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

Greta K Wood; Brendan F Sargent; Zain-Ul-Abideen Ahmad; Kukatharmini Tharmaratnam; Cordelia Dunai; Franklyn N Egbe; Naomi H Martin; Bethany Facer; Sophie L Pendered; Henry C Rogers; Christopher Hübel; Daniel J van Wamelen; Richard A I Bethlehem; Valentina Giunchiglia; Peter J Hellyer; William Trender; Gursharan Kalsi; Edward Needham; Ava Easton; Thomas A Jackson; Colm Cunningham; Rachel Upthegrove; Thomas A Pollak; Matthew Hotopf; Tom Solomon; Sarah L Pett; Pamela J Shaw; Nicholas Wood; Neil A Harrison; Karla L Miller; Peter Jezzard; Guy Williams; Eugene P Duff; Steven Williams; Fernando Zelaya; Stephen M Smith; Simon Keller; Matthew Broome; Nathalie Kingston; Masud Husain; Angela Vincent; John Bradley; Patrick Chinnery; David K Menon; John P Aggleton; Timothy R Nicholson; John-Paul Taylor; Anthony S David; Alan Carson; Ed Bullmore; COVID-CNS Consortium

doi: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

Greta K Wood, Brendan F Sargent, Zain-Ul-Abideen Ahmad, Kukatharmini Tharmaratnam, Cordelia Dunai, Franklyn N Egbe, Naomi H Martin, Bethany Facer, Sophie L Pendered, Henry C Rogers, Christopher Hübel, Daniel J van Wamelen, Richard A I Bethlehem, Valentina Giunchiglia, Peter J Hellyer, William Trender, Gursharan Kalsi, Edward Needham, Ava Easton, Thomas A JacksonColm Cunningham, Rachel Upthegrove, Thomas A Pollak, Matthew Hotopf, Tom Solomon, Sarah L Pett, Pamela J Shaw, Nicholas Wood, Neil A Harrison, Karla L Miller, Peter Jezzard, Guy Williams, Eugene P Duff, Steven Williams, Fernando Zelaya, Stephen M Smith, Simon Keller, Matthew Broome, Nathalie Kingston, Masud Husain, Angela Vincent, John Bradley, Patrick Chinnery, David K Menon, John P Aggleton, Timothy R Nicholson, John-Paul Taylor, Anthony S David, Alan Carson, Ed Bullmore, COVID-CNS Consortium

Department of Public Health - National Centre for Register-based Research

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

6 Citations (Scopus)

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.

Original language	English
Article number	101417
Journal	Nature Medicine
Volume	31
Issue	1
Pages (from-to)	245–257
Number of pages	13
ISSN	1078-8956
DOIs	https://doi.org/10.1038/s41591-024-03309-8
Publication status	Published - Jan 2025

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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., ... COVID-CNS Consortium (2025). 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), 245–257. Article 101417. https://doi.org/10.1038/s41591-024-03309-8

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title = "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.",

author = "Wood, {Greta K} and Sargent, {Brendan F} and Zain-Ul-Abideen Ahmad and Kukatharmini Tharmaratnam and Cordelia Dunai and Egbe, {Franklyn N} and Martin, {Naomi H} and Bethany Facer and Pendered, {Sophie L} and Rogers, {Henry C} and Christopher H{\"u}bel and {van Wamelen}, {Daniel J} and Bethlehem, {Richard A I} and Valentina Giunchiglia and Hellyer, {Peter J} and William Trender and Gursharan Kalsi and Edward Needham and Ava Easton and Jackson, {Thomas A} and Colm Cunningham and Rachel Upthegrove and Pollak, {Thomas A} and Matthew Hotopf and Tom Solomon and Pett, {Sarah L} and Shaw, {Pamela J} and Nicholas Wood and Harrison, {Neil A} and Miller, {Karla L} and Peter Jezzard and Guy Williams and Duff, {Eugene P} and Steven Williams and Fernando Zelaya and Smith, {Stephen M} and Simon Keller and Matthew Broome and Nathalie Kingston and Masud Husain and Angela Vincent and John Bradley and Patrick Chinnery and Menon, {David K} and Aggleton, {John P} and Nicholson, {Timothy R} and John-Paul Taylor and David, {Anthony S} and Alan Carson and Ed Bullmore and {COVID-CNS Consortium}",

note = "{\textcopyright} 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.",

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doi = "10.1038/s41591-024-03309-8",

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Wood, GK, Sargent, BF, Ahmad, Z-U-A, Tharmaratnam, K, Dunai, C, Egbe, FN, Martin, NH, Facer, B, Pendered, SL, Rogers, HC, Hübel, C, van Wamelen, DJ, Bethlehem, RAI, Giunchiglia, V, Hellyer, PJ, Trender, W, Kalsi, G, Needham, E, Easton, A, Jackson, TA, Cunningham, C, Upthegrove, R, Pollak, TA, Hotopf, M, Solomon, T, Pett, SL, Shaw, PJ, Wood, N, Harrison, NA, Miller, KL, Jezzard, P, Williams, G, Duff, EP, Williams, S, Zelaya, F, Smith, SM, Keller, S, Broome, M, Kingston, N, Husain, M, Vincent, A, Bradley, J, Chinnery, P, Menon, DK, Aggleton, JP, Nicholson, TR, Taylor, J-P, David, AS, Carson, A, Bullmore, E & COVID-CNS Consortium 2025, 'Posthospitalization COVID-19 cognitive deficits at 1 year are global and associated with elevated brain injury markers and gray matter volume reduction', Nature Medicine, vol. 31, no. 1, 101417, pp. 245–257. https://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. / Wood, Greta K; Sargent, Brendan F; Ahmad, Zain-Ul-Abideen et al.
In: Nature Medicine, Vol. 31, No. 1, 101417, 01.2025, p. 245–257.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Posthospitalization COVID-19 cognitive deficits at 1 year are global and associated with elevated brain injury markers and gray matter volume reduction

AU - Wood, Greta K

AU - Sargent, Brendan F

AU - Ahmad, Zain-Ul-Abideen

AU - Tharmaratnam, Kukatharmini

AU - Dunai, Cordelia

AU - Egbe, Franklyn N

AU - Martin, Naomi H

AU - Facer, Bethany

AU - Pendered, Sophie L

AU - Rogers, Henry C

AU - Hübel, Christopher

AU - van Wamelen, Daniel J

AU - Bethlehem, Richard A I

AU - Giunchiglia, Valentina

AU - Hellyer, Peter J

AU - Trender, William

AU - Kalsi, Gursharan

AU - Needham, Edward

AU - Easton, Ava

AU - Jackson, Thomas A

AU - Cunningham, Colm

AU - Upthegrove, Rachel

AU - Pollak, Thomas A

AU - Hotopf, Matthew

AU - Solomon, Tom

AU - Pett, Sarah L

AU - Shaw, Pamela J

AU - Wood, Nicholas

AU - Harrison, Neil A

AU - Miller, Karla L

AU - Jezzard, Peter

AU - Williams, Guy

AU - Duff, Eugene P

AU - Williams, Steven

AU - Zelaya, Fernando

AU - Smith, Stephen M

AU - Keller, Simon

AU - Broome, Matthew

AU - Kingston, Nathalie

AU - Husain, Masud

AU - Vincent, Angela

AU - Bradley, John

AU - Chinnery, Patrick

AU - Menon, David K

AU - Aggleton, John P

AU - Nicholson, Timothy R

AU - Taylor, John-Paul

AU - David, Anthony S

AU - Carson, Alan

AU - Bullmore, Ed

AU - COVID-CNS Consortium

PY - 2025/1

Y1 - 2025/1

N2 - 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.

AB - 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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U2 - 10.1038/s41591-024-03309-8

DO - 10.1038/s41591-024-03309-8

M3 - Journal article

C2 - 39312956

SN - 1078-8956

VL - 31

SP - 245

EP - 257

JO - Nature Medicine

JF - Nature Medicine

IS - 1

M1 - 101417

ER -

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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