Reviving a bit of an old thread after the BBC had a couple of items on the news last night about AZ blood clots, also seen to a lesser extent in the J&J vaccine. Something that I've not seen reported in the mainstream media is a pre-print paper released last week by a team in Germany with a possible explanation for the clots that also suggests why the incidence between AZ & J&J vaccine-related clots show an approximately 10-fold difference (far fewer with J&J) and why the mRNA vaccines have not experienced the same issue, or more correctly that the incidence of issues is far more consistent with expected normal baseline level non vaccinated population incidence.
A simplified but I would say slightly inaccurately summarised news report is here -
https://www.bloomberg.com/news/articles ... ting-links . It should be noted that (a) this is a not yet peer-reviewed pre-print paper, and also that Astrazeneca's response is quoted as...
The U.K. pharma company said the theory put forward by the Goethe University laboratory in Frankfurt on Wednesday is one of many that AstraZeneca scientists are investigating.
... so clearly, and reassuringly, there is a lot of work going on behind the scenes to understand this.
The full paper is here -
https://www.researchsquare.com/article/ ... -558954/v1For those that do like to delve into the details it is also worth reading the comments at the end of the page linked to above since one of the authors (Rolf Marschalek) is engaging actively in the comments section. I note in particular in one of his replies in answer to the question...
Are there any long term harmful effects to your findings? In other words, if a person who receives an adenovirus vaccine does not have a blood clot event, is there any other long term concerns of this spike splicing happening?
He answers (with my bolding)...
Based on the present data, I would say no. If the first shot didnt caused any problem, the second will be tolerated as well. Most severe side effects were observed between 4-16 days after first vaccination. Knowing this, it will be much easier to counteract these severe side effects in the future. I still think that this vaccine is a good vaccine, but could be made much better if certain things has been changed.
The basic thrust of their theory, as I understand it, is related to the fact that as a DNA vaccine the spike protein that the vaccine is designed to generate is encoded as DNA, a requirement since it has to be encoded within the DNA of the adenovirus, and so that code has to first be transcribed from DNA to RNA in the host cell's nucleus and the transcribed mRNA then migrates into the cytoplasm for translation into proteins whereas the mRNA vaccines deliver the desired mRNA directly into the cytoplasm without needing that DNA -> RNA transcription stage.
The issue as suggested in this paper is in the transcription where the transcription process within the nucleus, as well as transcribing the spike DNA sequence into a complete mRNA sequence for the desired spike protein (as intended by the vaccine designers), can also transcribe only sub-sections of the spike protein into mRNA and it is some of these sub-units that they suggest are causing the problems since, as for the full mRNA sequence, the sub-sequences also migrate to the cytoplasm and are translated into proteins that in those cases generate not the full spike protein but rather a fragment of it. The particularly troublesome fragments are those that still contain a sufficiently intact binding domain such that they can bind with ACE2 receptors but do not contain the bit of the spike protein that allows the spike to anchor itself to the cell membrane such that, when those fragments exit the cytoplasm, rather than presenting themselves on the surface of the host cells to mimic a spike attached to the outside of a real SARS-CoV-2 viral particle, they instead drift off into the bloodstream where, if the host's existing antibodies don't manage to neutralise them in time, they bind with cells on the walls of the blood vessels where ultimately inflammatory responses can lead to blood clots.
From reading the comments it sounds as if this team has a few more experiments that it is in the process of running that are quite important in determining the credibility of this suggested mechanism of action but I found it an interesting read none the less. I think it will be a good step forward once there is some strong evidence and consensus regarding what is going on in terms of any underlying mechanisms causing these clots whatever that mechanism ends up being. To address a problem one needs to understand it first and all findings, good or bad, contribute to knowledge going forward.
- Julian