SARS-CoV-2 Infects Peripheral and Central Neurons of Mice Before Viremia

https://www.biorxiv.org/content/10.1101/2022.05.20.492834v1

71 12 4 years ago

timr5• 4 years ago

A few very important things to note here:

1) This is a paper in mice. Mice are not humans.

2) Half of the experiments are in a mouse that is engineered to express the ACE2 receptor. Samples from this kind of mouse show clear signs of infection, as you would expect (ACE2 is the receptor to which SARS-CoV2 is known to bind, and is not known to be expressed on neurons).

3) Mice that are not engineered to express ACE2 show much lower signs of infection. In fact, I can't see a negative control in the figures, so I don't know if these are real at all (caveat: I haven't read this fully, so maybe there's some argument why they didn't need to do this. My specific critique is that the immuno-staining for samples from wild-type mice look like they could be spurious. Amplification of mRNA from tissue samples is also prone to false-positives.)

Also the title is blatantly editorialized, and should be changed to the title of the paper (which clearly mentions that this is not a human study):

SARS-CoV-2 Infects Peripheral and Central Neurons of Mice Before Viremia, Facilitated by Neuropilin-1

FollowingTheDao5• 4 years ago

It’s more about NRP1 than ACE2. NRP1 is how they think it infects the neuron. I changed the subject to summarize/translate what the study was saying.

The role of NRP1 in human sars2 infection is already well know. This study is just showing the infection in the neuron can/may/does precede it’s appearance in the serum.

Also, ACE2 is most certainly expressed in the neurons and his greatly expressed in the hippocampus.

https://www.sciencedirect.com/science/article/pii/S258900422...

timr5• 4 years ago

That is an argument they are making to explain the putative infection of wild-type mice, yes. Maybe it is true, but it doesn't invalidate any of the things I wrote.

The headline you used doesn't mention that this is a paper in mice, so you failed to accurately summarize one of the most important parts. So important, in fact, that it's in the title of the paper.

Edit: the link you are citing does not say what you're suggesting. "Neuroepithelium" means "epithelial cells surrounding the neurons". The paper is suggesting that they found signs of ACE2 expression in this epithelial tissue.

vmception• 4 years ago

This study is just showing the infection in the neuron can/may/does precede it’s appearance in the serum.

That's pretty interesting, what does this mean for anything. Like does it change how tests should work? vaccines? any mitigation measure?

kaczordon• 4 years ago

Always learn a bunch when you comment on this stuff. It's hard to parse through scientific papers like this and tell how much they're exaggerating or hiding that someone else with more knowledge around this could see.

timr5• 4 years ago

Just to be clear, I'm not suggesting that the authors are exaggerating or hiding anything. They seem to be making careful claims (and though I still have questions about the controls, this is well within the bounds of my own possible misunderstanding of the methods). I'm only pointing out the limits of what you can reasonably conclude from an experiment like this. Also, if laypeople look at the pictures of red cells and histograms and don't realize that "the infected half" are actually engineered to be susceptible, it's pretty easy to be misled.

The poster is/was out on a limb with the title and the suggestion that this means something for humans. At most, it's a hypothesis that remains to be validated. It also makes a claim that contradicts a bunch of other papers (i.e that neurons get infected), so you have to take it with a grain of salt.

SARS-CoV-2 Infects Peripheral and Central Neurons of Mice Before Viremia

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