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Review 1: "Cognitive deficits in people who have recovered from COVID-19 relative to controls: An N=84,285 online study"

Reviewers: Lisbeth Evered (Weill Cornell Medicine) | 📒📒📒 ◻️◻️

Published onMay 04, 2022
Review 1: "Cognitive deficits in people who have recovered from COVID-19 relative to controls: An N=84,285 online study"
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key-enterThis Pub is a Review of
Cognitive deficits in people who have recovered from COVID-19 relative to controls: An N=84,285 online study
Description

AbstractCase studies have revealed neurological problems in severely affected COVID-19 patients. However, there is little information regarding the nature and broader prevalence of cognitive problems post-infection or across the full spread of severity. We analysed cognitive test data from 84,285 Great British Intelligence Test participants who completed a questionnaire regarding suspected and biologically confirmed COVID-19 infection. People who had recovered, including those no longer reporting symptoms, exhibited significant cognitive deficits when controlling for age, gender, education level, income, racial-ethnic group and pre-existing medical disorders. They were of substantial effect size for people who had been hospitalised, but also for mild but biologically confirmed cases who reported no breathing difficulty. Finer grained analyses of performance support the hypothesis that COVID-19 has a multi-system impact on human cognition.Significance statementThere is evidence that COVID-19 may cause long term health changes past acute symptoms, termed ‘long COVID’. Our analyses of detailed cognitive assessment and questionnaire data from tens thousands of datasets, collected in collaboration with BBC2 Horizon, align with the view that there are chronic cognitive consequences of having COVID-19. Individuals who recovered from suspected or confirmed COVID-19 perform worse on cognitive tests in multiple domains than would be expected given their detailed age and demographic profiles. This deficit scales with symptom severity and is evident amongst those without hospital treatment. These results should act as a clarion call for more detailed research investigating the basis of cognitive deficits in people who have survived SARS-COV-2 infection.

RR:C19 Evidence Scale rating by reviewer:

  • Potentially informative. The main claims made are not strongly justified by the methods and data, but may yield some insight. The results and conclusions of the study may resemble those from the hypothetical ideal study, but there is substantial room for doubt. Decision-makers should consider this evidence only with a thorough understanding of its weaknesses, alongside other evidence and theory. Decision-makers should not consider this actionable, unless the weaknesses are clearly understood and there is other theory and evidence to further support it.

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Review:

This is an important area for investigation as it becomes increasingly apparent many COVID-19 survivors have long-term symptoms affecting their recovery and quality of life. There are obvious limitations with linking cognitive impairment to an event when no baseline cognition assessment is available. The authors have attempted to adjust for this by comparing COVID-19 patients to controls which is a sensible study design given the available data. There are a number of details missing that I think are required to accurately interpret the results. First, there is no information provided regarding the temporal relationship between the COVID-19 diagnosis and the assessments (what was the average (SD) time between COVID-19 diagnosis and assessment?). This is important if it is highly variable. Second, although the overarching sample size is large, the numbers in some of the analyses are quite small and I am concerned there is insufficient power to be undertaking adjusted multivariable analyses. Third, why were individuals without a positive test (suspected COVID-19) included? This may have introduced some bias – did you conduct a sensitivity analysis with suspected COVID-19 in versus out? Lastly, I am particularly concerned about exponential p-values and how robust the reported outcomes are. The authors have included a diverse population which is to be commended and improves the generalisability of the results. The positive ‘dose – response’ observed between severity of cognitive symptoms and severity of cognitive impairment provides important information for future studies. I believe this work is potentially informative and should guide further longitudinal studies. The main claims made are not strongly justified by the methods and data, but may yield some insight. Whilst this does not provide an actionable solution, it confirms there are long-term cognitive consequences in COVID-19 survivors which require further investigation to determine magnitude and potential intervention strategies.

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