Cognitive deficits in people who have recovered from COVID-19, 2021, Hampshire et al

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.

Open access, https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00324-2/fulltext

 

https://twitter.com/user/status/1418696473177362432

 

The cross-sectional nature of the study precludes from inferring causality between symptomatic Covid infection and cognitive impairments, but this study is an excellent application of large-scale, publicly promoted, collaborative citizen science (BBC Horizon's Great British Intelligence Test).

My wish is that a large-scale prospective study on the risk of developing ME/CFS after infectious illness(es) would include similar cognitive testing at baseline (enrollment into the study), then at 6 months, 1 and 2 years post-infection, to provide strong evidence of a causal link between infectious triggers and cognitive impairments in patients meeting ME/CFS diagnosis criteria.

In fact, the cohort of people who have already taken the Great British Intelligence Test can be harnessed for this purpose. Given that they have baseline data, it suffices that those who did not develop symptomatic Covid (i.e. non-diseased controls in this study) but who do develop another symptomatic infection be identified through electronic medical records, then be asked to complete another round of the test. This would only require a negative Covid test and, arguably, a positive test for the infection.

There are some important caveats.

First, the Great British Intelligence Test may not have been designed to assess changes in cognitive abilities over time. In this case, it would not be a suitable test despite the presence of baseline data.

Second, testing for other infections than Covid (e.g. flu or glandular fever) is virtually always restricted to severe forms -- i.e. hospitalized patients --. On the other hand, identification of diseased participants via electronic medical records precludes solely self-reporting an infectious illness, as it implies clinical confirmation by a medical doctor. This may be considered reliable enough of a proof of infection.

Third, the infection would have to occur at most a few years after baseline data collection, as cognitive abilities decline with ageing, and no other event that would have significantly impacted cognitive performance must have occurred in between.

Fourth, accessing the electronic medical records of all persons who have taken Great British Intelligence Test may not be feasible, or the researchers may not be given the permission to do so. If they were limited to the records of a few NHS trusts, they could limit their search to the largest one and possibly a few more. This would introduce sampling bias, although it could be assessed given that in-depth personal information is available for all participants.

Fifth, and perhaps most importantly, selecting patients who have received a diagnosis of ME/CFS requires that the diagnosis be made in the first place, which can be problematic, excludes patients who have developed cognitive impairments but not ME/CFS, and thus narrows the cohort when it could potentially be much larger.

If the idea is brought forward to the authors of the study, they may show interest in pursuing work on other infections. Without necessary looking at ME/CFS, I believe the data would be interesting and possibly far-reaching.

 

I have a wish that there was a more nuanced understanding of the various types of cognitive functioning in order to better understand which parts are likely most affected.

 

Wouldn't scoring on the test be affected by physical symptoms (concentrating less because you feel lousy) and changes in activities during the day (being less active due to feeling lousy) and changes in lifestyle (vegging out in front of TV rather than reading, crafting, etc)?

 

I skimmed this a bit yesterday and one interesting thing is that the test actually appears to be relevant, puzzles requiring reasoning and short-term memory. Unlike the usual "well, they can identify the giraffe on the dementia test therefore there's nothing wrong with them".

I hope it gets developed more. There's still a huge misunderstanding of what cognitive functions are degraded and this is a problem that can only be identified with the right test. Which is always the case but we are in the exemption land of being troll-faced with "all tests are normal" as if this is somehow our fault that people didn't do their job. Basically the equivalent of "it works on my development machine" in software, not a serious excuse.

But there's timing also, and being able to compare back. When I first got seriously ill I basically lost the ability to read for weeks, it was so difficult to make sense of anything or even remembering the start of the sentence by the time I got to the end. Eventually it improved but still far lower than my normal language abilities, which in exchange for being terrible at maths are pretty good. It also degraded again with time, as my health declined further. Tests that work to a standardized norm will never pick up such things because of the wide range of skills within any population.