8 ms·

> If the evidence available on the efficacy of vaccines for kids is so ridiculously wide that it goes from -99% to +370% risk of infection, then surely Norway i

by timr 4y ago

> If the evidence available on the efficacy of vaccines for kids is so ridiculously wide that it goes from -99% to +370% risk of infection, then surely Norway is _also_ drastically overstating its case when it says (about kids) "previous infection offers as good of protection as the vaccine against reinfection" esp since it _also_ seems like the protective effect of prior infection is both uncertain and changing. The protective effect of prior infection is not uncertain, nor is it changing. There have been dozens of papers now, all saying the same thing: natural infection is at least as protective (if not more so) than even 3 doses of the current vaccines. If you are hearing otherwise, you are being misinformed. Full stop. Here's the latest paper in a long line of consistent evidence, last week in the NEJM: https://www.nejm.org/doi/full/10.1056/NEJMoa2203965 https://www.nejm.org/doi/full/10.1056/NEJMoa2203965 > No discernable differences in protection against symptomatic BA.1 and BA.2 infection were seen with previous infection, vaccination, and hybrid immunity. Vaccination enhanced protection among persons who had had a previous infection. Hybrid immunity resulting from previous infection and recent booster vaccination conferred the strongest protection. Norway is saying what it is, because we know that most people -- vaccinated or previously infected -- will eventually get re-infected. But even if you are re-infected, you will be well-protected against severe illness.

wrycoder 4y ago
I can understand how previous infection can confer immunity, especially since the immune response is built against live virus, not just spike protein. What I don’t understand is how vaccination and boosting using an mRNA vaccine that contains only spike protein from the original SARS2, and which is almost completely evaded by the BA.4 and BA.5 variants, can confer protection against severe illnesses caused by those variants. What is the biochemical process that provides that protection? EDIT: Is this protection just a happy mantra, or is it actually that there is no protection against the new variants, but the intensity of the disease from them is far less than from the original variant (and our treatment is getting better)?
- MuchoMaas 4y ago
  One theory I have heard to explain this is that the vaccine is simply suppressing immune response, which helps prevent the cytokine storm that led to severe disease. Of course, this might also make infection more likely, which may explain why so many governments have stopped publishing the case rate breakdowns by vax status. It makes a kind of intuitive sense: if you make your own body produce some key portion of the virus, maybe your immune system gets tricked into thinking it's not such a big issue?
  - zzleeper 4y ago
    > the vaccine is simply suppressing immune response, which helps prevent the cytokine storm that led to severe disease. "Response" is many different things. The vaccine boosts response b/c you have antibodies, so it's much less likely that your body has to do a hail mary las ditch (cytok storm). > why so many governments have stopped publishing the case rate breakdowns by vax status. But there's enough data out there to have a clear picture: vaccines or previous infections won't protect you from being infected by the recent strains (BA.2.75, BA.5, etc) but will protect you from severe disease or dying. Maybe it can be improved by nasal vaccines (what happened to those?) but who knows... > It makes a kind of intuitive sense: if you make your own body produce some key portion of the virus, maybe your immune system gets tricked into thinking it's not such a big issue? This one is completely off the mark. For starters, not all vaccines have your "body produce part of the virus", yet all help to prevent severe cases and death.
- timr 4y ago
  There is protection against the new variants. The human immune system has different levels of protection, and these mRNA vaccines seem particularly effective at triggering one of the most flexible, long-term forms -- cellular immunity. At a very high level, this is the explanation: the spike protein in Omicron has many differences from the vaccine strain spike, but it's still largely the same protein. The immune system is chopping up the protein into chunks, and T- and B-Cells are specializing to recognize those chunks. This kind of immune response (the "cellular immune response") is slower to ramp up than the antibody response that many people have fixated on, but it's a much more robust defense mechanism; B- and T-Cells are very good at providing generalized antigen recognition. There have been at least 2-3 papers I'm aware of where labs have directly demonstrated that vaccinated people are producing robust immune responses to Omicron proteins. I'd have to dig these up again, and they're not exactly comprehensible by non-specialists, but the executive summary is that we have laboratory and clinical and epidemiological data that the vaccines are still very effective against severe disease. What the vaccines don't do anymore, is protect against infection. That was probably never a realistic goal for a respiratory virus, but it's definitely not practical with a vaccine that produces antibodies that target a very old spike protein.
  - wrycoder 4y ago
    If you have a link, I’d be interested in reading the paper!
    - timr 4y ago
      Here's one from Cell -- as I said, it's very technical, but the TL;DR is that 84% of CD4+ and 85% of CD8+ memory T cell responses to the Omicron spike protein are preserved, compared to an average of 90% and 87% respectively for the other variants: https://www.sciencedirect.com/science/article/pii/S0092867422000733 https://www.sciencedirect.com/science/article/pii/S009286742... Here's another: https://www.nature.com/articles/s41586-022-04460-3 https://www.nature.com/articles/s41586-022-04460-3 > Between 70% and 80% of the CD4+ and CD8+ T cell response to spike was maintained across study groups. Moreover, the magnitude of Omicron cross-reactive T cells was similar for Beta (B.1.351) and Delta (B.1.617.2) variants, despite Omicron harbouring considerably more mutations. In patients who were hospitalized with Omicron infections (n = 19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those in patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants (n = 49). Thus, despite extensive mutations and reduced susceptibility to neutralizing antibodies of Omicron, the majority of T cell responses induced by vaccination or infection cross-recognize the variant. I may have read a third, but I can't find it easily, and these two should be more than enough to back up what I wrote / get you started.
scifibestfi 4y ago
What's odd is how many people ignored, denied or actively resisted the idea of natural infection conferring immunity.
- cm2187 4y ago
  And at the same time supported severe covid restrictions until a vaccine is available. The paradox of course is that the likelihood of there being an efficient vaccine is very low if you don’t develop immunity naturally.
  - ImPostingOnHN 4y ago
    > the likelihood of there being an efficient vaccine is very low if you don’t develop immunity naturally where did you read this?
    - cm2187 4y ago
      The way traditional vaccines work is by injecting an attenuated virus and letting the natural immunity do the rest. If natural immunity doesn’t work on the original virus, it is unlikely it will work on the attenuated virus.
      - ImPostingOnHN 4y ago
        what does that have to do with the restrictions? the logical corollary to your statement seems to be, if the body IS capable of natural immunity, then it is likely that it will work on the attenuated virus (provided it's not too attenuated, maybe)
- ryanobjc 4y ago
  That isn't it at all, the question isn't "does natural immunity happen", but "what's the overall population cost of natural immunity". Long covid, and greater impact on certain individuals were well known by that point. Just saying "let 'er rip, go natural immunity" isn't the responsible move. Perhaps you're ok with the risks for you, but faulting a health officer for taking a different more conservative position is hardly a reasonable opinion.
stonogo 4y ago
> natural infection is at least as protective (if not more so) than even 3 doses of the current vaccines. This claim is directly contradicted in the paper you linked: > The effectiveness of previous infection alone against symptomatic BA.2 infection was 46.1% (95% confidence interval [CI], 39.5 to 51.9). ... > The effectiveness of three doses of BNT162b2 and no previous infection was 52.2% (95% CI, 48.1 to 55.9).
- timr 4y ago
  Those confidence intervals overlap. You're cherry picking one plot, for one outcome, for one vaccine, out of the entire paper, and it's not refuting the conclusion of the paper.
  - ImPostingOnHN 4y ago
    if they overlap, how do you support your statement that the opposite is true?
    - timr 4y ago
      "natural infection is at least as protective (if not more so) than even 3 doses of the current vaccines." GP is citing a part of the paper where they show...that natural infection is statistically indistinguishable from 3 doses. QED.
      - ImPostingOnHN 4y ago
Retric 4y ago
Symptomatic infection is not the point of vaccination. The important bit is this: “Previous infection alone, BNT162b2 vaccination alone, and hybrid immunity all showed strong effectiveness (>70%) against severe, critical, or fatal Covid-19 due to BA.2 infection.” Though they didn’t list actual percentages, other studies showed vaccination provided ~90% reduction in deaths. That said there are conflicting studies: “This report details the findings of a case-control evaluation of the association between vaccination and SARS-CoV-2 reinfection in Kentucky during May–June 2021 among persons previously infected with SARS-CoV-2 in 2020. Kentucky residents who were not vaccinated had 2.34 times the odds of reinfection compared with those who were fully vaccinated (odds ratio [OR] = 2.34; 95% confidence interval [CI] = 1.58–3.47).” https://www.cdc.gov/mmwr/volumes/70/wr/mm7032e1.htm?s_cid=mm7032e1_e&ACSTrackingID=USCDC_921-DM63289&ACSTrackingLabel=MMWR%20Early%20Release%20-%20Vol.%2070%2C%20August%206%2C%202021&deliveryName=USCDC_921-DM63289 https://www.cdc.gov/mmwr/volumes/70/wr/mm7032e1.htm?s_cid=mm... The nuances are complicated. False positives are a real concern for people avoiding vaccination. People that survive the first infection without vaccination are a meaningfully different population than the vaccinated population. Similarly people that get vaccinated after infection have received vaccination more recently etc.
- timr 4y ago
  That MMWR study was a pile of flaming garbage. First, it was conducted in May 2021 (before the Delta wave) so everyone who was vaccinated was well within the first few months of their second dose. We now know that protection against infection rapidly fell after about 4 months. But also, it was just methodologically flawed -- they didn't bother to correct for the bias that people who were vaccinated after infection in early 2021 were probably behaving differently than those who had not been vaccinated at that time. If you're going to cite an old MMWR article as "evidence" against the now overwhelming pile of papers demonstrating that the immune system works pretty much as we expect from immmunology 101, don't forget that in early 2022 they released this much better, much larger (N=1.1M people) cohort study, which dramatically showed the opposite of what you're claiming. Prior infection obviously provided robust protection against Delta, on par with the vaccines: https://www.cdc.gov/mmwr/volumes/71/wr/pdfs/mm7104e1-H.pdf https://www.cdc.gov/mmwr/volumes/71/wr/pdfs/mm7104e1-H.pdf
abeppu 4y ago
> The protective effect of prior infection is not uncertain, nor is it changing. The paper you linked shows effectiveness of previous infection alone at 46%, 3 vaccine doses at 52% (and slightly above the upper end of the confidence interval for infection only), and previous infection and 3 doses at 77%. When I looked for earlier studies, the first one that popped up was this one from Sept 2021, which finds that previous infection gives a 90% reduced risk re-infection. This seems to be consistent with what has been reported more popularly; in 2020-2021 it seemed that the immune benefit from a previous infection could last several months, and that this informed the timing on when boosters were recommended. Whereas now it seems it's significantly easier to be re-infected with an omicron variant relatively soon after a previous infection. The finding of 90% in late 2021 vs <50% now does sound like the protective effect of prior infection _is_ changing.
- timr 4y ago
  You're quoting numbers concerning protection against symptomatic infection. While perhaps scientifically interesting, this is irrelevant. You are going to get Covid multiple times in your life, regardless of your vaccination or infection status. Look a Figures 1, 2 and 4, and you'll see clearly that protection against severe disease remains quite robust. Protection against severe, critical or fatal Covid-19 due to any Omicron infection is shown at 91% (95% CI 60-100) after prior infection (Figure 2D). https://www.nejm.org/doi/full/10.1056/NEJMoa2203965 https://www.nejm.org/doi/full/10.1056/NEJMoa2203965
  - abeppu 4y ago
    Why is protection against symptomatic infection not relevant? Because the bar for "severe" is set rather high, there's plenty of room for symptomatic illness to be personally, economically, and systematically damaging without being "severe", and I think a lot of people find that waning protection to be quite relevant. > You are going to get Covid multiple times in your life, regardless of your vaccination or infection status. Yeah but whether you expect to get it once every couple years or multiple times a year is meaningful to what living in a post-covid world looks like. Earlier your very firm statement did not qualify the unchanged protective effect as being limited to severe, critical or fatal disease, and I think you're moving goalposts. > The protective effect of prior infection is not uncertain, nor is it changing.

by timr 4y ago

wrycoder 4y ago

I can understand how previous infection can confer immunity, especially since the immune response is built against live virus, not just spike protein. What I don’t understand is how vaccination and boosting using an mRNA vaccine that contains only spike protein from the original SARS2, and which is almost completely evaded by the BA.4 and BA.5 variants, can confer protection against severe illnesses caused by those variants. What is the biochemical process that provides that protection? EDIT: Is this protection just a happy mantra, or is it actually that there is no protection against the new variants, but the intensity of the disease from them is far less than from the original variant (and our treatment is getting better)?

MuchoMaas 4y ago
One theory I have heard to explain this is that the vaccine is simply suppressing immune response, which helps prevent the cytokine storm that led to severe disease. Of course, this might also make infection more likely, which may explain why so many governments have stopped publishing the case rate breakdowns by vax status. It makes a kind of intuitive sense: if you make your own body produce some key portion of the virus, maybe your immune system gets tricked into thinking it's not such a big issue?
- zzleeper 4y ago
  > the vaccine is simply suppressing immune response, which helps prevent the cytokine storm that led to severe disease. "Response" is many different things. The vaccine boosts response b/c you have antibodies, so it's much less likely that your body has to do a hail mary las ditch (cytok storm). > why so many governments have stopped publishing the case rate breakdowns by vax status. But there's enough data out there to have a clear picture: vaccines or previous infections won't protect you from being infected by the recent strains (BA.2.75, BA.5, etc) but will protect you from severe disease or dying. Maybe it can be improved by nasal vaccines (what happened to those?) but who knows... > It makes a kind of intuitive sense: if you make your own body produce some key portion of the virus, maybe your immune system gets tricked into thinking it's not such a big issue? This one is completely off the mark. For starters, not all vaccines have your "body produce part of the virus", yet all help to prevent severe cases and death.
timr 4y ago
There is protection against the new variants. The human immune system has different levels of protection, and these mRNA vaccines seem particularly effective at triggering one of the most flexible, long-term forms -- cellular immunity. At a very high level, this is the explanation: the spike protein in Omicron has many differences from the vaccine strain spike, but it's still largely the same protein. The immune system is chopping up the protein into chunks, and T- and B-Cells are specializing to recognize those chunks. This kind of immune response (the "cellular immune response") is slower to ramp up than the antibody response that many people have fixated on, but it's a much more robust defense mechanism; B- and T-Cells are very good at providing generalized antigen recognition. There have been at least 2-3 papers I'm aware of where labs have directly demonstrated that vaccinated people are producing robust immune responses to Omicron proteins. I'd have to dig these up again, and they're not exactly comprehensible by non-specialists, but the executive summary is that we have laboratory and clinical and epidemiological data that the vaccines are still very effective against severe disease. What the vaccines don't do anymore, is protect against infection. That was probably never a realistic goal for a respiratory virus, but it's definitely not practical with a vaccine that produces antibodies that target a very old spike protein.
- wrycoder 4y ago
  If you have a link, I’d be interested in reading the paper!
  - timr 4y ago
    Here's one from Cell -- as I said, it's very technical, but the TL;DR is that 84% of CD4+ and 85% of CD8+ memory T cell responses to the Omicron spike protein are preserved, compared to an average of 90% and 87% respectively for the other variants: https://www.sciencedirect.com/science/article/pii/S0092867422000733 https://www.sciencedirect.com/science/article/pii/S009286742... Here's another: https://www.nature.com/articles/s41586-022-04460-3 https://www.nature.com/articles/s41586-022-04460-3 > Between 70% and 80% of the CD4+ and CD8+ T cell response to spike was maintained across study groups. Moreover, the magnitude of Omicron cross-reactive T cells was similar for Beta (B.1.351) and Delta (B.1.617.2) variants, despite Omicron harbouring considerably more mutations. In patients who were hospitalized with Omicron infections (n = 19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those in patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants (n = 49). Thus, despite extensive mutations and reduced susceptibility to neutralizing antibodies of Omicron, the majority of T cell responses induced by vaccination or infection cross-recognize the variant. I may have read a third, but I can't find it easily, and these two should be more than enough to back up what I wrote / get you started.

scifibestfi 4y ago

What's odd is how many people ignored, denied or actively resisted the idea of natural infection conferring immunity.

cm2187 4y ago
And at the same time supported severe covid restrictions until a vaccine is available. The paradox of course is that the likelihood of there being an efficient vaccine is very low if you don’t develop immunity naturally.
- ImPostingOnHN 4y ago
  > the likelihood of there being an efficient vaccine is very low if you don’t develop immunity naturally where did you read this?
  - cm2187 4y ago
    The way traditional vaccines work is by injecting an attenuated virus and letting the natural immunity do the rest. If natural immunity doesn’t work on the original virus, it is unlikely it will work on the attenuated virus.
    - ImPostingOnHN 4y ago
      what does that have to do with the restrictions? the logical corollary to your statement seems to be, if the body IS capable of natural immunity, then it is likely that it will work on the attenuated virus (provided it's not too attenuated, maybe)
ryanobjc 4y ago
That isn't it at all, the question isn't "does natural immunity happen", but "what's the overall population cost of natural immunity". Long covid, and greater impact on certain individuals were well known by that point. Just saying "let 'er rip, go natural immunity" isn't the responsible move. Perhaps you're ok with the risks for you, but faulting a health officer for taking a different more conservative position is hardly a reasonable opinion.

stonogo 4y ago

> natural infection is at least as protective (if not more so) than even 3 doses of the current vaccines. This claim is directly contradicted in the paper you linked: > The effectiveness of previous infection alone against symptomatic BA.2 infection was 46.1% (95% confidence interval [CI], 39.5 to 51.9). ... > The effectiveness of three doses of BNT162b2 and no previous infection was 52.2% (95% CI, 48.1 to 55.9).

timr 4y ago
Those confidence intervals overlap. You're cherry picking one plot, for one outcome, for one vaccine, out of the entire paper, and it's not refuting the conclusion of the paper.
- ImPostingOnHN 4y ago
  if they overlap, how do you support your statement that the opposite is true?
  - timr 4y ago
    "natural infection is at least as protective (if not more so) than even 3 doses of the current vaccines." GP is citing a part of the paper where they show...that natural infection is statistically indistinguishable from 3 doses. QED.
    - ImPostingOnHN 4y ago

Retric 4y ago

Symptomatic infection is not the point of vaccination. The important bit is this: “Previous infection alone, BNT162b2 vaccination alone, and hybrid immunity all showed strong effectiveness (>70%) against severe, critical, or fatal Covid-19 due to BA.2 infection.” Though they didn’t list actual percentages, other studies showed vaccination provided ~90% reduction in deaths. That said there are conflicting studies: “This report details the findings of a case-control evaluation of the association between vaccination and SARS-CoV-2 reinfection in Kentucky during May–June 2021 among persons previously infected with SARS-CoV-2 in 2020. Kentucky residents who were not vaccinated had 2.34 times the odds of reinfection compared with those who were fully vaccinated (odds ratio [OR] = 2.34; 95% confidence interval [CI] = 1.58–3.47).” https://www.cdc.gov/mmwr/volumes/70/wr/mm7032e1.htm?s_cid=mm7032e1_e&ACSTrackingID=USCDC_921-DM63289&ACSTrackingLabel=MMWR%20Early%20Release%20-%20Vol.%2070%2C%20August%206%2C%202021&deliveryName=USCDC_921-DM63289 https://www.cdc.gov/mmwr/volumes/70/wr/mm7032e1.htm?s_cid=mm... The nuances are complicated. False positives are a real concern for people avoiding vaccination. People that survive the first infection without vaccination are a meaningfully different population than the vaccinated population. Similarly people that get vaccinated after infection have received vaccination more recently etc.

timr 4y ago
That MMWR study was a pile of flaming garbage. First, it was conducted in May 2021 (before the Delta wave) so everyone who was vaccinated was well within the first few months of their second dose. We now know that protection against infection rapidly fell after about 4 months. But also, it was just methodologically flawed -- they didn't bother to correct for the bias that people who were vaccinated after infection in early 2021 were probably behaving differently than those who had not been vaccinated at that time. If you're going to cite an old MMWR article as "evidence" against the now overwhelming pile of papers demonstrating that the immune system works pretty much as we expect from immmunology 101, don't forget that in early 2022 they released this much better, much larger (N=1.1M people) cohort study, which dramatically showed the opposite of what you're claiming. Prior infection obviously provided robust protection against Delta, on par with the vaccines: https://www.cdc.gov/mmwr/volumes/71/wr/pdfs/mm7104e1-H.pdf https://www.cdc.gov/mmwr/volumes/71/wr/pdfs/mm7104e1-H.pdf

abeppu 4y ago

> The protective effect of prior infection is not uncertain, nor is it changing. The paper you linked shows effectiveness of previous infection alone at 46%, 3 vaccine doses at 52% (and slightly above the upper end of the confidence interval for infection only), and previous infection and 3 doses at 77%. When I looked for earlier studies, the first one that popped up was this one from Sept 2021, which finds that previous infection gives a 90% reduced risk re-infection. This seems to be consistent with what has been reported more popularly; in 2020-2021 it seemed that the immune benefit from a previous infection could last several months, and that this informed the timing on when boosters were recommended. Whereas now it seems it's significantly easier to be re-infected with an omicron variant relatively soon after a previous infection. The finding of 90% in late 2021 vs <50% now does sound like the protective effect of prior infection _is_ changing.

timr 4y ago
You're quoting numbers concerning protection against symptomatic infection. While perhaps scientifically interesting, this is irrelevant. You are going to get Covid multiple times in your life, regardless of your vaccination or infection status. Look a Figures 1, 2 and 4, and you'll see clearly that protection against severe disease remains quite robust. Protection against severe, critical or fatal Covid-19 due to any Omicron infection is shown at 91% (95% CI 60-100) after prior infection (Figure 2D). https://www.nejm.org/doi/full/10.1056/NEJMoa2203965 https://www.nejm.org/doi/full/10.1056/NEJMoa2203965
- abeppu 4y ago
  Why is protection against symptomatic infection not relevant? Because the bar for "severe" is set rather high, there's plenty of room for symptomatic illness to be personally, economically, and systematically damaging without being "severe", and I think a lot of people find that waning protection to be quite relevant. > You are going to get Covid multiple times in your life, regardless of your vaccination or infection status. Yeah but whether you expect to get it once every couple years or multiple times a year is meaningful to what living in a post-covid world looks like. Earlier your very firm statement did not qualify the unchanged protective effect as being limited to severe, critical or fatal disease, and I think you're moving goalposts. > The protective effect of prior infection is not uncertain, nor is it changing.