So where are we on the rare clotting disorder linked to AZ and J&J shots? What do we know? How do risks and benefits compare? What does it mean long-term and around the world?
@GretchenVogel1 and I tried to answer some questions, thread to come in a bit.…
First off:
This is complex and I‘m tired of people pretending it‘s all obvious.

So a few general points about the decisions that have to be made here:
They are
- local, but with global implications
- based on imperfect data in an evolving pandemic
- about individual decisions as well as population-level effects (and these two things can point in opposite directions)
- about rational arguments on risk, when humans are often irrational about risks
- dependent on what alternatives are available
- about perception and politics as well as evidence
- about trust in the processes ensuring vaccine safety as much as trust in one particular vaccine
One more note: After VIPIT, then VITT, the name that seems to be taking hold is TTS (thrombosis with thrombocytopenia syndrome) and I’ll use this from now on.
So let’s take AZ (where we have the most data) and look at population level first:
The rate of #TTS observed in countries seems to be somewhere between 1 in 40,000 vaccinations (Norway, Denmark) and 1 in 150,000 (Sri Lanka).
About 1 in 5 of these patients have died.
The risk of severe #covid19 in the population is clearly higher.
So at a population level the benefits of vaccination with AZ clearly outweigh not vaccinating at all as long as there is transmission.
(Note that this does not apply to say New Zealand which is now using Pfizer)
This is essentially what WHO’s expert group SAGE said recently:

“In countries with ongoing SARS-CoV-2 transmission, the benefit of vaccination in protecting against COVID-19 far outweighs the risks.”…
They did add:
“However, benefit–risk assessments may differ from country to country, and countries should consider their epidemiological situation, individual and population-level risks, availability of other vaccines, and alternate options for risk mitigation.”
Context matters!
It is more complicated when you get to an individual’s benefit-risk assessment.
First, the risk:
While there is uncertainty about the exact frequency of TTS, it’s essentially a fixed number, on the order of somewhere around 1 in 100,000 say.
Can we identify groups that are at higher risk?
Not yet. Researchers say there is no strong evidence that women or men or younger or older people are at a higher risk. Nor is there a sign that a previous history of blood clotting or even HIT increases risk.
What about the benefit of immunization?
That is clearly higher the older someone is and the higher the level of infections around them.
I’ve tweeted graphs from @EMA_News showing how risks and benefits look in different age groups at different infection levels before:
We tried to condense this into two tables in our story, one for low-risk (55 infections per 100,000 people per month), one for high-risk (886 infections) setting.
Numbers are per 100,000 people over 4 weeks:
You can see that in young people the benefits and risks over 4 weeks at low infection levels are not all that different.
Of course, hospitalisations and deaths are not everything. “Don’t underestimate the impact of Long COVID,” for instance, @JeremyFarrar told me.
@JeremyFarrar One way of thinking about the risk-benefit on an individual basis is:
How many weeks of not being vaccinated add up to the same risk of dying from #covid19 as the risk of dying from #TTS when getting the shot?
@JeremyFarrar The answer in Norway, for a woman aged between 45 and 49 years, is 79 weeks, according to @camisto.
So it makes sense for a 45 year old woman to wait one and a half years for a different vaccine.
Remember: Norway has few infections and has seen high levels of #TTS!
@JeremyFarrar @camisto So this an extreme case but it lays out the crux of the problem clearly:
On a population level you want everyone vaccinated asap. But on an individual level for some people in some places it makes absolute sense to wait for a different shot.
@JeremyFarrar @camisto Again: It's about context. In many places waiting for a different vaccine makes little sense.
As @MPaiMD told us: “Crossing the street is a risk. But if there’s a bear running toward you on your side of the street, that risk suddenly looks different. This virus is a bear.”
@JeremyFarrar @camisto @MPaiMD Two things to consider:
1. What happens long-term?
As immunizations ramp up, infections should hopefully go down and more vaccines become available. So over time more and more places will look a bit more like Norway. And so even this very low risk of TTS will loom larger.
@JeremyFarrar @camisto @MPaiMD 2. Global equity
In many places the luxury of different vaccines is a distant dream. Most countries are desperate for any vaccine.
I'll have to tackle what decisions in Europe/US/Canada mean for these countries and for perceptions of vaccine equity in a separate thread.

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More from @kakape

23 Apr
In the US the Advisory Committee on Immunization Practices (ACIP) is meeting at the moment to discuss data on the rare clotting disorders seen after immunization with J&J’s #covid19 vaccine and to make recommendations on future use of the vaccine.
I’ll tweet along a bit.
Outcomes from the rare clotting disorders are likely to improve from "recognition among physicians also recognition in the public that if you develop a severe headache, severe abdominal pain that you really need to see your doctor", says @mstreif1.
@mstreif1 As of 21 April, 15 confirmed cases of the rare clotting disorder (here called TTS, Thrombosis with Thrombocytopenia Syndrome) after about 8 million vaccinations with J&J’s #covid19 vaccine, says @CDCgov's Tom Shimabukuro
Read 50 tweets
23 Apr
So @EMA_News is finally doing some decent communication/visualization of risks/benefits of vaccination with AstraZeneca’s #covid19 shot.

Quick thread with their graphs:
@EMA_News They looked at hospitalisations, ICU admissions and deaths from #covid19 separately.

Also 3 scenarios for monthly infection rates:
low (55 per 100,000 people)
medium (401 per 100,000 people) high (886 per 100,000 people)

Here are the graphs for hospitalisations:
@EMA_News Here are the three graphs for ICU admissions:
Read 8 tweets
20 Apr
“We have now heard of 8 cases of these very rare side effects as part of the rollout in the US, where the vaccine has been given to over 7 million vaccinees”, says EMA head Emer Cooke at press briefing on the safety review of J&J's #covid19 vaccine.
“This is a very rare effect but it also makes it very important for doctors and patients to be aware of the signs so that they can spot any concerns and seek specialist help as soon as possible”, says Cooke. "Early intervention by specialists can change the outcome."
"The scientific assessment that PRAC has concluded on today will allow vaccination programs in member states to take decisions on how to roll out this vaccine based on their national situation” (infections, hospitalizations, ICU admissions, vaccine availability), says Cooke.
Read 18 tweets
16 Apr
Getting a bit annoyed at everyone using numbers from yesterday’s Oxford pre-print to compare how often CVST occurs after mRNA vaccines and AstraZeneca vaccine.
We cannot directly compare these numbers because they came about in completely different ways.
The authors say so themselves IN the preprint:
"we cannot directly compare the risks of CVT associated with ChAdOx1 nCoV-19 with any of the other vaccines, or with COVID-19, since we are using data collected by the EMA monitoring system, not from the electronic health records..."
And yes, @UniofOxford press release does exactly that anyway:
"Compared to the AZ-Oxford vaccine, the risk of a CVT from COVID-19 is about 8 times greater."

This is one reason (of many) why we need science journalists and not just press releases.…
Read 5 tweets
15 Apr
There is an interesting new preprint out that will probably generate a lot of coverage at least in the UK. Essentially it argues that the risk of CVST is much higher from #covid19 than from vaccines.
Quick thread on this:
Here is an image from the paper that is likely to feature heavily in debates around this.
As you can see the risk of CVST here seems to be 8-10 times higher in people with CVST than in people who received mRNA vaccines or AstraZeneca.
BUT: A lot of caveats here.
First of all:
The paper really only makes a like-with-like comparison with mRNA vaccines (as authors pointed out in presser this morning too: “I think our data say actually nothing about the AZ vaccine.”).
That’s why the data on AstraZeneca is greyed out in that graph.
Read 11 tweets
14 Apr
Most fascinating bit of ACIP meeting so far is a detail on the 25-year old male in J&J trial, who developed CVST with hemorrhage after 8 days.
J&J representative says it was retrospectively determined that he was negative for anti-PF4 antibodies before vaccination, positive after
Case reports are fascinating.
Here are some details on the case from previous tweet.
(Short sentence on anti-PF4 antibodies is a bit misleading here: he was negative at baseline, positive post-vaccination according to the presentation)
Helpful timeline here:
Read 36 tweets

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