This is great news for Africa which really needs vaccines right now. It's great that all this vaccine research is going on. But the inequality of access is a huge problem.
Up to now Africa hasnt had a big wave of covid, but this 3rd wave has hit us really hard (and I know, Africa is not a country, I live in South Africa).
What experts warned about might happen is happening now: because of insufficient vaccinations the Covid pandemic will stick around and mutate in poor countries.
This is one of the things that depresses me the most… rich countries don’t even need to be altruistic here. Be entirely selfish: send vaccines to worse off countries to cut down on the number of mutations that will inevitably arrive on your shores.
The really depressing part is that the exact same logic applies to climate change, so I’m not exactly full of hope for the future right now.
It doesn't matter whether your justification for why this should happen is altruism or selfishness, the same problem remains: a vaccination program of the scale and speed we've already seen is literally unprecedented, it's astounding that everyone managed this much, and yet even with that incredible effort there still aren't the doses to vaccinate the planet any time in the imminent future let alone the on-the-ground infrastructure to deliver them everywhere - and even the rich, developed countries with the best vaccine rollouts out there probably haven't reached herd immunity before new variants made that impractical or even impossible with the current vaccines.
This isn't that remarkable. Previous attempts to deal with respiratory disease pandemics using vaccines have proved pretty futile, even though it is a standard part of pandemic planning.
I think the remarkable thing is that vaccine development and manufacturing is one of the smallest costs of the pandemic.
For example the cost of a dose of Biontech Pfizer vaccine is roughly the same as the cost of getting a single antigen test performed in Germany (both roughly 20 EUR).
With the variants/mutations it seems we should invest much more in vaccine capacity to avoid spending 2022 in another lockdown.
> there still aren't the doses to vaccinate the planet any time in the imminent future let alone the on-the-ground infrastructure to deliver them everywhere
I think the vaccinations campaigns everywhere (in the developed world at least) have shown that the infrastructure to vaccinate everyone is there if only we have enough supplies of vaccines.
Half the worlds population lives on less than $5.50 per day. If you offered them 20 EUR they wouldn’t use it on a vaccine for a highly survivable disease (Compared to HIV, Malaria, and TB), they’d use it to buy food and water.
It's not entirely impossible, I'm sure we would be fine with in in South Africa, and many African countries. Just need consistent power. But yes that is a hindrance.
It is not a matter of not willing to share, but a capacity problem. All production is fully bought up. Throwing more money at it won't increase the supply.
> It is not a matter of not willing to share, but a capacity problem. All production is fully bought up. Throwing more money at it won't increase the supply.
This is why we should suspend IP / patent protection and increase production.
There’s IP and then there’s IP. If Moderna published their complete protocols, cell lines, etc and allowed any qualified manufacturer to pay $5k/hr to consult with Moderna experts on how exactly to manufacture the vaccine, I wonder if there would be more supply.
The only reasonable counter argument I’ve heard is the lead time on spinning up the new plants. It’s always been throwing money at the problem won’t fix it right now.
If they invested in building new plants what happens in a few years? Is covid still an issue? Would they need to close the plant because of a lack of need?
IDK, but not screwing this up is absolutely crucial.
If ramping up the production comes at a cost of cutting some corners, and a contaminated/dangerous batch of mRNA vacciness comes along as a result, the antivaxx movement will have a field day whose impacts will be felt even fifty years from now. We (as humanity) cannot affort a massive vaccine screw up.
It's not really about being rich but availability (at least at first). The vaccine costs between $3 and $20[1] which is accessible for most of the third-world and even in most countries in Africa.
> so I’m not exactly full of hope for the future right now
Don't be. The vaccine is being used as a political tool currently (Pfizer good, Sinovac bad, etc...) and to restrict/grant movement around countries.
In covid deaths occurring in the under 65 population, there is often a significant comorbidity that contributed to severe illness. Obesity, diabetes, etc, are at the top of that list.
Africa by and large does not have the same health profile or concerns as Japan, the UK, or the U.S.
None of this is to suggest that vaccines should not be distributed there. I think they should.
What I'm questioning is if COVID-19 deserves to be even on, let's say, the top 10 list of problems facing Africa in 2021. Probably not.
Most of us in our mid 30's have mild cases. Until I see evidence of it, I'm going to treat it as media driven hysteria.
Like masks on 4 year olds.
From the first link above: "loss of taste and/or smell (28%, 17/61), fatigue (21%, 13/61), dyspnea (13%, 8/61), impaired concentration (13%, 8/61) and memory problems (11%, 7/61)."
Does anyone really consider these to be a serious syndrome caused by covid infection? I'm pretty sure I experienced most of these from the lockdowns alone. Lots of folks also think they have fibromyalgia and that it's not just in their head (it is).
From the second link:
“It remains to be established if these immune alterations are unique to COVID-19, or whether they are also observed following other severe respiratory infections."
Lucky for you that you haven't personally seen any case of long covid, I personally know two people suffering from it and third one bit more distant.
Two of those are in people 30-40 years old. Third one is over 60. One had some unusual brain fog and memory issues, second one is unable to work and still treated for various symptoms. The older one became housebound while before that she was self sufficient and even taking care for young girl from extended family. To think of it I also know of one very young person in family of my friends that had to be hospitalized multiple times for post covid stuff. He's not even 20.
You may of course discount all of this that it couldn't happen spontaneously or after a bad flu. That's why I believe long covid is a thing mostly because of reports comming from all over the globe and associated research not because of those personal stories.
If you need evidence of your own eyes to believe something I don't envy you or anyone that relies on your decisions.
> I haven't seen anything remotely convincing. But I am open to changing my mind.
It was so obvious that you're statement was just a fluff.
Long covid isn't easy to measure. Eg. Not everyone was admitted to the hospital, what are the symptoms related, are those symptoms unique to long covid, ...
But by now, it should be clear that long covid exists and covid deaths aren't the only problem related to this disease.
Being in a denial state is your problem, not mine. I think it's currently a specific US political motivated issue, as I haven't encountered anyone in Belgium that claimed it's irrelevant/not existing.
The state wants people to be vaccinated as quick as possible and a political party + Anon is dismissing it as "just a cold/5G/nanobots" and some people believe it.
It's more like propaganda against the state and a lot of Americans believe that misinformation.
At least other countries / citizens seem to have more common sense.
No one here is talking about 5G. That is always the go to "gotcha" for anyone pushing covid hysteria.
The reason I post here anonymously is because tying my identity to this can lead to consequences elsewhere. Everyone knows there is unprecedented censorship around this issue. Which is part of why we have failed so utterly to comprehend and contextualize this virus.
This is a statistically shoddy talking point. The average of all causes of death is right at the average life expectancy, by definition. Any cause of death weighted towards the elderly will have an average age above the average life expectancy.
This is precisely my point. Quite easy to miss the spread of a virus when:
1) Your population is by and large not susceptible to severe illness from the virus. Rates of asymptomatic & mild cases are much higher than in developed countries. Tragically, this is because most do not live long enough to be in the high risk group.
2) No widespread testing. Pneumonia deaths are just pneumonia.
I was wondering if these companies put a much higher concentration to make sure the vaccine works. it was a race to be the first mass producer of vaccine, so I imagine a discussion like "the vaccine is probably effective with a dose of X, but let's do 2*X to be sure".
or in other words, if the vaccine proves not effective, at least they know it's not because of a low concentration.
A huge oversight was when it was approved for phrase III they should have run many (a dozen?) different trials at different dose amounts. It was already proven to be safe and nailing the dosing would have helped get shots into arms faster in the US and elsewhere.
I'm on the extreme end of thinking it should have been approved faster - but even if you are a bit of a traditionalist I don't see how running concurrent trials on such an important potential vaccine wouldn't be a huge win.
Or at least started running a second run of modified trials as soon as the phase 3 trials passed.
The trials take something like 3 months from first shot to results, I think. It took a lot more than 3 months from phase 3 completed to most people vaccinated in most Western countries and obviously much longer in developing ones.
But there is very little financial incentive to run such trials once you have a vaccine approved...
The problem is on the government side. They should have paid for this. It would have saved them money too - if it turned out they only needed to give out one shot of the mRNA doses or that they could cut down on dosage.
It would still only be the same number of people per trial. They wouldn't have gotten trouble finding volunteers.
And even if they just prioritized starting the first one ASAP - they didn't do any dosage testing until after it had been released to general public for months. Even if not ideal they could have started dosage trials in November after all the data from the original was done. Instead, they waited six months before even considering this.
Even if you find all those multiple number of volunteers, you still need additional vaccine doses to be manufactured, which can take longer because they need more supplies from third parties, and scale up early. Not to mention all the extra staff to run the trials.
If somehow they're able to run trials on 12x the volunteers, I would rather that they increase the participants by 12x for the final dose so that you get more confidence in the Phase 3 study results and in finding rare side effects.
It would be hard to recruit that many volunteers and staff to run a dozen trials, and reducing the study group size would mean less confidence in the results. Already we have seen blood clots and heart inflammation show up at rates that won't be caught even in larger scale trials.
Finding the optimal dose is done in phase II, where various dose levels are tested on different groups of people. Phase III happens after the dose level is confirmed, and then you roll that out to tens of thousands of people. I think the main point of phase III is to test the final candidate, so you're not really experimenting with the formula at that point.
If you check the papers for the mRNA vaccines, you can see that they did run several different dose levels and got pretty clear feedback that some were too high or too low, before moving on to phase III.
If you read the abstract in phase II they gave it to a small amount of people and looked in detail how the immune system responded in these individuals. This is very granular data.
Phase III is more like "We have no idea what the immune system did in certain people - but only 0.1% of vaccinated people ended up in hospital compared to 2% of placebo" or whatever.
The important thing for the vaccine was too limit death and hospitalization. And phase II didn't tell us clear info on that.
What if they had found that half the dosage ended up in the same number of hospitalizations? There's no way to get that from phase II data.
Are you saying that my use of "clear feedback" isn't accurate? I mean this with respect to what was in scope for phase II, although I could see an argument against using that subjective language. Also, even more dosages were tested in phase I, again on a few number of people, but I'm not sure if that's different from how it's usually done.
> The important thing for the vaccine was too limit death and hospitalization. And phase II didn't tell us clear info on that.
Phase II is primarily to test that the "candidate is safe, sufficiently immunogenic, and maybe protective"[1]. It's not clear to me that testing hospitalization percentage is in scope.
You said in your previous comment that phase II was about finding the "optimal dose" but that testing hospitalization data is not within the scope of phase II.
In a very real-world sense the "optimal dose" is 100% about finding hospitalization/health data. The "optimal dose" in phase II is about the microbiology and isn't very precise in terms of how it translates to real world effects.
Sure, the phrase "optimal dose" can be dependent on context. Maybe the optimal dose with respect to a decrease in hospitalization turns out to be 79.19 ug, and of course that's not going to be found when you only try 25, 50, 100, and 250.
But while a decrease in hospitalization is important, I disagree that it's the only thing that we should be optimizing against. I'm not sure what you mean by health data, but safety and immunogenicity (which might be upstream of hospitalization) are incredibly important to consider in the choice of dosage as well, and that's what optimal dose in the context of trials means. This is the context which I meant it in, and I'm just borrowing this terminology from other places, e.g.:
After reading your links I think it is more clear that "optimal dose" does not mean optimal dose for the patient or total population. It is optimal dose such that a single phase III trial would detect a measurable effect.
Once its approved already at a set dose, the "ideal dose" for future use is probably not the same as the "optimal dose" that maximized probability of approval.
"We propose a Bayesian utility approach (BUART) to randomized Phase II clinical trials which uses a first-order bivariate normal dynamic linear model for efficacy and safety in order to determine the optimal dose and study population in a subsequent Phase III clinical trial. "
Back when this news hit (https://www.dailymail.co.uk/news/article-9033881/Half-dose-O...) I suspected that we might end up finding that ever smaller amounts of vaccine would be as effective as "full" doses. Obviously I didn't make any big public predictions of such since I'm a nobody but it's interesting to see it play out.
to expand on this... while it is encouraging to see that there is a good immune system response to such a low level of the vaccine it's also true that in the real world for pfizer the two shot course is the only way to be really protected against the Delta variant.
its use in places that don't have enough doses to go around would be huge though.
Does anyone yet know why only the pfizer two shot course is effective against the delta variant yet? Slightly different spike analog, different delivery, you just need huge efficacy?
> the 30µg of genetic material in the Pfizer/BioNTech vaccine vs. closer to 100µg in Moderna's indicates to me that their RNA optimization was probably superior, and is likely part of the reason for the less severe side effects
> Moderna probably used a higher dose than they needed to. This was discussed with the vaccine advisory committee. Apparently the dose they settled on for phase 3 trials was decided prior to having all the phase 2 data. They decided to error on the side of effectiveness when they picked the current dose. They basically admitted, if they knew then what they know now, they probably would have used a lower dose in phase 3.
so basically 6 months ago they knew it was probably too much
as to why the pfizer is effective against the delta it's probably just picking the right sequence that is slightly closer to the delta by chance.
>as to why the pfizer is effective against the delta it's probably just picking the right sequence that is slightly closer to the delta by chance.
The encoded spike protein in Pfizer and Moderna is identical,[0] so it's probably not going to be that.
It could be a difference in the mRNA encoding leading to better transcription by our cells, or something to do with the nanoparticles used to smuggle in the mRNA.
yeah it could be all of that and it could also be supply chain delivery/manufacturing techniques that cause the difference... who knows? I've worked with some generic drug manufacturers and some big name drug manufacturers and the clean room/processes are definitely different. it's above my paygrade as to why it is more effective though; that's for sure.
It seems fairly likely to me that dividing the dose by 100 and giving it to 100 different individuals will have more benefit to the population than giving it to 1% of a population and leaving the other 99% unvaccinated.
It's likely that had this strategy been done 6 months ago, a large number of dead people would be alive today.
The only major downside is the population may come to believe the 'vaccine' is ineffective and not trust future vaccination efforts.
The current phase 2/3 trials Pfizer is doing for children under 12 is using a 1/3rd dose for 5-11 year olds and 1/10th dose for 6 months to 4 year olds, based on an earlier phase 1 trial.
I bet we could optimize the dose depending on sex, weight, age or other factors (if we knew how it depended on them) but this is not how it is done. The dose is the same for all adults.
Not really, as the trials were done on representative samples of the general population, we know at least we are not underdosing anyone wrt those metrics.
Reducing the dose as much as possible would be minimizing it.
Most likely we are just looking at this from two different points of view because in my opinion minimizing use of a resource is a form of optimization?
You're absolutely right, one could optimize with respect to any of the infinite attributes a thing has. We could have optimized for the shininess of the doses, or how good they smelled, and those would be ridiculously irrelevant properties to optimize for.
The question is how relevant the use of which resources as a metric in comparison to people not getting sick? Does it even take more resources to distribute a 10x dose vaccine vs x? Is the production of the active ingredient a linear contributor to the overall cost function, which probably is dominated by a lot of the constant costs? We're not talking about 250mg vs 500mg tylenol after all.
In the earliest trial of Moderna’s mRNA-based vaccine, study participants received one of three dose levels: 25, 100 or 250 micrograms. The top dose proved too toxic. The low dose elicited the weakest immune response. The middle dose seemed to offer the best balance: it triggered strong immunity and had acceptable side effects.
That somewhat contradicts the article's claim.
If you under-dose, there may have to be a booster shot. Then the whole inoculation program has to do the job twice.
I think that calculation will vary depending on age and at risk groups. If those 25% in the second option are older folks and/or obese/diabetic, deaths might be lower in that scenario.
We can do better than 65-70%. Here in San Mateo County, CA, 86.6% of the population over 12 has been vaccinated. Local authorities are pushing to get that higher, because there are still some cases.
"Our on-the-ground experience is that we have a steady flow of positive cases – 22 new cases since yesterday, people requiring hospitalization (7 today) and supports to quarantine and isolate (6 in hotel rooms) – and that the majority of these are members of our remaining unvaccinated population ages 12+." - San Mateo County health officer.
The difference is that in that trial they weren't looking at health outcomes. They were looking at people's blood and measuring antibodies.
If it turns out that 25mg produces a small amount of antibodies - but that small amount is still more than enough to prevent the same number of hospitalizations that 100mg does - then it make sense to go with that.
The dosage trials were only used to study the microbiology. Not the death/hospitalization outcomes.
The risk is that even if that lower dose with a lower antibody response works fine with existing variants, it might not fare so well against future mutations. I think this has already happened to a certain extent with the currently circulating variants - vaccination programs that gave worse antibody responses fared OK against the original variant, but not so well against newer ones.
I think that is fair but I also find the status quo bias strange.
If you think that variant changing is a bigger deal than getting them out fast what makes you so sure we shouldn't increase dosage another 50% or another booster?
Right now it seems like the mRNA vaccines work fine and the variants are actually getting better at spreading but not killing.
> the variants are actually getting better at spreading but not killing
I've heard that this is not unexpected, that it's to a viruses advantage to not kill people. That would jive with the fact that the several already endemic coronaviruses are much less likely that sars-cov-2 to cause severe problems.
I agree with what you're saying, and I noticed that trend earlier when people were talking about 70% vs 99% effective vaccines...
But IMO, the flu vaccine is pretty useless. I've never had any confidence that it's actually doing anything for me or anyone I know. I notice no difference between years I get it and years I don't. And if the Covid vaccines were only providing 10-40% protection, this whole situation would be a lot worse.
As a Canadian, I’d caution against firm conclusions from our experience. I’m inclined to think first doses provide good protection, but cases collapsed last summer too despite a relaxing of NPIs. It is hard to overstate how much canadians are outside in summer vs. other seasons:
* School is out, university is out
* Air conditioning is comparatively rare. Or if present, unnecessary. People open their windows and doors instead. I’m typing this now with an open door with bug screen in front.
* Drivers roll down their windows
* People socialize outside in parks and backyards
* The population tans all of a sudden, raising vitamin D levels. Normal respiratory virus spread collapses
* Patios flourish at bars and restaurants. Often the inside is fairly empty. Window-walls open completely leaving restaurant/bar interiors open to the fresh air
* Many offices and professions have summer holidays
Then by mid September we hermetically seal ourselves inside and everyone gets sick once school is back.
I’m cautiously optimistic we’re past needing lockdowns but it is still too soon to tell. Our summer had a powerful seasonal effect last year and seems to have this year too.
(Past needing lockdowns = we’ll get enough new first and second doses in over summer while the season is on our side)
I think this makes great sense at the world population level. And after all, the Pfizer vaccine is only 30μg per dose, with equivalent (marginally higher) efficacy at preventing disease. The RNA sequences are highly similar as well, so I doubt that one expresses much more robustly. It’s been long speculated that the moderna vaccine has more side effects with same efficacy due to the aggressive dosing, and reducing to 50μg or even 25 is supported by a plethora of reasonable data.
So, I think it's great that they're looking at this, and I even believe that on balance it is probably the best bet to go ahead with this idea in countries that have a vaccine shortage. However, I just have to point out:
"Levels of both antibodies and T cells were comparable to those found in people who have recovered from COVID-19."
I can think of another reason this might be true. Maybe, you know, most of these people actually got covid-19, in the months after their quarter-strength vaccination. Now, this might still indicate that it helped them out, since they apparently were asymptomatic or at least did not have a serious enough case to attract the attention of the researchers, but it would not help stop the spread of the virus. So, the idea that there is no downside or risk to going with the quarter-dose, is not necessarily true. It could be that a quarter-dose leaves you just as likely to get (and perhaps spread) the virus, although it does prevent death or serious hospitalization.
Again, I think on balance it's worth the risk, given the situation many countries are in, but I just think it should be acknowledged that it is still a risk.
> Maybe, you know, most of these people actually got covid-19, in the months after their quarter-strength vaccination.
No need to speculate. This is easily disproven simply by checking for antibodies against the viral capsid and other non-RBD proteins. Those antibodies would not be present in someone unless they were actually infected.
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[ 3.8 ms ] story [ 112 ms ] threadUp to now Africa hasnt had a big wave of covid, but this 3rd wave has hit us really hard (and I know, Africa is not a country, I live in South Africa).
What experts warned about might happen is happening now: because of insufficient vaccinations the Covid pandemic will stick around and mutate in poor countries.
The really depressing part is that the exact same logic applies to climate change, so I’m not exactly full of hope for the future right now.
This isn't that remarkable. Previous attempts to deal with respiratory disease pandemics using vaccines have proved pretty futile, even though it is a standard part of pandemic planning.
For example the cost of a dose of Biontech Pfizer vaccine is roughly the same as the cost of getting a single antigen test performed in Germany (both roughly 20 EUR).
With the variants/mutations it seems we should invest much more in vaccine capacity to avoid spending 2022 in another lockdown.
> there still aren't the doses to vaccinate the planet any time in the imminent future let alone the on-the-ground infrastructure to deliver them everywhere
I think the vaccinations campaigns everywhere (in the developed world at least) have shown that the infrastructure to vaccinate everyone is there if only we have enough supplies of vaccines.
This is why we should suspend IP / patent protection and increase production.
https://www.theguardian.com/world/2021/may/06/covid-vaccines...
If throwing money at it won't help, there should be specific answers to that question.
Only a few specialists knew how, and industrial production was a hypothetical dream.
The ramping up to billions of doses since have gone as fast as is humanly possible, with very little expense or effort spared.
Everyone would like it to go even faster, but there are limits to what money can buy.
(This is what I've heard. I'm not any kind of insider)
If ramping up the production comes at a cost of cutting some corners, and a contaminated/dangerous batch of mRNA vacciness comes along as a result, the antivaxx movement will have a field day whose impacts will be felt even fifty years from now. We (as humanity) cannot affort a massive vaccine screw up.
> so I’m not exactly full of hope for the future right now
Don't be. The vaccine is being used as a political tool currently (Pfizer good, Sinovac bad, etc...) and to restrict/grant movement around countries.
1: https://www.theguardian.com/world/2020/dec/18/belgian-minist...
By and large Africa doesn't do mass testing the way the developed world does. No tests, no cases. Young population, very few deaths.
Voila. No pandemic.
In covid deaths occurring in the under 65 population, there is often a significant comorbidity that contributed to severe illness. Obesity, diabetes, etc, are at the top of that list.
Africa by and large does not have the same health profile or concerns as Japan, the UK, or the U.S.
None of this is to suggest that vaccines should not be distributed there. I think they should.
What I'm questioning is if COVID-19 deserves to be even on, let's say, the top 10 list of problems facing Africa in 2021. Probably not.
You don't need to die from COVID-19 to experience health issues, even without previous issues.
I haven't seen anything remotely convincing. But I am open to changing my mind.
https://www.healtheuropa.eu/research-shows-long-covid-is-lin...
https://www.nature.com/articles/s41591-021-01283-z
https://www.gov.uk/government/news/new-research-shows-2-mill...
https://www.nihr.ac.uk/news/nihr-publishes-second-themed-rev...
https://www.forbes.com/sites/ninashapiro/2021/06/20/study-do...
What exactly are you not convinced about?
What's your resource that long covid isn't a thing @chitowneats?
I don't understand how people can think that dying is the only issue with covid.
I know young people ( mid 30), that had it very bad. And I was scared as shit to have the same. I'm vaccinated now though.
Like masks on 4 year olds.
From the first link above: "loss of taste and/or smell (28%, 17/61), fatigue (21%, 13/61), dyspnea (13%, 8/61), impaired concentration (13%, 8/61) and memory problems (11%, 7/61)."
Does anyone really consider these to be a serious syndrome caused by covid infection? I'm pretty sure I experienced most of these from the lockdowns alone. Lots of folks also think they have fibromyalgia and that it's not just in their head (it is).
From the second link:
“It remains to be established if these immune alterations are unique to COVID-19, or whether they are also observed following other severe respiratory infections."
Uh, ok...
Two of those are in people 30-40 years old. Third one is over 60. One had some unusual brain fog and memory issues, second one is unable to work and still treated for various symptoms. The older one became housebound while before that she was self sufficient and even taking care for young girl from extended family. To think of it I also know of one very young person in family of my friends that had to be hospitalized multiple times for post covid stuff. He's not even 20.
You may of course discount all of this that it couldn't happen spontaneously or after a bad flu. That's why I believe long covid is a thing mostly because of reports comming from all over the globe and associated research not because of those personal stories.
If you need evidence of your own eyes to believe something I don't envy you or anyone that relies on your decisions.
It was so obvious that you're statement was just a fluff.
Long covid isn't easy to measure. Eg. Not everyone was admitted to the hospital, what are the symptoms related, are those symptoms unique to long covid, ...
But by now, it should be clear that long covid exists and covid deaths aren't the only problem related to this disease.
Being in a denial state is your problem, not mine. I think it's currently a specific US political motivated issue, as I haven't encountered anyone in Belgium that claimed it's irrelevant/not existing.
The state wants people to be vaccinated as quick as possible and a political party + Anon is dismissing it as "just a cold/5G/nanobots" and some people believe it.
It's more like propaganda against the state and a lot of Americans believe that misinformation.
At least other countries / citizens seem to have more common sense.
https://news.ycombinator.com/item?id=27824447
The reason I post here anonymously is because tying my identity to this can lead to consequences elsewhere. Everyone knows there is unprecedented censorship around this issue. Which is part of why we have failed so utterly to comprehend and contextualize this virus.
Some guy even put my governments politicians through AI and nothing happened to him either.
https://mashable.com/article/flemish-politicians-ai-phone-us...
1) Your population is by and large not susceptible to severe illness from the virus. Rates of asymptomatic & mild cases are much higher than in developed countries. Tragically, this is because most do not live long enough to be in the high risk group.
2) No widespread testing. Pneumonia deaths are just pneumonia.
I'm on the extreme end of thinking it should have been approved faster - but even if you are a bit of a traditionalist I don't see how running concurrent trials on such an important potential vaccine wouldn't be a huge win.
The trials take something like 3 months from first shot to results, I think. It took a lot more than 3 months from phase 3 completed to most people vaccinated in most Western countries and obviously much longer in developing ones.
But there is very little financial incentive to run such trials once you have a vaccine approved...
The problem is on the government side. They should have paid for this. It would have saved them money too - if it turned out they only needed to give out one shot of the mRNA doses or that they could cut down on dosage.
And even if they just prioritized starting the first one ASAP - they didn't do any dosage testing until after it had been released to general public for months. Even if not ideal they could have started dosage trials in November after all the data from the original was done. Instead, they waited six months before even considering this.
If somehow they're able to run trials on 12x the volunteers, I would rather that they increase the participants by 12x for the final dose so that you get more confidence in the Phase 3 study results and in finding rare side effects.
Edit: ridiculous that HN community downvotes attempts to have conversation; you're part of the problem.
Transport, preparation and process are very operationally challenging.
If you check the papers for the mRNA vaccines, you can see that they did run several different dose levels and got pretty clear feedback that some were too high or too low, before moving on to phase III.
If you read the abstract in phase II they gave it to a small amount of people and looked in detail how the immune system responded in these individuals. This is very granular data.
Phase III is more like "We have no idea what the immune system did in certain people - but only 0.1% of vaccinated people ended up in hospital compared to 2% of placebo" or whatever.
The important thing for the vaccine was too limit death and hospitalization. And phase II didn't tell us clear info on that.
What if they had found that half the dosage ended up in the same number of hospitalizations? There's no way to get that from phase II data.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871769/
> The important thing for the vaccine was too limit death and hospitalization. And phase II didn't tell us clear info on that.
Phase II is primarily to test that the "candidate is safe, sufficiently immunogenic, and maybe protective"[1]. It's not clear to me that testing hospitalization percentage is in scope.
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944327/
In a very real-world sense the "optimal dose" is 100% about finding hospitalization/health data. The "optimal dose" in phase II is about the microbiology and isn't very precise in terms of how it translates to real world effects.
But while a decrease in hospitalization is important, I disagree that it's the only thing that we should be optimizing against. I'm not sure what you mean by health data, but safety and immunogenicity (which might be upstream of hospitalization) are incredibly important to consider in the choice of dosage as well, and that's what optimal dose in the context of trials means. This is the context which I meant it in, and I'm just borrowing this terminology from other places, e.g.:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944327/ https://pubmed.ncbi.nlm.nih.gov/29420118/
Once its approved already at a set dose, the "ideal dose" for future use is probably not the same as the "optimal dose" that maximized probability of approval.
"We propose a Bayesian utility approach (BUART) to randomized Phase II clinical trials which uses a first-order bivariate normal dynamic linear model for efficacy and safety in order to determine the optimal dose and study population in a subsequent Phase III clinical trial. "
its use in places that don't have enough doses to go around would be huge though.
> the 30µg of genetic material in the Pfizer/BioNTech vaccine vs. closer to 100µg in Moderna's indicates to me that their RNA optimization was probably superior, and is likely part of the reason for the less severe side effects
https://www.reddit.com/r/medicine/comments/kp1a00/moderna_vs...
> Moderna probably used a higher dose than they needed to. This was discussed with the vaccine advisory committee. Apparently the dose they settled on for phase 3 trials was decided prior to having all the phase 2 data. They decided to error on the side of effectiveness when they picked the current dose. They basically admitted, if they knew then what they know now, they probably would have used a lower dose in phase 3.
so basically 6 months ago they knew it was probably too much
as to why the pfizer is effective against the delta it's probably just picking the right sequence that is slightly closer to the delta by chance.
The encoded spike protein in Pfizer and Moderna is identical,[0] so it's probably not going to be that.
It could be a difference in the mRNA encoding leading to better transcription by our cells, or something to do with the nanoparticles used to smuggle in the mRNA.
[0] https://twitter.com/adamjmacneil/status/1407019597757390850
It's likely that had this strategy been done 6 months ago, a large number of dead people would be alive today.
The only major downside is the population may come to believe the 'vaccine' is ineffective and not trust future vaccination efforts.
Reducing the dose as much as possible would be minimizing it.
The question is how relevant the use of which resources as a metric in comparison to people not getting sick? Does it even take more resources to distribute a 10x dose vaccine vs x? Is the production of the active ingredient a linear contributor to the overall cost function, which probably is dominated by a lot of the constant costs? We're not talking about 250mg vs 500mg tylenol after all.
That somewhat contradicts the article's claim.
If you under-dose, there may have to be a booster shot. Then the whole inoculation program has to do the job twice.
"Our on-the-ground experience is that we have a steady flow of positive cases – 22 new cases since yesterday, people requiring hospitalization (7 today) and supports to quarantine and isolate (6 in hotel rooms) – and that the majority of these are members of our remaining unvaccinated population ages 12+." - San Mateo County health officer.
1 death in the county this week.
Moderna is adding more production lines.
If it turns out that 25mg produces a small amount of antibodies - but that small amount is still more than enough to prevent the same number of hospitalizations that 100mg does - then it make sense to go with that.
The dosage trials were only used to study the microbiology. Not the death/hospitalization outcomes.
If you think that variant changing is a bigger deal than getting them out fast what makes you so sure we shouldn't increase dosage another 50% or another booster?
Right now it seems like the mRNA vaccines work fine and the variants are actually getting better at spreading but not killing.
I've heard that this is not unexpected, that it's to a viruses advantage to not kill people. That would jive with the fact that the several already endemic coronaviruses are much less likely that sars-cov-2 to cause severe problems.
The flu vaccine is around 10-40% effective. Bu suddenly we pretend like if a vaccine doesn't give us 98% immunity, it's useless? Seriously?
But IMO, the flu vaccine is pretty useless. I've never had any confidence that it's actually doing anything for me or anyone I know. I notice no difference between years I get it and years I don't. And if the Covid vaccines were only providing 10-40% protection, this whole situation would be a lot worse.
* School is out, university is out
* Air conditioning is comparatively rare. Or if present, unnecessary. People open their windows and doors instead. I’m typing this now with an open door with bug screen in front.
* Drivers roll down their windows
* People socialize outside in parks and backyards
* The population tans all of a sudden, raising vitamin D levels. Normal respiratory virus spread collapses
* Patios flourish at bars and restaurants. Often the inside is fairly empty. Window-walls open completely leaving restaurant/bar interiors open to the fresh air
* Many offices and professions have summer holidays
Then by mid September we hermetically seal ourselves inside and everyone gets sick once school is back.
I’m cautiously optimistic we’re past needing lockdowns but it is still too soon to tell. Our summer had a powerful seasonal effect last year and seems to have this year too.
(Past needing lockdowns = we’ll get enough new first and second doses in over summer while the season is on our side)
"Levels of both antibodies and T cells were comparable to those found in people who have recovered from COVID-19."
I can think of another reason this might be true. Maybe, you know, most of these people actually got covid-19, in the months after their quarter-strength vaccination. Now, this might still indicate that it helped them out, since they apparently were asymptomatic or at least did not have a serious enough case to attract the attention of the researchers, but it would not help stop the spread of the virus. So, the idea that there is no downside or risk to going with the quarter-dose, is not necessarily true. It could be that a quarter-dose leaves you just as likely to get (and perhaps spread) the virus, although it does prevent death or serious hospitalization.
Again, I think on balance it's worth the risk, given the situation many countries are in, but I just think it should be acknowledged that it is still a risk.
No need to speculate. This is easily disproven simply by checking for antibodies against the viral capsid and other non-RBD proteins. Those antibodies would not be present in someone unless they were actually infected.