Thread by @kakape

A lot to say about AZ vaccine pause in Europe, but I will try to stick to a two key questions in this thread (more later):
1. What are the symptoms that have led to the pause?
2. Is there a plausible mechanism for the vaccine causing them?

Story is here: sciencemag.org/news/2021/03/i…

1. There has been a lot of general talk about blood clots and deep vein thrombosis, but the picture described to @GretchenVogel1 and me by doctors and regulatory agencies is a much more complicated one and based on at least 13 previously healthy individuals from 5 countries.

@GretchenVogel1 Main characteristics seem to be:
- widespread blood clots
- few platelets (thrombocytopenia)
- internal bleeding
- cerebral venous thrombosis

As @steinarma told us: “It’s a very special picture”.

@GretchenVogel1 @steinarma In Germany, at least 7 cases of cerebral venous thrombosis within 4-16 days after vaccination have been reported (and I talked to a doctor treating another such case, which brings it to eight).
@PEI_Germany has stated that it would normally have expected just 1 case.

@GretchenVogel1 @steinarma @PEI_Germany That was enough for @PEI_Germany to bring in an outside group of experts on Monday and they “agreed unanimously that there seemed to be a pattern here and that a link to the vaccine was not implausible and that this should be investigated,” PEI head Klaus Cichutek told me.

@GretchenVogel1 @steinarma @PEI_Germany Now, to be very clear:
We do not know whether this is caused by the vaccine.
Rare medical events happen every day and when you vaccinate a lot, some of them will happen to people who were vaccinated.
And sometimes several rare events happen together, just by chance.

@GretchenVogel1 @steinarma @PEI_Germany But one reasonable question to ask is the second I want to concentrate on:
Is there any plausible mechanism by which a #covid19 vaccine could even cause something like this?
What has become clearer to me through our reporting is that this is not all that implausible.

@GretchenVogel1 @steinarma @PEI_Germany We know that #covid19 leads to clotting disorders in some people.
And this paper showed that #sarscov2’s spike protein can activate an arm of the immune system called the complement system, which then damages blood vessels and leads to clotting: ashpublications.org/blood/article/…

@GretchenVogel1 @steinarma @PEI_Germany What happens?
The virus binds to heparan sulfate on the surface of cells lining blood vessels. That might interfere with a molecule in the complement cascade, Factor H. That then leads to an activation of the complement system, which attacks the blood vessels.

@GretchenVogel1 @steinarma @PEI_Germany (Just realised I made a really stupid mistake, suggesting the AZ vaccine carries the spike on its surface, which, of course, it doesn’t. It just carries the gene for it into the cells it infects.
@nytimes has a nice explanation here for instance: nytimes.com/interactive/20…)

@GretchenVogel1 @steinarma @PEI_Germany @nytimes I probably just shouldn’t tweet this late…
But back to the thread. The question is: Could the AZ vaccine somehow trigger that same or a similar cascade, either through the spike protein whose recipe it carries or even the adenovirus vector itself if it reaches blood vessels?

@GretchenVogel1 @steinarma @PEI_Germany @nytimes One interesting aside here: Some people seem to be particularly prone to this type of complement dysregulation. So you could imagine that they might then be particularly at risk for this kind of reaction to the vaccine, but that they would also be at high risk of severe #covid19.

@GretchenVogel1 @steinarma @PEI_Germany @nytimes Anyway, all of this just to show that some fairly specific symptoms have been observed and that you can kind of see how a link to a #covid19 vaccine is not implausible. All of which makes me understand why the people making the decisions here have taken this so seriously.

@GretchenVogel1 @steinarma @PEI_Germany @nytimes I think the communication has been abysmal (I would have liked to have all this information days ago and publicly available and clearly explained.)
But there is a signal here that warrants investigation.
Was it right to pause vaccinations in the meantime? Debate for another day.

@GretchenVogel1 @steinarma @PEI_Germany @nytimes Most likely scenario to me still seems that we will restart vaccinations with AZ soon, maybe with an extra eye on certain symptoms that could signal a rare side effect.
At this moment in countries like Germany the cost of not vaccinating hundreds of thousands of people is huge.

@GretchenVogel1 @steinarma @PEI_Germany @nytimes Anyway, I hope the article clearly lays out what we know and what we don‘t know.
And thanks to my awesome colleague @GretchenVogel1 and my amazing editor @martinenserink
sciencemag.org/news/2021/03/i…