1/ Omicron seems to be a strain that specializes in gaining entry to human cells by endocytosis (ie being engulfed by the cell rather like an amoeba engulfing its prey)
2/ Om's different from previous variants such as Delta because it doesn’t seem to fuse cell membranes (fusion allows other strains to gain entry to cells and to move into and infect neighboring cells) doi.org/10.1101/2021.1…
4/ I guess that's why it can tolerate so many mutations in spike. IMO its very unlikely that something as complicated & finely-tuned as the realignment mechanism can work with 36 mutations, without yrs of evolutionary refinement, epistatic adaptation etc en.wikipedia.org/wiki/Coronavir…
5/ These new mutations presumably have the effect of binding ACE2 tightly (note that binding no longer needs to operate the realignment switch) and/or stimulating endocytosis
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1🧵Thoughts on the timing of Covid-19.
Key points to note:
First, the extraordinary stability of CoV-2 during 2020
Second, a lot can be explained if CoV-2 in Wuhan mutated to become more TRANSMISSIBLE in Oct/Nov 2019 (rather like Omicron)
2/ As @mattwridley and @Ayjchan point out in their excellent #OriginOfCovid book, this may well have started with the authorities in Wuhan deciding to cover up a small local problem.
3/ How might events have unfolded?
Covid-19 started with either a lab-leak or a zoonotic spill-over. But when?
CoV-2 was extraordinarily stable from Jan 2020 to the arrival of Alpha in Nov 2020.
1/ I feel there are still some important points to make about this question of whether and how quickly Covid will become like a common cold
2/ The first point is CoV-2 is a respiratory virus. It spreads straight from your nose and throat to mine. This is a very distinct group of viruses with something surprising (and, really, unexplained) in common – the illnesses they cause are much more common in cold weather.
3/ They’re also mild in the vast majority of cases – so CoV-2 will be very unusual if it remains as pathogenic as this for long. (Though of course rhinovirus, adenovirus, parainfluenza etc regularly hospitalize children and others 👇)
Fig 1 of Kanduc & Shoenfeld (2020) uses a very simple analysis: shows that CoV-2 shares many 6-chain amino acid sequences with human and mouse genomes, but not other genomes such as cow, pig, gorilla, chimp, rhesus monkey, fruit bat
2/ The same applies to polio, measles, dengue, influenza H1N1, smallpox, HPV, and Ebola viruses. Also bacterial pathogens like anthrax, plague and toxoplasmosis; all overlap more with mouse (and rat) than other animals.
3/ This implies we have frequently swapped pathogens with rodents - which we live very closely with. (Apparently bat experts say bats have the most dangerous viruses. But rodent experts say THEY, rodents, harbour the worst viruses!)
1/ Important observation: many respiratory viruses are much easier to culture at 33°C than 37°C – as predicted by temperature dependent viral tropism #TDVT
However, virologists normally put this down to the thermal sensitivity of the host CELLS – less interferon may be produced by cells at 33°C than 37°C doi.org/10.1073/pnas.1…
3/ Actually our immune defences do seem to be weaker when we breath cold air –this may explain the observation that standing still outdoors is correlated with increased mortality from respiratory disease (while outdoor exertion sufficient to cause sweating seems to be protective)
The problem is that we essentially have ONE observation - that hundreds of often unrelated viruses in all regions (outside the Tropics) with very diverse climates, have winter seasonality
2/
If we say the winter surge of colds in one place is due to eg school buses, business travel and humidity, but somewhere else it's sports events, snow and sunshine, we are cheating. We’re “overfitting” - we are using too many variables to model a 1-d phenomenon
3/
One reason I’m convinced that viruses moderate their pathogenicity much more than is often appreciated comes from observations of hemorrhagic fevers, which give fascinating insights
/1
People occasionally pick up viruses from animals especially rodents & bats. Usually they cause mild flu-like symptoms but here's the extraordinary thing: if they get a hold they often cause internal & external bleeding & are fatal – in spite of NOT being well-adapted to humans
/2
Ebola is one example. There are many others eg Rift Valley, Lujo, Bolivian and Brazilian hem. fevers. Ebola, Marburg, Crimean-Congo and Lassa hem. fevers can spread from person to person.
/3