Changes in memory and cognition during the SARS-CoV-2 human challenge study, 2024, Trender et al.

Changes in memory and cognition during the SARS-CoV-2 human challenge study
William Trender; Peter J. Hellyer; Ben Killingley; Mariya Kalinova; Alex J. Mann; Andrew P. Catchpole; David Menon; Edward Needham; Ryan Thwaites; Christopher Chiu; Gregory Scott; Adam Hampshire

BACKGROUND
Patient-reported outcomes and cross-sectional evidence show an association between COVID-19 and persistent cognitive problems. The causal basis, longevity and domain specificity of this association is unclear due to population variability in baseline cognitive abilities, vulnerabilities, virus variants, vaccination status and treatment.

METHODS
Thirty-four young, healthy, seronegative volunteers were inoculated with Wildtype SARS-CoV-2 under prospectively controlled conditions. Volunteers completed daily physiological measurements and computerised cognitive tasks during quarantine and follow-up at 30, 90, 180, 270, and 360 days. Linear modelling examined differences between ‘infected' and ‘inoculated but uninfected' individuals. The main cognitive endpoint was the baseline corrected global cognitive composite score across the battery of tasks administered to the volunteers. Exploratory cognitive endpoints included baseline corrected scores from individual tasks. The study was registered on ClinicalTrials.gov with the identifier NCT04865237 and took place between March 2021 and July 2022.

FINDINGS
Eighteen volunteers developed infection by qPCR criteria of sustained viral load, one without symptoms and the remainder with mild illness. Infected volunteers showed statistically lower baseline-corrected global composite cognitive scores than uninfected volunteers, both acutely and during follow up (mean difference over all time points = −0.8631, 95% CI = −1.3613, −0.3766) with significant main effect of group in repeated measures ANOVA (F (1,34) = 7.58, p = 0.009). Sensitivity analysis replicated this cross-group difference after controlling for community upper respiratory tract infection, task-learning, remdesivir treatment, baseline reference and model structure. Memory and executive function tasks showed the largest between-group differences. No volunteers reported persistent subjective cognitive symptoms.

INTERPRETATION
These results support larger cross sectional findings indicating that mild Wildtype SARS-CoV-2 infection can be followed by small changes in cognition and memory that persist for at least a year. The mechanistic basis and clinical implications of these small changes remain unclear.

FUNDING
This study was funded through the UK Vaccine Taskforce of the Department for Business, Energy and Industrial Strategy (BEIS) of Her Majesty's Government. WT was funded by the EPSRC through the CDT for Neurotechnology Imperial College London.


Link | PDF (Lancet: eClinicalMedicine) [Open Access]

 

In case anyone was in doubt whether memory and cognition have been widely affected across the entire population.

 

Holy cow, I didn't know this was a thing.

 

See thread https://www.s4me.info/threads/recru...lenge-study-covhic002-imperial-college.32184/
and Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge in young adults (2022, Nature Medicine)

 

Without having time to look at anything closer these results would appear to be very significant.

There's the caviat that this study was conducted with the wildtype strain, their follow-up study with the Delta-strain should yield more clues. However the results would still remain significant for anyone infected with the wildtype strain, i.e. millions of people. Secondly it is extremely doubtful whether these individuals were truely uninfected until inoculation, with the study running in March 2021. Thirdly it remains questionable whether the both groups remained without additional infection for a full year. I can only see those things making the results even stronger (for example community re-infection rates would have been stronger in the uninfected control group). Is there anything that could weaken the results, are there methodological flaws? One thing one might need is to have a control group infected with a different virus.

Looking at the recruitment page for the Delta strain I wonder if there is an ethics conflict here. They recruited for that study without mentioning these effects, which they long since had discovered. On the other hand people are anways getting infected.... It seems rather bad practice to me, to only publish these results now, given that they published their study titled "Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge in young adults" 2.5. years ago. The long-term follow-up and analysis will have taken it's time, but the short-term results would have been known for several years by now.

 

Ironically, if they had the whole thing could have been dismissed as nocebo and thus ignored. Which I'm sure some people will do anyway, with the absence of subjective awareness. Doesn't matter that it means the opposite, in psychosomaticland, everything is backward and you're always right until someone convincingly proves you wrong.

 

https://twitter.com/user/status/1838439864406094229


Mike Hoerger, PhD MSCR MBA:

"As an expert in psychological assessment who has testified in court on cognitive assessments I've conducted, people should interpret carefully the new eClinicalMedicine paper on Covid-related cognitive changes."

---

"The study did not use one of the well-established, normed, broadband tests of cognition. Instead, it used a novel app-based hodgepodge of tests with little empirical history.

People should be very cautious in interpreting results. There is no vast literature on the tests.

Many seem to frame the finding as a general decline in cognitive skills, or even as an "IQ loss" of 5 or more points.

This is wrong on many levels.

If you look at their hodgepodge of relatively unvalidated tests, you see really only one test stands out.

It's something called, "Object Memory -- Immediate." Again, this is not a test anyone would use in a clinical or forensic setting. I had to look it up."



---

"It's a short-term memory test of how well one can remember an object AND how it was oriented. This is an atypically specialized test to include in a general cognitive battery.

We see from another figure that the main change was not in recognizing the correct image, but in remembering the orientation.

E.g., Covid didn't impede recognizing the cherry, but did throw off recognizing whether it was the one with leaves on the left side or right.

So, it seems Covid impairs the specialized skill of "spatial encoding" or putting an orientation into memory."

---

"So, let's assume Covid causes a huge decline in spatial encoding (putting directional orientation into short-term memory), what are the implications?

This could be one of the factors underlying increases in accidents, especially car accidents.
-Remembering someone's blinker as left instead of right and crashing into them
-Turning left instead of right
-Remembering directions wrong, and changing course last minute.
etc.

Occupations like air traffic control would seem particularly problematic.

But there are other areas.

Examples:
-Language learning (b vs d)
-Arithmetic/accounting/finance (+ vs x, 6 vs 9)
-Operating novel/complex equipment & machines
-Using a kitchen stove

See, the issue is not general cognitive decline (at least in this study), but disruption to a highly specialized skill vastly important for very particular tasks.

That's an important distinction.

This suggests the need for more research on spatial encoding and other plausible processes (attention, processing speed, spatial skills) & neuroimaging focused on what's happening in areas like DG-mediated mossy fibers in the CA3 region of the hippocampus.

Take-home points:
-Declines in spatial encoding, not general cognition
-Be careful to avoid claims about "IQ"
-Need more research to rule out more general cognitive processes
-Need neuroimaging studies"

More tweets in full thread.

 

It appears they used a battery of tests (11 tests in total) to assess cognitive performance via the online platform cognitron developed by Adam Hampshire. This is the same platform used in Post-hospitalisation COVID-19 cognitive deficits at one year are global and associated with elevated brain injury markers and grey matter volume reduction and Cognition and Memory after Covid-19 in a Large Community Sample (where a lot of the same tests were also used) where I seemingly wrote the following comment which I had long since forgotten about