8 ms·

Longer interval between Covid-19 Pfizer vaccine doses boosts immunity

75 points by lnyan 5y ago

simlevesque 5y ago
Now I'm glad I've waited 8 weeks !
ip_addr 5y ago
Is it practical to ask people to wait 8 weeks? Will people be significantly less likely to show up to the second appointment after 8 weeks instead of 3 weeks?
- barnabee 5y ago
  In the UK the minimum wait is 8 weeks and there doesn't appear to be an issue with people failing to get 2nd doses.
  - fredley 5y ago
    Until a few weeks ago the minimum wait was 12 weeks! Data on rates here: https://coronavirus.data.gov.uk/details/vaccinations https://coronavirus.data.gov.uk/details/vaccinations
    - ip_addr 5y ago
      Looking at just the Cumulative data, ~79% of people in the UK that have taken the first dose have taken the second dose. Looks like it is practical. And that number doesn't account for people that haven't had their second appointment yet.
  - gambiting 5y ago
    I had my second dose in the UK after 5 weeks, by just going to a walk in centre and asking - apparently they had way too many doses they would be wasted otherwise, so they were happy to give it to anyone asking. Apparently the absolute NHS-mandated minimum is 3 weeks between doses, that's the one they can't disobey. But the 8 week minimum is much more flexible.
- guerrilla 5y ago
  That's about what it has been the whole time in my region and there's no sign of a problem yet.
- elchief 5y ago
  The wait period in British Columbia is about 7 weeks, and our #2 dose numbers look just as good as #1 (80% first dose, and 58% second dose, still averaging 60k doses a day)
- tgsovlerkhgsel 5y ago
  The main risk I'd be worried about that people will engage in more risky behavior after the first but before the second dose. It's a lot easier to hold out and skip some fun activities if there's a goal 4 (or rather 6) weeks ahead than if it's 8 (or rather 10) weeks.
voisin 5y ago
Man, the messaging around the vaccines is so damn frustrating. No wonder people are skeptical. “Get whatever is available when you are eligible” —> “Oh but not J&J unless you are over a certain age” —> “Or AZ unless over a certain age” —> “Don’t mix mRNA” —> “OK Mix mRNA if available. Just get fully vaxx’ed ASAP” —> “Just kidding, wait 8 weeks” Like come on! I follow this reasonably closely and I am ready to storm the Ivory Tower over this messaging. I cannot imagine what someone who doesn’t follow this feels.
- detaro 5y ago
  The main message here is not "you have to/absolutely should wait 8 weeks". The main point is "countries that did stretch the schedule compared to what was in the initial studies probably didn't make a massive mistake by doing so" (EDIT: and of course it's a press release for a single study, not an official policy announcement)
- planet-and-halo 5y ago
  That's complex decision-making under conditions of uncertainty for you. The authorities themselves are partly to blame for not being totally clear that they're human and figuring this out on the fly like everyone else, but the general population is also to blame for acting like a bunch of spoiled children and feeling entitled to perfect answers and zero mistakes.
  - voisin 5y ago
    Admitting the uncertainty is my point. Instead they change the messaging week by week and act like this latest messaging is certain.
    - detaro 5y ago
      Each of those steps had more nuance being communicated than the half-sentence you summarize it with, often with intense public debate and different judgment calls from different health authorities. (AZ and if/how to use it is probably the biggest example, vaccination for children is another (at least here in DE that's a massive thing)) None of these things were "this is the absolute truth forever".
mistermann 5y ago
> For the longer schedule, the antibody levels dropped off between first and second dose, which included the loss of any neutralising effect against the Delta variant. However, T cell responses were consistent, indicating they may contribute to important protection against Covid-19 during this time. Does this suggest that ~8 weeks after the second dose one will still have protection from plain covid, but protection again Delta variants will be diminished?
- tgsovlerkhgsel 5y ago
  The sentence you quoted refers to the period between first and second dose. My understanding is that "if you get exposed to the Delta variant on the day before the second dose, you won't have neutralizing antibodies". It does not make a statement about what happens after the second dose.
  - mistermann 5y ago
    Agreed, but it is suggestive that this is within the realm of possibilities, no? Otherwise, something interesting would have to be happening where after the first shot you lose delta ~immunity in eight weeks, but after the second you ~do not?
    - tgsovlerkhgsel 5y ago
      Possibilities sure, but IMO that doesn't translate to "likely". Other vaccines also give you only minimal or short protection after the first dose with long-lasting protection after the second (or third) one.
mchusma 5y ago
This is of course exactly what was expected, and why First Dose First was so clearly the right strategy until countries had plenty of supply. Good for the UK recognizing this early. The US hasn't.
- peytn 5y ago
  It’s unethical to gamble your citizenry on untested medical interventions regardless of outcome. There was enough time to sponsor a trial.
  - moultano 5y ago
    Come on, we didn't even have time for the trials we actually ran. Thousands died while we waited for rubber stamps.
  - tnorthcutt 5y ago
    So was it ethical to gamble on a four week interval when it wasn’t proven to be the best option?
    - nradov 5y ago
      No one ever claimed that it was the best option, just that it was the only option clinically tested. It would have been irresponsible to recommend a different option without at least some limited clinical trials. Sometimes you can't wait for perfect data.
    - ttul 5y ago
      Gamble is the wrong word for this. It was a calculated risk as is everything in a pandemic or other evolving threat to public health.
    - inglor_cz 5y ago
      I still think that something else was unethical: not running challenge tests. There were enough volunteers for them.
  - 5y ago
inglor_cz 5y ago
In my country, we had 6 weeks between the doses. The main reason was shortage of vaccines, of course; nowadays the 6-week interval has been abolished and you can actually get the second dose earlier if you will, b/c "peak jab" is over and further interest wanes. I am one of the "six week vaccinees", which sits just in the middle of the two sets studied in this paper. I wonder what the results for 6 week delay are. Accidentally, Delta does not seem to be a problem yet in my country. IDK if it is luck, an early phase of a future wave or an effect of Pfizer doses being given 6 weeks apart, but our current Covid numbers are much more moderate than expected.
- deleted 5y ago
  [deleted]
- gurleen_s 5y ago
  What country, if you don’t mind me asking?
  - lousken 5y ago
    by the nickname i'd assume czechia
wrayste 5y ago
It is not a good study: "A total of 503 healthcare workers were recruited to the study, of which 223 (44%) had previously had Covid-19." The sample group is not representative of the population and with a large proportion already having had COVID, it is expected that the first dose of the vaccine acts like the second dose, and a second dose as a booster. It is also ignoring the downsides of the longer gap, the main one being the increased likelihood of creating a vaccine resistant escape variant. The UK government admits that this is a risk: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/954990/s1015-sars-cov-2-immunity-escape-variants.pdf https://assets.publishing.service.gov.uk/government/uploads/... "There is therefore an increased risk of virus replication under partial immunity after one dose than after two doses, so in the short- term, delaying the second dose would be expected to somewhat increase the probability of emergence of vaccine resistance - but probably from a low base." Last time I looked, UK now had the 3rd highest case rate in the world. A variant factory you could call it. Part of the justification of the risks of the increased gap was the high death rate at the time. "Is such an increase material? It is not currently possible to quantify the probability of emergence of vaccine resistance as a result of the delayed second dose, but it is likely to be small. The UK currently has more than 1,000 COVID-19 related deaths each day and has limited supplies of vaccine. In the current UK circumstances the unquantifiable but likely small probability of the delayed second dose generating a vaccine escape mutant must be weighed against the measurable benefits of doubling the speed with which the most vulnerable can be given vaccine-induced protection." That is no longer the case, vaccine supply is good and take-up is falling. The Oxford AstraZeneca vaccine did have clinical trials with a longer gap as far as I understand, but Pfizer didn't. The mRNA vaccines have different properties but the UK government is treating all vaccines as the same. Now with every small and pretty weak bit of evidence the government jumps on to justify their decision, which initially may have been the right choice but the unlocking and delta variant have changed the situation massively. There was a similar study in Israel with some strong arguments against its findings: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01046-1/fulltext https://www.thelancet.com/journals/lancet/article/PIIS0140-6... And more good reading: http://www.thelancet.com/retrieve/pii/S0140673621004554 http://www.thelancet.com/retrieve/pii/S0140673621004554 "We have no concerns regarding the second dose of AZD1222 at 12 weeks, as this is supported by evidence. However, if escape variants arise due to sub-optimal dosing with BNT162b2, they will likely be resistant to other vaccines that target the same viral spike protein. In conclusion, we would strongly recommend that the UK Government reverts to the two doses in a 3-week schedule (94% efficacy) for BNT162b2; or, as recently supported by WHO and the US Centers for Disease Control and Prevention, adopt no more than a 6-week delay to the second dose “in exceptional circumstances”."
guilhas 5y ago
One study of few people does not seem enough. They started this longer interval, against manufacturers recommendation, supposedly because of stock and to give to more people, but kept the this longer interval even after the daily vaccination numbers dropped 10x
syntaxing 5y ago
Uhhh, has anyone read the article rather than confirming their confirmation bias...The header after the title is literally "One of the world’s most in-depth studies into Covid-19 immune response to vaccines shows a short and long dosing interval of the Pfizer jab generated strong antibody and T cell immune responses." Which means get both of your shots, regardless of gap. Evidence suggest longer gap gives better long term immunity but you are more vulnerable between both doses which can be can issue during an active pandemic. The article never suggests the "optimal" dosing schedule.
technofiend 5y ago
After two doses, overall T cell levels were 1.6 times lower after the long compared with the short dosing schedule. However, after the longer dosing interval, a higher proportion of T cells present were ‘helper’ T cells, which are important for long-term immune memory and helping generate antibodies to prevent infection. The data I'd like to see discovered is if and when this effect tapers off. Surely we need that to know the optimal time to take a booster? (This is assuming the vaccine makeup hadn't changed and you're not taking a booster to immunize against variants.)
988747 5y ago
That only matters to people who get vaccinated because they are afraid of COVID. I got my second dose ASAP, because I needed a certificate for travel, so I could go for well deserved vacation. I don't give a fuck about effectivness.
- zwaps 5y ago
  Not worried about long covid? Other article on HN suggests that even mild cases might cost you some IQ points
  - 988747 5y ago
    I have plenty of IQ points to spare. Also, I did get vaccinated, just didn't care about the few points of effectiveness I lose from a fast vaccination. EDIT: also, what you claim is illogical: you say that even mild cases of COVID cause IQ loss, and yet no know vaccine protects against mild cases, best case scenario they turn severe cases into mild ones. So getting vaccinated is useless in that regard.
    - zwaps 5y ago
      I mean, the Pfizer/Moderna vaccines still have between 90% and, let's say, 60% efficacy against mild cases, and the long covid severity scales with "how mild" your case is going to be. There is a likelihood that Covid gives you so much brain fog that you'll have trouble continuing your high-IQ work, and vaccines reduce that likelihood. If, due to the vaccine, you get a mild case or a case without any symptoms, perhaps all that happens is that your spatial reasoning is less speedy. And, as you say, you have plenty of that to spare. So, it seems to me you should have quite some interest in vaccine efficacy across the severity scale. It's your choice though, of course.
- Aachen 5y ago
  This sounds selfish, caring about your holiday not about infecting others, but the way it's written it also seems on purpose? I can't tell if this is flamebait. In case you're serious and don't find this selfish, what would be even better for (everyone's, and thus also yours) holidays would be no more pandemic. We'd get there with fewer extensions (mutations) if we have fewer hosts for it to breed resistance in. More immunity is more better as far as I know. I'm also not fully on board with letting regulations or social things pressure you into doing a medical thing to your body for reasons other than because you believe it's the best option for your personal health. Not that I think you made a bad choice, it's probably also the best choice for your own health, but it should be a fully free and informed choice for everyone. I suppose that, whatever the thought process and reasoning here, I'm happy you went with the option that benefits everyone. Keep it up and maybe one day you can't pretend to be a selfish person anymore :P (if that was, perhaps subconsciously idk, the goal here in the first place)
senectus1 5y ago
I had mine three weeks apart, I wonder if I'll get different responses to the booster when it comes through (at this stage) next year.

75 points by lnyan 5y ago

Now I'm glad I've waited 8 weeks !

Is it practical to ask people to wait 8 weeks? Will people be significantly less likely to show up to the second appointment after 8 weeks instead of 3 weeks?

barnabee 5y ago
In the UK the minimum wait is 8 weeks and there doesn't appear to be an issue with people failing to get 2nd doses.
- fredley 5y ago
  Until a few weeks ago the minimum wait was 12 weeks! Data on rates here: https://coronavirus.data.gov.uk/details/vaccinations https://coronavirus.data.gov.uk/details/vaccinations
  - ip_addr 5y ago
    Looking at just the Cumulative data, ~79% of people in the UK that have taken the first dose have taken the second dose. Looks like it is practical. And that number doesn't account for people that haven't had their second appointment yet.
- gambiting 5y ago
  I had my second dose in the UK after 5 weeks, by just going to a walk in centre and asking - apparently they had way too many doses they would be wasted otherwise, so they were happy to give it to anyone asking. Apparently the absolute NHS-mandated minimum is 3 weeks between doses, that's the one they can't disobey. But the 8 week minimum is much more flexible.
guerrilla 5y ago
That's about what it has been the whole time in my region and there's no sign of a problem yet.
elchief 5y ago
The wait period in British Columbia is about 7 weeks, and our #2 dose numbers look just as good as #1 (80% first dose, and 58% second dose, still averaging 60k doses a day)
tgsovlerkhgsel 5y ago
The main risk I'd be worried about that people will engage in more risky behavior after the first but before the second dose. It's a lot easier to hold out and skip some fun activities if there's a goal 4 (or rather 6) weeks ahead than if it's 8 (or rather 10) weeks.

voisin 5y ago

Man, the messaging around the vaccines is so damn frustrating. No wonder people are skeptical. “Get whatever is available when you are eligible” —> “Oh but not J&J unless you are over a certain age” —> “Or AZ unless over a certain age” —> “Don’t mix mRNA” —> “OK Mix mRNA if available. Just get fully vaxx’ed ASAP” —> “Just kidding, wait 8 weeks” Like come on! I follow this reasonably closely and I am ready to storm the Ivory Tower over this messaging. I cannot imagine what someone who doesn’t follow this feels.

detaro 5y ago
The main message here is not "you have to/absolutely should wait 8 weeks". The main point is "countries that did stretch the schedule compared to what was in the initial studies probably didn't make a massive mistake by doing so" (EDIT: and of course it's a press release for a single study, not an official policy announcement)
planet-and-halo 5y ago
That's complex decision-making under conditions of uncertainty for you. The authorities themselves are partly to blame for not being totally clear that they're human and figuring this out on the fly like everyone else, but the general population is also to blame for acting like a bunch of spoiled children and feeling entitled to perfect answers and zero mistakes.
- voisin 5y ago
  Admitting the uncertainty is my point. Instead they change the messaging week by week and act like this latest messaging is certain.
  - detaro 5y ago
    Each of those steps had more nuance being communicated than the half-sentence you summarize it with, often with intense public debate and different judgment calls from different health authorities. (AZ and if/how to use it is probably the biggest example, vaccination for children is another (at least here in DE that's a massive thing)) None of these things were "this is the absolute truth forever".

mistermann 5y ago

> For the longer schedule, the antibody levels dropped off between first and second dose, which included the loss of any neutralising effect against the Delta variant. However, T cell responses were consistent, indicating they may contribute to important protection against Covid-19 during this time. Does this suggest that ~8 weeks after the second dose one will still have protection from plain covid, but protection again Delta variants will be diminished?

tgsovlerkhgsel 5y ago
The sentence you quoted refers to the period between first and second dose. My understanding is that "if you get exposed to the Delta variant on the day before the second dose, you won't have neutralizing antibodies". It does not make a statement about what happens after the second dose.
- mistermann 5y ago
  Agreed, but it is suggestive that this is within the realm of possibilities, no? Otherwise, something interesting would have to be happening where after the first shot you lose delta ~immunity in eight weeks, but after the second you ~do not?
  - tgsovlerkhgsel 5y ago
    Possibilities sure, but IMO that doesn't translate to "likely". Other vaccines also give you only minimal or short protection after the first dose with long-lasting protection after the second (or third) one.

mchusma 5y ago

This is of course exactly what was expected, and why First Dose First was so clearly the right strategy until countries had plenty of supply. Good for the UK recognizing this early. The US hasn't.

peytn 5y ago
It’s unethical to gamble your citizenry on untested medical interventions regardless of outcome. There was enough time to sponsor a trial.
- moultano 5y ago
  Come on, we didn't even have time for the trials we actually ran. Thousands died while we waited for rubber stamps.
- tnorthcutt 5y ago
  So was it ethical to gamble on a four week interval when it wasn’t proven to be the best option?
  - nradov 5y ago
    No one ever claimed that it was the best option, just that it was the only option clinically tested. It would have been irresponsible to recommend a different option without at least some limited clinical trials. Sometimes you can't wait for perfect data.
  - ttul 5y ago
    Gamble is the wrong word for this. It was a calculated risk as is everything in a pandemic or other evolving threat to public health.
  - inglor_cz 5y ago
    I still think that something else was unethical: not running challenge tests. There were enough volunteers for them.
- 5y ago

inglor_cz 5y ago

In my country, we had 6 weeks between the doses. The main reason was shortage of vaccines, of course; nowadays the 6-week interval has been abolished and you can actually get the second dose earlier if you will, b/c "peak jab" is over and further interest wanes. I am one of the "six week vaccinees", which sits just in the middle of the two sets studied in this paper. I wonder what the results for 6 week delay are. Accidentally, Delta does not seem to be a problem yet in my country. IDK if it is luck, an early phase of a future wave or an effect of Pfizer doses being given 6 weeks apart, but our current Covid numbers are much more moderate than expected.

deleted 5y ago
[deleted]
gurleen_s 5y ago
What country, if you don’t mind me asking?
- lousken 5y ago
  by the nickname i'd assume czechia

wrayste 5y ago

It is not a good study: "A total of 503 healthcare workers were recruited to the study, of which 223 (44%) had previously had Covid-19." The sample group is not representative of the population and with a large proportion already having had COVID, it is expected that the first dose of the vaccine acts like the second dose, and a second dose as a booster. It is also ignoring the downsides of the longer gap, the main one being the increased likelihood of creating a vaccine resistant escape variant. The UK government admits that this is a risk: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/954990/s1015-sars-cov-2-immunity-escape-variants.pdf https://assets.publishing.service.gov.uk/government/uploads/... "There is therefore an increased risk of virus replication under partial immunity after one dose than after two doses, so in the short- term, delaying the second dose would be expected to somewhat increase the probability of emergence of vaccine resistance - but probably from a low base." Last time I looked, UK now had the 3rd highest case rate in the world. A variant factory you could call it. Part of the justification of the risks of the increased gap was the high death rate at the time. "Is such an increase material? It is not currently possible to quantify the probability of emergence of vaccine resistance as a result of the delayed second dose, but it is likely to be small. The UK currently has more than 1,000 COVID-19 related deaths each day and has limited supplies of vaccine. In the current UK circumstances the unquantifiable but likely small probability of the delayed second dose generating a vaccine escape mutant must be weighed against the measurable benefits of doubling the speed with which the most vulnerable can be given vaccine-induced protection." That is no longer the case, vaccine supply is good and take-up is falling. The Oxford AstraZeneca vaccine did have clinical trials with a longer gap as far as I understand, but Pfizer didn't. The mRNA vaccines have different properties but the UK government is treating all vaccines as the same. Now with every small and pretty weak bit of evidence the government jumps on to justify their decision, which initially may have been the right choice but the unlocking and delta variant have changed the situation massively. There was a similar study in Israel with some strong arguments against its findings: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01046-1/fulltext https://www.thelancet.com/journals/lancet/article/PIIS0140-6... And more good reading: http://www.thelancet.com/retrieve/pii/S0140673621004554 http://www.thelancet.com/retrieve/pii/S0140673621004554 "We have no concerns regarding the second dose of AZD1222 at 12 weeks, as this is supported by evidence. However, if escape variants arise due to sub-optimal dosing with BNT162b2, they will likely be resistant to other vaccines that target the same viral spike protein. In conclusion, we would strongly recommend that the UK Government reverts to the two doses in a 3-week schedule (94% efficacy) for BNT162b2; or, as recently supported by WHO and the US Centers for Disease Control and Prevention, adopt no more than a 6-week delay to the second dose “in exceptional circumstances”."

guilhas 5y ago

One study of few people does not seem enough. They started this longer interval, against manufacturers recommendation, supposedly because of stock and to give to more people, but kept the this longer interval even after the daily vaccination numbers dropped 10x

syntaxing 5y ago

Uhhh, has anyone read the article rather than confirming their confirmation bias...The header after the title is literally "One of the world’s most in-depth studies into Covid-19 immune response to vaccines shows a short and long dosing interval of the Pfizer jab generated strong antibody and T cell immune responses." Which means get both of your shots, regardless of gap. Evidence suggest longer gap gives better long term immunity but you are more vulnerable between both doses which can be can issue during an active pandemic. The article never suggests the "optimal" dosing schedule.

technofiend 5y ago

After two doses, overall T cell levels were 1.6 times lower after the long compared with the short dosing schedule. However, after the longer dosing interval, a higher proportion of T cells present were ‘helper’ T cells, which are important for long-term immune memory and helping generate antibodies to prevent infection. The data I'd like to see discovered is if and when this effect tapers off. Surely we need that to know the optimal time to take a booster? (This is assuming the vaccine makeup hadn't changed and you're not taking a booster to immunize against variants.)

988747 5y ago

That only matters to people who get vaccinated because they are afraid of COVID. I got my second dose ASAP, because I needed a certificate for travel, so I could go for well deserved vacation. I don't give a fuck about effectivness.

zwaps 5y ago
Not worried about long covid? Other article on HN suggests that even mild cases might cost you some IQ points
- 988747 5y ago
  I have plenty of IQ points to spare. Also, I did get vaccinated, just didn't care about the few points of effectiveness I lose from a fast vaccination. EDIT: also, what you claim is illogical: you say that even mild cases of COVID cause IQ loss, and yet no know vaccine protects against mild cases, best case scenario they turn severe cases into mild ones. So getting vaccinated is useless in that regard.
  - zwaps 5y ago
    I mean, the Pfizer/Moderna vaccines still have between 90% and, let's say, 60% efficacy against mild cases, and the long covid severity scales with "how mild" your case is going to be. There is a likelihood that Covid gives you so much brain fog that you'll have trouble continuing your high-IQ work, and vaccines reduce that likelihood. If, due to the vaccine, you get a mild case or a case without any symptoms, perhaps all that happens is that your spatial reasoning is less speedy. And, as you say, you have plenty of that to spare. So, it seems to me you should have quite some interest in vaccine efficacy across the severity scale. It's your choice though, of course.
Aachen 5y ago
This sounds selfish, caring about your holiday not about infecting others, but the way it's written it also seems on purpose? I can't tell if this is flamebait. In case you're serious and don't find this selfish, what would be even better for (everyone's, and thus also yours) holidays would be no more pandemic. We'd get there with fewer extensions (mutations) if we have fewer hosts for it to breed resistance in. More immunity is more better as far as I know. I'm also not fully on board with letting regulations or social things pressure you into doing a medical thing to your body for reasons other than because you believe it's the best option for your personal health. Not that I think you made a bad choice, it's probably also the best choice for your own health, but it should be a fully free and informed choice for everyone. I suppose that, whatever the thought process and reasoning here, I'm happy you went with the option that benefits everyone. Keep it up and maybe one day you can't pretend to be a selfish person anymore :P (if that was, perhaps subconsciously idk, the goal here in the first place)

senectus1 5y ago

I had mine three weeks apart, I wonder if I'll get different responses to the booster when it comes through (at this stage) next year.