Thread by @SGriffin_Lab

Righto, just going to throw this out there but take none of the credit as the person behind this would rather avoid any ensuing debate...

In brief, there's huge debate around Omicron being "mild'. This is misleading as, whilst populations may be better equipped immunologically

to stave off severe disease, this is not generally due to reduced virulence per se...the virus would be just as nasty in a naive cohort.

So, obviously most of the information we have comes from South Africa. This is important because omicron is doubling so fast there literally

hasn't been enough time for severe disease to develop in any but the very first amongst those infected in the UK. We're used to the lags and thankfully different trajectories of severe disease and deaths now due to the high vaccine efficiency vs alpha and Delta, less so for the

latter...
Now, we know antibodies wane over time, so the ridiculous prevalence we still have for Delta was driving huge need for boosters in the UK - this is of course a highly privileged position for a country to be in, to supply 3rd and possibly 4th jabs to most of its populus

...for me, this makes the UK govt decision to rely 100% on vaccines all the more about exceptionalism...most countries would never be in a position to contemplate this...

However, I digress...

So, the question is, why have SA seemingly escaped a massive wave of severe disease and death (so far, anyway...), which some are peddling as this virus being the GBD wet dream of a benign virus that will harmlessly pass amongst us and provide life long protection vs SARS2...

Well, it's possible that omicron might preferentially infect the upper rather than the lower airway, and there has been some lab data to support this. However, Delta was similar, and I think we know how that's going...also, it simply isn't true that respiratory viruses that in

the main infect the upper airway don't cause lower respiratory tract disease...I'm talking Rhino and others here.
So, why is @CMO_England rightly concerned at present (no pun intended), despite the mixed messages from others that like to be surrounded by union Jack flags? Well,

firstly, even if the omicron variant was much less pathogenic than delta, the sheer number of infections we're predicting means huge human suffering and massive NHS pressure...
Why are we predicting so many infections? Simply because the majority of the really hard hitting

antibodies we make in response to our Wuhan based vax, or indeed following infection with alpha or delta aren't going to trouble omicron. This is because 3 out of the 4 main sites on the omicron spike have profound changes that prevent sera from binding. Now, this CAN be fought

with boosters, which not only reboot the levels of protective antibodies, they also refine them into being better precision weapons that can bind to our new omicron companion...

So, in our present situation, PLEASE GET YOUR BOOSTERS!

Remember, whilst the risk of infection is at least for the moment approaching spring 2020 levels again if you haven't been boosted recently, we DO still have our cellular immunity induced by our vaccines that should help

reduce the incidence of severe disease, hopefully to a great deal, but again that pesky denominator means trouble for a lot of people I'm afraid...
So, why are the vaccines not preventing infections as they did for our previous VOCs? Well, SARS2 has been changing in different

ways across the planet, but there are often common themes in terms of the patterns of mutations that arise separately in different places because they address the same need, or evolutionary pressure, that the virus faces in its environment. The two main ones so far have been to

get better at infecting humans, and to avoid their immune responses. Primarily, antibody responses drive this change because SARS2, like many respiratory viruses, gets in, amplifies and passes on to others so quickly that your cellular immunity doesn't act at the population level

as much, i.e. SARS2 simply doesn't care if it makes you poorly, it just wants to move on. This is also why the notion that viruses naturally attenuate is Frankly Bollox...it's your severe disease protection that helps us here...look at what happens if we drop measles vax rates...

So, again, where was I? Well, there's a particular path of SARS2 evolution that is far more focused upon avoiding antibodies than improving transmission, and these are represented by the Beta and gamma VOC. These have a number of changes in those regions of spike where antibodies

bind in the main, just nowhere as many as omicron. The gamma VOC arose in Brazil, most likely in the region around Manaus, where it was able to reinfect huge numbers of people that had previously seen the original Wuhan virus...back to GBD types, Manaus was once touted as a model

for herd immunity following infection...the death toll from both waves was catastrophic, just out of interest.

Similarly, beta arose in South Africa and notoriously evades antibodies induced by the AZ vaccine.

Interestingly, beta and gamma are thought to represent paradigms for

how SARS2 might evolve over long term infection within immunosuppressed patients, such as those with poorly treated HIV...see this fascinating study for details...
medrxiv.org/content/10.110…

So, I finally come to my point! Turns out that if you consider the antigenic profile of

Omicron (so the nature of the parts of spike to which antibodies bind), it belongs squarely in a gang with its mates beta, gamma, and also a subpopulation of delta that has acquired a mutation at position 484 in spike, a big antibody evasion mutation...

So, one possibly overly

simplified explanation for why SA is seemingly doing OK (for now...), is that their second wave was mainly beta, and huge numbers were infected. We know antibodies are a huge correlate of protection versus severe COVID as well, as they not only prevent infection, they reduce

spread around the body once you're infected. Hence, even though vaccine coverage in SA is pretty woeful, seeing beta first may well be handy when your then faced by omicron...note, this does NOT condone immunity following infection as a deliberate strategy vaccines are ALWAYS

the right path...by all means, tweak your vaccines...or, suppress cases and reduce the likelihood of VOC in the first place...🤦‍♂️ that's another thread!

So, are we in trouble? Yes, I'm afraid I think that's the case. Many of us will be protected from severe disease, but without

boosters our antibodies will not stop omicron. Severe disease will ensue in some vaccinees, but mainly non-vaxd, plus kids are nowhere near protected and DO get sick. Again, CEV and long COVID are overlooked.
Xmas is endangered because it's too little, too late...again 🤦‍♂️🏴󠁧󠁢󠁥󠁮󠁧󠁿