Summary: A new study finds a relationship between declines in cognitive performance and attention, and the severity of respiratory symptoms COVID-19 patients experienced. Those with more server COVID symptoms fared worse on cognitive tests, specifically associated with reasoning and problem-solving.
Source: King’s College London
The research found that those with more severe COVID-19 symptoms scored lower on an online series of tests, with performance on reasoning and problem-solving tasks being most affected.
Further analysis of the data indicated that those who received mechanical ventilation to help them breathe whilst in hospital had the greatest impairment on cognitive tasks.
Published in the journal EClinicalMedicine, the research was a collaboration between King’s College London, Imperial College London and Cambridge University. It was part-funded by the UK Dementia Research Institute Care Research & Technology Centre and the National Institute of Health Research (NIHR) Maudsley Biomedical Research Centre.
Online cognition tests
A series of online tests, developed by first author on the study and Reader in Restorative Neuroscience at Imperial College London Dr Adam Hampshire had been opened up to the general public just before the pandemic for the BBC2 Horizon’s Great British Intelligence test.
In early 2020 the study team extended the questionnaires to gather information on SARS-CoV-2 infection, the symptoms experienced and the need for hospitalisation.
Out of the 81,337 who provided complete data, 12,689 people suspected they had COVID-19. Participants reported a range of severity of illness, with many experiencing respiratory symptoms whilst still being able to stay at home (3,559 participants).
Nearly 200 were hospitalised (192 participants) and about a quarter of these (44 participants) required mechanical ventilation.
The time since illness onset was around 1-6 months, meaning the study could not draw any definitive conclusions about whether these effects on cognition were long-lasting.
Thinking problems and respiratory symptoms
The study found a relationship between deficits in overall cognitive performance and the severity of respiratory symptoms experienced.
The research also found that not all areas of thinking ability correlated in the same way with COVID-19 illness and that some abilities were spared, which included emotional discrimination (recognition of faces that were expressing the same emotion) and working memory (remembering where a sequence of squares appears on the screen).
In comparison ‘executive’ tasks that required skills in reasoning (e.g. Deciding if relationships between words were similar) and problem solving (working out how many moves it would take to go from one arrangement to another) seemed to show the greatest deficit.
To understand the size of the deficits the authors compared the pattern of scores on the tests to cognitive changes that occur for other reasons. The effects in those hospitalised with mechanical ventilation were similar to the average cognitive decline seen over a period of ten years of aging and equivalent to a seven-point difference in IQ.
Ruling out other explanations
The researchers carried out a series of checks to ensure these cognitive deficits were associated with COVID-19 and not explicable by other variables. These included separating out those who had a confirmed positive test for SARS-CoV-2 and demonstrating that the cognitive deficits were indeed greater in those with positive tests.
Further checks suggested the results were not due to a minority with pre-existing conditions or on-going symptoms of COVID-19. Analysis also indicated that it was unlikely that the results could be explained by the fact that those who contracted more severe COVID-19 disease were less cognitively able before they were ill.
Dr Adam Hampshire, first author of the study, said: “Our study adds to an increasing body of research that is looking at different aspects of how COVID-19 might be impacting the brain and brain function. This research is all converging to indicate that there are some important effects of COVID-19 on the brain that need further investigation.
“Going forward it would be valuable to bring together brain imaging and cognitive tests with other information on mental health and everyday function, ideally in studies that track peoples’ trajectories for months or even years. To really know what the long-term effects are for people will require people to be followed up over time.”
New studies, such as COVID-19 Clinical Neuroscience Study (COVID-CNS), led by King’s College London and University of Liverpool, and the REACT Long COVID study, led by Imperial College London, are now applying these cognitive tools to study the long-term impacts of COVID-19.
“A critical question remains as to why some cognitive functions are more affected than others,” said Mitul Mehta, Professor of Neuroimaging from King’s College London and senior author on the study.
“It is already known that hypoxia and mechanical ventilation are associated with cognitive deficits similar to those observed in this study, and there is now evidence of neurological complications in some patients, as well as psychiatric consequences.
“As we are coming through the third wave of the pandemic, there are more available options that can reduce the severity of COVID-19 such as vaccination and effective treatments whilst in hospital.
“The findings from this study suggest that by reducing the severity of illness through these different approaches we may also be able to reduce the severity of cognitive difficulties people may experience.”
Cognitive deficits in people who have recovered from COVID-19
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.
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.
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. 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. 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