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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,
  • Gerome Breen,
  • Adam Hampshire,
  • Ali M. Alam,
  • Ammar Al-Chalabi,
  • Christopher M. Allen,
  • Jay Amin,
  • Cherie Armour,
  • Mark R. Baker,
  • Suzanne Barrett,
  • Neil Basu,
  • Rahul Batra,
  • Laura Benjamin,
  • Alex Berry,
  • Richard A. I. Bethlehem,
  • Bethan Blackledge,
  • Sarah A. Boardman,
  • John Bradley,
  • David P. Breen,
  • Judith Breuer,
  • Matthew Broome,
  • Ed Bullmore,
  • Matthew Butler,
  • Hannah Castell,
  • Jonathan Cavanagh,
  • David Christmas,
  • David M. Christmas,
  • Jonathan R. I. Coleman,
  • Alaistair Coles,
  • Ceryce Collie,
  • Nadine Cossette,
  • David Cousins,
  • Alastair Darby,
  • Nicholas Davies,
  • Sylviane Defres,
  • Katherine C. Dodd,
  • Alex Dregan,
  • Eugene Duff,
  • Mark A. Ellul,
  • Nikos Evangelou,
  • Peter M. Fernandes,
  • Richard Francis,
  • Ian Galea,
  • Afagh Garjani,
  • Lily George,
  • Valentina Giunchiglia,
  • Kiran Glen,
  • Rebecca Gregory,
  • Michael Griffiths,
  • Victoria Grimbly,
  • Alexander Grundmann,
  • Savini Gunatilake,
  • Shahd H. M. Hamid,
  • Marc Hardwick,
  • Jade D. Harris,
  • Ewan Harrison,
  • Paul J. Harrison,
  • Monika Hartmann,
  • Claire Hetherington,
  • Orla Hilton,
  • Julian Hiscox,
  • Eva Maria Hodel,
  • Angela E. Holland,
  • Yun Huang,
  • Stella Hughes,
  • Sarosh Irani,
  • Thomas M. Jenkins,
  • Johan Kallberg Zvrskovec,
  • Sandar Kyaw,
  • Gabriella Lewis,
  • James B. Lilleker,
  • Michael P. Lunn,
  • Claire L. MacIver,
  • Daniel Madarshahian,
  • Parisa Mansoori,
  • Naomi Martin,
  • Gavin McDonnell,
  • Emily McGlinchey,
  • Stephen McKeever,
  • Ryan McIlwaine,
  • Andrew M. McIntosh,
  • Karla L. Miller,
  • Dina Monssen,
  • Christopher M. Morris,
  • Ciaran Mulholland,
  • Akshay Nair,
  • Virginia Newcombe,
  • Nathalie Nicholas,
  • Timothy R. Nicholson,
  • Ronan O’Malley,
  • Obioma Orazulume,
  • Marlies Ostermann,
  • Alish Palmos,
  • Arvind Patel,
  • Sharon Peacock,
  • Sophie L. Pendered,
  • Thomas A. Pollak,
  • Angela Roberts,
  • Silvia Rota,
  • Rustam Al-Shahi Salman,
  • Merna Samuel,
  • Brendan F. Sargent,
  • Stephen J. Sawcer,
  • Adam W. Seed,
  • Scott Semple,
  • Rajish S. K. Shil,
  • Adam Sieradzki,
  • Bhagteshwar Singh,
  • Craig J. Smith,
  • Jacqueline Smith,
  • Stephen M. Smith,
  • Leonie Taams,
  • Arina Tamborska,
  • Rhys H. Thomas,
  • Emma Thomson,
  • William Trender,
  • Zain-Ul-Abideen Ahmad,
  • Jonathan Underwood,
  • Tonny Veenith,
  • Annalena Venneri,
  • Daniel J. van Wamelen,
  • Guy Williams,
  • Sui Hsien Wong,
  • Michael S. Zandi,
  • Benedict D. Michael,
  • Stella-Maria Paddick,
  • E. Charles Leek

摘要

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.