Posthospitalization COVID-19 cognitive deficits at 1 year are global and associated with elevated brain injury markers and gray matter volume reduction
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.
Authors
- Eugene Duff (ORCID: https://orcid.org/0000-0001-8795-5472)
- Greta K. Wood (ORCID: https://orcid.org/0000-0001-6098-2331)
- Matthew H. Hotopf (ORCID: https://orcid.org/0000-0002-3980-4466)
- Franklyn Egbe (ORCID: https://orcid.org/0000-0002-9547-4609)
- Timothy R. Nicholson (ORCID: https://orcid.org/0000-0002-2350-2332)
- Gerome D. Breen (ORCID: https://orcid.org/0000-0003-2053-1792)
- Tom Solomon (ORCID: https://orcid.org/0000-0001-7266-6547)
- Anthony S. David (ORCID: https://orcid.org/0000-0003-0967-774X)
- Patrick Francis Chinnery (ORCID: https://orcid.org/0000-0002-7065-6617)
- Richard A. I. Bethlehem (ORCID: https://orcid.org/0000-0002-0714-0685)
- Kukatharmini Tharmaratnam (ORCID: https://orcid.org/0000-0002-8255-9822)
- Thomas Jackson (ORCID: https://orcid.org/0000-0001-6320-9600)
- William R. Trender (ORCID: https://orcid.org/0000-0003-3947-5532)
- Sarah Pett (ORCID: https://orcid.org/0000-0002-4851-4727)
- Colm Cunningham (ORCID: https://orcid.org/0000-0003-1423-5209)
- E. Charles Leek (ORCID: https://orcid.org/0000-0001-9258-7504)
- Nathalie Kingston (ORCID: https://orcid.org/0000-0002-9190-2231)
- Fernando Zelaya (ORCID: https://orcid.org/0000-0002-9525-1560)
- Matthew R. Broome (ORCID: https://orcid.org/0000-0002-6963-8884)
- Guy Williams (ORCID: https://orcid.org/0000-0001-5223-6654)
- Masud Husain (ORCID: https://orcid.org/0000-0002-6850-9255)
- Adam Hampshire (ORCID: https://orcid.org/0000-0002-5176-5420)
- Brendan Sargent (ORCID: https://orcid.org/0000-0003-2262-7755)
- Thomas Pollak (ORCID: https://orcid.org/0000-0002-6171-0810)
- Edward Needham (ORCID: https://orcid.org/0000-0001-7042-7462)
- Edward Thomas Bullmore (ORCID: https://orcid.org/0000-0002-8955-8283)
- Valentina Giunchiglia (ORCID: https://orcid.org/0000-0002-2165-7840)
- Steven Williams (ORCID: https://orcid.org/0000-0003-4299-1941)
- Daniel J. van Wamelen (ORCID: https://orcid.org/0000-0003-0921-5158)
- Neil Andrew Harrison (ORCID: https://orcid.org/0000-0002-9584-3769)
- Ava Easton (ORCID: https://orcid.org/0000-0002-1739-2915)
- Alan Carson (ORCID: https://orcid.org/0009-0001-3647-1686)
- Gursharan Kalsi (ORCID: https://orcid.org/0000-0002-5156-7176)
- Rachel Upthegrove (ORCID: https://orcid.org/0000-0001-8204-5103)
- David Krishna Menon (ORCID: https://orcid.org/0000-0002-3228-9692)
- Cordelia Dunai
- Angela Vincent (ORCID: https://orcid.org/0000-0003-2395-8695)
- John P. Aggleton (ORCID: https://orcid.org/0000-0002-5573-1308)
- Nicholas William Wood (ORCID: https://orcid.org/0000-0002-9500-3348)
- Stephen M. Smith (ORCID: https://orcid.org/0000-0001-8166-069X)
- Simon S. Keller (ORCID: https://orcid.org/0000-0001-5247-9795)
- Henry C. Rogers (ORCID: https://orcid.org/0000-0003-2531-7496)
- Naomi Martin (ORCID: https://orcid.org/0000-0002-0210-7536)
- John R. Bradley (ORCID: https://orcid.org/0000-0002-7774-8805)
- Karla L. Miller (ORCID: https://orcid.org/0000-0002-2511-3189)
- Peter John Hellyer (ORCID: https://orcid.org/0000-0002-5139-3401)
- Peter Jezzard (ORCID: https://orcid.org/0000-0001-7912-2251)
- Christopher Hübel (ORCID: https://orcid.org/0000-0002-1267-8287)
- Zain Ahmad (ORCID: https://orcid.org/0000-0002-6940-8851)
- Bethany Facer (ORCID: https://orcid.org/0000-0001-9214-8229)
- Pamela J. Shaw (ORCID: https://orcid.org/0000-0002-8925-2567)
- John‐Paul Taylor (ORCID: https://orcid.org/0000-0001-7958-6558)
- Sophie Pendered
Institutions
- Queen's University Belfast (GB)
- Belfast Health and Social Care Trust (GB)
- NHS Lothian (GB)
- University of Nottingham (GB)
- Radboud University Nijmegen (NL)
- University of Liverpool (GB)
- Queen Mary University of London (GB)
- University of Dundee (GB)
- King's College London (GB)
- Liverpool School of Tropical Medicine (GB)
- South London and Maudsley NHS Foundation Trust (GB)
- Aarhus University (DK)
- Trinity College Dublin (IE)
- Cumbria Northumberland Tyne and Wear NHS Foundation Trust (GB)
- University of Cambridge (GB)
- Aintree University Hospitals NHS Foundation Trust (GB)
- Royal Stoke University Hospital (GB)
- Mental Health Research UK (GB)
- Cambridge University Hospitals NHS Foundation Trust (GB)
- Millennium Science Initiative (CL)
- John Radcliffe Hospital (GB)
- Edinburgh Royal Infirmary (GB)
- Walton Centre (GB)
- Stroke Association (GB)
- Radboud University Medical Center (NL)
- Warneford Hospital (GB)
- University of Manchester (GB)
- Northern Health and Social Care Trust (GB)
- National Institute for Health and Care Research (GB)
- University of Oxford (GB)
- Cambridge School (PT)
- MRC Clinical Trials Unit at UCL (GB)
- Institute of Mental Health (GB)
- Wellcome Centre for Integrative Neuroimaging (GB)
- Sheffield Teaching Hospitals NHS Foundation Trust (GB)
- Gateshead Health NHS Foundation Trust (GB)
- Salford Royal Hospital (GB)
- UK Dementia Research Institute (GB)
- Encephalitis Society (GB)
- King's College Hospital (GB)
- Birmingham Women’s and Children’s NHS Foundation Trust (GB)
- Institute of Genetics (HU)
- Health Protection Research Unit in Emerging and Zoonotic Infections at University of Liverpool (GB)
- University of Southampton (GB)
- University College London (GB)
- Imperial College London (GB)
- Charité - Universitätsmedizin Berlin (DE)
- University of Glasgow (GB)
- MRC Mitochondrial Biology Unit (GB)
- Cardiff University (GB)
- University of Birmingham (GB)
- Newcastle University (GB)
- University of Sheffield (GB)
- University of Edinburgh (GB)
Publication Details
- Journal
- Nature Medicine
- Published
- 2024-09-23
- DOI
- https://doi.org/10.1038/s41591-024-03309-8
- Citations
- 42
- Primary Topic
- Long-Term Effects of COVID-19
- Type
- article
- Field-Weighted Citation Impact
- 15.50
Funders
- Wellcome
- Wellcome Trust
- UK Research and Innovation
- National Institute for Health Research Health Protection Research Unit
- International Seafood Sustainability Foundation
- National Institute for Health and Care Research
- King's College London
- NIHR BioResource
- NIHR Maudsley Biomedical Research Centre
- Medical Research Council
- NIHR Newcastle Biomedical Research Centre