (GB)
- Northern Care Alliance NHS Foundation Trust (GB)
- University of Dundee (GB)
- NHS Lothian (GB)
- Imperial College London (GB)
- Liverpool School of Tropical Medicine (GB)
- University of Manchester (GB)
- Stroke Association (GB)
- Sheffield Teaching Hospitals NHS Foundation Trust (GB)
- Royal Stoke University Hospital (GB)
- Warneford Hospital (GB)
- Belfast Health and Social Care Trust (GB)
- Institute of Mental Health (GB)
- South London and Maudsley NHS Foundation Trust (GB)
- National Institute for Health and Care Research (GB)
- Queen's University Belfast (GB)
- Aintree University Hospitals NHS Foundation Trust (GB)
- Liverpool University Hospitals NHS Foundation Trust (GB)
- University of Sheffield (GB)
- Gateshead Health NHS Foundation Trust (GB)
- Corresponding author
- Michael, Benedict D.
- ORCID
- Wood, Greta K.
- Tharmaratnam, Kukatharmini
- Egbe, Franklyn N.
- Facer, Bethany
- Rogers, Henry C.
- Hübel, Christopher
- Hellyer, Peter J.
- Kalsi, Gursharan
- Needham, Edward
- Easton, Ava
- Jackson, Thomas A.
- Cunningham, Colm
- Upthegrove, Rachel
- Hotopf, Matthew
- Solomon, Tom
- Pett, Sarah L.
- Shaw, Pamela J.
- Wood, Nicholas
- Harrison, Neil A.
- Jezzard, Peter
- Duff, Eugene P.
- Williams, Steven
- Zelaya, Fernando
- Keller, Simon
- Kingston, Nathalie
- Husain, Masud
- Vincent, Angela
- Chinnery, Patrick
- Menon, David K.
- Aggleton, John P.
- Taylor, John-Paul
- David, Anthony S.
- Carson, Alan
- Breen, Gerome
- Hampshire, Adam
- Benjamin, Laura
- Berry, Alex
- Breuer, Judith
- Cousins, David
- Defres, Sylviane
- Dodd, Katherine C.
- Evangelou, Nikos
- Galea, Ian
- Garjani, Afagh
- Harrison, Paul J.
- Hetherington, Claire
- Hilton, Orla
- Hiscox, Julian
- Irani, Sarosh
- Jenkins, Thomas M.
- Lilleker, James B.
- Lunn, Michael P.
- McGlinchey, Emily
- Mulholland, Ciaran
- Nair, Akshay
- Newcombe, Virginia
- Rota, Silvia
- Salman, Rustam Al-Shahi
- Smith, Craig J.
- Taams, Leonie
- Thomas, Rhys H.
- Veenith, Tonny
- Wong, Sui Hsien
- Zandi, Michael S.
- Michael, Benedict D.
- Paddick, Stella-Maria
- Leek, E. Charles
- Venue
- Nature Medicine
- Published
- 2024-09-23
- Volume
- 31
- Issue
- 1
- Pages
- 245-257
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC11750706
- OpenAlex
- W4402748246
- Cited by
- 67
- References
- 71
- Citations by year
- 2026: 28 · 2025: 31 · 2024: 8
- FWCI
- 17.93
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Nature Medicine (publishedVersion, cc-by)
- Research Square (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (publishedVersion)
- ePrints Soton (University of Southampton) (acceptedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- Brunel University Research Archive (BURA) (Brunel University London) (submittedVersion, cc-by)
- Research Portal (King's College London) (submittedVersion, other-oa)
- Research Portal (Queen's University Belfast) (submittedVersion, cc-by)
- Wolverhampton Intellectual Repository and E-Theses (University of Wolverhampton) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity) (cc-by)
- Funders
- RCUK | Medical Research Council (MR/V03605X/1, MC_PC_19059, MR/V007181/1, MR/T028750/1)
- DH | National Institute for Health Research (CO-CIN-01, ACF-2022-07-007)
- Wellcome Trust (ISSF201902/3)
- Topics
- Health Sciences › Medicine › Neurology › Long-Term Effects of COVID-19
- Health Sciences › Medicine › Infectious Diseases › Infectious Encephalopathies and Encephalitis
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Intensive Care Unit Cognitive Disorders
- Keywords
- long COVID, brain injury markers, gray matter volume reduction, anterior cingulate cortex, encephalopathy, cognitive recovery, serum biomarkers, neuroimaging
- MeSH terms
- COVID-19, SARS-CoV-2, Adult, Aged, Brain Injuries, Female, Gyrus Cinguli, Hospitalization, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Prospective Studies, Biomarkers, Neuroimaging, Cognitive Dysfunction, Gray Matter
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