What's particularly worrying is that all vaccines use the same spike protein (although AZ doesn't have the pre-fusion conformation stabilising mutation which a number of other vaccines do). So if this substantially lowers efficacy of one vaccine it will have directionally the same effect on all of them. Of course the response of efficacy to antibody titre and other correlates of protection is non-linear so it could be that AZ was just low enough for the mutation to kick them into the "doesn't work" zone.
I expect that come late summer we'll all be getting another booster of some sort against whatever mix of variants is around. The trick will be prediction although we are helped by the fact that both mRNA and vectored vaccines can be changed and produced quite quickly.
I also think that the emergence of this variant may save lives in the end because it forces to the front of everyone's mind the necessity of vaccinating the entire world and may make it politically easier to ship vaccine to the poor countries of the world before the rich countries have finished their vaccination programmes.
In the US, it's been ramping up to about 1.5 million shots a day and a one-shot J&J vaccine will presumably be coming on line. But, yes, depending upon the assumptions you care to make, it'll probably be later in the summer before the majority of people in the general population pool <65 years old get a vaccine.
I think there's enough evidence from 2020 that your views aren't cynical, but instead realistic. The feasibility of world-wide coordination should no longer be expected regardless how high the stakes.
Would new shots adapted to novel strains have to pass the same trial process as the first versions of the vaccine? Or are there some provisions for an even faster approval? I don't know how it works for the flu vaccine.
The flu vaccine skips the effective part of the trail, but still needs to go through safety tests for a few months.
I'm not sure at what point we are comfortable enough with vaccine technology to agree to that. There have been a few vaccine candidates in the past that made things worse, we think we understand the flu well enough to not worry about that. However for the new vaccines we don't have as much information.
Although if the virus keeps mutating there will be pressure to bypass the process to approve faster. That pressure is why the flu vaccine bypasses steps, if we did everything "by the book" we wouldn't have a working flu vaccine ever.
The FDA has announced that boosters to address novel strains will undergo a rapid review process. Full details of what that will involve are expected in 2 to 3 weeks.
In my Algorithms in Drug Design class in school, one of the research projects was using docking software to do an alpha/beta search for mutations that would alter protein structure while preserving binding affinity, with the idea of heading off vaccine escape (in this case HIV) by predicting the mutations likely to escape antibody binding.
Is anything like that being done with covid?
Edit: the Alpha move was to mutate the antibody and the Beta move was to mutate the viral protein iirc.
Because vaccines are in short supply. The choice isn't AZ+Moderna+JJ+PB vs Moderna+JJ+PB. the real choice today is AZ+Moderna+JJ+PB+NOTHING vs Moderna+JJ+PB+NOTHING, with the size of nothing being larger in the second case.
So really it is c: you vaccinate everyone with whatever you can get your hands on. Once everyone has had some vaccine you look at data of what is working and give everyone with a less effective vaccine an additional dose of whatever works - which will probably be a new vaccine that doesn't exist yet!
Don't forget that mutations are continuous. We might be looking at another mutation in 3 months as supply catches up that evades vaccines in a completely new way.
As a) is likely to reduce the serious cases faster, that seems like a point in its favor.
One complication might be if people getting mild cases end up spreading the variant faster, because they are not incapacitated by it - but it is not as if it is having much difficulty spreading now, despite the serious cases it creates, as it seems to spread before it incapacitates. I don't think this possibility demands that we stop using this vaccine until this issue is unequivocally settled.
Healthcare professionals are first in line in the South African vaccine rollout. It's possible that not protecting against moderate to severe illness is an inadequate outcome for this group. Skipping this group in order to vaccinate others may not be politically palatable.
Skipping this group is not an inevitable consequence of continuing to uze the AZ vaccine. The rate at which this group can be vaccinated with other vaccines is an orthogonal issue.
people in other groups may be unwilling to take the AZ vaccine, but so long as they are not being coerced to do so, this is not an issue.
There have been serious side effects documented for these vaccines. Bruising, soreness, "covid mouth", miscarriages, deaths, anaphylactic shock, etc. The vaccine has also not been out long enough to know of any long term health issues.
The data is not in whether they are effective against death. They didn't test the super vulnerable in the studies. If you look at the places that have high vaccination numbers, you don't actually see any significant drop in covid cases or deaths. If anything, those places are staying high while the rest of the world is dropping. They were released under emergency authorization which means that they haven't fully testing and verified them to the level that would normally be done.
If they are as effective as the hype, we should be seeing significant positive results by now.
If you look at places that have high vaccination numbers, oh wait, there aren't any. Israel is leading the world with only about 20% of their population having undergone a full vaccination regimen, and it takes a few weeks after the second dose for immunity to reach its highest level. Given how fast they are vaccinating, a very high proportion of that 20% was given that second shot in the last few days.
In other words, there is no place on Earth where we would expect vaccination to have an impossible to dispute effect on the top-line deaths or hospitalization numbers... yet. Give it 6 weeks.
To your other points about side effects, nearly 100m people globally have gotten at least one shot. The mild side effects which require a day off work are completely worth it, and the severe ones happen extremely rarely, to where a risk adjusted decision even for a very young and healthy person would still be to get the vaccine.
Only one of your points is even mildly valid, that the vaccines haven't been out long enough to know if there are any long term health issues. While we won't know this for generations, because of the definition of "long term," we also have no reason to believe that there would be long term health issues, while we know that SARS-COV-2 infection can DEFINITELY cause long term health issues in a significant minority of people infected.
Lastly, many folks pushing anti-vaxxer propaganda are selling something: usually quack cures. Ignore the parent comment, and focus on the facts.
Worth noting that the JJ vaccine (which is similar) showed 89% efficacy against severe disease (hospitalization) wrt the SA variant. So - it's very likely that all vaccines will prevent healthcare systems getting stressed and significant excess mortality. Additionally if the vaccines are retarding the viral loads (it seems likely) then they should reduce transmission.
...which means that the optimal strategy is still go ahead with the Oxford-AstraZeneca phase 3 trial DESPITE these disappointing results, because they don't have another vaccine in SA and they really need to reduce hospitalizations and transmissability.
Unfortunately, the vaccine review system is not setup to allow such nuanced approvals.
I wouldn't be surprised if that's what SA does; the health minister kind of signaled that it may be resumed. I'm sure they're at least considering it. Normal approval processes for vaccines are getting modified all over the place, nowadays.
The 501.V2 variant is widespread in South Africa and is troubling due to its potential for vaccine evasion [1]:
> On 6 February 2021, The Financial Times reported that provisional trial data from a study undertaken by South Africa's University of the Witwatersrand in conjunction with Oxford University demonstrated reduced efficacy of the Oxford–AstraZeneca COVID-19 vaccine against the 501.V2 variant. [68] The study found that in a sample size of 2,000 the AZD1222 vaccine afforded only "minimal protection" in all but the most severe cases of COVID-19. [69] On 7 February 2021, the Minister for Health for South Africa suspended the planned deployment of around 1 million doses of the vaccine whilst they examine the data and await advice on how to proceed. [70]
Looking at the bigger picture I think the world will suffer from those countries that handle Covid the worst because
the virus will not disppear in those countries and it has time to mutate there until it reaches a state that can evade the vaccines and then re-infect the other countries.
Several epidemiologist are trying to warn the developed nations that the current battle for covid vaccines provisioning is doing the world a disservice since it allows the virus to mutate in parts of the world that can't compete economically for vaccine shots (Manaus, South Africa, etc.)
But Nash equilibrium is still more powerful than everything else ...
Since we don't have enough doses or dosing capacity yet to make anywhere reach herd immunity, not even tiny Israel (although hopefully they are getting close), it's not like shipping everything to South Africa would change anything. Also, given the refrigeration requirements of the early vaccines, shipping it to lower income countries would probably just increase the chance of some of the doses spoiling.
Really, it's in virtually every country, so there's not a place on Earth where it's not mutating.
Animals carry lots of nasty diseases, Ebola, rabies, SARS, MERS, etc., yet these are under control in large parts of the world, thanks to basic hygiene. If we were willing to follow e.g. New Zealand's example, committing to actually applying what we have learned about containing local outbreaks, maybe we couldn't eradicate SARS-CoV-2 and its variants, but we could do so much better at controlling it, allowing us to largely go back to normality.
Yeah, I haven't seen a lot of discussion of this, but cats, hamsters, guinea pigs, and mink is a lot of other mammal species already proven to be able to pass it on. I think we will never live in a covid-19 free world again, it will be like measles; always in circulation, but hopefully we get effective vaccines against it.
The important thing to note is that the significance of this study goes beyond the AZ vaccine. Please correct me if I've missed one, but from what I've seen there aren't any other vaccines that have completed similar trials in South Africa. The "good news" about the other vaccines' effectiveness against the variant have been based on in vitro immune response[1], not real-world trials. What would be good to know though is what response the AZ vaccine had in tests similar to the ones performed with other vaccines.
Readit News
I expect that come late summer we'll all be getting another booster of some sort against whatever mix of variants is around. The trick will be prediction although we are helped by the fact that both mRNA and vectored vaccines can be changed and produced quite quickly.
I also think that the emergence of this variant may save lives in the end because it forces to the front of everyone's mind the necessity of vaccinating the entire world and may make it politically easier to ship vaccine to the poor countries of the world before the rich countries have finished their vaccination programmes.
A booster? I don't think I will be able to get my first dose by then...
(I am an amateur not a doctor)
I'm not sure at what point we are comfortable enough with vaccine technology to agree to that. There have been a few vaccine candidates in the past that made things worse, we think we understand the flu well enough to not worry about that. However for the new vaccines we don't have as much information.
Although if the virus keeps mutating there will be pressure to bypass the process to approve faster. That pressure is why the flu vaccine bypasses steps, if we did everything "by the book" we wouldn't have a working flu vaccine ever.
Is anything like that being done with covid?
Edit: the Alpha move was to mutate the antibody and the Beta move was to mutate the viral protein iirc.
https://www.biorxiv.org/content/10.1101/2020.12.31.425021v1....
[1] https://jbloomlab.github.io/SARS-CoV-2-RBD_DMS/
All the data we have suggests AZ is probably 100% effective at preventing death from the South African strain.
(Mostly) everyone agrees we want to have a vaccine that is:
-safer than not vaccinating
-effective against death
-actually available to use
AZ is all 3 of these in South Africa (and everywhere).
It also provides some additional benefits, like:
-cheap
-no cold storage
-easier to administer
By banning AZ you aren't trading it for Pfizer, you are trading it for no vaccine.
b) Let's say you vaccinate all south-africans with Moderna+JJ+PB, then all the population will be protected.
If you pay the same in both scenarios, why on earth would you choose a)?
So really it is c: you vaccinate everyone with whatever you can get your hands on. Once everyone has had some vaccine you look at data of what is working and give everyone with a less effective vaccine an additional dose of whatever works - which will probably be a new vaccine that doesn't exist yet!
Don't forget that mutations are continuous. We might be looking at another mutation in 3 months as supply catches up that evades vaccines in a completely new way.
One complication might be if people getting mild cases end up spreading the variant faster, because they are not incapacitated by it - but it is not as if it is having much difficulty spreading now, despite the serious cases it creates, as it seems to spread before it incapacitates. I don't think this possibility demands that we stop using this vaccine until this issue is unequivocally settled.
Deleted Comment
people in other groups may be unwilling to take the AZ vaccine, but so long as they are not being coerced to do so, this is not an issue.
The data is not in whether they are effective against death. They didn't test the super vulnerable in the studies. If you look at the places that have high vaccination numbers, you don't actually see any significant drop in covid cases or deaths. If anything, those places are staying high while the rest of the world is dropping. They were released under emergency authorization which means that they haven't fully testing and verified them to the level that would normally be done.
If they are as effective as the hype, we should be seeing significant positive results by now.
If you look at places that have high vaccination numbers, oh wait, there aren't any. Israel is leading the world with only about 20% of their population having undergone a full vaccination regimen, and it takes a few weeks after the second dose for immunity to reach its highest level. Given how fast they are vaccinating, a very high proportion of that 20% was given that second shot in the last few days.
In other words, there is no place on Earth where we would expect vaccination to have an impossible to dispute effect on the top-line deaths or hospitalization numbers... yet. Give it 6 weeks.
To your other points about side effects, nearly 100m people globally have gotten at least one shot. The mild side effects which require a day off work are completely worth it, and the severe ones happen extremely rarely, to where a risk adjusted decision even for a very young and healthy person would still be to get the vaccine.
Only one of your points is even mildly valid, that the vaccines haven't been out long enough to know if there are any long term health issues. While we won't know this for generations, because of the definition of "long term," we also have no reason to believe that there would be long term health issues, while we know that SARS-COV-2 infection can DEFINITELY cause long term health issues in a significant minority of people infected.
Lastly, many folks pushing anti-vaxxer propaganda are selling something: usually quack cures. Ignore the parent comment, and focus on the facts.
I've seen coverage of anaphylaxis, but not death and miscarriages. Anaphylaxis is also extremely rare and causality is unproven.
Would you please provide references for the other severe side effects you listed?
Unfortunately, the vaccine review system is not setup to allow such nuanced approvals.
> On 6 February 2021, The Financial Times reported that provisional trial data from a study undertaken by South Africa's University of the Witwatersrand in conjunction with Oxford University demonstrated reduced efficacy of the Oxford–AstraZeneca COVID-19 vaccine against the 501.V2 variant. [68] The study found that in a sample size of 2,000 the AZD1222 vaccine afforded only "minimal protection" in all but the most severe cases of COVID-19. [69] On 7 February 2021, the Minister for Health for South Africa suspended the planned deployment of around 1 million doses of the vaccine whilst they examine the data and await advice on how to proceed. [70]
[1] https://en.wikipedia.org/wiki/501.V2_variant#Vaccine_evasion
[68] https://www.reuters.com/article/us-health-coronavirus-astraz...
[69] https://www.bbc.co.uk/news/world-africa-55975052
[70] https://www.washingtonpost.com/world/europe/astrazeneca-oxfo...
1. Reinfection is most likely driving the selection pressure that results in antibody escaping variants.
2. SARS-CoV-2 Antigens are present in the gut of many individuals for months after the initial infection.
[1] https://www.microbe.tv/twiv/twiv-717/
(Scroll down past the first few paragraphs)
https://ig.ft.com/coronavirus-vaccine-tracker/
But Nash equilibrium is still more powerful than everything else ...
Really, it's in virtually every country, so there's not a place on Earth where it's not mutating.
Once a country reaches herd immunity, then by all means get vaccines to other countries, but until then non-vaccinated people are fungible.
Natural reservoirs of covid-19 means we'll all need boosters yearly for the rest of our lives.
[1]And we know the issues with that standard https://xkcd.com/1217/
Source: https://twitter.com/EricTopol/status/1358486648359591937/pho...