AstraZeneca Covid-19 vaccine study put on hold due to suspected adverse reaction

https://www.statnews.com/2020/09/08/astrazeneca-covid-19-vaccine-study-put-on-hold-due-to-suspected-adverse-reaction-in-participant-in-the-u-k/

by aaavl2821 • 6 years ago

262 211 6 years ago

statnews.com

aphextron2• 6 years ago

It's important to note that the AstraZeneca vaccine is adenovirus based [0], not mRNA based like the Pfizer and Moderna candidates. It was to be expected that this approach could cause more complications. mRNA vaccines have their own issues, but they do not involve live viruses being injected [1]. Instead they use lipid nanoparticles as a substrate to enter the body's cells [2].

[0] https://www.astrazeneca.com/media-centre/press-releases/2020...

[1] https://www.phgfoundation.org/briefing/rna-vaccines

[2] https://www.nature.com/articles/s41586-020-2639-4

mrfusion4• 6 years ago

So how does this one work? Live adeno’s?

aphextron2• 6 years ago

So how does this one work? Live adeno’s?

Yes. It uses a live (weakened) chimpanzee adenovirus to insert the spike protein.

https://www.drugs.com/history/azd1222.html

ethbr06• 6 years ago

The chimpanzee adenovirus is used as a vector, with its payload replaced with instructions to manufacture SARS-CoV-2 spike protein.

Virus enters body, hopefully survives immune system long enough to insert instructions into your cells, your cells churn out tons of copies of coronavirus spike protein, your immune system sees the surfeit of spike protein and develops a response (antibodies and T* cells).

https://blogs.sciencemag.org/pipeline/archives/2020/04/23/a-...

karmicthreat• 6 years ago

Thought Emporium has a decent video where he modifies an Adenovirus to inject the lactase gene into the cells of his intestinal tract. https://www.youtube.com/watch?v=J3FcbFqSoQY

kevin_b_er• 6 years ago

It could still be an immune system misfire. A vaccine is trying to create an large immune system response enough that the real infection is thwarted.

With that, a misfire can happen with any vaccine attempt, because an immune response is what's required.

EForEndeavour• 6 years ago

rather than producing them outside the body and then injecting them

That's not what the Oxford/AZ vaccine does, is it? From what I understand, it's a viral vector vaccine engineered to deliver DNA that encodes the SARS-CoV-2 spike protein into human cells and induce them to express the protein, stimulating the immune response.

The plan was never to introduce spike protein "produced outside the body." The mechanism of action is getting the body to produce spike protein and learn to attack it as foreign. If the Oxford/AZ vaccine doesn't "take advantage of your own cells to produce the spike protein," I don't know what does.

https://labblog.uofmhealth.org/rounds/top-5-covid-19-vaccine...

sudosysgen• 6 years ago

Yes, that was made in comparison to conventional vaccines that either use inactivated viruses or viral proteins

kurthr3• 6 years ago

Yes, the ChAdOx is an adenovirus carrier (chimp? to minimize human pre-infection) while Moderna and BioNTech as the parent states involve injection of mRNA (not DNA although there are other vaccines that do that) lipid particles that human cells then generate spike protein to simulate viral infection.

There are still other attenuated virus and other vaccines under development, they just haven't reached Phase III. Novavax even does something similar to what you describe (spike proteins with adjuvant), but it's also not past Phase I/II.

axaxs• 6 years ago

I think COVID is going to be make or break for mRNA, at least for infectious disease. It's either going to usher in an exciting new era of treatments, or we're going to see a lot of funding dry up and shops close. I for one obviously hope for the former, but given the prior actions/statements of some in Inovio, Moderna, et al, it gives me pause.

raxxorrax2• 6 years ago

You cannot roll out such a vaccine on a large scale within a at least a year. Far too many unknowns compared to the virus itself.

yread• 6 years ago

Where it says "serious adverse reaction" do they mean the adverse reaction was serious or that it's an actual grade 3 adverse event (SAE)? https://en.wikipedia.org/wiki/Serious_adverse_event

SparkyMcUnicorn• 6 years ago

The article seems to indicate that this could be a SAE, but also that "the participant is expected to recover".

_jahh2• 6 years ago

surviving with quadriplegia would be recovery but I believe an SAE

emmanueloga_• 6 years ago

how do they find volunteers for such a trial? If I get it right, the risks are high (including death?) so seems like a big risk, and I suppose they need to start with someone that's healthy to avoid confounding factors?

jedberg• 6 years ago

The risk of getting the virus is death too. If you're already in a risky position (say you're a teacher in a district that is insisting on in school teaching or a paramedic or cashier at a grocery store) then the vaccine trial might be the less risky option.

refurb5• 6 years ago

The risk of death or serious injury with an investigational product is very low, but it does happen.[1]

Clinical trials start after a lot of toxicology screening in vitro and then in animals. For first in human trials, the doses are sub-clinical and then dose-escalation studies are done to find out when adverse events start.

They basically work their way up to therapeutic doses very slowly, monitoring the health of subjects very closely.

[1]https://en.wikipedia.org/wiki/Theralizumab

klmadfejno2• 6 years ago

I don't the answer to this either, but I was surprised at the scale (30,000 people!). It makes sense, but wow, sounds hard.

dahfizz• 6 years ago

how do they find volunteers for such a trial?

They pay them. Being a construction worker is another example of young, healthy people doing something dangerous and being compensated.

animationwill• 6 years ago

I heard decades ago that prisoners will sometimes be recruited in exchange for reduced sentences, but not sure if that was the United States or elsewhere.

Edit: I hope I am not spreading a myth further

notatoad• 6 years ago

maybe this is off-topic, but it's interesting to me that this is the first time i've heard this referred to as the "astrazeneca vaccine". all the previous good-news stories seemed to call it the oxford vaccine.

dekhn3• 6 years ago

This is a US trial, AZ is listed as the Sponsor for the trial, https://clinicaltrials.gov/ct2/show/NCT04516746 and the PIs listed are both at US.

seedless-sensat• 6 years ago

Except the adverse reaction was not in the US trial.

mikeyouse• 6 years ago

So Oxford (the Jenner Institute / Oxford Vaccine Group) developed the vaccine but they're partnering with AZ to get it tested and then manufactured and distributed if the testing goes well. Oxford sponsored the initial studies and AZ is taking over now that it's more sophisticated and expensive.

Short background here:

https://www.cnbc.com/2020/05/21/coronavirus-us-gives-astraze...

cblconfederate4• 6 years ago

yeah just realized it s the ChAdOx vaccine. Perhaps a more systematic naming scheme would be appropriate here, as people do watch these studies. There are a lot of adenoviruses studies going on in russia, china etc, and they are somewhat related.

hartator• 6 years ago

Is this one of the two favorites?

Marazan• 6 years ago

Yes. The one in pole position.

Until now.

mrfusion4• 6 years ago

Is that why the market was down today?

zerobits4• 6 years ago

The Moderna mRNA vaccine was producing 103 degree fevers (and passing out) in a Phase 1 volunteer. [1]

If that's the reaction in small sample with a healthy 29 year old (most volunteers had high fevers), I can't imagine old or unhealthy people will be unharmed. I was more concerned about the mRNA vaccines being at risk initially.

Things aren't looking great...

[1] https://www.statnews.com/2020/05/26/moderna-vaccine-candidat...

DebtDeflation2• 6 years ago

Meanwhile, the CEOs of Pfizer and BioNTech have been talking up how their vaccine will be ready for approval in mid/late October the last few days. It's honestly a little disconcerting.

roody15• 6 years ago

“The platform has not been used in an approved vaccine, but has been tested in experimental vaccines against other viruses, including the Ebola virus.”

hmmm... this method of vaccination has never been used in an approved vaccine.

alkonaut• 6 years ago

You’ll find that’s the case for several of the front runners.

manicdee4• 6 years ago

All medicines were new at some point in time.

Your anti-vax fear mongering doesn't belong here.

pieceofcakedude2• 6 years ago

LOL! Pointing out that an unfamiliar vaccine technology has never been used before is now officially anti-vax fear mongering.

toast0• 6 years ago

Plenty of medicines were new and then removed from the market.

Being cautious about new techniques seems reasonable, given the history of medicine. (And frankly, a lot of other fields)

It would be nice to be able to say this new vaccine is based on existing methods that we know from years of experience are very safe; but we can't for this candidate. That doesn't make it less safe (or more safe), but it makes the risk more unknown.

anoncake7• 6 years ago

"New" medicines have been tested for years before they're used on a large scale.

tuna-piano2• 6 years ago

There's nothing inherently safe about injecting stuff into humans. There's nothing inherently crazy about questioning if injecting specific things into people is safe.

Vaccines on the market today are only safe because they've been studied and trialed extensively. Many vaccines, doses, additives, etc have and will continue to be proven to not be safe.

A recent example of an approved vaccine which may have caused deaths: https://en.wikipedia.org/wiki/Dengvaxia_controversy

pieceofcakedude2• 6 years ago

hmmm... this method of vaccination has never been used in an approved vaccine.

Yes, frightening isn't it? Anyone else worried that we're going WAY too fast with vaccine business? Typical development time is 5-10 years now down to less than a year? Its insane to me but yeah I get it, people are so sick of masks they might be willing to accept _any_ vaccine, efficacious or not.

We almost owe Trump a thank you for saying "lets get this out by October 31st" (almost, but not really). The media predictably took the opposite stance as Trump as it always does and now we're beginning to have much needed discussion on the safety risks of rushing a vaccine. Vaccine safety is a topic that is rarely talked about (mostly due to censorship) and frankly, even suggesting such a topic gets you called an "anti-vaxxer". Clown world.

linuxftw2• 6 years ago

vaccine business

Key phrase here. Cui bono? It just so happens there are multiple, patented competing technologies hoping to get approved. The biggest advertising spenders for the media. The media hyping up a 'vaccine.' Governments handing over hundreds of billions of dollars to private corporations so they can race to release a newly patented product that they're hoping will be forced on literal billions of people.

No, it's totally all above board.

volkse• 6 years ago

The russian vaccine is also based on adenovirus vectors. Not clear if the method of delivery is to be blamed here, but it could be the cause for the adverse effects..

YarickR2• 6 years ago

They (russians) are conducting large scale phase 3 experiment, with up to 40k volunteers. Need to watch closely; most of the volunteers are in Moscow, and it will be difficult to conceal high rate of side effects .

kurthr3• 6 years ago

Careful, because a "high rate" would be ~1/100k. Even a two SAEs in that cohort size, would be a huge deal and enough to shut down most efforts.

Edit: also note that the Russian Gamaleya vaccine is actually 2 vaccines one with a human adeno virus carrier and the other with a (chimp?) Ad5 and Ad26. So you could have a response to either one of them, or both. The problem with using a human viral carrier is that pre-exposed might fight it off without developing nCoV immunity.

ck2• 6 years ago

can't find the link at the moment but there is now some academic comment that the russian data has some fakeness to it

dang• 6 years ago

Other ongoing Covid vaccine thread: https://news.ycombinator.com/item?id=24411540

fancyfredbot• 6 years ago

Not good news, but don't panic - as the article says "Clinical holds are not uncommon", and “in large trials illnesses will happen by chance but must be independently reviewed to check this carefully.”

klmadfejno2• 6 years ago

I agree, don't panic. However that phrase isn't especially useful. Clinical trials failing isn't uncommon either.

dvirsky• 6 years ago

One bit of positive impact this might have is to increase people's confidence in the safety of the process.

ummonk4• 6 years ago

Yeah given the size of their trial there's a good chance this is a reaction to something else rather than the vaccine.

redisman• 6 years ago

There are also multiple other vaccines using completely different techniques to trigger immunity in stage 3 trials if this ultimately fails

zobzu3• 6 years ago

I wonder what are informed positions about these vaccines potentially modifying and patenting your DNA or using aerogels (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539078/) since these stories float around in particular for this vaccine to my understanding.

Are these all bs? What's the risk?

zamalek2• 6 years ago

modifying and patenting your DNA

In order to do what, exactly? These bizarre conspiracy theories always lack a specific goal by the supposed perpetrators.

using aerogels

So, what if they did?

mandelbrotwurst• 6 years ago

You're lacking in imagination if you can't come up with ways that someone might be able to profit from legal rights to or the ability to modify the genetic code of other persons.

djsumdog5• 6 years ago

I'm having trouble more details information on how the messenger-RNA based vaccines work. They appear to transcribe proteins in the cytoplasm. I think the fear is that these vaccines may contain some combination of Reverse Transcriptase and Integrase enzymes. Do they contain these enzymes? If not, do they simply try to get your cells to create spike proteins?

pvaldes• 6 years ago

modifying and patenting your DNA In order to do what, exactly?

Lotta money selling it, example:

https://en.wikipedia.org/wiki/HeLa

"as Lack's cells were popularized and used more frequently throughout the scientific community, Lacks's relatives received no financial benefit and continued to live with limited access to healthcare"

zobzu3• 6 years ago

I'm not really interested in the goals but on what parts are true/not true.

But it seems easier to get upset and downvote rather than explain, which in turns fuels conspiracy theories. Now I understand most of us arent biomedical engineers or something like that - but I'm just hoping someone sees it and gives an informed reply.

tus88• 6 years ago

Someone better come up with one. I don't want another year of this bull.

djsumdog5• 6 years ago

It's unlikely. I'm much more likely fatalities will drop to zero per week before the end of the year in countries with high spread and we'll have herd immunity (which is where Sweden is at now).

0x1A567BBF• 6 years ago

Sweden is nowhere close to achieving herd immunity (as everyone knows).

thehappypm4• 6 years ago

This community refuses to acknowledge that Sweden’s strategy has merit.

jessaustin3• 6 years ago

Herd immunity isn't possible when antibodies are as transient as those seen for COVID-19. Only a massive public push with an actually effective vaccine will control this pandemic.

kjaftaedi2• 6 years ago

Even most 'high spread' countries have less than 10% of the population that have contracted the virus.

To get to herd immunity levels, millions of people would likely die.

kuhewa7• 6 years ago

we'll have herd immunity (which is where Sweden is at now).

No, even Sweden's epidemiologists say that up to 30% of their population could be immune.[1] They tried to shoot the moon but missed. They are in a similar place to nearby countries now but got there with a much higher death toll

[1] https://www.marketwatch.com/story/uk-abandoned-herd-immunity...

cblconfederate4• 6 years ago

maybe we re more likely to find a cure rather than vaccine. most epidemiologists think a vaccine won't even be possible considering past experience with coronaviruses

stirlo• 6 years ago

most epidemiologists think a vaccine won't even be possible

Unsourced statements like this are unhelpful.

The language I've heard is "there is no guarantee of a vaccine" which is very different to thinking it won't be possible at all. I'd suggest with the 200+ plus vaccine candidates being developed that many believe it is possible.

tuna-piano2• 6 years ago

At a certain point, the choice between: "Do I want to lose a few days of my life to a disease with a tiny chance of a bad outcome?" vs "Do I want to lose a year+ of my life not doing what I enjoy?" becomes overwhelmingly obvious.

In March/April - I didn't leave my apartment for a month (besides tossing trash across the hall).

I still avoid most any indoor spaces, wear n95 masks and am not planning any plane travel (one of my biggest enjoyments) or visiting friends/family indoors this winter...

But I'm starting to seriously debate licking every door knob I pass just to get it over with already.

sergiomattei3• 6 years ago

Getting sick puts not just you at risk, but your family, friends, coworkers, and anyone you come in contact with after and during the fact.

It also could generate unnecessary strain on our health system that is already over capacity.

There's no need. Stay at home, stay protected, and don't take an unnecessary risk because you can't be mildly inconvenienced to save someone else's life.

manicdee4• 6 years ago

"Do I want to lose a few days of my life to a disease with a tiny chance of a bad outcome?"

There's a high chance of a bad outcome, there's a tiny chance of death. The virus affects your lungs and brain, and who knows what other parts of the body we haven't been alerted to yet.

As time goes on we'll be back to "plague doors" for cafes and restaurants. We'll adjust our way of doing business so that we don't rely on having all the key people in a company in one room for irrelevant meetings (I mean we can dream, right?).

jameson2• 6 years ago

It was not immediately clear who placed the hold on the trial, though it is possible it was placed voluntarily by AstraZeneca and not ordered by any regulatory agency. The nature of the adverse reaction and when it happened were also not immediately known, though the participant is expected to recover, according to an individual familiar with the matter.

What would be a reason why they don't disclose this detail immediately but only to tell public the trial is on hold?

lowwave2• 6 years ago

It is big pharm. What else do you expect? A little research you will find no big pharm can be trusted.

lowwave2• 6 years ago

What is meant by that is vaccine and all FDA type of drug should not be trusted unless they have several decade if not intergeneration studies to back it up.

TheSpiceIsLife• 6 years ago

This is a medical treatment sort of scenario, trial participant confidentiality regulations probably prevent release of anything specific about the case.

tptacek• 6 years ago

What would be the reason to disclose the details publicly? You can't do anything with the information right now; the vaccine isn't available to you.

roland00• 6 years ago

The illusion of control. It is the same reason people doomscroll on twitter hoping more information will somehow how change the result. Our brains, all human brains, are not rational but instead are their own thing.

jameson2• 6 years ago

I'd say for transparency reasons. I tend to prefer disclosing information when they are certain to not to unnecessary give false hopes or panic.

elliekelly• 6 years ago

Investor disclosure. That the trial is on hold is material information to investors but the medical reasons why it’s in hold (like the type of adverse reactions) probably isn’t.

refurb5• 6 years ago

At least for the details of the adverse reaction, it's not unusual for it take 1-2 weeks to collect all the details and form a complete picture. No sense in rushing out initial details, only to have the conclusion change a week from now.

Don't forget that the drug companies sponsor the studies, they don't actually run them. They are typically run by academic centers supported by third party vendors who handle the data collection, etc.

Someone will likely need to go back and look at the patient's clinical data to see if anything was amiss before this event. Then you'd need to collect a bunch of data to make a determination of the cause - was it the vaccine? was it some unrelated medical condition? a combination of the two?

reese_john• 6 years ago

According to the NY times, the adverse reaction was transverse myelitis

The individual also said that a volunteer in the U.K. trial had been found to have transverse myelitis, an inflammatory syndrome that affects the spinal cord and is often sparked by viral infections.

More at: https://www.nytimes.com/2020/09/08/world/covid-19-coronaviru...

joshgel• 6 years ago

Transverse myelitis, usually causes by viral infections, can cause complete paralysis below the level of the lesion. Just like a transection of the spinal cord. Quite serious, I would guess determining the etiology in this case is going to be critical, but very hard to do.

Can also be autoimmune, perhaps triggered by vaccine. Or, in this case, could be triggered by the adenoviral vector used in the vaccine.

tdrp• 6 years ago

So if this was triggered by the vaccine (rather than the adenoviral vector), would it mean that this person might have also had TM if they had caught Covid19?

est31• 6 years ago

That's what you have studies for! Glad they caught it before it got into the wild.

Also, it's really great that there are multiple vaccines. Just imagine what happens when everyone gets a single vaccine that turns out to very often cause an adverse reaction...

LeoNatan253• 6 years ago

And this is why trials must be allowed to run their course, not use vaccines as political propaganda, like what the Russian gangster and the orange clown are doing for their own political gains.

WalterBright• 6 years ago

All drugs have adverse side effects. The idea is the "therapeutic index" being the ratio of the good to the bad. In this case, balancing the risk of the vaccine against the reality of all the deaths that covid is causing.

Waiting for a zero risk vaccine is not the optimal decision.

anoncake7• 6 years ago

Not everyone. Just the ones who thought it was a good idea to get injected with a rushed vaccine.

lysp• 6 years ago

I read some comments online that said the control group is being given a meningococcal vaccine.

Transverse myelitis is apparently a rare complication with that vaccine.

It's possible (although not confirmed), the adverse reaction may have been from the control group.

nikk1• 6 years ago

"... the participant was injected with the company’s Covid-19 vaccine and not a placebo, Soriot said on the conference call..."

https://www.statnews.com/2020/09/09/astrazeneca-covid19-vacc...

tjmc• 6 years ago

Question for people who understand the Phase 3 process - would the first step in an investigation of this type be to "unblind" the patient with the adverse reaction to see if they got the vaccine or a placebo?

Seems to me if the reaction wasn't caused by the vaccine there's a 50/50 chance this person received a placebo. In which case, you could instantly discount the vaccine being the cause.

abiogenesis• 6 years ago

Interestingly placebo-induced adverse reaction is also a thing: https://pubmed.ncbi.nlm.nih.gov/10367099/

lbeltrame5• 6 years ago

The principal investigator of the trial knows who got placebo and who did not, although neither the people working on the data nor the clinical staff know.

It's likely that the participant will be "unmasked" to see why the adverse event occurred.

ageitgey2• 6 years ago

I'm in the trial. We all got little cards with our trial number to keep in our wallet. If we get seriously ill or end up in a hospital, there's a number for the doctor to call to unblind us if necessary. So there is definitely a procedure in place.

Even if the person got the vaccine, the illness could be unrelated. They need time to investigate and this is the proper procedure to follow. This happened once before earlier in the trial, but it wasn't reported as widely and there want a media frenzy.

There is nothing wrong with the media reporting this, but it would be great if the media was better at contextualizing information instead of maximizing clicks with scary headlines.

yalogin• 6 years ago

This is the vaccine trump set his hopes on to be available by November. Isn’t it?

hestefisk3• 6 years ago

One of them. It’s funded through Operation (OS/2) Warp Speed.

aaron695• 6 years ago

What's really funny is even if they can prove it's not an adverse reaction the anti-vaxers will run with this forever.

If you can prove anything.

If it's not real.

And absolutely this is just the beginning.

These things normally don't make the news. This will be all the time over the hundreds of vaccines and when they get rolled out properly there will be hundreds of stories to pick from.

AstraZeneca Covid-19 vaccine study put on hold due to suspected adverse reaction

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