Thread by @DoomsdayDebunks

@dgurdasani1 Yes and idea it will evolve to mild is based on 4 coronaviruses. 229E + NL63 may have a common ancestory around the year 1100.
+ we don't know for sure any were originally serious or if so how long they took to become mild.
My summary:
Graphic from ncbi.nlm.nih.gov/pmc/articles/P…

@dgurdasani1 Timescale of 1-2 years comes from flu, a very different virus. Some think the pandemic in 1889 was OC43 but evidence is weak, could easily be just another flu pandemic. Polio, smallpox, measles, don't change virulence after decades of evolution. No experience from coronaviruses.

@dgurdasani1 If OC43 was always mild and pandemic in 1889 was flu - that eliminates the only observational evidence for rapid loss of virulence.
We noticed SARS / COVID / MERS because serious.
Suppose HKU1 was recent and always mild?
+ COVID could be the exception.
ncbi.nlm.nih.gov/pmc/articles/P…

@dgurdasani1 I mean - they might be right but it's often said with a lot of confidence, when you look at the evidence they have it is very weak indeed, on both timescale and whether the end result is less severe. It's certainly not enough to plan policy around it.

@dgurdasani1 Question. Apart from flu (a very different disease), is there any other case of a deadly human disease that evolves to be mild on a timescale of 1-2 years?

@dgurdasani1 More on evolution of coronaviruses. HKU1 is now though to have crossed to humans in the 1950s.
cell.com/action/showPdf…
It was likely milder than COVID since we'd have notice a disease as serious as COVID even back then. IFR about 3 in 1000 for 1950s USA. onlinelibrary.wiley.com/doi/epdf/10.11…

@dgurdasani1 Modern virulence theory sees virulence as a trade off. For SARS-CoV2, decreased virulence might not have much advantage because severe symptoms and death occur at > 14 days.

Meanwhile increased virulence may be associated with increased transmissibility early on in disease.

@dgurdasani1 They discuss the avirulence theory. But they observe that specializing in colonizing the upper respiratory tract might increase transmission, and reduce severity. The D614G variant however seems to have increased affinity for URT but without reducing its affinity for the LRT.

@dgurdasani1 They also mention one variant of interest that seems to have increased transmissibility although it has more affinity for the lower respiratory tract. They speculate it might achieve this by evading nasal swabs, so Test Trace Isolate may be an evolutionary pressure to move to LRT

@dgurdasani1 My graphic summary:

1/ Most deaths start after 14 days. Evolution favours more infectiousness. Almost no pressure to reduce death.

@dgurdasani1 2/ HKU1 may have been mild all along.
No evidence of acute pandemic of HKU1 in 1950s
Other coronaviruses had centuries of evolution.

@dgurdasani1 3/ Three possible scenarios for trade off of virulence & transmission rate.
So far virulence of COVID is increasing. Trade offs could mean it becomes more virulent as a side effect of the increased viral loads to become more transmissible. Or delta might be most virulent it gets

@dgurdasani1 4/ COVID could get milder by specializing
in infecting upper respiratory tract
- more transmissible & immune
response weaker

However D614G increases load in URT
without reducing loads in LRT.

One VOI infects lower respiratory tracts, perhaps to evade nasal swabs.

@dgurdasani1 5/ COVID could become less virulent by infecting kids when it's less severe so adults are already immune.

However immunity from COVID is short lived.
When variants evolve to escape immunity, this may not reduce virulence.

@dgurdasani1 Timeline for coronavirus crossovers from:
cell.com/action/showPdf…
Family graphic from:
upload.wikimedia.org/wikipedia/comm…
Nasal swab graphic
cdc.gov/coronavirus/20…
Main paper summarized:
onlinelibrary.wiley.com/doi/epdf/10.11…

@dgurdasani1 This shows the importance of the WHO advice to continue with public health measures and #DOITALL to stop emergence of variants and keep transmission down as we DON'T KNOW how this virus will evolve. debunkingdoomsday.quora.com/Yes-we-can-sti…

@dgurdasani1 So, we need to do better than "live with it".

Marvellous 2nd & 3rd generation vaccines on the way.

WHO say we can tame this virus - endemic but low prevalence.

No need for COVID to be hyperendemic like flu, killing thousands every year.

See my:
debunkingdoomsday.quora.com/Easy-to-tweak-…

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