All of Matthew Lewis's Comments + Replies

I proposed in a another thread that variolation of the GI tract, where there are known cell populations expressing ACE2, might be preferred to lung. Avoiding the lung infection from the the apical surface of AT2 lung cells sounds like a good idea.

6[anonymous]
Study of symptoms in hospitalized patients: "Patients with COVID-19 who have digestive symptoms were shown to have a worse prognosis than those without." https://www.practiceupdate.com/content/clinical-characteristics-of-covid-19-patients-with-digestive-symptoms-in-hubei-china/98000

It's unclear to me that you wouldn't end up with a worse clinical course in this case - perhaps you wouldn't, but I'm not sure why you'd assume it's safer.

Exactly like variolation, except you do it intelligently to minimize lung infection.

SARS and SARS-Cov2 are both ACE2 dependent for cell entry.

ACE2 expression in AT2 cells in the lower respiratory track is known to be on the apical surface, that is the side of the cell facing airspace, not the basal surface facing vasculature. Hypothesis would be that lung infection is much more efficient and virulent by droplet delivery rather than by virus circulating in blood stream. I am also under the understanding that the kidney and heart complications are due to po... (read more)

2gwillen
Cool, thanks for expanding on that. You might want to link this comment in your other comments about this idea, so people have some details to read. It's a lot more informative than the one I was responding to!

Innoculate GI tract with live virus. Suffer GI symptoms. Get immunity. Avoid respiratory complications.

1Nicholas Campbell
Neat idea, although immune responses can be tissue specific (to a certain degree).
4gwillen
This is an interesting idea but would benefit from more elaboration. Why the GI tract in particular -- do you have evidence that this will significantly reduce the risk of respiratory symptoms, or just speculation / "common sense"? Is there evidence that the GI tract as the initial site of exposure will produce an infection / an immune response, but with a reduced chance of the infection spreading to the lungs / respiratory tract? Or with it taking longer to get there, similar to Robin Hanson's thoughts about deliberate exposure with a low dose, like variolation of old? If you have any links/references, please definitely post them. If it's just speculation, it's interesting speculation but tell us what it's based on.

The peer-reviewed literature has several papers talking about GI symptoms of COVID19, and there are several GI cells that are ACE2+ that are plausible targets. What I am wondering is the following a potential vaccine strategy?

innoculate with live strain in GI tract to avoid respiratory infection

1jmh
Related to that observation I have wondered, but never posted/asked, if how one gets infected might influence severity as well. If I touch a contaminated surface and then rub my eye or then eat a sandwich without washing my hand is that more likely to end up somewhere other than my upper and lower respiratory systems?
2Davidmanheim
Interesting - I'd ask Robin Hanson if that fits with his variolation suggestion.