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 Sargent, Zain Ahmad, Kukatharmini Tharmaratnam, Cordelia Dunai, Franklyn Egbe, Naomi Martin, Bethany Facer, Sophie 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 Jackson, Colm Cunningham, Rachel Upthegrove, Thomas Pollak, Matthew Hotopf, Tom Solomon, Sarah Pett, Pamela J. Shaw, Nicholas Wood, Neil A. Harrison, Karla L. Miller, Peter Jezzard, Guy Williams, Eugene Duff, Steven Williams, Fernando Zelaya, Stephen M. Smith, Simon S. Keller, Matthew R. Broome, Nathalie Kingston, Masud Husain, Angela Vincent, John R. Bradley, Patrick F. Chinnery, David Menon, John P. Aggleton, Timothy R. Nicholson, John‐Paul Taylor, Anthony S. David, Alan Carson, Edward T. 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
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.