AstraZeneca Covid-19 vaccine study put on hold due to suspected adverse reaction | Hacker News Reader

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

statnews.com

262 pointsaaavl2821223 comments

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

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

>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

Do the adenos actually have to infect the cells to produce the spikes?

Yes, they don’t replicate virons that could be assembled the virus was modified to mainly replicate the spike proteins since your cells send samples of anything they replicate to the cell wall for your immune system to monitor and sample this is how the adaptive immune response is achieved.

Exactly, for strong long term response you want T-cell involvement.

> cells send samples of anything they replicate to the cell wall for your immune system to monitor

Wow nature is truly a marvel! How do they do that? Or where could I read more?

> Wow nature is truly a marvel! How do they do that? Or where could I read more?

Read about the HLA/MHC class I pathway. And also about JAK/STAT1, which is how cells decide if they are infected.

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-...

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

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

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

I'm going to print this out and frame it.

Yeah, I just wrote this down to remember for later. What a quote.

Repressed humour from the programmer son of a pathologist.

My favorite dad quip was 'Biology itself is proof against an intelligent designer.'

Biology is too "complicated" for our intelligence at least.

His point was more along the lines of it being poorly designed.

Evolution isn't going to nicely separate functionality into clean, single-purpose biochemical pathways.

It's going to overload something that it already has to support a new feature, leading to a rat's nest of intertwined effects.

The hard part in drug development isn't affecting your target: that's pretty easy to guarantee with modern tools. It's finding out that that target also governs 10 other, completely unrelated bodily functions.

> It's going to overload something that it already has to support a new feature,

Some companies in the valley just call that Wednesday.=)

Absolutely, which gives me a chuckle when people trivialize biology, but run screaming from a (gasp!) 20 year old legacy codebase.

And it has to work on 7 billion similar but slightly different operating systems

> unit testing.

Did you mean integration testing?

Absolutely not.

Evolution unit tests, then integrates in prod.

> 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.

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.

It sounds harmless because it omits the incredibly complex process of developing immunity.

Your body basically is trying to do a sort of brute force/random combination of immune cells on the retrieved virus spike proteins until it comes up with the right combination.

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

This process can result in B cells that produce antibodies which stick to virus proteins but also stick to your own cells. The B cells are essentially permanent, that’s how you develop lasting immunity, that unfortunately also means you have lasting immunity on one of your own cell types — autoimmunity https://en.wikipedia.org/wiki/Autoimmune_disease

A 50000 people study is likely to see adverse events completely unrelated to the vaccine. Halting the trial is not a sign that they think it is related either, since it is protocol to rule things out before continuing.

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

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.

> 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...

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

Plenty of vaccines both today and historically used LAV or other natural strains of the virus when possible.

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.

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.

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.

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...

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.

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?

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...

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.

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.

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

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

The situation in Sweden suggests that any serious risk model cannot accept a wide scale vaccine solution within a near time window.

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

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.

"... 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...

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

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

surviving with quadriplegia would be recovery but I believe an SAE

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?

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.

That's a terrific invitation for bias.

Unless you're a teacher over the age of 55, your risk, even around a bunch of school children, is incredibly low (95% of fatalities in the US are over 55, with most of those being over 65).

I've read a few of these "long term damage" studies that are scaring everyone. Of the 60+ people in the UK one published by the journal in Charlottesville, most of them were elderly or in "high risk" jobs (it didn't mention what jobs for privacy. Health care workers? grocery store? who knows).

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.

> "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.

One adverse effect after X amount of time, hopefully this doesn't get any worse... :(

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...

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

Risk of death may be lower but we still don't understand the long-term impact.

Italy is just starting to look at this after their recovery and the initial signs are not great: https://www.washingtonpost.com/world/2020/09/08/bergamo-ital...

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

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.

> 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.

The Oxford trial isn't paying anyone. I'm in the trial myself. I assume other people are volunteering because they want a COVID vaccine to come out.

Volunteers for this trial range in age from 5 to 75+. Not everyone is perfectly healthy.

People here are reacting like the vaccine isn't safe and is cancelled now. All this news means is that one person out of tens of thousands had a possible reaction and they have to investigate to see if it is even related to the vaccine (which is the proper procedure). This isn't even the first time that this has happened during this trial - it just wasn't reported so widely last time. The most likely outcome is they pause for a few days and then keep going as normal.

Thanks for the context.

Thanks this is very helpful. I also just read in the Guardian that they paused it back in April due to a similar issue. Fingers crossed it resumes to plan.

> Volunteers for this trial range in age from 5

I'm sure that 5-year old has carefully considered their decision.

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

That's something that is explicitly not done, unless there is a very good rationale for why it would need to be prisoners studied. The reason being, it is all but impossible for a prisoner to give a proper informed consent. There is just too large a conflict for testing to be considered voluntary, especially if there is some kind of quid pro quo. See here [0] for a list of permitted research on prisoners (45 CFR 46).

True, it has been done in the past, but there are many... many horror stories associated with the practice [1].

[0] https://www.ecfr.gov/cgi-bin/retrieveECFR?gp=&SID=83cd09e1c0...

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

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.”

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

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

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

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

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..

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 .

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.

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.

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

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.

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.

Except the adverse reaction was not in the US trial.

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.

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.

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.

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...

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.

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

> 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?

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

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.

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

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.

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.

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.

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.

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.

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?

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.

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

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.

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.

Is this one of the two favorites?

Yes. The one in pole position.

Until now.

Is that why the market was down today?

No, the AZN announcement was made after the market closed. Take for instance Moderna, who was -13% today, and is +3.7% after-hours

Not tracking the real world anymore

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...

Phase 1 trials are used to determine dosage. Different participants are given different doses of the vaccine so researchers can identify the proper dosage with maximal efficacy and minimal side effects.

The 29 year volunteer who experienced the 103° fever received the highest dose of the vaccine given out during the Phase 1 trial. Such a adverse reaction is not unexpected during a Phase 1 trial, but the vaccine did move forward to Phase 2 and Phase 3 so it appears that the lower dosages do not trigger such a reaction.

Even the "mild / moderate" reactions were pretty bad though. They sounded substantially worse than your average cold.

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).

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.

> 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.

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

> modeRNA

I can't believe I didn't notice that until now.

Every time we see or hear an expert on the topic of COVID-19 vaccines, she/he is either circumspect to the point of pessimism (this is rare, but see e.g. Robert Gallo) or obviously trapped in a spiral of wishful thinking (this is common). We've never made anything like this hypothetical drug. Forget about election day. I'll be surprised if we have a commonly-available and effective COVID vaccine in 2021.

Not the question you asked but the Chinese company Sinopharm has started phase 3 trials of a classic inactivated virus vaccine (and Bharat Biotech is starting phase 2 trials as well in India). The difficulty will be mass-producing it, of course, but we aren't necessarily reliant on novel vaccine technologies.

That was at the 250ug dose, current dose is 100ug. At that dose, even the elderly didn’t have bad side effects.

It’s disingenuous to call it “the Moderna mRNA vaccine” when it was more accurately “one early Moderna mRNA vaccine candidate, which was ruled out for being far too high of a dose”.

Thanks for the valid correction.

I didn’t mean to be disingenuous. I forgot they rejected that dosage.

Overall, the picture does look potentially concerning for the side effects of that vaccine and efficacy is still unclear.

What makes it concerning? Tylenol is concerning if you take 2.5x the safe dose. Of course the efficacy is unclear — it’s still in trials!

There was a pretty high severe systemic adverse rate in the high dose group (20%). Severe local response rate was 5% in the middle dose. [1]

I have no idea how this compares to other vaccines, and you can pessimistically extrapolate a bit from this tiny, healthy sample from the high dose (n=15 in middle dose group).

I'd imagine some % of people when this scales to millions will have a bad response, and the high dose group might provide some model of the worst cases.

[1] https://www.nejm.org/doi/full/10.1056/nejmoa2022483

I think the comparison most are making is to Shingrix. Have a look at Table 2[1].

[1] https://www.nejm.org/doi/pdf/10.1056/NEJMoa1603800

Fevers are very common in vaccines, normally. It is an indication that the immune system developing an immune response. It is not an indication of complication.

Yes, but at some threshold wouldn’t this indicate a problem?

103F+ fevers are relatively rare from typical vaccines, and from my understanding a lot of the damage from COVID is immune response related.

mRNA vaccines and our immune responses to these are uncharted territory, so I’m not sure how much we can reason by analogy from other vaccines vs. first principles.

High fevers are not uncommon in babies receiving their first vaccines.

I'm not sure it indicates a problem. A fever is, itself, just an immune system response, not a "symptom" of disease.

You are correct that there is a threshold beyond which a fever becomes unsafe, but it's above 103. But fevers of 103 in the test group do not indicate that fevers of say 105 will occur in some patients.

mRNA would not have hit Phase III if found unsafe in earlier phases. If mRNA succeeds things will look really great, since it in principle it can protect against many other viruses and upcoming pandemics with slight modifications. The most reported side effect for mRNA is mild stiffness at application spot.

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.

Where are you seeing that? Pfizer's CEO's comments seems quite measured.

"Last week, he said the company could have results from its late-stage coronavirus vaccine trial as early as October after enrolling 23,000 volunteers."

https://www.cnbc.com/2020/09/08/coronavirus-vaccine-pfizer-c...

The BioNTech CEO wasn't nearly as measured in his comments.

https://www.cnn.com/2020/09/08/health/pfizer-biontech-vaccin...

"Pfizer and BioNTech are confident they can have a vaccine against the novel coronavirus ready for regulatory approval by the middle of October or early November."

This doesn't seem extreme to me. "ready for regulatory approval" just means they've submitted a complete package to the FDA.

However, this is a really stupid comment.

"It has an excellent profile and I consider this vaccine ... near perfect, and which has a near perfect profile,"

And at least according to FDA regulations, that statement violates a number of rules around the promotion of unapproved products.

If memory serves right, the CEOs were talking about it late August but from yesterday's announcement[0] : "Nine drug companies issued a joint pledge on Tuesday that they would “stand with science” and not put forward a vaccine until it had been thoroughly vetted for safety and efficacy"

[0]https://www.nytimes.com/2020/09/08/world/covid-19-coronaviru...

As if how much risk is acceptable were a matter that could be objectively and scientifically decided.

“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.

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

All medicines were new at some point in time.

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

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

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.

I mean you could check the other comments under that one to see that it's a deliberate trigger for anti-vax fearmongering.

It's one thing to be skeptical, it's another to be a denier. If you can't pick up on the cues then you'll never be able to fight misinformation.

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.

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

That's right, testing is part of scientific medicine.

Once it's been through the usual tests and we have some idea of efficacy and understand how to manage the side effects, it will be approved for use.

How to manage the short-term side effects. Testing for long-term ones cannot be done quickly.

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

>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.

> 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.

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.

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

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).

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

Then home come their case rate just keeps falling? And their death rate. And unlike the countries that locked down, they're not experiencing a second wave of cases.

Even in countries where a second wave is happening, it’s a wave of infection only, not deaths. There is not reason to be scared of a disease that don’t kill. International travel restrictions should be lifted. We don’t need to wait for a vaccine that might be more a dangerous than to virus it’s supposed to fight. Current practices in East-Asia have shown to be enough to handle the thing.

  There is not reason to be scared of a disease that don’t kill.

What about one that causes permanent lung and/or heart damage?

You mean like other viral infections, or bacterial pneumonia? As grave as the effects are, they are absolutely not unique to SARS-CoV-2.

Sure, and those grave effects are a 'reason'

The incidence of these effects can be a reason. Unfortunately there are no reliable data on how they are prevalent.

My point is insofar as one would/should fear death, they would/should fear a decent probability long term nonfatal consequences to some degree. Incomplete information doesn't obviate that.

Nonfatal=/=nothing to fear

This is not universally true. In parts of California there was a jump in death rate reasonably close to a partial reopening. And has very slowly been trending downwards since they re-closed everything.

https://www.worldometers.info/coronavirus/usa/california/

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

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?

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'

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.

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.

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.

10M is a lot. It’s a population larger than the majority of US states and by far enough to draw conclusions from.

Sweden allows gatherings above 500 now (https://www.thelocal.se/20200827/breaking-sweden-to-allow-pu...). And it never forced business closures, which is way more open than most US states.

Because the virus isn't coming back in Sweden, whereas its neighbours are already experiencing a second wave. Sweden's argument was always that it was "front-loading" the infections, so over the long-term other countries would see a similar number of infections as they experienced multiple waves.

Plus they avoided the rise in depression and domestic violence that countries with lockdowns endured. As well as avoiding massive violations of human rights, although you leftists seem to care nothing about that.

  Because the virus isn't coming back in Sweden, whereas its neighbours are already experiencing a second wave. Sweden's argument was always that it was "front-loading" the infections, so over the long-term other countries would see a similar number of infections as they experienced multiple waves.

That doesn't appear to be what's happening.

https://ourworldindata.org/coronavirus-data-explorer?zoomToS...

Also, Sweden didn't avoid an uptick in domestic violence.

https://webcache.googleusercontent.com/search?q=cache:iuGdja...

Something recent that's been under-reported. The US, the country pulling an accidental Sweden, has seen a 33% decline in new cases since mid-July. The narrative is still that the US has done worse than any other developed country, but look at Spain and France. Both have surpassed their ~April peaks, have per capita new infection rates above the US.

How's Sweden's new case rates? Stable, and 1/4 of the US's.

The list of countries that have been able to maintain their low case counts is getting shorter, and the US is looking less exceptional in its response.

"Listen to the epidemiologists" only works for a bit. It turns out psychology was just as important.

France sent students back to school, and re-opened its universities, and allowed gatherings of 5,000 or more people, and did not require masks in public, or in workplaces, with predictable results.

Their response, and the results mirror that of the worst-performing US states.

In what sense? Lots of elderly people have died. Is that ethical?

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.

There have been what, three cases of people being infected twice? And they barely got sick?

The antibodies from infected people are being shown to last somewhere on an average of 3 months.

Kinda hard to be immune if you have nothing to protect you.

How sick you get from the disease is irrelevant in this context.

Your understanding of the immune system is not quite correct. Just because you can't detect antibodies doesn't mean you lack immunity.

B-cells can stop producing antibodies and reactivate production in response to an antigen. T-cell memory appears to be quite robust for coronaviruses (and this one in particular)

To establish a lack of durable antibody response, challenge trials would need to be done, where the host is challenged by the virus (or something that looks like the virus like it's spike protein). These trials have not been run.

We can only guess without data specific to SARS-COV-2, but for seasonal coronaviruses, antibodies disappear after ~6 months and reinfection with the same strain can occur after 1 year.

It isn't entirely irrelevant. If you can get reinfected but not get sick twice, it's as if we reached herd immunity at 100%.

And it's perfectly normal that antibodies don't stay in the bloodstream forever. The immune system remembers how to make them and can produce new ones when needed.

Reinfection is problematic for herd immunity strategy as it keeps the transmission rate , R high. This keeps the less healthy vulnerable.

That's just flat out wrong. If that were the case, than the Spanish Flu would still be killing millions of people per year.

SARS-CoV-2 and A/H1N1 aren't even in the same phylum. It would be silly to expect them to have precisely the same effect. Besides, when people gush about "herd immunity" they don't usually include the caveat "of course it's going to kill fifty million people first!"

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.

Are you talking about antibodies? There are papers on T-cell immunity and clicks who've tested staff a month apart with no increase in antibody positive tests.

It's probably WELL over 10%. There are more ways our immune system can develop memory than just antibodies and a number of studies are showing that.

> 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...

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

> 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.

There are many different concerns. I havent done a rigorous meta-analysis but they also come from very respectable scientists.

> https://www.businessinsider.com/coronavirus-vaccine-may-be-i...

https://www.telegraph.co.uk/global-health/science-and-diseas...

And notice that there haven't been very exciting news from the vaccine developmnent trials. If anything there were more setbacks than pleasant surprises.

There were concerns because SARS vaccine attempts hadn't been further developed due to apparent cytokine storm problems. I think we're far enough along to be confident that that isn't an issue with vaccines for this virus.

Some people also make a comparison to the common cold coronaviruses which have a lot of strains and might be rapidly mutating. Honestly, it's a bad comparison because it's clear this coronavirus isn't mutating rapidly, and besides we haven't really tried to target common cold coronaviruses - why would we when rhinoviruses are the most frequent cause of the common cold?

There's a bit more to it. The reason vaccines weren't developed previously for other coronaviruses is because in trials for a RSV vaccine, 80% of treated kids that got infected needed hospitalisation and two died, while something like 5% of the control infections needed hospitalisation. Due to antibody-dependent enhancement.

So yes there are immunopathology concerns with eliciting a T-cell response, and inducing a humoral immune response has the potential to make things worse.

That's why most trials take a look at the Th1 vs Th2 response to see if there's any indication of ADE. The currently available data do not seem to point to that.

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.

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.

> you can't be mildly inconvenienced to save someone else's life.

A major disruption for a year isn't a "mild inconvenience." The longer this goes on, expect more and more people to feel like GP.

> "Do I want to lose a year+ of my life not doing what I enjoy?"

Sounds like a mild inconvenience to me. Any other reason wouldn't be.

And of not doing what you want. At a year, you start going through math around the likelihood you'd die from the virus and realizing that even with a 1% mortality rate, for someone with the whole life ahead of them, the time/opportunity EV is negative.

There are people who set a monetary value on human life, and we have good estimates on that. What we don't have a good number for is what's the value of different degrees of freedom. Is a life where traveling is impractical, meeting people is challenging, you can't go to Disneyland, all that stuff, is it worth 75% of a life at 2019 levels? I don't mean this economically, I mean this as living life.

> , you start going through math around the likelihood you'd die from the virus and realizing that even with a 1% mortality rate, for someone with the whole life ahead of them, the time/opportunity EV is negative.

Could you elaborate on this? By EV you mean the expected value?

Yeah. It's not quite the same as EV, but the idea is that living one year of your life 75% "fully" is like reducing your life expectancy by 3 months. If you have another 50 years to live, if the choice is between 75% fully and any less than a 1 in 200 chance of dying or having lasting complications, you take your chances. Where this gets awkward is the elderly because it takes away one of their five good years left, but the alternative is a 15% chance of dying.

Really starting to get sick of this moral posturing. 1 year isn't a "mild inconvenience", the lockdown have been absolutely devastating to many many people, but of course you wouldn't know that because you probably WFH on a comfy salary for a tech company?

Once again, you misread.

I said their specific reasoning is a mild inconvenience.

And no, funnily enough, I'm unemployed (working on an early stage startup) and my savings are in the low triple digits -- total -- thanks to the pandemic. Might want to start limiting the number of assumptions you make.

> "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?).

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

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

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?

> 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?

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.

But nobody's DNA is being modified with these vaccines.

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?

They do not contain reverse transcriptases or integrases. Just wondering why you think they would?

> 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"

Practically nobody sells HeLa cells - They're gifted among researchers like plant cuttings or burned DVDs

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.

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.

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...

People are downvoting you because what you said is so nonsensical, there's not even a good place to begin the conversation. None of the vaccines modify your genome, so they can't "patent your DNA". And aerogels have nothing to do with vaccines.

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