Thread by @ewanbirney

A view of COVID from here: April has started pretty cold and drab in London, but there is a real sense of anticipation as pub gardens, gyms and shops open up on Monday.

Context: I am an expert in human genetics and computational biology. I know experts in viral genomics, infectious epidemiology, testing, clinical trials and immunology. I have COIs: I am paid consultant to Oxford Nanopore and on the Ox/Az clinical trial.

Reminder: SARS-CoV-2 is a highly infectious virus which causes a horrible disease, COVID, in a subset of people, often leading to death. A different subset have no symptoms and can be asymptomatic carriers.

If SARS-CoV-2 infection is left unchecked in a population very quickly many people would catch this disease; as well as a large number of people dying even with the best healthcare, every healthcare system could not accommodate this number of patients at once.

To prevent this happening all countries have created behaviours (NPIs in the jargon) which has suppressed transmission of the virus (in differing levels of success) or eliminated in a defined territory the virus. This is how the world got through 2020.

At the end of 2020 a variety of new variants of the virus with new biology emerged in force, notably B.1.1.7 in the UK and now Europe and Americas which transmits faster and causes more severe disease.

UK and then Ireland and Portugal saw high levels of transmission and consequent hospitalisation and sadly deaths at the start of 2021 due to B.1.1.7.

Remarkably a suite of vaccines have been developed against the virus which both change the immune response to the disease (the disease is best thought in my view as mainly a virus induced autoimmune disease) and blunts the rate of transmission.

Vaccine production continues to go up, and vaccination rates continue to increase in many countries. In one country, Israel, the outcome of deep vaccination has become clear; a far more normal life (though not 2019) with some (but not high) transmission and low hospitalisations.

However, this "end game" happens quite deep in the vaccination process. When it happens is complex to assess. The UK's first dose levels are quite high and testing for SARS-CoV-2 antibodies shows that the combination of vaccine and previous infection is over 50% and rising.

The UK is stepwise relaxing, and along with Israel's "opening with zero margin" approach in March represents two practical "exit paths" into the new vaccinated normal. It's worth noting that there is alot of momentum in the system even with vaccination

(ie, high vaccination with high transmission is really rather different from high vaccination with low transmission as the high transmission will go on to find pockets of unvaccinated individuals causing hospitalisation and deaths at some rate).

There are also other examples. Chile has also vaccinated to a reasonably high level quickly (the speed here is important as vaccination needs ~2 weeks to develop immunity - one needs to take the vaccination rate of 2 weeks ago into account) but cases + hosptialisations are rising

An arguably similar situation in playing out in Michigan in the US now, with again appreciable vaccination levels but rising cases. Other places in Europe are at the foothills of this and working out how to navigate a B.1.1.7 epidemic with a partially vaccinated

Again, assigning causality to why things happen is complex - there are many different components to each of these epidemic dynamics; however, it seems clear that vaccination at 30 or 40% of a population is unlikely to be enough to release a substantial amount of NPIs

(and, as frustrating as it is, as with Israel now we will be walking on egg shells with some restrictions in 2021 even in best case scenarios for a variety of reasons; pockets of unvaccinated individuals and potential new variants with new biology still)

Back to Europe, with vaccine production increasing, and increasing vaccination rates (delivery rates >> supply in most countries, which is the correct way around) the Israel and UK style endgames are within relatively easy reach this summer.

(Vaccination rates need to be high; vaccine hesitancy needs to be tackled and good communication around the very rare risks for blood clotting (Ox/Az) and, as previously noted in the clinical trials, anaphalatic shock (Pfzier) needs to be tackled)

Personally I think it will be best to strengthen NPIs across Europe to control transmission (I was so glad to see France tighten before Easter) and simply hold this until vaccination, noting carefully the experience of Israel and then UK's relaxation to get an idea of timings

(basically the first countries have to probably feel out the right balance on relaxation with more care and caution whereas the soon to follow countries should have more confidence seeing practical examples being executed).

Countries which have done well in suppression (Japan, South Korea) or elimination (NZ and Australia) have more time and less urgency, but I do worry that B.1.1.7 and other variants might change the epidemic too much (I hope not).

Across South America and Africa, two areas I have less of a deep understanding compared to Europe the epidemic is raging; it looks particularly bad in South America. I hope more vaccine supply can make it to these countries

The gnawing concern will be vaccine / immune escape variants, and we already have two ones with some differential immunity - P.1 (Brazil) and B.1.351 (South African) variants. Others are basically inevitable given the amount of transmission, the amount of immunity and vaccination

However it may well be that severe (hospitalisation) disease is different from infection/transmission and that vaccines are more pan-variant effective at preventing hospitalisation. There is good theoretical reasons to think this as it will involve T-cell immunity.

We know from Israel and UK that the current vaccines in those countries work well against B.1.1.7. It is hard to piece together real world efficacy data on P.1 and B.1.351 as numbers are far far lower. I think we should know more this coming month but it is thin pickings.

I can sense in the UK both societally and scientifically the horizon being lifted, though there are plenty of ways to screw up this summer, so one has to have a healthy level of paranoia.

Globally this phase is going to run easily into 2022 and then we need to have monitoring schemes and vaccination preparedness to tackle a new SARS-CoV-2 variant (a very real possibility) and of course a different pandemic.

Wise, thoughtful scientists and clinicians, such as @JeremyFarrar have been advocating the need for this for over a decade, and indeed much of what has worked well (eg, COVAX) internationally is due to his and others foresight in this area.

There were plenty of missed opportunities and a fundamental mis understanding of the risk of global harm to health and economy due to a pandemic over the last 30 years, despite the "trial runs" of SARS1 and MERS.

One of our current "benign" coronaviruses was probably a zoonoses (animal to human) transfer in the "Russian Flu" of 1888 so a reasonable estimate is that we will be doing this once or twice a century, may be more often.

Furthermore the miracle of antibiotics is being steadily undermined by the inventiveness of bacteria, as well as a host other infectious disease threats.

As a worldwide species - all humans as one - we've got to get better - far far better - at detecting and responding to pandemics, with layered detection and defenses.

Anyway, I am looking forward to swimming in my local pool regularly and sharing (coldish) pints outside with friends and colleagues. I am looking forward to seeing colleagues in person across @embl and science in the summer and autumn.