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Vincent Rajkumar Profile picture
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11 Apr, 13 tweets, 4 min read
Astra Zeneca vaccine & blood clots. Summary.

Rare form of blood clots plus low platelets. ~60% involve veins of brain. Almost all after 1st dose.

Risk (UK MHRA): 1 in 250,000 people
Risk (EU EMA): 1 in 100,000 people

Risk of dying: 20-25% of people with these clots have died
Approximately half of the deaths in the UK (11 of 19) were under age 50.

The benefits of the Astra Zeneca vaccine according to regulators appear to outweigh risks in all except those less than age 30. bmj.com/content/373/bm…
While blood clots occur at a certain rate in population what is unusual about these clots is the association with low platelets. Platelets help make blood clots & when platelets are low we are at risk of bleeding not clotting.

Low platelets in context of blood clots is unusual.
This type of combination of low platelets and blood clots occurs in unique conditions in medicine: some patients exposed to heparin. It can also occur with hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, and sometimes with antiphospholipid antibody syndrome.
It is the unusual location (veins of brain and veins draining the bowel) and the occurrence in conjunction with low platelets that makes these vaccine related clots suspicious for a true association. And a scientific puzzle.
There is new data emerging that the mechanism of the clots may involve antibodies generated (presumably by the vaccine) that target platelet factor 4 (PF4), similar to the process that happens in some people after exposure to heparin. @NEJM nejm.org/doi/full/10.10…
Similar findings were also reported in a separate case series.

In both series all patients had antibodies to PF4. @NEJM

nejm.org/doi/full/10.10…
Knowing the mechanism has significant implications:

-we may be able to identify who is at risk
-potentially develop a screening test to identity people who should get a different vaccine than Astra Zeneca
-monitor for and treat clots better to prevent deaths.

Making progress
Note that the Astra Zeneca vaccine is not approved in the US. But it is one of the most important vaccines for most of the world. As such the risk benefit decisions made by regulators in each country & how they are clearly communicated to their citizens is incredibly important.
Since COVID itself has been associated with blood clots as well as central venous sinus thrombosis (see below), it is possible that antibodies we generate against the spike protein (natural infection or vaccine) cross reacts with PF4. Hope we have data on precise mechanisms soon.
Why this occurs with Astra Zeneca and not with Pfizer/ Moderna is unclear and may be related to the specific epitopes involved.
For those interested in other mechanisms hypothesized by authors of the @NEJM papers are:

1) The strong immune response triggered by vaccine may lead to formation of autoimmune antibodies to PF4
2) Free DNA in vaccine forms immunogenic multimolecular complex with PF4

#VITT
Linking to today's news that the FDA is recommending a pause on another adenoviral vector based COVID vaccine: the J&J vaccine. Also related to unusual blood clots in young women. (6 events reported out of about 7 million people who have received the vaccine in the US).

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More from @VincentRK

Vincent Rajkumar Profile picture
10 Apr
If we have more COVID vaccines than people, but cannot get to herd immunity due to vaccine hesitancy then we have messed up the messaging.

The message should be clear and should come from every leader in the country.
How effective are the vaccines?
Forget who did what wrong on the messaging. Just focus on the messages going forward.

Don't get stuck in debates of whether vaccines prevent transmission. They do reduce transmission dramatically. (It's will also be a largely moot question once 80% have been vaccinated).
Read 4 tweets
Vincent Rajkumar Profile picture
8 Apr
Mortality rate of symptomatic COVID when healthcare system was overwhelmed early on (as in Italy, Spain, Belgium, & parts of the US) was incredibly high. As we flattened the curve & learnt to treat, the rate reduced to 2-3%.

cf. Australia didn't get overwhelmed. @OurWorldInData
It is indeed remarkable how across the world the mortality rate of confirmed, presumably symptomatic, COVID has coalesced to around 2-3%.
Although with improvements in treatment, mortality rates of symptomatic COVID may be lower that what we saw early last year in places that got overwhelmed, no country should be in a situation where the healthcare system is overwhelmed. That leads to much higher loss of life.
Read 5 tweets
Vincent Rajkumar Profile picture
7 Apr
570,000 Americans have died due to COVID.

Even if we assume every single American has already had COVID, the lowest possible infection fatality rate (IFR) is 0.17%.

The true IFR is likely ~0.5%.
This is similar to what I had estimated a year ago.

In symptomatic people with confirmed COVID, the mortality rate is ~2%.
IFR can vary: by population characteristics, time period, availability of treatments, health system capabilities, etc.

But the death rate in the US, 1700 deaths per million, shows how devastating COVID can be in a rich country with supposedly the best healthcare resources of any
Read 5 tweets
Vincent Rajkumar Profile picture
4 Apr
Few places in the world have suffered more losses from COVID than New York.

4 factors for disconnect below in cases and deaths:

-Health system not overwhelmed
-Better treatments
-More testing = milder cases detected
-Some are mild reinfections in people who already had COVID
One reason why I think immunity is playing a role is that the reduction in deaths with second wave seems to depend on how high the first wave was.
It's a complicated argument, but my summary after looking at this is that undiagnosed reinfections probably exist quite a bit more than we initially thought but they do not have the natural history of COVID for the first time: Much milder due to better prepared immune system.
Read 4 tweets
Vincent Rajkumar Profile picture
3 Apr
From Feb 1, the date COVID vaccine effect probably started: Israel provides a preview into what can happen in the US as we race to get 80% of eligible public vaccinated.

Deaths and hospitalizations eventually will be driven by cases in unvaccinated adults.
Deaths in the US have resumed their downward trend after a brief plateau. I hope this continues. Metrics of vaccine success to track will be hospitalizations, ICU admissions, and deaths.
I'm saying 80% of the eligible public as target for herd immunity as opposed to 80% of the whole country because while we are not vaccinating kids, we also do have at least 10% of the population who have had confirmed COVID and at least another 10% who have had undiagnosed COVID.
Read 4 tweets
Vincent Rajkumar Profile picture
1 Apr
How long will protection from COVID vaccines last?

If you are going by lab studies & antibody levels: Few months

If you are going based what we know about the immune system, and in terms of ability to prevent serious disease & deaths: Years or decades.

That's my opinion FWIW.
The big unknown is the ability of the virus to mutate to a variant that is both more infectious and more lethal while being different enough to evade vaccine generated immune response.

The reason I'm not alarmed by this prospect is the natural redundancy of the immune response.
Of course no one can know for sure, only time will tell. Whatever you hear is one persons opinion versus the other. No more, no less.

Again I'm using metrics of ability to prevent serious disease and deaths. Not any infection.
Read 5 tweets

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