Concerning data from PHE today suggesting that sequencing shows that there are 11 cases of the UK variant (B117) identified that also have the E484K mutation (the one found in the so-called South Africa and Manaus variants). This is important and concerning for many reasons. 🧵
To recap the B117 ('UK variant') is defined by a number of mutations, including the 501Y mutation thought to be associated with increased transmissibility, which is also shared by the so-called South Africa (B1351) and Manaus (P1) variants.
In addition, both B1351 (SA) & P1 (Manaus) variants also have the E484K mutation. This mutation has been associated with a high level of escape of neutralising antibodies directed at previous variants in the laboratory, raising concerns about vaccine efficacy.
So in addition to increased transmissibility, the B1135 variant also has the potential to escape immune response directed at previous variants. While this was a theoretical concern until v. recently, vaccine trials that have been carried out in SA have shown reduced effectiveness
To be clear, these vaccines are still highly effective against the new variant, effectiveness does appear to be reduced to an extent. E.g. Novavax showed an efficacy of 89% within the UK but 60% in South Africa. The J&J vaccine had 72% efficacy in the US & 57% in SA.
These are efficacy estimates for preventing disease. Efficacy is generally a pyramid -
efficacy against severe disease will usually be highest
efficacy in preventing disease will be lower
efficacy in preventing transmission lower
efficacy in preventing infection
The vaccines are likely to provide good protection against severe disease, but escape of variants from vaccine induced immune responses may mean efficacy to prevent disease, infection & transmission are reduced. This also has implications for reaching our herd immunity threshold.
We don't yet know what the effectiveness of vaccines is in reducing transmission, and what the impact would be, but this is concerning. To illustrate, Manaus estimated to have ~76% exposure to virus in the 1st wave is now seeing a surge of cases.

Whether this is due to the P1 variant in Manaus (which also carries the E484K mutation escaping immune response to the previous virus is not known, but this is possible. Even if this could partially escape immune response it could lead to a new population that becomes susceptible
What does this mean for herd immunity?
This means the herd immunity threshold would not be reached, as immunity levels directed against the previous virus may be high, but are not at a sufficient level to contain the new variant.
This threshold has not been reached in Manaus. There may be several reasons:
1. Overestimation of exposure
2. Waning of natural immunity after exposure
3. Herd immunity threshold higher due to more transmissible strain
4. New variant can escape previous immune response
Whatever the reason, this should be concerning to everyone. Even if the exposure is overestimated, given the data, the majority of the population is likely to have been exposed. Manaus still has an R well above 1, and healthcare capacity is overwhelmed.
Can't we just update our vaccines?
Most manufacturers are actively working to develop boosters against variants with the E484K mutation, but this is more complex and will likely take longer than we've been given to believe. Worth reading the thread here:

Worryingly, we're also seeing community transmission of the B1351 strain (South Africa) in the UK- initial cases were linked to travel, but we now have 11 cases in 8 areas in England. The govt is desperately trying to contain this now, but it's going to be hard to do this.
This is exactly why experts have been calling for months to revise our really inadequate border policies- to ensure these variants did not enter the country. Once they get established, it's hard to stamp them out.
Policies that allow people to exit quarantine 5 days in with a -ve test.
Policies that don't restrict travel the same way from all regions (viruses travel)
Lack of managed quarantine or monitoring of compliance

It wasn't impossible to prevent this. Australia & NZ have.
Now, it looks like B117(UK) is adapting further - developing the E484K mutation in line with the B1351 and P1 variants. This is an example of convergent evolution. These mutations have evolved independently again & again because they are favourable to the virus.
And we shouldn't expect that this process will magically stop here. As we vaccinate larger proportions of the population, the virus will come under even more selection pressure favouring mutations that are able to escape immune response.
The only way to prevent this is to eliminate transmission. We can't prevent the virus adapting any other way. And its clear that letting transmission continue at high levels will lead to more adaptation & more mutations with different properties. We can't afford to take this risk
These mutations may make our vaccine resources less effective. They may increase the chance of re-infection among people who've been exposed. They may be more transmissible. And as selection pressure grows across the population, we should expect more.
What's even more concerning in the recent report is that E484K appeared on a B117 variant background in many different events- this did not just happen one time, and then spread. It's clear that this evolved in the same direction independently several times.
It's absolutely clear that this is not a rare chance event- it's an event that will keep occurring unless we prevent transmission altogether. These mutants pose a huge risk to our pandemic response. We have >1000 daily deaths & its taken a national lockdown to reduce R below 1.
We can't afford to make the same mistakes again- easing lockdowns before cases are suppressed. Headlines like these suggest that our govt still doesn't understand this:

We need to work with Europe and coordinate on elimination. There is political will and support for this in parts of Europe now, and a roadmap for this, as outlined in this piece . The govt must change course, and follow.

thelancet.com/journals/lance…

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More from @dgurdasani1

3 Feb
I believe that claims that scientists make need to stand up to scrutiny, especially in the midst of a pandemic, where scientists have an ethical duty to inform accurately. Calling out false claims is not the same as trolling & harassing someone because they disagree with you.
During the past many weeks, I've engaged with scientists when I felt they made claims that were not in line with current evidence. I usually do this by first contacting the scientist directly & discussing why evidence cited may be flawed, &/or providing direct evidence against.
In my experience, this approach has not worked. Inevitably, it has led to people claiming personal attacks, which means they don't have to engage on the evidence. So evidence-based discussions don't happen, and discussions get shut down.
Read 18 tweets
3 Feb
It's being widely reported that 1 dose of the Astra/Oxford vaccine reduces transmission by 67%. My understanding is that this is not what the paper shows, or what the authors have claimed. I'm happy to be corrected if I've got this wrong. Short thread.

theguardian.com/society/2021/f…
The Astra/Oxford trial asked people enrolled to self-swab every week and send in swabs for testing. They also asked them to reach out and get tested if they had symptoms. So all tests carried out are a combination of:
1. asymptomatic testing
2. testing sought due to symptoms
When we break down efficacy by these categories, the trial reports an efficacy of 76% in preventing *disease* (or symptomatic infection) and ~16% efficacy (with a lot of uncertainty due to small numbers) for asymptomatic infection. The combined efficacy for PCR +ves is 67% Image
Read 8 tweets
3 Feb
A thread discussing recent evidence on longer gap dosing with Astra/Oxford, Pfizer, current gaps in our understanding of impacts, as well as the possible impact of new variants on vaccine effectiveness. Thread.
First, I want to say that this although thread may highlight uncertainties & gaps in current evidence I fully advocate taking the vaccine, as this will offer protection. But I also firmly believe that discussing uncertainties in evidence & transparency around data is important.
Astra/Oxford published data yesterday, suggesting that longer gaps between the 1st and 2nd dose may be associated with higher efficacy. Vaccine efficacy between 3-12 wks after a single dose was reported to be 76% with protection being similar throughout this period.
Read 24 tweets
1 Feb
I've recently come across a disinformation around evidence relating to school closures and community transmission that's been platformed prominently. This arises from flawed understanding of the data that underlies this evidence, and the methodologies used in these studies.
Let's look at the paper being cited here. This study published in Nature Human Behaviour examined >50,000 interventions (at fine scale) across >200 countries. The number of countries examined allowed examination of these in depth.

nature.com/articles/s4156…
As the authors state, the key strength of the study is that examination across so many different contexts allowed a disentanglement of interventions. The authors used four approaches, including a case-control analysis to specifically deal with this issue.
Read 13 tweets
30 Jan
These studies are heavily flawed, and are don't include any of the larger, and less biased studies that contradict this view. There are ample studies with larger sample sizes, including from the ONS, that show primary school children play an important role in transmission.
And completely misses the direct impact on children from Long COVID. 12% of primary school children have symptoms lasting > 5 wks. We need to look at this based on the breadth of evidence, and the design of these studies- which unfortunately even many scientists haven't done.
The ECDC paper is extremely flawed, and quotes largely studies from symptom based testing designs, which we know hugely underestimate the impact of children on transmission. And from periods when either community tranmission was low, or school attendance was low in many regions.
Read 8 tweets
26 Jan
On @BBCOS today discussing the tragedy of exceeding 100,000 COVID-19 deaths in the UK, and what led to this.

19:03 for a bit and then 19:23 onwards:
bbc.co.uk/iplayer/live/b…

Also, a few thoughts in a thread below:
The PM said during the briefing today, that the govt did the best they could. He was 'deeply sorry' for every single death.

If every single death is a tragedy, then why didn't we treat every death as preventable?

Why did we repeatedly talk about 'tolerable deaths'?
How on earth can he say he did his best, when UK policy was almost never evidence based - and the govt invited proponents of the ideology of naturally acquired herd immunity to brief him on policy- at a point in time we urgently needed to act to prevent thousands of deaths?
Read 16 tweets

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