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It's worth clarifying: un-boosted vaccination or past infection seem to have greatly reduced ability to prevent infection with Omicron. There is still substanti

It's worth clarifying: un-boosted vaccination or past infection seem to have greatly reduced ability to prevent infection with Omicron. There is still substantial (lessened, but not as drastically lessened) protection against serious illness / death. My understanding is that protection-against-infection and protection-against-death rely on different aspects of the immune system. The primary protection against initial infection comes from antibodies, which are narrowly targeted. Other systems are more flexible, but don't kick in quickly enough to ward off a mild infection. And the takeaway is still: get vaccinated, get boosted.

abduhl 5y ago
What you’re saying sounds correct, but is there any evidence that shows omicron is resulting in less serious illness/death because of the vaccines? The reports seem to indicate that the overall risk profile of omicron is lower including for unvaccinated people. Are we just parroting the same fact as for the alpha/delta variants without any substantial evidence here when we say vaccination helps avoid serious illness for omicron? Why would a variant which has apparently evolved to evade the vaccine continue to react to prior vaccination? We see the opposite with flu vaccines sometimes when vaccinations prime against the wrong strain.
- ugjka 5y ago
  give it a month or two and we'll see who's right or wrong
- snewman 5y ago
  Hard information regarding serious illness / death from Omicron is scanty; it's still early. I've read indications that the vaccines (and/or previous infection with another variant, such as Delta) do seem to provide substantial protection against serious illness/death, but I don't have a link handy. IIRC at least some of the data we're working with is based on lab experiments of how various immune system components react to Omicron, which of course is less definitive than clinical outcomes, but is worth something. > Why would a variant which has apparently evolved to evade the vaccine continue to react to prior vaccination? This is over-simplified. In particular, "react to prior vaccination" is conflating a bunch of different things, involving antibodies, B cells, T cells, etc. My understanding is that (1) such data as we have seems to generally point toward protection-from-infection being badly eroded but protection-from-illness/death being only moderately eroded, (2) if you're boosted, protection is less badly eroded, (3) all of this seems to fit with our general understanding of how the immune system works. I don't have the domain knowledge to unpack that further.
  - abduhl 5y ago
    Your argument boils down to “well the body learns what it looks like and so discriminates against similar looking viruses with more exposure allowing more targeted responses.” Under this theory, shouldn’t a natural immunity (as obtained from prior infection with alpha/delta) result in better immune response because it has learned “more” way to discriminate than the spike protein? Boosters seem inappropriate if the theory is to provide a wide database against which the immune system can check for similarities and associated response because they are targeted at the spike protein.
    - astrange 5y ago
      It might, but you don't want to get natural immunity because that would mean getting sick first. Getting booster shots doesn't simply give you more antibodies, it gives you better ones; each round finds new ways to match the spike protein.
      - hackerfromthefu 5y ago
        Can you provide a reference for this, as I thought the boosters were just the original vaccines, hence exactly the same antibodies. Yesterday I read that the customised omicron specific boosters being developed by pfizer and moderna are not going ahead as the existing boosters are deemed good enough, though I can't find the link for that now.
        astrange 5y ago
        They are the original vaccines. I suppose it works by giving your body another chance to study them.
      - didjathinkmess 5y ago
        Natural immunity followed by a single dose is the strongest immunity available supposedly. Many of us likely have cross reactive immunity from a previous Coronavirus infection from before the pandemic. Regarding "better antibodies", that doesn't make any sense to me. More in number perhaps, but better? It's the exact same formula being given as boosters.
- tfehring 5y ago
  Two doses of Pfizer's vaccine reduce hospitalization risk from Omicron by ~70% based on data from South Africa, with similar reductions across all age cohorts from 18 to 79. https://www.linkedin.com/pulse/discovery-health-releases-critical-insights-omicron-adrian-gore/ https://www.linkedin.com/pulse/discovery-health-releases-cri...
Symmetry 5y ago
I think it's more like, after a vaccination or infection you're now producing 20 different antibodies targeting different sites on the Covid spike. You start out producing high levels of the antibodies and less over time, but when you encounter the same virus you ramp up production of all 20 if your levels weren't high enough to prevent infection in the first place. With Omicron maybe only few of those antibodies still work and not as well. That won't be enough to prevent infection. But you can still ramp up production of the ones that work after infection and your body has a good blue print, though the wonders of memory B cells and somatic hypermutation, to start work on more effective Omicron specific antibodies that makes the process easier than developing covid antibodies from scratch.
- lamontcg 5y ago
  You're missing T-cells. There's something on the order of 1,000 T-cell epitopes against spike, not just 20, and some of them are densely packed in areas of the spike protein that are highly conserved. The spike is cleaved by proteosomes into small segments and those segments are attached to MHC-I in the ER and then shipped off to be expressed on the cell-surface to be identified by T-cell receptors. Those segments are long enough to be recgonized, but small enough that there's a ton of them (and since they're cleaved an no longer attached to the rest of the protein there's no steric hindering or conformation changes or any of that to worry about). And there's still about 80% overlap between Omicron and Delta/Wuhan-hu-1. That number will probably never get down to zero due to the highly conserved areas. CD4+/CD8+ T-cells will therefore still be able to identify infected cells and lyse them or drag them back to have a discussion with some memory B-cells. That is where somatic hypermutation might be important since some of those antibodies will match Omicron's spike and those B-cells can then be amplified and you can get Omicron-specific antibodies being produced -- all without having to start entirely from scratch. But its the CTLs that already identify the Omicron-infected cells which will do the bulk of responding to the virus and clearing the infection. This is also why we don't need to rush to update vaccines to be Omicron-specific or why neutralizing abs really matters that much at all (and if there's Original Antigenic Sin it really may not matter much at all since there may not be much Omicron-specific B-cell or Nabs response to an infection or variant-specific vaccination at all). > SARS-CoV-2 human T cell epitopes: Adaptive immune response against COVID-19 > Over the past year, numerous studies in the peer reviewed and preprint literature have reported on the virological, epidemiological and clinical characteristics of the coronavirus, SARS-CoV-2. To date, 25 studies have investigated and identified SARS-CoV-2-derived T cell epitopes in humans. Here, we review these recent studies, how they were performed, and their findings. We review how epitopes identified throughout the SARS-CoV2 proteome reveal significant correlation between number of epitopes defined and size of the antigen provenance. We also report additional analysis of SARS-CoV-2 human CD4 and CD8 T cell epitope data compiled from these studies, identifying 1,400 different reported SARS-CoV-2 epitopes and revealing discrete immunodominant regions of the virus and epitopes that are more prevalently recognized. This remarkable breadth of epitope repertoire has implications for vaccine design, cross-reactivity, and immune escape by SARS-CoV-2 variants. https://www.sciencedirect.com/science/article/pii/S1931312821002389 https://www.sciencedirect.com/science/article/pii/S193131282...
api 5y ago
> There is still substantial (lessened, but not as drastically lessened) protection against serious illness / death. My understanding so far is that the vaccine is much better at blunting the effects than preventing infection generally, even with "classic" COVID and delta. In Ohio where I live the statistic so far has been that >90% of all hospitalized cases are unvaccinated, and of the ~10% who are vaccinated the majority have other conditions that boost risk of severe COVID such as being immunocompromised, diabetes, obesity, etc. There are very very few healthy vaccinated people in the hospital.
squarefoot 5y ago
This, a million times. Over here 80-90% of Covid patients in ICUs are either never vaccinated or in need of a boost because of too much time past since their 2nd shot. So, yes, vaccination may not prevent being infected, but for sure it helps immensely in avoiding being hospitalized and shortening the infection, which does actually translate in less people being infected. And believe me, having both lived and seen this with my own eyes, there's a world of difference between staying home 2-3 weeks with a strong cough and living 2 months in an ICU with chances of being carried out from there in a brown bag.
- didjathinkmess 5y ago
  >So, yes, vaccination may not prevent being infected, but for sure it helps immensely in avoiding being hospitalized and shortening the infection, which does actually translate in less people being infected. On the flip side, infections in the vaccinated who are asymptomatic are more likely to leave the house, simply because they have no idea that they're sick. Perhaps they end up at a restaurant with their mask off and turn into a literal super spreaders (if we're to believe Omicron is 4X more transmissable). This was always a potential problem with vaccines that only reduce symptoms and don't prevent transmission. If Omicron is indeed mild and highly contagious as officials in South Africa claim, this could be a huge issue with anyone vaccinated.
  - lamontcg 5y ago
    Transmissions and symptoms are roughly correlated through viral load. The household attack rate of ultimately asymptomatic infections is much lower than ultimately symptomatic. The window for vaccinated people is also shorter since mRNA loads peak at about the same levels (where the entry criteria for the study was the same level of symptomology) but they decline faster and have less culturable, infectious virus for the same level of mRNA load. And delta already spikes viral loads much, much higher in the presymptomatic phase of an infection (doesn't matter if its naive, breakthrough or reinfection) so that people are walking around spreading it before they know they have it. That ship already sailed. Once someone is infected, then its better that they get less symptoms and less viral load / less shedding and that they're vaccinated.
Abishek_Muthian 5y ago
Is there data about infection + two doses of vaccines against omicron? Scientists/Doctors in India have been claiming that's the best combination of protection one could have and if true that would cover significant chunk of our population. There seems to be data from UK that two doses of type-X vaccine followed by a booster of type-Y vaccine being more effective against Omicron. Different types of vaccines platforms being mRNA vaccines(Pfizer, Moderna etc.), Inactivated whole virus vaccines(CoVaxin,CoronaVac etc.), Pure DNA Vaccine(Zydus), DNA vector vaccines(Astrazenica/Covishield etc.) and upcoming protein subunit vaccines.

abduhl 5y ago

What you’re saying sounds correct, but is there any evidence that shows omicron is resulting in less serious illness/death because of the vaccines? The reports seem to indicate that the overall risk profile of omicron is lower including for unvaccinated people. Are we just parroting the same fact as for the alpha/delta variants without any substantial evidence here when we say vaccination helps avoid serious illness for omicron? Why would a variant which has apparently evolved to evade the vaccine continue to react to prior vaccination? We see the opposite with flu vaccines sometimes when vaccinations prime against the wrong strain.

ugjka 5y ago
give it a month or two and we'll see who's right or wrong
snewman 5y ago
Hard information regarding serious illness / death from Omicron is scanty; it's still early. I've read indications that the vaccines (and/or previous infection with another variant, such as Delta) do seem to provide substantial protection against serious illness/death, but I don't have a link handy. IIRC at least some of the data we're working with is based on lab experiments of how various immune system components react to Omicron, which of course is less definitive than clinical outcomes, but is worth something. > Why would a variant which has apparently evolved to evade the vaccine continue to react to prior vaccination? This is over-simplified. In particular, "react to prior vaccination" is conflating a bunch of different things, involving antibodies, B cells, T cells, etc. My understanding is that (1) such data as we have seems to generally point toward protection-from-infection being badly eroded but protection-from-illness/death being only moderately eroded, (2) if you're boosted, protection is less badly eroded, (3) all of this seems to fit with our general understanding of how the immune system works. I don't have the domain knowledge to unpack that further.
- abduhl 5y ago
  Your argument boils down to “well the body learns what it looks like and so discriminates against similar looking viruses with more exposure allowing more targeted responses.” Under this theory, shouldn’t a natural immunity (as obtained from prior infection with alpha/delta) result in better immune response because it has learned “more” way to discriminate than the spike protein? Boosters seem inappropriate if the theory is to provide a wide database against which the immune system can check for similarities and associated response because they are targeted at the spike protein.
  - astrange 5y ago
    It might, but you don't want to get natural immunity because that would mean getting sick first. Getting booster shots doesn't simply give you more antibodies, it gives you better ones; each round finds new ways to match the spike protein.
    - hackerfromthefu 5y ago
      Can you provide a reference for this, as I thought the boosters were just the original vaccines, hence exactly the same antibodies. Yesterday I read that the customised omicron specific boosters being developed by pfizer and moderna are not going ahead as the existing boosters are deemed good enough, though I can't find the link for that now.
      - astrange 5y ago
        They are the original vaccines. I suppose it works by giving your body another chance to study them.
    - didjathinkmess 5y ago
      Natural immunity followed by a single dose is the strongest immunity available supposedly. Many of us likely have cross reactive immunity from a previous Coronavirus infection from before the pandemic. Regarding "better antibodies", that doesn't make any sense to me. More in number perhaps, but better? It's the exact same formula being given as boosters.
tfehring 5y ago
Two doses of Pfizer's vaccine reduce hospitalization risk from Omicron by ~70% based on data from South Africa, with similar reductions across all age cohorts from 18 to 79. https://www.linkedin.com/pulse/discovery-health-releases-critical-insights-omicron-adrian-gore/ https://www.linkedin.com/pulse/discovery-health-releases-cri...

Symmetry 5y ago

I think it's more like, after a vaccination or infection you're now producing 20 different antibodies targeting different sites on the Covid spike. You start out producing high levels of the antibodies and less over time, but when you encounter the same virus you ramp up production of all 20 if your levels weren't high enough to prevent infection in the first place. With Omicron maybe only few of those antibodies still work and not as well. That won't be enough to prevent infection. But you can still ramp up production of the ones that work after infection and your body has a good blue print, though the wonders of memory B cells and somatic hypermutation, to start work on more effective Omicron specific antibodies that makes the process easier than developing covid antibodies from scratch.

lamontcg 5y ago
You're missing T-cells. There's something on the order of 1,000 T-cell epitopes against spike, not just 20, and some of them are densely packed in areas of the spike protein that are highly conserved. The spike is cleaved by proteosomes into small segments and those segments are attached to MHC-I in the ER and then shipped off to be expressed on the cell-surface to be identified by T-cell receptors. Those segments are long enough to be recgonized, but small enough that there's a ton of them (and since they're cleaved an no longer attached to the rest of the protein there's no steric hindering or conformation changes or any of that to worry about). And there's still about 80% overlap between Omicron and Delta/Wuhan-hu-1. That number will probably never get down to zero due to the highly conserved areas. CD4+/CD8+ T-cells will therefore still be able to identify infected cells and lyse them or drag them back to have a discussion with some memory B-cells. That is where somatic hypermutation might be important since some of those antibodies will match Omicron's spike and those B-cells can then be amplified and you can get Omicron-specific antibodies being produced -- all without having to start entirely from scratch. But its the CTLs that already identify the Omicron-infected cells which will do the bulk of responding to the virus and clearing the infection. This is also why we don't need to rush to update vaccines to be Omicron-specific or why neutralizing abs really matters that much at all (and if there's Original Antigenic Sin it really may not matter much at all since there may not be much Omicron-specific B-cell or Nabs response to an infection or variant-specific vaccination at all). > SARS-CoV-2 human T cell epitopes: Adaptive immune response against COVID-19 > Over the past year, numerous studies in the peer reviewed and preprint literature have reported on the virological, epidemiological and clinical characteristics of the coronavirus, SARS-CoV-2. To date, 25 studies have investigated and identified SARS-CoV-2-derived T cell epitopes in humans. Here, we review these recent studies, how they were performed, and their findings. We review how epitopes identified throughout the SARS-CoV2 proteome reveal significant correlation between number of epitopes defined and size of the antigen provenance. We also report additional analysis of SARS-CoV-2 human CD4 and CD8 T cell epitope data compiled from these studies, identifying 1,400 different reported SARS-CoV-2 epitopes and revealing discrete immunodominant regions of the virus and epitopes that are more prevalently recognized. This remarkable breadth of epitope repertoire has implications for vaccine design, cross-reactivity, and immune escape by SARS-CoV-2 variants. https://www.sciencedirect.com/science/article/pii/S1931312821002389 https://www.sciencedirect.com/science/article/pii/S193131282...

api 5y ago

> There is still substantial (lessened, but not as drastically lessened) protection against serious illness / death. My understanding so far is that the vaccine is much better at blunting the effects than preventing infection generally, even with "classic" COVID and delta. In Ohio where I live the statistic so far has been that >90% of all hospitalized cases are unvaccinated, and of the ~10% who are vaccinated the majority have other conditions that boost risk of severe COVID such as being immunocompromised, diabetes, obesity, etc. There are very very few healthy vaccinated people in the hospital.

squarefoot 5y ago

This, a million times. Over here 80-90% of Covid patients in ICUs are either never vaccinated or in need of a boost because of too much time past since their 2nd shot. So, yes, vaccination may not prevent being infected, but for sure it helps immensely in avoiding being hospitalized and shortening the infection, which does actually translate in less people being infected. And believe me, having both lived and seen this with my own eyes, there's a world of difference between staying home 2-3 weeks with a strong cough and living 2 months in an ICU with chances of being carried out from there in a brown bag.

didjathinkmess 5y ago
>So, yes, vaccination may not prevent being infected, but for sure it helps immensely in avoiding being hospitalized and shortening the infection, which does actually translate in less people being infected. On the flip side, infections in the vaccinated who are asymptomatic are more likely to leave the house, simply because they have no idea that they're sick. Perhaps they end up at a restaurant with their mask off and turn into a literal super spreaders (if we're to believe Omicron is 4X more transmissable). This was always a potential problem with vaccines that only reduce symptoms and don't prevent transmission. If Omicron is indeed mild and highly contagious as officials in South Africa claim, this could be a huge issue with anyone vaccinated.
- lamontcg 5y ago
  Transmissions and symptoms are roughly correlated through viral load. The household attack rate of ultimately asymptomatic infections is much lower than ultimately symptomatic. The window for vaccinated people is also shorter since mRNA loads peak at about the same levels (where the entry criteria for the study was the same level of symptomology) but they decline faster and have less culturable, infectious virus for the same level of mRNA load. And delta already spikes viral loads much, much higher in the presymptomatic phase of an infection (doesn't matter if its naive, breakthrough or reinfection) so that people are walking around spreading it before they know they have it. That ship already sailed. Once someone is infected, then its better that they get less symptoms and less viral load / less shedding and that they're vaccinated.

Abishek_Muthian 5y ago

Is there data about infection + two doses of vaccines against omicron? Scientists/Doctors in India have been claiming that's the best combination of protection one could have and if true that would cover significant chunk of our population. There seems to be data from UK that two doses of type-X vaccine followed by a booster of type-Y vaccine being more effective against Omicron. Different types of vaccines platforms being mRNA vaccines(Pfizer, Moderna etc.), Inactivated whole virus vaccines(CoVaxin,CoronaVac etc.), Pure DNA Vaccine(Zydus), DNA vector vaccines(Astrazenica/Covishield etc.) and upcoming protein subunit vaccines.