Thread by @ewanbirney

My view of COVID from crisp, cold Helsinki (back to London - with PCR test - on Tue). TL;DR Omicron has thrown us back to a place of uncertainity; we have far more potent tools+understanding now but the trajectory will be mainly determined by the biological properties of Omicron

Context: I am expert in human genetics and computational biology. I know experts in viral genomics, infectious epidemiology, clinical trials and immunology. I have some conflicts of interest; I am paid consultant and shareholder of Oxford Nanopore and was on the Ox/Az trial.

Key background: COVID is a virus-triggered disease, with hallmarks of auto-immune disease, triggered by a novel, highly infectious Coronavirus, SARS-CoV-2. In naive populations many people would get this disease, many of those dieing, and healthcare would be overwhelmed

The combination of reducing contacts until vaccines have arrived (far faster than expected) and then prompt vaccination (though key holes of coverage in low income countries and vaccine hesitant/resistant populations in high income countries) was the trajectory across 2020/2021.

This was painful, complex, with many missteps, miscalculations and missed opportunties, but broadly was working on the succession of viral strains, named by Greek letters when they biology has changed and enter public discourse (Alpha, Beta, Delta etc).

Fast and excellent data gathering, analysis and transparency by Botswana and South African scientists have uncovered another variant of concern, now called Omicron, the next approrpiate letter in the Greek alphabet.

There are two key lines of concern. Firstly Omicron has a substantial number of changes, include many we know from other strains are responsible for faster transmission (eg, shared with Delta) or immune escape (eg shared with Beta).

Secondly, one mutation Omicron shares with Alpha is a deletion across a region used for testing, allowing many standard PCR tests to give a proxy of Delta vs Omicron readout.

This proxy allowed the South African scientists to show that Omicron was likely growing (from a low baseline) in multiple provinces in South Africa. This is still fragile information (it is damn complex in this world) but strong evidence for increased growth in the South Africa.

Although there are both short term (eg, travel restrictions on return/visits to suppress seeding events from high incidence omicron countries) and long term (eg, tailored vaccines) under human control, the key determinant of the future are biological properties of omicron

I think of this in a grid of six (3x2) - how transmissible is Omicron in naive, previously infected and vaccinated individuals and then how likely does an Omicron infection trigger severe disease in naive, previously infected and vaccinated individuals.

(Reality of course is more complex than this 3x2 grid - is the age dependence the same as previous strains? which strain were you infected by? transmission has source and infected individuals. Which vaccine course was followed? And probably factors we don't know yet).

The South African information gives us partial information on naive and probably previously infected transmission but far less so on the vaccinated column because vaccination is lower+it is more complex to analyse due to confounding

Similar understanding severe disease rates also is complex because often it takes time for a new variant to transmit at scale to more at risk populations (mainly - older age), and the numbers are just lower with yet again more confounding and complexity to get "pure" rates.

Something under our control is laboratory experiments with pseudoviruses and human cells or animal model and the virus. Watch particular carefully about the antibody neutralising (or not) for this virus, which seems like a good surrogate for transmission suppression.

Note that even if transmission is high over vaccine induced antibodies (which will be a pretty depressing finding) the fact that severe disease is a sort of T-cell dysfunction (a virus triggered auto-immune disease) does not automatically mean severe disease protection is null.

T-cell assays exist but are far far more fiddly and expensive, hard to do at scale and unclear whether they are surrogates or not for severe disease progression (meta, long term problem - we need cheaper, more scaleable T-cell assays).

All this means we will be in a state of uncertainity for at least 2 more weeks, and probably wont have everything nailed down (as we pretty much have with Delta) for months. Frustrating - and I wish one could do this faster - but the reality.

Once these parameters become more clear one can build strategies to get out which probably range from "hold the course we were on in Delta" through to the worse case (let's hope this doesn't happen!) "restrict transmission for tailored vaccines to be produced".

But many things to be hopeful here; The fast data and analysis by Botswana and South Africa is to be applauded again and again - and they deserve our full bodied support in help (materials - vaccines, drugs). A reminder as ever this is a human vs virus problem, not national

The gift of the S-gene target failure - so useful in the rise of Alpha, the replacement by Delta and now the rise in Omicron means that about ~50% of the RT-PCR labs have an effective pre-screen for Omicron.

One needs to tool up and understand this, and ideally have this dovetail into genomic sequencing (so one can work out that it really is Omicron). This gives me quite a bit of hope one can stamp out many Omicron seeds in Europe (UK, Denmark best placed for this).

Above all vaccines do work against many strains, with a fair bit of crossover, and that we are mainly interested in protection against severe disease which is a different process and due to T-cell processing (T-cells see segments, not the whole thing) many reasons to be hopeful.

So - don't panic, smart scientists (smarter than me!) are working flat out, and we are armed far better than a year ago. Do your bit - above all get vaccinated, ventilate rooms when crowded (just a crack of air will do wonders apparently) and wear masks in crowded settings.