Comment by timr | Hacker News Reader

Comment by timr | Hacker News Reader

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

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...

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.

I’m sorry, I don’t understand. You didn’t bring up NRP1 At all in your argument when clearly this is what the paper about.

SAR2 is entering the neuron via NRP1 and ACE2.

They infect mice that express ACE2 on their neurons, and see obvious signs of infection.

They also infect wild-type mice, and see greatly reduced response in the same experiment, but claim that this is still non-zero. They hypothesize that NRP1 is mediating the infection.

The evidence for this claim is not definitive. It's an intriguing hypothesis. It's still not a paper about humans.

The fact that NRP1 assists SARS2 infection has been known for over a year. I still don’t get your point.

This is important because it can explain the neurological symptoms of Covid and possible pathway for treatment of those neurological symptoms. To anyone, like me, who had psychosis at the beginning of their Covid infection, or people who are suffering from long Covid, this is very important.

There have been papers showing that NRP1 interacts with furin-cleaved spike protein. There have been some suggestions that this assists in entry for non-neural cells. There have never been papers (to my knowledge) that show that this plays a role in neuronal infection in humans. Like ACE2, NRP1 is associated with endothelial cells.

Again, this is a research paper, in mice. It has no direct relevance to any symptom you have personally experienced.

> It has no direct relevance to any symptom you have personally experienced.

You say this like the whole story of COVID is finished.

Story for you:

https://twitter.com/JamesMelville/status/1528046141715230721

> 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?

It will probably mean a lot regarding cognitive function and psychosis to those are risk genetically. Changes in NRP1 are linked to mood disorders like schizophrenia and depression.

I think it also shows that this is the pre-symptomatic time of the infection.

My own experiences with Covid was I had a psychotic break two days before I had a fever. I have a history of psychosis.

It’s also important to note that the Epstein-Barr virus also uses NRP1.

In my humble opinion, I feel that the destruction of NRP1 and ACE2 are responsible for many of the comorbidities we find after infection with SARS2.

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.

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.

Reply on news.ycombinator.com