Posthospitalization COVID-19 cognitive deficits at 1 year are global and associated with elevated brain injury markers and gray matter volume reduction
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., Breen G., Hampshire A., Alam AM., Al-Chalabi A., Allen CM., Amin J., Armour C., Baker MR., Barrett S., Basu N., Batra R., Benjamin L., Berry A., Bethlehem RAI., Blackledge B., Boardman SA., Bradley J., Breen DP., Breuer J., Broome M., Bullmore E., Butler M., Castell H., Cavanagh J., Christmas D., Christmas DM., Coleman JRI., Coles A., Collie C., Cossette N., Cousins D., Darby A., Davies N., Defres S., Dodd KC., Dregan A., Duff E., Ellul MA., Evangelou N., Fernandes PM., Francis R., Galea I., Garjani A., George L., Giunchiglia V., Glen K., Gregory R., Griffiths M., Grimbly V., Grundmann A., Gunatilake S., Hamid SHM., Hardwick M., Harris JD., Harrison E., Harrison PJ., Hartmann M., Hetherington C., Hilton O., Hiscox J., Hodel EM., Holland AE., Huang Y., Hughes S., Irani S., Jenkins TM., Zvrskovec JK., Kyaw S., Lewis G., Lilleker JB., Lunn MP., MacIver CL., Madarshahian D., Mansoori P., Martin N., McDonnell G., McGlinchey E., McKeever S., McIlwaine R., McIntosh AM., Miller KL., Monssen D., Morris CM., Mulholland C., Nair A., Newcombe V., Nicholas N., Nicholson TR., O’Malley R., Orazulume O., Ostermann M., Palmos A., Patel A., Peacock S., Pendered SL., Pollak TA., Roberts A., Rota S., Salman RA-S., Samuel M., Sargent BF., Sawcer SJ., Seed AW., Semple S., Shil RSK., Sieradzki A., Singh B., Smith CJ., Smith J., Smith SM., Taams L., Tamborska A., Thomas RH., Thomson E., Trender W., Ahmad Z-U-A., Underwood J., Veenith T., Venneri A., van Wamelen DJ., Williams G., Wong SH., Zandi MS., Michael BD., Paddick S-M., Leek EC.
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.