The very common vaccine ingredient at the center of J&J, AstraZeneca drama

Adenoviruses are an obvious link, but a puzzling suspect in the dangerous cases.

Read the whole story

 

[SraCet]

...
The incidence was 2 in 150,000 in Denmark

But if you want, you can always get a much higher percentage of risk if you only report numbers from the single hospital where the most cases occurred.

Reporting the total number of cases out of the total number of vaccines administered can hardly be considered trivializing the actual risk. In fact, it's the exact opposite.

Assuming you have high confidence in your count of total number of cases, that is.

(Talk to the UK about this...)

 

[Galapadoc]

If you’re going to talk about the actual risk at this point, don’t trivialize it - the incidence rate in Norway was 5 in 130.000: https://www.nejm.org/doi/full/10.1056/NEJMoa2104882

Why pick Norway as the sample population given figures are available for a much larger n?

Not to mention most Scandinavian countries are relatively homogeneous; the statement "small homogenous country with little in-or-out migration has out-of-scale results" sounds to me like a long way of saying "genetic bottlenecking happens".

Scandinavian countries haven't been all that homogeneous for a long time. A full quarter of Norway consists of first-generation immigrants.

 

[Galapadoc]

On an intellectual level I know the risk on getting Covid and having complications is several orders of magnitudes higher then complications from the adenoviruses based vaccine. On a personal level I'm glad that I was offered a mRNA Covid vaccine. We're just not wired to accurately assess risk even when we are a fully informed rational person or at least I like to think of myself as being a rational.

Totally irrational I know but I couldn't help it.

The reported efficacy of Pfizer is a little over 90 percent, and for J&J it's a little over 70 percent. It's not irrational to want the one with a higher efficacy.

It's not "irrational" because the rationale is based on a common misunderstanding.

The reported efficacy rate has more to do with when and where the clinical trial was held than the actual level of protection a specific vaccine provides. The efficacy rate is calculated based on how many fully vaccinated people were ultimately infected (i.e., had a positive PCR test) versus those who received placebo.

The Pfizer and Moderna vaccines had their trials last summer in the US when case rates were low and dropping, while the J&J vaccine had its trial primarily in December in South Africa when case rates were very high and rising. That means the subjects in the US trials were much less likely to become infected because their exposure was lower, not because of the vaccine.

The "efficacy rate" is not a good measure of the level of protection provided by any given vaccine. A better measure is how many fully vaccinated people required hospitalization or death.

As it stands now, all of the vaccines currently available (Pfizer, J&J, Moderna, AstraZeneca, Sputnik, Sinovac) have a 100% track record on that front. No fully vaccinated person has required hospitalization and there have been no deaths due to Covid. The overwhelming majority of those infections were completely asymptomatic. Those who did have symptoms had nothing more serious than a common cold.

 

[numerobis]

They shouldn't have paused it. I think people really don't understand how many people die from complications of medications every year and nothing special is done about those cases.

For instance Tylenol kills around 80 to 150 people every year in the US and send 80 thousand to the Hospital. The difference between an okay dose and a liver destroying dose is just a few mg. DO NOT TAKE MORE PILLS THAN WHAT THE BOX SAYS EVER!!!
https://www.propublica.org/article/tyle ... s-directed

(Emphasis added.)

According to the item you link, the recommended daily maximum dose of acetaminophen is 4 grams, with 25 percent more -- that's 1 gram - having been reported to cause liver damage. One thousand mg is not really "just a few" mg, but otherwise of course your point stands.

Acetaminophen (or paracetamol as we call it in the civilized world) is a strange one... in safe doses it really is remarkably safe. Of course it isn't entirely free of sideeffects (most notably headaches!), but you can take it for years without much risk of anything.
NSAIDs on the other hand - ibuprofen included, has significant risk in any dose (unsurprisingly risk increases with dose and time).

On the other hand, double the dose of acetaminophen and you go from "might get a headache" to "might die from liver failure". Double the dose of ibuprohen has the more intuitive change from "small risk of serious complication" to "slighty larger risk of serious complication".

EDIT: I belive there is a case report on fatal liver failure from a 7g dose of acetaminophen, but afaik it usually takes quite a bit more. Given the risk of accidental prolonged overdose, the ease of intentional overdose and the risk of other substances blocking the metabolic pathway, you can quite easily get significant doses though (and liver failure really is a shitty way to go).
I often come across old people who get a full dose every day, then they get a pain somewhere (or maybe even a headache), and start buying them on the side as well - not realising they're getting double dosage acetaminophen for a headache caused by acetaminophen...

Europe seems very worried about ibuprofen for some reason. We hand it out like candy over here when it comes to acute pain. For chronic pain it's problematic due to stomach bleeding but for acute pain it seems to be quite safe.

It's nearly impossible to get a fatal overdose. Unfortunately only nearly, but basically it's still publishable to write up case reports about such a rare event, whereas acetaminophen results in thousands of deaths per year.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1550881/

NSAIDs are cardiotoxic. While it has proven very hard to quantify the risk, it is well established that NSAIDs increase the risk of heart attack and stroke. As far as I'm aware, there is no known safe dose (although risk increases with dose and duration of treatment, so "lowest possible dosage for shortest possible time" is the general recommendation).
Ibuprofen is probably the least cardiotoxic NSAID, but that's hardly the same as completely safe.

While it is hard to quantify an increase in an already widespread cause of death, it is pretty easy to quantify liver failure caused by acetaminophen. People don't tend to get liver failure all of a sudden, and it is simple to spot in a bloodsample.
And while both accidental and intentional overdose is a very real risk, there is such a thing as a safe dose.


Here OTC painkillers have been regulated for a few years - you can only buy something like 10 doses at a time, 20 at a pharmacy. Afaik that massively reduced teenage suicide attempts using acetaminophen, and while they're using other means instead, they have better survival rates and fewer longterm complications now.
As with all medicine, it's a matter of weighing risk and benefit. With medication used as widely as ibuprofen and acetaminophen even the rare side effetcs are significant, and things like accidental and intentional overdoses become very significant issues that need to be addressed and regulated.
On the other hand, If there are no OTC painkillers, I'm sure people in pain would find other treatments with worse problems. Ibuprofen, acetaminophen and aspirin are probably the least bad choices.

The risk of heart attack or stroke can occur as early as the first weeks of using an NSAID. The risk may increase with longer use of the NSAID.

I read that as meaning it's for long-term use but the following indicates 1-7 days:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5423546/

 

[numerobis]

If you’re going to talk about the actual risk at this point, don’t trivialize it - the incidence rate in Norway was 5 in 130.000: https://www.nejm.org/doi/full/10.1056/NEJMoa2104882

Why pick Norway as the sample population given figures are available for a much larger n?

Not to mention most Scandinavian countries are relatively homogeneous; the statement "small homogenous country with little in-or-out migration has out-of-scale results" sounds to me like a long way of saying "genetic bottlenecking happens".

Scandinavian countries haven't been all that homogeneous for a long time. A full quarter of Norway consists of first-generation immigrants.

Wiki lists 17%:
https://en.wikipedia.org/wiki/Immigration_to_Norway

Sweden is more like a quarter.

Clearly this means the vikings are back at it, raiding talent worldwide now.

 

[SraCet]

...
The Pfizer and Moderna vaccines had their trials last summer in the US when case rates were low and dropping, while the J&J vaccine had its trial primarily in December in South Africa when case rates were very high and rising. That means the subjects in the US trials were much less likely to become infected because their exposure was lower, not because of the vaccine. ...

Infection rates were different during the J&J trials but maybe not by as much as one might think.

Cumulative incidence percentage in the placebo group after 28 days for the Pfizer trial was ~0.5%, same percentage during the J&J trial was ~1%.

That being said, the J&J trial didn't track mild disease (why not?!) so it's not apples-and-oranges.

Also, there is another reason to think that the conditions of the J&J trial were more adverse, when you look at the number of severe cases and deaths. In the J&J trial, 78 people in the placebo group got severe Covid and 5 died, whereas in the Pfizer trial, only 7 people got severe Covid and nobody died.

As it stands now, all of the vaccines currently available (Pfizer, J&J, Moderna, AstraZeneca, Sputnik, Sinovac) have a 100% track record on that front. No fully vaccinated person has required hospitalization and there have been no deaths due to Covid. The overwhelming majority of those infections were completely asymptomatic. Those who did have symptoms had nothing more serious than a common cold.

Quibble: for some reason, the CDC considers a J&J recipient "fully vaccinated" two weeks after receiving the vaccine. But during the trial, two vaccinated people caught severe Covid between 14 and 28 days after being vaccinated and had to be hospitalized.

. . .

My take is that, while we don't have the exact data necessary to prove that the Pfizer vaccine is better, that's not a reason to believe that the J&J vaccine is as good (or close).

So far, all of the data we have on the Pfizer vaccine suggests that it's better. There is zero data that suggests that the J&J vaccine is as good... there's only reason to believe that it might not be that much worse.

BTW, if you take a look at the neutralizing antibody titers after day 28 from the phase 2 studies of these vaccines:

- For the Pfizer vaccine, everybody had higher antibody levels than the HCS (Human Convalescent Serum) average, except for one person

- For the J&J vaccine, everybody had lower antibody levels than the HCS average, except for two people, and a few people had MUCH lower levels

So if you consider that, it's not a huge shock that the Pfizer is putting up excellent efficacy numbers and the J&J kinda isn't, even though circumstances are different...

 

[Furry_Beaver]

If you’re going to talk about the actual risk at this point, don’t trivialize it - the incidence rate in Norway was 5 in 130.000: https://www.nejm.org/doi/full/10.1056/NEJMoa2104882

Why pick Norway as the sample population given figures are available for a much larger n?

Not to mention most Scandinavian countries are relatively homogeneous; the statement "small homogenous country with little in-or-out migration has out-of-scale results" sounds to me like a long way of saying "genetic bottlenecking happens".

"genetic bottlenecking" That's a polite way of saying inbreeding on a country scale.

Correct me if I'm wrong. Doesn't homogeneousness help track down the cause of the vaccine error?

 

[Furry_Beaver]

They shouldn't have paused it. I think people really don't understand how many people die from complications of medications every year and nothing special is done about those cases.

For instance Tylenol kills around 80 to 150 people every year in the US and send 80 thousand to the Hospital. The difference between an okay dose and a liver destroying dose is just a few mg. DO NOT TAKE MORE PILLS THAN WHAT THE BOX SAYS EVER!!!
https://www.propublica.org/article/tyle ... s-directed

"just a few mg" The maximum dose per day of Paracetamol is 3000 mg. Now that value is based on the assumption of you having a healthy liver. Alcoholics, etc beware. Have a bad liver then take less. It's also incredibly stupid to take Paracetamol if you have alcohol in your system. Never do that. It'll put extra strain on the liver which is already working hard to remove the alcohol. This also includes taking other medications that puts a strain on the liver. If you're unsure than speak to your doctor first. As a side note: Some countries have a warning system that detects if your prescribed medications that do not go well together. US is lagging behind on that as far as I know. Have something to do with profits more important than human lives.

I've read a study that concludes that taking Paracetamol together with Ibuprofen increase their effectiveness in comparison to only taking one of them.

If you're the kind of person that dislikes to read and follow the instructions and follow doctors orders I suggest you switch to Ibuprofen. It's a lot more friendly to the liver however it's less friendly to the stomach so beware of that if you have stomach related issues.

If you do find that Paracetamol is not helping you I strongly recommend going to a doctor to get prescribed a more targeted medicine based on why you take Paracetamol. If it's not helping you at a reasonable dose of 500 mg then taking more of it is a very bad idea. More is not better if it's ineffective to begin with.

If you're pregnant you should definitely avoid Paracetamol. At least limit its use to the lowest effective dosage for the shortest possible time.

 

[jpdemers]

How does this particular type of clotting actually work when platelet counts also drop? Is it just a case of platelet count dropping by 5x but platelet clotting affinity increasing by 10x or something?

The missing platelets are probably glommed together in the clots.

 

[blarfiejandro]

On an intellectual level I know the risk on getting Covid and having complications is several orders of magnitudes higher then complications from the adenoviruses based vaccine. On a personal level I'm glad that I was offered a mRNA Covid vaccine. We're just not wired to accurately assess risk even when we are a fully informed rational person or at least I like to think of myself as being a rational.

I agree 100%.

The day before I was schedule to get my first shot I just happened to be driving by the convention center where the vaccine was being administered. Because I'd never been there before I decided to swing into the parking lot so I knew were I was going the following day. The workers were just breaking down their setups at the end of the day so I asked about the check-in procedure and which vaccine they were giving out. When they told me J&J I have to admit I was a bit disappointed even though there was no good reason to be.

The next day when I found out they were giving out the Pfizer vaccine that day I was a relieved and felt I had lucked out.

Totally irrational I know but I couldn't help it.

The reported efficacy of Pfizer is a little over 90 percent, and for J&J it's a little over 70 percent. It's not irrational to want the one with a higher efficacy.

Except for the fact that those numbers aren't really comparable. J&J Stage III trials were done later - with a higher prevalence of variants. Although the mRNA vaccines are effective against the (current) variant strains, the do show some lack of efficacy.

Which could mean that both numbers are roughly the same today.

You would have to trial them simultaneously to know if one was 'better' than the other. Then you would have to wait six to twelve months to see if that efficacy held.

TL;DR - they're basically the same - for now.

The Pfizer mRNA vaccine was evaluated against the newer strains in a lab setting. The conclusion was that the vaccine is effective against the variants in a lab setting. Obviously without human trials it's impossible to say conclusively, but my money is on the mRNA vaccines proving more effective than the viral vector vaccines even with the variants.

https://www.nature.com/articles/s41591-021-01270-4

 

[jpdemers]

That's pretty much baked into the system whenever there's a choice among vaccines. If you're living in a village in an impoverished country, you take what they give you. It'll be whatever is most amenable to being schlepped along dirt roads (or worse) and stored without electricity.

 

[jpdemers]

Out of 6.8 million people, how many will have a clot in the next few weeks WITHOUT getting a vaccination?

In the "general medical and surgical population" the incidence of HIT is 0.2% - so multiply that by whatever percentage of the population will be in the hospital in the next few weeks, for non-Covid-19 reasons. https://pubmed.ncbi.nlm.nih.gov/21640991/

 

[Galapadoc]

Out of 6.8 million people, how many will have a clot in the next few weeks WITHOUT getting a vaccination?

In the "general medical and surgical population" the incidence of HIT is 0.2% - so multiply that by whatever percentage of the population will be in the hospital in the next few weeks, for non-Covid-19 reasons. https://pubmed.ncbi.nlm.nih.gov/21640991/

This isn't HIT. HIT is a rare adverse effect of heparin use. The reason for all the concern is that none of the people who suffered this problem had previous exposure to heparin. The only thing they had in common was vaccination with an adenovirus vector vaccine, making it the most likely suspect.

 

[Galapadoc]

The Pfizer mRNA vaccine was evaluated against the newer strains in a lab setting. The conclusion was that the vaccine is effective against the variants in a lab setting. Obviously without human trials it's impossible to say conclusively, but my money is on the mRNA vaccines proving more effective than the viral vector vaccines even with the variants.

https://www.nature.com/articles/s41591-021-01270-4

The smart money would be on the inactivated virus vaccine (Sinovac). It stimulates production of antibodies against multiple parts of the virus, not just the spike protein like the mRNA vaccines. If there's a significant mutation in the spike protein, all the current mRNA vaccines could become completely ineffective. Given the amount of evolutionary pressure we're putting on the virus with so many vaccines that only target one protein, that eventuality is probably an inevitability.

 

[jpdemers]

Not so much inbreeding as less diversity. Unless you think marrying your third or fourth cousin is "inbreeding".

Relatively high homogeneity can be helpful to researchers looking for links between disease and genetic markers - essentially because there's a lot less noise in the data. Iceland in particular has been hugely valuable for those sorts of studies, and you can be sure scientists are scouring the country for cases of vaccine-induced thrombosis.

 

[jpdemers]

Just want to give props to Beth Mole, the author: this is an excellent article, well written, well organized, and scientifically literate. I love being able to read something like this without wincing or rolling my eyes.
I hope Ars Technica knows what they've got with this writer.

 

[Galapadoc]

...
I'm not going to bother continuing a COVID conversation with you given your prior history.

Good, I hope you don't.

Meanwhile, is anybody else getting sick of people just assuming that everybody has the same odds of catching Covid?

I would tell people in Australia, China, New Zealand, and Taiwan to definitely avoid these adenovirus vaccines for now. Why run the risk?

Likewise, I live in the US and have friends who just stay at home all day, conduct their work and social life online, and the only physical interaction they have with the outside world is when they get their groceries delivered (and they don't interact with the delivery person). These people seem to be at basically zero risk of catching Covid. I would definitely recommend they skip the J&J shot and wait for a Pfizer/Moderna appointment to open up, because why not?

"You should get whatever vaccine is available to you as soon as possible" is great advice in general but not necessarily great advice for any particular individual.

Based on your gestalt, I presume.

Why would anyone take a medical "recommendation" from someone who can never be held civilly or criminally liable for the advice they dispense?

 

[Chuckstar]

It makes one wonder if Adenoviruses themselves cause blood clots naturally which are unreported or attributed to other causes.

Seems unlikely. Adenoviruses are super-common. HIT-like blood clotting among people not receiving heparin is super-rare.

EDIT: It's certainly possible that the very rare incidence of HIT-like blood clotting among people not receiving heparin is the result of a very rare interaction of adenoviruses with the immune system. What is unlikely is that we will have to make any meaningful modification in our understanding of the morbidity/mortality associated with adenoviruses.

 

[Chuckstar]

How does this particular type of clotting actually work when platelet counts also drop? Is it just a case of platelet count dropping by 5x but platelet clotting affinity increasing by 10x or something?

The missing platelets are probably glommed together in the clots.

There are too many missing platelets for that to be the mechanism. The mechanism for reduced platelet count is likely to be reticuloendothelial clearance of affected platelets. That is, the immune system is removing platelets -- with the signal for removal either being immune cells sensing the antibodies attached to the PF4 cytokines or sensing the platelet activation itself. In HIT, it has been noted that patients whose immune systems have been compromised such that they have reduced reticuloendothelial clearance activity tend to experience greater amounts of clotting while their platelet counts do not fall as far. This would support the hypothesis that reticuloendothelial clearance is removing activated platelets from the bloodstream.

 

[eivinds]

Not so much inbreeding as less diversity. Unless you think marrying your third or fourth cousin is "inbreeding".

No, I'm pretty sure Astra Zeneca's PR department will say there's nothing wrong with the vaccine and blame the deaths on Nordic inbreeding.

--

If you trust the (lack of?) data from other regions, it seems likely that there's a genetic factor involved, or perhaps some other local factor in the Nordics.

 

[Cloudgazer]

https://www.ox.ac.uk/news/2021-04-15-ri ... 9-vaccines

In this study of over 500,000 COVID-19 patients, CVT occurred in 39 in a million patients.
In over 480,000 people receiving a COVID-19 mRNA vaccine (Pfizer or Moderna), CVT occurred in 4 in a million.
CVT has been reported to occur in about 5 in a million people after first dose of the AZ-Oxford COVID-19 vaccine.

Right now it seems very plausible that the problem isn't the adenoviruses, the problem is intrinsic to Covid, and to vaccines built to prevent it.

 

[blarfiejandro]

The Pfizer mRNA vaccine was evaluated against the newer strains in a lab setting. The conclusion was that the vaccine is effective against the variants in a lab setting. Obviously without human trials it's impossible to say conclusively, but my money is on the mRNA vaccines proving more effective than the viral vector vaccines even with the variants.

https://www.nature.com/articles/s41591-021-01270-4

The smart money would be on the inactivated virus vaccine (Sinovac). It stimulates production of antibodies against multiple parts of the virus, not just the spike protein like the mRNA vaccines. If there's a significant mutation in the spike protein, all the current mRNA vaccines could become completely ineffective. Given the amount of evolutionary pressure we're putting on the virus with so many vaccines that only target one protein, that eventuality is probably an inevitability.

One of the advantages of the mRNA vaccines is the ability to iterate faster, no? If so then it seems like the mRNA vaccines are better poised to respond to COVID mutations. Meanwhile the Sinovac vaccine doesn't seem to be faring too well in Chile (and there's debate about its efficacy against variants):

https://www.bbc.com/news/world-latin-america-56731801

 

[azazel1024]

On an intellectual level I know the risk on getting Covid and having complications is several orders of magnitudes higher then complications from the adenoviruses based vaccine. On a personal level I'm glad that I was offered a mRNA Covid vaccine. We're just not wired to accurately assess risk even when we are a fully informed rational person or at least I like to think of myself as being a rational.

I agree 100%.

The day before I was schedule to get my first shot I just happened to be driving by the convention center where the vaccine was being administered. Because I'd never been there before I decided to swing into the parking lot so I knew were I was going the following day. The workers were just breaking down their setups at the end of the day so I asked about the check-in procedure and which vaccine they were giving out. When they told me J&J I have to admit I was a bit disappointed even though there was no good reason to be.

The next day when I found out they were giving out the Pfizer vaccine that day I was a relieved and felt I had lucked out.

Totally irrational I know but I couldn't help it.

The reported efficacy of Pfizer is a little over 90 percent, and for J&J it's a little over 70 percent. It's not irrational to want the one with a higher efficacy.

Except for the fact that those numbers aren't really comparable. J&J Stage III trials were done later - with a higher prevalence of variants. Although the mRNA vaccines are effective against the (current) variant strains, the do show some lack of efficacy.

Which could mean that both numbers are roughly the same today.

You would have to trial them simultaneously to know if one was 'better' than the other. Then you would have to wait six to twelve months to see if that efficacy held.

TL;DR - they're basically the same - for now.

They aren't the same, but you just can't directly compare them.

If you need to though, Pfizer has been looked at by Israel and small trial in SA and it is showing a >90% efficacy still against strains of concern. So still significantly better than J&J.

But J&J is a single dose. I'd bet dollars to donuts if J&J had a booster 3-6 weeks after the 1st shot, 2 or so weeks after the booster I'd bet we'd find quite a bit of increased efficacy. Whether it would be AS effective, don't know. But it probably would be better.

And I think we will find from J&J's 2 shot trials, that the recommendation becomes to get a booster.

No matter how you want to slice it, you can't claim they are the same. The data we have does not establish without a doubt that Pfizer or Moderna are better than AZ or J&J. However, the data we do have, strongly indicates that they are.

Any of the approved in the US or by the EU vaccines are worlds better than not taking anything.

 

[Galapadoc]

One of the advantages of the mRNA vaccines is the ability to iterate faster, no? If so then it seems like the mRNA vaccines are better poised to respond to COVID mutations. Meanwhile the Sinovac vaccine doesn't seem to be faring too well in Chile (and there's debate about its efficacy against variants):

https://www.bbc.com/news/world-latin-america-56731801

The Sinovac vaccine is just as effective against the P1 variant as all the other vaccines in use and, just like with the other vaccines, nobody who was fully immunized has died of Covid. The problem in Chile is one of lowering restrictions too soon in the name of activating the economy, not one of vaccine efficacy. The mRNA technology is certainly a leap forward in bringing vaccines to market quickly.

However, that wasn't my point. Because the current mRNA vaccines only target the spike protein, a significant mutation in that protein will render them completely ineffective and we're right back to square one. A new target will have to be found and all the people who received the first formulation will have to be inoculated all over again. Moderna and Pfizer are already working on new targets because such a scenario was considered very likely from the beginning but the urgency of the situation didn't allow for a more broad-spectrum vaccine to be developed.

With the slow rollout of vaccination across most of the world, it now seems virtually inevitable. The advantage of inactivated virus vaccines is they already produce antibodies against multiple targets so no single mutation can outmaneuver them. Targeting a single protein rather than the whole virus will most likely breed resistance.

The problem is with the terminology. Vaccine efficacy is measured in its ability to prevent infections, which is not the endpoint we're really interested in. When we measure the efficacy of a diabetes drug, it's calculated based on its ability to lower blood sugar, not cure diabetes. A far better measure of Covid vaccine efficacy would be based on its ability to prevent death (or maybe need for mechanical ventilation, hospital admission, etc.) since that's the endpoint we are trying to prevent. Efficacy rates based on number of infections is fraught with too many uncontrollable variables to give us any useful information. As we are now seeing, its only really useful from a marketing point of view as people are now foolishly electing to delay vaccination to wait for one with a higher reported efficacy rate even though all of the vaccines have been shown to be 100% effective in preventing death.

 

[SraCet]

...
They aren't the same, but you just can't directly compare them.

If you need to though, Pfizer has been looked at by Israel and small trial in SA and it is showing a >90% efficacy still against strains of concern. So still significantly better than J&J.

But J&J is a single dose. I'd bet dollars to donuts if J&J had a booster 3-6 weeks after the 1st shot, 2 or so weeks after the booster I'd bet we'd find quite a bit of increased efficacy. Whether it would be AS effective, don't know. But it probably would be better.

And I think we will find from J&J's 2 shot trials, that the recommendation becomes to get a booster.

No matter how you want to slice it, you can't claim they are the same. The data we have does not establish without a doubt that Pfizer or Moderna are better than AZ or J&J. However, the data we do have, strongly indicates that they are.

Any of the approved in the US or by the EU vaccines are worlds better than not taking anything.

In the phase 2 trials, a booster shot at day 57 did significantly increase neutralizing antibodies.

It's weird to me that they didn't choose a 2-dose protocol for the phase 3 trials. I assume that was motivated by, essentially, marketing. Saying that your vaccine only requires one dose whereas all the other ones require two doses is pretty powerful.

Even with a booster shot, I don't think there's any reason to believe that the J&J vaccine might end up as effective as an mRNA vaccine. The J&J shot is basically the same idea as the AZ shot, and the AZ shot is only putting up efficacy numbers around 80% after the second shot. (Yes, yes, the efficacy numbers aren't comparable blah blah.)

I got the J&J shot. If a booster shot becomes the recommendation, I think I might ask for a shot of Pfizer. Unless there's some reason why the vaccines can't be mixed?

 

[Galapadoc]

No matter how you want to slice it, you can't claim they are the same. The data we have does not establish without a doubt that Pfizer or Moderna are better than AZ or J&J. However, the data we do have, strongly indicates that they are.

Any of the approved in the US or by the EU vaccines are worlds better than not taking anything.

You can assert they are the same if you "slice" efficacy as a function of preventing death rather than preventing infections. Given that death due to Covid is the only relevant endpoint, using the same formula we use for measuring the efficacy of the measles vaccine is not really the most sound approach. It may have been last September when we didn't know if vaccinated people who suffered a subsequent infection would end up hospitalized, but now that we know they don't there's really no point in arguing the point.

If you really want to slice and dice it, you can break down efficacy based on need for mechanical ventilation, hospitalization or even need for supplemental oxygen, but on those endpoints all the vaccines in use today also have the same track record. Efficacy is virtually 100% for all of them.

 

[SraCet]

... The problem is with the terminology. Vaccine efficacy is measured in its ability to prevent infections, which is not the endpoint we're really interested in. ... A far better measure of Covid vaccine efficacy would be based on its ability to prevent death (or maybe need for mechanical ventilation, hospital admission, etc.) since that's the endpoint we are trying to prevent. ...

Many/most of these vaccine trials have had different primary and secondary endpoints. So the problem isn't so much that these vaccines are only being evaluated in terms of preventing any infections at all (they aren't), it's that people are not reading the fine print for all of the efficacy numbers being thrown around.

A notable exception to the "they're counting efficacy against ALL infections" complaint is the J&J trial. The primary endpoint for that trial was preventing moderate-to-severe infections. It seems they didn't bother collecting data for mild infections, or if they did, they didn't report it.

So this is pretty stupid. Most other vaccine manufacturers are publishing efficacy numbers for preventing ANY symptomatic infection, and J&J's number just doesn't count [presumably] many symptomatic infections. WTF, J&J.

CoronaVac got roasted for the same bulls**t. They published efficacy numbers around 80% vs. moderate disease, everybody complained, and then they had to publish an efficacy number of ~50% that included mild disease.

Just based on that, I would suspect that J&J's efficacy against all symptomatic disease is probably around 50% or maybe less.

 

[SraCet]

...
If you really want to slice and dice it, you can break down efficacy based on need for mechanical ventilation, hospitalization or even need for supplemental oxygen, but on those endpoints all the vaccines in use today also have the same track record. Efficacy is virtually 100% for all of them.

I posted about this above, but if you missed it, there's a technicality with this number.

In the J&J trial, two people in the vaccinated group got severe Covid between days 14 and 28 and had to be hospitalized.

The CDC considers people to be "fully vaccinated" only two weeks after receiving the J&J vaccine.

So the J&J vaccine efficacy for "fully vaccinated" people was only 93% against hospitalization, not 100%.

If you're talking about 4 weeks after vaccination, then yes, it's 100%.

 

[.劉煒]

No fully vaccinated person has required hospitalization and there have been no deaths due to Covid.

https://abc7ny.com/covid-after-vaccine- ... /10508285/

This came across my feeds a few days ago, so I'm going with that's not an entirely accurate statement anymore.

 

[SraCet]

No fully vaccinated person has required hospitalization and there have been no deaths due to Covid.

https://abc7ny.com/covid-after-vaccine- ... /10508285/

This came across my feeds a few days ago, so I'm going with that's not an entirely accurate statement anymore.

Interesting. Sounds like this guy was probably infected between weeks 2 and 4 after receiving the vaccine, just like the two people in the trial who had to be hospitalized.

Seems like more evidence that J&J recipients should only be considered fully vaccinated 4 weeks after receiving the injection.

 

[Galapadoc]

No fully vaccinated person has required hospitalization and there have been no deaths due to Covid.

https://abc7ny.com/covid-after-vaccine- ... /10508285/

This came across my feeds a few days ago, so I'm going with that's not an entirely accurate statement anymore.

Again, the terminology is messing up the reporting. A "fully vaccinated" person is someone who has received the last dose of the vaccine and sufficient time has passed for the immune response to reach maturity. In some trials they tested this at 14 days, some at 21, but that only boils down to an arbitrary number the manufacturer settled on when they wrote up their study protocol based mostly on neutralizing antibodies (which is only one aspect of immunity). Those periods will certainly be revised over the coming months/years as we get more real-world data, but a good rule of thumb for all vaccinations (Covid or otherwise) is 28 days.

Sounds like this guy got infected sometime around 10 days after the vaccine, which doesn't qualify clinically as fully vaccinated. It would be akin to saying an antibiotic doesn't work against a given bacteria because a patient died after the first dose rather than after completing the entire regimen.

 

[Galapadoc]

...
If you really want to slice and dice it, you can break down efficacy based on need for mechanical ventilation, hospitalization or even need for supplemental oxygen, but on those endpoints all the vaccines in use today also have the same track record. Efficacy is virtually 100% for all of them.

The CDC considers people to be "fully vaccinated" only two weeks after receiving the J&J vaccine.

It's not what the CDC considers, it's the endpoint the manufacturer put in their study protocol.

And therein lies the rub. Every study is done in different populations in different epidemiological environments with different endpoints, endpoints that are based on little more than a "best guess" in the rush to get the product to market. There are no consistent definitions of "mild" or "severe" disease. Each manufacturer comes up with that themselves and the criteria can vary widely.

Since the point of the vaccine is to prevent people from dying from the virus, as a physician it's the only endpoint I consider relevant when determining efficacy. Hospitalization rates are also important, but there's a big difference between someone hospitalized in the ICU on mechanical ventilation and someone hospitalized on an internal medicine floor on nothing more than 3 lpm of oxygen via a nasal cannula, and even the criteria for determining who ends up with which vary tremendously depending on the country, resources available, bed space, etc., so we're only opening up the calculation to more confusion. At best, those can be secondary endpoints in a clinical trial, but they don't tell us much about efficacy.

For the record, I expect a lot of people who received any of the vaccines to ultimately end up dying of Covid for the simple fact that not everyone out there can mount an effective immune response to vaccination. However, I find all this comparison of "efficacy" rates to be counterproductive in ending the pandemic. I personally know of more than a few people who have foregone an opportunity to get vaccinated because they were waiting for a "better" vaccine to become available in their area.

 

[Galapadoc]

Many/most of these vaccine trials have had different primary and secondary endpoints. So the problem isn't so much that these vaccines are only being evaluated in terms of preventing any infections at all (they aren't), it's that people are not reading the fine print for all of the efficacy numbers being thrown around.

In public health school we were taught that you cannot blame the failure of a public health intervention on the public not being trained in public health. The people shouldn't have to read the fine print. The vast majority of them wouldn't understand it if they did. The problem is with the intervention, not the population.

The CDC should be tailoring the information in a way that the public can understand instead of letting the internet confuse people. There's an entire field of public health devoted to health promotion; what types of messaging works, what doesn't, what misconceptions are out there, how messaging can be better tailored to affect behaviors in a way that results in better health outcomes. Volumes of peer-reviewed studies are published on everything from getting people to wash their hands to going in for pap smears to eating a balanced diet. Psychologists, sociologists, anthropologists and even economists have earned PhDs in public health focused solely on getting the right message across to entire populations.

Clearly those PhDs aren't being listened to right now.

 

[SraCet]

...
Since the point of the vaccine is to prevent people from dying from the virus ...

Is it?

We definitely don't want people to die, obviously.

But it's useful to have more information about a vaccine. How much does a vaccine affect transmissibility? How much does a vaccine affect hospitalizations? How much does a vaccine affect organ damage and/or long Covid?

If nothing else, let's say you're in government and trying to choose which vaccines to invest in, which vaccines to purchase, and which vaccines to ultimately distribute. Just flipping a coin between a bunch of vaccines that all claim to be 100% effective at preventing death isn't a good way to do this.

 

[SraCet]

...
Clearly those PhDs aren't being listened to right now.

Au contraire, I think reading these internet forums might be giving you a skewed view of what people in the general public are thinking.

All of the "real-world" vaccine discussions I've participated in have basically revolved around people wanting the J&J vaccine because they don't want to bother with going in for a second appointment. Only one person I've encountered in "real life" seemed to be aware that the J&J vaccine might be less effective than the others.

 

[Galapadoc]

...
Since the point of the vaccine is to prevent people from dying from the virus ...

Is it?

We definitely don't want people to die, obviously.

But it's useful to have more information about a vaccine. How much does a vaccine affect transmissibility? How much does a vaccine affect hospitalizations? How much does a vaccine affect organ damage and/or long Covid?

If nothing else, let's say you're in government and trying to choose which vaccines to invest in, which vaccines to purchase, and which vaccines to ultimately distribute. Just flipping a coin between a bunch of vaccines that all claim to be 100% effective at preventing death isn't a good way to do this.

Basing vaccine efficacy on death rates is hardly just flipping a coin. Vaccines are being administered as fast as they can be produced. As far as hospitalizations go, we already know they all have the same effect. By the time we have enough data on organ damage or long Covid, the entire global population will have long ago been vaccinated.

 

[SraCet]

...
Basing vaccine efficacy on death rates is hardly just flipping a coin. Vaccines are being administered as fast as they can be produced. As far as hospitalizations go, we already know they all have the same effect. By the time we have enough data on organ damage or long Covid, the entire global population will have long ago been vaccinated.

All of the major vaccines that I'm aware of are claiming 100% efficacy against death.

If that's your only evaluation criteria, choosing between the vaccines is just flipping a coin.

I don't think flipping a coin is very responsible if you're ordering hundreds of millions of doses of these things...

 

[Galapadoc]

...
Clearly those PhDs aren't being listened to right now.

Au contraire, I think reading these internet forums might be giving you a skewed view of what people in the general public are thinking.

All of the "real-world" vaccine discussions I've participated in have basically revolved around people wanting the J&J vaccine because they don't want to bother with going in for a second appointment. Only one person I've encountered in "real life" seemed to be aware that the J&J vaccine might be less effective than the others.

I know at least half a dozen people who have based their decision solely on the reported efficacy rates. Then there's the mayor of Detroit who declined the J&J vaccine for his city because, in his words:

"So, Johnson & Johnson is a very good vaccine. Moderna and Pfizer are the best. And I am going to do everything I can to make sure the residents of the city of Detroit get the best,"

https://www.cnn.com/2021/03/04/health/d ... index.html

And that's the mayor of a major city in a developed country, someone with dozens of paid expert advisors and a direct line to state and federal public health officials. What chance does the average Joe with a Facebook account have of sifting through all the bad information? That's what the CDC is supposed to do for them and it's the job of their experts in health promotion to make sure the right message is getting across.

 

[Galapadoc]

...
Basing vaccine efficacy on death rates is hardly just flipping a coin. Vaccines are being administered as fast as they can be produced. As far as hospitalizations go, we already know they all have the same effect. By the time we have enough data on organ damage or long Covid, the entire global population will have long ago been vaccinated.

All of the major vaccines that I'm aware of are claiming 100% efficacy against death.

If that's your only evaluation criteria, choosing between the vaccines is just flipping a coin.

I don't think flipping a coin is very responsible if you're ordering hundreds of millions of doses of these things...

You think waiting months for data on organ damage or long Covid while the pandemic continues to rage is very responsible? And how do you get that data if you aren't administering the vaccines? More trials? For how long? How many more deaths are acceptable while you decide what is perfect?

The choice as to which vaccine to purchase is mostly being made on availability. Governments are purchasing them as fast as they can be produced. Other big factors are cost and cold-chain logistics. It's less flipping a coin than it is throwing a 20-sided die, but then again so is every decision when implementing a public health intervention.

This isn't like the HPV vaccine where we have decades to get as close as possible to a zero-risk situation. In the middle of a global pandemic with hundreds of thousands of new cases daily and rising, perfect is definitely the enemy of the good.

 

[SraCet]

...
I know at least half a dozen people who have based their decision solely on the reported efficacy rates.

It seems we know different people. I will happily admit that my experience is anecdotal.

Other than making the efficacy trial data secret, I don't know how to avoid the situation we're currently in, though.

Fauci and the CDC are distributing simple advice that's good for the population, and at least some people are paying attention to them and believing them and following the advice, so, good.

Other people are looking at the vaccine trial data for themselves, which is going to be inevitable unless the data is a secret, which is obviously not a viable option.

I understand your complaint that some people aren't taking the time to correctly understand the data that they're seeing/finding, it's a bummer, but again, seems inevitable.