1/🧵No one seemed to want to do this, so I finally went ahead and looked at vaccines/deaths in OurWorldInData ⬇️

I've plotted excess deaths in the last 12 months against CoV-19 booster doses ⬇️

There is a clear correlation (correl coeff = 0.50) 2/ Strangely, there's a much stronger correlation between vaccine doses given and CoV-19 deaths: apparently, more vaccine doses corresponded to more deaths in the last 12 months, corr coeff = 0.72 ⬇️

🧵1⃣ Why do we get more colds&flu - & Covid - in winter than summer?

This question has confused & perplexed scientists for ~60 yrs

Turns out the main explanation is quite simple: virtually all respiratory viruses - including CV2 - are thermally-sensitive
doi.org/10.1016/j.imj.… 2⃣CoV-2 has been shown to be thermally-sensitive in the wet-lab and in animals (see table⬇️from our letter)

Many other respiratory viruses have been shown to be thermally-sensitive in the wet-lab⬇️, although they may rapidly lose this sensitivity if they are propagated at 37°C

I’m reposting this thread re the evolution of viral proofreading / the puzzling shape of epidemics, to get it all in one place 🧵I haven’t yet seen any scientists tackling the puzzling surges and rapid collapses of cases that we often see in Covid-19, eg South Africa and India⬇️(where lockdowns may not be very effective). Also seen in other countries such the UK, Austria and France⬇️

1/ Once again I’m struck by something that’s been staring us in the face, but which we all seem to have missed
🧵 2/ Almost certainly, the main pandemic threat from “novel” viruses doesn’t arise when they first appear in humans. Whether they’re from animals or labs, it’s probably letting them fester that’s dangerous. Here’s why -

(Introduction)

🧵1⃣ Why do we get more colds and flu in winter?

And why are some respiratory viruses more likely to infect the lungs?

@JuliaLBach8 and I have a simple proposal called temperature dependent viral tropism (TDVT) 2⃣We suggest that (virtually all) respiratory viruses sense temperature in order to keep out of the lungs, so that they can keep us moving around
doi.org/10.1002/rmv.22…

1⃣There’s another way to look at the question of whether CoV-2 will evolve to become milder

The key observation is that CoV-2 is thermally-sensitive in the lab, and in animals:

i.e. it is more active at lower temperatures 2⃣Recent papers

Spike is thermally sensitive doi.org/10.1016/j.csbj…

Higher CoV-2 titres at 33°C V’kovski doi.org/10.1371/journa…

Golden hamsters doi.org/10.1093/cid/ci…

Elevated temperatures inhibit CoV-2 replication independently of the IFN response doi.org/10.1371/journa…

🧵1⃣The point about not expecting evolution to lower virulence doesn’t come directly from the recent paper⬇️, but is actually a citation of Day et al

https://twitter.com/EricTopol/status/1502024758862385182

2⃣I’ve read Day et al. and it has a strange omission

The authors don’t mention the fact that CoV-2 is what I'd call a “standard” respiratory virus, that is, it's transmitted directly from the nose and throat of one person to the nose and throat of another.

1/ I can't understand why anyone - let alone Nature - takes the @MichaelWorobey and Pekar et al preprints seriously

Their arguments seem so weak, and the assumptions about timing so odd

nature.com/articles/d4158… 2/ All big Chinese cities have dozens of seafood markets. I don't know how many sell animals, but I assume quite a few. During a large human epidemic, the pathogens responsible are BOUND to turn up all over those markets. How is that evidence?
doi.org/10.5281/zenodo…

1/ We now have several studies showing that CoV-2 is thermally-sensitive in the lab and in animals⬇️

Isn’t it time to accept that the traditional explanation – which is IMO also the simplest – is the correct explanation of the seasonality of respiratory viruses? 2/ we now know that CoV-2 binds to human ACE2 much more strongly at 37°C than 40°C

doi.org/10.1016/j.csbj…

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)

doi.org/10.1080/222217… 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…

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.

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.

1/ Fascinating

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

doi.org/10.1007/s12026… 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.

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

Examples from our paper, below
doi.org/10.1002/rmv.22… 2/ Interestingly, this is also seen for CoV-2 doi.org/10.1371/journa…

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…

I've noticed that explanations for resp-vir seasonality involving humidity are becoming more popular

Eg doi.org/10.1101/2020.0… by @EdsardRavelli
1/ 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/

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

en.wikipedia.org/wiki/Viral_hem… 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

THREAD (quite long - sorry!)

IMO you can’t understand CoV-2 or any other virus without understanding the "virulence-transmission trade-off hypothesis" This hypothesis was introduced in the 1950s to explain observations of myxomatosis. Basically, very mild strains became moderate, while very virulent ones also became moderate

cambridge.org/core/journals/…

1/ The Nobel laureate André Lwoff suggested part of the hypothesis in 1959, when he noted that the degree of virulence of viruses is often related to their level of thermal sensitivity

journals.asm.org/doi/pdf/10.112… … 2/ In 1979, Richman and Murphy developed this further, discussing many examples of thermal sensitivity in natural and lab‐made viral strains, and noting that the near‐universal attenuation of ts strains made them good candidates for vaccines.
doi.org/10.1093/clinid…

1/5

The UK 10-day self-isolation period is highly disruptive to industry.

But it may also be counter-productive in combating Covid-19. 2/ 5

We know that Covid-19 incubation periods vary hugely, with some illnesses appearing 2 or 3 days after exposure, but others taking 14 days or more.

Some of this variation is likely to be related to the properties of the particular “isolate” (ie strain) involved.

Is the SPIKE protein wrong target for vaxs?

• Unbiased screen found 29 "shared epitopes" that were main targets for T-cells

• Notably, only 3 of 29 epitopes were located in spike protein

• Most epitopes were located in ORF1ab / nucleocapsid protein

cell.com/immunity/fullt… Anyway

"Frequent BACTERIAL infections of respiratory tract are often a harbinger of ANTIBODY disorders"

"Respiratory VIRAL infections are more significant in patients with T-CELL immune deficiencies"

So why do virtually all vaxs target SPIKE PROTEIN?

ncbi.nlm.nih.gov/pmc/articles/P…