It's mentioned in the abstract that similar findings were noted in humans as well.
"Humans experiencing long-COVID with cognitive symptoms (48 subjects) similarly demonstrate elevated CCL11 levels compared to those with long-COVID who lack cognitive symptoms (15 subjects)."
Yeah, at least one of the things they report is irrelevant.
>Impaired hippocampal neurogenesis, decreased oligodendrocytes and myelin loss in subcortical white matter were evident at 1 week
I can forgive them for not knowing that the great "Do adults humans have neurogenesis in the dentate gyrus of the hippocampus (or EC)" debate has been pretty much ended. We don't. Adult humans don't make new neurons. Humans aren't like other mammals. So... I'm not sure how much the "impared hippocampal neurogenesis" bit applies. Our hippocampal neurogenesis is already impaired. Unless you're pre-pubescent.
Your linked paper talks about how the "adult mammalian brain can produce new neurons". That isn't controversial. What used to be controversial, but isn't anymore, is that adult humans brains don't produce new neurons. Not in the dentate gyrus, not in the entorhinal cortex between the hippocampus and cortex, not even in the olfactory bulb. Your linked paper does not have any human studies of neurogenesis, only BDNF serum levels and assumptions about what that means from mouse models. But mouse, even ape models, don't translate re: neurogenesis.
Like everyone else, yourself included, I used to think that THC's main anti-depressant effect was mediated through increasing survival of new neurons during their granual cell to neuron journey in the dentate. But nope.
Adult humans don't have new neurons.
https://www.jneurosci.org/content/41/12/2541
Looks like there is evidence.
Also are you claiming there are no stem-cells/MSCs in the brain?
I have read multiples papers about drugs that specialize unspecialized cells into olygoendrocytes (a microglia) in the human brain. I don't see why epigenetics wouldn't allow unspecialized cells to become neurons vs glial cells.
Finally if I recall correctly, some glial cells might not act like neurons but still release neurotransmitters.
More importantly, humans should preserve their neurons by actively fighting apoptosis, e.g. by taking skq1.
And as said previously, synaptothrophics exists and are very potent.
Finally, hypermnesics are a thing.
BTW children are generally happiers/more emotional than adults. One might wonder wether this is related to neuron/synapse density
I'll give that paper it's claim, that "DCX+ dentate granule cells are a dynamic cell population that undergoes progressive maturation" but I don't see new evidence from that paper suggesting they actually make it through the complex, multi-step, evolution of granule cells to neurons. There are a lot of stops and pitfalls on the way. The evidence from the 2022 paper I linked at the start of this thread shows the gene expression profiles of adult human dentate granule cells are very different from other mammals.
Biochemist here, this reply is pretty stale and also lazy. Many studies are done in mice. A better criticism would be that this is a preprint. In fact, there's a giant yellow box right above it that says:
"bioRxiv posts many COVID19-related papers. A reminder: they have not been formally peer-reviewed and should not guide health-related behavior or be reported in the press as conclusive."
You're free to check out the credentials of the people in the paper, which look great. A bunch of different people that have worked in COVID, virology, and vaccines.
Not a biochemist but: "Many studies are done in mice." Isn't this kind of the issue? Are mouse models really that good of a proxy for humans? How do you validate this?
The process in drug discovery is: invitro work, animal models (zebrafish, mice, rats), clinical trials, release to public. It is completely standard for work to be done in mice, and to dismiss it in this way is a nothing burger.
There is a piece of truth in that "animals models don't always pan out", but that's the state of the art whether we like it or not.
My point is, if you start the criticism at "mice model, opinion rejected", you are rejecting nearly all basic bioscience.
They certainly aren't perfect proxies for humans, but they have a lot of advantages:
1) They reproduce quickly.
2) We have inbred several different strains so that every member is genetically identical to all the others of the same sex.
3) There is a huge amount of scientific knowledge already accumulated on mice, and the inbred strains specifically. Different developmental checkpoints, what healthy looks like across basically every dimension.
These first two make it possible to do repeatable studies at relatively low costs. The latter allows you to do things like knock out or replace a gene and see see what impacts it has biologically and you can find out in weeks instead of years. Research mice the way biologists reduce their build times.
> A better criticism would be that this is a preprint.
Does this mean that of the two characteristics ("study in mice" and "is a preprint"), "is a preprint" is more predictive of the result failing to pan out in humans?
Preprint means that it has not been peer reviewed. It is likely in submission to various journals, where a few people in the field (hopefully peers in the field!) will discuss the edge cases of the study. In my experience this ranges from a rival lab you get along with giving you shit for not checking something out, to a lab that has no idea what genes are in a zebrafish accusing you that the gene you are studying does not exist in zebrafish.
You never know what kind of questions they might ask! Papers do in fact get rejected for shoddy work, or get sent to revision. Often it's not a huge problem, maybe fix a figure, double check some other work, or refer you to someone else's study that contradicts your claim. If you're not a fraud, you generally bring your strongest case, so the only tuning needed is details.
That being said, peer review doesn't always work, as there are cases of publishing fraud.
However, for labs that get exceptional scoops you can bet people are going to try to replicate it and if it turns out it doesn't work you've got some explaining to do. (Your academic reputation is now on the line.)
In my career (10y), I personally witnessed two people immolate their careers over publishing papers that didn't work or stole results from someone else.
Mice (and to a greater extent, animal models) are the current standard for advancing studies in biology. Are there problems with mouse models? Sure. Is there currently a better alternative? No.
Are preprints bad? No. It used to be there was no such thing as a preprint, you submitted your work to a journal and that was that. Accept or reject. You might have sent the preprint version to people in your field you were collaborating with, or some deconstructed version to verify parts of your work. Now with arxiv style publishing, it's up to the community at large to figure out what's what. I'm not saying one or the other is better. Us biodorks are catching up to physics people. However, anyone can publish to arxiv, including kooks.
Can preprints be bad? Yes. This work has no scrutiny to its claims by anyone outside of the authors, so for laypeople not in the field we don't have a good insight as to make heads or tails of these claims. Could you look it all up? Of course! Contrast that to someone in the field that might say on sight: "Yeah, Nichols' work has been pretty out there" or "That gene doesn't work the same way in zebrafish." :D
Mice are uncontroversial. Preprints are uncontroversial. I don't think I'd put money on either. I would be more interested to see follow up work than change the animal model.
Bluntly: your opinion on this will only be interesting when you can correctly explain (a) why mouse models are used (b) why mice and not some other mammal (c) what mouse models can and cannot tell us about humans, and lastly (d) why this mouse model isn’t consistent with (a)-(c).
This is a thought of science denial. Using mice as proxies for human biology has been a tool in medical science for decades and has led to many great discoveries.
Is there a specific issue you see where the usage of a mouse model is devastating to this study?
No, it isn't. There's a saying in medical research: "mice lie, and monkeys exaggerate". This is because most findings in mice don't translate to humans.
Representing an experimental result as directly relevant to humans when it wasn't done in humans is misleading.
The results shown in Figure 3 are essentially unrelated to the rest of the paper. It's an experiment that they've included to claim some relevance to humans, and head off the criticism that this is a paper about mice.
At best, you can argue that they show a different inflammatory marker in a group of people who were already unwell. Here's the paper describing the people from whom the 9 samples were chosen:
> We performed conventional histopathological examination of the brains of 18 patients. Fourteen patients had chronic illnesses, including diabetes and hypertension, and 11 had been found dead or had died suddenly and unexpectedly. Of the 16 patients with available medical histories, 1 had delirium, 5 had mild respiratory symptoms, 4 had acute respiratory distress syndrome, 2 had pulmonary embolism, and the symptoms were not known in 3
I can't tell which of these patients were used in this study, but...there's a lot going on with these samples. One of the patients was a meth addict, and another was a heroin addict, yet another was an alcoholic, and two others had recurrent seizures from prior head injuries!
I wasn't talking about the results and relevance of this particular paper but I was replying to a cheap, offhand generalisation.
No doubt that one needs to be cautious about animal tests but they do work and are highly effective in many cases, especially for finding indications of possible effects on humans. Or is that not true?
That's not as bad as you might think, depending on your specific concern. We're basically worms with extra doodads glommed on. Cake hole connected to poop hole, with gonads. Also, sometimes brains, but mostly gonads.
Sorry, I don't know your level of knowledge of things cell-biology and genomics. If your concern is mouse != human, than that's not really a good argument by itself. If your concern is that many diseases / therapies that seem to work in mice don't readily translate to humans, then yeah, I agree.
I wonder that also. At this point, a lot of this seems like a situation of damned if you do damned if you don't. I saw a TikTok of a guy being able to show that whatever your preference, you can prove it through scientific papers. Seeing as COVID has been here for 2 years and even long haul COVID is exceedingly rare, I'm not too worried about any of it.
I'd love more data on this kind of thing in general. I developed a neurological disorder as a teenager with no apparent cause that affects me to this day, it's not like some bitter life-long crusade of having to know but I've always had a vague hunch it was a genetic disposition triggered by some external event and I'd be so curious to have that confirmed or debunked.
It's one of those ones that doesn't show up on an MRI but an fMRI shows characteristic changes, which suggests something wrong at a lower level I think.
We've been studying SARS-CoV2 a lot more than most other viruses, and in humans, it's often associated with confounding variables, so it's good to take studies with a grain of salt because the 200 common cold viruses probably haven't been studied this closely, and you have to be really careful to factor in emotional distress in human studies.
Yes, this. COVID-19 is topical now, so we're looking hard, here. Is this something we've looked for with other diseases/conditions, in the past? If we go looking now, do we find that other insults that we thought we understood do this too?
Yes, this. COVID-19 is topical now, so we're looking hard, here.
I'd say more than 1 million confirmed deaths and over 81 million confirmed cases (in the US) in two years is more than just topical. We are approaching half a billion cases globally with over 6 million deaths.
Yes, there have been lots of Corona viruses in the past, some of which result in things as ubiquitous as the common cold.
It's called a novel Corona virus for a reason: humans had essentially zero immunity to this virus and its ability to evade the body's defenses and mutate so quickly at this scale is something we haven't seen before. Each major variant is more transmissible and more elusive than the previous one. BA.2 is now the dominant strain and the FDA just authorized another booster [2]. In many ways, we are still coming to grips with what we're dealing with.
We don't have a choice but to continue to look hard at COVID-19--the results of allowing it spread so widely are right in our faces and we have to deal with it.
I sense that we may me talking past one another. You seem to be focusing on my word choice and and justifying that we should spend resources studying COVID-19. My post does not dispute this at all.
What I'm saying is that to conclude that effect X (demyelination) is a cause for additional concern with respect to disease A (COVID-19), we should go back and see whether effect X is also present with respect to other diseases such as B, C, D (common cold, flu, etc). Because we may have found X linked to A because we are looking so hard at A, and not have found it previously with respect to B, C, D because we weren't looking as hard then.
Topical may imply temporary, which may have struck a chord with you, but this brings a genuine curiosity to the burning question, what are the conditions if any for returning to normal? I chuckle as I write this as living in western Canada, we just recently got the public place mask mandate removed so it's back to "normal" for some people even more, except we are dealing with record high inflation across the board (lumber too) -- c'est la vie...
Like, there have been mini-pandemics in the past (Spanish Flu is one I read a bit about), how do we "win" against it instead of just "minimize damage"? Herd immunity? Given headlines like OP, it makes one pause to think.
SARS-CoV-2 is sufficiently contagious that there will be no significant herd immunity effect to protect those who lack immunity. Everyone will be exposed. Fortunately the vaccines and other treatments are fairly effective at preventing deaths.
The mask mandates implemented in most of North America were never an effective public health intervention. Areas which never had mandates, or removed them sooner, had similar outcomes. Correlations with death rates were weak at best, and confounded by multiple other factors.
Humans had a high level of immunity to COVID-19 before it even appeared. Many patients clear the infection entirely with the innate immune system, and suffer few or no symptoms. It's just like any other respiratory virus in that respect. Our species never would have survived so long if that wasn't the case.
The best evidence indicates we have seen something like this before, specifically in the 1889 pandemic. That was most likely caused by the HCoV-OC43 coronavirus (genetically very similar to SARS-CoV-2), although at this point we probably won't be able to prove the cause 100%.
Additional boosters may be beneficial for some patients with defective immune systems. But they're not advised for the general population. We can't boost our way out of the pandemic.
Pretty sure I caught COVID March 2020, but wasn't tested. I lost my smell for 5 months and had chest pains. Just tried the trail making test and completed A in 20 sec and B in 52 sec, so seems like I don't have damage yet.
This is a paper in mice, and looks at a broad-spectrum markers or inflammation, focusing on CCL11, which has been associated with a large number of things, including allergic rhinitis:
Importantly, they also note that the virus is not invading the neurons.
Be very cautious about extrapolating from this paper. They see up-regulation of microglial cells, which are macrophages (and are expected to be active during infection) and use that plus some other papers to make the claim. They show one figure concerning axonal myelin loss in mice showing a slight effect between groups, but that's a long way from any sort of link to a disease state, let alone in humans (I have updated this portion of my comment, after having more time to read the paper). Certainly, I wouldn't leap to any wild conclusions about other diseases related to myelin.
In short, they see some inflammatory signs in the brains of mice that are not associated with direct infection. That's interesting scientifically, but absolutely not worth panic or exaggeration.
> This is a non sequitur. the idea that you expect brain inflammation when you get a mild cold is just dishonest.
I don't know what one "expects", but that's quite literally what the allergic rhinitis paper implies. It's also not the only paper that associates CCL11 with innocuous things.
The non sequitur is taking something like this and leaping to the conclusion that CCL11 is indicative of a severe problem.
There are several endemic coronaviruses that typically cause common cold symptoms. Viruses aren't "creative", and coronaviruses adapt slower than some other viruses such as influenza.
They seem to report results from human subjects as well.
> Human brain tissue from 9 individuals with COVID-19 or SARS-CoV-2 infection exhibits the same pattern of prominent white matter-selective microglial reactivity. [...] Humans experiencing long-COVID with cognitive symptoms (48 subjects) similarly demonstrate elevated CCL11 levels compared to those with long-COVID who lack cognitive symptoms (15 subjects).
Figure 3 shows some CD68 staining of a handful of human brain samples from people who died (not necessarily from Covid), and were subsequently found to test positive for Covid. The argument is that this is one sign of inflammation in the white matter (axons), but not gray matter (neural bodies) of these samples.
While this allows them to claim some connection to humans in a paper that is almost entirely about mice, it's so different from the bulk of the experiments that it is essentially a tangent.
Edit: Out of curiosity, I dug up the paper describing the people from whom these 9 samples were taken.
These patients...let's just say they were not well prior to Covid:
> We performed conventional histopathological examination of the brains of 18 patients. Fourteen patients had chronic illnesses, including diabetes and hypertension, and 11 had been found dead or had died suddenly and unexpectedly. Of the 16 patients with available medical histories, 1 had delirium, 5 had mild respiratory symptoms, 4 had acute respiratory distress syndrome, 2 had pulmonary embolism, and the symptoms were not known in 3
I can't tell which of these patients' samples were used in this latest study, but...there's a lot going on. One of the patients was a meth addict, and another was a heroin addict, yet another was an alcoholic, and two others had recurrent seizures from prior head injuries:
This just goes to show that you must dig into results like these before drawing any conclusion. If five of the nine samples used here were from people with drug addiction and chronic brain diseases, would it change your perception of the results?
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[ 4.1 ms ] story [ 114 ms ] thread"Humans experiencing long-COVID with cognitive symptoms (48 subjects) similarly demonstrate elevated CCL11 levels compared to those with long-COVID who lack cognitive symptoms (15 subjects)."
>Impaired hippocampal neurogenesis, decreased oligodendrocytes and myelin loss in subcortical white matter were evident at 1 week
I can forgive them for not knowing that the great "Do adults humans have neurogenesis in the dentate gyrus of the hippocampus (or EC)" debate has been pretty much ended. We don't. Adult humans don't make new neurons. Humans aren't like other mammals. So... I'm not sure how much the "impared hippocampal neurogenesis" bit applies. Our hippocampal neurogenesis is already impaired. Unless you're pre-pubescent.
ref: "Transcriptomic taxonomy and neurogenic trajectories of adult human, macaque, and pig hippocampal and entorhinal cells" Franjic et al., 2022 https://www.cell.com/neuron/pdf/S0896-6273(21)00866-7.pdf
laymen ref: https://neurocritic.blogspot.com/2022/02/the-ongoing-debate-...
Like everyone else, yourself included, I used to think that THC's main anti-depressant effect was mediated through increasing survival of new neurons during their granual cell to neuron journey in the dentate. But nope. Adult humans don't have new neurons.
one question though: what about that study that measured carbon-14 levels in the brains of people born before atomic bomb testing? [0]
I don't doubt you're correct re: neurogenesis, I'm just confused how different studies saw different things.
0. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394608/
"bioRxiv posts many COVID19-related papers. A reminder: they have not been formally peer-reviewed and should not guide health-related behavior or be reported in the press as conclusive."
You're free to check out the credentials of the people in the paper, which look great. A bunch of different people that have worked in COVID, virology, and vaccines.
There is a piece of truth in that "animals models don't always pan out", but that's the state of the art whether we like it or not.
My point is, if you start the criticism at "mice model, opinion rejected", you are rejecting nearly all basic bioscience.
These first two make it possible to do repeatable studies at relatively low costs. The latter allows you to do things like knock out or replace a gene and see see what impacts it has biologically and you can find out in weeks instead of years. Research mice the way biologists reduce their build times.
Does this mean that of the two characteristics ("study in mice" and "is a preprint"), "is a preprint" is more predictive of the result failing to pan out in humans?
Note: this happened to me, and there is google maps for zebrafish genes, this is easy: https://zfin.org/search?category=&q=SHC
You never know what kind of questions they might ask! Papers do in fact get rejected for shoddy work, or get sent to revision. Often it's not a huge problem, maybe fix a figure, double check some other work, or refer you to someone else's study that contradicts your claim. If you're not a fraud, you generally bring your strongest case, so the only tuning needed is details.
That being said, peer review doesn't always work, as there are cases of publishing fraud.
However, for labs that get exceptional scoops you can bet people are going to try to replicate it and if it turns out it doesn't work you've got some explaining to do. (Your academic reputation is now on the line.)
Here's a short list of notes on retractions: https://en.wikipedia.org/wiki/Retractions_in_academic_publis...
In my career (10y), I personally witnessed two people immolate their careers over publishing papers that didn't work or stole results from someone else.
Fun retraction watch site here: https://retractionwatch.com
To directly answer your questions:
Mice (and to a greater extent, animal models) are the current standard for advancing studies in biology. Are there problems with mouse models? Sure. Is there currently a better alternative? No.
Are preprints bad? No. It used to be there was no such thing as a preprint, you submitted your work to a journal and that was that. Accept or reject. You might have sent the preprint version to people in your field you were collaborating with, or some deconstructed version to verify parts of your work. Now with arxiv style publishing, it's up to the community at large to figure out what's what. I'm not saying one or the other is better. Us biodorks are catching up to physics people. However, anyone can publish to arxiv, including kooks.
Can preprints be bad? Yes. This work has no scrutiny to its claims by anyone outside of the authors, so for laypeople not in the field we don't have a good insight as to make heads or tails of these claims. Could you look it all up? Of course! Contrast that to someone in the field that might say on sight: "Yeah, Nichols' work has been pretty out there" or "That gene doesn't work the same way in zebrafish." :D
Mice are uncontroversial. Preprints are uncontroversial. I don't think I'd put money on either. I would be more interested to see follow up work than change the animal model.
PS: Wow, I had good coffee this morning!
Is there a specific issue you see where the usage of a mouse model is devastating to this study?
Representing an experimental result as directly relevant to humans when it wasn't done in humans is misleading.
The authors point out that the same observation was made in human brain tissue of covid patients as well, it is literally in the paper.
"We had the opportunity to examine human cortex and subcortical white matter samples from a cohort of nine individuals[...]"
At best, you can argue that they show a different inflammatory marker in a group of people who were already unwell. Here's the paper describing the people from whom the 9 samples were chosen:
https://www.nejm.org/doi/full/10.1056/NEJMc2033369
> We performed conventional histopathological examination of the brains of 18 patients. Fourteen patients had chronic illnesses, including diabetes and hypertension, and 11 had been found dead or had died suddenly and unexpectedly. Of the 16 patients with available medical histories, 1 had delirium, 5 had mild respiratory symptoms, 4 had acute respiratory distress syndrome, 2 had pulmonary embolism, and the symptoms were not known in 3
I can't tell which of these patients were used in this study, but...there's a lot going on with these samples. One of the patients was a meth addict, and another was a heroin addict, yet another was an alcoholic, and two others had recurrent seizures from prior head injuries!
https://www.nejm.org/doi/suppl/10.1056/NEJMc2033369/suppl_fi...
No doubt that one needs to be cautious about animal tests but they do work and are highly effective in many cases, especially for finding indications of possible effects on humans. Or is that not true?
Sorry, I don't know your level of knowledge of things cell-biology and genomics. If your concern is mouse != human, than that's not really a good argument by itself. If your concern is that many diseases / therapies that seem to work in mice don't readily translate to humans, then yeah, I agree.
"Molecular imaging uncovers effects of Covid-19 on the brain": https://news.ycombinator.com/item?id=30710807
"Covid can shrink brain and damage its tissue": https://news.ycombinator.com/item?id=30592494
It's one of those ones that doesn't show up on an MRI but an fMRI shows characteristic changes, which suggests something wrong at a lower level I think.
Many are new too. Viral dynamics... changed with the rise of cities a few thousand years back.
I'd say more than 1 million confirmed deaths and over 81 million confirmed cases (in the US) in two years is more than just topical. We are approaching half a billion cases globally with over 6 million deaths.
Yes, there have been lots of Corona viruses in the past, some of which result in things as ubiquitous as the common cold.
It's called a novel Corona virus for a reason: humans had essentially zero immunity to this virus and its ability to evade the body's defenses and mutate so quickly at this scale is something we haven't seen before. Each major variant is more transmissible and more elusive than the previous one. BA.2 is now the dominant strain and the FDA just authorized another booster [2]. In many ways, we are still coming to grips with what we're dealing with.
We don't have a choice but to continue to look hard at COVID-19--the results of allowing it spread so widely are right in our faces and we have to deal with it.
[1]: https://www.worldometers.info/coronavirus/country/us/
[2]: https://www.fda.gov/news-events/press-announcements/coronavi...
What I'm saying is that to conclude that effect X (demyelination) is a cause for additional concern with respect to disease A (COVID-19), we should go back and see whether effect X is also present with respect to other diseases such as B, C, D (common cold, flu, etc). Because we may have found X linked to A because we are looking so hard at A, and not have found it previously with respect to B, C, D because we weren't looking as hard then.
Like, there have been mini-pandemics in the past (Spanish Flu is one I read a bit about), how do we "win" against it instead of just "minimize damage"? Herd immunity? Given headlines like OP, it makes one pause to think.
https://www.businessinsider.com/delta-variant-made-herd-immu...
https://www.medpagetoday.com/opinion/vinay-prasad/94646
The mask mandates implemented in most of North America were never an effective public health intervention. Areas which never had mandates, or removed them sooner, had similar outcomes. Correlations with death rates were weak at best, and confounded by multiple other factors.
The best evidence indicates we have seen something like this before, specifically in the 1889 pandemic. That was most likely caused by the HCoV-OC43 coronavirus (genetically very similar to SARS-CoV-2), although at this point we probably won't be able to prove the cause 100%.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7252012/
Additional boosters may be beneficial for some patients with defective immune systems. But they're not advised for the general population. We can't boost our way out of the pandemic.
https://youtu.be/jAjKQY0_BQA
https://www.sciencedirect.com/topics/immunology-and-microbio...
https://www.spandidos-publications.com/10.3892/etm.2020.9078
also cannabis use:
https://www.sciencedirect.com/science/article/abs/pii/S02785...
Importantly, they also note that the virus is not invading the neurons.
Be very cautious about extrapolating from this paper. They see up-regulation of microglial cells, which are macrophages (and are expected to be active during infection) and use that plus some other papers to make the claim. They show one figure concerning axonal myelin loss in mice showing a slight effect between groups, but that's a long way from any sort of link to a disease state, let alone in humans (I have updated this portion of my comment, after having more time to read the paper). Certainly, I wouldn't leap to any wild conclusions about other diseases related to myelin.
In short, they see some inflammatory signs in the brains of mice that are not associated with direct infection. That's interesting scientifically, but absolutely not worth panic or exaggeration.
This paper in the OP is pretty much confirmation of many presumptions that Physicians have had about COVID for the last few years.
Coronaviruses are adapting rapidly and are getting more creative in how they debilitate who they infect.
I don't know what one "expects", but that's quite literally what the allergic rhinitis paper implies. It's also not the only paper that associates CCL11 with innocuous things.
The non sequitur is taking something like this and leaping to the conclusion that CCL11 is indicative of a severe problem.
> Human brain tissue from 9 individuals with COVID-19 or SARS-CoV-2 infection exhibits the same pattern of prominent white matter-selective microglial reactivity. [...] Humans experiencing long-COVID with cognitive symptoms (48 subjects) similarly demonstrate elevated CCL11 levels compared to those with long-COVID who lack cognitive symptoms (15 subjects).
While this allows them to claim some connection to humans in a paper that is almost entirely about mice, it's so different from the bulk of the experiments that it is essentially a tangent.
Edit: Out of curiosity, I dug up the paper describing the people from whom these 9 samples were taken.
https://www.nejm.org/doi/full/10.1056/NEJMc2033369
These patients...let's just say they were not well prior to Covid:
> We performed conventional histopathological examination of the brains of 18 patients. Fourteen patients had chronic illnesses, including diabetes and hypertension, and 11 had been found dead or had died suddenly and unexpectedly. Of the 16 patients with available medical histories, 1 had delirium, 5 had mild respiratory symptoms, 4 had acute respiratory distress syndrome, 2 had pulmonary embolism, and the symptoms were not known in 3
I can't tell which of these patients' samples were used in this latest study, but...there's a lot going on. One of the patients was a meth addict, and another was a heroin addict, yet another was an alcoholic, and two others had recurrent seizures from prior head injuries:
https://www.nejm.org/doi/suppl/10.1056/NEJMc2033369/suppl_fi...
This just goes to show that you must dig into results like these before drawing any conclusion. If five of the nine samples used here were from people with drug addiction and chronic brain diseases, would it change your perception of the results?
https://www.cell.com/neuron/fulltext/S0896-6273(20)30716-9
The histamine blockers are for the common mast-cell reactions during/after covid.
But Montelukast is a leukotriene receptor antagonist which inhibits a specific enzyme.
https://en.wikipedia.org/wiki/Antileukotriene