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; Stephen M. Smith; John Bradley; Stephen M. Smith; Craig J. Smith; Ciaran Mulholland; Andrew M. McIntosh; Stephen McKeever; Emily McGlinchey; Gavin McDonnell; Stella Hughes; Matthew Butler; John Bradley; Suzanne Barrett; Mark R. Baker; Cherie Armour; Christopher M. Allen; 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. 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, Stephen M. Smith, John Bradley, Stephen M. Smith, Craig J. Smith, Ciaran Mulholland, Andrew M. McIntosh, Stephen McKeever, Emily McGlinchey, Gavin McDonnell, Stella Hughes, Matthew Butler, John Bradley, Suzanne Barrett, Mark R. Baker, Cherie Armour, Christopher M. Allen, COVID-CNS Consortium

Research output: Contribution to journal › Article › peer-review

56 Citations (Scopus)

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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.

Original language	English
Journal	Nature Medicine
Early online date	23 Sept 2024
DOIs	https://doi.org/10.1038/s41591-024-03309-8
Publication status	Early online date - 23 Sept 2024

Keywords

COVID-19
Posthospitalization COVID-19 cognitive deficits
COVID-19 cognitive deficits
elevated brain injury markers

ASJC Scopus subject areas

General Biochemistry,Genetics and Molecular Biology

Access to Document

10.1038/s41591-024-03309-8Licence: CC BY

Posthospitalization COVID-19 cognitive deficits at 1 year are global and associated with elevated brain injury markers and gray matter volume reduction
Copyright 2024 the authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 4.41 MBLicence: CC BY

56 Citations
1 Comment/debate

Author Correction: Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses
Michael, B. D., Dunai, C., Needham, E. J., Tharmaratnam, K., Williams, R., Huang, Y., Boardman, S. A., Clark, J. J., Sharma, P., Subramaniam, K., Wood, G. K., Collie, C., Digby, R., Ren, A., Norton, E., Leibowitz, M., Ebrahimi, S., Fower, A., Fox, H. & Tato, E. & 32 others, Stewart, J. P., Bradley, J. R., Scott, J. T., Takats, Z., Thompson, A. A. R., Shaw, C. A., Carson, G., Lyttle, M., Morgan, P., Murphy, M., Smith, R., Bakshi, S., Davis, C., Jones, C. B., Zhang, J. E., McIntosh, A. M., Armour, C., Allen, C. M., Mulholland, C., Smith, C. J., McGlinchey, E., McDonnell, G., Bradley, J. R., Baker, M. R., Butler, M., Harrison, N., Harrison, N., Barrett, S., Hughes, S., Smith, S., ISARIC4C Investigators & COVID-CNS Consortium, 04 Apr 2024, In: Nature Communications. 15, 2918.
Research output: Contribution to journal › Comment/debate › peer-review

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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 (2024). Posthospitalization COVID-19 cognitive deficits at 1 year are global and associated with elevated brain injury markers and gray matter volume reduction. Nature Medicine. Advance online publication. 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.",

keywords = "COVID-19, Posthospitalization COVID-19 cognitive deficits, COVID-19 cognitive deficits, elevated brain injury markers",

author = "Wood, \{Greta K.\} and Sargent, \{Brendan F.\} and Ahmad, \{Zain Ul Abideen\} 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 Smith, \{Stephen M.\} and John Bradley and Smith, \{Stephen M.\} and Smith, \{Craig J.\} and Ciaran Mulholland and McIntosh, \{Andrew M.\} and Stephen McKeever and Emily McGlinchey and Gavin McDonnell and Stella Hughes and Matthew Butler and John Bradley and Suzanne Barrett and Baker, \{Mark R.\} and Cherie Armour and Allen, \{Christopher M.\} and \{COVID-CNS Consortium\}",

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Wood, GK, Sargent, BF, Ahmad, ZUA, 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, Smith, SM, Bradley, J, Smith, SM, Smith, CJ, Mulholland, C, McIntosh, AM, McKeever, S, McGlinchey, E, McDonnell, G, Hughes, S, Butler, M, Bradley, J, Barrett, S, Baker, MR, Armour, C, Allen, CM & COVID-CNS Consortium 2024, 'Posthospitalization COVID-19 cognitive deficits at 1 year are global and associated with elevated brain injury markers and gray matter volume reduction', Nature Medicine. https://doi.org/10.1038/s41591-024-03309-8

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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 - Smith, Stephen M.

AU - Bradley, John

AU - Smith, Stephen M.

AU - Smith, Craig J.

AU - Mulholland, Ciaran

AU - McIntosh, Andrew M.

AU - McKeever, Stephen

AU - McGlinchey, Emily

AU - McDonnell, Gavin

AU - Hughes, Stella

AU - Butler, Matthew

AU - Bradley, John

AU - Barrett, Suzanne

AU - Baker, Mark R.

AU - Armour, Cherie

AU - Allen, Christopher M.

AU - COVID-CNS Consortium

PY - 2024/9/23

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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.

KW - COVID-19

KW - Posthospitalization COVID-19 cognitive deficits

KW - COVID-19 cognitive deficits

KW - elevated brain injury markers

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DO - 10.1038/s41591-024-03309-8

M3 - Article

C2 - 39312956

AN - SCOPUS:85208633557

SN - 1078-8956

JO - Nature Medicine

JF - Nature Medicine

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Fingerprint

Research output

Author Correction: Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

Cite this