Matthew Lewis

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Taking Initial Viral Load Seriously

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.

April Coronavirus Open Thread

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 poor oxygenation due to the respiratory distress, not a primary viremia in those organs.


https://www.ncbi.nlm.nih.gov/pubmed/15141377

Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis.

"In conclusion, ACE2 is abundantly present in humans in the epithelia of the lung and small intestine, which might provide possible routes of entry for the SARS-CoV. "


ACE2 expression by colonic epithelial cells is associated with viral infection, immunity and energy metabolism

https://www.medrxiv.org/content/10.1101/2020.02.05.20020545v1.full.pdf


The digestive system is a potential route of 2019-nCov infection: a bioinformatics analysis based on single-cell transcriptomes

https://www.biorxiv.org/content/10.1101/2020.01.30.927806v1.full.pdf


Covid-19 and the Digestive System.

https://www.ncbi.nlm.nih.gov/pubmed/32215956

"Studies have identified the SARS-CoV-2 RNA in stool specimens of infected patients, and its viral receptor angiotensin converting enzyme 2 (ACE2) was found to be highly expressed in gastrointestinal epithelial cells. These suggest that SARS-CoV-2 can actively infect and replicate in the gastrointestinal tract. This has important implications to the disease management, transmission, and infection control."



Severe acute respiratory syndrome and its lesions in digestive system

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4611772/

April Coronavirus Open Thread

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

LessWrong Coronavirus Agenda

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