Tuesday, March 09, 2021

More musing about vaccines

We vets vaccinate dogs against infectious canine hepatitis. Many, many years ago we used a live vaccine derived from the adeno-1 virus, unless the animal was a sight hound, Salukis or Borzois being particular concerns. For these we had a less effective/convenient inactivated vaccine (not sure which adenovirus strain this came from) because sight hounds (no pun) were particularly prone to blindness with the live attenuated A-1 vaccine. As the manufacturers of the A-1 vaccine stated, from memory, it "may cause corneal oedema which is usually transient".

If you translate that in to real terms it comes out as "can cause blindness which can be permanent".

Woe betide you if your boss found you had inadvertently picked up the wrong vaccine vial for a sight hound. Obviously, not all sight hounds went blind after the A-1 live vaccine.

The whole problem disappeared with the advent of the A-2 live vaccine (which we love), free from the corneal side effect, so I doubt kiddie vets are even aware that blindness was a predictable problem following a routine vaccination if you (and your patient) were unlucky. The modern A-2 vaccine is so effective I doubt we ever see infectious canine hepatitis nowadays but I recall seeing transient corneal oedema in at least one clinical viral hepatitis case in my early days.



I am one of those selfish people who is intending to defer my SARS-CoV-2 vaccination. The Queen does not approve. 



Why should I be so selfish? Many reasons, but the main one is an uncomfortable feeling about how m-RNA vaccines work. As I understand it, you inject a section of m-RNA enclosed in a vesicle which is muscle absorbed. The m-RNA is used by normal ribosomes to generate viral spike protein which is presented to the immune system on the surface of the muscle cells affected. The immune system sees the protein and responds as to the virus. You become immune. The residual m-RNA is fairly rapidly degraded and disappears until you get your next dose. I stand to be corrected if I am misunderstanding this.

I have no idea whether muscles infected with the field virus express spike protein on their surface. I suppose they might. Or they might not.

Does anyone think that expressing a viral spike protein on muscle cells will only generate an immune response to only that spike protein? Or, in the immune melee which results from muscle expressing an highly immunogenic foreign protein, would an immune response to other components of muscle surface occur?

How might you recognise such a response?

Myalgia perhaps?

Would it be better or worse the second time you played this game?

What would happen if you had already recovered from the field virus and so were very primed to effectively attack anything looking remotely like a SARS-CoV-2 virus surface protein?

So many questions.

Myalgia is common after vaccination, worse after the second dose and worse still if given to someone who has previously recovered from the field virus infection.

Heart muscle is not skeletal muscle. It probably "looks" different to the immune system. But it's not completely different. I, personally and just for myself, am not comfortable with making antibodies which might precipitate an attack on my myocardium. Which might not occur. Or, if it did, might be temporary. Or not. I remember the live A-1 adenovirus vaccine. This is just one of the problems of being as old as I am but still remembering my clinical experiences from the early 1980s.

So. Does myocarditis occur in the aftermath of SARS-CoV-2 m-RNA vaccination? Of course not. Do you have any concept of how much money is involved in these vaccines?

This is just from twitter so can be ignored if you wish:


I have no ideal who the tweeter is and I don't read Hebrew, so I have no way of following this up.

But I note that the Queen's recently vaccinated hubby has been passed around from hospital to hospital and has gravitated to being managed by cardiologists for his mystery illness. He's very elderly so this is probably just random chance and nothing to do with any vaccine.

The first Swine Flu pandemic vaccination program was halted in 1976 due to worries about Guillain-Barré syndrome from the vaccine. The same happened in the second Swine Flu pandemic of 2009-10 when narcolepsy halted that vaccination program.

The m-RNA vaccine will obviously be problem free.

I'm so selfish.

Peter

BTW, each person should assess their own risk from the virus vs their concern re the vaccine. Personally I consider my risk from the virus is very low so am un-enthused at any risk from the vaccine. Certainly for the next couple of years. It remains to be seen how much coercive pressure is going to be applied nation-wide and especially to myself to get vaccinated. I've ignored six invitations so far.

76 comments:

Holly said...

The sad part of this post is the fact when our generation (probably close in age) dies, so goes a lot of knowledge.

At least in my area (southern US) healthcare systems, as a rule, are not requiring Covid vaccination of staff? This is curious, no?

Considering that about 20 years ago, flu vaccinations became mandatory in US medical facilities. Why? Not because it was effective but flu vaccinations started declining and both pharma and big healthcare were losing money.

The industry required flu vaccinations be ordered a year in advance! Couldn't change the volume of the order as flu season grew close. If we didn't use it, we just threw away the vials and lost money. No refunds.

We started ordering smaller volumes in advance, knowing that sometimes we could get an additional order in during flu season.

Obviously industry noticed a) that many patients declined flu shots because their doctors / nurses didn't take it b) by making it mandatory both the pharm industry and medical industry increased profits.

The rub my family knows this yet most still roll up their sleeves.

Peter said...

Hi Holly, yes, there is little logic to anything. For flu vaccines I work on the basis of antigenic drift meaning I survived last year so am pretty good for this year. Antigenic shift means the vaccine is useless, so what's the point?

Plus I'm reasonably confident I've had the virus during the first wave so would definitely want an IGRA test for cell mediated immunity before accepting a vaccine for a disease to which I'm likely to be immune to for life... Assuming the original SARS virus immunity is anything to go by.

Peter

Holly said...

Family member is a hospital-based psychiatrist. Pretty confident we've been exposed as the hospital never closed/limited admissions. How many people are aware that authorities furloughed prisoners but for-profit psych hospitals never missed a dollar (in our region of US).

A few staff had mild cases, some tested positive for antigen and some patients were ill with mild flu-like symptoms.

Given that some of this population practices less than stellar hygiene, mask wearing is definitely optional, as this would require physical altercations with staff and some psych meds induce T2D, it's all very puzzling why this population hasn't been affected as severely as people in care homes. Maybe the anti-inflammatory benefits of psych meds?

Numbbum said...

My work will be taking me into the public areas of a couple of GP surgeries for short periods. In order to be allowed to do this, the NHS is insisting that I am vaccinated for a host of unlikely diseases including a Diptheria booster (there were only 10 cases of Diptheria in the UK last year!). My family have a history of immune-mediated diseases and I am showing a similar pattern. I am nervous about having unnecessary vaccinations. Obviously, I'll have the truly necessary, but I feel this is over-kill given my contact with patients/staff will be no more than the type of contact they would be exposed to in their normal daily lives - I will be performing no procedures, just talking to people. Sadly, I have no choice about this. It's not up for discussion. To mention any concern is to be assumed to be an 'anti vaccer'. No jabs, no job.

Peter said...

Holly, yes, that is strange!

Hi Numbbum, is that quite legal in the UK? I guess it's like making sure surgeons are vaccinated against hepatitis, including being seropositive, for patient safety...

Peter

cavenewt said...

Re the tweet linked in your post, here was a link tweeted by Tucker in response. https://bmcpharmacoltoxicol.biomedcentral.com/articles/10.1186/s40360-018-0211-8
"Recurrence of pericarditis after influenza vaccination: a case report and review of the literature"

Holly said...

Read this blogpost to hubby. He said "Look up malaria vaccination side-effects."

Here's a sampling of why malaria vaccinations are NOT given routinely:

https://www.theguardian.com/australia-news/2017/jun/03/veterans-say-report-on-anti-malaria-drug-mefloquine-downplays-side-effects

https://www.drugs.com/sfx/mefloquine-side-effects.html#professional

Passthecream said...



"Australia's health minister hospitalised with 'suspected infection'
Greg Hunt is expected to make a full recovery and his condition is not thought to be related to the Covid vaccine he received on the weekend"

Good optic huh?

cavenewt said...

Mefloquine isn't a vaccine, it's an anti-malarial drug, given prophylactically during possible exposure to malaria-carrying mosquitoes. Malaria itself isn't bacterial or viral, it's parasitic. As such, this example might be of limited usefulness in a discussion about vaccines.

Ariadne R said...

I'm curious about how an adenovirus vaccine (like Johnson & Johnson's) would differ from the mRNA vaccines. ... Um, so from what I'm gathering, it sounds like when mRNA vaccine is injected, the mRNA inserts itself into whatever cells are nearby that it happens to bump into. So in a standard upper arm injection, that'll be mostly muscle cells.
Does the adenovirus-vaccine likewise "infect" cells near the injection site? Or, since the virus is a type of respiratory ailment, does that mean it can only infect certain types of cells (not muscle cells)?

Bob said...

I do appreciate your musings here. And I appreciate the included tweet, from which I found Tucker's contribution on reading the replies. I'd been thinking about Tucker, because he previously linked to a post on ADE by Derek Lowe. Last night I read another Derek Lowe post about the challenges associated with making an mRNA vaccine.

https://blogs.sciencemag.org/pipeline/archives/2021/03/03/how-to-administer-rna-and-how-to-do-it-again

It's basically celebratory given the pandemic, but it left me uneasy about taking the shot given the lack of human trials. So, I expect I will be selfish, too, for quite awhile.

Peter said...

Ariadne, the mechanism will be completely different. Which cells will be targeted by the adenovirus (which is non replicative) might depend on which the virus-derivative being used and the target species, ie the vector might be selective about which cells it targets, not just local muscle/regional lymphnode. Not looked in to that one but I would expect less problems. But phase three trials (mostly due to complete in 2023 I think) would be helpful, even if there is no placebo group.

Bob, ADE is still on my radar. The at-risk population would be elderly people with poor CMI. The disease would be indistinguishable from clinical COVID-19 except for more rapid progression in vaccinated vs unvaccinated people. And it requires field virus as well, in the aftermath of an antibody dominant response to the vaccine. Interesting the data published from Israel excludes care home residents. I would expect these people to be most at need for the vaccine and most at risk of ADE. And most at risk of dying of old age too. Messy.

The best documented ADE was actually mediated by CMI and was to a vaccine against RSV in children (a potentially serious disease made worse by its vaccine, with a lot of QALYs to be lost if a child dies). Immune disease enhancement is a better generic term I guess.

Pass, that's almost funny. But not quite.

Peter

Gyan said...

I wonder if the vaccine trials screened for covid antibodies before enrolling volunteers?
As millions of mRNA based vaccines have been given, we should be able to estimate probability of specific scenario sketched here. I think USA has about 1000 vaccine-related fatalities.

Peter said...

Gyan, that would be interesting. I don't think people were screened for abs in the trials. I think one has also to be very careful about semantics such as "vaccine-related". It's quite reasonable to assume frail elderly people at likely to die, they at the normal end of their normal lifespan. If that occurs after a vaccination it is age/frailty related, clearly not the vaccine. As far as I'm aware there was never any sort of controlled trial of these vaccines in the elderly/frail population, so we'll never know if vaccines extended or shortened the life expectancy in this difficult population. No one checked, AFAIK...

Peter

David said...

Peter, when people die of old age it is normal, in these abnormal times, to say it was of Covid or after a Covid test. What will they about a death which follows a vaccine? Could it be that the only people dying of old age are the recently vaccinated?

Peter said...

David, obviously the vaccine status of every person is known, whatever their age, whether they are alive or deceased. If such data are ever made available they will be an interesting read.

Peter

Numbbum said...

I wonder if dosing up on paracetamol/ibuprofen (cbd?) might get you your vaccine passport whilst attenuating any over-enthusiastic immune response?

altavista said...

Love watching all these pols everywhere getting a phase3 2023 jab on TV for the greater good.

Should be the standard for all experimental drugs. Every Sunday :)

Eric said...
This comment has been removed by the author.
Eric said...

Reposted minus typos:

Peter, your blog entry had me slightly confused. You talked about an adenovirus-vectored vaccine causing problems in dogs, but then voice your concerns about the mRNA vaccines.

Was the dog hepatitis vaccine #1 the same principle as the current AZ vaccine, i.e. genetically engineered, non-replicative adenovirus vector? How was the vaccine #2 changed from #1?

As far as I can tell, the AZ vaccine ends up releasing mRNA in infected cells, so not too different from the mRNA vaccines.
https://www.nytimes.com/interactive/2020/health/oxford-astrazeneca-covid-19-vaccine.html?smid=url-share

The only difference might be that the adenovirus might be able to travel farther then the encapsulated mRNA, so it might get to infect more than muscle cells.

Side question: if the adenovirus is non-replicative, how do they grow it? Or does it get zapped after it has multiplied? Or does this mean it does not replicate in human cells but in other, e.g. chimpanzee?

cavenewt said...

"I wonder if dosing up on paracetamol..."

If you mean more than the recommended dose, is liver failure worth it?

My four-year-old son had to be life-flighted with liver failure after taking an over-the-counter cold medication that contained acetaminophen; it turned out he had pneumonia. Most people don't know how dangerous that crap is, especially in overdoses or in weakened persons. He spent five days in intensive care and almost died. The liver specialist later calculated he had been getting a 1/3 dose for his body weight.

Numbbum said...

Hi Cavenewt,

I'm really sorry to hear about your son. I hope he's ok now.

I didn't mean to suggest taking more than the recommended dose of paracetamol - I'm aware it's dangerous stuff - it really shouldn't be available so freely.

I was thinking more in terms of taking the recommended dose of an immune-suppressing drug, such as paracetamol, ibuprofen, or maybe antihistamines or cbd might mitigate potential harms due to any over-enthusiastic immune responses to vaccines for those of us who don't have the luxury of watching and waiting.

Use of immune-suppressants for this purpose is purely speculation on my part. I have no relevant expertise.

cavenewt said...

Heya Numbbum—no worries, he's 24 now so he survived. Sorry to sound like a scold. An experience like that makes one sort of sensitive to the subject.

I guess I didn't quite understand your (partly tongue in cheek?) suggestion. I suppose one could also wonder if taking an immune suppressing drugs right before a vaccine might render the vaccine sort of pointless...?

Personally, I was half hoping to get infected and get natural immunity that way, counting on my robust LC/HF mitochondrial health to fend off severe symptoms. Alas, my normal life is pretty isolated and infection-free, and the people around me are mostly frail white-hairs, so in deference to their peace of mind I just got my first shot. I'm 67, a recent cancer survivor (no chemo though), and have a mystery supposedly autoimmune neuropathy, otherwise disgustingly healthy. My upper arm was a little bit sore for a couple of days, no other side effects.

Peter said...

Cave and numbbum, yes, some caution with paracetamol, though most of us will be fine most of the time with therapeutic doses. How much good either would do at time of vaccination is hard to guess. They certainly ameliorate the normal cytokine response to traditional vaccines.

Eric, yes, it's a confusion that my lesson in serious vaccine adverse reactions happened to be learned from a clinical canine adenovirus hepatitis and its assorted canine adenovirus vaccines. It's random that the OAZ vacc uses an adenovirus vector. You would have to know which tissue tropism the modified vector has in humans to decide which tissues would express spike protein, so where you might be thinking about triggering inflammatory responses, with the potential for auto immune diseases. Completing phase three trials will give us much more information.

Of course if you consider you might die from COVID-19 then clearly grab any vaccine with both hands.

Adenovirus vectors have been around for some time and are routinely used in gene therapy but quite how labs generate them is not something I've looked in to. Fascinatingly, the vector triggers an immune response to itself which screws up repeated gene therapy administrations. They immunosupress people with steroids at the time of therapy to partially get round this.

Peter

Peter said...

cave, we were lucky, of all the time for my wife to visit London it was late February 2020, at the absolute peak of infection there. Sardines in tube trains, multiple meetings etc. Cough/transient fever 4 days later, coughed badly for a week then bronchitis for 2-3 weeks. We didn't isolate her in any way. I was clincially unaffected, the kids had a mild tummy upset around the same time. No one else in the family was affected (we mixed lots, she tried not to cough over anyone except me, which was unavoidable).

I can appreciate your decision and why you've made it. I less appreciate the immune deniers in UK's SAGE!

Peter

Lael said...

What I wonder is -- what made the sight hounds in particular different from other dogs to react that way sometimes?
For the vaccine - I feel like it is kinda a crap-shoot either way at this point in time-- take the chance of getting COVID and hope my immune system is robust enough, or get the vaccine and hope the same? % wise it appears any of the vaccines is the best choice there given age and other factors, but only time will tell.

Peter said...

Hi Lael,

They will have an MHC class I receptor which is specific for a viral protein component which results in an antibody which cross reacts with corneal protein. The corneal oedema will be an effect of labelling your dog's cornea as foreign. Temporary if the antibody production is temporary, permanent if the corneal tissue becomes a trigger too. Their particular (and unknown) HLA Class I molecule will have been present randomly in the canine population and sight hounds will have a founder effect secondary to line-breeding to fix the desired hunting capability of the breed, well before Crufts was thought up. Generally a small breeding population gives occasional weird random genetic linkages.

Peter

Marius said...

Hey Peter,

A bit off topic here. I was wondering what you think about Lings A-I-Hypothesis and Pollacks EZs nowadays?

Thanks,
Marius

Malcolm said...

I guess it comes down to risk from the vaccine vs risk of "long covid" or worse (post viral fatigue?) from the virus itself. I'm assuming most people are not too concerned about the possibility of a few days of flu, it's the serious outcomes that are a real concern.

If a person has had the virus already then I can see skipping the vaccine being an attractive option, if not, then maybe best to get the vaccine. Trouble is, I'm not sure if I've had it or not! :-)

Eric said...

@ Peter, what is your take on the current continental panic about the AZ vaccine causing clotting problems? Apparently, quite young and fit people died in Italy within days of being vaccinated. The German Paul-Ehrlich-Institute was quite late to the moratorium party, but the news articles about the German ban said something about brain vein trombosis. Didn't even know that existed...

@ Malcolm, I suppose the issue is that some variants seem to be able to reinfect. Just look at what happened in Manaus around the turn of the year and now has spread to most of Brazil. That P1 variant seems to reinfact people who had a confirmed infection, and it also seems to kill a surprising number of rather young people, many of which supposedly should be immune.

Eric said...

Of course, if there are 30 suspect blood clotting cases in 5 million vaccinated people on the continent, what about the UK were at least an equal number should have received the AZ vaccine?

Eric said...

Sorry, one more post, just came across this:
https://www.zeit.de/wissen/gesundheit/2021-03/bund-setzt-corona-impfung-mit-astrazeneca-in-deutschland-aus

Seven reported cases of cerebral thromoboses in 1.6 million who have receive first dose of AZ in Germany. And up to about a week ago, these were all active medical personel because AZ was restricted to those under 65 and vaccinations of teachers, police etc. are just starting.

Deepl translation of one pertinent paragraph:

Spahn recommended those vaccinated with AstraZeneca to consult a doctor immediately in case of clear symptoms. This applies in particular to people who feel increasingly unwell more than four days after the vaccination, who suffer from severe headaches or "pinpoint bleeding on the skin".

So how do clots and skin bleeding go together? Do all those clots deplete platelets elsewhere?

Peter said...

Eric, we’ll get more of an idea as the phase three trials complete in 2022 or 2023, or at least we would if they still had a placebo group, which they won’t have. Other than that it’s “compare to the normal population”, i.e. those figures for 2019 and before. Who knows?

I’m not completely overwhelmed by the integrity of Big Pharma in general, it seems comparable to that of Boris Johnson.

Re clotting vs haemorrhage: Excess clotting absolutely depletes platelets, but there has to be a lot of clotting to do this. Unadulterated loss of platelets gives bruising w/o the need for clots. No reason there shouldn’t be a combination of both.

Malcolm, yes, getting a T cell response, something like an IGRA test, is neither simple nor available. That’s why I describe myself as lucky in that we live in a remote rural area but got infected early on after a trip to the Big City. By one of us anyway. Long COVID is undoubtedly real but is even more likely to represent linoleic acid toxicity. There can be active on going pulmonary fibrosis. My default is LA as the cause in any such scenario.

Marius, I still view Ling as deeply insightful, probably correct but I find it near impossible to view routine metabolic processes in the terms he uses. I have way to much familiarity with the more normal nomenclature of how things happen…

I’m much too invested in the thermodynamic flow model of alkaline hydrothermal vents, Nick Lane and associates, to go much with the EZ ideas, certainly for the origin of life. Though cellular water is undoubtedly structured.

Peter

Eric said...

"cellular water is undoubtedly structured"

What does mean for us uninitiated? Not homeopathy?

Peter said...

Haha! Water is a dipole, there is a charge distribution with the oxygen being more negative compared to the hydrogens. If you place a positive ion in to water the negative “point” (H2O is a bent molecule) will align with the positive ion forming a shell of water around the ion. The hydrogens on the outside of this shell of fixed water are positive so will attract another layer of negative oxygens to themselves, but not as well as the original ion. Further layers out become less well attached. The same happens round any charged point of a protein. Cells are full of charged points, most water will be attached to one or another. It doesn’t just bounce around. Moving stuff around in cells is not a simple matter of diffusion. Ling articulates this in to a view of physiology on which the MRI scanner is based. MRI scanners work. I have more problems with Pollack’s idea that structured water can form and unform as an energetic storage system at the origin of life. Though it’s more plausible than any “prebiotic soup” concept. Life is thermodynamic, Lane, Martyn et al explain the origin of life from basic energy flow in geophysical systems. I like that.

Peter

Eric said...

Ok, just plain old hydration of ions. Didn't think that qualified as structured water :)

But that is baked into the diffusion coefficients of ions. And its obvious that you need to adjust these when there are several species of ions.

Eric said...

From spiegel.de (cannot permalink as this is a newsticker):

3.27 p.m.: The seven cases of a specific thrombosis that were the reason for the suspension of the AstraZeneca vaccinations affected people between about 20 and 50 years of age. This was announced by the Paul Ehrlich Institute on Tuesday. Six of them had had a so-called sinus vein thrombosis, all of them women of younger to middle age. Another case with brain haemorrhages due to a lack of blood platelets was medically very comparable, it said. "All cases occurred between 4 and 16 days after vaccination with the AstraZeneca Covid 19 vaccine," it said. Three of the seven people affected had died.

All experts consulted for the assessment were unanimous in their opinion that a pattern could be recognised here and that a connection between the reported illnesses and the AstraZeneca vaccination was "not implausible", the PEI said.

According to the report, the number of cases after such a vaccination is statistically significantly higher than the number of cerebral vein thromboses that normally occur in the population without vaccination: "About one case would have been expected, seven cases had been reported." The severe cerebral venous thrombosis with platelet deficiency did not affect the age group at high risk for a severe or fatal Covid 19 course, he said. It is not senior citizens who are affected, but people of younger to middle age, he said.

"After overall consideration and consideration of the above facts, the Paul Ehrlich Institute has recommended that vaccination with the AstraZeneca COVID-19 vaccine be suspended in Germany as a precautionary measure in order to further analyse the cases," the Institute concluded. Accordingly, experts from the European Medicines Agency (Ema) will now examine in the course of the week whether and how the findings affect the benefit-risk profile of the AstraZeneca vaccine and the EU approval of the vaccine.

Translated with www.DeepL.com/Translator (free version)

Interesting. A number of 4-5 cases / million and year was quoted by zeit.de. No idea if the majority of these were women between 20 and 50, but I am pretty sure that the age profile of recent vaccinees in Germany was bimodal: those in the 80+ and 70+ receiving priority vaccinations after AZ was cleared for 65+ a few weeks ago and health care professionals. Might end up being more than a factor of 7 too high.

Peter said...

Ha, just logged in to note the Paul Ehrlich Institute FAQ page! I believe this is why phase three trials normally go on for a couple of years. The incidence is still way below that of the narcolepsy from Pandemrix in the last swine flu pandemic which aborted that whole vaccination program.

Paul Ehrlich Institute web page in English is here for anyone else who would like it

https://www.pei.de/SharedDocs/Downloads/EN/newsroom-en/hp-news/faq-temporary-suspension-astrazeneca.pdf?__blob=publicationFile&v=5

Peter

Eric said...

Here actually:
https://www.pei.de/EN/home

8 cases being reported this morning, by the way.

Eric said...

https://www.zeit.de/2021/12/astrazeneca-nebenwirkungen-thrombosen-corona-impfung-impfstoff/seite-2

Another explanation is the special situation in Germany: in contrast to other European countries, it is mainly younger people who have received the vaccine here, because the Standing Commission on Vaccination at the Robert Koch Institute initially recommended it only for people younger than 65 years due to a lack of data. And younger people statistically have an increased risk of cerebral venous thrombosis; if the vaccine increases it further, it could be dangerous for young people in particular.

In other words, if there is a causal connection with the vaccination, it will be noticed earlier in Germany because more younger people were probably vaccinated with AstraZeneca here. Very rare side effects of an active ingredient only become visible when many people have been administered it.

But even if there is no causal connection between vaccination and side effects, there could be an accumulation of cases due to the special nature of the German vaccine distribution, simply because there are more younger people with an increased risk of cerebral venous thrombosis among those vaccinated. The seven reported cases fit the pattern exactly: they are under 50 years old. If this theory is correct, there should soon be visibly more cases in the other countries as well, as soon as many young people have been vaccinated there.

The age of those affected is then also the solution for how the current situation could be dealt with, the PEI hints at it itself: "The group of persons affected by the severe cerebral venous thromboses ... affected by the serious cerebral venous thromboses ... is not the group of people in younger to middle age who are at high risk of a severe or even fatal covid 19 course."

So vaccinating them with the AstraZeneca vaccine doesn't benefit them that much. So why not give it to older people whose risk of cerebral venous thrombosis is low? That would be a complete about-face in Germany's dealings with AstraZeneca. And it shows why every vaccine remains under scrutiny after its initial approval.

Translated with www.DeepL.com/Translator (free version)

Bob said...

This news from the BMJ is, uh, interesting.

https://www.bmj.com/content/bmj/372/bmj.n627.full.pdf

Peter said...

Bob,

People have this idea that they can screw up, discuss it via email and no one will ever be any the wiser. There are similar cyber attacks showing the pressure put on regulators by pharma for emergency vaccine approval. Can't recall which entities. It's so naive to think their private emails will remain private for ever!

As an aside, one of the standard bullshit tests is when a study publishes relative risk vs absolute risk reduction. It's a good principle. I say no more.

Peter

Eric said...

What is more worrying to me is that they worry mostly about efficacy of a vaccine with 55% vs. 75% undamaged mRNA. Hell, real world dosing with syringes is probably only 10% accurate, body weight of the recipients varies by a lot more than that.

The altered proteins made by altered mRNA are worth half a sentence. Granted, most of these will be gibberish, but some might end up being a powerful mutation of the spike protein.

Where is the risk assessment what these might do on their own? Or if they make it back into life virus?

Eric said...

Somebody at Malcolm's blog found the Australian product information for the AZ vaccine:
https://www.tga.gov.au/sites/default/files/auspar-chadox1-s-covid-19-vaccine-astrazeneca-210215-pi.pdf

"This product contains genetically modified organisms (GMOs). "

There, it's been said, by a regulator.

"COVID-19 Vaccine AstraZeneca contains the excipients histidine, histidine hydrochloride
monohydrate, sodium chloride, magnesium chloride hexahydrate, disodium edetate (EDTA),
sucrose, ethanol absolute, polysorbate 80 and water for injections.
COVID-19 Vaccine AstraZeneca does not contain any preservatives and the vial stopper is not
made with natural rubber latex"

Not so keen on a detergent, but other than that, composition looks ok to me.

"3 PHARMACEUTICAL FORM
Solution for injection.
Clear to slightly opaque, colourless to slightly brown, particle free with a pH of 6.1 – 7.1."

"COVID-19 Vaccine AstraZeneca is a colourless to slightly brown, clear to slightly opaque solution.
The vaccine should be inspected visually for particulate matter and discolouration prior to
administration. Discard the vial if the solution is discoloured or visible particles are observed. Do
not shake. "

Is it normal for the appearance and acidity of a live vaccine to be all over the place? How do you inspect for particles if you must not shake? Why must one not shake?



Eric said...

EMA decided not to stop AZ but to add a patient advisory. I think this is the right call, as the overall risk of contracting Covid is a lot larger, as is the risk of dying of clotting complications when you contract Covid.

At the same time, the count just in Germany has grown to 13, out of which 3 fatal:
https://www.bundesgesundheitsministerium.de/coronavirus/faq-covid-19-impfung/faq-impfung-astrazeneca.html#c20802

Maybe it is a good idea to be selective about demographics that should receive the AZ vaccine.

Bob said...

"Why must one not shake?"

Hi, Eric.

I thought I had seen that caution before, and with your question, I looked it up.

https://www.pharmacist.com/article/ask-experts-shake-rattle-or-roll-preparing-vaccines-administration

"Some vaccines are suspensions, while some are solutions. Some need to be shaken vigorously, others need to be shaken gently, and some don't need any shaking, whether they are in a vial or a syringe."

There follows a chart listing some vaccines and their "preparation prior to administration".

The CDC instructions for the Pfizer vaccine are here:

https://www.cdc.gov/vaccines/covid-19/info-by-product/pfizer/downloads/prep-and-admin-summary.pdf

"With the vaccine at room temperature, gently invert vial 10 times. Do not shake the vial. If the vial is shaken, contact the manufacturer."

Obviously, there are people who have forgotten more about vaccine development, preparation, and administration than I will ever know. And there are probably more ways to screw it up than I care to know.

Bob said...

"It's so naive to think their private emails will remain private for ever!"

Peter,

I'm more concerned (and this goes to the point of your post) that all the people so eager to be vaccinated naively think everything will go according to Hoyle! Like you I'm in wait-and-see mode, and the BMJ revelation reinforced my view.

Passthecream said...

Hmmm 'lipid nanoparticles', vs tissue targeting.

Which lipid? I wonders to mesself.
What particles?
Is that an LDL-bourne delivery system?
Is it a small dense vaccine or a light fluffy one?

altavista said...

This is fun

https://www.sciencemag.org/news/2021/03/it-s-very-special-picture-why-vaccine-safety-experts-put-brakes-astrazeneca-s-covid-19

Eric said...

Norwegian scientist claims to have found the reason for those platelets. Apparently, this is an autoimmune reaction to platelets:
https://sciencenorway.no/covid19/norwegian-experts-say-deadly-blood-clots-were-caused-by-the-astrazeneca-covid-vaccine/1830510

A Greifswald based group has very similar findings (article is too long to post, you'll have to deepl it yourself):
https://www.spiegel.de/wissenschaft/medizin/astrazeneca-greifswalder-forscher-haben-offenbar-ursache-fuer-thrombosen-gefunden

Justin said...

So wife is considering the J&J vaccine so she can travel for work. Anyone aware of a nasally administered vaccine that is available in the US to accompany this traditional type? I feel like this could be the best approach by allowing more of a mucosal immune response.

Justin said...

https://www.biospace.com/article/releases/adcovid-altimmune-s-single-dose-intranasal-covid-19-vaccine-candidate-prevents-sars-cov-2-induced-disease-and-blocks-viral-replication-in-preclinical-studies-of-sars-cov-2-infection/

Eric said...

There it is finally in English:
https://idw-online.de/en/news765335

And now for something completely different and very much off topic. Well, maybe not so much. All we need is a virus that can fool around with the genetic switch and we are ready for planet of the apes. Anyone notice that post-apocalyptic movies have gone out of style, even as we have become no better about mending our ways? ok, enough of a rant, here goes:

https://www.theguardian.com/science/2021/mar/24/scientists-discover-why-the-human-brain-is-so-big

Captain Sunset said...

I got my eighth txt from the GP/NHS yesterday. I've also had two letters - luck me! Anyway, my take on most of this débâcle is that it's becoming ever clear(er) to me that the whole SAGEology et al approach is not much different than... astrology. All the hyper-fear ridden MSM/SAGE dingbats have ever done in their lives is scribble on bits of paper or, poke at computers. They are just not in the real world. They never were. They just make it up as it goes along. They are akin to shape-shifting gods. I thought it was getting more religious-like, but no, it's not St. Covid-like it is more astrological. A (live) wild virus challenge (or live vaccination) would be part of the natural worlds remit to get your immune system updated - and it even offers protection against the humanized Wuhan-mouse cluster-fuck. Such 'updates' produce broad-spectrum immune protection which is fundamentally different to today's narrow dead-virus oil/attenuated do$$ar 'vaccinations'

Peter said...

Hi Captain Sunset,

You're one ahead of me in the invitation stakes. Such a relief Tony Blair is organising our imminent vaccination passports to follow. At least he's not bombing us, yet. I guess.

Peter

Justin said...

Captain Sunset, I guess that kind of answers my question. I like the narrow band analogy! Lol!

Peter said...

Hi Justin,

Sorry I missed that. I've no idea if anyone is marketing an intranasal vaccine. If so I suspect it would produce better immunity, espec IgA, but I've no idea if it's available...

Peter

karl said...

OT - lead exposure - OA - CAD - T2D..

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3132016/
https://pubmed.ncbi.nlm.nih.gov/16670857/
https://www.thelancet.com/journals/lanpub/article/PIIS2468-2667(18)30025-2/fulltext
https://www.thelancet.com/journals/lanpub/article/PIIS2468-2667(18)30128-2/fulltext

Bob said...

Justin,

I think you answered your own question in the link provided. It says "vaccine candidate".

AstraZeneca begins clinical trials on the nasal vaccine.

https://www.ft.com/content/48fe2e97-f9e5-4291-b965-0728bfc42213

I think we're some way from "availability". Remember, the messaging for the intravenous vaccine is badly mangled. It's "We don't know if it prevents infection" vs "Take the shot to protect others."

Bob said...

Peter, I'd like to find someone giving IgA tests. A company in my state (Salimetrics in Calfornia) has a saliva test, but it's for folks doing "studies". They don't offer it to individuals (I asked), and they don't know of any labs using it.

Everything else I've seen is serology.

A few weeks ago I ago I spoke with a retired molecular biologist. I wanted his take on IgA, ADE, and so on. He said, "Those are good questions, but they are not the important questions. The important thing is to get this plague behind us".

What a fustercluck.

Captain Sunset said...

Hi Peter,The GP/NHS txt’s keep coming, but it’s not the hypodermic, but the hyperbole that bothers me. I’ve been jabbed up more than most folk in the UK, but what actually does bother me is the sheer amount of rank, and comprehensive technocratic stealth being pushed. I’ve experienced this global-like fervour before when called up for National Service/The Vietnam War in Australia (in ‘72), and later (in ‘78) when I was country manager for a small UK engineering group in Iran. Having arrived in Tehran for a 3-year stint in March it soon became evident to me that matters were not good in the country. As such, I kept sending back reports to London, and so in November the Chairman, and the MD of a subsidiary rerouted a visit to Australia to come and check matters out. In a few days, we managed to meet a lot of people including the local MI6 man, Bankers, and the British Ambassador (Anthony Parsons - the ambassador of the UK’s second-largest Embassy, after Washington). Well, all kinda poo-pooed my fears, and not least the BBC, and the US and UK MSM, as well as the (large) US Military contingent. So, they soon left for Australia after some heated words with me. When they arrived in Sydney on the 5th November they bought the first Newspaper they could in the transit lounge, and the front page of most of the Sydney Morning Herald was a picture of an armed mob who had taken over the whole of the British Embassy and ransacked its main building. I finally left Tehran on the 24th of December on one of the last scheduled flights out - Singapore Airlines to Copenhagen. Anyway, sorry for the digression!

E-S said...

@Peter did you see the BBc’s fresh evidence of faulty practices in NHs testing for Covid ? https://www.bbc.com/news/uk-56556806

This is so disgraceful I have no words.

@Eric - what about the smooth transition of brain size along hominins & hominids ? Also a larger brain has big thermodynamic implications, hence why homo sapiens has innovations for keeping the braincase from overheating, like plenty of vascularized foramina. Doesn’t look like a singular switch at all...

salix said...

Hi Peter, would love to hear your thoughts on impaired mitochondrial function in people who get too much exercise:

https://www.nature.com/articles/d41586-021-00703-x

Peter said...

Bob, I’ve spent the last 20 years watching apparently sensible people being incredibly stupid. At times I despair of humans…

Captain, I still think late 2023 we might have some idea re vaccine safety and efficacy. Until then it’s a matter of managing the degree of coercion. At the moment it feels like there is some kickback starting, but LC vs LF felt that way for 15 years before we now finally have some progress.

E-S, no I didn’t but the twitter-sphere gives the impression it’s much as you might expect running 1,000,000 PCR tests a day with inexperienced staff. The sceptics have been saying this all year. They are fully vindicated, not that they need vindication.

Eric, I looked briefly at the abstract of the study a little while ago. Do you follow Miki Bendor? He has a paper out with Raphi looking at the selective pressure to develop brain size in this way. Brains are expensive in the extreme. Having a gene which gives you a big brain is a metabolic massive cost. It would only persist if it provided a survival advantage, which it clearly did. I have a lot of time for Miki’s ideas as to what that survival advantage might have been.

salix, no, not something I’ve thought much about but the article gives some clues. Athletes have major blood glucose excursions both up and down. What crap do athletes eat? And I would assume that these people have constructed their inner mitochondrial membranes and cardiolipins out of linoleic acid or its derivatives. Throw a few ROS at these and the mitochondria are f*cked… Would we expect to see the same change in an athlete who never, ever was hyperglycaemic and who never, ever consumed heartheathypolyunsaturates? Interesting questions.

Peter

Peter said...

Oh, BTW E-S, I also worry about cross contamination at the sampling sites. Can't help but recall the Dilbert cartoon about the hazmat suit. https://dilbert.com/strip/2020-10-20

Peter

Eric said...

Greifswald study published as a preprint:
https://www.researchsquare.com/article/rs-362354/v1


https://www.zeit.de/wissen/gesundheit/2021-03/astrazeneca-corona-impfstoff-regelung-alter-nebenwirkungen-zweite-impfung-faq
Now 31 cases in Germany in 2.7 million vaccinated, all under 60, most significantly younger and 29 female. In the UK, 5 cases among ??, but UK seems to have vaccinated mainly 80+ with this vaccine.

As of 29 March, the Paul Ehrlich Institute (PEI) has been notified of 31 cases of specific cerebral venous thrombosis that occurred following vaccination with Vaxzevria from AstraZeneca. 19 of the affected people suffered from a deficiency of blood platelets at the same time, nine people died. 29 of those affected were women aged between 20 and 63. The men were aged 36 and 57.
In the meantime, 2.7 million people across Germany have received the vaccine from AstraZeneca. So there is one case for every 87,000 people vaccinated. This means that although the complication is very rare, it mainly affects those who do not have an increased risk of contracting Covid-19 - namely younger people. "Thus, this particular complication seems to occur much more frequently among younger people after vaccination with AstraZeneca than previously known," said infectiologist and vaccine researcher Leif Erik Sander to ZEIT ONLINE.

To put this into perspective: when about 1.6 million doses had been vaccinated on 16 March, only one case of a complication such as cerebral venous thrombosis could have been expected by chance, according to the Paul Ehrlich Institute. However, with more than 2.7 million vaccinations in the meantime, the few cases that have occurred are now an accumulation that must be investigated.

Recently, the UK announced that 30 million people in the UK have now received their first dose of an approved vaccine. However, it is not entirely clear how many of these have received AstraZeneca's Vaxzevria vaccine and, more importantly, how old they were. As of 14 March, five cerebral vein thromboses occurred after vaccination with Vaxzevria - more recent figures have not yet been published. This means that this complication seems to be much rarer. The reason for this is currently being investigated. An obvious hypothesis: the average age of those who received the drug from AstraZeneca is probably much higher than in Germany, for example. An analysis of more than one million vaccinated people in Scotland shows that Vaxzevria was mainly given to people over 80, while those under 65 were mainly given the vaccine from BioNTech (KHub: Bernal et al. 2021). And an accumulation of cerebral venous thrombosis and platelet deficiency after vaccination with Vaxzevira was only found in Germany in people under 60 years of age.

Translated with www.DeepL.com/Translator (free version)

Marius said...

Hey Peter,

Have you ever had a look into the epidemic of hair loss among young men? I haven‘t looked yet but the simple „too much T/DHT“ which some people give as an answer doesn‘t strike me as convincing or even as being an answer.

Thanks,
Marius

Eric said...

This was in this morning's newsfeed at Zeit.de. I can't permalink because it keeps changing:

30 blood clot cases after AstraZeneca vaccination in the UK

Nowhere have so many people been vaccinated with the AstraZeneca drug as in the United Kingdom, but it is only now that a cluster of blood clots is coming to light: According to authorities, 30 cases have been recorded there in which a rare blood clot occurred after vaccination with the drug. The number of cases has risen sharply in the past two weeks - from an initial five to 30.

According to our medical editor Tom Kattwinkel, that's probably because in the U.K., only people over 80 initially received the AstraZeneca vaccine, and it's only now being used for younger people, who are at higher risk for these thromboses.

The UK Medicines and Healthcare products Regulatory Agency says no thromboses have been recorded following use of the BioNTech/Pfizer vaccine.

Translated with www.DeepL.com/Translator (free version)

Numbbum said...

"Captain, I still think late 2023 we might have some idea re vaccine safety and efficacy. Until then it’s a matter of managing the degree of coercion. At the moment it feels like there is some kickback starting, but LC vs LF felt that way for 15 years before we now finally have some progress."

Stents are still being fitted and statins are still being handed out like Smarties to ever younger people. Don't hold your breath.

Captain Sunset said...

@Peter / @Numbbum, I am 70 in July. Until about a year ago the game of golf was on a bit of a decline, but since the lockdowns, it has now (seemingly) exploded in popularity, which I find interesting as I come at golf from a rugby heritage. Anyway, back in the summer (2020) I tried to get a board member of England Golf to team up with the Ramblers to do a quick survey on active members to see who had suffered with covid. My thinking was that the older demographic might throw up some surprises in respect of vitamin d3 levels (...I am a vit D believer from way back!), but alas it repeatedly fell on deaf ears. Anyway, along similar lines, I have discussed LDL & Cholesterol and Statins & the pros of LCHF with many fellow golfers, and it is virtually impossible to have anything of a sensible 'grown-up' conversation with those who take the statin view. Dogma rules. Discussions often descend into food spluttering 'madness'. This has never happened before - with the exception of discussions on religion! My mind was turned on statins about 10 years back over the effects they had on some elderly family members, and the efforts of DR MK. As Peter stated such matters do become something of a long-haul! Highly defensive sunk cost errors run very deep.

Bob said...

"What would happen if you had already recovered from the field virus and so were very primed to effectively attack anything looking remotely like a SARS-CoV-2 virus surface protein?"

I might have a hint of a preliminary answer to that. I know someone who works on a food processing assembly line. Despite double-masking, face shields, gowns, boots, and gloves, she was diagnosed with symptomatic COVID last December. PCR-positive. I was almost certainly exposed as I took her to urgent when she was first ill (and swabbed) and present to help her get her results over the phone. I never had any symptoms.

On Thursday she got her first Moderna shot, courtesy of her employer. I would have suggested she not bother, but this would not have worked as a subject for discussion. On Friday she complained of headache, trembling, and a very sore and swollen left arm. I suddenly imagined legions of IgG antibodies (and probably cytotoxic T-cells) attacking her "infected" muscle cells.

We'll see how long she takes to recover. But I'm of the opinion now that getting the mRNA vaccine after a field infection is not only unnecessary but probably a bad idea. Hopefully not a very bad idea.

Captain Sunset said...

@Bob, As I understand it (from a recent paper - but can't recall which one!) if you have recently had Covid you can get up to a 6-fold reaction to any of the 'new' vaccines. Further, I do know of many doctors (such as Dr Micheal Eades), who do not recommend children or infected folk getting the vaccine. In fact, Dr Eades has stated that he is horrified at the thought of children getting the vaccine. Dutiful colleagues of mine who have had both Covid and the vaccine generally were totally whacked out for a week. Interestingly, as I also understand it there is 100-fold greater amount of ACE2 receptors in the gut as opposed to the lungs. Hence why sewage farms can be good places to pick up Covid levels. I don't think I have had Covid19 but I did have had some odd gut issues in the summer of 2020. Also, I think I believe I have had coronaviruses and other virus infections over the last few years from playing golf in all weathers with all sorts of people, but with no issues. I seem to get quite a few winter sniffles, but they only last a day or so. My take is that these are just simple virus 'update's. They keep me healthy.

Bob said...

Captain Sunset,

Talked to my friend a little while ago (Saturday night in California), and she said her arm is much better. Says she left work early yesterday as she simply couldn't work. Good to know she's getting better.

I am and have been completely aligned with Peter's parting advice in the next post: Unless you feel mortally threatened from COVID, don't jump mindlessly at the jab.

Astonishing we've thrown out everything the US FDA was purportedly created for in the rush to stop a disease which is particularly severe for such a relatively small portion of the population.

See also: https://twitter.com/puddleg/status/1377825141401391104

Bob said...

Eric, there was speculation in the comments to a Derek Lowe post that inadvertent IV injection of the adenovirus-vectored vaccine might be to blame. Might also explain that more women are suffering than men because of their lower shoulder muscle mass. Aspiration of the syringe is discussed as well. Someone also mentioned these problems are happening in the US with the mRNA vaccines, too.

https://blogs.sciencemag.org/pipeline/archives/2021/03/30/blood-clots-and-the-az-vaccine-revisited

As always, lotta speculation, not enough time yet to know.

Outlaw said...

First evidence of ADE: https://www.medrxiv.org/content/10.1101/2021.04.06.21254882v1/

Peter said...

I have to say that crossed my mind too but I'm not certain. It's quite convincing from the Israeli data that immunosuppression after the first dose of the Pfizer vaccine, as documented in early reports, is real and that goes a long way to explaining the catastrophe in the UK where vaccination coincided with a moderate winter resurgence. Leucopaenia + virus = badness. In Israel infection rates were plummeting at the time of roll out, much as they were in the UK at the time of the now defunct phase 3 trials starting last year.

Peter