Covid-19 #17: Covid Is For Ever

[Mudguard]

2 hours ago, Knight Of Winter said:

Here's one interesting case.

When pandemic started, Brazilian city of Manaus failed to react in any way: they had no distancing, no masks and no obligatory disinfection in stores. Naturally, they were hit hard - and I mean really hard - by the virus. Hospitals ran out of beds very quickly, death toll skyrocketed to such a degree that impromptu mass graves were dug to accommodate all the bodies. It'd not be far-fetched to say that Manaus was one on the worst places to be during the corona-crisis.

But recently, something changed. Not the population - who still don't wear masks and don't practice distancing - but the disease itself. Number of fatalities suddenly plummeted - having gone from 120 daily in May to almost zero recently. So scientists speculate that maybe enough people survived the virus to develop the herd immunity. Far from anything definite, but certainly interesting food for thought.

There is something similar going on in Sweden too, where the case numbers, and particularly the number of deaths, rapidly plummeted around the end of June, despite little change to official health guidelines.  The Swedish health authorities have also speculated that herd immunity may be playing a role, but the numbers of infected determined by antibody testing studies isn't anywhere near the required levels to achieve herd immunity.  Better infection control management at nursing homes has also played an important role in keeping the numbers of deaths low.

People have speculated that perhaps there is some level of cell-based immunity that is not being detected by antibody testing, but this needs a lot more work before it is proven.  Perhaps a portion of the population already has some level of immunity based on previous infection with a related coronavirus strain.  If this is the case, it's another reason why a control group is needed for the vaccine studies.  Otherwise, the efficacy of the vaccine will be overstated.  Perhaps the people that are most at risk are taking more care, but the rest of the general population still remains relatively lax.  

It's something to monitor, especially as winter approaches.  If the hardest hit areas such as Manaus, Stockholm, NYC, northern Italy, etc., all avoid a second wave this winter or as measures are relaxed, there may be something to this.  Even if this turns out to be the case, most places in the world have not been hit nearly that hard, so we cannot assume that many other places are at or close to herd immunity levels.

 

[Fragile Bird]

Canada has had single digits in deaths for weeks now, even though 2,500 to 3,500 new cases are added every week. But then again 80% of our deaths were in old age homes, and that has been brought under control.

[Fragile Bird]

I’m watching CNBC and they are reporting that AstraZeneca’s Phase 3 testing has apparently been put on hold because of an adverse safety reaction in some participants.

No news on what the nature of the adverse reaction was.

[williamjm]

19 minutes ago, Fragile Bird said:

I’m watching CNBC and they are reporting that AstraZeneca’s Phase 3 testing has apparently been put on hold because of an adverse safety reaction in some participants.

No news on what the nature of the adverse reaction was.

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

The story suggests it is difficult to know at the moment whether this is something significant, although it's clearly not going to help the timeline of getting results from the trial.

[Mudguard]

11 minutes ago, Fragile Bird said:

I’m watching CNBC and they are reporting that AstraZeneca’s Phase 3 testing has apparently been put on hold because of an adverse safety reaction in some participants.

No news on what the nature of the adverse reaction was.

Wow, hopefully it turns out the adverse event was not caused by the vaccine, and they can resume the clinical trials soon.  Also hope they release more information soon.  It's possible though that they'll wait until they figure out whether the vaccine was responsible.

If none of the first three vaccines pans out, we could be waiting a while for a vaccine.  I'm not sure how far along the traditional inactivated or live attenuated virus vaccines are.  Inactivated virus vaccine candidates are probably much further along than live attenuated virus vaccines though.  China has published results from a phase 1/2 trial of an inactivated virus vaccine, so they are certainly well underway.

[The Anti-Targ]

 

Moved too early out of level 3?

Report last night that a student at an Auckland school tested positive. They were at school on Friday and went home feeling unwell. This is a student associated with a sub-cluster at an evangelical Church. The Health Minister said in a news interview that some members of that congregation have been uncontactable because they don't believe in the science. This student was an undisclosed contact of this church sub-cluster and they are investigating whether the non-disclosure of the connection was deliberate.

[Fez]

15 minutes ago, Mudguard said:

Wow, hopefully it turns out the adverse event was not caused by the vaccine, and they can resume the clinical trials soon.  Also hope they release more information soon.  It's possible though that they'll wait until they figure out whether the vaccine was responsible.

If none of the first three vaccines pans out, we could be waiting a while for a vaccine.  I'm not sure how far along the traditional inactivated or live attenuated virus vaccines are.  Inactivated virus vaccine candidates are probably much further along than live attenuated virus vaccines though.  China has published results from a phase 1/2 trial of an inactivated virus vaccine, so they are certainly well underway.

Even if the vaccine is responsible, I would assume that doesn't necessarily doom the vaccine, right? Like if the conditions required for the vaccine to harm people mean that 1 in a million, or even 1 in 10,000 people can't get it, wouldn't the vaccine still be approved so long as it was precisely known what causes the adverse reaction?

People with really severe egg allergies can't get the flu vaccine, but the vaccine still exists for the public.

[The Anti-Targ]

12 minutes ago, Mudguard said:

Wow, hopefully it turns out the adverse event was not caused by the vaccine, and they can resume the clinical trials soon.  Also hope they release more information soon.  It's possible though that they'll wait until they figure out whether the vaccine was responsible.

If none of the first three vaccines pans out, we could be waiting a while for a vaccine.  I'm not sure how far along the traditional inactivated or live attenuated virus vaccines are.  Inactivated virus vaccine candidates are probably much further along than live attenuated virus vaccines though.  China has published results from a phase 1/2 trial of an inactivated virus vaccine, so they are certainly well underway.

Depends on the adverse event, and how common it is. if it's a 1:100,000 event and it is not severe then the vaccine could still get approval. Drugs are approved all the time with a laundry list of side-effects, and people have adverse reactions to existing vaccines.

Quote

The nature of the adverse reaction and when it happened were also not immediately known, though the participant is expected to recover, according to an individual familiar with the matter.

"Expected to recover" isn't really a phrase you want to see in vaccine / drug side effects. It means the reaction, if it is due to the vaccine, was serious enough that there is a chance the person wouldn't recover. Doesn't necessarily mean death, but could mean a permanent debility.

Quote

the finding is having an impact on other AstraZeneca vaccine trials underway — as well as on the clinical trials being conducted by other vaccine manufacturers.

Interesting, so they possibly think it is about other components of the vaccine, not the viral antigen itself. So a reformulation may be needed but not scrapping the vaccine completely.

[Mudguard]

2 minutes ago, Fez said:

Even if the vaccine is responsible, I would assume that doesn't necessarily doom the vaccine, right? Like if the conditions required for the vaccine to harm people mean that 1 in a million, or even 1 in 10,000 people can't get it, wouldn't the vaccine still be approved so long as it was precisely known what causes the adverse reaction?

People with really severe egg allergies can't get the flu vaccine, but the vaccine still exists for the public.

No way to know until they release more information.  If the vaccine is responsible, it really depends on the nature of the adverse event, why it happened, and how likely it could happen again.  But yes, an adverse reaction caused by the vaccine wouldn't necessarily doom the vaccine.  For example, maybe it was a dosing error, or contamination issue, both of which could be fixed.  

[Mudguard]

13 minutes ago, The Anti-Targ said:

Depends on the adverse event, and how common it is. if it's a 1:100,000 event and it is not severe then the vaccine could still get approval. Drugs are approved all the time with a laundry list of side-effects, and people have adverse reactions to existing vaccines.

"Expected to recover" isn't really a phrase you want to see in vaccine / drug side effects. It means the reaction, if it is due to the vaccine, was serious enough that there is a chance the person wouldn't recover. Doesn't necessarily mean death, but could mean a permanent debility.

Interesting, so they possibly think it is about other components of the vaccine, not the viral antigen itself. So a reformulation may be needed but not scrapping the vaccine completely.

Because the vaccine has probably been given to less than 30,000 subjects, the current risk is going to be at least 1 in around 20,000 to 30,000 (however many have been dosed so far), at least for now.  For a vaccine that is going to be given to hundreds of millions of people, that might be too much.  Hope it's not caused by the vaccine.  

Eta:. Trials are only paused for serious adverse events, like things that require hospitalization or end in death.

[Impmk2]

5 minutes ago, The Anti-Targ said:

Interesting, so they possibly think it is about other components of the vaccine, not the viral antigen itself. So a reformulation may be needed but not scrapping the vaccine completely.

Not sure this follows. The AstraZenica is the adenovirus vector vaccine. So they're relying on infection by the virus and expression of the SARS-CoV-2 spike protein by the host. Honestly I'm not familiar enough with the other uses of the technology (gene therapies etc) to know what other components there'd be besides the virus (ie if you'd even need an adjuvent). Anyway, I doubt they'd be the same as a traditional vaccine, and I'd think the one constant across the various vaccines is the viral antigen, as near everyone is going for a neutralising antibody response to the receptor binding domain of the spike protein from what I've read.

[The Anti-Targ]

1 minute ago, Impmk2 said:

Not sure this follows. The AstraZenica is the adenovirus vector vaccine. So they're relying on infection by the virus and expression of the SARS-CoV-2 spike protein by the host. Honestly I'm not familiar enough with the other uses of the technology (gene therapies etc) to know what other components there'd be besides the virus (ie if you'd even need an adjuvent). Anyway, I doubt they'd be the same as a traditional vaccine, and I'd think the one constant across the various vaccines is the viral antigen, as near everyone is going for a neutralising antibody response to the receptor binding domain of the spike protein from what I've read.

I thought the adenovirus "base" was an already known quantity in terms of vaccine development, i.e. it's already in use in existing vaccines. So the only new thing is the SARS-COV-2 spike protein antigen. But maybe this adenovirus is also a new thing. 

13 minutes ago, Mudguard said:

Because the vaccine has probably been given to less than 30,000 subjects, the current risk is going to be at least 1 in around 20,000 to 30,000 (however many have been dosed so far), at least for now.  For a vaccine that is going to be given to hundreds of millions of people, that might be too much.  Hope it's not caused by the vaccine.  

Eta:. Trials are only paused for serious adverse events, like things that require hospitalization or end in death.

If the adverse reaction is to something other than the spike protein (ref concern about other vaccines in development at AZ) then there might be more than the ~20K SARS-COV-2 trialist involved.

We need to know more, but information might be fairly slow in coming into the public domain, especially at this level of trial detail.

[Impmk2]

1 minute ago, The Anti-Targ said:

I thought the adenovirus "base" was an already known quantity in terms of vaccine development, i.e. it's already in use in existing vaccines. So the only new thing is the SARS-COV-2 spike protein antigen. But maybe this adenovirus is also a new thing.

AFAIK (and just did another quick google to confirm) they've only previously been used in other applications such as gene therapies and animal vaccines. There's been a fair bit of research into them, but none have so far been approved in a commercial human vaccine.

[Mudguard]

18 minutes ago, The Anti-Targ said:

I thought the adenovirus "base" was an already known quantity in terms of vaccine development, i.e. it's already in use in existing vaccines. So the only new thing is the SARS-COV-2 spike protein antigen. But maybe this adenovirus is also a new thing. 

If the adverse reaction is to something other than the spike protein (ref concern about other vaccines in development at AZ) then there might be more than the ~20K SARS-COV-2 trialist involved.

We need to know more, but information might be fairly slow in coming into the public domain, especially at this level of trial detail.

Adenovirus based vaccines have been in R&D for decades, but have yet to result in a commercial vaccine.  Impmk2 has described it correctly.  You are using a genetically modified adenovirus that has been modified to include a gene that encodes the spike protein and whatever other antigens you'd like to use.  You are not delivering the antigen itself directly.  Oxford is using a chimpanzee adenovirus to try and get around antibodies against common human adenoviruses that are present in many people.  I have no idea how much testing in people the chimpanzee adenovirus has undergone.

ETA: Technically, the Russian vaccine is also an adenovirus based vaccine (using a human adenovirus), so there is now one product sort of on the market, albeit with limited testing.

[The Anti-Targ]

2 minutes ago, Impmk2 said:

AFAIK (and just did another quick google to confirm) they've only previously been used in other applications such as gene therapies and animal vaccines. There's been a fair bit of research into them, but none have so far been approved in a commercial human vaccine.

Ohhh, that's a bit of a worry.

[The Anti-Targ]

Well, lets hope that other cliche they used, "abundance of caution", means the person's illness has naught to do with the vaccine.

[Wilbur]

Well, Sturgis turned out about as poorly as possible.

Anecdata: https://www.washingtonpost.com/health/2020/09/02/sturgis-rally-death-coronavirus/

Study: http://ftp.iza.org/dp13670.pdf

In the end it looks like it would have been cheaper for the government to pay each of the participants about $25,000 a piece to stay away than to pay for the actual medical outcomes.

[williamjm]

36 minutes ago, The Anti-Targ said:

Well, lets hope that other cliche they used, "abundance of caution", means the person's illness has naught to do with the vaccine.

Some of the other stories now appearing about it point out that this is the second time the trial has been paused, I don't remember any coverage of a previous pause but maybe it was just something routine.

[Altherion]

19 hours ago, DaveSumm said:

Putting the ethics aside for a minute, there are many other reasons why you should simulate the actual means of infection rather than just shooting them up with some covid. We don’t really know how the virus might manifest if contracted through air particles, or touching surfaces, or how these means affect the viral load, or how a vaccine might be efficacious against these different methods, if at all. People are contracting this virus naturally in their every day lives, and that is the environment it should be tested in. It’s also not black and white, it might work in some circumstances and some not, it might work 75% of the time (in which case we most definitely need data on the circumstances of the 25%). We’ll need a robust understanding of how it works to compare it to other candidates, when you might administer one or the other, what time scales they remain effective for.

And double blind tests are the gold standard for scientific experiments, you don’t just stop bothering cos we’re in a hurry. It’s more important in this instance, not less.

I think that at this point we do know quite a bit about the various means of transmission. It's true that letting people become infected naturally is a better experiment, but again, the price of this is several thousand lives for every day the vaccine is delayed. Also, keep in mind that this slow method of testing with two orders of magnitude more people than will get the virus has a different set of drawbacks. For example, if you follow a random 30000 people over a period of a few months, it's quite likely that one of them will develop a serious health condition that is completely independent of the vaccine... but of course you have to stop and prove that it's actually independent of the vaccine (which is exactly what happened to one of these vaccines just now).

15 hours ago, Mudguard said:

I don't know what you mean by "type of vaccine."

I mean whether it is the type of vaccine that is 95%+ effective (like the one for measles) or the one that is of order 50% effective (like the one for the flu). The underlying techniques used are not relevant, only the effectiveness.

15 hours ago, Mudguard said:

All the early vaccine candidates are based on unproven technologies that have yet to result in a commercially sold vaccine.  Consequently, there is even more uncertainty around these vaccines than usual.  We have no idea how well any of these vaccines will work.  It could range anywhere from actually increasing your chance of getting infected to 80+% effective.

Your comment that they should just come up with a better vaccine rather than do the testing if the effectiveness is around 50% or less is nonsensical.  Again, the effectiveness of the vaccine is unknown until it's tested in clinical trials.  I don't get why you think this is something that is known beforehand.  Normally your posts are logical, even if they may be controversial, but there appears to be a big disconnect here.  There are over 150 vaccine candidates under development, and we have no idea about the efficacy of any of them.

The disconnect is that I am perhaps misunderstanding the vaccine development process. I don't know the details (from what I've read, they appear to differ among the various vaccines being considered), but the vaccine is not just a randomly selected chemical compound with a completely unknown efficacy -- it usually does something to provoke an immune response against this specific virus and they ought to have some idea of how it works before it has made it to the third and final stage of testing. Of course, this understanding is not perfect -- that's why they test -- but it should be considerably better than complete ignorance of the efficacy. That said, if they really don't know anything about the efficacy, then the test where they simply administer the vaccine followed by the virus to a small number of people is far more critical because it would give you a very good estimate of the effectiveness on timescales that are of order a week.

Regarding a vaccine with a 50% effectiveness: what I meant was that such a vaccine might be worse than no vaccine at all because it would encourage people to behave less cautiously.

[karaddin]

@Zorral While I agree with your assessment of the ideology behind intentional infection of trial participants, Anti-Targ was merely attempting to translate the poster who was actually advocating for doing that and AT stated that doing so would be both unethical and probably illegal. You may have seen other comments from him at other times but in this case I don't think he was suggesting anything untoward himself.

I would very much apply the same moniker as you to the poster who was suggesting that approach though.