
AstraZeneca Covid-19 vaccine study put on hold due to suspected adverse reaction - aaavl2821
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/
======
aphextron
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...](https://www.astrazeneca.com/media-centre/press-
releases/2020/astrazeneca-and-oxford-university-announce-landmark-agreement-
for-covid-19-vaccine.html)

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

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

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

~~~
ethbr0
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-...](https://blogs.sciencemag.org/pipeline/archives/2020/04/23/a-close-
look-at-the-frontrunning-coronavirus-vaccines-as-of-april-23)

~~~
mrfusion
This sounds pretty harmless. Any idea how they got a bad adverse event out of
it?

~~~
ethbr0
Imagine a 4 billion year old codebase, written by dice throws and unit
testing.

The immune system is a "complicated" thing to work with.

~~~
webmaven
_> Imagine a 4 billion year old codebase, written by dice throws and unit
testing._

That's a _great_ analogy, except it doesn't go quite far enough. The code for
the toolchain that compiles the codebase (not to mention the unit testing
framework) is just as old, and written the same way.

~~~
webmaven
Note to self: while the code (including the toolchain code etc.) is in a
monorepo, it is actually surprisingly modular. OTOH, much of the functionality
was implemented by copy-and-paste of existing code elsewhere in the repo, and
the copies then diverged with subsequent modification.

------
reese_john
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...](https://www.nytimes.com/2020/09/08/world/covid-19-coronavirus.html?smtyp=cur&smid=tw-
nytimes)

~~~
est31
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...

~~~
WalterBright
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.

~~~
LeoNatan25
But waiting for a reasonably safe and risk-free vaccine is, which is the point
of the trials.

~~~
_jahh
it is also true that this does not mean that this vaccine will not be the
reasonably safe and risk-free one

------
yread
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](https://en.wikipedia.org/wiki/Serious_adverse_event)

~~~
emmanueloga_
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
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.

~~~
osivertsson
Getting COVID-19 now you would know the risk of death is very low, especially
if you live in a society where you would have access to adequate intensive
care.

With the vaccine trial you are taking on an unknown risk which to me seems way
worse.

I think there are factors that drive people to join these trials though. For
example if you have a loved one that has a much higher risk of severe
complications if they catch the virus. Then it is in your interest to help get
a vaccine ready.

~~~
Reason077
> _" With the vaccine trial you are taking on an unknown risk which to me
> seems way worse."_

There's a reason why clinical trials are done in phases. If you are one of the
very first to receive a new medicine or vaccine, then yes, you are taking a
risk - and are compensated accordingly.

By the time it gets to phase 3 trials, you already have a pretty good idea of
the safety. One possible adverse event amongst 30,000 participants doesn't
seem so bad to me. Certainly it's less than the risk of developing serious
illness if you are infected with SARS-CoV-2.

~~~
jimmydorry
That would be 11,000 people with quadriplegia or worse amongst a population of
330M.

And keep in mind that the people participating in this trial are already pre-
screened, taking the healthiest of the potential candidates. Known side
effects would typically occur at higher frequency amongst the population than
found in a clinical trial.

EDIT: To add to this. The cost of rolling out medicine with SAEs at this rate
would cost the company / government in the order of about $4,730,000,000 (430k
x 11k) [1], which is about the equivalent to the amount paid out for all other
vaccine caused injuries over the last 30 years. This is likely low-balling it
though, as I bet the families sueing would get more than $430k with the
numbers of eyes on this.

[1]
[https://www.theatlantic.com/health/archive/2019/05/vaccine-s...](https://www.theatlantic.com/health/archive/2019/05/vaccine-
safety-program/589354/)

~~~
Reason077
My comment was in regard to the risks of clinical trial participation, not
approved vaccines.

There is some precedent for the scenario you describe, however: the 2009/10
H1N1 vaccine “Pandemrix” caused permanent narcolepsy in 1 in 55,000 children
it was administered to:

[https://www.narcolepsy.org.uk/resources/pandemrix-
narcolepsy](https://www.narcolepsy.org.uk/resources/pandemrix-narcolepsy)

------
fancyfredbot
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.”

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

------
volkse
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
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 .

~~~
kurthr
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.

~~~
tinus_hn
Pretty dumb because the damage from the real virus, both the damage from the
illness and from the measures against it, is much worse than that.

------
notatoad
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.

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

~~~
seedless-sensat
Except the adverse reaction was not in the US trial.

~~~
dekhn
I followed the first link in the stat article, which says "A large, Phase 3
study testing a Covid-19 vaccine being developed by AstraZeneca and the
University of Oxford at dozens of sites across the U.S. has been put on hold
due to a suspected serious adverse reaction in a participant in the United
Kingdom"

As I read that, it was a UK participant in a AZ and US-run study.

~~~
BickNowstrom
AstraZeneca and Oxford have subjects in the US, UK, Brazil, and South-Africa.
The aim was to have diverse make-up of the testing groups, to have an order of
magnitude more people in the Phase 3 trial than normal for a vaccine, to test
in countries with high infection rates, and to deliver the results on 15th of
September. A British subject from the British trial got ill.

I presume these countries have deals with Oxford/AstraZeneca so if a safe
vaccine is available, they get guaranteed access. I've heard India is already
producing the vaccine ahead of the Phase 3 conclusion. The phase 3 is only on
hold since it is not clear if the vaccine was the cause. There are other
causes for the adverse reaction, such as viral herpes infection, or onset
nerve diseases not caught during subject checkup. Since not all vaccines offer
100% protection (while still being useful), COVID may have also been the cause
of spinal nerve inflammation.

~~~
dekhn
As I would classify it, they're running _multiple_ phase 3 trials in multiple
countries, but applying _policy_ as if it's one big study (that wasn't clear).
An action in the UK study caused all the studies to halt. This is not strictly
required, but it's clear they're playing things conservatively.

------
dang
Other ongoing Covid vaccine thread:
[https://news.ycombinator.com/item?id=24411540](https://news.ycombinator.com/item?id=24411540)

------
jameson
> 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?

~~~
tptacek
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
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.

~~~
repsilat
Vaccine progress is of enormous practical consequence. Effective reporting of
material information can move markets, and that means it's useful for
efficient capital allocation.

Of course, there's diminishing returns and problems with many kinds of noise,
and AstraZenica isn't strongly interested in marginal efficiencies in the
broader market.

------
tjmc
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.

~~~
lbeltrame
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.

------
hartator
Is this one of the two favorites?

~~~
Marazan
Yes. The one in pole position.

Until now.

~~~
zerobits
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...](https://www.statnews.com/2020/05/26/moderna-vaccine-candidate-
trial-participant-severe-reaction/)

~~~
djsumdog
The idea a vaccine can be safely made in less than a year is absolutely
insanity. Many of these things shouldn't even be considered vaccines in the
traditional sense.

Are there any vaccines out on the market today that are not one of the two: 1)
inactivated virus, 2) attenuated virus (run through another host/egg or a
related virus found in an animation that's less harmful to humans)?

Everything I've found indicates all our current viral vaccines are one of
those two (excluding bacterial vaccines, which shouldn't be called vaccines
either).

~~~
cblconfederate
The modeRNA vaccine is an mRNA vaccine, a completely new type of vaccine.
While theoreticall less likely to have adverse effects, it did have adverse
effects, and its efficacy remains a question. These are completely new types
of vaccine, that presumably would need even more testing than the relatively
well understood attenuated viruses.

~~~
linuxftw
> completely new type of vaccine

Then is it a vaccine at all? Vaccines were traditionally live, dead, or
attenuated virus/bacteria injections, some with adjutants, to stimulate an
immune response.

Technologically speaking, it's bicycle vs airplane. Similar underlying
purpose, entirely different implementation.

~~~
LeoNatan25
Both a bicycle and an airplane are transportation vehicles. Likewise, anything
that illicits imunity is a vaccine, regardless of how novel the approach is.

------
roody15
“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.

~~~
manicdee
All medicines were new at some point in time.

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

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

~~~
puranjay
I swear the pro vaxxers are as much of a cult now as the anti vaxxers. I've
been attacked so many times for simply saying that I would wait a while for
results before trusting a rushed vaccine, especially one that has a massive
financial upside for the creator.

------
aaron695
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.

------
tus88
Someone better come up with one. I don't want another year of this bull __ __.

~~~
djsumdog
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).

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

~~~
vkou
Ten times the cases, and ten times the deaths of its neighbors, and a 8.6%
drop in GDP in Q2.

Meanwhile, Norway lost 5.3% of its GDP, and Finland lost 4.9%.

Exactly which part of this strategy has merit?

~~~
anoncareer0212
Not to mention Sweden is more locked down than the US - _0_ gatherings over 50
people allowed. 0.

I'm astounded there's still people doing the 'debate me!' act about it, most
gave up by July in the US, we had already clearly chose a more intense version
of the Swedish 'strategy'

~~~
puranjay
I'm amazed that smart people have been advocating Sweden's strategy. Sweden
has a population of 10 million. New York alone has more people than that.

It's as if population size, distribution and density aren't even a
consideration, let alone local practices.

~~~
logicchains
It was also the strategy of South Dakota, Nebraska, Iowa, Arkansas, Oklahoma,
Wyoming and Utah, and they seem to be doing a lot better in terms of both GDP
hit and caseload than places like California and New York with heavy
lockdowns.

~~~
vkou
Iowa has a projected 9.5% GDP hit. New York has a projected ~14% GDP hit, and
due to its density and reliance on elevators and public transit, will _of
course_ have a higher case load, and require harsher measures to control the
spread.

Half of the population of Iowa can fit in the 22 square miles of Manhattan.
Oh, and infection rates in Iowa are climbing, whereas infection rates in New
York peaked five months ago... And they are currently neck-and-neck in per-
capita cases.

So, how did a mostly rural state get a case rate that's as bad as a state that
packs half of its population into a single sardine-can of a city? Is their
strategy actually working, if they are getting the same outcome, despite
having a much easier set of starting conditions to deal with?

Meanwhile, in Canada, BC is projected to take a ~6% GDP hit... While having
1/10th the per-capita case load of Iowa, and higher population densities.

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

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

------
zobzu
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/](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?

~~~
zamalek
> 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?

~~~
zobzu
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.

~~~
zamalek
If there is no reason for them to do it, no goal, then would they spend money
doing it? No? Then the crazy is untrue.

~~~
zobzu
Money.. but still that's just a side topic. The document linked is pretty
official and pretty clear, but i guess no one reads it...

