Cognitive deficits in people who have recovered from COVID-19

Abstract

Background: There is growing concern about possible cognitive consequences of COVID-19, with reports of 'Long COVID' symptoms persisting into the chronic phase and case studies revealing neurological problems in severely affected patients. However, there is little information regarding the nature and broader prevalence of cognitive problems post-infection or across the full spread of disease severity.

Methods: We sought to confirm whether there was an association between cross-sectional cognitive performance data from 81,337 participants who between January and December 2020 undertook a clinically validated web-optimized assessment as part of the Great British Intelligence Test, and questionnaire items capturing self-report of suspected and confirmed COVID-19 infection and respiratory symptoms.

Findings: People who had recovered from COVID-19, including those no longer reporting symptoms, exhibited significant cognitive deficits versus controls when controlling for age, gender, education level, income, racial-ethnic group, pre-existing medical disorders, tiredness, depression and anxiety. The deficits were of substantial effect size for people who had been hospitalised (N = 192), but also for non-hospitalised cases who had biological confirmation of COVID-19 infection (N = 326). Analysing markers of premorbid intelligence did not support these differences being present prior to infection. Finer grained analysis of performance across sub-tests supported the hypothesis that COVID-19 has a multi-domain impact on human cognition.

Interpretation: Interpretation. These results accord with reports of 'Long Covid' cognitive symptoms that persist into the early-chronic phase. They should act as a clarion call for further research with longitudinal and neuroimaging cohorts to plot recovery trajectories and identify the biological basis of cognitive deficits in SARS-COV-2 survivors.

Funding: Funding. AH is supported by the UK Dementia Research Institute Care Research and Technology Centre and Biomedical Research Centre at Imperial College London. WT is supported by the EPSRC Centre for Doctoral Training in Neurotechnology. SRC is funded by a Wellcome Trust Clinical Fellowship 110,049/Z/15/Z. JMB is supported by Medical Research Council (MR/N013700/1). MAM, SCRW and PJH are, in part, supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London.

Keywords: Attention; COVID-19; Cognition; Deficits; Long covid; Memory; Online assessment; Planning; Reasoning.

Conflict of interest statement

Dr. Hampshire reports grants from UK Dementia Research Institute, outside the submitted work and is Co-director and owner of H2CD Ltd, and owner and director of Future Cognition Ltd, which support online studies and develop custom cognitive assessment software respectively. Dr. Hellyer reports personal fees from H2CD Ltd, outside the submitted work. Dr. Chamberlain reports grants from Wellcome, personal fees from Elsevier, personal fees from Prometis (not current), outside the submitted work. Dr. Grant reports grants from Otsuka, grants from Biohaven, grants from Avanir, outside the submitted work. Dr. Patrick reports grants from H Lundbeck A/S, non-financial support from Astra Zeneca, non-financial support from Janssen, outside the submitted work. Dr. Mehta reports grants from H Lundbeck A/S, non-financial support from Astra Zeneca, non-financial support from Janssen, outside the submitted work. Dr. Williams has nothing to disclose. Dr. Mazibuko has nothing to disclose. Dr. Jolly has nothing to disclose. Mr. Trender has nothing to declare. Dr. Barnby has nothing to disclose.

© 2021 The Author(s).

Figures

Fig. 1

Cognitive tests included within the great British intelligence test. 1. Block rearrange, a test designed to measure spatial problem solving. 2. Tower of London, designed to test measures of spatial planning. 3. Digit span, a test designed to measure working memory. 4. Spatial span, a test designed to measure spatial short-term memory capacity. 5. Target detection, designed to measure spatial visual attention 6. 2D mental rotations, a test designed to measure the ability to spatially manipulate objects in mind. 7. Analogical reasoning, measuring semantic reasoning abilities. 8. Rare word definitions, assessing the ability of individuals to identify the correct definitions of words. 9. Face emotional discrimination, designed to measure an individual's ability to identify and discern between emotions.

Fig. 2

. Cognitive deficits in people with suspected and confirmed COVID-19 illness. A | People who reported having recovered from COVID-19 performed worse in terms of global score. The scale of this deficit increased with the level of treatment received for respiratory difficulty. B | In individuals who did not receive medical assistance, the scale of this deficit was greater in biologically confirmed cases versus suspected cases of COVID-19. Error bars report the standard error.