BC GOVERNMENT
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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.
This meant the 2nd dose was added months after the start of the trial. Because of the nature of the trial- younger people recruited into the trial first & older people recruited once it was decided that 2 doses should be used, younger participants were given the 2nd dose later.
To complicate matters there was an error early in the trial which meant that ~1,400 participants were given a low 1st dose by mistake. Given the first tranche of participants were <55 years, the low dose (1st dose)/standard dose (2nd dose) combination was only used in this group
So approximately 42% of participants <55 yrs had the lowdose/standard dose (LD/SD) combination, and all the older ones had the SD/SD combination. And the gap between doses was higher among <55 yr olds vs >55 yr olds, although I couldn't find the breakdown of this in the paper.
The efficacy results that are reported suggest an efficacy of ~60% in reducing disease for the SD/SD group, and ~90% for the LD/SD group. What is less clear is whether these differences are due to the lower first dose, younger participants, or longer gaps between doses.
So let's look at efficacy by age group and dose.
Vaccine efficacy among 18-55 yr olds SD/SD dosing was 59% vs LD/SD dosing at 90%.

Is this due to dosing, or differences in gaps between doses?
Differences in gaps don't appear to impact efficacy in this analysis.
Of course we can't evaluate this in ages >55 as they only had a short gap in dosing. So we don't have any data on longer gaps in >55 yr olds, at least in the data that are public.
I have seen reports that unpublished data support longer gaps between doses. But without seeing the data, I can't evaluate the basis for this. Presumably MHRA has evaluated the evidence before granting approval for the current dosage protocol.

https://t.co/9yaSAyHcKR
What about the efficacy after the first dose?
It looks like the first dose prevented all severe disease (although numbers were small) in the SARS-CoV-2 vaccine group compared to vaccine control after the first 21 days of vaccination, and <14 days after the 2nd dose.
SUMMARY: the Oxford/Astra trial examined dosing with gaps between 4-12 wks- although longer gaps appear to be limited mostly to younger participants. There was no difference reported in published data between these & efficacy from the 1st dose seems high for severe disease.
Given this, I can understand the plan for longer dosing gaps for this vaccine, although I do think that it's important that the unpublished data that support this are released for transparency & to build public trust which is essential at this point.
The application of the same principle to the Pfizer/BioNtech vaccine is more difficult to evaluate. This vaccine was studied with a strict protocol of 21 days between doses & the company has since issued a warning that they cannot ensure efficacy if protocol is changed
While the Pfizer trial shows reasonably high efficacy after the 1st dose of vaccine (~80%), the duration of this following 21 days is unclear. So there is a risk that this level may decline after this period, as we don't have direct data on this from trials.
However, there are also arguments for the approach the govt is taking, as outlined below. Essentially the thinking is that given the urgency, roll-out across double the numbers with 80% efficacy is better than rolling out half numbers with 95% efficacy.

https://t.co/966V4EYw13
The assumptions key to this argument are of course that:
1. Resources for roll-out are limited & fixed & we need to optimise how best to use them within limitations
2. There isn't significant decline in immunity after the 3 wk mark
3. Later dosing will not affect overall efficacy
I'm not a vaccinology expert so can't really comment on 2. and 3. From reading views from other experts, the general view seems to be that later dosing is unlikely to impact overall efficacy. What level of immunity lasts up to 12 weeks is less clear, I think.
I'm also not entirely clear about the impact of a longer period of partial immunity (if immunity declines following 3 wks) on viral adaptation. I know some experts have raised concerns about this. I think this is dependent on how much immunity declines prior to the 2nd dose.
Given a lot of this is conjecture, it's hard to know whether this is the right strategy for the Pfizer vaccine. I am naturally cautious about changing a protocol that's tried & tested to one where we don't have data on, particularly given the warnings issued by Pfizer.
I'm also concerned by the poor planning around this. Given these data were available for a while, it's not clear to me why this decision was made now, when hundreds of thousands have had their second appts booked in. Cancelling these is also time-consuming & undermines trust.
Irrespective of how and why the MHRA approved this, I think it's important to release the thinking & the data around it - to create transparency & build trust with the public, and with health-care workers. It's very clear that HCWs were not consulted in this, which led to chaos.
Such actions really risk undermining public trust, when it's already very low. We are counting on high vaccine uptake to be able to contain the pandemic - we can't afford to not take the public along on decisions such as this. Good communication & transparency is key.
Given the urgency of vaccine roll-out now, these are complex decisions. While there may be good scientific reasons for which these decisions have been made, it's important that these reasons are made clear & the public and HCWs are engaged in this decision-making process.
Just wanted to highlight one last point- it looks like the govt have released a document around this today.

A key part of the rationale appears to be a bottleneck in vaccine supply (rather than roll-out).

https://t.co/mccavkBGeb

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Deepti Gurdasani
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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
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Deepti Gurdasani
Deepti Gurdasani
@dgurdasani1
Thread on the recent report on the possible risk of increased death associated with the new UK variant (B117)- with a discussion of the evidence around this, and what this means.

First, there is strong evidence to support increased transmissibility of B117 - current estimates of increased transmissibility range between 30-70% - from epidemiological evidence examining the differential rate of growth of B117 with respect to other variants & increase in R

There is also evidence from PHE contact studies that the risk of transmission from those carrying the B117 variant is ~50% greater than with other non-B117 variants.

Increased transmissibility, even if a variant has the same fatality rate can increase deaths substantially, because the rate of growth of cases is higher- & more cases means more deaths.

Increased fatality rates also increase deaths- but do so


So how was risk of death with the variant studied?
We don't routinely sequence all samples for the virus. We've found that the variant has a particular deletion which means that some PCR tests on samples with the variant give a different read-out when the variant is present.
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Deepti Gurdasani
Deepti Gurdasani
@dgurdasani1
We've been falsely told 'schools are safe', 'don't drive community transmission', & teachers don't have a higher risk of infection repeatedly by govt & their advisors- to justify some of the most negligent policies in history. 🧵


data shows *both* primary & secondary school teachers are at double the risk of confirmed infection relative to comparable positivity in the general population. ONS household infection data also clearly show that children are important sources of transmission.

Yet, in the parliamentary select meeting today, witnesses like Jenny Harries repeated the same claims- that have been debunked by the ONS data, and the data released by the @educationgovuk today. How many lives have been lost to these lies? How many more people have long COVID?

has repeatedly pointed out errors & gaps in the ONS reporting of evidence around risk of infection among teachers- and it's taken *months* to get clarity on this. The released data are a result of months of campaigning by her, the @NEU and others.

Rather than being transparent about the risk of transmission in school settings & mitigating this, the govt (& many of its advisors) has engaged in dismissing & denying evidence that's been clear for a while. Evidence from the govt's own surveys. And global evidence.

Why?
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Deepti Gurdasani
Deepti Gurdasani
@dgurdasani1
Brief thread to debunk the repeated claims we hear about transmission not happening 'within school walls', infection in school children being 'a reflection of infection from the community', and 'primary school children less likely to get infected and contribute to transmission'.

I've heard a lot of scientists claim these three - including most recently the chief advisor to the CDC, where the claim that most transmission doesn't happen within the walls of schools. There is strong evidence to rebut this claim. Let's look at


Let's look at the trends of infection in different age groups in England first- as reported by the ONS. Being a random survey of infection in the community, this doesn't suffer from the biases of symptom-based testing, particularly important in children who are often asymptomatic

A few things to note:
1. The infection rates among primary & secondary school children closely follow school openings, closures & levels of attendance. E.g. We see a dip in infections following Oct half-term, followed by a rise after school reopening.


We see steep drops in both primary & secondary school groups after end of term (18th December), but these drops plateau out in primary school children, where attendance has been >20% after re-opening in January (by contrast with 2ndary schools where this is ~5%).
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Deepti Gurdasani
Deepti Gurdasani
@dgurdasani1
This is the exact problem with our government's thinking & response- despite this strategy of 'tolerating deaths' and half-way measures having spectacularly failed, it's quite amazing that our govt still hasn't learned anything, & continues to promote a policy of death. Thread


Had we adopted an elimination strategy early on, rather than one of tolerating a certain level of infection, we wouldn't be here now. The reason we're here is because the govt never committed to elimination.

We eased lockdown in May when infection levels were much higher than when other countries in Europe did this. The govt was warned about this, but did this to 'help the economy'. Not only did this lead us into the 2nd wave, the need for further lockdowns harmed the economy further

It's very clear from global evidence that we cannot 'tolerate a level of community transmission' and maintain 'R at or just below 1', which has been our governments policy for a long time. This isn't sustainable & very rapidly gets out of control, leading to exponential rises

Coupled with late action to contain these surges, not only does this lead to many more deaths, and much more morbidity with Long COVID, it also creates a fertile ground for viral mutations to accumulate with a greater risk of adaptation, which is exactly what happened in the UK
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First, it helps to know where we are in the budget process. From today through Feb. 24, the council will meet about the General Fund budget. The council will then agree on a budget with their changes (if any); 15 days after doing so, they can vote to make the budget official.


In other words, there’s still time to use your voice! The #refundcleveland tool can help. Create the #CLEBudget you want and send it to your council member. Click “Change the Budget” on the homepage and follow the on-screen instructions from there.

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And don’t forget: all these meetings are livestreamed on City Council’s YouTube channel. They’re slated to start at 9 a.m. every business day from today through the 24th. You can also follow along with #CLEDocumenters live-tweet threads and
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[thread] on a suggestion of a speech at the last

and how to vote for this deal on 30th December 2020

Mr Speaker

May I congratulate Boris Johnson

Truly

He is our Lion King as Robert Halfon calls him

Our herd leader with his massive success of coronavirus where as Priti Patel says we have always been ahead of the curve.

A Prime Minister whose achievements will go down in the annals of British history in infamy.

The focus of my speech shall be three pillars.

How did you win?

What did you win?

Where do we go from here?

But first I want to change tack and go to what I know is a favourite topic of the Prime Minister's: American Presidents.

I Know the Prime Minister has a deep ancestral hatred - sorry respect - for American Presidents.

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As our national civics lesson continues to unfold on its march toward our 59th Presidential Inauguration on January 20, 2021 and Donald Trump’s second term, 45’s unmasking exercise (that’s a large part of what his first term had to be) continues toward its big climax.

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In his 2017 Inaugural Address, President Trump proclaimed on behalf of his administration, “we are transferring power from Washington, D.C., and giving it back to you, the people.”

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From my very biased vantage point, here’s how I like to think of that sentence.

It likely was the announcement of his two-pronged military campaign.

The first prong is obvious; it’s against foreign interference.

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As we now clearly see, nothing short of a military campaign would suffice when global influencers have totally co-opted elements of our two major political parties.

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The other prong has an internal focus: Washington, D.C.
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I know you’ve all been waiting for my thread on today’s @DHSCgovuk White Paper https://t.co/lrNsuFoCum
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3/9 Very pleased to see issues core to @RichmondGroup14 priorities at the centre of the challenges the White Paper aims to address: namely the growing needs of people with long-term and multiple conditions, the role of mental health in that mix and the impact of Covid on that.


4/9 White Paper rightly acknowledges that a new legal framework is a necessary but not a sufficient condition for integration and improvement. Culture, behaviour, relationships and leadership will be what make the most difference, though a better governance platform will help.


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Today, if Johnson bothers to show up for the impeachment trial, he’ll hear a flimsy defense of the indefensible. Then he faces an existential, character-defining choice: Country and Constitution, or party and personal power. We have a guess. But first, let’s review some clues.

Just a couple of days before the impeachment trial began, Ron Johnson said that there was “no reason” to hold the trial—and that barring Trump from ever holding federal public office again would “pre-emptively” disenfranchise people.

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He went on Fox News to claim there was voter fraud, that “millions of Americans have suspicions,” and made accusations about the validity of absentee

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