6 ms·

So what happens if the second dose arrives very (eg. many months) late? Can you start again and give 3? And is there any chance all the partial immunities wil

So what happens if the second dose arrives very (eg. many months) late? Can you start again and give 3? And is there any chance all the partial immunities will catalyze resistant mutations?

generationP 6y ago
Disclaimer: not an immunologist. > So what happens if the second dose arrives very (eg. many months) late? Can you start again and give 3? WHO guidance on incomplete vaccine courses (pre-COVID): https://www.who.int/immunization/policy/Immunization_routine_table3.pdf https://www.who.int/immunization/policy/Immunization_routine... In almost all cases, the suggestion is "resume without repeating the previous dose". The only exceptions are typhoid and cholera vaccinations. I don't know what these suggestions are based upon, but the source is as close to expert consensus as it can go (the WHO has gotten a lot of flak on COVID, but I have never heard anyone seriously doubt its guidance on standard vaccinations). > And is there any chance all the partial immunities will catalyze resistant mutations? Apparently this doesn't even happen much for antibiotics ( https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2536180 https://jamanetwork.com/journals/jamainternalmedicine/articl... ), so I wouldn't worry about it happening for vaccines. See https://www.pnas.org/content/115/51/12878 https://www.pnas.org/content/115/51/12878 for a comparison. If it were a major issue, it would just as well be an issue with fully delivered vaccination courses, as they don't offer 100% immunity either. The amount of mutations arising should still be proportional to the sick population (or, rather, to its total prevalence over time and population), and anything that reduces the latter should reduce the former. Any vaccine-immune mutation can just as easily come up before the vaccine, unless it hampers the virus so strongly that it is unviable until the evolutionary landscape has shifted. At that point, however, we're looking at a much simpler problem.
est31 6y ago
> So what happens if the second dose arrives very (eg. many months) late? Can you start again and give 3? Stockpiling of vaccines is a method to obtain certainty that you can vaccinate on schedule. There are better methods of ensuring certainty, e.g. by supporting manufacturers as well as possible to meet schedules, analyze weaknesses in supply chains, trying to counter them early, etc. The issue is the cost of maintaining the stockpile: > she and her colleagues projected that frontloading vaccine doses would avert between 34 and 42 per cent more symptomatic coronavirus infections, compared with a strategy of keeping half the shipments in reserve. What's the cost of delaying the second shot for some groups? It's certainly non-zero, but 34 to 42 percent less symptomatic infections is a lot of prevented infections (and death). The cost-benefit analysis gives a clear conclusion: don't stockpile.
- trhway 6y ago
  you described precisely the reason why anyone wielding deciding power on the matter and acting rationally wouldn't allow the second doses be administered until [almost] everybody (in the country or on the whole planet) gets the first one. To prevent such a situation the subjects of that power have to stockpile.
- toast0 6y ago
  The last year has been supply chain disruption after supply chain disruption. If the vial manufacturer has a covid outbreak at their facility and has to stop manufacturing for two weeks, your scheduled shipments aren't going to be on time. As supply goes up, and we get past the priority recpients to the general public, it probably makes sense to reduce the stockpile requirement; some general public aren't going to come back for their second dose anyway, and more risk is appropriate for general public than high risk groups.
  - est31 6y ago
    > The last year has been supply chain disruption after supply chain disruption. Indeed, but even if 20% of people don't get their second shot on time and the impact of that is equal to them not being vaccinated at all (we don't know but likely the impact is smaller), even then the impact would be lower than stockpiling vaccines which increases the number of symptomatic infections by 34 to 42 percent. > If the vial manufacturer has a covid outbreak at their facility and has to stop manufacturing for two weeks, your scheduled shipments aren't going to be on time. That's precisely where the government can step in and ensure that antibiotics therapies are available to workers in those facilities as well as daily tests. Then it doesn't have to shut down. > As supply goes up, and we get past the priority recpients to the general public, it probably makes sense to reduce the stockpile requirement At that point it's less relevant which strategy you choose.
    - toast0 6y ago
      > Indeed, but even if 20% of people don't get their second shot on time I think my worst case expectation is much worse than yours. With a two week production shut down, I expect my corner of the world would not get new shipments for more than two weeks; higher priority places would be getting their previous orders filled before us, and we'd only get more once the backlog was filled. Also, I fully expect any production will take at least a week to be made public, so too late for an eager dosing regimine to start holding back. Keep in mind, we're in winter, and winter storms often cause logistical problems. The one dose efficacy data is too low confidence to make good decisions with. I'm open to the argument that it's better to use two doses to give two people one dose than to give one person two doses, but it would have been nice if that was trialed. There's also a related question of if you have a dose, if it's better to give that to a properly timed first dose recipient, or to give it to someone who hasn't received a dose yet. Again, there's not quality data; I would lean towards following the trial parameters. > That's precisely where the government can step in and ensure that antibiotics therapies are available to workers in those facilities as well as daily tests. Where has this suddenly competent government been for the past year? Yes, we expect a new executive in the US in a month, but the handoff takes time in normal conditions, and we have reason to believe this one will be more abrupt than many. How do antibiotics help for covid? How do daily tests help avert a shutdown when you can spread the disease while testing negative? One person could infect most of a shift of workers, given the right circumstances; more than one shift if they do handoff work to the next shift. Supply chain workers for the vaccine aren't in the priority lists for the vaccine either. Anyway, covid isn't the only communicable disease possibility.
Siira 6y ago
Sometimes taking chances is worth it. As far as I have heard, every single vaccine trial has concluded “yeah, our vaccine is effective.” So if people had been allowed to take experimental vaccines, the pandemic would have been a lot better. In this circumstance as well, taking a chance is worth it. Even if the virus mutates, changing the mRNA vaccines shouldn’t take more than a week.
- afavour 6y ago
  > So if people had been allowed to take experimental vaccines, the pandemic would have been a lot better. > In this circumstance as well, taking a chance is worth it. Nope nope nope nope. This is the literal example of survivor bias. You can't look at the results and use them to inform prior behaviour. The vaccine could have had catastrophic side effects.
  - sieabahlpark 6y ago
    > This is the literal example of survivor bias. This isn't the type of bias people care about. They only care whether it has a right-leaning bias.
  - handmodel 6y ago
    I think it is clear the regulatory framework wasn't ideal. The last stage of the trial (which took three months) was not about if they were safe - but simply if they worked. Meaning, they were cleared to have minimal side effects, just unclear if it worked. If you had approved people to choose to take the vaccine in August we could have had 50M people with shots already. A lot of people have my skepticism that the main reason that the FDA didn't want to do that since it might be a bit of a media heartache for them, but so what. Even if you thought it would only work 20% of the time that 20% of the time it saves 100,000+ lives.
    - vvillena 6y ago
      50M doses isn't something that gets suddenly summoned. It's a big logistics problem. Your assumption is valid only if the pharmas have capacity to make a extremely big amount of vaccine doses. That costs money and (I guess) materials, and both of those things could go towards a vaccine that is proven to be effective.
Guereric 6y ago
I got the Pfizer vaccine in Alberta, Canada. Our vaccine FAQ says that getting the second injection 21d to 28d after the first is recommended. Up to 3 months after is allowed, but not advised. For delays longer than 3 months, the person simply won't get the second dose.

So what happens if the second dose arrives very (eg. many months) late? Can you start again and give 3? And is there any chance all the partial immunities will catalyze resistant mutations?

generationP 6y ago

Disclaimer: not an immunologist. > So what happens if the second dose arrives very (eg. many months) late? Can you start again and give 3? WHO guidance on incomplete vaccine courses (pre-COVID): https://www.who.int/immunization/policy/Immunization_routine_table3.pdf https://www.who.int/immunization/policy/Immunization_routine... In almost all cases, the suggestion is "resume without repeating the previous dose". The only exceptions are typhoid and cholera vaccinations. I don't know what these suggestions are based upon, but the source is as close to expert consensus as it can go (the WHO has gotten a lot of flak on COVID, but I have never heard anyone seriously doubt its guidance on standard vaccinations). > And is there any chance all the partial immunities will catalyze resistant mutations? Apparently this doesn't even happen much for antibiotics ( https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2536180 https://jamanetwork.com/journals/jamainternalmedicine/articl... ), so I wouldn't worry about it happening for vaccines. See https://www.pnas.org/content/115/51/12878 https://www.pnas.org/content/115/51/12878 for a comparison. If it were a major issue, it would just as well be an issue with fully delivered vaccination courses, as they don't offer 100% immunity either. The amount of mutations arising should still be proportional to the sick population (or, rather, to its total prevalence over time and population), and anything that reduces the latter should reduce the former. Any vaccine-immune mutation can just as easily come up before the vaccine, unless it hampers the virus so strongly that it is unviable until the evolutionary landscape has shifted. At that point, however, we're looking at a much simpler problem.

est31 6y ago

> So what happens if the second dose arrives very (eg. many months) late? Can you start again and give 3? Stockpiling of vaccines is a method to obtain certainty that you can vaccinate on schedule. There are better methods of ensuring certainty, e.g. by supporting manufacturers as well as possible to meet schedules, analyze weaknesses in supply chains, trying to counter them early, etc. The issue is the cost of maintaining the stockpile: > she and her colleagues projected that frontloading vaccine doses would avert between 34 and 42 per cent more symptomatic coronavirus infections, compared with a strategy of keeping half the shipments in reserve. What's the cost of delaying the second shot for some groups? It's certainly non-zero, but 34 to 42 percent less symptomatic infections is a lot of prevented infections (and death). The cost-benefit analysis gives a clear conclusion: don't stockpile.

trhway 6y ago
you described precisely the reason why anyone wielding deciding power on the matter and acting rationally wouldn't allow the second doses be administered until [almost] everybody (in the country or on the whole planet) gets the first one. To prevent such a situation the subjects of that power have to stockpile.
toast0 6y ago
The last year has been supply chain disruption after supply chain disruption. If the vial manufacturer has a covid outbreak at their facility and has to stop manufacturing for two weeks, your scheduled shipments aren't going to be on time. As supply goes up, and we get past the priority recpients to the general public, it probably makes sense to reduce the stockpile requirement; some general public aren't going to come back for their second dose anyway, and more risk is appropriate for general public than high risk groups.
- est31 6y ago
  > The last year has been supply chain disruption after supply chain disruption. Indeed, but even if 20% of people don't get their second shot on time and the impact of that is equal to them not being vaccinated at all (we don't know but likely the impact is smaller), even then the impact would be lower than stockpiling vaccines which increases the number of symptomatic infections by 34 to 42 percent. > If the vial manufacturer has a covid outbreak at their facility and has to stop manufacturing for two weeks, your scheduled shipments aren't going to be on time. That's precisely where the government can step in and ensure that antibiotics therapies are available to workers in those facilities as well as daily tests. Then it doesn't have to shut down. > As supply goes up, and we get past the priority recpients to the general public, it probably makes sense to reduce the stockpile requirement At that point it's less relevant which strategy you choose.
  - toast0 6y ago
    > Indeed, but even if 20% of people don't get their second shot on time I think my worst case expectation is much worse than yours. With a two week production shut down, I expect my corner of the world would not get new shipments for more than two weeks; higher priority places would be getting their previous orders filled before us, and we'd only get more once the backlog was filled. Also, I fully expect any production will take at least a week to be made public, so too late for an eager dosing regimine to start holding back. Keep in mind, we're in winter, and winter storms often cause logistical problems. The one dose efficacy data is too low confidence to make good decisions with. I'm open to the argument that it's better to use two doses to give two people one dose than to give one person two doses, but it would have been nice if that was trialed. There's also a related question of if you have a dose, if it's better to give that to a properly timed first dose recipient, or to give it to someone who hasn't received a dose yet. Again, there's not quality data; I would lean towards following the trial parameters. > That's precisely where the government can step in and ensure that antibiotics therapies are available to workers in those facilities as well as daily tests. Where has this suddenly competent government been for the past year? Yes, we expect a new executive in the US in a month, but the handoff takes time in normal conditions, and we have reason to believe this one will be more abrupt than many. How do antibiotics help for covid? How do daily tests help avert a shutdown when you can spread the disease while testing negative? One person could infect most of a shift of workers, given the right circumstances; more than one shift if they do handoff work to the next shift. Supply chain workers for the vaccine aren't in the priority lists for the vaccine either. Anyway, covid isn't the only communicable disease possibility.

Siira 6y ago

Sometimes taking chances is worth it. As far as I have heard, every single vaccine trial has concluded “yeah, our vaccine is effective.” So if people had been allowed to take experimental vaccines, the pandemic would have been a lot better. In this circumstance as well, taking a chance is worth it. Even if the virus mutates, changing the mRNA vaccines shouldn’t take more than a week.

afavour 6y ago
> So if people had been allowed to take experimental vaccines, the pandemic would have been a lot better. > In this circumstance as well, taking a chance is worth it. Nope nope nope nope. This is the literal example of survivor bias. You can't look at the results and use them to inform prior behaviour. The vaccine could have had catastrophic side effects.
- sieabahlpark 6y ago
  > This is the literal example of survivor bias. This isn't the type of bias people care about. They only care whether it has a right-leaning bias.
- handmodel 6y ago
  I think it is clear the regulatory framework wasn't ideal. The last stage of the trial (which took three months) was not about if they were safe - but simply if they worked. Meaning, they were cleared to have minimal side effects, just unclear if it worked. If you had approved people to choose to take the vaccine in August we could have had 50M people with shots already. A lot of people have my skepticism that the main reason that the FDA didn't want to do that since it might be a bit of a media heartache for them, but so what. Even if you thought it would only work 20% of the time that 20% of the time it saves 100,000+ lives.
  - vvillena 6y ago
    50M doses isn't something that gets suddenly summoned. It's a big logistics problem. Your assumption is valid only if the pharmas have capacity to make a extremely big amount of vaccine doses. That costs money and (I guess) materials, and both of those things could go towards a vaccine that is proven to be effective.

Guereric 6y ago

I got the Pfizer vaccine in Alberta, Canada. Our vaccine FAQ says that getting the second injection 21d to 28d after the first is recommended. Up to 3 months after is allowed, but not advised. For delays longer than 3 months, the person simply won't get the second dose.