A rare form of a blood clotting disorder called cerebral venous sinus thrombosis started to rise among recipients of the AstraZeneca and Johnson and Johnson (Janssen) COVID vaccines.
What is the cerebral venous system?
Blood and cerebrospinal fluid are drained from the brain by the cerebral venous system. Let’s call it CVS for now to shorten it. They can be found in the dura mater surrounding the brain and shown as blue in the image below.
Rarely, blood clots or thromboses can form in the CVS, creating a condition called cerebral venous system thrombosis or CVST.
Having a CVST is terrible. The blood clot blocks the blood flow and pressure inside the veins increases. Then it ruptures, and the patient gets an intracranial hemorrhage and can die. CVST has a high mortality rate of 47%. If two people have CVST. One dies.
One reason for the high mortality rate is a delay in diagnosis. CVST usually presents as headache, blurred vision, or fainting. If that person goes to an emergency room or urgent care and is seen by someone who has a low suspicion of CVST, they may only do a non-contrast or “dry” CT scan or the head, which may or may not show the CVST, especially if it has not yet bled.
The definitive imaging to diagnose the CVST are Magnetic Resonance Imaging (MRI) or Digital Subtraction Angiography (DSA) of the brain. Both take longer to do and are not usually done in urgent care or a busy emergency department. It can be done if the attending physician is astute enough to suspect a CSVT based on the history and risk factors (like pregnancy, obesity, or a recent COVID shot.
A CSVT patient with “negative” imaging will be sent home but will eventually return with a brain bleed.
CVST and COVID shots
This year there is an increase of CVST among people who got the AstraZeneca (AZ) (ChAdOx1 or AZD1222, Vaxzevria) and the Johnson and Johnson J&J – Janssen (Ad26.COV2.S).
These CVST cases have been described in several peer-reviewed journals like the European Journal of Neurology (213 cases), The Lancet (95 patients), The Journal of the American Medical Association (116 patients), and Frontiers in Neurology (two patients). The mRNA shots like the Pfizer and Moderna can also cause CSVT to a much lower extent.
If you search, cvst post covid vaccine NCBI in duck duck go. Bear in mind that CVSTs are probably underreported due to the reasons I mentioned, and thus the numbers can be higher.
All of them have thrombocytopenia, or very low platelet counts too. Platelets are involved in the formation of blood clots.
The commonality between the AstraZeneca and J&J shots is that they are both vector-based or recombinant vaccines.
What is a vector-based vaccine?
A vector-based vaccine is also called a recombinant vaccine. The part of the SARS-CoV-2 virus that elicits an immune response, the spike protein, is combined with another virus known to infect humans. In this case, the adenovirus. The adenovirus is the vector.
Examples of Vector-Based vaccines
- The Oxford-AstraZeneca ChAdOx1 or AZD1222/Vaxzevria uses a chimpanzee adenovirus vector.
- In India, it is known as Covishield.
- Ad26.COV2.S from Janssen and Johnson and Johnson uses adenovirus type 26.
- Convidecia or AD5-nCOV is a single-dose and developed by CanSino Biologics. AD5-nCOV uses adenovirus type 5.
Why did they have to combine them?
The SARS-CoV-2, the cause of COVID-19 is an RNA virus. The part of the virus used to make the vaccine is the spike protein RNA. However, RNA is delicate and easily destroyed. If RNA is injected into people, it won’t work. That is why the Pfizer and Moderna shots are coated in fat to protect the spike RNA.
In recombinant COVID shots, the spike protein RNA is changed to DNA and attached to the DNA of an adenovirus.
Below is a representation of the spike protein and adenovirus DNA. The ACE2 is the part of the spike protein that attaches to human cells.
After injection, the recombinant shot goes inside the cell nucleus, and the spike DNA undergoes a critical transformation to RNA again.
Changing the spike DNA to RNA again is vital because the RNA has to go outside the nucleus of the cells to be translated into spike proteins.
The spike proteins are the ones that elicit the immune response. The formation of the spike protein happens in the cytoplasm of the cell.
Below is a cell showing the cytosol or cytoplasm labeled faintly as 11 on the left side and the nucleus as the large purple ball on the right marked 2.
Why do Blood clots form with recombinant shots
The reason why blood clots form can be traced to when the Spike DNA is converted back to RNA inside the nucleus. The spike RNA has to be reassembled correctly. If errors occur during the RNA formation, different spike protein variants can form in the cytoplasm.
The figure below shows the desired spike protein on the topmost with a sequence for the ACE2 receptor(1). Undesired spike variants are below it.
The spike variants may be too short (2), not have the ACE2 sites (3), or have other unwanted RNAs(4).
The ideal spike protein can interact with the immune system and elicit an immune response like antibodies, which we want. However, the undesired spike variants stimulate blood clot formation.
The left lower part of the image below shows the spike proteins in the middle (orange bars with blue) and the resulting immune responses.
Desired spike proteins go to the outer surface of cells (membrane-bound) and stay there and get the targeted immune response.
However, the spike protein variants are soluble and travel in the bloodstream. If they stick to the inner lining of blood vessels, they stimulate an immune reaction leading to inflammation and blood clot formations in different parts of the body, like the brain’s cerebral venous system (CSV).
Vaccine-induced low platelets
The study also answered another question. Why are the platelets low? Isn’t it that platelets are needed to produce blood clots?
The adenovirus proteins and their DNA can stimulate the formation of antibodies towards platelet factor 4. These autoantibodies bind platelets together and lower their number. That condition is now called Vaccine-Induced Thrombotic Thrombocytopenia or VITT.
Those results are from a German study “Vaccine-Induced Covid-19 Mimicry” Syndrome: Splice reactions within the SARS-CoV-2 Spike open reading frame result in Spike protein variants that may cause thromboembolic events in patients immunized with vector-based vaccines that is available as a preprint. [1]
The research was done by scientists from the Goethe University of Frankfurt and the Department of Gene Therapy of Ulm University.
The authors explained that the veins in the CSV do not have valves like in other parts of the body. This makes the blood stay there longer, produces more significant inflammation, and makes it more prone to develop blood clots.
More CSVT cases in the young compared to the older age group
CVST is more common in younger people since they mount a more significant immune response compared to the elderly.
Many older adults are also on blood thinners like aspirin and warfarin for other medical conditions which prevent clot formation.
In summary, vector-based vaccines can produce variant spike proteins that travel in the bloodstream and form blood clots.
If you are still thinking of getting jabbed after reading this, you should read, Know the Signs of Vaccine-Induced Blood Clotting.
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References:
- Kowarz E, Krutzke L, Reis J, et al. “Vaccine-Induced Covid-19 Mimicry” Syndrome: Splice reactions within the SARS-CoV-2 Spike open reading frame result in Spike protein variants that may cause thromboembolic events in patients immunized with vector-based vaccines. Research Square; 2021. DOI: 10.21203/rs.3.rs-558954/v1
- Perry et al. Cerebral venous thrombosis after vaccination against COVID-19 in the UK: a multicentre cohort study. Lancet Aug 06, 2021, DOI:https://doi.org/10.1016/S0140-6736(21)01608-1.
- Sánchez van Kammen et al. Characteristics and Outcomes of Patients With Cerebral Venous Sinus Thrombosis in SARS-CoV-2 Vaccine-Induced Immune Thrombotic Thrombocytopenia. JAMA Neurol. 2021;78(11):1314–1323. doi:10.1001/jamaneurol.2021.3619
- Krzywicka et al. Post-SARS-CoV-2-vaccination cerebral venous sinus thrombosis: an analysis of cases notified to the European Medicines Agency. Eur J Neurol. 2021 Nov;28(11):3656-3662. doi: 10.1111/ene.15029. Epub 2021 Aug 04. PMID: 34293217; PMCID: PMC8444640.
- Braun et al. Case Report: Take a Second Look: Covid-19 Vaccination-Related Cerebral Venous Thrombosis and Thrombotic Thrombocytopenia Syndrome. Front Neurol. 2021;12:763049. Published 2021 Nov 22. doi:10.3389/fneur.2021.763049
- Tsilingiris D, et al. Vaccine-induced thrombotic thrombocytopenia: The shady chapter of a success story. Metabol Open. 2021 Sep;11:100101. doi: 10.1016/j.metop.2021.100101. Epub 2021 Jun 18. PMID: 34179744; PMCID: PMC8217988.
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