I've been seeing a lot of discussion around the dosage gaps recommended by government for the Astra/Oxford & Pfizer/BioNTech vaccines. My thoughts on the potential benefits & risks of such an approach, and the need for much greater transparency around these decisions. Thread.

The UK govt announced recently that both the Oxford & BioNTech vaccines would be now administered with a gap of between 4-12 weeks (so prioritise administration of first dose, given limited resources).

What is the basis of this?

The basis that's been discussed seems to be that
1) the first dose is likely to confer some degree of protection against disease, so better to roll this out as fast as possible, and
2) that for Oxford/Astra efficacy may be higher when the gap between doses is greater.

I discuss some of the technical details around the Oxford trial below for those interested in these. If you'd just like a summary of this, please skip to the summary tweet titled 'SUMMARY'.

What does published evidence show? The Astra/Oxford data are a bit messy because of protocol changes during the trial. This is because the trial was originally planned as a single dose trial, but a booster dose was added when developers realised that this would likely help.

I'm honestly at a loss as to understanding what our government is thinking & what evidence they're considering in enacting gravely negligent policies that will almost certainly lead to tens of thousands of deaths in the coming weeks. Thread.

To recap - NHS capacity is critical in many places. Hospitals have reported oxygen shortages, and doctors are talking about having to choose who to put on ventilatory support. We have rapidly rising case numbers, >50,000 daily reported cases & 981 deaths reported yesterday.

Let's remember that the impact of socialising over christmas hasn't even begun to show in our numbers yet. And that hospitalisations are indicative of infections that happened ~2-3 wks ago (since then we have been seeing exponential rises in cases).

This means even if we act today, and bring R to below 1 right now, hospitalisations will continue to rise for another 2 wks or so - in line with exponential rises in cases over the past 2 weeks. And deaths will continue to rise for 2-4 wks after we act.

Given current doubling periods, this means very conservatively, 20-30,000 deaths over the next 4 weeks or so, which we sadly can't do anything about now, because most of those who will die during this period have already been infected.

My thoughts on the govt announcement yesterday regarding a new viral strain potentially driving an increase in cases in London. The claim, at least from listening to the daily briefing seems to be based on the strain increasing in frequency more recently. 1/N

Cases have been rising exponentially in England- much of the increase being attributed to the South, although declines have slowed even in the North following easing of lockdown. Much of this is anticipated, and expected, given the behaviour of the virus. 2/N

SARS-CoV-2, like any other viruses mutates as it multiplies (albeit slower than influenza). Mutations occur randomly and most are 'neutral' - i.e. have little to no effect on transmission, ability to evade the natural or vaccine-related immune response

Having said that, few mutations have been shown to be less likely to be neutralised by plasma from patients infected by the usual (wild-type) virus. Whether this translates to a lower response to vaccines or higher risk of re-infection is unclear at the moment.

Also worth noting that just because a variant becomes more frequent in a region doesn't necessarily mean it offers a fitness advantage to the virus. Many mutations rise to different frequencies in different regions due to random processes. The frequency of strains varies globally