The Molecular Basis of Long Covid Brain Fog | Hacker News Reader

The Molecular Basis of Long Covid Brain Fog

yokohama-cu.ac.jp

133 pointsonnnon48 comments

The headline overstates the findings. The researchers aren't saying that this is the underlying basis of COVID brain fog. They hypothesized that AMPA receptors might be involved. They compared Long COVID patients to controls and found a difference.

This doesn't mean that AMPA receptors are the root cause of post-COVD brain fog, nor does it necessarily mean that drugs modulating AMPA receptors could reverse it. It only shows that this is one of the changes observed in patients reporting post-COVID brain fog. It could be a side effect of some other change or it could be part of a long cascade of changes.

It also needs to be replicated further. I've read at least at dozen headlines claiming to have found the underlying cause of COVID brain fog in the past year and all of them pointed to different biomarkers.

Consider this another piece of the puzzle, not a discovery of the underlying mechanism.

Thanks. I love this comments that spare time for everybody else. But honestly, anything biology/medicine related, you KNOW the title is exaggerated, right out of the bat

It'd be nice to find out if there's any overlap with the "brain fog" from fibromyalgia. My college years would have been far less torturous if I could have lived without that, even if I still had to deal with the pain.

There's an assumption going around that idiopathic-ish conditions like fibromyalgia may be caused (or a subset of those with that diagnosis) by long-tail after effects of various infections, COVID-19 being one of many.

It sounds like you’re reading too much into it.

It doesn’t say root cause, or drug target. It doesn’t say reverse or cure. It quite specifically doesn’t say “the basis”. The word basis doesn’t have to refer to one root cause. It could be something foundational, but there can be many elements of a foundation. It certainly isn’t the entire structure.

I’d argue it’s quite tame as academic press releases go.

> It quite specifically doesn’t say “the basis”

The headline quite specifically does say: "Uncovering the Molecular Basis of Long COVID Brain Fog"

The article also implies that AMPA drugs could address COVID brain fog:

> For example, drugs that suppress AMPAR activity could be a viable approach to mitigate brain fog.

This was one of the points I was trying to counter.

It also claims to have "resolved key uncertainties":

> In summary, the team’s findings resolve key uncertainties about the biological basis of Long COVID brain fog

Which is obviously not true. This is only one biomarker, not the resolution to a key uncertainty.

I disagree that I'm reading too much into it. These are direct quotes from the article I was responding to.

It does not say “the basis.” It is concerning you don’t understand the discrepancy there.

You are welcome to your opinion about what is key, but reading comprehension does not seem to be your strong suit.

> "Uncovering the Molecular Basis [...]"

> "the [...] Basis"

The adjective molecular doesn't narrow "the basis" down much, for a condition which could safely be assumed to be molecular.

Sounds like the authors ought to have titled it: "Uncovering a Molecular correlation to Long COVID Brain Fog"

Which can still be extremely useful, for targeting further investigation.

To be fair, the real authors of the paper had a much more accurate title: "Systemic increase of AMPA receptors associated with cognitive impairment of Long COVID"

It's the university PR team that exaggerated, as usual.

https://phdcomics.com/comics/archive.php?comicid=1174

>The headline overstates the finding.

On a long covid news article? What are the chances!

It does imply AMPA antagonists or NAMs might be of interest to people with this problem, though. I wonder if high-dose L-theanine might be of interest; most of the -ampanel family antagonists are liable to abuse and a little sketchy regarding side effects and *NQX family aren't usable outside lab settings, so limited other options. Memantine might help but itself has anecdotal reports of inducing brain fog.

I'd also remark that their methodology has issues; we do not have a clear etiology or diagnostic criteria for "long covid" and its presentation. Participants had previously been infected (this is essentially everyone) and reported subjective "brain fog" type symptoms which is a terrible way to attempt to isolate anything about this "long covid". It's possible this is just a generalized syndrome that results from behavioral or lifestyle factors. I.e. we have no way to know what is "long covid" versus other things, no way to reliably trust patient history, and no way to know we are seeing that particular type of "brain fog".

> It does imply AMPA antagonists or NAMs might be of interest to people with this problem, though

It does not necessarily.

For example, if the increased AMPA density is a counter-regulatory response to reduced baseline AMPA activation, further antagonizing the receptor system would worsen rather than improve the situation.

Possible, which is why I said "might be" and brought up that memantine seems to contribute positively to brain fog.

The biggest impact I've made on my brain fog (post COVID) is using nicotine. Even 2mg a day makes a big difference for me.

What do you do for managing dependency / tolerance?

Sometimes I take the weekends off. Also I get irritable if I don't get enough sleep AND not enough nicotine. It's a trade-off.

As for tolerance, I haven't noticed the brain fog come back since I started, and I've been on this for 6 or 8 months so far.

Go in cycles. Ween dose down to zero for 1-N weeks then restart.

up the mg until im like a roided out monster

Every person has their own body. For me:

I've never smoked cigarettes, but decided to try Nicorette gum as an alternative to a second cup of coffee (if I drink after 12:00, I wont go to sleep on time).

I've been using it for 8+ years now and have found a sustainable dosage that doesn't give me withdrawal/depenency. I've never had an issue with tolerance.

I buy a big box of 4mg gum and go through around half to one piece a day. I discovered consuming 2+ pieces (+8mg) led to withdrawal symptoms (empathetic lightbulb moment for me for smokers who want to quit!)

Regarding dependency, I don't take any when Im traveling/on vacation, and have never felt the need to use it then.

Any desire comes from wanting to continue the alertness once the caffeine starts to wear off.

> Regarding dependency, I don't take any when Im traveling/on vacation, and have never felt the need to use it then.

> Any desire comes from wanting to continue the alertness once the caffeine starts to wear off.

Anecdotally, this sounds a lot like two of my friends (married couple) who used similar amounts of nicotine gum years ago.

For years they said the same thing: That they didn't go into withdrawals on vacation and that they weren't addicted to the gum, they just wanted to feel awake.

Their experience changed when they decided to quit for a while. As they discovered, actually quitting for an extended period of time was a lot harder than they thought it would be.

They were very much in the "I can quit whenever I want" mindset because they could skip it on vacations, but as they discovered their cravings were intense when they tried to go without the gum during their normal weekly routine.

They finally tapered down with the lower doses and splitting gum over a long period of time.

This does not surprise me, it does have many neuroprotective benefits after all.

I vape like a fiend and I'm probably never going to stop

Interesting! I feel I’ve been kinda foggy in my head since I quit smoking a year or two before covid and it then got worse with the pandemic. And I’ve felt there’s been more effect from a night out with party smoking than just seeing an old friend. Might need to try my own home grown snuff when it’s done and not just give it away.

Well aged leaf smells amazing. I've often thought about getting into pipe smoking, but my guess is its like coffee, it smells better than it tastes.

If it's like coffee, you don't necessarily like it at first.

I don't smoke cigarettes or pipes, but at least with cigars, it's very easy to get into. You're tasting the smoke in this case, not inhaling it. You'll still get something of a buzz, since there are looooots of entry points into the bloodstream in the mouth, but even for someone like me who's a gigantic baby when it comes to inhaling smoke, it's easy-breezy to enjoy a cigar.

If you like smoked food, you'll love the taste of smoking. Though, I highly recommend limiting it to serious celebrations, for obvious reasons. I generally only have them at weddings.

My meditation teacher says what works for him is cannabis.

Last year there was a lot of discussion about mitochondrial changes, especially epigenetics and respiration.

https://pmc.ncbi.nlm.nih.gov/articles/PMC11336094/

I would be curious if these markers could result from the same problems, or might indicate a complete separate root cause.

In the unknown chemical factory of the brain it is very difficult to dealinate the begin and consequent steps of all degenerative diseases: Alzheimer's - Parkinson's, chronic fatigue syndrome - post-Covid, schizophrenia- autism etc. At most it is possible to discover an intermediate step.

From the paper's abstract: "A partial least squares model trained on the index of AMPAR density data demonstrated high diagnostic accuracy, achieving 100% sensitivity and 91.2% specificity." That seems to mean there's a diagnostic test now.

There's been more than one way to reliably differentiate CFS patients from controls announced this year. However, there's no clinical diagnostic yet.

There's so much we don't know about this yet. It's great to see new knowledge being generated! I had Covid last February (vaccinated and boosted, thankfully). It was a mild course, but I wound up sensitized to caffeine for three to four months after.

I normally drink 100-150mg/day, but I had to cut that back to 50-60mg and only in the morning. It seems to have passed, so I'm back on my drip.

I had the same thing with my caffeine sensitivity, but my nicotine sensitivity hasn’t gone back and it’s been over a year. I used nicotine lozenges daily for years but even after 12 months post-covid my body does not tolerate them.

Mine has never recovered. I have to drink decaf now! I feel a small amount of relief that I'm not alone.

Slow Bloom's Decaf is the best I've tried, and I really like like Savorista's Swiss Water Ethiopian too. Both can yield a passable pourover.

You can also find some good decaf black tea. Jones Coffee Roasters in Pasadena stocks some, and I'll see it online occasionally.

thanks, I appreciate the recommendations!

Related - I've been very impressed with Perc Coffee's instant decaf. Of course you can tell it is instant but it's not unpleasant at all.

Thank you for sharing. I have the same thing and it is from my first bout with Covid in 2021. I have now had Covid 4 times and the caffeine sensitivity remains along with PVCs and chest pain. Brain fog has been almost debilitating and overall the impact on my career performance is noticeable.

Have you been getting the annual booster? There is no agenda or gotcha coming, I am genuinely just curious.

Take it how you will but I had brain fog and greatly diminished sense of smell for like 4 years and then for unrelated reasons decided to try some methylene blue as a supplement, started with a minuscule dose and within a week my sense of smell was fully restored and the brain fog was reduced to “normal levels”.

If we assume the hypothesis that long covid is caused by mitochondrial dysfunction, then there are plausible mechanisms by which MB could improve mitochondrial function (though a week sounds really fast?) Glad you're feeling better!

Very cool. Surprising that having more AMPA receptors would lead to decreased cognition, as learning & memory is hypothesized to particularly involve processes that increase the number of in-position AMPA receptors.

> Surprising that having more AMPA receptors would lead to decreased cognition

The study only looked at one marker. It doesn't confirm that increased AMPA receptor density is the cause of decreased cognition. It only suggests that decreased cognition is correlated with increased AMPA receptor density.

There are many processes in the body where reduced activation of a receptor system results in an increased number of those receptors. So don't conclude that this is the reason why patients have brain fog. I would guess it's just more of a symptom than a cause until there's more research

Maybe it's an attempt by the body to compensate?

Just a shot in the dark here, I'm just some guy on the internet, not a microbiologist or doctor.

In biology, cause and effect do not work the way they work in other fields. Effect is highly context-specific and things often work in the opposite direction than you might assume.

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