Sunday morning in London; strong sunlight but sharp air and the Coronavirus situation is still on track in the UK; I have more concerns across Europe, but there are good solutions (namely vaccination). The global situation is far far more concerning.
Context: I am an expert in genetics and computational biology. I know experts in infectious epidemiology, viral genomics, clinical trials, testing. I have some COIs; I am long established consultant to Oxford Nanopore which makes sequencing machines and I was on the Ox/Az trial.
Reminder: SARS-CoV-2 is an infectious virus which causes a horrible disease (COVID) in a subset of people, often leading to death. If we let infection progress at the virus' natural rate many people would die, and no healthcare system can cope with this rate of disease.
Because of this restrictions on social contacts and ways to suppress transmission have been implemented over most of the world during 2020 and at the start of 2021. These have been variably successful and "wave" like patterns triggered by shifts in behaviour over the year
(there is a host of details about this behaviour and suppression which deserve their own threads. The two things I'd say is that (a) backtracing works (see Japan) and (b) ventilation is key to lower risk - be outdoors, exchange air)
As expected, the virus mutates all the time, and some of these mutations change the biology of the virus. Those biological shifts were small (but measureable in retrospect) over early 2020 but more substantial changes in biology occurred at the end part of 2020
The B.1.1.7 (first seen in England), the B.1.351 (first seen in South Africa) and the P.1 (first seen in Brazil) lineages are 3 now well known lineages, with high transmissbility (B.1.1.7) and some immune escape (P.1 / B.1.351)
(side note: it is hard to disentangle transmission from partial immune escape from aggregate numbers and pinning down the biology of these viruses "in the wild" is far more complex than one might imagine)
Thankfully in 2020 a number of vaccines have been produced, currently in two groups - mRNA vaccines (BioNtech/Pfzier + Moderna) and Adenovirus vaccines (Ox/Az and J&J). Chinese and Russian vaccines are also present with less data present (at least in developed world publishing)
All these vaccines work against the old strain and have low number of adverse events; we know the BioNtech/Pfzier and Ox/Az vaccines work due to the high vaccination levels in the UK and Israel with this strain.
The two adenovirus vaccines (Ox/Az and J&J) do have a very rare adverse reaction, also an immune reaction, but in the 1 in million to 1 in 100,000 level. Different countries are handling this discovered in roll-out ADR in different ways.
A consistent view is that this risk from this ADR is well below many other healthcare and life risks, and the benefits, in particular for old and middle aged individuals of avoiding COVID is far far higher. Still, it is complex to navigate.
Both in vitro and small scale trials say that the Ox/Az vaccine is less effective with B.1.351 (SA) and BioNtech/Pfzier with some decrease; a similar mixed tale is true for the P.1 strain, with my read being that the B.1.351 is the most clearly "escaped" from antibodies.
However, we have virtually no data on severe disease. This is unsurprising because the number of people who get severe disease is that much lower and countries with high vaccination levels and good national data collection (UK and Israel mainly currently) do not have much B.1.351
There are many reasons to think severe disease will have more "cross-strain" protection - firstly all the vaccines have shown strong protection against severe disease (though not complete; nothing in biology is complete).
Secondly severe disease is really a viral-triggered auto-immune disease, where the body turns on itself. A key part of regulated the finely tuned immune system are T-cells. T-cells "see" a virus in a different way (small peptides- a bit like the dismembered limbs of the virus)
Indeed, in vitro studies and studies from vaccinated individuals show strong T-cell response which unsurprisingly is far harder (not impossible) for a strain to create a work around in terms of mutation
But nothing here beat just straightforward real world data. I am hope that French studies in the Moselle area (higher B.1.351) will give us a BioNtech/Pfzier readout and there should be an accumulation of data in the UK over time.
It is going to be thin pickings because in both these settings the TTI want to eliminate the B.1.351 strain and other potential immune escape strains quite rightly.
Over to tactics this summer - Israel has exited into what feels from my London standpoint something like the summer of 2020 - there are some controls, face masks, "Green passports" to go inside, lots of outdoor stuff but it looks like a pretty normal life. Bravo Israel!
The UK and the US are heading the same way. The UK has a series of step down relaxations; the first step (schools opening, groups of 6 in gardens/outside) seem to have gone ok. We are still getting a read out of the second step now (outdoor pubs and restaurants, more mixing)
The rise in infection levels in Northern Ireland though is telling that this level of vaccination (~45% with one dose) *by itself* will not suppress transmission, and there are plenty, of people who could get this horrible disease, some of which would die, many suffer v badly
Chile is another moderately high vaccination but still has high transmission country, but with the added complication of a third vaccine (Sinopharm).
It looks like Israel made its first transition at around 55% with one dose (but note with a higher second dose level, and all BioNTech/Pfzier); that said the complex relationship with Palestine with less vaccination in that population makes the "real world" mapping complex.
European countries have picked up their vaccination rates, which now are within a factor of 2 from UK and US rates. A key thing has been the improvement of supply from BioNTech/Pfzier (go Marburg!)
This puts all of Europe on the same basic path as Israel, UK and US - ie, a vaccinated population which both protects the at risk from disease and does much over the heavy lifting for transmission suppression which one needs to add a bit more into
Indeed, my biggest fear for Europe is that the rather straightforward solution of "sit tight, suppress transmission until enough people are vaccinated" feels somehow ... unacceptable or complex to take on.
(Now - I know that "sit tight" does not come at zero cost, and a failing of this pandemic is that we never got economic welfare and healthcare operations/delivery into the same framework in most countries where hard decisions have to be made >>
<< however, in a time where there is a good solution - shown by Israel, tracked internally and clearly working - of more vaccination and you can have a time horizon on this - it is probably one of the easier decisions to make relative to the economics; contrast autumn of 2020)
Indeed, for European countries they will have probably three countries to look at in terms of "when and how to relax NPIs" being Israel, UK and US. None of these things are one to one mappings, but they are informative
Denmark is interesting now; with really high levels of testing (RT-PCR and LFDs) and good isolation support, with some vaccination level they look in a stable situation with B117 as the majority strain. So there are other ways of making this suppression "bridge" work well
But the developed world has a path this summer; Brazil and India are showing the challenges of this in large countries with less vaccine availability and smaller but large in absolute terms at risk populations.
I am not close to these countries but what I read is heartbreaking and goes to the fact that this a global problem. Again the foresight of COVAX and @gavi is remarkable but the developed world has to shoulder the way out for the whole world here.
The key feature here is vaccine creation rates and vaccine supply/logistics rates into arms. Nothing else probably matters compared to these rates.
Looking ahead - what are my worries? By far my biggest is that due to politics and narrow mindedness we do not vaccinate the world with the vaccines we have (Adenoviruses included!). The knockon health and economics would be awful.
Next up will be a "full" immune escape variant. It is *possible* that B.1.351 is pretty full wrt to severe disease, but I think it is unlikely - I think we would have known already from Moselle, but I want to see data and analysis.
On variants, a good case is to be walking on eggshells a bit over this summer in Europe (UK included) and then variant-aware boosters (in particular E484K mutation!) for the at risk population in Europe. But this should not distract from vaccinating the world now.
I should add, the extraordinarily depressing scenario is a full immune escape mutant which triggers a similarly bad disease on top of vaccinated individuals. I think this is unlikely - perhaps pretty unlikely - but definitely, definitely not zero probability.
If this happened, we'd have to do it all again (sort of from Feb/March 2020) but of course with far better understanding, better testing, knowing which vaccine scaffolds to work from etc.
It is definitely one to keep the "reasonable worse case scenario" planners up at night.
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