Covid-19 vaccines thread

[CharonY]

1 hour ago, Duda Jarek said:

18th November Pfizer 95 percent https://www.theguardian.com/world/2020/nov/18/pfizer-covid-19-vaccine-95-effective-and-safe-further-tests-show

Time for another bid for Sputnik and Moderna

I think Pfizer submitted their report for approval, which is a good sign. I think Sputnik V is not a contender yet as they only reported 20 cases. And perhaps just as some additional info, the vaccine from Pfizer was  developed by a small German company (BioNTech). Pfizer has taken over the costly bits (including manufacturing and distribution).

Also perhaps as a sidenote, one of the reasons why they managed to hit their milestone is because so many people are getting infected...

[J.C.MacSwell]

What exactly does the 95% effective mean? Only one in 20 gets the virus? To what degree and with what degree of exposure? One in 20 never gets sick? Never gets symptoms? Never tests positive? Never able to spread the virus? Get it but not as badly as they would have? (how would they compare this?)

I'm assuming never tests positive but what exposure level is tested? How would the numbers look with no vaccine and same test?

[CharonY]

One would need to look at the full report to see what kind of measure was used. A typical design would involve self-monitoring for symptoms and participants will be regularly called to see how they are doing. So unless they specifically monitored for asymptomatic cases (which would increase complexity of the trial and I suspect is somewhat unlikely), it is more likely the reported cases are symptomatic ones. 

In other words, among the whole cohort we find 5% of folks having symptoms (and then tested) despite being vaccinated and the remaining infected folks only had the placebo. The overall cohort was only 30k people and while they try to be representative of the population, it also means that we will only have limited data regarding who has been infected and why. There are also other considerations, e.g. whether folks getting sick while vaccinated may have a much higher exposure than the rest.

Also, one thing to consider is that, assuming the vaccine acts as promised, it basically means they do not get sick. However, it does not mean that they may not get infected and perhaps even spread the disease. I suspect that many folks will believe that once vaccinated they are immune and can get everywhere, but I hope it will be communicated that they still need to keep their distance from unvaccinated folks.  Often, vaccinations will reduce the viral titer sufficiently to only pose a problem in rare cases. However, with this disease we simply do not know.

[J.C.MacSwell]

Thanks CY!

[J.C.MacSwell]

13 hours ago, CharonY said:

One would need to look at the full report to see what kind of measure was used. A typical design would involve self-monitoring for symptoms and participants will be regularly called to see how they are doing. So unless they specifically monitored for asymptomatic cases (which would increase complexity of the trial and I suspect is somewhat unlikely), it is more likely the reported cases are symptomatic ones. 

 

So generally speaking, you can't directly compare a 90% claim to a 95% one, you have to look further and the 90% claim could be the better one? (without even considering statistical variance but just method)

13 hours ago, CharonY said:

In other words, among the whole cohort we find 5% of folks having symptoms (and then tested) despite being vaccinated and the remaining infected folks only had the placebo. The overall cohort was only 30k people and while they try to be representative of the population, it also means that we will only have limited data regarding who has been infected and why. There are also other considerations, e.g. whether folks getting sick while vaccinated may have a much higher exposure than the rest.

 

Thinking about the numbers:

If I'm interpreting it correctly, since it is unlikely that 5% of even the placebo group would get the virus with only a normal exposure distribution....would that mean that the unvaccinated group is simply 20 times more likely to get it given overall similar circumstances and makeup of each group? (or something close to that?)

Not asking specifically about the latest claims...just generally what 95% would mean, or perhaps should mean for such claims.

[CharonY]

4 hours ago, J.C.MacSwell said:

So generally speaking, you can't directly compare a 90% claim to a 95% one, you have to look further and the 90% claim could be the better one? (without even considering statistical variance but just method)

It depends on at least two things. First, the endpoint measurement. I.e. how did you determine a positive event. If a trial consists of regular testing of even asymptomatic folks your final infected cohort will contain cryptic infections. If you only measure symptomatic cases, your study will ignore those. I do think that the trials are likely only focusing on symptomatic events and are therefore comparable (but I could be wrong). The second issue is that the number may be derived from a differently sized infection cohort. If you only have very few infected folks the numbers you get can be highly biased. Therefore any efficacy measurement with a small cohort is unreliable. There are therefore target numbers that the study has to hit, which given infection rates turn out not to be a problem. For rarer diseases this can lead to very long trials.

4 hours ago, J.C.MacSwell said:

If I'm interpreting it correctly, since it is unlikely that 5% of even the placebo group would get the virus with only a normal exposure distribution....would that mean that the unvaccinated group is simply 20 times more likely to get it given overall similar circumstances and makeup of each group? (or something close to that?)

Yes that is the basic idea. You create two cohorts that typically are similar in composition (to avoid bias) and then let them out in the wild and see what happens. The Null hypothesis is that after some time both groups should have similar infection rates if the vaccine does not do anything. What folks hope to see is that among the (much smaller) infected group, we see disparity between treatment and control.

The big challenge is to get enough folks infected and there is a risk of confounding factors leading to who gets infected in the first place. The idea is then that both (control and vaccinated group) are similar enough to each other to cancel that out. That is potentially not always the case. Just as a random example, it is possible that the vaccine does not work for elderly female Asian folks (for some reasons). But since so few are in either group we have no information about that.

 

[J.C.MacSwell]

Thanks again!

[koti]

Looks like China are getting there too:

"...We investigated CoronaVac (Sinovac Life Sciences, Beijing, China), an inactivated vaccine candidate against COVID-19, containing inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for its safety, tolerability and immunogenicity..."

https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30843-4/fulltext?fbclid=IwAR211ftWnJx464kgl_HtmiBdI1YUUfvOXkMh_anmW_Gj8KMGWvmZ64TWtbE

Edited November 19, 2020 by koti

[CharonY]

25 minutes ago, koti said:

Looks like China are getting there too:

"...We investigated CoronaVac (Sinovac Life Sciences, Beijing, China), an inactivated vaccine candidate against COVID-19, containing inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for its safety, tolerability and immunogenicity..."

https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30843-4/fulltext?fbclid=IwAR211ftWnJx464kgl_HtmiBdI1YUUfvOXkMh_anmW_Gj8KMGWvmZ64TWtbE

They still need to go phase III, though.

[koti]

10 minutes ago, CharonY said:

They still need to go phase III, though.

Lets hope they do.

[CharonY]

1 hour ago, koti said:

Lets hope they do.

It is actually still in a trial with around 60k people. I do not think that they have released results yet. One interesting bit about this one is that it is developed using traditional approaches and looking at the paper it also seems to have a faster immune response. 

[koti]

11 hours ago, CharonY said:

...One interesting bit about this one is that it is developed using traditional approaches and looking at the paper it also seems to have a faster immune response.

It might be that theyre terryfied more than others of the possibility that they will screw something up thats why the traditional approaches.

[CharonY]

8 hours ago, koti said:

It might be that theyre terryfied more than others of the possibility that they will screw something up thats why the traditional approaches.

I doubt it. It is more that before the trials mRNA vaccine candidates so far had low immunogenicity and  it the approach was considered to have a low success rate. The technology was around for some time, but it was not considered to be that competitive to traditional approaches. That is also why the drugs were developed by somewhat smaller companies, which have been working on drugs since 2005/2013, respectively, rather than being adopted by the big pharmas. Especially in the middle of an outbreak you would want a vaccine that creates strong immediate responses rather than multiple dosages, which is likely another incentive to go the traditional route. Considering that up until now no mRNA vaccines had been approved it is a high-risk scenario where the vaccine might have failed for a number of reasons. On top, there is still the issue that we won't have any long-term data on mRNA vaccines. It is really because out of despair and necessity where mRNA vaccines have been propelled to prominence.

And in the end, it is crucial to have a range of methods available as we won't have the time to gather sufficient data. Despite promising phase 3 results, we have no guarantee that it will play out the same way in the broader population.

[empleat]

https://covid.postera.ai/covid is non-profit organization, their research is free of intellectual property - they share it with scientific community and everyone with scientific knowledge can design a molecule! It is being crowdsourced to public, using shared computing FAH@Home. So you can crunch on your PC! I am sick of pharma corporations and their patents, Biden said he will do something - perphaps... They get funding mainly from philanthropy and bootstrap grants. Public can donate, but they got only 46k out of 2M so far 

News is there are ready to test most 500 promising compounds on animals - can't find where i read it... But they don't have as high funding, probably won't be sooner, than other vaccines. But still if some vaccine wouldn't be good, or country would decide not to share it... That's what has been happening in Russia e.g. which was not tested well and crap probably anyways so

They have powerful installation using X-Rays to study biology of the virus at microscopic level:

https://test.foldingathome.org/2020/05/28/the-covid-moonshot/

Edited November 22, 2020 by empleat

[CharonY]

The AstraZeneca vaccine seems to be working, too. They had 131 infections. However, they tested two dose regimens, with one (halved first dose and standard second dose) seemingly being more effective (90% vs 62%).

[MigL]

I read that too, and was puzzled by it.
Can you shed any light on why a half dose followed by a full dose would be more effective than a full dose followed by another full dose ?
And not just by a bit, but 50% more effective ?

[CharonY]

1 hour ago, MigL said:

I read that too, and was puzzled by it.
Can you shed any light on why a half dose followed by a full dose would be more effective than a full dose followed by another full dose ?
And not just by a bit, but 50% more effective ?

It is often difficult to predict how the immune system reacts and how (and whether) it generates long-lasting immunity. In this particular case I cannot tell you what happened, but it is common that the reaction of the immune system have weird, non-linear relationship. Which is why statements like "strengthening the immune system" are tricky as it consists of feed back loops on many levels involving many different cell types. There are cases where initial strong responses are not building up memory, for example, which might be the case here. However, it must also be noted that it could be an issue of small numbers, as the half-dosage group effectively splits the total cohort. So it could also be a statistical fluke at that point.

I should also add that there is not just one immune response, the immune system fundamentally has different elements, and typically when we talk about vaccinations we look at the adaptive response. However, the innate immunity also plays a role and interacts with adaptive responses. And even more complicated, in vertebrates now also something similar to innate memory has been discovered (often called trained immunity).

 

[MigL]

AstraZeneca is reporting some dosing irregularities which have eroded confidence in the results reported last week.
This may affect their application to have their vaccine authorized for emergency use by regulators, in time for early 2021 roll out.

[CharonY]

1 hour ago, MigL said:

AstraZeneca is reporting some dosing irregularities which have eroded confidence in the results reported last week.
This may affect their application to have their vaccine authorized for emergency use by regulators, in time for early 2021 roll out.

Yeah, it is odd that they accidentally injected some with half the planned dose, which is a weird thing to happen in a trial.

[StringJunky]

1 hour ago, CharonY said:

Yeah, it is odd that they accidentally injected some with half the planned dose, which is a weird thing to happen in a trial.

Isn't one of the two doses given for this drug a half dose? Can't remember if it's the first or second dose.

Edited November 26, 2020 by StringJunky

[MigL]

Apparently they also combined the results of two separate trials ( the other is in Brazil ? ), which isn't really accepted procedure.

I got the impression that the half-dosing, which resulted in better outcomes, was not intentional, but an 'error' on the part of a 'contractor', Srtingy.
They still have some serious work to do, before they can make any more claims.

[StringJunky]

25 minutes ago, MigL said:

Apparently they also combined the results of two separate trials ( the other is in Brazil ? ), which isn't really accepted procedure.

I got the impression that the half-dosing, which resulted in better outcomes, was not intentional, but an 'error' on the part of a 'contractor', Srtingy.
They still have some serious work to do, before they can make any more claims.

The BBC have a write up on it: https://www.bbc.co.uk/news/health-55086927

Edited November 26, 2020 by StringJunky

[Duda Jarek]

U.K. Approves Pfizer Coronavirus Vaccine, a First in the West

https://www.nytimes.com/2020/12/02/world/europe/pfizer-coronavirus-vaccine-approved-uk.html

[Externet]

What are the requirements to receive the vaccine ?

Do recipients need to not be infected or tested negative for the virus ?

Do recipients need to not have antibodies for it ?

Do recipients must be healthy or not hospitalized with other illnesses ?

Is that depending on the vaccine manufacturer like each manufacturer having their rules ?

Will a certificate be issued to the recipient as to allow travel ?

[iNow]

It will vary from one location to the next, or from state to state, and while central governments will offer recommendations on how best to distribute, decisions on how best to prioritize delivery for the most part will be made by local officials.