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?
"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)."
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.
"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.
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!
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.
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.
>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-...
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.
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.