Thread by @BillyBostickson

1. From Day 1, SARS-COV-2 was very well adapted to humans .....and transgenic hACE2 Mice
"we generated a mouse model expressing hACE2 by using CRISPR/Cas9 knockin technology. In comparison with wild-type C57BL/6 mice, both young & aged hACE2 mice sustained high viral loads...

Coincidence?
"....in lung, trachea & brain upon intranasal infection. Although fatalities were not observed, interstitial pneumonia & elevated cytokines were seen in SARS-CoV-2 infected-aged hACE2 mice"
A Mouse Model of SARS-CoV-2 Infection & Pathogenesis
ncbi.nlm.nih.gov/pmc/articles/P…

NOT JUST ANY OLD hACE2 MICE FIT THE BILL
"investigators responded by evaluating potential for already-generated hACE2 transgenic mice to support SARS-CoV-2 infection & pathogenesis. These models supported low level SARS-CoV-2 replication with minimal morbidity or lung pathology"

from Discussion Section ncbi.nlm.nih.gov/pmc/articles/P…

Place your bets!
K18-hACE2 or B6 Ad-hACE2?
Importantly, a number of these models including K18, CAG, HFH4, and knock-in mice show neuroinvasion and high titer replication in the brain, which may contribute to lethality.

"K18-hACE2 mice show weight loss, cytokine/chemokine production, mortality & extra-pulmonary viral replication are end-points. Brain infection observed in K18-hACE2 mice, while reported in humans, are not the primary cause of death in most COVID-19 patients"

"We developed a SARS-CoV-2 hACE2 mouse (HFH4-hACE2 in C3B6 mice) infection model, generating interstitial pneumonia & pathology similar to COVID-19 patients
Viral quantification revealed lungs as major infection site
Viral RNA also found in eye, heart, & brain in some mice"

Zheng Li Shi's Mice
Pathogenesis of SARS-CoV-2 in Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2
ncbi.nlm.nih.gov/pmc/articles/P…

Zheng Li Shi's hACE2 Mice (HFH4-hACE2 in C3B6 mice)
"SARS-CoV-2 replicated in mouse lung but may also target brain, heart, & eyes of hACE2 mice. Brain infections were only observed in deceased mice, neuroinvasion is sporadic & likely represents the cause of death"
Male Mice Die!

Too many similarities?
hACE2 mice
Interstitial pneumonia + inflammatory cell infiltration
Dissolved & necrotic alveolar cells
Terminal bronchioles blocked
Higher male death rate
Lung, Eye, Heart and Brain
All "Same Same" as pathological findings in COVID-19 patients

Zhengli Shi still using Baric's second-hand Mice!
"HFH4-hACE2 micefrom Ralph S. Baric’s lab"
HFH4-hACE2 mice bred & maintained in specific pathogen free (SPF) environment at Laboratory Animal Center of WIV
Viral infections were performed in at BSL3 facility

Conclusion?
@WHO, demand to see WIV Lab breeding records for HFH4-hACE2 mice in 2019!
@WHO, demand to see WIV BSL3 & 4 Lab Reports!
@WHO, demand to see WIV Safety Incident Logs!
WE KNOW they experimented on Transgenic Mice at BSL4 Level as well as BSL3.
Why?
What Viruses?

Tracing Ariadne's Thread in Reverse - "Addendum"
Different hACE2 Mice = Different Results
This needs investigation to determine precisely which mouse model shows highest similarity to Covid-19 in terms of pathogenicity & replication, etc.
ncbi.nlm.nih.gov/pmc/articles/P…

Forgot to add the Peking Mouse Model
"cerebral vasculitis & haemorrhage in SARS-CoV-infected hACE2 mice. However, only interstitial pneumonia observed in these SARS-CoV-2-infected hACE2 mice, implying disparity in pathogenicity between the 2 coronaviruses"
nature.com/articles/s4158…

Unroll Do Uncle Ralph & Auntie Shi's used & serially abused hACE2 Mice show the the strongest match to all features of COVID-19 Pathogenicity in Humans?
@threadreaderapp