[gibba999]

The million dollar questions include:

- Long COVID post-vaccine. >10% of people have brain damage visible on MRIs, including mild cases.

- Future mutations. People have been overly optimistic for 15 months now, and believed bad things couldn't happen. They do. There's no reason to believe Delta or Gamma are the end, or anywhere close.

[inter_netuser]

brain damage after vaccine, or "mild" disease in vaccinated people?

can you point to that MRI imaging? curious to see.

[gibba999]

This is the major one:

https://www.medrxiv.org/content/10.1101/2021.06.11.21258690v...

This one scared me since it was a large, relatively unbiased sample, with before-and-after imaging. It also showed brain damage even in mild cases of COVID19 in >10% of cases.

There are a lot of supporting smaller-scale studies too, replicating the same general result. E.g.

https://www.khou.com/article/news/health/coronavirus/covid-1... https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066611/

If you Google, you'll find dozens of other small-scale studies.

[timr]

> This one scared me since it was a large, relatively unbiased sample, with before-and-after imaging. It also showed brain damage even in mild cases of COVID19 in >10% of cases.

It shows no such thing. It's an analysis of MRIs where the authors infer loss of gray matter in specific regions of the brain. This is in no way "brain damage", and representing it this way is leaping to wild conclusions.

Lest you not believe me, here is a randomized controlled trial, showing that "excessive online video gaming" reduces orbitofrontal gray matter:

https://pubmed.ncbi.nlm.nih.gov/29057579/

(...so your Mom was right: gaming is turning your brain to mush!)

Here is a review that shows that similar losses in gray matter are associated with anxiety and sleep loss (two problems that I'm sure didn't affect anyone in 2020):

https://pubmed.ncbi.nlm.nih.gov/29244642/

Similarly: "Profound and reproducible patterns of reduced regional gray matter characterize major depressive disorder"

https://pubmed.ncbi.nlm.nih.gov/31341158/

Just for fun: here's a paper that shows that "tooth loss was a causal factor for volume reduction in brain areas related to memory, learning and cognition"

https://pubmed.ncbi.nlm.nih.gov/29475808/

(bonus points: can you spot the missing correlate?)

The fact is, you can find research literature associating "loss of gray matter" with pretty much anything. And if a reliable trend does exist across this literature, it seems to be that gray matter changes are often seen in...wait for it: depressed people and the aged.

But I'm sure that Covid has done nothing to depress people or affect the aged, so we can probably safely ignore that little detail.

[gibba999]

I think a lot of this comes down to replication, effect size, and sample size.

Yes, there are studies which show virtually everything, but in this case, we have:

- >10% of mild cases reporting long COVID brain fog (without MRIs)

- Visible correlations on MRIs with large n (cited study)

- Lots of small-scale studies / looking at specific cases

- Some understanding of a relevant mechanism-of-action (see: olfactory loss)

Together, that's about as strong evidence as you'd expect after 15 months. We have effect, we have correlation, we have case studies, and we understand why it's plausible.

The big question is whether it strikes vaccinated mild / asymptomatic cases. We don't know. There are a lot of cases like this.

[timr]

> >10% of mild cases reporting long COVID brain fog (without MRIs)

"Brain fog" is not a diagnosis. It has no definition. It has no test. Literally anyone could say they have it, and not be wrong.

It also overlaps substantially with "fatigue"...which we all know comes along with a lot of other common issues. Such as depression.

> Visible correlations on MRIs with large n (cited study)

The size of n doesn't matter if the thing you're reporting is not a meaningful metric. Here, we have a paper that has gone on a fishing expedition for a quasi-subjective metric with unknown levels of noise, which is widely "shown" to be associated with many common and uncommon issues across the research literature.

This is a low-quality data set. But yes, it is a larger low-quality data set.

> Lots of small-scale studies / looking at specific cases

Collections of anecdotes are not data.

> Some understanding of a relevant mechanism-of-action (see: olfactory loss)

...for a single symptom (loss of smell). But no, we don't know why that happens, and to the extent we do, the current best hypothesis has nothing to do with neurons, but rather, the scaffolding around those neurons.

> Together, that's about as strong evidence as you'd expect after 15 months.

Nonsense. We've been debating this "long covid" for more than a year now. There are apparently many sufferers. We could have easily conducted randomized, longitudinal, controlled trials. We have not.

The total evidence for "long covid" continues to be anecdotes and self-reported "symptoms", of indeterminate duration, amongst populations that are mostly self-selected for having "long covid". I believe that we'll eventually find out that some of these things are real, but right now, this is just hysteria.

[gibba999]

My hypothesis is that COVID leads to a Gaussian distribution in reduction in general neurological function, and that we will see a bell curve distribution reduction in e.g. general IQ.

Can you please propose a "randomized, longitudinal, controlled trials" one might conduct to figure that out?

Preferably, one which would pass an IRB review. We can't randomly infect 10,000 ethnic minorities with COVID19 anymore, which I think what you're suggesting. The Tuskegee Syphilis Study and the Nuremberg Trials took care of that for us.

Short of something like that, we work from mixed methods evidence.

As a footnote, a year isn't a long time in the world of research. That's sometimes quite literally how long it takes from when you apply for a grant to when funding lands in your account. And you're asking about a phenomenon which often occurs months later.

[ianlevesque]

Denial is quite a river these days. Where else are you going to get a brain imaging study with before and after data on thousands of people? If that's not persuasive and concerning to you I don't think anything will be.

[native_samples]

Why should a "study" in the abstract automatically be persuasive and concerning? Scientists get paid to publish studies, so the literature is full of nonsensical studies that show correlations between anything and everything. User timr just explained to you why this specific study cannot be used to conclude anything, but you're saying he's the one in denial?

[gibba999]

A study in isolation should not be persuasive. There's a pipeline from idea to hypothesis the theory to fact, which includes many studies with many methodologies.

On the other hand, a handful of studies, one correlational with large n, a few causal, a good theoretical basis, etc. do move us up that pipeline quite a bit.

Mild and asymptomatic cases of COVID19 due seem to cause brain damage leading to brain fog.

- Reports of brain fog in isolation? Psychosomatic.

- Correlational studies? Correlation is not causation.

- Case studies? Anecdotal.

- Extrapolation from olfactory symptoms? Theoretical.

And so on.

Put together, though, it's a pretty strong case. It's not airtight, but it's well into the well-supported theory range.

[timr]

> Where else are you going to get a brain imaging study with before and after data on thousands of people?

Why does the size of the study matter so much if the endpoint of the study is absurd, the gathering process was a fishing expedition, and the whole thing is subject to confirmation bias?

Even if you believe that these researchers are finding real signals in these MRI scans (which I don't automatically grant; even they admit that some of the "pathologies" they've identified aren't significant, and they didn't pre-declare the endpoints anyway, so you can't rely on conventional statistical significance thresholds), the fact that they know the outcome for each subject hopelessly poisons the data.

> Denial is quite a river these days.

People have a habit of inventing fictions they believe wholeheartedly in order to ignore a truth they cannot accept.

[elcomet]

> bonus points: can you spot the missing correlate?)

Concussions ?

[marton78]

Poverty, drug use, poor life choices.

[timr]

I was thinking of all of the lifestyle factors that might make one susceptible to tooth loss for >10 years prior to the study (this was a selection criteria for the participants): lack of education, nutrition, medical care, etc. The paper never controls for why these people lost their teeth.

(To be fair to the researchers of this paper, they do discuss some of this, but they focus on a causal relationship between tooth loss and the other factors. They never really consider that the relationship between these factors and tooth loss could be reversed.)

[eloff]

I couldn't find where it talks about vaccinated patients in the study you linked.

It's not surprising that covid19 can cause brain damage (and heart damage, and death) to unvaccinated people.

[gibba999]

That was listed under "The million dollar questions include"

I'm now realizing formatting / phrasing was unclear.

1. >10% of mild / asymptomatic cases have brain damage.

2. The million dollar question is whether this includes vaccinated cases. Vaccines reduce hospitalizations and deaths by far more than they do mild and asymptomatic cases.

[eloff]

Ah, now I see what you mean. That is worrying. I hope that the rate of mild cases in vaccinated people is lower than the article would lead one to believe. I also hope the protection given is enough to avoid that kind of brain damage.

[wesleywt]

The article says nothing about vaccinated people.

[peytn]

That first pre-print is wild. 8 pages of methods for 8 pages of results (incl. figures). Quite a "pipeline."

[Tepix]

Interesting!