Multivariate profile and acute-phase correlates of cognitive deficits in a COVID-19 hospitalised cohort

Abstract

Background: Preliminary evidence has highlighted a possible association between severe COVID-19 and persistent cognitive deficits. Further research is required to confirm this association, determine whether cognitive deficits relate to clinical features from the acute phase or to mental health status at the point of assessment, and quantify rate of recovery.

Methods: 46 individuals who received critical care for COVID-19 at Addenbrooke's hospital between 10th March 2020 and 31st July 2020 (16 mechanically ventilated) underwent detailed computerised cognitive assessment alongside scales measuring anxiety, depression and post-traumatic stress disorder under supervised conditions at a mean follow up of 6.0 (± 2.1) months following acute illness. Patient and matched control (N = 460) performances were transformed into standard deviation from expected scores, accounting for age and demographic factors using N = 66,008 normative datasets. Global accuracy and response time composites were calculated (G_SScore & G_RT). Linear modelling predicted composite score deficits from acute severity, mental-health status at assessment, and time from hospital admission. The pattern of deficits across tasks was qualitatively compared with normal age-related decline, and early-stage dementia.

Findings: COVID-19 survivors were less accurate (G_SScore=-0.53SDs) and slower (G_RT=+0.89SDs) in their responses than expected compared to their matched controls. Acute illness, but not chronic mental health, significantly predicted cognitive deviation from expected scores (G_SScore (p=​​0.0037) and G_RT (p = 0.0366)). The most prominent task associations with COVID-19 were for higher cognition and processing speed, which was qualitatively distinct from the profiles of normal ageing and dementia and similar in magnitude to the effects of ageing between 50 and 70 years of age. A trend towards reduced deficits with time from illness (r∼=0.15) did not reach statistical significance.

Interpretation: Cognitive deficits after severe COVID-19 relate most strongly to acute illness severity, persist long into the chronic phase, and recover slowly if at all, with a characteristic profile highlighting higher cognitive functions and processing speed.

Funding: This work was funded by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC), NIHR Cambridge Clinical Research Facility (BRC-1215-20014), the Addenbrooke's Charities Trust and NIHR COVID-19 BioResource RG9402. AH is funded by the UK Dementia Research Institute Care Research and Technology Centre and Imperial College London Biomedical Research Centre. ETB and DKM are supported by NIHR Senior Investigator awards. JBR is supported by the Wellcome Trust (220258) and Medical Research Council (SUAG/051 G101400). VFJN is funded by an Academy of Medical Sciences/ The Health Foundation Clinician Scientist Fellowship. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.

Keywords: Attention; COVID-19; Cognition; Cognitive assessment; Memory; Planning; Reasoning.

Figure 1

Analysis of composite deviation from expected cognitive performance scores A. Analysis of DfE composite scores showed that COVID-19 survivors were on average less accurate and slower to respond than expected given their age and demographic profiles. Scale is standard deviation units relative to the control population. B. Left. Clinical features from the acute phase, age, sex and mental health and time from illness at the point of assessment showed strong correlations with a clear natural clustering of acute clinical severity vs mental health scores at the time of cognitive assessment. Colour represents bivariate correlation strength where yellow = 1 and dark blue = -1. Right. Principal Component Analysis identified three components with eigenvalues greater than 1. Centre. After varimax rotation one general component included heavy loadings from acute illness severity, a second component more heavily loaded towards respiratory support features and a third component included high loadings from depression, anxiety and PTSD questionnaires. C. Acute clinical severity (component 1) showed statistically significant correlations with DfE composite scores that were of medium effect size. (X axis is clinical component score. Y axis is DfE score in SD units relative to the control population).

Figure 2

Multivariate profile of cognitive deficits after severe COVID-19 and relationship to age and dementia Upper. Patients showed a consistent pattern of cognitive underperformance in terms of reduced accuracy and slowed processing time that varied in magnitude across tasks. * p < 0.05, **p < 0.01, ***p < 0.001 one tailed FWE corrected for 18 multiple comparisons. Executive tasks tapping higher cognitive functions showed particularly strong associations, which was qualitatively different to the association with age-related decline or dementia. Y axis scale in standard deviation units relative to controls. Lower. The scale of DfE score for severe COVID-19 survivors was similar in scale to normal age-related decline in cognition between individuals in their seventies when compared to individuals in their fifties (but less than age related decline in cognition between 20 and 70 years of age), and less than cognitive problems in people with dementia 3 years post diagnosis. However, the pattern of deficits across cognitive domains was quite distinct to either of these comparisons. NB dementia patients had not undertaken Spatial Planning or 3D Perspective Rotation. Y axis scale is standard deviation units relative to controls.