AstraZeneca vaccine doesn't prevent B1351 Covid in early trial | Hacker News Reader

AstraZeneca vaccine doesn't prevent B1351 Covid in early trial

cidrap.umn.edu

263 pointsreddotX208 comments

FYI it’s the same study as the previous news about this, as in the same 2000 individuals study with no severe cases (hospitalization) or deaths in either group and very wide margins for confidence.

This is just the actual paper rather than the leaked abstract from a few weeks ago.

They commissioned a new study to assess the efficacy more precisely especially for severe cases.

I seriously don't understand this.

How does J&J vaccine offer 50%+ protection, but AZ does not?

Don't they use the same technology?

Don't they target the same spike protein?

Different tech. J&j isn’t an mrna vaccine

Nor is AZ. The Pfizer is one with the mRNA technology.

Pfizer and Moderna use mRNA.

neither of those are astrazeneca

neither is AZ

The J&J and AZ vaccines both use a similar viral vector with a modified gene.

They target the same protein but just like with the mRNA vaccine they usually do not encode the entire protein but rather target specific amino acid chains in various regions of interest on the protein itself.

Other differences in the vaccine would be the level and type of immune response generated in general which will be based on the specific viral vector used, dose and regiment, adjuvants etc.

The study which measured the J&J efficacy also used a different methodology to this one.

Overall this is a very limited study and should be taken in context.

Another key part is that the T-cell response for the AZ vaccine group seems to remain intact.

>Although the correlation between antibody response and vaccine efficacy is high, which suggests that the neutralizing antibody response is important, T-cell responses may contribute to protection from Covid-19 even in the presence of lower neutralizing antibody titers.32 In a post hoc analysis reported here, we found that in spike-specific T cells that expanded after vaccination with ChAdOx1 nCoV-19, the majority of antigens and epitopes remained intact in recognition of the B.1.351 variant.

Until we have data on actual severe cases it seems that the AZ vaccine is still effective at preventing hospitalization and deaths. There were also no tracking of non-symptomatic cases in the study so the actual prevalence of infections in either group is unkown.

Thanks, somehow with my software engineering mindset, I thought they somehow just copy&pasted the whole ARN sequence for encoding the spike protein from one virus to the other, and the end result should have been the same, but if its only parts of the S protein, then it makes sense that the outcome will be different.

If you want a software analogy, then I think it's more like using regular expressions to try to match inconsistent data, where new data (which is potentially inconsistent in new and exciting ways) is coming in all the time.

Like a virus scanner.

That’s a pretty good analogy the signature isn’t often not a simple hash of the malware but rather a more fuzzy signature based on core functions that are harder to alter without loss of function.

I don’t know if they even have enough room to encode the entire protein, that said even if they do it’s quite likely better to focus on specific amino acid chains that relate to specific structural areas of the protein that serve a critical function like interfacing with the receptors these aren’t likely to mutate without loss of function and it increases the likelihood of more targeted immune response.

If for example each vaccine selected 30 amino acid chains say 15 common ones and 15 that are varied between vaccines you can end up with vaccines that are more effective against certain mutations than others.

Realistically COVID-19 isn’t going anywhere and it will likely become very much endemic and will require a yearly vaccine especially for risk groups just like influenza.

Well now that casts this in a significantly different light. I have read that T-cell response is much more labor intensive to measure than antibodies, but it seems to not uncommonly tell a very different story.

That is starting to change. The FDA recently authorized Adaptive Biotechnology’s T cell assay. It's still more expensive than an antibody test.

https://www.t-detect.com/

They don't target the exact same protein and they use a different vector.

J&J uses a similar vector adenovirus just the human type instead of the chimp adenovirus.

But yes none of the vaccines use the actual spike protein, they all target slightly different amino acid chains on that protein.

They don't translate the spike protein from the original to the target the same way, they might have minor modifications for stability, etc

AZ tested every patient weekly for covid, regardless of self reported symptoms.

No other trial did this. Which means the 95% efficacy for phizer/moderna is not actually correct. we have no way of knowing how many were asymptomatic.

Data from Israel suggests that the Pfizer/Biontech vaccine prevents 97% of symptomatic and 94% of asymptomatic cases.

(After the intial trial phases had concluded Pfizer only reported how many symptomatic cases were prevented which might be the "95%" number you have in mind)

Is this the Israel study you're referring to?

https://www.nejm.org/doi/full/10.1056/NEJMoa2101765

Just curious, as I've received the Pfizer/Biontech vaccine.

I think it was more recent than that but I only saw reports about the numbers, not the thing itself.

I assumed every vaccine trial would be testing people regularly. I'm a little shocked if what you're saying is true. Is there not a lot on the line here? Maybe because it was in their interest to hide bad news?

These are for-profit companies shielded from liability. They're going to do only the bare minimum to get the product to market.

For other classes of drugs, these same companies have been sued and fined for billions of dollars for covering up problems with their drugs.

The regulators are beyond incompetent, they're typically industry shills.

The fact that the regulators have only issued Emergency Use Authorization for the vaccines shows that less than the bare minimum has been done to bring these products to market. The bare minimum used to be FDA Approval.

If "used to be" counts, then the bare minimum is whatever it takes to get someone to pay for it, like in the literal snake oil days.

It is such a weird stance, implying that it can never make sense for the FDA to change how they do things.

> If "used to be" counts, then the bare minimum is whatever it takes to get someone to pay for it, like in the literal snake oil days.

I’m advocating for higher standards, not lower. With regards to the COVID vaccine, we’ve decreased the quality and quantity of research performed over what we’ve done for previous vaccines.

It sounds like you’re saying that the research on these vaccines is better than before. Which is confusing because they have not obtained FDA Approval. If they had been tested to the same rigor as other vaccines, they would have received this Approval.

> implying that it can never make sense for the FDA to change how they do things.

Again, that’s not what I’m implying. I’m implying that we should change how they do things in only one direction- more safe. Long term research and vigorous testing.

Not rushed testing who’s new rules are dictated by industry-captured regulators.

What evidence are you basing this on?

Below are some top results for the google search "FDA revolving door".

I mean, is this a serious question?

https://www.citizen.org/article/outrage-of-the-month-revolvi...

https://www.npr.org/sections/health-shots/2016/09/28/4956945...

https://www.sciencemag.org/news/2018/07/fda-s-revolving-door...

Prevention of severe disease is a perfectly reasonable standard to use to evaluate a vaccine.

Just look at the hospitalization and death rates for old people in the countries with high vaccination rates.

Fair enough, I don't mean to discount the value of the metrics they did use. However I can think of two things that could be gained from testing people weekly.

1) If it actually prevents detectable infection altogether, it's some evidence of preventing spread, sooner. (as I understand we have some of that evidence now that it's in wide use)

2) If there are long term effects of even asymptomatic cases, we'd have some reason to believe that those are mitigated as well.

That's a bold claim. Any sources to back it up?

I am in a different Astrazeneca vaccine trial in the USA. (Got jabbed in December) I get my blood drawn monthly, and have weekly symptom check ins via smart phone. I do not get tested weekly

Is there a way to detecy COVID-19 infection post vaccination from blood?

I presume you already have a lot of antibodies after vaccination.

From the Oxford study[1]:

"To test for asymptomatic infections, participants in COV002 in the UK were asked to provide a weekly self-administered nose and throat swab for NAAT testing from 1 week after first vaccination using kits provided by the UK Department of Health and Social Care (DHSC)."

With notes:

"In Brazil, there was no testing plan for asymptomatic infections. In South Africa, asymptomatic infections were detected from swabs obtained at study visits attended, but are not summarised here as there were only a small number of timepoints for detection of these cases."

And you can see results here [2], which includes both symptomatic and asymptomatic cases (if someone could confirm)?

From Pfizer study [3]:

"Confirmed Covid-19 was defined according to the Food and Drug Administration (FDA) criteria as the presence of at least one of the following symptoms: fever, new or increased cough, new or increased shortness of breath, chills, new or increased muscle pain, new loss of taste or smell, sore throat, diarrhea, or vomiting, combined with a respiratory specimen obtained during the symptomatic period or within 4 days before or after it that was positive for SARS-CoV-2 by nucleic acid amplification–based testing, either at the central laboratory or at a local testing facility (using a protocol-defined acceptable test)."

And per their news release [4]:

"Data from this study, including longer term safety, comprehensive information on duration of protection, efficacy against asymptomatic SARS-CoV-2 infection, and safety and immunogenicity in adolescents 12 to 15 years of age will be gathered in the months ahead."

  [1] https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32661-1/fulltext#cesec100
  [2] https://www.evaluate.com/vantage/articles/news/snippets/astrazeneca-looks-us-data-and-next-gen-vaccine
  [3] https://www.nejm.org/doi/full/10.1056/NEJMoa2034577
  [4] https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-announce-publication-results-landmark

Imagine a world where competent regulators require a reasonable commonality of what data is gather across all the different vaccine trials. (Plus whatever extra stuff data they want to gather - a common baseline, not a takeover)

Maybe someday.

> Which means the 95% efficacy for phizer/moderna is not actually correct.

It is correct, it just efficacy against covid-19 disease, not against SARS-CoV-2 infection. Infection and disease are two distinct concepts.

> efficacy against covid-19 disease, not against SARS-CoV-2 infection.

There is no distinction between "disease" and "infection" in medicine. There is asymptomatic infection, mild, serious and fatal. Even then its not as clear cut as that.

We don't yet have clear data on asymptomatic infection for J&J, moderna, phizer or novavax.

I'm not suggesting that we stop jabbing people, quite the opposite. Even if AZ is less effective, roll it the fuck out. The quicker we get 60-70% of people immune, or partially immune, the quicker this shitshow will be over.

> There is no distinction between "disease" and "infection" in medicine.

That's completely false. An infection is an invasion by a foreign pathogen, a disease is a set of observed symptoms[0].

For other examples of infection/disease distinctions, see HIV and AIDS.

[0]: https://www.ncbi.nlm.nih.gov/books/NBK235412/

I have made an in incorrect assertion.

Obviously there is a distinction, auto immune diseases/cancer/congenintal are the overwhelming example.

What I should have said is: that in this instance we are measuring infection. disease is marketing speak.

This is also incorrect. "Prevention of disease" and "prevention of infection" are two related but clinically-distinct objectives for these vaccines. So far, early clinical trials were generally testing the first objective, and less so the second. It is thus not "marketing speak", but precise language about what was actually tested.

> Understanding infection vs. disease

> There's a difference between infection and disease. Infection, often the first step, occurs when bacteria, viruses or other microbes that cause disease enter your body and begin to multiply. Disease occurs when the cells in your body are damaged — as a result of the infection — and signs and symptoms of an illness appear.

https://www.mayoclinic.org/diseases-conditions/infectious-di...

Here is a great read on infectious agents and the differences between infection and disease.

* Infection does not necessarily lead to disease. Infection occurs when viruses, bacteria, or other microbes enter your body and begin to multiply. Disease, which typically happens in a small proportion of infected people, occurs when the cells in your body are damaged as a result of infection, and signs and symptoms of an illness appear.*

https://www.ncbi.nlm.nih.gov/books/NBK209710/

It's against a defined endpoint. It's a reasonable one, as a vaccine that prevents severe disease is a lot better than no vaccine.

That people don't bother to understand what they read is a problem of course.

This article talks about at least one tweak that Pfizer, Moderna and J&J do that AZ doesnt

https://cen.acs.org/pharmaceuticals/vaccines/tiny-tweak-behi...

I've heard this multiple times, but never with a citation. Can you point us at anything? Trying to prove a negative with searches hasn't worked for me so far, and this vaccine is not a good option for me so I haven't trying looking up and parsing its spike protein nucleotide or amino acid sequence.

However all these vaccines you listed coerce a small number of your cells to make spike proteins of whatever sort, which results in bits of them being put on the surface of the cells. I don't know how much of the spike protein gets outside cells, either through direct escape or creation of new viruses, have not looked up the exact details of what J&J and Oxford mean by their viral vectors being replication deficient. That is, they don't produce new viruses that can attack other cells.

Without any knowledge of how vaccines work, it's pretty trivial to determine that there are significant differences between AZ and J&J vaccines; J&J only needs one dose while AZ needs two. That alone implies that there are differences in technology or targeted protein, even if the specifics aren't clear to a non-expert.

There are essentially no differences, except J&J's platform had been successful in an European Phase III trial for an Ebola vaccine, but not the one widely used in the last big outbreak, and Oxford's had an 8 year history of Phase I failures. Both replication deficient adenovirus vectors, with the spike protein spliced in, although maybe significantly different versions of the protein.

The biggest difference is their goals, Oxford was intended to be a regular vaccine, J&J intended to get the very best protection from a single vaccination, with an initial goal of protecting a billion people in 2021, now increased to 3 billion. Besides J&J's press releases and slow but sure development methodology see the difference in their Phase III trial primary endpoints, here's J&J's https://www.jnj.com/coronavirus/ensemble-1-study-protocol:

To demonstrate the efficacy of Ad26.COV2.S in the prevention of molecularly confirmed, moderate to severe/critical coronavirus disease-2019 (COVID-19), as compared to placebo, in SARS-CoV-2 seronegative adults

As in, not stopping people from getting the disease, that's a secondary objective.

AZ/Oxford will be hard to track down because they did several different Phase III trails in even more countries. I'd start with ClinicalTrials.gov, look for Primary Outcome Measures and this is a good search to start with: https://clinicaltrials.gov/ct2/results?term=ChAdOx1&cond=Cov... For the US trial:

The efficacy of 2 IM doses of AZD1222 compared to saline placebo for the prevention of COVID-19

J&J is also doing a 2 dose 8 weeks apart US based Phase III trail to see what that can accomplish.

This was discussed in the press several weeks back, there was a Downing Street briefing that day about it - they hammered home two points

1) The data isn't in on severe disease and hospitalization - and they strongly suspect that it will still have a positive impact on that

2) B1351 is not our dominant strain (in the UK and elsewhere) and since it's not more infectious than our already very infectious strain, probably won't be

But it will be dominant if it's the only strain capable of spreading within a population immune against other strains, no?

Yes but they made the point that by time it is we could already be rolling out a booster

So is it that it could be the next seasonal COVID-22 and vaccines will be ready by then?

Yup, trials have been happening for months already with mRNA vaccines targeted specifically for these variants, so if there is any risk of deadly seasonal COVID from them there will likely be vaccines to address them.

Interesting, did not know this. Any links / sources on ongoing trials?

Moderna ready to test version of Covid-19 vaccine aimed at worrisome variant: https://www.statnews.com/2021/02/24/moderna-ready-to-test-ve...

Covid-19: Where are we on vaccines and variants? https://www.bmj.com/content/372/bmj.n597

Sorry, yes - the context was that they were encouraging uptake of the AstraZeneca vaccine in the here and now.

Prof. Sarah Gilbert (who developed it) did the rounds on TV explaining that they're tweaking it for new strains and booster shots will be ready by autumn if needed.

Keep wearing masks and social distance.

The past year has taught me that this type of comment is generally anti-measures, so I am asking you this: do you think that letting it run loose through the population is a decent approach?

I was not being sarcastic.

After a year of watching a lot of people not do that, I am not particularly optimistic.

Well we are dumb. But We need to hold the line.

After a year of watching people do that and curves still going up, I am not particularly optimistic either.

I think it's pretty clear that some combination of mask wearing, case tracing, and social distancing can absolutely clamp down on this disease, as we've seen in Southeast Asia. I also think it's pretty clear that patience for such things in America is at an end, and compliance will be low even if the new variant continues to kill.

Not just America but Europe, too. Several health ministers have openly said that their populations are tired of restrictions and no longer observing them. Of course health ministers keep pushing for new restrictions regardless, because their job performance is mainly judged on how proactive they look, not whether those restrictions actually prove effective.

We can’t afford to be tired. Nonsense.

Maybe I am wrong, but I feel they have published this a bit prematurely? The data is reported honestly, but their power (as indicated by the confidence intervals) is pretty terrible. I wish they had waited longer.

At the same time the trend looks bad, and one would suspect it will continue to look bad. But the group with the outcome is pretty small. I hope they plan to keep monitoring this population.

EDIT: I should point out that they backup their data with antibody activity assays which do support the narrative in their primary outcome data.

EDIT2: ahh, I think I just don't like this result. Frankly it doesn't look good. Boy am I glad I live somewhere there isn't any circulating COVID.

Moon?

No, Australia. But there are a fair few developed, isolated countries with little to no COVID.

> with little to no COVID.

To be fair there was a time it could have gone out of control but Aussies followed the rules, trusted the govt and they got it under control.

And more importantly the government actually tried to stop it while that was still possible. In most countries there was a progression of "no evidence for human to human transmissoin" to "just the flu" to "flatten the curve" to "huh, I guess we want to avoid most people getting it but our caseloads too high high for contact tracing to work".

> The finding underscores the importance of genomic surveillance

Sounded dystopian until I realized it was in reference to sequencing the virus variants, not the hosts.

It is a viral dystopia though, they are being persecuted and decimated left and right and have to fight for survival.

(this post is tongue in cheek of course)

The anti-vaxx alliance is their only hope.

> You move to an area and you multiply and multiply until every natural resource is consumed. The only way you can survive is to spread to another area. There is another organism on this planet that follows the same pattern. Do you know what it is? A virus.

This quote always puts me off.

In individual virus might be that - but thats not how virus live as a species/group/form of existence. Usually they are a thriving and useful part of the ecosystem they belong to.

Virus, under normal circumstances, will live happily along a bunch of other guests in foreign hosts.

No issue.

It's human that give virus a bad raputation! We breed the fuck out of them and then are shocked when this bits us in the ass.

Or in other words: The only way this comparison (human==virus) gets accurate, is when you use the human-super-breed version of "virus"

(edit: leave vs. live)

I bet on some dark corner of the internet those sentiments are echoed tounge firmly outside of cheek.

If anyone is curious, one of the Moderna scientists who helped develop their mRNA vaccine had a thread about this when this first made the rounds:

Twitter thread: https://twitter.com/sailorrooscout/status/135886946241446708...

Easier to read version: https://threadreaderapp.com/thread/1358869469125296135.html

> Let’s talk about immunity and why it’s important to take certain factors into consideration when we look at these studies and maybe why the most recent one on AstraZeneca’s effectiveness on the B.1.351 is a tad bit bothersome. For starters this beauty wasn’t tweeted initially.

> See that last bullet point? The one of T-cell immunity. Yeah, that’s vital. Why? The study failed to discuss this aspect. You cannot disregard T-cells in the same breath you are discussing B-cells, vaccines and their respective induced antibody responses. It’s a package deal.

> T-cells help protect against severe disease. Their analysis shows 76 out of 87 TCB sites (87%) are NOT impacted by the mutations seen in B.1.351. What does this mean? It means the T-cell response generated by AstraZeneca’s vaccine should be highly effective against this variant.

> How are you going to disregard our actual immune systems and their ability to make antibodies for later? Which may I remind you are DRIVEN by vaccines. They teach our bodies to make antibodies for later, not just during active infection (memory T-cells anyone). That’s immunity!

If I’m not mistaken, this study doesn’t have enough information on severe disease and hospitalisations since there were no cases in either group. I think we still need more information from the looks of it.

Weird. Are you sure the tweets talk about the same study?

The study in the article didn’t look at antibody response, but at the clinical outcome - just like the original Phase III studies did, just with a smaller group of people.

As for the claim that we don’t know how the vaccine protects from hospitalisations - if there is literally no difference in mild cases, why would there be any difference in severe?

Is there a single vaccine for any disease that offers no protection against mild cases, but a high protection from severe?

Regarding the question about how the vaccine could protect against severe but not mild infection, I think they answer that here:

> Antibodies can prevent infection, your T cell-responses ensure that those antibodies keep doing their job and they kick in after you're infected OR oh my goodness stop the presses- VACCINATED (how about them apples). In other words, while robust T-cells responses cannot protect you from a mild or moderate infection sometimes (think cough, sniffles, etc.) they can however proliferate rapidly and prevent the build up of viral load. Psst- you want this to be LOW. VL drives disease severity.

> Weird. Are you sure the tweets talk about the same study?

Yes, this is in reference to B.1.351 and the AZ SA study.

I don't see their credentials, where did you see they were one of the Moderna scientists?

Unfortunately it's all a mess trying to find it on Twitter, but most mentions are of her and the teams efforts[1][2]. She’s often referenced by others in the field as well [3].

There’s too much out there and I found Twitter quite difficult to search for things like this.

If you search for “chise vaccine” on LinkedIn[4], a few people in the field also referencing her tweets.

Wish I had something more definitive to give you.

  [1] https://twitter.com/sailorrooscout/status/1371159231618019337?s=20
  [2] https://twitter.com/sailorrooscout/status/1358118660737540097?s=21
  [3] https://twitter.com/andrew_croxford/status/1356312317714169856?s=20
  [4] https://www.linkedin.com/search/results/all/?keywords=chise%20vaccine&origin=GLOBAL_SEARCH_HEADER

B1351 was also detected in the US.

https://www.doh.wa.gov/Newsroom/Articles/ID/2639/First-case-...

The late summer booster for AZ that will be issued (prob in the UK first) has already been adapted to this variant specifically and is in advanced trials.

https://www.bloomberg.com/news/articles/2021-02-07/new-astra...

And other vaccines (e.g. Novavax) have been shown to be pretty effective against it

https://www.fox5atlanta.com/news/novavax-vaccine-has-96-effi...

So - AZ will catch up... with a second shot?

*whoops, confused AZ and J&J, nevermind this.

Wouldn’t this be a third shot?

It’s 2 shots for the AZ vaccine. And a third booster.

Everyone I know has been out of action 1-2 days after the AZ vaccine. So three shots could be a week out of action. Similar to people who have had corona virus. It had better be worth it.

Just a side note, everyone I know who’s had a symptomatic case (n=3) were out for more than two weeks. Not that it changes your point much. Having to keep getting booster shots that knock you out for a day or two is not a great situation

I think that can vary hugely though. I know of two people that had AZ jabs who said they experienced mild flu symptoms, and another two (including my partner) who didn't really notice anything.

If we're in the realm of anecdotes, my 71 years old mother only experienced mild tiredness for 2 days.. She described it as the same as if she had been out hiking for half a day.

Definitely a lot less than if she actually had covid.

If you have a harsh reaction to the AZ vaccine (an attenuated/weakened form) then it’s likely you would have had a much more harsh reaction to the unattenuated real virus.

I don’t think it’s been studied so its just a personal theory (ie read this as if it might be nonsense) but i suspect the people with bad reactions to the vaccine are also likely to be the people who would have had a more serious case of the real virus.

Don't use "it's likely" if you don't know what you're talking about, please. I appreciate you're qualifying your statement in the second paragraph, but please don't get in the habit of it regardless.

Side effects from the vaccines have a different cause and mechanism to most of COVID's symptoms. When people say they're out of it due to a vaccine, it's usually because of the fever that comes from the immune system kicking into gear. While COVID usually does cause a fever, its more dangerous aspects are from other reactions to the virus itself.

Anecdotally...in a very small sample size of three (over 50's) who have had their first AZ shot there have been: * 1 person with a few chills. lasted one day. no time off work * 1 person with chills and had to take 1 sick day from work * 1 person with absolutely no symptoms except for tender arm at the injection spot. i went for a 40 mile bike ride the day after.

I have heard stories of people faring worse. But in my little bubble, the result wasn't too bad.

My experience (34 with possible earlier COVID case last March): I had chills that night, and I felt gross the next day. But I didn't need time off... And the chills went away with Tylenol.

Experts say that a strong reaction is much less likely for the second shot. So anyone who suffered a strong reaction for the first one should not be too alarmed and should certainly not skip the second shot.

Strong side effects are usually not consistent between shots. You might have a strong reaction to the first one and none to the second (which is what everyone I know experienced).

I had a CureVac trial shot recently and was quite a bit knocked out, but we will see if my second one hits me as hard; I was told that it's rare.

Anectodal I got mine last week, i had some mild discomford in the arm that i got vaccine in, and nothing else.

I am not sure what to make out of latest news about AstraZenica.

Not even sure how much vaccine will help me since I am on biological drugs (that lover the immune response)

I think the accepted phrasing is one or two shots initially and the (yearly?) booster shots as long as you choose.

The two shots for the AZ vaccine are the same (compositionally), though. So, in principle, if the booster is slightly modified version it might simply replace the second shot. That's how Sputnik V works: it's basically two different adenovirus vaccines.

probably 3rd since AZ one is still 2 shot vaccine. Of course it depends when you had your shot, if you only had 1 probably you'll get only the "updated" one as 2nd But this discussion is ongoing for all vaccines in order to tackle the new/future strains, not only for the AZ one

Autumn, not late summer, according to the Bloomberg article.

https://www.nejm.org/doi/full/10.1056/NEJMoa2102214

CONCLUSIONS

A two-dose regimen of the ChAdOx1 (AstraZeneca) nCoV-19 vaccine did not show protection against mild-to-moderate Covid-19 due to the B.1.351 variant.

(Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT04444674. opens in new tab; Pan African Clinical Trials Registry number, PACTR202006922165132. opens in new tab).

I thought the point of the vaccines wasn't to provide an absolute block against the virus but to reduce the incidence of severe symptoms and hospitalisations? Rather than running rampant and killing hundreds of thousands, it'll be pushed down to mild flu or common cold kind of levels?

That's definitely not "the" point. Reducing spread is also extremely important.

It most certainly is the point. Many other vaccines also do not provide sterilising immunity.

That makes them a significantly worse vaccine.

If you had a vaccine that only prevented spread, not illness, it would still be useful.

Well, it's what we got, and it's how we plan to get out of this (apparently). Also, what's wrong with a vaccine that stops people dying?

It still allows the virus to replicate and mutate, potentially into a variant that is different enough that the vaccine no longer prevents people from dying.

Like I said - so do many vaccines. I suppose we need to all lock ourselves back in our houses for a few more years while researchers make a new vaccine for Covid-19, that does provide sterlising immunity?

This is why creating a vaccine for coronaviruses is a fool's errand. This is all very predictable. We have to look at the actual harm being done, and decide if all this is worth it.

Indeed, some realism to the coronavirus aftermath has been lacking.

If the vaccines do reduce hospitalizations and ultimately deaths, then we can live with it and can forget about vaccine passes and restrictions.

Getting your optional and yearly coronavirus booster is a likely and realistic outcome of all this.

Sure, but your normal immune response applies the same selective pressures and allows order of magnitude more replication prior to that giving the virus orders of magnitude more chances to come up with a mutation to circumvent them. Even without preventing infection entirely vaccination still seems drastically better than the alternative.

> it's what we got

Citation needed.

(And I don't mean citing someone that says "not yet proven")

> and it's how we plan to get out of this

Are we hearing the same news? There is so much emphasis on stopping spreading.

> Also, what's wrong with a vaccine that stops people dying?

...? Nothing. Where did you get the idea I was saying that?

Vaccines have two primary goals. If a vaccine only does one it's a huge downgrade but still valuable.

It's what we have, according to the designers of the various vaccines. Unless you are suggesting that all things are true unless proven otherwise, in which case I'd ask you to go back and check some books on elementary logic.

There is some work after the fact to measure the effect on Covid transmission of the vaccines, but even that isn't very promising.

It's odd when "stopping people dying" is "a huge downgrade". I suspect what you mean is that the vaccines in their current form will not get us out of the restrictions we are currently living under, which is true (and incredibly predicable).

> It's what we have, according to the designers of the various vaccines. Unless you are suggesting that all things are true unless proven otherwise, in which case I'd ask you to go back and check some books on elementary logic.

That's not a citation. And vaccines are designed with a very general goal of "make the body fight this". That can potentually affect both symptoms and transmission. Don't argue in bad faith and equate that to "anything could be true"

> There is some work after the fact to measure the effect on Covid transmission of the vaccines, but even that isn't very promising.

Huh? Checking if the vaccine does anything at all is after the design is done. The choice of when to test symptoms vs. spreading is more about difficulty of getting the data than anything else.

> It's odd when "stopping people dying" is "a huge downgrade".

Stopping one person from a chance of dying is a downgrade from both stopping that and stopping transmission to more people that have their own chance of dying.

>That's not a citation. And vaccines are designed with a very general goal of "make the body fight this". That can potentually affect both symptoms and transmission. Don't argue in bad faith and equate that to "anything could be true"

>Huh? Checking if the vaccine does anything at all is after the design is done. The choice of when to test symptoms vs. spreading is more about difficulty of getting the data than anything else.

You're the one arguing in bad faith, demanding evidence of a negative. When the vaccines were released, the published testing only covered a few key endpoints - primarily, incidences of lab-tested Covid cases. Any work on measuring effects on transmission was done by 3rd parties (in this case, I believe it was researchers in Israel).

Covid has a very specific (and small) risk profile. That's the idea we were all sold - vaccinate the vulnerable, get on with our lives. Given that it presents very little risk to the vast majority of people, it doesn't really matter about transmission. Except that is, now we are apparently trying to surpress potential mutations, which means we'll be battling a relatively harmelss (compared to the great pandemics of the past) disease forever.

> You're the one arguing in bad faith, demanding evidence of a negative.

I demanded evidence because you stated it as a fact.

And are you trying to imply it's one of those things that's impossible to prove? It's not. You collect some data and it either shows that transmission rates differ or that they don't differ.

> That's the idea we were all sold - vaccinate the vulnerable, get on with our lives.

We were also sold on "vaccinate the people near the vulnerable so they won't spread it to the vulnerable".

It's a fact that the various vaccines were released without any information about their effectiveness on transmission. It's not impossible to prove, it's just not been done (nor, if the tests were done, do we know what the results would be).

>"vaccinate the people near the vulnerable so they won't spread it to the vulnerable"

Why does that matter, if the vulnerable are already vaccinated? That was the whole point of vaccinating them in the first place.

> It's a fact that the various vaccines were released without any information about their effectiveness on transmission. It's not impossible to prove, it's just not been done (nor, if the tests were done, do we know what the results would be).

So do you withdraw the claim that "what we got" are vaccines that do not provide sterilizing immunity?

> Why does that matter, if the vulnerable are already vaccinated? That was the whole point of vaccinating them in the first place.

Not everyone can be vaccinated and supplies have been limited.

And less people getting sick is good even if it's milder.

If you really want to nitpick, "what we got" are vaccines that are not known to provide sterilising immunity, and the 3rd party testing that has been done shows limited effect on reducing transmission. That being the case, it would be surprising if they did have sterilising immunity.

You still haven't said a single number, url, or searchable phrase.

Asking for a source is not nitpicking.

For what it's worth if I search for "covid vaccine transmission effectiveness" my top results are "COVID-19 vaccines are probably less effective at preventing transmission than symptoms", which is vague on the term "less" but still suggests a large improvement over not being vaccinated, "New research suggests vaccines reduce risk of COVID-19 spread through nose and mouth", and "Pfizer vaccine shots actually stop asymptomatic transmission, too"

It's not nitpicking to ask for a source for the statement "it's not known if the various vaccines give sterilising immunity", it's asking for proof of a negative. The only possible refutation of such a statement is a counterexample (that is, evidence of it providing sterilising immunity). If we were to set this discussion up properly, the burden of proof would be on the person making the statement "this vaccine provides sterilising immunity".

I'm fully aware of the results you found, as I already indicated with statements like "3rd party testing that has been done shows limited effect on reducing transmission". As I already said, it would be very surprising if a vaccine had limited effectiveness at reducing transmission (as your search results indicate), and also provided sterilising immunity. In fact, it seems to me that the known fact that transmission does still occur, preculdes the idea that the vaccines have sterilising immunity.

I don't get what your point is. I suggest you work out what that is, before delving into more complicated subjects. As I have essentially repeated what I said before, it seems we are now going in circles.

> It's not nitpicking to ask for a source for the statement "it's not known if the various vaccines give sterilising immunity", it's asking for proof of a negative.

You're rewriting history. You definitely did not say "it's not known" originally, you made a very clear statement that they didn't confer it.

> I don't get what your point is.

That if "limited" is 80% then you are grossly misrepresenting the situation to talk like transmission isn't affected.

I already clarified my statement, quite a few replies ago. I've also already suggested that the known low effectiveness of reducing transmission would indicate that it does not have sterilising immunity.

But wait!

> 80%

Now, you've made a pretty positive statement there. My turn to ask you for a link, or other proof.

> I already clarified my statement, quite a few replies ago.

You didn't "clarify" because I asked if you were withdrawing the original statement and you ignored the question entirely.

You also accused me of "nitpicking" your new statement, when the new statement is a very different thing from what I originally replied to.

> Now, you've made a pretty positive statement there. My turn to ask you for a link, or other proof.

Sure, that's in the first article I quoted the title of. https://theconversation.com/covid-19-vaccines-are-probably-l... It's talking about the Pfizer vaccine.

> I've also already suggested that the known low effectiveness of reducing transmission would indicate that it does not have sterilising immunity.

Your original statement, and some of your followup statements, argued against the vaccine reducing spread at all. If you're talking purely about sterilizing immunity now, ignoring any other reduction in spread, then either you're moving the goalposts or some massive miscommunication happened multiple times in a row. But sure, it might not be sterilizing. And in that case I say: This whole conversation was pointless because I don't care if it's sterilizing, I care if it reduces spread by a lot.

When you were talking about "80%", I thought you were referring to reduction in transmission. The article you linked only talks about the reduction in numbers of cases (and mostly symtomatic cases), which is not the same thing. By "reduction in transmission", we are talking about the chances of someone catching Covid from someone already infected with it.

>Your original statement, and some of your followup statements, argued against the vaccine reducing spread at all.

Not that it matters much, but I started by saying that it does not confer sterilising immunity (something even the article you linked suggests could be true), later correcting it "it's not know if it does". I've also said, many times now, that it may have some limited effect on reducing transmission.

I'm still not sure why the obsession with transmissison, anyway.

If it reduces the chance you have an asymptomatic case by 80%, and reduces the chance you have a symptomatic case by even more, then almost certainly the reduction in transmission is at least 80%, isn't it?

> but I started by saying that it does not confer sterilising immunity

But you were replying to a comment about reducing transmission. And when I kept talking about reducing transmission you said "limited" sometimes and acted like it was none other times.

80% would be more than enough...

> I'm still not sure why the obsession with transmissison, anyway.

Because stopping people from getting sick is much better than reducing how sick they get. And transmission is the only factor that actually stops the virus.

Vaccines generally drastically reduce the spread of disease with needing to provide sterilizing immunity. If you just reduce spread by a factor of 20 that's enough to bring R0 down below 1 for almost any disease. It's a numbers game.

"just a factor of 20" is a huge number. At this point, it's not even clear if the vaccines stop you becoming infected in the first place, or just reduces your symptoms. In that case, a vaccinated person is no better for transmission than an unvaccinated, "asymptomatic carrier".

I chose that number because people who are infected but remain asymptomatic through their infection seem to cause 20 times fewer infections according to a couple of contact tracing studies I saw. It seems pretty clear that the amount of fluid you have to get from an infected person, droplet or aerosol, has to be inversely proportional to their viral load if you're to get infected. Current guesses of an infectious dose I've seen are 100 to 1000 virions via the aerosol route. We can see that different people reach peak viral loads that are orders of magnitude apart which helps make sense of why this disease has such a high k, driven by superspreaders whereas half of people fail to infect anyone else even without protective measures.

So if I promise to isolate myself if I get symptoms, and am not concerned about Covid, why should I get vaccinated?

It's the people who remain asymtomatic through their infections who barely infect others. For people who end up becoming symptomatic their viral load and infectiousness peaks somewhere in the day before symptoms first appear. That's the one thing we've found about this virus so far that's genuinely weird. It seems to be very good at evading the automatic immune system but once the Interferon starts flowing the viral population starts crashing immediately.

Yes, that's often neglected. However this paper states that the lack of severe reactions may be down to the age of participants (around 30 years) so it is basically unknown if it reduces those.

If the vaccine doesn’t protect from mild symptoms, there is no reason to think it would protect from severe.

I mean if you actually read the published data that is categorically wrong.

The variant in question escapes Antibody detection, but T-Cells still seem to provide significant protection against severe disease and death.

https://academic.oup.com/cid/advance-article/doi/10.1093/cid...

https://www.biorxiv.org/content/10.1101/2021.03.11.435000v1

The main published results aren't yet from human scale studies but here is one in hamsters showing a comparison in organ damage and results between unvaccinated and vaccinated with the Oxford/AZ vaccine.

This paper is looking at a small scale human study in SA with mostly younger participants, which does make the results difficult to apply to the wider population.

They also only use a 4 week dosing schedule where the suggestion and actual rollout in the UK is following the 10-12 week schedule between first and second doses.

The variant in question seems to escape the majority of Antibody detection, but T-Cells still seem to provide significant protection against severe disease and death.

https://academic.oup.com/cid/advance-article/doi/10.1093/cid...

https://www.biorxiv.org/content/10.1101/2021.03.11.435000v1

In other news Norway is considering completely stopping with AZ due to unreliable shipments and longer interval between doses. They are saying they can get everyone vaccinated faster

https://direkte.vg.no/nyhetsdognet/news/fhi-norge-kan-bli-va...

I wonder if the differential response between AZ and J&J/Pfizer/Moderna is due to the use of the stabilised form of the spike used by the latter and not the former?

The real boogeyman here is the P1 and P2 variants found in Brazil. These are the ones which mutated offspring can evade vaccines completely.

Damn, and this was the best hope due to price and once early lead. Let's hope J&J fills their void (Not all countries can afford $60 shots and have ultra cold fridges)

Well this isn't ideal, its not like this means the vaccine is useless.

"I'm vaccinated" when you really aren't is dangerous.

No vaccine is 100%. They don't have to be to be useful.

Study only talked about mild-moderate cases of one specific variant. Well i would like it to work across the board, working well against the other variants and preventing severe cases of the problematic variant, is still a win, even if a qualified one.

they mean that a person who thinks they are vaccinated is more dangerous than one who doesnt, because they change their behavior

Yes, but it doesn't follow that someone with this vaccine is more dangerous than someone without one. The result of this study is not that this vaccine is totally useless, just that its not ideal. There is big gap between what is reported here and having nothing. Its still likely to be beneficial.

100% and not effective are quite far apart. Their suspected efficiency is hospitalizations is probably due to the young population this was tested on.

I suspect that the SA version will spread since nothing that stop it and the boosters will be delayed to those countries. Yet, "I'm vaccinated" many will say.

There's also Novavax which only needs to be refrigerated.

mRNA don’t need ultra cold fridges any more.

Also, even if, you don’t need fridges, you need boxes with dry ice, that is relatively cheap.

As for the price - you’re sure it’s $60 not $30? Regardless, you’re right that it’s an issue.

Pfizer I think it's like $20 a shot (need 2), Moderna $30 or so, at least at this stage when they can't make them fast enough

Almost all EU has banned AZ because of blood cluttering sideeffects. Happens in perfectly healthy humans.

It’s clotting, not cluttering. And that decision was taken by politicians keen to cover their ass, afraid of idiotic anti-vaxxers.

Here’s what the EU regulator says. The European Medicines Agency is 'firmly convinced' benefits outweigh risks - https://www.bbc.co.uk/news/health-56411561

> And that decision was taken by politicians keen to cover their ass, afraid of idiotic anti-vaxxers.

It's more of the EU playing "well, we didn't want it anyway" after getting the short end of the stick in AZ vaccine production (the EU has been a net exporter of AZ vaccine, but AZ deliveries are lagging behind significantly compared to UK).

They didn't get the short stick.

EU deliveries of the AZ vaccine are behind the UK ones because they started production at least 3 months later and it takes time to debug pharmaceutical plants for new drugs.

Even in the UK the production process is still inconsistent with fluctuating yields

One of the production places in the EU mentioned in the EU contract still isnt up and running because AZ has refused to file the proper paperwork to be able to use it. Its insane.

Is that Halix in NL - https://www.politico.eu/article/breton-no-astrazeneca-jabs-e...

UK got many of its initial doses from plants in the EU (Netherlands and Belgium).

The decision is also due to legal issues, at least in Germany. The number of cases for clots exceed the threshold. The govt has no choice to stop or face lawsuits since it is a state vaccination program.

If that is the case, why then isn't the Pfizer also suspended? Since it generated the same deaths

The number of cases or deaths are conditional on the cases in the general population, it’s not an absolute number. The cases for AZ - 7 cerebral vein thombrosis in 1.6M vaccinations - which is higher than in general population. AZ will get back on the market with a restricted use or a warning label.

Its not done by politicians. Its done by the national agencies that investigate and approve medicines.

This is false.

Some countries have temporary suspended using it well they investigate a very small number of people who got blood clots, which very well might be random chance. Nobody has permenently banned and in all probability the clots are a coincidence (healthy people get blood clots sometimes) and the suspension will likely be reversed once it is fully investigated.

On one hand, you are right.

On the other, even Sweden suspended it (Astra-Zeneca is a British-Swedish company). I wish HN would stop pretending everything is fine with this vaccine - it might really be problematic.

https://www.reuters.com/article/health-coronavirus-sweden-va...

I don't see why sweden suspending it makes any more difference than any other county. They're a non-corrupt first world country. I doubt they play favourites because its a domestic company.

Anyways, im not saying don't investigate, we should investigate all possible side effects. However so far it sounds more like a coincidence so im not worried. Healthy people get sick randomly sometimes when you're looking at groups of millions of people. Sometimes by chance it will happen near when they got the vaccine. Its important to keep perspective.

There's been plenty of suggestion that other EU countries' decision to suspend AZ is somehow a political decision, and not primarily motivated by health concerns.

> Its important to keep perspective.

Yes, it is - on both sides. Just because, as someone here said, "I'm a lever puller" doesn't automatically mean that your opinion is better and more informed than that of health authorities across EU. (note that I'm not accusing you personally of being a "lever puller", I'm just venting about what I perceive to be HN propensity to take risks on other people and dismiss concerns).

What's a lever puller?

> doesn't automatically mean that your opinion is better and more informed than that of health authorities across EU

I agree that health authorities know better than I do, but i don't think i'm disagreeing with any health authorities. There are some health authorities saying its safe to keep on using it and there are some temporarily suspending while the situation is being investigated out of an abundance of caution. Unless i missed something, not a single one is saying that the vaccine is unsafe or confirmed to cause blood clots.

> I'm just venting about what I perceive to be HN propensity to take risks on other people and dismiss concerns

There is no risk free view here. Less vaccinated people means more people with covid, which among other things means more blood clots because covid can sometimes cause that (although obviously that's not the primary concern with covid).

Obviously if we can confirm a link between the blood clots and the vaccine, we should stop the vaccine. But as it stands the evidence is extremely weak bordering on non existent, and stopping using that vaccine will cost lives.

> What's a lever puller?

Sorry - trolley problem, pull the lever to kill one person and save 3 others, that kind of metaphor.

> stopping using that vaccine will cost lives

In the EU, there are alternatives (e.g. in my country I could actually register to Moderna and due to the shorter time between shots I'd actually be completely vaccinated faster with Moderna than with AZ).

Look, I'm not saying AZ should be killed either. Just that in my mind, precaution is justified. Symptoms are bizarre, affected people are young with no other obvious reasons to be affected. Also read what this guy says: https://news.ycombinator.com/item?id=26473368

Again, I'm not saying "AZ=bad". I'm saying precaution is reasonable, and the view that precautions states are "obviously wrong" and should just plough through with vaccination using AZ is a bit simplistic and less informed than people would care to admit.

40-ish cases of blood clots out of 17 million injections is not problematic even if they were indeed caused by the vaccine (which is not proven at the moment, afaik).

People should really keep a sense of perspective and compare that with the risk of blood clots in general, the risk of Covid complications, and even more generally the risk of mundane things like going out or driving. E.g. based on the numbers above someone in my country, the UK, is 10x more likely to die in a car accident in any given year than to develop a blood clot after a jab of that vaccine...

> a very small number of people who got blood clots, which very well might be random chance

To put it in concrete numbers: it's seven people in a sample where it's expected to be one. We're not talking hundreds or thousands of people, but seven.

Yes but still 7-fold increase over normal, therefore it is likely that the vaccine is the issue.

The question to answer is what exactly causes this, so we can learn. It's almost unthinkable that a vaccine which has vastly greater benefits than risks will be banned over this.

I disagree with halting the vaccination, as timing is vital now. It's prime time for mutations with these infection rates since evolutionary pressure is really high right now (mixture of high spread and increasing immunity).

Third waves are rolling over Europe at this moment and we need to stop spread as much as possible to lower the chance of further mutations.

> Yes but still 7-fold increase over normal, therefore it is likely that the vaccine is the issue.

As was my point, it could be just a coincidence. The sample size isn't truly random, it's people who were picked to receive a vaccine. Correlation =/= causation. Investigation needs to be completed for the cases to be attributed to the vaccine.

The blood clots are apparently of a specific type, not a localized big one, but many small clots all over the body. This was on danish news Monday but I can't find an english reference.

This makes it different from the blood clots healthy people sometimes get.

The EMA disagrees, and this is a really foolish move IMO which will directly lead to thousands or tens of thousands more people dying from coronavirus across Europe.

Well, the vaccine was halted in Germany because the Paul-Ehrlich-Institut, which is not a political entity, had this to say:

"Compared to the status on 11 March 2021, additional cases (as of Monday, 15 March 2021) have now been reported in Germany. Analysing the new data status, the experts of the Paul-Ehrlich-Institut now see a striking accumulation of a special form of very rare cerebral vein thrombosis (sinus vein thrombosis) in connection with a deficiency of blood platelets (thrombocytopenia) and bleeding in temporal proximity to vaccinations with the COVID-19 vaccine AstraZeneca.

The data are being further analysed and evaluated by the European Medicines Agency (EMA).

Vaccinations with AstraZeneca's COVID-19 vaccine in Germany will be suspended until the EMA's evaluation is complete. Today's decision affects both initial and follow-up vaccinations."

These things are not done lightly.

While they may not be being done lightly, the reasoning is still based on legal concerns rather than medical ones. https://twitter.com/leonardocarella/status/13718299183388016...

Maybe this kind of vaccines under suspicion should be reserved for those age segments more vulnerable to the virus?

This way we avoid deaths due to Covid and at the same time don't put healthy individuals at risk that would have only mild symptoms due to Covid.

Don't know why you were downvoted on this. I agree - if there's a certain small risk of a blood clot complication, keep giving the vaccine to older people, that have a higher risk of serious COVID complications, and suspend it for younger people, whose benefit doesn't outweigh the risk.

In order to maintain confidence in vaccines in general this sort of thing has to be taken seriously. You can't say that the vaccines are perfectly safe and then have a bunch of anti-vaxxers shout that people are dying from blood-clots and no action is being taken. That would severely damage trust in the health authorities which would lead to fewer people getting the vaccine from any company, not just AZ.

Better to stop everything, be clear that action is being taken, transparently evaluate the risk and then start back up or stop as appropriate.

It's worth pointing out that if the population vaccinated with AZ had been unvaccinated instead, then given the base frequency of Covid cases and how often severe clotting shows up in Covid cases we should have expected several hundred cases of severe clotting in the same population. Which isn't to say this isn't a potential problem. The very fact that Covid causes clotting problems lends credence to the idea that the vaccine against it could do the same thing through an auto-immune pathway. But we're in the middle of a pandemic, this problem happens in at most a tiny number of people, and I'd take this vaccine in a heartbeat.

Irecived my first doze previous week, I was supposed to get next doze in 3 weeks, but now its delivery is suspended here.

Not sure what will happen, if they do pull it alltogether, get 2 doses of some other vaccine ?

30% of children in Germany have mental issues due to the coronavirus-measures and it looks bad in other countries as well:

https://www.bbc.com/news/health-55863841

This is a typical situation when the cure (coronavirus measures) is worse than the disease.

30% of children in Germany have mental issues due to the coronavirus-measures

Citation needed. The only thing I could find is this[1], which is just nonsense. It's probably similar to the much more sensible numbers from the UK, maybe a bit better since, so far, Germany hasn't had a lockdown as strict as the UK.

[1] https://www.meinbezirk.at/c-lokales/corona-krise-30-prozent-...

30% may be bullshit but the mental health issues are clearly a problem in Germany.

[German] https://www.zdf.de/nachrichten/panorama/corona-kinder-psychi...

Which is one of the reasons I do not understand Norway's recent tightening of restrictions: https://www.reuters.com/article/us-health-coronavirus-norway...

In this matter lifting restrictions like Texas, Mississippi and other US states have done seems more reasonable.

In Denmark nearly everybody who is at risk has been vaccinated, but still the government hesitates to remove restrictions.

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