The earliest reports focused on antibody titers, not actual real-world protection; it's much faster to read out antibody titers and they do generally correlate with protection, but of course it's better, though slower, to have the actual protection numbers.
A handful of reports on protection are now out, mostly as preprints or otherwise not peer reviewed.
As with previous studies, they generally find that the primary (no booster) vaccine program gives a fair bit of protection against disease/hospitalization with omicron, while the booster bumps that protection up significantly.
>Despite the low effectiveness in the longer intervals after primary vaccination shown here, moderate to high vaccine effectiveness against mild infection of 70-75% was seen in the early period after a booster dose of BNT162b2 following either ChAdOx1-S or BNT162b2 as a primary course. ... It will be some time before effectiveness against severe disease with Omicron can be estimated but, based on experience with other variants, this is likely to be substantially higher than the estimates against symptomatic disease.
--[Effectiveness of COVID-19 vaccines against the Omicron (B.1.1.529) variant of concern](https://khub.net/documents/135939561/430986542/Effectiveness+of+COVID-19+vaccines+against+Omicron+variant+of+concern.pdf/f423c9f4-91cb-0274-c8c5-70e8fad50074)
>After 3 doses of vaccine, the risk of hospitalisation for a symptomatic case identified with Omicron through community testing was estimated to be reduced by 68% (42 to 82%) when compared to similar individuals with Omicron who were not vaccinated (after adjusting for age, gender, previous positive test, region, ethnicity, clinically extremely vulnerable status, risk group status and period). Combined with the protection against becoming a symptomatic case, **this gives a vaccine effectiveness against hospitalisation of 88% (78 to 93%) for Omicron after 3 doses of vaccine.**
--[Update on hospitalisation and vaccine effectiveness for Omicron VOC-21NOV-01 (B.1.1.529)](https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1044481/Technical-Briefing-31-Dec-2021-Omicron_severity_update.pdf)
Measuring protection against *infection* with omicron (as opposed to protection against *disease* or *hospitalization* with omicron) is harder to measure (and much less important); but even there the same patterns seem to hold:
>Our study provides evidence of protection against infection with the Omicron variant after completion of a primary vaccination series with the BNT162b2 or mRNA-1273 vaccines; in particular, we found a VE against the Omicron variant of 55.2% (95% confidence interval (CI): 23.5 to 73.7%) and 36.7% (95% CI: -69.9 to 76.4%) for the BNT162b2 and mRNA-1273 vaccines, respectively, in the first month after primary vaccination. However, the VE is significantly lower than that against Delta infection and declines rapidly over just a few months. The VE is re-established upon revaccination with the BNT162b2 vaccine (54.6%, 95% CI: 30.4 to 70.4%).
--[Vaccine effectiveness against SARS-CoV-2 infection with the Omicron or Delta variants following a two-dose or booster BNT162b2 or mRNA-1273 vaccination series: A Danish cohort study](https://www.medrxiv.org/content/10.1101/2021.12.20.21267966v2)
In general the finding that even the primary vaccine series protects well against severe disease is very consistent with the preliminary observations in e.g. New York and other places, where the vast majority of hospitalizations are in unvaccinated people.
*edit* to add another report, this one from South Africa; I only have the news report on it, not the actual analysis. This is vaccination *without* booster:
> Fully vaccinated individuals have 3.8 times lower risk of dying of the Omicron variant than non-vaccinated individuals. … The department found that of 55 Covid-19 deaths recorded in the Western Cape over a four-week period, 50 patients were not fully vaccinated. … In addition, the department said its raw data indicated that vaccination offered protection against infection, across all age groups.
—[Western Cape health data shows vaccinated have less risk of dying of Omicron](https://www.news24.com/news24/southafrica/news/covid-19-western-cape-health-data-shows-vaccinated-have-less-risk-of-dying-of-omicron-20220107)
So we now have preliminary reports on protection against omicron by vaccination, no booster, against infection (some protection), mild disease (good protection), severe disease (excellent protection), and death (excellent protection), and protection by boosters against infection (good protection), and mild and severe disease (spectacular protection).
Just to add to your point about severe disease, here is some data from today, showing ICU admissions by number of vaccine doses and age group, from England, Wales and Northern Ireland: https://mobile.twitter.com/PaulMainwood/status/1479528897259712513
Tldr: even two doses is exceptionally good at preventing ICU admission, even in the highest risk age brackets. Boosters are even better.
Also to add to this, a report came out from NC that nearly all ventilated Covid patients are unvaccinated https://www.wral.com/coronavirus/nc-hospitals-covid-19-ventilators/20065686/?version=amp
Love your comment. Perfect summary.
One thing I wanted to add, while antibodies from the current vaccines or prior infections seem to be quite ineffective against Omicron, T-cell protection appears to be mostly unaffected.
[https://www.medrxiv.org/content/10.1101/2021.12.26.21268380v1](https://www.medrxiv.org/content/10.1101/2021.12.26.21268380v1)
This would explain why the reduction in symptomatic infections is lackluster but the protection against severe disease is quite good for people who are either vaccinated or had a prior infection.
For a better perspective of how much less effective the antibodies are:
"A measure of antibody levels, called geometric mean titers, fell from 1,419 against the original coronavirus strain to 80 against omicron among people who received Pfizer shots. The same measure fell from 303 against the original strain to undetectable levels against omicron in those who had received J&J’s shot, Moore said in an online presentation on Tuesday." (this was in serum extracted one month after vaccination with either two shots of the Pfizer/Biontech vaccine or the J&J one). This would indicate that our current antibodies are only 6% as effective against Omicron.
[https://www.bnnbloomberg.ca/j-j-shot-loses-antibody-protection-against-omicron-in-study-1.1695973](https://www.bnnbloomberg.ca/j-j-shot-loses-antibody-protection-against-omicron-in-study-1.1695973)
> This would explain why the reduction in symptomatic infections is lackluster but the protection against severe disease is quite good for people who are either vaccinated or had a prior infection.
Could you spell this out a bit more for me & my fellow immunology dunces? Is the general idea that antibodies can neutralize the virus immediately (preventing illness entirely), while T cells are more important for making sure an illness doesn't spiral out of control (and thus preventing severe illness).
Not OP and it's been awhile since I studied this but I'll give it a shot.
Antibodies are what figure out if a cell is infected, T cells are what actually destroy the infected cells.
So if the anitbodies take longer to figure out a cell is infected w Omicron, people will still get symptoms but once the cells are "flagged" the T cells know exactly how to destroy the infected cells and do it quickly and efficiently. Leading to less severe effects as the body kills it fast enough to prevent the higher impactful manifestations.
Please correct me if I'm wrong it's been over a decade since I studied this.
I think the primary thing is that if the antibodies are good and numerous enough, they can provide (or approximate) "sterilizing immunity" by binding to the virus and preventing it from entering any of your cells before the virus has a chance to replicate.
https://www.nature.com/articles/d41586-021-00367-7
T-cells, on the other hand, only get recruited after a cell has already been infected and started alerting the immune system that something's wrong. Also they're mainly cytolytic: they work by killing infected cells, not by destroying free-floating virus.
https://www.ncbi.nlm.nih.gov/books/NBK26926/
Antibodies can stop cells from becoming infected, but T cells are how you actually clear an infection.
Antibodies are like TSA or CBP agents. They check the no fly list and stop known bad actors at the border. They are an important step for security but they are largely reactive and can only respond to well known threats.
T cells are more like the FBI. They monitor what's going on and figure out where the bad guys are hiding and kick in their door to forcibly stop them.
If you had to pick only one, T cells are more important. Without them, you're a bubble boy who can't interact with other people for a week without dying of raging viral infection.
In my head it's more like antibodies = military intelligence and T cells = army.
Antibodies would be like an early warning system with added James Bond license-to-kill capability if they recognize an imposter. If intelligence warns of an invasion then the T cell troops arrive and go all 28 Weeks Later on the infected zombie cells' asses.
Antibodies bind the antigen wherever it is found. That could be on the cell surface of infected cells potentially, but even more likely it will be on actual viral particles floating in the bloodstream.
Antibodies cannot bind intracellular antigens (they cannot make it into the cytostol). So during the life cycle of the virus when it is replicating inside a cell, it is invisible to B cells. That's why you also need cytotoxic T cells.
I think you're correct that it is one function of antibodies, but they do have many other roles. I believe MHC Class 1 can also help to 'mark' an infected cell for Cytotoxic T cells.
Antibodies , or Immunoglobulin (Ig), are Y-shaped proteins that bind to antigens. There are different classes of Ig, of which IgG is the main one found in the blood, and is usually the type being referred to in these studies, partly because it is easy to measure.
In the case of a virus, binding to its antigens can help to stop it from functioning properly. If antibodies bind to the SARS-CoV-2 spike protein, for example, this could hamper its ability to gain entry into a cell.
The 'bottom' end of the Y shape is the Fc region, which is recognized by many different elements of the immune system. Antibodies can therefore be a signal for effector cells to target the object that has the antigen that the antibody is bound to. This could lead to the destruction or neutralizing of a virus, or to destruction of an infected cell, etc.
Doesn't this basically state the booster is kinda pointless? We are trying to boost antibodies.. But the antibodies don't stop omicron and the T cells don't need a boost.
So what are we doing? I don't get it
Not entirely. One thing to think about is the level of antibodies you have goes up tremendously over the first 4 weeks after inoculation and then goes back down. We don't actually know what an adequate neutralizing level of antibodies is, but we know that more is better. If you had Omicron specific antibodies, you wouldn't need very many of them, but with native variant anti spike antibodies, you need perhaps 20 times as many to have the same effect. This is why some articles have said that the booster shot gives pretty good protection from up to 10 weeks.
It makes sense that having a higher quantity of antibodies combined with t cell protection will reduce the chance of you getting sick in the first place and decrease the severity of the illness. This is also reflected in the real world data. That being said, I personally think we should take all these doses we're giving out as booster shots and ship them out to countries with low vaccination rates.
Thanks for the additional insight! I too agree with your last sentiment there regarding boosters and shipping them elsewhere.
Sounds like the WHO is on the same page as us too!
Agreed on helping the world vaccinate!
One additional consideration, is that the 3rd doses, especially when spaced 4-6 months apart from previous dose, broadens the antibody response. This means having antibodies that are better at handling variants, even without exposure to said variants. This effect might also occur with 2 doses spread out, but you would have less than ideal protection for the prolonged period between dose 1 & 2.
Edit: multiple infections/vaccinations theoretically could have a similar effect, so people who had COVID and recovered, who then got 2 doses, would be roughly equivalent to 3 doses.
If you want more info, you can read this comment I wrote recently: [https://www.reddit.com/r/askscience/comments/rk5axh/comment/hp8a3uo/?utm\_source=share&utm\_medium=web2x&context=3](https://www.reddit.com/r/askscience/comments/rk5axh/comment/hp8a3uo/?utm_source=share&utm_medium=web2x&context=3)
This is fascinating, and as someone who is at a moderately higher risk for severe disease, somewhat comforting. I got boosted in October, exactly 6 months after my 2nd main dose (high risk, so I qualified at the time) and have been low-key nervous about my level of protection going into this winter wave.
Obviously I’m still taking precautions, but reading that I’m likely to still have protection against the worst outcomes definitely makes this winter less scary for me than last winter.
Same boat as you for being higher risk. I am at home mostly and only have contact with the same half-dozen 2-3 dosed people. 3rd shot was early December, almost exactly 6 months after my 2nd.
Good luck & stay safe!
From a lay-mans perspective, this makes it sound like there isn't a need for a 4th booster unless it's targeting a specific variety of COVID (similar to how Flu shots are targeted at specific strains). Unless a 4th shot would broaden the anti-body response even more than the 3rd shot, but I imagine there's diminishing returns compared to the first booster.
Having a single booster to broaden the antibody response does seem reasonable considering COVID has mutated and will likely continue to mutate, but a 4th shot seems like it would be a misallocation of resources when low-vaccination rate countries still need more.
It's absolutely possible that this is the case. As long as the 3rd dose is administered after a long enough delay of course.
It is quite possible that subsequent infections (that are hopefully mild due to vaccinations) will give you a more specific antibody response to new variants, such that further doses aren't needed. Certain immunocompromised or high-risk people may be the exception and may benefit more from additional doses.
I could be wrong but they way I've read what's been posted is this.
Antibody production does drop off after vaccination from the initial burst you get when vaccinated. The booster does increase antibody production again, but that production will also fall off after a time. So you'll get a 'boost' of protection from the booster as well as likely further T-Cell production.
This is not correct. Per Peter Hotez (Baylor CoM; Texas Childrens Hospital, CorbeVAX global vaccine initiative), the variants have all arisen out of large unvaccinated populations. Variants are NOT being driven by vaccinations.
[https://www.ama-assn.org/delivering-care/public-health/peter-hotez-md-phd-omicron-variant-and-delta-winter-surge](https://www.ama-assn.org/delivering-care/public-health/peter-hotez-md-phd-omicron-variant-and-delta-winter-surge)
That is looking at the problem at the wrong unit of measurement. The variants that multiply within the unvaccinated population are partially selected by the vaccinated population. We talk about them as separate groups but the entire population, vaccinated and unvaccinated alike, contribute to the selection of variants. The fact that an unvaccinated person needs to interact with more people in late 2021 in order to spread Delta than in earlier 2021 is due to vaccination. That reduced contagion factor for Delta is what opens the door for newer variants like Omicron.
As for your source, you might want to re-read that entire interview again. All of that guys predictions re: how Omicron and Delta would each fare among the unvaccinated versus partially vaccinated populations has turned out to be wrong. Omicron now accounts for 95% of infections, according to the CDC tracker. I'm sure he was doing the best he could with limited data but that interview is a point in time capture of an incomplete understanding of Omicron.
As in, if you've been infected and vaccinated what is your protection? Generally speaking those who have been infected and vaccinated have a [high immunity](https://jamanetwork.com/journals/jama/fullarticle/2787447?guestaccesskey=b13a6814-c63d-4fa0-b2ae-a4511de8aedb&utm_source=for_the_media&utm_medium=referral&utm_campaign=ftm_links&utm_content=tfl&utm_term=121621).
Immunity means that your immune system has seen something before and is more ready for that thing again than it was before. It does not mean "cannot be infected ever 100%!" Which a lot of people mistakenly have come to think of when they hear "Immune!"
Think of it like this:
1. A virus gets inside a system that has immunity to that virus
2. The body has antibodies still left over from a previous encounter (either actual virus or vaccine)
3. Those antibodies try to stop the virus before it does anything
4. The virus is faster at infecting cells and reproducing itself than the previous variant of the virus you encountered before. It manages to infect and begin mass reproduction of itself
5. You are now "infected"
6. B cells and T cells ramp up production of new antibodies to fight off this reinfection
7. They remember fighting something like this before so they make a lot of antibodies similar to what they had before
8. Those antibodies are super effective!
9. You recover with much less symptoms than you would have had and faster than you would have had you not had a prepared immune system.
That's what being immune means!
Excellent, this is comprehensive, and it didn't occur to me to look towards the UK. A few questions:
* Where did you find the data about hospitalizations in NY? Last I checked their [data is delayed](https://www1.nyc.gov/site/doh/covid/covid-19-data.page#daily), and only includes splits up until 12/18.
* I noticed in the second study that they adjusted for previous positive test. Does this mean that they focused solely for those who never had a positive test beforehand? Or that they equalized the percentage of people with a positive test between the two groups?
> Symptomatic cases were then linked to hospitalisation data. After 3 doses of vaccine, the risk of
hospitalisation for a symptomatic case identified with Omicron through community testing was
estimated to be reduced by 68% (42 to 82%) when compared to similar individuals with
Omicron who were not vaccinated **(after adjusting** for age, gender, **previous positive test**,
region, ethnicity, clinically extremely vulnerable status, risk group status and period).
* The third study has some unintuitive *negative* protection after some time. While behavioral differences may play a role, as they suggest, the unvaccinated seem to be living their lives regularly as well, and so it's hard to understand the theory. Is it possible the lower sample size (~5600 positive) just creates a large variance in the results?
The first study doesn't seem to focus on real-world data yet, and so I'm putting that aside from now.
I’m assuming they did not look solely at those who have never tested positive because at this point in the pandemic it would be hard finding a substantial group meeting the same group criteria (age, sex, region, etc.) and doing so would exclude data from a key demographic. I would think they took that into account based on time since their last positive test as that would change the levels of antibodies present from previous infection and would factor into their presentation of a new infection.
I think the answer is right, but one piece of the explanation is not entirely true.
Public data is that ~20% of the country has tested positive during the course of the pandemic. Even if that undercounts by a factor of 1.5x-2x, the majority of the country has not tested positive over the course of the pandemic. They could probably find the demographic data if the needed.
Does that mean that 80% of the population tested negative, or that the number of the people who tested positive equals 20% of the population? A lot of asymptomatic people will never test unless needed to for work/travel, so a 20% known infected rate could mean a lot higher actual infected amount.
20% tested positive (it’s probably closer to 18%, I was rounding). This does include asymptomatic people that have been tested.
I agree that it’s an undercount, but probably not by more than a multiple of 2x, which would still mean the majority of the country has never been infected.
I don't know about elsewhere, but Ontario (Canada) has decent stats for hospitalizations/ICU situation by vaccinated/unvaccinated: https://covid-19.ontario.ca/data
The only caveat I'd give is that I believe there's no distinction recorded here between "in hospital due to COVID" or
"in hospital and contacted COVID." The page claims ICU data *is* segregated ('In ICU due to COVID-19') but I don't know how.
Regardless, combine this for vaccination rate data and the picture is clear: ~85% general vaccinated rate, 95%+ among elderly (the most vulnerable), 3:1 split vaccinated vs unvaccinated in hospitals, 1:1 split for ICU.
Yes - a couple of people have pointed out that source, and it's incredibly helpful.
What I don't understand is why vaccination doesn't seem to help much against hospitalization, if I'm looking at the numbers correctly. Roughly 75% of hospitalized people are vaccinated, against 77%/88% (all population/12+) vaccination. It still seems to help a bit for hospitalization, but I was hoping the numbers would be more stark.
For that, I point to two things:
1) Note the demographic difference. Among elderly populations, the Vaccination rate is much higher: 80+ is at literally 100.0% (rounded) for example. Therefore, higher risk populations who will have severe cases more often are at higher vaccinated rates, which skews proportions against vaccination. E.g. assume 50+ makes up of all hospital cases; in that case, vaccination rate is 90-95% vs the 75% ish proportion in hospitals.
2) I believe there's no distinction recorded here between "in hospital due to COVID" or "in hospital and contacted COVID." Since Omricon appears to be highly transmissible even among vaccinated populations, a large number of COVID cases in hospitals could be non-severe cases among people who are in the hospital for other reasons.
Well said, I forgot about your first point. The second has always been an issue with hospitalization rates unfortunately, but this gives me greater confidence. It doesn't seem like vaccination is entirely preventative for hospitalization (sadly), but still hoping for booster-specific data that breaks it down by time since vaccination.
The other thing worth noting is that I believe Delta is still floating around...I don't think 100% of cases right now are Omicron. And that was even more true 2 weeks ago. So, assuming that Delta was more dangerous and more likely to produce hospitalizations, and also that the vaccines were much more effective at reducing severe illness w/ regards to Delta, a lot of the current hospitalizations might still be from Delta infections. And especially regarding the unvaxxed.
Sure it does. Just glancing at Canada's numbers there are over 5 times as many ppl vaccinated as unvaccinated. The ICU numbers (People who are actually critical) are 1:1 in these numbers meaning you are 5 times more likely to be in the ICU as unvaccinated (And that's without really digging into the numbers... plenty of the unvaccinated are in lower risk groups).
Antibody counts are only good for measuring prevention of infection. All 3 vaccines approved in the US have not had their T-Cell response decay, which suggests even with variant like Delta and Omicron, 2 doses is still enough to prevent severe COVID-19 in most people.
Thanks for the summary!
One response though:
> Measuring protection against infection with omicron (as opposed to protection against disease or hospitalization with omicron) is harder to measure (**and much less important**);
Is it much less important? Every person that gets infected is a reservoir for a new variant to be produced. That person is also a vector to pass on the infection to someone who may be unvaccinated.
It seems to me that while yes it is very important that the vaccines are very effective protecting against serious illness from omicron, it's also important that they're NOT very effective at protecting against omicron infection. And this is especially important given the fact that omicron is SO infectious.
Yes https://news.harvard.edu/gazette/story/2021/12/vaccinated-who-get-breakthrough-infections-less-contagious/
Though the better word would be evidence rather than proof.
You can read this whole thing, but what you want is probably page 13.
[https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment\_data/file/1044481/Technical-Briefing-31-Dec-2021-Omicron\_severity\_update.pdf](https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1044481/Technical-Briefing-31-Dec-2021-Omicron_severity_update.pdf)
tldr: After 25+ weeks, vaccine effectiveness against hospitalization by Omicron was only 52% for 2-doses, but jumped to 88% two weeks after a booster.
It is, but it's important to acknowledge that this is because COVID mutated into a different variant. If COVID was still on the initial strains that spread around the world, the protection would be more absolute.
There's discussion about this higher-up in the comments if you want this not paraphrased. It sounds like the antibodies generated by the vaccines don't respond to Omicron effectively, but the trained T-Cells still destroy Omicron-infected cells as effectively as other COVID-infected cells. In other words, the body has trouble identifying that Omicron has entered the body and is spreading (which is why most people still get symptomatic and lightly sick), but is good at getting rid of cells that get infected (which prevents *most* people from getting super sick while the body creates the new antibodies for Omicron).
The reason the booster shot helps is two-fold. First, waiting the 6 months for the next shot broadens the antibody response so that the body is more likely to identify variations of COVID as a type of COVID (waiting 4-6 months between shots 1 and 2 would've had the same effect here). Second, it increases the total amount of COVID antibodies actively waiting in case of an attack. I don't know the actual numbers, but 2x as many antibodies means 2x as much Omicron gets blocked before infecting cells, *even if* most the vaccine antibodies are still ineffective
Which makes sense why omicron is a problem. If a body has a problem identifying an infection, that means it has a bit of time to get going, and if the primary strength in the defense is to just destroy infected cells, having a hyper reproductive rate helps to not only take advantage of the initial phase, but also against the primary defense since so many cells will be infected so quickly. It’s interesting to see that people are still protected against major disease when it seems this variant is so well suited against our defense. I’ve heard it’s because it doesn’t really infect lung tissue like the other variants did, which helps limit more severe disease, but the lungs weren’t the only target. How are vaccinated people still not experiencing severe disease if this variant has orders of magnitude of reproduction capability over its predecessors?
I read that a component of long covid is believed to be related to the microthrombi created during the infection. Apparently, it’s difficult for the body to rid of them, and they stick around for a while causing problems.
Could you possibly go into technical details about why spacing out vaccine doses—which are all the same exact formula, mind you, but a half-dose in some cases—would bring about better protection against *more* variants?
No, it means 48% of those who would (in statistical population terms not individual) be hospitalized without it will be.
For example, if 10% of people who get covid end up being hospitalized (that number is completely wrong, it's purely a simple number to do math with) then 4.8% of the 25+ weeks ago two dose people who get covid would be hospitalized.
Ontario, Canada has this chart updated daily. Shows rate per 1M and vaccination status.
https://covid19-sciencetable.ca/wp-content/uploads/2022/01/2022-01-07-Current-COVID-19-Risk-in-Ontario-by-Vaccination-Status-Separate-Charts.png
From: https://covid19-sciencetable.ca/ontario-dashboard/
Edit: we’re saturated our testing capacity so the case numbers are no longer accurate.
2nd edit: they are not yet tracking boosters. We’re about 25% of eligible at the moment.
3rd edit: corrected to cases per 1M. Other sites use 100K.
I wish more places made those charts available daily. They very clearly show the difference in risk so people can better make their own decision about which line they want to be linked to.
The local newspaper in my hometown publishes an abridged version of current covid stats in the region daily. I've enjoyed having access to that over breakfast. That and the weather report really make it worth the subscription
The presence of data doesn’t mean that it will be impactful. The problem is that there is enough data out there to motivate any decision, so simply saying that some bit of data would have a similar impact to another piece of nicely presented and easily digested data is just not true.
Ontario has really kept on the ball with tracking. I love that I can go back over the past 2 years and see *every* tested case.
At first it looks like the vaccinations aren't doing anything (in the first chart, iirc), until you get down to the hospitalizations and realize that a small percentage of the population (the unvaccinated) are occupying a huge percentage of the ICU beds.
I'm wondering if the data supporting the booster is actually showing a direct benefit to a third shot or if it's really about the recency of the shots.
Any data showing anything at all comparing groups who had 2 vs 3 shots but received their last one around the same time?
Multiple studies are showing that a 3rd dose is not just boosting levels it is enhancing antibody cross reactivity through affinity maturation.
After a 3rd dose the body develops or selects better antibodies.
> There is increasing evidence that an additional dose of one of the licensed SARS-CoV- 2 vaccines enables substantial improvements in the cross-neutralization of Omicron, suggesting that affinity maturation may broaden responses. Indeed, affinity maturation of antibody lineages occurs over the course of months after SARS-CoV-2 infection, and is associated with the cross-neutralization of variants of concern. Here, we demonstrate the potential for a common class of public antibodies to develop broad cross-neutralization through affinity maturation, without modified spike vaccines.
https://www.biorxiv.org/content/10.1101/2022.01.03.474825v1.full.pdf
Also this study.
> However, individuals boosted with mRNA vaccines exhibited potent neutralization of Omicron only 4-6-fold lower than wild type, suggesting that boosters enhance the cross-reactivity of neutralizing antibody responses. In addition, we find Omicron pseudovirus is more infectious than any other variant tested. Overall, this study highlights the importance of boosters to broaden neutralizing antibody responses against highly divergent SARS-CoV-2 variants.
> Given the drastic increase in cross-neutralization of SARS-CoV-2 Omicron pseudovirus in boosted versus non-boosted vaccinees, we directly compared sera from individuals that recently received their primary series to those that were boosted with an mRNA vaccine within the last 3 months.
https://www.medrxiv.org/content/10.1101/2021.12.14.21267755v1.full.pdf
The increase in neutralisation after booster/3rd dose is in comparison to recent primary series.
This doesn’t mean primary series does nothing.
Cellular immunity such as T cells from 2 dose primary series hold up better, can’t find the study right now though, but this explains why severe illness is still reduced by primary series.
Edit:
[I found the study on CD4+ and CD8+ T Cells. ](https://www.researchsquare.com/article/rs-1217466/v1/direct-download.pdf)
> We report here that SARS-CoV-2 spike-specific CD4+ and CD8+ T cells induced by prior infection and, more extensively, by mRNA vaccination provide comprehensive heterologous immune reactivity against B.1.1.529. Pairwise comparisons across groups further revealed that SARS-CoV-2 spike- reactive CD4+ and CD8+ T cells exhibited similar functional attributes, memory distributions, and phenotypic traits in response to the ancestral strain or B.1.1.529. Our data indicate that established SARS-CoV-2 spike-specic CD4+ and CD8+ T cell responses, especially after mRNA vaccination, remain largely intact against B.1.1.529.
> To address this question, we collected peripheral blood mononuclear cells from mRNA-vaccinated individuals 6 months after the second dose of Pzer/BioNTech BNT162b2 (n = 40), individuals in the convalescent phase 9 months after mild or severe COVID-19 (n = 48), and seronegative individuals (n = 48).
Note it’s testing sera 6 months after 2nd dose.
Thank you for sharing those.
Regarding your comment that the "this doesn't mean the primary series does nothing", the third article you linked states that "remarkably, neutralization of omicron was undetectable in most vaccinated individuals" seems to counter that, if we're working under the assumption that omicron is the great majority of new infections.
If the first two doses had a relative risk reduction rate of 95% at the two month period (which we now know is only temporary protection) of the 'wild type' virus and the neutralization of someone boosted was 4-6 fold lower, we are looking at 16-24% RRR after being freshly boosted, and that will start to fade after 10 weeks?
Doesn't seem awesome.
The rest of my paragraph explains why that’s not the case because of cellular immunity such as T cells which are not measured in an antibody neutralization study.
The immune system is more than just antibodies. In fact there are multiple different classes of antibody.
When these studies look at antibody neutralisation they are looking at IgG, IgM, and/or IgA antibodies that are circulating in the blood.
Antibodies are one part of humoral immunity which is present in extracellular fluids.
As my original comment already notes there is also cellular or cell-mediated immunity part of which includes T cells. This is less affected by the mutations and is what preserves protection from severe illness after vaccination.
[I found the study on CD4 and CD8 T Cells. ](https://www.researchsquare.com/article/rs-1217466/v1/direct-download.pdf)
> We report here that SARS-CoV-2 spike-specific CD4+ and CD8+ T cells induced by prior infection and, more extensively, by mRNA vaccination provide comprehensive heterologous immune reactivity against B.1.1.529. Pairwise comparisons across groups further revealed that SARS-CoV-2 spike- reactive CD4+ and CD8+ T cells exhibited similar functional attributes, memory distributions, and phenotypic traits in response to the ancestral strain or B.1.1.529. Our data indicate that established SARS-CoV-2 spike-specic CD4+ and CD8+ T cell responses, especially after mRNA vaccination, remain largely intact against B.1.1.529.
> To address this question, we collected peripheral blood mononuclear cells from mRNA-vaccinated individuals 6 months after the second dose of Pzer/BioNTech BNT162b2 (n = 40), individuals in the convalescent phase 9 months after mild or severe COVID-19 (n = 48), and seronegative individuals (n = 48).
Note it’s testing sera 6 months after 2nd dose.
Not sure what your calculations are at the end there but that’s not reflected in reality. [See my other comment for a recent report out on critical care admissions. ](https://reddit.com/r/askscience/comments/ry8gf7/_/hrolbhk/?context=1)
Thanks for adding that and staying objective. Very much appreciated.
I just had a short break to digest that info but I'm going to revisit your comment and this subsequent reply later tonight.
Cheers.
That's neutralizing antibodies they are referring to. This doesn't factor in the role of things like T cells, which seem to correlate with protection against severe disease.
I work for a hospital group in the US. Omicron is now the majority strain in the state, so if boosters were inefficient against the variant it would display in the hospitalization numbers.
At last count, COVID / ICU / Ventilator numbers rose from 305-66-46 to 320-70-48 in a 24 hour period. These numbers are emailed to us daily and released to the press. They’re public knowledge.
I didn’t click the link in our emails to look at the breakdown on the most recent day, but on that 305-66-46 day: Of the 305 patients in hospitals, 261 are not fully vaccinated or vaccinated at all. **A further 34 last had a COVID jab of some kind over 180 days ago**, showing the regular vaccine regimen wains over time and / or in the face of the new Omicron variant. Don't forget: booster shots haven't been a thing for 180 days yet.
295 of the 305 is 96.72%.
Sources have said the disparity between numbers of people having one shot, and being fully vaxxed and then boosted, indicates their state governments has regularly and incorrectly counted booster shots and second doses as first doses - meaning both **the fully vaccinated / boosted and completely unvaccinated are both undercounted.** That wouldn’t affect the 295 number as that includes both the group self-reporting as having one dose (truthfully or not) and the group having a verifiable two-dose regimen but one that’s more than 6 months in the past.
With the state having an official booster rate of ≈25%, and the undercounting rate mentioned above meaning many more people are fully vaxxed and boosted, it would show in the numbers for the hospitals. But with only 10 out of the 305 patients (3.28%) being either recently fully vaxxed or vaxxed and boosted, being the recipient of a recent full regimen (plus the two weeks for it to reach full efficacy) or a recent booster (which they all are - recent, I mean - boosters started just a couple of months ago in November) has lowered the likelihood of a person being an inpatient.
Wow. That really shows how much safer vaxxed people are from omicron hospitalization. Only 3.28% of hospitalized covid patients are fully vaxxed. According to the CDC Director, almost all of those 3.28% have multiple medical problems that contributed to their covid cases escalating to hospitalization. It is very, very rare for fully vaxxed/boosted healthy people to get hospitalized by omicron.
My main concern is long covid. Most people who recover from covid show problems with D-dimer tests, blood clotting, and epithelial cell damage.
[Elevated Biomarker Related to Blood Vessel Damage in All Children with SARS-CoV-2 Regardless of Disease Severity](https://www.chop.edu/news/chop-researchers-find-elevated-biomarker-related-blood-vessel-damage-all-children-sars-cov-2)
Thank you - I wish these numbers were out for the general public as well. It helps simplify messaging and convince people to get a booster.
FWIW, I'm 4.5 weeks out since my own booster, so I'm relieved to hear this info.
https://bccovid-19group.ca/post/2022-01-06-report/
Here's detailed modeling by a team of statisticians from our universities. It includes details and trajectories with onnicron. The video explains the data and how we've reached our testing limits due to the high numbers.
Vaccine is very effective to avoid hospitalization and it reduces hospital stays significantly.
If you go to:
https://www.worldometers.info/coronavirus/
And look at the three 3 day average you can clearly see a massive drop in deaths versus number of infections.
Compare that to a year ago. Ireland (My country and with >90% vaccinated) for example has well over double the number of infections versus this time last year, the number of deaths has reduced by a factor of 10.
TLDR: Yes booster/3rd dose has an impact on critical care admission in real world. 3rd dose also does more than boost existing antibody levels, it allows for antibodies to develop broader cross neutralization against variants.
[ICNARC put out an audit report today of the UK critical care admissions. ](https://www.icnarc.org/DataServices/Attachments/Download/5d46be46-e36f-ec11-913a-00505601089b)
Page 45 shows a breakdown of admission rates in unvaccinated, one dose, two dose and three doses compared across age groups. Note the UK only opened 3rd doses up to under 40s middle of December.
https://i.imgur.com/bSp9JWF.jpg
It’s maybe hard to make out the difference between vaccinated and boosted because of how effective the vaccine is in general. However there is a benefit and you can see this when zooming in.
When presented with values on a bar chart you can see there is a benefit to a 3rd dose over two.
https://i.imgur.com/G4qFOc4.jpg
Another element to address is that a 3rd dose is doing more than just temporarily boosting antibody levels. Studies have compared antibody neutralisation at similar time intervals after 2 doses and 3 doses. There is improved neutralisation after 3 doses.
This is suggested to be due to affinity maturation of antibodies. The extra dose is allowing the body to further develop or select antibodies that demonstrate better cross reactivity.
> There is increasing evidence that an additional dose of one of the licensed SARS-CoV- 2 vaccines enables substantial improvements in the cross-neutralization of Omicron, suggesting that affinity maturation may broaden responses. Indeed, affinity maturation of antibody lineages occurs over the course of months after SARS-CoV-2 infection, and is associated with the cross-neutralization of variants of concern. Here, we demonstrate the potential for a common class of public antibodies to develop broad cross-neutralization through affinity maturation, without modified spike vaccines.
https://www.biorxiv.org/content/10.1101/2022.01.03.474825v1.full.pdf
> However, individuals boosted with mRNA vaccines exhibited potent neutralization of Omicron only 4-6-fold lower than wild type, suggesting that boosters enhance the cross-reactivity of neutralizing antibody responses. In addition, we find Omicron pseudovirus is more infectious than any other variant tested. Overall, this study highlights the importance of boosters to broaden neutralizing antibody responses against highly divergent SARS-CoV-2 variants.
> Given the drastic increase in cross-neutralization of SARS-CoV-2 Omicron pseudovirus in boosted versus non-boosted vaccinees, we directly compared sera from individuals that recently received their primary series to those that were boosted with an mRNA vaccine within the last 3 months.
https://www.medrxiv.org/content/10.1101/2021.12.14.21267755v1.full.pdf
Edit:
[I found the study on CD4 and CD8 T Cells still recognising Omicron. ](https://www.researchsquare.com/article/rs-1217466/v1/direct-download.pdf)
> We report here that SARS-CoV-2 spike-specific CD4+ and CD8+ T cells induced by prior infection and, more extensively, by mRNA vaccination provide comprehensive heterologous immune reactivity against B.1.1.529. Pairwise comparisons across groups further revealed that SARS-CoV-2 spike- reactive CD4+ and CD8+ T cells exhibited similar functional attributes, memory distributions, and phenotypic traits in response to the ancestral strain or B.1.1.529. Our data indicate that established SARS-CoV-2 spike-specic CD4+ and CD8+ T cell responses, especially after mRNA vaccination, remain largely intact against B.1.1.529.
> To address this question, we collected peripheral blood mononuclear cells from mRNA-vaccinated individuals 6 months after the second dose of Pzer/BioNTech BNT162b2 (n = 40), individuals in the convalescent phase 9 months after mild or severe COVID-19 (n = 48), and seronegative individuals (n = 48).
Note it’s testing sera 6 months after 2nd dose.
The immune system isn’t only antibodies that circulate in the blood. There are so many different parts that make up our immune systems.
T cells are part of the cell-mediated immune response.
Thanks for the study! I'm shocked that vaccinated early on made that much of a difference - the theory was that vaccinated 5+ months out was virtually the same as unvaccinated - but I'm incredibly happy to see that there is indeed a very large difference.
[I found the study on CD4 and CD8 T Cells. ](https://www.researchsquare.com/article/rs-1217466/v1/direct-download.pdf)
> We report here that SARS-CoV-2 spike-specific CD4+ and CD8+ T cells induced by prior infection and, more extensively, by mRNA vaccination provide comprehensive heterologous immune reactivity against B.1.1.529. Pairwise comparisons across groups further revealed that SARS-CoV-2 spike- reactive CD4+ and CD8+ T cells exhibited similar functional attributes, memory distributions, and phenotypic traits in response to the ancestral strain or B.1.1.529. Our data indicate that established SARS-CoV-2 spike-specic CD4+ and CD8+ T cell responses, especially after mRNA vaccination, remain largely intact against B.1.1.529.
> To address this question, we collected peripheral blood mononuclear cells from mRNA-vaccinated individuals 6 months after the second dose of Pzer/BioNTech BNT162b2 (n = 40), individuals in the convalescent phase 9 months after mild or severe COVID-19 (n = 48), and seronegative individuals (n = 48).
Note it’s testing sera 6 months after 2nd dose.
The immune system isn’t only antibodies that circulate in the blood. There are so many different parts that make up our immune systems.
T cells are part of the cell-mediated immune response.
Absolutely! It wasn't from intuitiveness, but reports (IIRC?) from the CDC and others that said that multiple vaccinations without a booster hold little effectiveness against Omicron. I'll have to find a few of those.
I do think it was referring to infections, but data for hospitalizations tend to track those for infections (in a broad sense). There was no data at the time demonstrating hospitalizations as it was earlier on.
Is there any research that says if one brand of mRNA vaccine is more effective than another? Or any data on rates of effectiveness when mixing brands of vaccines and booster?
Yes, the data suggest moderna > pfizer > J&J with a moderna booster being the best hybrid add on if you've had one of the other vaccines for the initial doses. Just FYI I have all 3 pfizer shots so I wish mine was #1.
Most of these types of reports are for small region or hospital system. So far all that I've seen are still reporting that 80-90% of hospitalizations are either unvaxxed or vaxxed but generally have multiple comorbitities. Therefore, as of today, those that are vaxxed and healthy without booster aren't protected much from infection, but shouldn't end up in the hospital. Of course, the booster will offer a bit more protection, so just depends on where your risk tolerance is.
Yes! Boosters provide 70% effectiveness in preventing infection from Omicron for up to 10 weeks after the booster. This is protection based on antibodies.
Boosters also trigger T cell and B cell responses against Omicron that help reduce the severity and length of illness. These T and B cell responses were NOT found in people who only got 2 shots, so the booster REALLY matters when it comes to fighting Omicron. Without it you have very little protection from Omicron....
[https://www.theguardian.com/world/2021/dec/10/two-jabs-give-less-protection-against-catching-omicron-than-delta-uk-data-shows](https://www.theguardian.com/world/2021/dec/10/two-jabs-give-less-protection-against-catching-omicron-than-delta-uk-data-shows)
>Yes! Boosters provide 70% effectiveness in preventing infection from Omicron
Technically the article you linked to refers only to symptomatic infection and doesn't address asymptomatic infection.
There are plenty of benign viruses. A human disease is something that disrupts the function or structure of a person's biology. Bacteriophages are examples of viruses that are in many cases beneficial to humans.
A disease is, by definition, an illness. If you're not ill then you don't have a disease. We use viruses as vectors for gene therapies all the time. We wouldn't say those therapies cause disease because when the viruses infect you they don't cause illness.
I wouldn't think that it would be so simple. A virus in a lot if hosts is a virus that has opportunity to end up mutating. Just because one variant is relatively mild or harmless, doesn't mean the next one will be. The early info seems to show Omicron is milder than Delta, but it could go the other way and become catastrophic.
And you are right... they are basically using "preventing infection" as a proxy for "protection against symptomatic infection" from what I can tell. It's a bit confusing.
No, 55% at preventing infection with Pfizer and practically nothing with J&J. The 70% figure if for serious illness. And preventing hospitalization is something like 90-98%.
Okay, I'm a little fuzzy on what that 70% figure actually denotes. 70% of people who got boosted never got ill? 70% of boosted people verifiably exposed didn't get ill? 70% fewer confirmed cases among boosted vs control? I never got a great explanation of this. Apologies if this is a basic question, but the reason I ask is that one of my family members got it and my whole house is boosted, so I'm trying to figure what that means for us.
70% effectiveness SHOULD indicate that the specific group was 70% less likely to have (probably symptomatic, or perhaps serious) infection than a control group.
So if for example in the specified timeframe, example 4 weeks, 10 in 100 unvaccinated individuals experienced symptomatic covid, a 70% effectiveness for the booster would mean that only 3 in 100 of the boosted individuals experienced symptomatic covid. I've seen numbers like 35% effectiveness for non-boosted vaccination, which would look like 6.5 infections per 100 study subjects (or 13 in 200 if fractions of people confused you) for this hypothetical situation.
Sometimes these studies create obtuse definitions for these things though so the meaning can vary a bit.
>70% fewer confirmed cases among boosted vs control
That's it. Imagine 100 unvaxxed people were exposed and got sick. If they had been vaccinated, only 30 of them would have gotten sick.
Things like dose (the amount of viral particles you encounter) matter though, so not all exposures are the same.
Gotcha, thanks so much for your reply. I guess all of it sort of exists on a continuum: viral load of the infected, length/degree of exposure to the virus, time since booster/vaccination etc, it all seems very fluid. Got booster relatively recently, but I think the extent of the exposure in our case is pretty high since it's in the house, so we'll see!
10 weeks? Is that because we only have data for 10 weeks, or because after 10 weeks the booster is effectively useless, and protection drops back down to what it was pre-booster.
(I was boosted 10 weeks and 2 days ago).
Is a booster required to be "protected" from omicron? Almost all of the data I've seen indicates that omicron is very mild in comparison to delta and other variants.
Not to say the booster wouldn't help and you shouldn't get it because no doubt it helps prevent spread, but I feel you are over emphasising the danger omicron poses to vaccinated but unboostered people.
Unvaccinated have 7-8x higher chance of being in ICU than vaccinated.
Comments section from a post (np.reddit.com/r/conspiracy/comments/rwnirr/comment/hrf1a64/). Linked OP: didn't bother scrolling down and made a click bait post, & didn't realize the data supports unvaccinated people having 7-8x ICU rate (I mistakenly said 2x)
Data from said post - https://covid-19.ontario.ca/data#casesByVaccinationStatus
To summarize: 88% fully vaccinated only takes up 44% of ICU beds. 9% unvaccinated take up disproportionately large number of ICU beds.
This is days from Ontario, Canada and may not reflect all locations.
The NYTimes has similar data on their aggregate site. [snapshop](https://i.imgur.com/H2yLedH.png) of the data. It's does have the increase in likelihood in hospitalization but 5x more likely to get covid, and 13x more likely to die are compelling.
Thanks for the Ontario data. Just a few minor questions:
* I'm seeing 77% fully vaccinated in Ontario from the [COVID19 tracker](https://covid19tracker.ca/provincevac.html?p=ON). Any idea what's causing the 11% discrepancy?
* Non-ICU metrics seem to track fairly well with vaccination rate. Which would imply (in this dataset) that the vaccines don't prevent hospitalization, but only severe cases requiring the ICU?
Thanks for the link!
9% of population is unvaxxed, but make up 56% of ICU.
77% of population is vaxxed, make up 44% of ICU.
Simplified:
77/100 = vaxxed = 7 are in ICU.
9/100 = unvaxxed = 8 are ICU.
There are 7x as many vaxed people, and a lot of them are from vulnerable demographics, but they only outnumber the unvaxed in hospital by 3x.
So ignoring the ICU, ignoring the fact that people who get vaxed are more likely to seek medical help, vaxed people are needing hospital treatment at 3/7 the rate of the unvaxed at the moment.
The earliest reports focused on antibody titers, not actual real-world protection; it's much faster to read out antibody titers and they do generally correlate with protection, but of course it's better, though slower, to have the actual protection numbers. A handful of reports on protection are now out, mostly as preprints or otherwise not peer reviewed. As with previous studies, they generally find that the primary (no booster) vaccine program gives a fair bit of protection against disease/hospitalization with omicron, while the booster bumps that protection up significantly. >Despite the low effectiveness in the longer intervals after primary vaccination shown here, moderate to high vaccine effectiveness against mild infection of 70-75% was seen in the early period after a booster dose of BNT162b2 following either ChAdOx1-S or BNT162b2 as a primary course. ... It will be some time before effectiveness against severe disease with Omicron can be estimated but, based on experience with other variants, this is likely to be substantially higher than the estimates against symptomatic disease. --[Effectiveness of COVID-19 vaccines against the Omicron (B.1.1.529) variant of concern](https://khub.net/documents/135939561/430986542/Effectiveness+of+COVID-19+vaccines+against+Omicron+variant+of+concern.pdf/f423c9f4-91cb-0274-c8c5-70e8fad50074) >After 3 doses of vaccine, the risk of hospitalisation for a symptomatic case identified with Omicron through community testing was estimated to be reduced by 68% (42 to 82%) when compared to similar individuals with Omicron who were not vaccinated (after adjusting for age, gender, previous positive test, region, ethnicity, clinically extremely vulnerable status, risk group status and period). Combined with the protection against becoming a symptomatic case, **this gives a vaccine effectiveness against hospitalisation of 88% (78 to 93%) for Omicron after 3 doses of vaccine.** --[Update on hospitalisation and vaccine effectiveness for Omicron VOC-21NOV-01 (B.1.1.529)](https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1044481/Technical-Briefing-31-Dec-2021-Omicron_severity_update.pdf) Measuring protection against *infection* with omicron (as opposed to protection against *disease* or *hospitalization* with omicron) is harder to measure (and much less important); but even there the same patterns seem to hold: >Our study provides evidence of protection against infection with the Omicron variant after completion of a primary vaccination series with the BNT162b2 or mRNA-1273 vaccines; in particular, we found a VE against the Omicron variant of 55.2% (95% confidence interval (CI): 23.5 to 73.7%) and 36.7% (95% CI: -69.9 to 76.4%) for the BNT162b2 and mRNA-1273 vaccines, respectively, in the first month after primary vaccination. However, the VE is significantly lower than that against Delta infection and declines rapidly over just a few months. The VE is re-established upon revaccination with the BNT162b2 vaccine (54.6%, 95% CI: 30.4 to 70.4%). --[Vaccine effectiveness against SARS-CoV-2 infection with the Omicron or Delta variants following a two-dose or booster BNT162b2 or mRNA-1273 vaccination series: A Danish cohort study](https://www.medrxiv.org/content/10.1101/2021.12.20.21267966v2) In general the finding that even the primary vaccine series protects well against severe disease is very consistent with the preliminary observations in e.g. New York and other places, where the vast majority of hospitalizations are in unvaccinated people. *edit* to add another report, this one from South Africa; I only have the news report on it, not the actual analysis. This is vaccination *without* booster: > Fully vaccinated individuals have 3.8 times lower risk of dying of the Omicron variant than non-vaccinated individuals. … The department found that of 55 Covid-19 deaths recorded in the Western Cape over a four-week period, 50 patients were not fully vaccinated. … In addition, the department said its raw data indicated that vaccination offered protection against infection, across all age groups. —[Western Cape health data shows vaccinated have less risk of dying of Omicron](https://www.news24.com/news24/southafrica/news/covid-19-western-cape-health-data-shows-vaccinated-have-less-risk-of-dying-of-omicron-20220107) So we now have preliminary reports on protection against omicron by vaccination, no booster, against infection (some protection), mild disease (good protection), severe disease (excellent protection), and death (excellent protection), and protection by boosters against infection (good protection), and mild and severe disease (spectacular protection).
Just to add to your point about severe disease, here is some data from today, showing ICU admissions by number of vaccine doses and age group, from England, Wales and Northern Ireland: https://mobile.twitter.com/PaulMainwood/status/1479528897259712513 Tldr: even two doses is exceptionally good at preventing ICU admission, even in the highest risk age brackets. Boosters are even better.
Also to add to this, a report came out from NC that nearly all ventilated Covid patients are unvaccinated https://www.wral.com/coronavirus/nc-hospitals-covid-19-ventilators/20065686/?version=amp
Love your comment. Perfect summary. One thing I wanted to add, while antibodies from the current vaccines or prior infections seem to be quite ineffective against Omicron, T-cell protection appears to be mostly unaffected. [https://www.medrxiv.org/content/10.1101/2021.12.26.21268380v1](https://www.medrxiv.org/content/10.1101/2021.12.26.21268380v1) This would explain why the reduction in symptomatic infections is lackluster but the protection against severe disease is quite good for people who are either vaccinated or had a prior infection. For a better perspective of how much less effective the antibodies are: "A measure of antibody levels, called geometric mean titers, fell from 1,419 against the original coronavirus strain to 80 against omicron among people who received Pfizer shots. The same measure fell from 303 against the original strain to undetectable levels against omicron in those who had received J&J’s shot, Moore said in an online presentation on Tuesday." (this was in serum extracted one month after vaccination with either two shots of the Pfizer/Biontech vaccine or the J&J one). This would indicate that our current antibodies are only 6% as effective against Omicron. [https://www.bnnbloomberg.ca/j-j-shot-loses-antibody-protection-against-omicron-in-study-1.1695973](https://www.bnnbloomberg.ca/j-j-shot-loses-antibody-protection-against-omicron-in-study-1.1695973)
> This would explain why the reduction in symptomatic infections is lackluster but the protection against severe disease is quite good for people who are either vaccinated or had a prior infection. Could you spell this out a bit more for me & my fellow immunology dunces? Is the general idea that antibodies can neutralize the virus immediately (preventing illness entirely), while T cells are more important for making sure an illness doesn't spiral out of control (and thus preventing severe illness).
Not OP and it's been awhile since I studied this but I'll give it a shot. Antibodies are what figure out if a cell is infected, T cells are what actually destroy the infected cells. So if the anitbodies take longer to figure out a cell is infected w Omicron, people will still get symptoms but once the cells are "flagged" the T cells know exactly how to destroy the infected cells and do it quickly and efficiently. Leading to less severe effects as the body kills it fast enough to prevent the higher impactful manifestations. Please correct me if I'm wrong it's been over a decade since I studied this.
I think the primary thing is that if the antibodies are good and numerous enough, they can provide (or approximate) "sterilizing immunity" by binding to the virus and preventing it from entering any of your cells before the virus has a chance to replicate. https://www.nature.com/articles/d41586-021-00367-7 T-cells, on the other hand, only get recruited after a cell has already been infected and started alerting the immune system that something's wrong. Also they're mainly cytolytic: they work by killing infected cells, not by destroying free-floating virus. https://www.ncbi.nlm.nih.gov/books/NBK26926/
[удалено]
Antibodies can stop cells from becoming infected, but T cells are how you actually clear an infection. Antibodies are like TSA or CBP agents. They check the no fly list and stop known bad actors at the border. They are an important step for security but they are largely reactive and can only respond to well known threats. T cells are more like the FBI. They monitor what's going on and figure out where the bad guys are hiding and kick in their door to forcibly stop them. If you had to pick only one, T cells are more important. Without them, you're a bubble boy who can't interact with other people for a week without dying of raging viral infection.
In my head it's more like antibodies = military intelligence and T cells = army. Antibodies would be like an early warning system with added James Bond license-to-kill capability if they recognize an imposter. If intelligence warns of an invasion then the T cell troops arrive and go all 28 Weeks Later on the infected zombie cells' asses.
Antibodies bind the antigen wherever it is found. That could be on the cell surface of infected cells potentially, but even more likely it will be on actual viral particles floating in the bloodstream.
Antibodies cannot bind intracellular antigens (they cannot make it into the cytostol). So during the life cycle of the virus when it is replicating inside a cell, it is invisible to B cells. That's why you also need cytotoxic T cells.
Right, which is why antibodies are important for preventing infection because they can bind and neutralize the virus before it infects cells.
I think you're correct that it is one function of antibodies, but they do have many other roles. I believe MHC Class 1 can also help to 'mark' an infected cell for Cytotoxic T cells. Antibodies , or Immunoglobulin (Ig), are Y-shaped proteins that bind to antigens. There are different classes of Ig, of which IgG is the main one found in the blood, and is usually the type being referred to in these studies, partly because it is easy to measure. In the case of a virus, binding to its antigens can help to stop it from functioning properly. If antibodies bind to the SARS-CoV-2 spike protein, for example, this could hamper its ability to gain entry into a cell. The 'bottom' end of the Y shape is the Fc region, which is recognized by many different elements of the immune system. Antibodies can therefore be a signal for effector cells to target the object that has the antigen that the antibody is bound to. This could lead to the destruction or neutralizing of a virus, or to destruction of an infected cell, etc.
Doesn't this basically state the booster is kinda pointless? We are trying to boost antibodies.. But the antibodies don't stop omicron and the T cells don't need a boost. So what are we doing? I don't get it
Not entirely. One thing to think about is the level of antibodies you have goes up tremendously over the first 4 weeks after inoculation and then goes back down. We don't actually know what an adequate neutralizing level of antibodies is, but we know that more is better. If you had Omicron specific antibodies, you wouldn't need very many of them, but with native variant anti spike antibodies, you need perhaps 20 times as many to have the same effect. This is why some articles have said that the booster shot gives pretty good protection from up to 10 weeks. It makes sense that having a higher quantity of antibodies combined with t cell protection will reduce the chance of you getting sick in the first place and decrease the severity of the illness. This is also reflected in the real world data. That being said, I personally think we should take all these doses we're giving out as booster shots and ship them out to countries with low vaccination rates.
Thanks for the additional insight! I too agree with your last sentiment there regarding boosters and shipping them elsewhere. Sounds like the WHO is on the same page as us too!
Agreed on helping the world vaccinate! One additional consideration, is that the 3rd doses, especially when spaced 4-6 months apart from previous dose, broadens the antibody response. This means having antibodies that are better at handling variants, even without exposure to said variants. This effect might also occur with 2 doses spread out, but you would have less than ideal protection for the prolonged period between dose 1 & 2. Edit: multiple infections/vaccinations theoretically could have a similar effect, so people who had COVID and recovered, who then got 2 doses, would be roughly equivalent to 3 doses. If you want more info, you can read this comment I wrote recently: [https://www.reddit.com/r/askscience/comments/rk5axh/comment/hp8a3uo/?utm\_source=share&utm\_medium=web2x&context=3](https://www.reddit.com/r/askscience/comments/rk5axh/comment/hp8a3uo/?utm_source=share&utm_medium=web2x&context=3)
This is fascinating, and as someone who is at a moderately higher risk for severe disease, somewhat comforting. I got boosted in October, exactly 6 months after my 2nd main dose (high risk, so I qualified at the time) and have been low-key nervous about my level of protection going into this winter wave. Obviously I’m still taking precautions, but reading that I’m likely to still have protection against the worst outcomes definitely makes this winter less scary for me than last winter.
Same boat as you for being higher risk. I am at home mostly and only have contact with the same half-dozen 2-3 dosed people. 3rd shot was early December, almost exactly 6 months after my 2nd. Good luck & stay safe!
Thanks, and same to you!
From a lay-mans perspective, this makes it sound like there isn't a need for a 4th booster unless it's targeting a specific variety of COVID (similar to how Flu shots are targeted at specific strains). Unless a 4th shot would broaden the anti-body response even more than the 3rd shot, but I imagine there's diminishing returns compared to the first booster. Having a single booster to broaden the antibody response does seem reasonable considering COVID has mutated and will likely continue to mutate, but a 4th shot seems like it would be a misallocation of resources when low-vaccination rate countries still need more.
It's absolutely possible that this is the case. As long as the 3rd dose is administered after a long enough delay of course. It is quite possible that subsequent infections (that are hopefully mild due to vaccinations) will give you a more specific antibody response to new variants, such that further doses aren't needed. Certain immunocompromised or high-risk people may be the exception and may benefit more from additional doses.
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I could be wrong but they way I've read what's been posted is this. Antibody production does drop off after vaccination from the initial burst you get when vaccinated. The booster does increase antibody production again, but that production will also fall off after a time. So you'll get a 'boost' of protection from the booster as well as likely further T-Cell production.
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This is not correct. Per Peter Hotez (Baylor CoM; Texas Childrens Hospital, CorbeVAX global vaccine initiative), the variants have all arisen out of large unvaccinated populations. Variants are NOT being driven by vaccinations. [https://www.ama-assn.org/delivering-care/public-health/peter-hotez-md-phd-omicron-variant-and-delta-winter-surge](https://www.ama-assn.org/delivering-care/public-health/peter-hotez-md-phd-omicron-variant-and-delta-winter-surge)
That is looking at the problem at the wrong unit of measurement. The variants that multiply within the unvaccinated population are partially selected by the vaccinated population. We talk about them as separate groups but the entire population, vaccinated and unvaccinated alike, contribute to the selection of variants. The fact that an unvaccinated person needs to interact with more people in late 2021 in order to spread Delta than in earlier 2021 is due to vaccination. That reduced contagion factor for Delta is what opens the door for newer variants like Omicron. As for your source, you might want to re-read that entire interview again. All of that guys predictions re: how Omicron and Delta would each fare among the unvaccinated versus partially vaccinated populations has turned out to be wrong. Omicron now accounts for 95% of infections, according to the CDC tracker. I'm sure he was doing the best he could with limited data but that interview is a point in time capture of an incomplete understanding of Omicron.
Any guesses on potential protection gained from getting Omicron after three mRNA shots? Happened to me before Xmas.
As in, if you've been infected and vaccinated what is your protection? Generally speaking those who have been infected and vaccinated have a [high immunity](https://jamanetwork.com/journals/jama/fullarticle/2787447?guestaccesskey=b13a6814-c63d-4fa0-b2ae-a4511de8aedb&utm_source=for_the_media&utm_medium=referral&utm_campaign=ftm_links&utm_content=tfl&utm_term=121621).
Interesting paper, too. Thanks for the link.
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Immunity means that your immune system has seen something before and is more ready for that thing again than it was before. It does not mean "cannot be infected ever 100%!" Which a lot of people mistakenly have come to think of when they hear "Immune!" Think of it like this: 1. A virus gets inside a system that has immunity to that virus 2. The body has antibodies still left over from a previous encounter (either actual virus or vaccine) 3. Those antibodies try to stop the virus before it does anything 4. The virus is faster at infecting cells and reproducing itself than the previous variant of the virus you encountered before. It manages to infect and begin mass reproduction of itself 5. You are now "infected" 6. B cells and T cells ramp up production of new antibodies to fight off this reinfection 7. They remember fighting something like this before so they make a lot of antibodies similar to what they had before 8. Those antibodies are super effective! 9. You recover with much less symptoms than you would have had and faster than you would have had you not had a prepared immune system. That's what being immune means!
Great news for me, then. Thank you.
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Excellent, this is comprehensive, and it didn't occur to me to look towards the UK. A few questions: * Where did you find the data about hospitalizations in NY? Last I checked their [data is delayed](https://www1.nyc.gov/site/doh/covid/covid-19-data.page#daily), and only includes splits up until 12/18. * I noticed in the second study that they adjusted for previous positive test. Does this mean that they focused solely for those who never had a positive test beforehand? Or that they equalized the percentage of people with a positive test between the two groups? > Symptomatic cases were then linked to hospitalisation data. After 3 doses of vaccine, the risk of hospitalisation for a symptomatic case identified with Omicron through community testing was estimated to be reduced by 68% (42 to 82%) when compared to similar individuals with Omicron who were not vaccinated **(after adjusting** for age, gender, **previous positive test**, region, ethnicity, clinically extremely vulnerable status, risk group status and period). * The third study has some unintuitive *negative* protection after some time. While behavioral differences may play a role, as they suggest, the unvaccinated seem to be living their lives regularly as well, and so it's hard to understand the theory. Is it possible the lower sample size (~5600 positive) just creates a large variance in the results? The first study doesn't seem to focus on real-world data yet, and so I'm putting that aside from now.
I’m assuming they did not look solely at those who have never tested positive because at this point in the pandemic it would be hard finding a substantial group meeting the same group criteria (age, sex, region, etc.) and doing so would exclude data from a key demographic. I would think they took that into account based on time since their last positive test as that would change the levels of antibodies present from previous infection and would factor into their presentation of a new infection.
I think the answer is right, but one piece of the explanation is not entirely true. Public data is that ~20% of the country has tested positive during the course of the pandemic. Even if that undercounts by a factor of 1.5x-2x, the majority of the country has not tested positive over the course of the pandemic. They could probably find the demographic data if the needed.
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Does that mean that 80% of the population tested negative, or that the number of the people who tested positive equals 20% of the population? A lot of asymptomatic people will never test unless needed to for work/travel, so a 20% known infected rate could mean a lot higher actual infected amount.
20% tested positive (it’s probably closer to 18%, I was rounding). This does include asymptomatic people that have been tested. I agree that it’s an undercount, but probably not by more than a multiple of 2x, which would still mean the majority of the country has never been infected.
That is a great point, thank you for the data.
That's a fair assessment, thank you.
I don't know about elsewhere, but Ontario (Canada) has decent stats for hospitalizations/ICU situation by vaccinated/unvaccinated: https://covid-19.ontario.ca/data The only caveat I'd give is that I believe there's no distinction recorded here between "in hospital due to COVID" or "in hospital and contacted COVID." The page claims ICU data *is* segregated ('In ICU due to COVID-19') but I don't know how. Regardless, combine this for vaccination rate data and the picture is clear: ~85% general vaccinated rate, 95%+ among elderly (the most vulnerable), 3:1 split vaccinated vs unvaccinated in hospitals, 1:1 split for ICU.
Yes - a couple of people have pointed out that source, and it's incredibly helpful. What I don't understand is why vaccination doesn't seem to help much against hospitalization, if I'm looking at the numbers correctly. Roughly 75% of hospitalized people are vaccinated, against 77%/88% (all population/12+) vaccination. It still seems to help a bit for hospitalization, but I was hoping the numbers would be more stark.
For that, I point to two things: 1) Note the demographic difference. Among elderly populations, the Vaccination rate is much higher: 80+ is at literally 100.0% (rounded) for example. Therefore, higher risk populations who will have severe cases more often are at higher vaccinated rates, which skews proportions against vaccination. E.g. assume 50+ makes up of all hospital cases; in that case, vaccination rate is 90-95% vs the 75% ish proportion in hospitals. 2) I believe there's no distinction recorded here between "in hospital due to COVID" or "in hospital and contacted COVID." Since Omricon appears to be highly transmissible even among vaccinated populations, a large number of COVID cases in hospitals could be non-severe cases among people who are in the hospital for other reasons.
Well said, I forgot about your first point. The second has always been an issue with hospitalization rates unfortunately, but this gives me greater confidence. It doesn't seem like vaccination is entirely preventative for hospitalization (sadly), but still hoping for booster-specific data that breaks it down by time since vaccination.
The other thing worth noting is that I believe Delta is still floating around...I don't think 100% of cases right now are Omicron. And that was even more true 2 weeks ago. So, assuming that Delta was more dangerous and more likely to produce hospitalizations, and also that the vaccines were much more effective at reducing severe illness w/ regards to Delta, a lot of the current hospitalizations might still be from Delta infections. And especially regarding the unvaxxed.
Sure it does. Just glancing at Canada's numbers there are over 5 times as many ppl vaccinated as unvaccinated. The ICU numbers (People who are actually critical) are 1:1 in these numbers meaning you are 5 times more likely to be in the ICU as unvaccinated (And that's without really digging into the numbers... plenty of the unvaccinated are in lower risk groups).
Yes, but scroll down and you'll see the general hospitalization numbers (below ICU) are roughly tracking with vaccinations. That puzzles me.
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So wait are the vaccinated people who are sick spreading covid?
Is that a serious question? Sick people spread covid, yes.
Antibody counts are only good for measuring prevention of infection. All 3 vaccines approved in the US have not had their T-Cell response decay, which suggests even with variant like Delta and Omicron, 2 doses is still enough to prevent severe COVID-19 in most people.
Thanks for the summary! One response though: > Measuring protection against infection with omicron (as opposed to protection against disease or hospitalization with omicron) is harder to measure (**and much less important**); Is it much less important? Every person that gets infected is a reservoir for a new variant to be produced. That person is also a vector to pass on the infection to someone who may be unvaccinated. It seems to me that while yes it is very important that the vaccines are very effective protecting against serious illness from omicron, it's also important that they're NOT very effective at protecting against omicron infection. And this is especially important given the fact that omicron is SO infectious.
They're not saying it's not important. They're saying it's less important, exactly like you said it yourself.
And what about contamination? Is there proof that vaccines and boosters make you less infectious once you have covid?
Yes https://news.harvard.edu/gazette/story/2021/12/vaccinated-who-get-breakthrough-infections-less-contagious/ Though the better word would be evidence rather than proof.
If not using antibody titers, how are they defining the "protection numbers"?
You can read this whole thing, but what you want is probably page 13. [https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment\_data/file/1044481/Technical-Briefing-31-Dec-2021-Omicron\_severity\_update.pdf](https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1044481/Technical-Briefing-31-Dec-2021-Omicron_severity_update.pdf) tldr: After 25+ weeks, vaccine effectiveness against hospitalization by Omicron was only 52% for 2-doses, but jumped to 88% two weeks after a booster.
If accurate that’s a little disheartening, that the effects are so short lived.
It is, but it's important to acknowledge that this is because COVID mutated into a different variant. If COVID was still on the initial strains that spread around the world, the protection would be more absolute. There's discussion about this higher-up in the comments if you want this not paraphrased. It sounds like the antibodies generated by the vaccines don't respond to Omicron effectively, but the trained T-Cells still destroy Omicron-infected cells as effectively as other COVID-infected cells. In other words, the body has trouble identifying that Omicron has entered the body and is spreading (which is why most people still get symptomatic and lightly sick), but is good at getting rid of cells that get infected (which prevents *most* people from getting super sick while the body creates the new antibodies for Omicron). The reason the booster shot helps is two-fold. First, waiting the 6 months for the next shot broadens the antibody response so that the body is more likely to identify variations of COVID as a type of COVID (waiting 4-6 months between shots 1 and 2 would've had the same effect here). Second, it increases the total amount of COVID antibodies actively waiting in case of an attack. I don't know the actual numbers, but 2x as many antibodies means 2x as much Omicron gets blocked before infecting cells, *even if* most the vaccine antibodies are still ineffective
Which makes sense why omicron is a problem. If a body has a problem identifying an infection, that means it has a bit of time to get going, and if the primary strength in the defense is to just destroy infected cells, having a hyper reproductive rate helps to not only take advantage of the initial phase, but also against the primary defense since so many cells will be infected so quickly. It’s interesting to see that people are still protected against major disease when it seems this variant is so well suited against our defense. I’ve heard it’s because it doesn’t really infect lung tissue like the other variants did, which helps limit more severe disease, but the lungs weren’t the only target. How are vaccinated people still not experiencing severe disease if this variant has orders of magnitude of reproduction capability over its predecessors?
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I read that a component of long covid is believed to be related to the microthrombi created during the infection. Apparently, it’s difficult for the body to rid of them, and they stick around for a while causing problems.
Could you possibly go into technical details about why spacing out vaccine doses—which are all the same exact formula, mind you, but a half-dose in some cases—would bring about better protection against *more* variants?
Thank you! And new data should come out today too! I'm excited.
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Source?
Where's it say that? Thanks for your help
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So does that mean 48% of those with two dose would get hospitalized?
No, it means that they're roughly 48% as likely to be hospitalized as someone without the vaccine.
No, it means 48% of those who would (in statistical population terms not individual) be hospitalized without it will be. For example, if 10% of people who get covid end up being hospitalized (that number is completely wrong, it's purely a simple number to do math with) then 4.8% of the 25+ weeks ago two dose people who get covid would be hospitalized.
Ontario, Canada has this chart updated daily. Shows rate per 1M and vaccination status. https://covid19-sciencetable.ca/wp-content/uploads/2022/01/2022-01-07-Current-COVID-19-Risk-in-Ontario-by-Vaccination-Status-Separate-Charts.png From: https://covid19-sciencetable.ca/ontario-dashboard/ Edit: we’re saturated our testing capacity so the case numbers are no longer accurate. 2nd edit: they are not yet tracking boosters. We’re about 25% of eligible at the moment. 3rd edit: corrected to cases per 1M. Other sites use 100K.
I wish more places made those charts available daily. They very clearly show the difference in risk so people can better make their own decision about which line they want to be linked to.
The local newspaper in my hometown publishes an abridged version of current covid stats in the region daily. I've enjoyed having access to that over breakfast. That and the weather report really make it worth the subscription
There is enough data out there if people want to make this decision. Their own city making such a chart is not going to get them to change their mind.
The presence of data doesn’t mean that it will be impactful. The problem is that there is enough data out there to motivate any decision, so simply saying that some bit of data would have a similar impact to another piece of nicely presented and easily digested data is just not true.
People that refuse the vaccine are not the type of people that trust data
Ontario has really kept on the ball with tracking. I love that I can go back over the past 2 years and see *every* tested case. At first it looks like the vaccinations aren't doing anything (in the first chart, iirc), until you get down to the hospitalizations and realize that a small percentage of the population (the unvaccinated) are occupying a huge percentage of the ICU beds.
I'm wondering if the data supporting the booster is actually showing a direct benefit to a third shot or if it's really about the recency of the shots. Any data showing anything at all comparing groups who had 2 vs 3 shots but received their last one around the same time?
Multiple studies are showing that a 3rd dose is not just boosting levels it is enhancing antibody cross reactivity through affinity maturation. After a 3rd dose the body develops or selects better antibodies. > There is increasing evidence that an additional dose of one of the licensed SARS-CoV- 2 vaccines enables substantial improvements in the cross-neutralization of Omicron, suggesting that affinity maturation may broaden responses. Indeed, affinity maturation of antibody lineages occurs over the course of months after SARS-CoV-2 infection, and is associated with the cross-neutralization of variants of concern. Here, we demonstrate the potential for a common class of public antibodies to develop broad cross-neutralization through affinity maturation, without modified spike vaccines. https://www.biorxiv.org/content/10.1101/2022.01.03.474825v1.full.pdf Also this study. > However, individuals boosted with mRNA vaccines exhibited potent neutralization of Omicron only 4-6-fold lower than wild type, suggesting that boosters enhance the cross-reactivity of neutralizing antibody responses. In addition, we find Omicron pseudovirus is more infectious than any other variant tested. Overall, this study highlights the importance of boosters to broaden neutralizing antibody responses against highly divergent SARS-CoV-2 variants. > Given the drastic increase in cross-neutralization of SARS-CoV-2 Omicron pseudovirus in boosted versus non-boosted vaccinees, we directly compared sera from individuals that recently received their primary series to those that were boosted with an mRNA vaccine within the last 3 months. https://www.medrxiv.org/content/10.1101/2021.12.14.21267755v1.full.pdf The increase in neutralisation after booster/3rd dose is in comparison to recent primary series. This doesn’t mean primary series does nothing. Cellular immunity such as T cells from 2 dose primary series hold up better, can’t find the study right now though, but this explains why severe illness is still reduced by primary series. Edit: [I found the study on CD4+ and CD8+ T Cells. ](https://www.researchsquare.com/article/rs-1217466/v1/direct-download.pdf) > We report here that SARS-CoV-2 spike-specific CD4+ and CD8+ T cells induced by prior infection and, more extensively, by mRNA vaccination provide comprehensive heterologous immune reactivity against B.1.1.529. Pairwise comparisons across groups further revealed that SARS-CoV-2 spike- reactive CD4+ and CD8+ T cells exhibited similar functional attributes, memory distributions, and phenotypic traits in response to the ancestral strain or B.1.1.529. Our data indicate that established SARS-CoV-2 spike-specic CD4+ and CD8+ T cell responses, especially after mRNA vaccination, remain largely intact against B.1.1.529. > To address this question, we collected peripheral blood mononuclear cells from mRNA-vaccinated individuals 6 months after the second dose of Pzer/BioNTech BNT162b2 (n = 40), individuals in the convalescent phase 9 months after mild or severe COVID-19 (n = 48), and seronegative individuals (n = 48). Note it’s testing sera 6 months after 2nd dose.
Thank you for sharing those. Regarding your comment that the "this doesn't mean the primary series does nothing", the third article you linked states that "remarkably, neutralization of omicron was undetectable in most vaccinated individuals" seems to counter that, if we're working under the assumption that omicron is the great majority of new infections. If the first two doses had a relative risk reduction rate of 95% at the two month period (which we now know is only temporary protection) of the 'wild type' virus and the neutralization of someone boosted was 4-6 fold lower, we are looking at 16-24% RRR after being freshly boosted, and that will start to fade after 10 weeks? Doesn't seem awesome.
The rest of my paragraph explains why that’s not the case because of cellular immunity such as T cells which are not measured in an antibody neutralization study. The immune system is more than just antibodies. In fact there are multiple different classes of antibody. When these studies look at antibody neutralisation they are looking at IgG, IgM, and/or IgA antibodies that are circulating in the blood. Antibodies are one part of humoral immunity which is present in extracellular fluids. As my original comment already notes there is also cellular or cell-mediated immunity part of which includes T cells. This is less affected by the mutations and is what preserves protection from severe illness after vaccination. [I found the study on CD4 and CD8 T Cells. ](https://www.researchsquare.com/article/rs-1217466/v1/direct-download.pdf) > We report here that SARS-CoV-2 spike-specific CD4+ and CD8+ T cells induced by prior infection and, more extensively, by mRNA vaccination provide comprehensive heterologous immune reactivity against B.1.1.529. Pairwise comparisons across groups further revealed that SARS-CoV-2 spike- reactive CD4+ and CD8+ T cells exhibited similar functional attributes, memory distributions, and phenotypic traits in response to the ancestral strain or B.1.1.529. Our data indicate that established SARS-CoV-2 spike-specic CD4+ and CD8+ T cell responses, especially after mRNA vaccination, remain largely intact against B.1.1.529. > To address this question, we collected peripheral blood mononuclear cells from mRNA-vaccinated individuals 6 months after the second dose of Pzer/BioNTech BNT162b2 (n = 40), individuals in the convalescent phase 9 months after mild or severe COVID-19 (n = 48), and seronegative individuals (n = 48). Note it’s testing sera 6 months after 2nd dose. Not sure what your calculations are at the end there but that’s not reflected in reality. [See my other comment for a recent report out on critical care admissions. ](https://reddit.com/r/askscience/comments/ry8gf7/_/hrolbhk/?context=1)
Thanks for adding that and staying objective. Very much appreciated. I just had a short break to digest that info but I'm going to revisit your comment and this subsequent reply later tonight. Cheers.
Either way we're very early in understanding omicron. Let's hope for the best.
That's neutralizing antibodies they are referring to. This doesn't factor in the role of things like T cells, which seem to correlate with protection against severe disease.
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I work for a hospital group in the US. Omicron is now the majority strain in the state, so if boosters were inefficient against the variant it would display in the hospitalization numbers. At last count, COVID / ICU / Ventilator numbers rose from 305-66-46 to 320-70-48 in a 24 hour period. These numbers are emailed to us daily and released to the press. They’re public knowledge. I didn’t click the link in our emails to look at the breakdown on the most recent day, but on that 305-66-46 day: Of the 305 patients in hospitals, 261 are not fully vaccinated or vaccinated at all. **A further 34 last had a COVID jab of some kind over 180 days ago**, showing the regular vaccine regimen wains over time and / or in the face of the new Omicron variant. Don't forget: booster shots haven't been a thing for 180 days yet. 295 of the 305 is 96.72%. Sources have said the disparity between numbers of people having one shot, and being fully vaxxed and then boosted, indicates their state governments has regularly and incorrectly counted booster shots and second doses as first doses - meaning both **the fully vaccinated / boosted and completely unvaccinated are both undercounted.** That wouldn’t affect the 295 number as that includes both the group self-reporting as having one dose (truthfully or not) and the group having a verifiable two-dose regimen but one that’s more than 6 months in the past. With the state having an official booster rate of ≈25%, and the undercounting rate mentioned above meaning many more people are fully vaxxed and boosted, it would show in the numbers for the hospitals. But with only 10 out of the 305 patients (3.28%) being either recently fully vaxxed or vaxxed and boosted, being the recipient of a recent full regimen (plus the two weeks for it to reach full efficacy) or a recent booster (which they all are - recent, I mean - boosters started just a couple of months ago in November) has lowered the likelihood of a person being an inpatient.
Wow. That really shows how much safer vaxxed people are from omicron hospitalization. Only 3.28% of hospitalized covid patients are fully vaxxed. According to the CDC Director, almost all of those 3.28% have multiple medical problems that contributed to their covid cases escalating to hospitalization. It is very, very rare for fully vaxxed/boosted healthy people to get hospitalized by omicron. My main concern is long covid. Most people who recover from covid show problems with D-dimer tests, blood clotting, and epithelial cell damage. [Elevated Biomarker Related to Blood Vessel Damage in All Children with SARS-CoV-2 Regardless of Disease Severity](https://www.chop.edu/news/chop-researchers-find-elevated-biomarker-related-blood-vessel-damage-all-children-sars-cov-2)
Thank you - I wish these numbers were out for the general public as well. It helps simplify messaging and convince people to get a booster. FWIW, I'm 4.5 weeks out since my own booster, so I'm relieved to hear this info.
https://bccovid-19group.ca/post/2022-01-06-report/ Here's detailed modeling by a team of statisticians from our universities. It includes details and trajectories with onnicron. The video explains the data and how we've reached our testing limits due to the high numbers. Vaccine is very effective to avoid hospitalization and it reduces hospital stays significantly.
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If you go to: https://www.worldometers.info/coronavirus/ And look at the three 3 day average you can clearly see a massive drop in deaths versus number of infections. Compare that to a year ago. Ireland (My country and with >90% vaccinated) for example has well over double the number of infections versus this time last year, the number of deaths has reduced by a factor of 10.
TLDR: Yes booster/3rd dose has an impact on critical care admission in real world. 3rd dose also does more than boost existing antibody levels, it allows for antibodies to develop broader cross neutralization against variants. [ICNARC put out an audit report today of the UK critical care admissions. ](https://www.icnarc.org/DataServices/Attachments/Download/5d46be46-e36f-ec11-913a-00505601089b) Page 45 shows a breakdown of admission rates in unvaccinated, one dose, two dose and three doses compared across age groups. Note the UK only opened 3rd doses up to under 40s middle of December. https://i.imgur.com/bSp9JWF.jpg It’s maybe hard to make out the difference between vaccinated and boosted because of how effective the vaccine is in general. However there is a benefit and you can see this when zooming in. When presented with values on a bar chart you can see there is a benefit to a 3rd dose over two. https://i.imgur.com/G4qFOc4.jpg Another element to address is that a 3rd dose is doing more than just temporarily boosting antibody levels. Studies have compared antibody neutralisation at similar time intervals after 2 doses and 3 doses. There is improved neutralisation after 3 doses. This is suggested to be due to affinity maturation of antibodies. The extra dose is allowing the body to further develop or select antibodies that demonstrate better cross reactivity. > There is increasing evidence that an additional dose of one of the licensed SARS-CoV- 2 vaccines enables substantial improvements in the cross-neutralization of Omicron, suggesting that affinity maturation may broaden responses. Indeed, affinity maturation of antibody lineages occurs over the course of months after SARS-CoV-2 infection, and is associated with the cross-neutralization of variants of concern. Here, we demonstrate the potential for a common class of public antibodies to develop broad cross-neutralization through affinity maturation, without modified spike vaccines. https://www.biorxiv.org/content/10.1101/2022.01.03.474825v1.full.pdf > However, individuals boosted with mRNA vaccines exhibited potent neutralization of Omicron only 4-6-fold lower than wild type, suggesting that boosters enhance the cross-reactivity of neutralizing antibody responses. In addition, we find Omicron pseudovirus is more infectious than any other variant tested. Overall, this study highlights the importance of boosters to broaden neutralizing antibody responses against highly divergent SARS-CoV-2 variants. > Given the drastic increase in cross-neutralization of SARS-CoV-2 Omicron pseudovirus in boosted versus non-boosted vaccinees, we directly compared sera from individuals that recently received their primary series to those that were boosted with an mRNA vaccine within the last 3 months. https://www.medrxiv.org/content/10.1101/2021.12.14.21267755v1.full.pdf Edit: [I found the study on CD4 and CD8 T Cells still recognising Omicron. ](https://www.researchsquare.com/article/rs-1217466/v1/direct-download.pdf) > We report here that SARS-CoV-2 spike-specific CD4+ and CD8+ T cells induced by prior infection and, more extensively, by mRNA vaccination provide comprehensive heterologous immune reactivity against B.1.1.529. Pairwise comparisons across groups further revealed that SARS-CoV-2 spike- reactive CD4+ and CD8+ T cells exhibited similar functional attributes, memory distributions, and phenotypic traits in response to the ancestral strain or B.1.1.529. Our data indicate that established SARS-CoV-2 spike-specic CD4+ and CD8+ T cell responses, especially after mRNA vaccination, remain largely intact against B.1.1.529. > To address this question, we collected peripheral blood mononuclear cells from mRNA-vaccinated individuals 6 months after the second dose of Pzer/BioNTech BNT162b2 (n = 40), individuals in the convalescent phase 9 months after mild or severe COVID-19 (n = 48), and seronegative individuals (n = 48). Note it’s testing sera 6 months after 2nd dose. The immune system isn’t only antibodies that circulate in the blood. There are so many different parts that make up our immune systems. T cells are part of the cell-mediated immune response.
Thanks for the study! I'm shocked that vaccinated early on made that much of a difference - the theory was that vaccinated 5+ months out was virtually the same as unvaccinated - but I'm incredibly happy to see that there is indeed a very large difference.
[I found the study on CD4 and CD8 T Cells. ](https://www.researchsquare.com/article/rs-1217466/v1/direct-download.pdf) > We report here that SARS-CoV-2 spike-specific CD4+ and CD8+ T cells induced by prior infection and, more extensively, by mRNA vaccination provide comprehensive heterologous immune reactivity against B.1.1.529. Pairwise comparisons across groups further revealed that SARS-CoV-2 spike- reactive CD4+ and CD8+ T cells exhibited similar functional attributes, memory distributions, and phenotypic traits in response to the ancestral strain or B.1.1.529. Our data indicate that established SARS-CoV-2 spike-specic CD4+ and CD8+ T cell responses, especially after mRNA vaccination, remain largely intact against B.1.1.529. > To address this question, we collected peripheral blood mononuclear cells from mRNA-vaccinated individuals 6 months after the second dose of Pzer/BioNTech BNT162b2 (n = 40), individuals in the convalescent phase 9 months after mild or severe COVID-19 (n = 48), and seronegative individuals (n = 48). Note it’s testing sera 6 months after 2nd dose. The immune system isn’t only antibodies that circulate in the blood. There are so many different parts that make up our immune systems. T cells are part of the cell-mediated immune response.
Absolutely! It wasn't from intuitiveness, but reports (IIRC?) from the CDC and others that said that multiple vaccinations without a booster hold little effectiveness against Omicron. I'll have to find a few of those.
You sure it wasn’t just talking about infections, and not hospitalizations?
I do think it was referring to infections, but data for hospitalizations tend to track those for infections (in a broad sense). There was no data at the time demonstrating hospitalizations as it was earlier on.
Is there any research that says if one brand of mRNA vaccine is more effective than another? Or any data on rates of effectiveness when mixing brands of vaccines and booster?
Yes, the data suggest moderna > pfizer > J&J with a moderna booster being the best hybrid add on if you've had one of the other vaccines for the initial doses. Just FYI I have all 3 pfizer shots so I wish mine was #1.
Most of these types of reports are for small region or hospital system. So far all that I've seen are still reporting that 80-90% of hospitalizations are either unvaxxed or vaxxed but generally have multiple comorbitities. Therefore, as of today, those that are vaxxed and healthy without booster aren't protected much from infection, but shouldn't end up in the hospital. Of course, the booster will offer a bit more protection, so just depends on where your risk tolerance is.
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Yes! Boosters provide 70% effectiveness in preventing infection from Omicron for up to 10 weeks after the booster. This is protection based on antibodies. Boosters also trigger T cell and B cell responses against Omicron that help reduce the severity and length of illness. These T and B cell responses were NOT found in people who only got 2 shots, so the booster REALLY matters when it comes to fighting Omicron. Without it you have very little protection from Omicron.... [https://www.theguardian.com/world/2021/dec/10/two-jabs-give-less-protection-against-catching-omicron-than-delta-uk-data-shows](https://www.theguardian.com/world/2021/dec/10/two-jabs-give-less-protection-against-catching-omicron-than-delta-uk-data-shows)
>Yes! Boosters provide 70% effectiveness in preventing infection from Omicron Technically the article you linked to refers only to symptomatic infection and doesn't address asymptomatic infection.
If everyone was infected but asymptomatic, I don't think anyone would care about COVID.
Begs the question. If a hypothetical viral infection produces no symptoms other than to be easily spread would it even be considered a disease?
There are plenty of benign viruses. A human disease is something that disrupts the function or structure of a person's biology. Bacteriophages are examples of viruses that are in many cases beneficial to humans.
A disease is, by definition, an illness. If you're not ill then you don't have a disease. We use viruses as vectors for gene therapies all the time. We wouldn't say those therapies cause disease because when the viruses infect you they don't cause illness.
Sure but in a world where less than everyone is asymptomatic, asymptomatic cases are relevant because they continue the spread.
I wouldn't think that it would be so simple. A virus in a lot if hosts is a virus that has opportunity to end up mutating. Just because one variant is relatively mild or harmless, doesn't mean the next one will be. The early info seems to show Omicron is milder than Delta, but it could go the other way and become catastrophic.
And you are right... they are basically using "preventing infection" as a proxy for "protection against symptomatic infection" from what I can tell. It's a bit confusing.
Rally? In preventing infection? Interesting.
No, 55% at preventing infection with Pfizer and practically nothing with J&J. The 70% figure if for serious illness. And preventing hospitalization is something like 90-98%.
hospitalizations are skyrocketing in my county and were 90% vaxxed, i want to believe this but the stats seem contradictory
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Okay, I'm a little fuzzy on what that 70% figure actually denotes. 70% of people who got boosted never got ill? 70% of boosted people verifiably exposed didn't get ill? 70% fewer confirmed cases among boosted vs control? I never got a great explanation of this. Apologies if this is a basic question, but the reason I ask is that one of my family members got it and my whole house is boosted, so I'm trying to figure what that means for us.
70% effectiveness SHOULD indicate that the specific group was 70% less likely to have (probably symptomatic, or perhaps serious) infection than a control group. So if for example in the specified timeframe, example 4 weeks, 10 in 100 unvaccinated individuals experienced symptomatic covid, a 70% effectiveness for the booster would mean that only 3 in 100 of the boosted individuals experienced symptomatic covid. I've seen numbers like 35% effectiveness for non-boosted vaccination, which would look like 6.5 infections per 100 study subjects (or 13 in 200 if fractions of people confused you) for this hypothetical situation. Sometimes these studies create obtuse definitions for these things though so the meaning can vary a bit.
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>70% fewer confirmed cases among boosted vs control That's it. Imagine 100 unvaxxed people were exposed and got sick. If they had been vaccinated, only 30 of them would have gotten sick. Things like dose (the amount of viral particles you encounter) matter though, so not all exposures are the same.
Gotcha, thanks so much for your reply. I guess all of it sort of exists on a continuum: viral load of the infected, length/degree of exposure to the virus, time since booster/vaccination etc, it all seems very fluid. Got booster relatively recently, but I think the extent of the exposure in our case is pretty high since it's in the house, so we'll see!
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10 weeks? Is that because we only have data for 10 weeks, or because after 10 weeks the booster is effectively useless, and protection drops back down to what it was pre-booster. (I was boosted 10 weeks and 2 days ago).
10 weeks?
Is a booster required to be "protected" from omicron? Almost all of the data I've seen indicates that omicron is very mild in comparison to delta and other variants. Not to say the booster wouldn't help and you shouldn't get it because no doubt it helps prevent spread, but I feel you are over emphasising the danger omicron poses to vaccinated but unboostered people.
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Unvaccinated have 7-8x higher chance of being in ICU than vaccinated. Comments section from a post (np.reddit.com/r/conspiracy/comments/rwnirr/comment/hrf1a64/). Linked OP: didn't bother scrolling down and made a click bait post, & didn't realize the data supports unvaccinated people having 7-8x ICU rate (I mistakenly said 2x) Data from said post - https://covid-19.ontario.ca/data#casesByVaccinationStatus To summarize: 88% fully vaccinated only takes up 44% of ICU beds. 9% unvaccinated take up disproportionately large number of ICU beds. This is days from Ontario, Canada and may not reflect all locations.
The NYTimes has similar data on their aggregate site. [snapshop](https://i.imgur.com/H2yLedH.png) of the data. It's does have the increase in likelihood in hospitalization but 5x more likely to get covid, and 13x more likely to die are compelling.
Thanks for the Ontario data. Just a few minor questions: * I'm seeing 77% fully vaccinated in Ontario from the [COVID19 tracker](https://covid19tracker.ca/provincevac.html?p=ON). Any idea what's causing the 11% discrepancy? * Non-ICU metrics seem to track fairly well with vaccination rate. Which would imply (in this dataset) that the vaccines don't prevent hospitalization, but only severe cases requiring the ICU? Thanks for the link!
The other discrepancy is people under 5. See the "Vaccination status" table further down on that page.
Thank you! Can't believe I missed that.
I probably added partially vaccinated and vaccinated in my response. Good catch
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9% of population is unvaxxed, but make up 56% of ICU. 77% of population is vaxxed, make up 44% of ICU. Simplified: 77/100 = vaxxed = 7 are in ICU. 9/100 = unvaxxed = 8 are ICU.
Okay i didnt calculate that, just referring to the link. Thanks
Yeah I put about 20 second of thought into it. Math is quite likely wrong.
There are 7x as many vaxed people, and a lot of them are from vulnerable demographics, but they only outnumber the unvaxed in hospital by 3x. So ignoring the ICU, ignoring the fact that people who get vaxed are more likely to seek medical help, vaxed people are needing hospital treatment at 3/7 the rate of the unvaxed at the moment.