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A runaway process (15/03/21 22:31:58) Reply
    The AZ vaccine has had a number of cases of thrombocytopenia and intravascular thromboses - so it could be what used to be called DIC - disseminated intravascular coagulation - or consumption coagulopathy, where thromboses and bleeding are seen together. The platelets are low because they are being used up to build thromboses.

    It looks like a runaway process.

    If this phenomenon is unique to the AZ vaccine, it will be withdrawn because the competitors are better. Possibly it will be dumped cheap in less discerning markets than Europe, where it undoubtedly will save thousands of more lives than it is going to take.

    Ugly. Time will show.
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An afterthought (15/03/21 22:51:42) Reply
    It could be that the prescribed dose is too high, and that the antibody response would be just as good with a lower dose, say one-tenth, with hugely improved safety..

    If I were a regulator, I would have taken a closer look at the dose finding studies of the vaccine.
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Re: An afterthought (17/03/21 06:56:57) Reply
    It might be that the DIC patients are specially unlucky: Suppose the injection goes intravenously instead of intramuscularly in the deltoid muscle. From what I have seen - on TV and in real life - the injection is given like this: Penetrate the skin with the needle and press the plunger in a split-second bolus or one-secoond. No aspiration.

    It is very unlikely that the injection goes intravenously. But if it does, it might be held back by the lungs, or some of it might pass to the arterial side of the heart and get distributed with arterial blood to wherever. Or - if there is shunting in the heart - like a minimally patent foramen ovale - some might enter the arterial system without passing the lungs. So the substance might settle in small vessels and initiate clotting by producing antigen in places where it induces clotting and where clotting becomes a runaway process. Not like in the deltoid, where it is confined to the muscle and any clotting can be limited and harmless.

    Statistics and epidemiology cannot explain rare events.
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Investigation (AstraZeneca vaccine) (20/03/21 09:39:37) Reply
    It seems the coagulationists amd platelet people have found platelet-activating antibodies. They attribute the thrombotic complications to them.

    I learnt from another source that the clinical picture of the victims was - unusual - if there is such a term. The victims had thrombosis of venous sinuses of the cranium
    https://en.wikipedia.org/wiki/Dural_venous_sinuses
    and in deep abdominal veins.

    Venous thrombosis is most commonly associated with leg muscles, extending into the pelvis.

    Now even the UK has reported such cases, even though they denied seeing them at first. It is explainable: Vaccines have been inject-and-forget types of drugs, in contrast to other drugs, where there is follow-up by the prescriber. It is typical that the Norwegian cases were previously completely healthy health personnel, with a short communication pathway to the reporting system.

    A serious vaccine manufacturer with a long-term commitment would already be in the process of refining the composition of the vaccine to eliminate the danger hotspots of the antigen RNA.


    ---

    It bring to mind a side effects emergency of the nineteen-seventies. I was a student when Eraldin (practolol) was launched as the first cardioselective beta blocker - by ICI, later known as Zeneca. It was withdrawn from the marked because of severe rashes in the palms of the hands, and destruction of tear glands and maybe salivary glands IIRC. In the wake of this withdrawal, two new cardioselective betablockers were introduced: ICI's Tenormin (atenolol) and Astra's Seloken (metoprolol). They were competing fiercely, and there was a balance for many years. One Astra representative leactured at a congress that Astra had synthesized practolol at an early stage, but decided not to follow it up because they saw one side chain details as a possible focus of dangerous metabolic activation. Just rearranging a few atoms eliminated the reactivity, and metoprolol is still going strong. The Astra people (Swedes) obviously were better at drawing board toxicology than their UK competitors.

    A university is not set up to maintain a product. Academics are set up to publish - or to say it irreverently: they go for likes and get rewarded for likes. If I were to choose a partner for vaccine development, I would rather choose a startup with good people than a university institute. The culture is widely different.
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When? (20/03/21 10:12:40) Reply
    will AZ announce that they have available a test batch of a modified version for testing?

    Will they open-source it?
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Opensourcing when there is $ to be made? (07/04/21 10:53:36) Reply
    "Vaccitech, the start-up that owns crucial biotechnology behind the Oxford/AstraZeneca vaccine, has confidentially filed for an initial public offering in the US.

    The Oxford start-up, co-founded by Sarah Gilbert, who led the development of the AstraZeneca vaccine, could price its offering as early as this month, according to people familiar with the matter. Vaccitech declined to comment."

    rf
rf

Re: Opensourcing when there is $ to be made? (11/04/21 09:46:24) Reply
    https://github.com/NAalytics/Assemblies-of-putative-SARS-CoV2-spike-encoding-mRNA-sequences-for-vaccines-BNT-162b2-and-mRNA-1273/blob/main/Assemblies%20of%20putative%20SARS-CoV2-spike-encoding%20mRNA%20sequences%20for%20vaccines%20BNT-162b2%20and%20mRNA-1273.docx.pdf


An interesting question. (29/04/21 17:28:21) Reply
    Opensourcing will save a number of lives, but will diminish profits for the designer systems of new products. Water, electricity, health care - how much private, how much state? So the question to be aired is a political one. The USA seems to be taking an extremist view with full privatisation of all sorts of healthcare, and extreme profits for the pharma industry. For those who only expose themselves to right-wing media, this extreme view may look like mainstream. Brainwashing.

    License fees will still be a possibility. Building factories, teaching personnel. Profits, but not windfall profits.
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Off/on topic: Xenotransplants (20/04/21 08:49:40) Reply
    If I have understood correctly, the AZ vaccine uses a virus capable of infecting chimpanzee as vector for the RNA - in contrast to the Janssen vaccine and the Russian vaccine. Chimpanzee viruses of course never enter the human body normally - even hugging won't do.

    I admit that I am far behind on this topic: I read up on it about 20 years ago when I had my compulsory year of internal medicine together with some of the now famous people.

    If you wish to genetically modify a pig to deliver kidneys for transplantation into humans, the first thing to be tried and tested was tissue compatibility antigens: change them from those of the porcine species to the human variety. First, of course, they tested the principle - harmonising HLA and blood type between donor and recipient, then transplanting. Wht could go wrong when the targets for the immune reactions were taken away?

    What happened, was that the tranplant triggered the coagulation system of the recipient, so the donated organ clogged almost instantly.

    So - what does this vector do with the levels of coagulation activation in the recipient? Tests have shown an increasing bleeding tendency in recipients of the AZ vaccine, suggesting that a subclinical event related to the catastrophic clogging is far more common than the clinical cases leading to death.

    If this is even remotely relevant, it might mean that the Janssen vaccine may have a future even if the AZ vaccine will have to be scrapped (eventually). But in countries heavily hit by the virus the risk of the AZ vaccine seems minimal compared to the dangers associated with living inside a cloud of infectious material, such as in the slums of big cities.
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Re: Off/on topic: Xenotransplants (20/04/21 13:45:25) Reply
    According to this Oxford study[1,2] it places the CVT from mRNA very closely to AZ(4 vs 5 in 1M), why do you believe AZ to be scrapped?

    [1] https://osf.io/a9jdq/
    [2] https://www.ox.ac.uk/news/2021-04-15-risk-rare-blood-clotting-higher-covid-19-vaccines
rf

Scrapped or "scrapped"? (29/04/21 16:36:30) Reply
    It seems the AZ has lower safety than some of the others. So in settings where safety (quantified as a 1:20 000 risk of potentially lethal thrombosis risk) is important compared to the lethality of the disease, and unacceptable, others will be preferred. In settings where the infection burden is so high that infection-related lethality overwhelmingly overshadows the risk of adverse reactions, the vaccine will be a blessing.

    The Norwegian deaths were healthy health personnel with an excellent prognosis if they were to be infected. So they were vaccinated mainly to protect others.
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