I have previously written about whether thrombosis (formation of blood clots) is linked to the AstraZeneca COVID-19 vaccine – my conclusion was that they probably weren’t. But still, there are nagging anecdotes and government decisions that may concern those of you who are looking to get the vaccine.
Recently, the government of Quebec recently decided that the AstraZeneca vaccine will only be used on individuals 55 years and older. Of course, this caused some parts of the anti-vaccine world to froth at the mouth claiming the vaccine isn’t safe.
I think that many of the adverse events that are claimed to be associated with any of the COVID-19 vaccines involve the post hoc ergo propter hoc fallacy, which states that because one event precedes another event, they must be linked. It is entirely possible that thrombosis occurs after vaccinations because of random chance rather than actual correlation (let alone causation).
Because the AstraZeneca COVID-19 vaccine is one of the four main vaccines (along with those from Pfizer, Moderna, and JNJ) to be given in the USA, Canada, the EU, Australia, and New Zealand, I want to make sure that the potential of a causal link to thrombosis events are given a thorough analysis. I especially want to focus on why the Government of Quebec decided to make this change – and it’s a lot more complicated than the narratives pushed by the anti-vaccine crowd.
What is the AstraZeneca vaccine?
The AstraZeneca COVID-19 vaccine is very different than the Pfizer and Moderna mRNA vaccines but is similar to the JNJ vaccine. The vaccine still induces an adaptive immune memory response to the S-protein of the SARS-CoV-2 virus which causes COVID-19.
The AstraZeneca COVID-19 vaccine utilizes a recombined adenovirus vector, chimpanzee ChAdOx1, which causes the production of the S-subunit of the SARS-CoV-2 virus which induces an immune response to that S-subunit. Basically, the adenovirus vector “carries” the genes for the S-subunit to the cell which will reproduce the protein, then inducing the immune response.
Adenovirus-based vaccines have been investigated for several decades. In fact, JNJ has received approval for an Ebola adenovirus vaccine in July 2020, so the technology did not just appear suddenly to be used to fight COVID-19-19. However, like the mRNA vaccines, these adenovirus vaccines, also used by JNJ, can be quickly developed to deliver the most important antigen on the SARS-CoV-2 virus, which is the S-protein.
There is an advantage to adenovirus-based vaccines – they are much less fragile than mRNA vaccines because they are based on DNA which is more rugged than RNA.
Once the AstraZeneca vaccine is injected into the arm, the adenoviruses enter cells and moves to the nucleus, where the cell’s genes (DNA) are located.
The adenovirus then injects its DNA into the nucleus. The adenovirus is engineered so it can’t make copies of itself, but the gene for the coronavirus spike protein can be read by the cell and copied into a molecule called messenger RNA, or mRNA.
At this point, it is similar to the mRNA vaccines.
Normally, during the process called transcription, RNA polymerase makes a copy of a gene from its DNA to a corresponding mRNA fragment whenever required by the cell. In other words, the mRNA sequences in the cell usually correspond directly to the DNA sequences in our genes. These mRNA sequences “carry” that genetic message to a ribosome for translation, where tRNA triplets, which code for one amino acid, attach to the appropriate mRNA triplet, adding one amino acid to the protein chain.
As in DNA, genetic information in mRNA is contained in the sequence of nucleotides, which are arranged into codons consisting of three ribonucleotides each. Each codon codes for a specific amino acid, except the stop codons, which terminate protein synthesis.
Like with mRNA vaccines, the adenovirus does not change the genetic code of any of the 50 trillion cells that are in a human. All that happens is that the adenovirus injects DNA that is coded for the S-protein and the cell produces mRNA from that DNA that then causes the ribosomes to produce the S-protein.
Those S-proteins migrate to the surface of the cell which is then recognized by the immune system as foreign invaders. The immune system then remembers those antigens – when the actual SARS-CoV-2 virus attacks, the immune system is ready to attack.
The AstraZeneca COVID-19 vaccine also has one additional advantage over the mRNA vaccines – the adenovirus itself provokes the immune system to activate immune cells that are nearby. This leads to the immune system reacting more strongly to the spike proteins.
The AstraZeneca COVID-19 vaccine and clots – observations
The European Medicines Agency (or EMA, which functions as the FDA for the European Union) reported that of the 20 million people vaccinated with the AstraZeneca COVID-19 vaccine (as of 18 March 2021), there were only 25 cases of reported blood clotting events. The EMA concluded that “a causal link with the vaccine is not proven, but is possible and deserves further analysis.”
To put this into some perspective, let’s do the basic math. The risk of these thromboembolic events is around 1.25 per 1 million people given the AstraZeneca COVID-19 vaccine. And the risk of death from COVID-19 is around 1-2 per 100, over 10,000X greater risk than the risk of thrombus (if it exists) from the vaccine.
Further, we have no information about potential comorbidities that may have been the causal factor for clots or potentially increasing the risk of clots from the vaccine.
This compares to the overall risk of these blood clot events which is about 1 in 1000 in the general population, substantially higher than the “risk” after the AstraZeneca COVID-19 vaccine. I’m not saying that getting the vaccine prevents blood clots, but a bad use of statistics would lead one to such a conclusion.
Furthermore, the large, well-controlled clinical trials for the AstraZeneca and JNJ (which is also based on adenovirus vector technology) have not shown any increased risk for blood clots.
Yes, the SARS-CoV-2 virus seems to cause thrombi in many patients, which might lead one to believe that there is some biological plausibility to the blood clot issue. However, no live virus is used in the Pfizer, Moderna, JNJ, and AstraZeneca vaccines. All four of these vaccines induce the production of one small part of the virus, the spike protein, for a limited time. A real infection by SARS-CoV-2 will have billions of viruses all replicating and causing havoc to the body.
Right now, the risk of thrombus after receiving the AstraZeneca COVID-19 vaccine is no worse than the risk of thrombosis in a population of unvaccinated individuals. And it is a whole lot less risky than the risk of death from COVID-19 itself.
AstraZeneca COVID-19 vaccine thrombosis issues
However, more data is coming out about certain thrombosis events that may make me take a backward step in any endorsement of the AstraZeneca COVID-19 vaccine.
As I mentioned above, the government of Québec has stopped using the AstraZeneca COVID-19 vaccine for those 55 and under, pending further investigation about whether it causes thrombus. They are following the Canadian guidelines regarding this issue, especially since the US Government has decided to provide this vaccine to Canada and Mexico.
The government of Canada stated that:
This adverse event is being referred to as Vaccine-Induced Prothrombotic Immune Thrombocytopenia (VIPIT). This entity is associated with the development of antibodies that “activate” platelets, which stimulate the formation of clots and result in thrombocytopenia. The mechanism of action is similar to heparin-induced thrombocytopenia (HIT). The exact mechanism by which the AstraZeneca vaccine triggers VIPIT is still under investigation. At this time, no other risk factors have consistently been identified in patients who develop VIPIT. This adverse event has not been identified following receipt of mRNA COVID-19 vaccines to date.
And after new data showed a slight increase in the risk of sinus vein thrombosis (SVT), a very rare thromboembolic event, health authorities in various German states made the decision to temporarily halt vaccinations for younger people after receiving more data about these clots.
The Paul Ehrlich Institute said a total of 31 SVT events were reported by March 29 out of some 2.7 million doses of the AstraZeneca COVID-19 vaccine that have been administered across the whole of Germany. Nine of the people died and all but two of the cases involved women, who were aged 20 to 63, it said.
The Institute also reported:
…experts of the Paul-Ehrlich-Institut now see a striking accumulation of a special form of very rare cerebral vein thrombosis (sinus vein thrombosis) in connection with a deficiency of blood platelets (thrombocytopenia) and bleeding in temporal proximity to vaccinations with the COVID-19 vaccine AstraZeneca.
Summary
Of course, regulatory authorities, public health organizations, AstraZeneca, and others will not ignore this, and they will all work together to investigate whether there is an actual link between thrombosis events and the AstraZeneca COVID-19 vaccine.
Admittedly, I am deeply troubled by the data out of Germany that shows a strong correlation with sinus vein thrombosis with the vaccine, especially in some women.
If this link is supported by more data in more countries (observations in one country can be affected by all kinds of bias), then AstraZeneca must be transparent in what is being observed and give warnings to healthcare workers to prepare for it.
Do I distrust AstraZeneca? I am getting really close to that. With their massive issues with their clinical trial design (which would not have any impact on safety just effectiveness), the issues with clotting, and their lack of an application to the Food and Drug Administration for an Emergency Use Authorization, I’m moving from a lukewarm supporter of this vaccine to stating that a lot more research needs to be done and fast.
All vaccines have some risks, almost always very minor ones – anti-vaxxers frequently fail to understand the vaccine risk-benefit equation by rounding up rare events to 100% and rounding down effectiveness to 0%. This is a perfect example of the Nirvana fallacy, which states that if something isn’t perfect, it’s crap.
But this is a serious risk, so despite the effectiveness of the vaccine, public health authorities and governments need to weigh that risk with the benefits to their country in reducing COVID-19.
Right now, there are three other very effective and very safe vaccines from Pfizer, Moderna, and JNJ that will do the job. Now, some parts of the world may have bungled their vaccine rollout, so the AstraZeneca vaccine is the only choice.
Would I get the vaccine? No, unless there were no choices. The risk of these thrombosis events after receiving the AstraZeneca COVID-19 vaccine is just high enough that I’d rather get the other COVID-19 vaccines. But if there is no choice, I would be fine with the AstraZeneca version. But, I’m still troubled by AstraZeneca’s actions throughout this process.
Finally, the anti-vaxxers are going to claim that this 1 in a million risk means that all vaccines are bad. No it doesn’t, it only shows that science is damn good at finding causation and correlation. Instead of scaring people about this vaccine, they should feel great comfort that science and medicine are constantly self-correcting when new data is available.
But for now, even though the risk is small and we cannot determine causality, I think in the abundance of caution, governments are doing the right thing.
Citations
- Cushman M. Epidemiology and risk factors for venous thrombosis. Semin Hematol. 2007 Apr;44(2):62-9. doi: 10.1053/j.seminhematol.2007.02.004. PMID: 17433897; PMCID: PMC2020806.
- Moll S, Waldron B. Cerebral and sinus vein thrombosis. Circulation. 2014 Aug 19;130(8):e68-70. doi: 10.1161/CIRCULATIONAHA.113.008018. PMID: 25135131.
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