Thread by @SGriffin_Lab

Spoke to someone from @moderna_tx this week at a conference.
Weirdly, SARS2 vaccines came up!

I was told that 3 separate new large-scale syntheses were prepped last Yr, with only one (XBB) eventually used. These are $bn processes.
Hence, vax sales need to recoup this outlay...

This isn't anything sinister on the company's part, far from it - it's an entirely sensible & precautionary approach given the current situation.
As I've mentioned once or twice b4😉, we are still playing catch up when it comes to SARS2 evolution, both the skips and the Jumps!

This is most unlike the situation with SEASONAL influenza, where emergent strains for fluA/B can be detected early and effective vax generated.
That's not to say many don't retain good protection vs severe COVID from previous vax, but each (re)infection is a roll of the dice...

Immunity, including vs severe disease, wanes. Younger kids (u5s) face their 1st infections, and any number of people continually join the millions of clinically vulnerable folks that have been continually gaslit and ignored by Govt since it dropped shielding...BEFORE vax 🙄💔

Hence, we still see 10s of 1000s of people dying annually, and the incidence of #LongCovid shows no sign of slowing.
Vax mitigates both dreadful outcomes...yet the latter NEVER receives due recognition during JCVI assessments.

As shown by @trvrb, SARS2 evolution (function of inherent mutagenic rate and ensuing tolerance of resulting changes) is currently ~3x faster than H3N2, the fastest seasonal Influenza.
This is accompanied by occasional "jumps", as recently for BA.2.86/JN1.
bedford.io/papers/kistler…

The jumps, assuming the resulting strain becomes dominant, then lead to the same phenomenon repeating...the BA.2.86 branch of the tree looks like it will be just as bushy as XBB was last year...

H/T @dfocosi

Some say the virus will inevitably start to slow down as it runs out of options in terms of the beneficial changes it's able to accommodate.
This is based primarily on how flu has behaved following 20/21st century pandemics; immunity balances after 1 or 2 large waves, eg 2009.

But, we really have no idea how this process plays out with a CoV pandemic, let alone a Sarbeco. Yes, endemic CoVs have stabilised and follow some predictable seasonality.
Some say that the Russian flu of the 1890s was the emergence of the OC43 ancestor, but serology doesn't fit.

It seems more likely that OC43 emerged from cattle towards the end of that century, during an albeit nasty pneumonia epidemic in 1899/1900, which had previously been dismissed as a late Russian flu wave (5 yrs after it ended!). This also fits phylogeny.

theconversation.com/some-believe-t…

Many think the 1889-93 Russian flu was H3N8 flu, which is a longer outbreak than most flu pandemics, with four peaks of varying severity.
Of course, this event is pre-vax, as was Spanish flu. Flu vax started trials in the 1930s, then en masse after 1945.

ncbi.nlm.nih.gov/pmc/articles/P…

Spanish flu had 3/4 waves, Hong Kong 57/8 had 2, swine flu 09 had 3.
Compare with our current friend. SARS2 had 6/7 major waves by spring 2022, I've lost count since, plus XBB had multiple overlapping waves of dominance.
So, flu pandemics vary by no of waves...but not like this!

Clearly, population immunity was able to catch up with flu fairly quickly, limiting these larger waves. This may be from seeing flu's previously, but also the capacity for change in the virus couldn't sustain epidemic waves, leading to more predictable endemic patterns.

This point is key. Endemic ≠ benign.
It is also certainly NOT carte blanche to capitulate or embrace fatalistic "what's the point, it's here forever" type stances...which sadly seems to be the default.
Imagine if seasonal flu vax coverage was comprehensive rather than optional.

We seem so keen to normalise our response to the pandemic that we fail to see how much better our management of seasonal viruses could be.
We have some of THE best clinical virologists and public health scientists in the world, but, perhaps unsurprisingly, investment is lacking.

A tragic example, which still beggars belief, is knowing how many more susceptibles there would be after dropping pandemic restrictions, knowing how bad the southern hemisphere was hit, NOTHING was done to accelerate seasonal flu vax in winter 2022/3.

This led to coincident severe waves of flu, RSV, and SARS2, followed, predictably, by increased group A strep...
What's is put down to? Immunity smegging debt. The most bizarre immunological fiction since the hygiene hypothesis...🤬🤦‍♂️💔
Some who evoke this jolly well know better.

It's critical to remember that the nature/scale of population immunity is dynamic, not constant, and viral evolutionary rates vary tremendously...
Saltatory SARS2 represents almost a halfway house bw the original pandemic scenario and a potential future endemic one. Waves are BIG

Of course, our incidence of severe disease has dropped dramatically overall, and long COVID is less likely per exposure than in 2020...BUT repeat exposure increases risk.

So, why do we continue to see 1000s dying and suffering longer term problems still?

Simple. Prevalence.

Any individual risk is scaled by prevalence. Someone kindly reminded me that I've been banging on about this (like a broken record!) for a while now, H/T @sadams_s

Pains me to see that nothing has really changed since then...

https://twitter.com/SGriffin_Lab/status/1515590728709296128?t=RuC7R3H3qI9cCY28e9tnFw&s=19

Anyway, all round the houses, so back to the original point...

We are forced to play catch up with vax, unlike flu. The recent switch to private provision is just typical of the UK Govt pandemic response...sweeping under the carpet, no long-term outlook, minimise obvious harm.

I and @IndependentSage have always advocated #VaccinesPlus as a long-term solution.
This isn't just whimsical lumping of our collective views into one basket, these ideas will SYNERGISE, and ideally create a virtuous circle (sorry, yukky grant management speak!) for future vax...

Think about it...
1. Slow transmission via NPIs, reduce prevalence, reduce exposure for @cv_cev, reduce #LongCovid, SLOW VIRUS EVOLUTION.
2. With proper vax coverage, beginning preschool, with catch up and then boosts 4 >50s and vulnerable (FDA recommended this), immunity builds.

3. Lower viral variation means given vaccines last for longer, reducing costs, suppressing prevalence further, limiting exposure, improving population immunity.
4. Eventually, SARS2 is slowed sufficiently that we begin to overtake.
5. We arrive finally at predictability or ish.

6. Reduced prevalence/evolution with improved population immunity means less disease, less LC, vax now ahead, reduced cost...and iteratively onwards.
Repeat 4 other viruses.

This isn't beyond our means, but it remains outwith our collective consciousness...for "most people" 💔