Immunity Generated from Covid-19 Vaccines Differs from an Infection | Hacker News Reader

Immunity Generated from Covid-19 Vaccines Differs from an Infection

directorsblog.nih.gov

240 pointsrolph231 comments

The spike protein targeting antibodies produced by the vaccine do indeed target a wider range of spike mutations than the spike protein antibodies from previous infection. However, vaccines only target spike protein, while a previous infection will cause your body to produce antibodies for a much larger set of targets on the virus, which in practice leads to a more robust immunity. This is supported by data from Israel and some recent studies.

https://www.israelnationalnews.com/News/News.aspx/309762

https://www.israelnationalnews.com/News/News.aspx/310963

https://www.medrxiv.org/content/10.1101/2021.08.24.21262415v...

That really depends on which vaccine. There are several inactivated virus vaccines such as Sinovac used in other countries which we would expect to produce antibodies for more than just the spike protein. However it's unclear whether those vaccines are more or less effective in practice.

I think on a personal basis all of them are better than nothing. It's like advice about taking the first bus out of town.

Are there such vaccines available in the US? It seems like those would make for effective boosters.

There are no inactivated virus vaccines authorized in the US. I'm not aware of any research on the effectiveness of using such vaccines as boosters after other types of vaccines.

Thanks

Valneva has an inactivated virus vaccine and they will soon apply for authorisation (phase 3 i think right now)

I was confused about that as well. The article suggests that targeting "other portions of the spike protein" (as immune systems previously infected with COVID do) results in the immune system being _less_ robust against variants of the virus than targeting "places on the RBD" (as immune systems exposed to Moderna's mRNA vaccine do):

> Specifically, antibodies elicited by the mRNA vaccine were more focused to the RBD compared to antibodies elicited by an infection, which more often targeted other portions of the spike protein. Importantly, the vaccine-elicited antibodies targeted a broader range of places on the RBD than those elicited by natural infection.

> These findings suggest that natural immunity and vaccine-generated immunity to SARS-CoV-2 will differ in how they recognize new viral variants. What’s more, antibodies acquired with the help of a vaccine may be more likely to target new SARS-CoV-2 variants potently, even when the variants carry new mutations in the RBD.

Anyone with more experience in immunology care to weigh in on why the second paragraph there follows from the first? Naively, one might expect targeting a wider variety of places on on the COVID spike protein to result in better immunity against variants, not worse. Why is the article saying the opposite?

when you target many epitopes, you are shooting at the 10 inch ring; target one epitope of critical function [put one in center of mass] you are shooting the 2 inch ring.

immune systems dont look at everything at once, they find something that sticks and and over trials sharpen the response until highest efficacy of antibody epitope combination is found.

the vaccine is like a laser guided munition, natural immunity is like carpet cluster bombing; both highly effective but in different modalities.

The way I read it is that vaccine immunity is engineered towards COVID in general. It'll catch variants because they're still COVID.

Natural immunity knows only of COVID-19 Alpha. But it knows it well. All those nooks and crannies the other variants may not have, the natural antibodies can latch on to.

I think it's because the other parts of the virus are more likely to change over time, because there's lots of neutral mutations available: changes which don't affect fitness but do affect antibody response. The RBD by contrast is much more constrained: most mutations there result in a virus which can no longer infect cells, so it's much less likely to change (though of course any mutations which increase its effectiveness will be heavily selected for). This I think was one of the main reasons the spike protein was targeted by the mRNA viruses.

> Why is the article saying the opposite?

The cited study in OP may have a slightly pro-vaccine bias, potentially because two authors have "the potential to receive a share of IP revenue" on a relevant patent, and because one author consults for Moderna. Regardless, the study presents scientifically accurate findings, but in a few places it tries to stretch those into questionable conclusions. For example, the authors write:

> At first glance, the RBD targeting of the vaccine sera neutralization might seem likely to increase susceptibility to viral mutations, but the rest of our results suggest that this MAY not be the case. [4]

So keep that tilt in mind when reading it.

> one might expect targeting a wider variety of places on on the COVID spike protein to result in better immunity against variants

Yes this is good intuition, here are excerpts from other literature illustrating why targeting a wide variety of SARS-COV-2 proteins can provide better immunity. In fact, this reasoning is why ongoing vaccine research is investigating formulations beyond the current solely spike protein focused vaccines. Notably, one shortcoming of the current mRNA vaccine formulations is that they do not induce nucleocapsid (N) protein antibodies - whereas natural infection does.

> The nucleocapsid protein of SARS-CoV-2 has been suggested to be an important target for T cell responses. [1]

> Firstly, this protein contains conserved cross-reactive T cell epitopes that are present among different coronaviruses, suggesting that it could be an ideal target for universal coronavirus vaccines. [1]

> Secondly, the nucleocapsid protein is among the most abundant structural proteins in the coronavirus lifecycle, which may facilitate early antigen presentation and recognition by T cells. [1]

> Previous knowledge on other related coronaviruses and the prompt sequencing of the SARS-CoV-2 genome early in the pandemic allowed to identify the spike (S) and the nucleocapsid (N) structural proteins as major targets of antibodies. [2]

> The surface glycoprotein S, which contains the receptor-binding domain (RBD), has a better known function in immunity and is the leading antigen candidate for vaccine development. N is smaller than S, lacks a glycosylation site, and is extensively used in leading serodiagnostics kits due to its abundant expression during infection and early antibody response but its immunological relevance is less established. [2]

> N forms ribonucleoprotein complexes during the virion assembly process by binding to the viral RNA genome and packing it into long helical structures. Its main function is to regulate viral RNA transcription during replication, promoting the synthesis of its own proteins while interfering with the metabolism, protein translation, and proliferation of the infected host cell. During the process of infection, N dissociates itself from the genome and is exposed to the host immune system, and its high immunogenicity has also prompted its exploration as vaccine target. [2]

> Interestingly, significant protein similarity between SARS-CoV-1, SARS-CoV-2, and other HCoV has been reported for N, including a highly conserved motif in the N-terminal (NT) half of the protein (FYYLGTGP) and relevant immunodominant epitope regions. [2]

> Evidence from multiple experimental studies showing that single RBD point mutations can lead to resistance to neutralizing convalescent plasma from multiple donors suggests that specific single mutants may be able to evade spike-targeting vaccinal immunity in many individuals and rapidly lead to spread of vaccine-resistant SARS-CoV-2. [3]

[1] Combining spike- and nucleocapsid-based vaccines improves distal control of SARS-CoV-2 https://www.cell.com/cell-reports/pdf/S2211-1247(21)01108-6....

[2] Immunogenicity and crossreactivity of antibodies to the nucleocapsid protein of SARS-CoV-2: utility and limitations in seroprevalence and immunity studies https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879156/

[3] Risk of rapid evolutionary escape from biomedical interventions targeting SARS-CoV-2 spike protein https://pubmed.ncbi.nlm.nih.gov/33909660/

[4] Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection https://pubmed.ncbi.nlm.nih.gov/34103407/

Thanks for the detailed review. We need AI bots and media metadata to enable automated "supply chain analysis" of media and journal articles, including social network analytics of finance and other influence networks.

Such analytics are now beginning for software supply chains, thanks to a Presidential Executive Order. As warfare spreads from kinetic to cyber to psychological, we will need more tooling to keep pace with the analytical descendants of Cambridge Analytica. Social discourse can be mined in real time to identify high-leverage, transient gaps in narratives, to influence far-reaching real world policy.

Individual humans, parsing text for meaning, have an uphill journey.

TODO: create Streisand bot to extract downvoted comments from HN, differentiate between legitimate vs targeted downvotes, then republish to an audience for critical response on any valid points, i.e. use the infrastructure and human resources of would-be censors, to generate new signals.

Particularly when even just with the comments here, someone else was mentioning that targeting the nucleocapsid had led to concerns of ADE in past animal tests, which makes it even more fascinating to try to connect all those bits.

Inoculation with an mRNA vaccine provides recognition of few antigena (e.g. RBD). The size of the vaccine dosage and the delay of a month between doses is designed to create a strong recognition of the chosen antigens.

Infection's response to key antigens like RBD is inherently more limited because: 1) immunity creates antibodies and T cells that target a wider range of antigens, and 2) exposure to COVID antigens usually fades after 7-10 days, limiting the immune system's time to build further defenses.

> Anyone with more experience in immunology care to weigh in on why the second paragraph there follows from the first? Naively, one might expect targeting a wider variety of places on on the COVID spike protein to result in better immunity against variants, not worse. Why is the article saying the opposite?

The RBD is the part of the spike protein that latches onto the cell. Specifically it latches onto the ACE2 receptor. If the RBD changes too much then the virus can no longer infect its target cells (because it can't attach to ACE2 receptors). This means that there are probably strong limits on how much this section of the virus can change.

Because we expect the RBD to change less than other areas, and because the mRNA vaccines recognize more of these possible changes, then we have a reasonable expectation that mRNA based immunity should continue to be effective.

To make a crude analogy, ACE2 is a phillips head screw. The spike protein is a phillips screw driver. The tip of the screw driver is the RDB. Infection elicited antibodies recognize random spots all over the screw driver. mRNA vaccine elicited antibodies recognized spots all over the tip. Eventually you can turn the handle into a shape that won't be recognized, but there are strict limits on how much you can change the tip while still having it function as a philips screw driver. And of the ways that you can change the tip, the mRNA antibodies will match more of them than the naturally acquired ones. At least that's the expectation.

There are still possible ways that the virus might evade; perhaps by making shields for the tip that block portions of the antibody, but this seems like it might be harder than changing the handle's shape.

What about inactivated vaccines such as Sinovac? Does that immune response resemble natural infection?

Does this mean inacticated vaccines work better against variants?

Another consequence of this is that, theoretically, the virus could mutate and be unrecognizable by the antibodies produced by the vaccine.

The same could be said for convalescent immunity too.

One reason the vaccines target the spike protein is that it's how the virus breaks into human cells.

It it mutates to a different spike shape, it's very unlikely that it will keep that breakin power.

Or at least that is the assumption :)

and given that vaccines target only a segment and pretty much the same segment, such mutation based escape from all of the vaccines at the same time is of very high probability - https://journals.plos.org/plosone/article?id=10.1371/journal... . And the fact that the current vaccines don't prevent delta infection seems to confirm it. Whereis natural immunity targets multitude of the segments (and not only of the spike protein) thus naturally providing much more robust immunity.

We need a vaccine for delta. Unfortunately from MBA perspective it is much more profitable to push the current vaccines down the throat of the populace through forced mandates and hysteric propaganda instead of investing additional billions in the vaccine for the mutated virus.

2 shots don't work, thus the 3rd, "booster", then what? the 4th? It is pretty typical for the medical industrial complex to push to sell more and more product in response to low effect, like that opioid dosage increase.

> However, vaccines only target spike protein, while a previous infection will cause your body to produce antibodies for a much larger set of targets on the virus, which in practice leads to a more robust immunity. This is supported by data from Israel and some recent studies

No, it does not.

The data from Israel only supports the claim that immunity from infection is longer lasting than from the vaccine, which should not have been a surprise to anyone.

It does not support any specific mechanistic explanation.

Honestly I have yet to see any convincing scientific evidence that is free from confounding factors which suggests that there is waning immunity.

And there's reason to believe from HCoV-229E that immunity against coronaviruses is actually durable and that reinfection is due to mutation and immune escape.

https://journals.plos.org/plospathogens/article?id=10.1371/j...

Thank you. I don’t understand why more people won’t argue like you do. We have 4 endemic human CoVs. Why not learn from the experience we had there?

I get the impression anything we could learn which doesn't support a foregone hyperbolic conclusion gets vastly ignored by the media and misconstrued as fringe in the court of popular opinion. All of this started with panic-buying toilet paper and baker's yeast from the grocery stores. I'm not surprised despite a considerable majority of US citizens being vaccinated, all reporting is underscored by pandemic levels of fear and sensation. The general public will still hatefully rebuke any claim that among a significantly vaccinated population Covid-19 statistics are largely comparable to many other endemic diseases. We were told this whole time that it wasn't just another flu, but to a vaccinated person it is just another illness. You don't want to get the flu, you don't want to spread it around, but you don't let fear of it consume your everyday life. But here we are, front page circa 2021, a bunch of vaccinated adults obsessing over reinfection.

Millions of people have died in less than two years, 650,000 where I live in the US. More specifically here in Florida, ICU capacity is at 93%, and cases/hospitalizations/deaths are at record highs for the entire duration of the pandemic. People are being turned away for cancer treatments because there is simply no room at the hospital. The peak of daily deaths and infections in our state is right now.

This is news because the flu doesn’t do that every year or any year since 1919. It’s news because it’s the deadliest pandemic in over a century, and the death rate in some areas is at its peak and climbing, despite higher vaccination rates then a typical flu season.

I cannot understand why denial of this information is so important to you, but if you continue to spread doubt about taking more precautions than the flu, people may listen to you and those people may die.

Exactly. Modern day healthcare is keeping most Covid patients alive. But the disease is also putting a strain on modern day healthcare more than anything else ever has.

Note that I actually agree more with you two about the overall impact of the pandemic and the collapse of the hospital system, not with ManBlanket up there.

I'm coming at this more from the perspective that the panic over delta being something straight out of a Big Bad TV Trope that breaks all the previous rules, is that it completely undermines the effectiveness of the vaccination campaign. The current best antivaxxer argument right now is just that all the headlines show that the vaccines don't work. I'm pushing back against that. It still looks to me like nobody has given me any indications the vaccines don't work. I think their VE against delta has been dramatically understated, the waning immunity has not been proven, and their efficacy against transmission is probably a lot higher than currently assumed.

At some point in the future I'll agree with the perspective that we need to start treating this more like the flu, but if the hospital systems are falling over we aren't there yet.

COVID-19 just recently surpassed the number of war casualties from World War I forward.

625K war casualties[1] < 635K COVID-19 casualties[2]

[1]: https://en.wikipedia.org/wiki/United_States_military_casualt... [2]: https://www.nytimes.com/interactive/2021/us/covid-cases.html

I don't deny any of this information, on the contrary I'm well aware of it. Average age 79, 99% of had a significant confounding illness. The vast majority of people who have died were already sick and living in a nursing home, literally waiting to die. Meanwhile in my state until March of last year deaths from child abuse, which has sky-rocketed at unprecedented rates world wide since the start of the pandemic, outstripped deaths from Covid. I don't understand why you and so many other are living in denial of that information. It's like you don't even care about the costs of your actions, just a the vague justification of the number of people who have died from covid. The fact is people are going to die no matter what you do about it, so not acknowledging these policies themselves have caused suffering, let alone seriously consider whether or not they were effective, is a more egregious sleight than not doing anything at all. 5 years from now people are going to look back at humanity's reaction to Covid and say, "wow, that was astonishingly stupid."

There may be no scientific reason but it would make focusing on mRNA vaccine exclusively look like a strategic mistake. The driving factor behind the approach is the belief that the encoded domain is essential to virulence. Immune escape from mutation would imply failure of that reasoning. Unfortunately other approaches that focus exlusively on a segment of the S protein would face the same challenges.

You're thinking in absolutes, and there very likely will be immune escape eventually against the mRNA vaccines, and that is pretty much expected.

But that doesn't mean the mRNA vaccines would be failures.

Focusing on the spike was also done because mRNA vaccines against the nucleocapsid protein of SARS-CoV-1 showed evidence of ADE in animals models so nobody wanted to go down that road. That decision to run with the spike protein is very unlikely to be shown to ever be a mistake in hindsight and will have been the right choice (and certainly the right choice given the information at the right time and a decision which produced an entirely successful vaccine).

It is also a really pretty safe bet that this virus will evolve to achieve immune escape just like HCoV-229E does and will start reinfecting everyone again. That won't make this vaccine a failure. And that's a good thing since its more likely that forcing it to evolve to achieve immune escape will force it to made tradeoffs between immune escape and transmissibility/virulence/fitness.

From the last link: "Conclusions: This study demonstrated that natural immunity confers longer lasting and stronger protection against infection, symptomatic disease and hospitalization caused by the Delta variant of SARS-CoV-2, compared to the BNT162b2 two-dose vaccine-induced immunity. Individuals who were both previously infected with SARS-CoV-2 and given a single dose of the vaccine gained additional protection against the Delta variant."

Note the "longer lasting and stronger".

GP is not disputing that. They're pointing out that we know this, but not why.

It might seem small but they only said it was longer lasting, not that it was stronger:

> is longer lasting than from the vaccine

Hmm. This smells of literal survivor bias. The group that survives the delta variant is a smaller set than all who got infected while all vaccinated persons survived, even ones that wouldn’t have survived without the vaccine.

While true, it's not by much; mortality for covid-19 is less than a percent of all hospitalizations, iirc.

Right. The point of the vaccines is to not have to find out if you are in the 99% who survive Covid or the 1% who don’t.

and if virus keeps mutating... twice-annual booster shots all over the earth?

I really hope we don't end up with a Marek's disease, but in humans.

https://en.wikipedia.org/wiki/Marek%27s_disease#Prevention

It seems more likely that after we've all developed some immunity to it and some variants, we'll have some level of resistance to what most strains bring to bear, and so milder and less lethal, like existing colds (also a coronavirus...) and flus.

You make it sound as if that's good news.

If this was missed in the design of the study, why would it be good news?

I do not think you remember it correctly. Cumulatively mortality is around 2% and sometimes higher of all known cases.

That seems wildly optimistic.

In the UK, 2% of people who tested positive have died. In the US, 1.7% of people who tested positive have died.

The mortality rate among hospitalized people even higher.

[1] https://coronavirus.jhu.edu/data/mortality

That's about right for those who tested positive, but current CDC estimate is that for each one that tests positive, 3.3 others got it and never got tested. That makes the actual rate something like 0.38%. Which is a lot more than 0, and is even a lot more than a normal flu, but it's not 1.7%.

Sure, but the CDC is mostly talking about the United States and the world is a lot larger than that. People are still dying all over the globe from this in fairly high numbers. And in the developing part of the world we don't even really know the numbers at all, we only do for those places that have a reasonable infrastructure and where healthcare did not completely collapse.

Developing countries will probably have a larger undercount so estimates derived from the US may already be projecting a more conservative figure.

I wasn't impressed by your point at first, but it occurs to me that the vaccination rate was way higher among older people, at least in the U.S. and probably in many countries. On the other hand, the rate of those who got covid-19 was higher among younger people. So, you may have a point there.

> It does not support any specific mechanistic explanation.

You're right that the recent pre-print cited by GP - regarding the data out of Israel - does not prove or disprove any specific mechanistic explanation.

However, interpreting GPs comment charitably, that study does support the notion that immunity acquired through natural infection may be more robust to mutations and variants - the mechanisms of which have been articulated in a variety of other literature. See my sibling comment [1] for supporting citations and excerpts.

[1] https://news.ycombinator.com/item?id=28320340

which should not have been a surprise to anyone

Why is that? I have no background in immunology so it's mildly surprising to me.

The vaccine is a basically partial copy of the virus, so it stands to reason that the virus would be more dangerous as well as trigger a broader immune response.

But now we're back to speculation about mechanism, which GP was opposed to.

>> No, it does not.

But is is acknowledged in the article linked here:

>> Specifically, antibodies elicited by the mRNA vaccine were more focused to the RBD compared to antibodies elicited by an infection, which more often targeted other portions of the spike protein. Importantly, the vaccine-elicited antibodies targeted a broader range of places on the RBD than those elicited by natural infection.

It does not follow that vaccination conveys better immunity than previous infection. Only better response to mutations in one area of the spike protein. Nothing else is being claimed in this paper.

>The data from Israel only supports the claim that immunity from infection is longer lasting than from the vaccine, which should not have been a surprise to anyone.

I find that surprising. Why did you expect that? Why should I have expected that?

The vaccine is effectively a small part of the virus, for the immune system to learn to recognise. The virus itself has many parts for which an immune response can be developed.

>>>> The data from Israel only supports the claim that immunity from infection is longer lasting than from the vaccine, which should not have been a surprise to anyone.

Apparently it is a surprise for USA and Europe as the former only recognize infection based immunity for three months and the latter recognizes it for 6 months, while some EU member states recognize vaccine based immunity for 8 months.

please do not make stuff up to fit your narrative.

As other commentators have noted, it's quite a leap in logic to use reinfection data to make a mechanistic claim on how natural infection may or may not improve the immune response compared to vaccination.

In addition, the naturally-infected and vaccine populations are not the same. For example, having a bad experience with a natural infection of Covid may cause people to not participate as much in virus-risky behavior. On the other hand, people who seek out vaccinations may have done so for business or personal reasons that make them more prone to expose themselves to the virus. It is also possible that (re)infection for the two groups are not monitored at the same rate. Without controlling for these factors (which your first link does not) you cannot make any judgement about which immunity is stronger from your cited data.

Lastly, your second link and your last link directly contradict each other — the second link claims "Recovered COVID patients don't benefit from vaccine" but your last link says "Individuals who were both previously infected with SARS-CoV-2 and given a single dose of the vaccine gained additional protection...." If you're going to cite sources, they should probably have a consistent message :).

That mechanism of action is just what I’ve seen put forth by immunologists commenting on the these kinds of results.

While the author’s opinions on the necessity of vaccines do differ, they do agree on my main point: that empirically, natural immunity is indeed robust and tentatively even better than vaccine acquired immunity.

It looks like getting a vaccine helps boost immunity in all cases, whether you had a previous infection or if you had 2 doses and I would bet even after the booster, each additional shot will continue to provide some marginal benefit. So keep getting jabs, I guess, or you’re killing grandma.

I think at this point throwing in “you should vaccinate (regardless of your individual circumstance)” into your conclusion, even if it’s a complete non-sequitor, is a hedge against losing your job/funding/respect of your equally frightened peers. The COVID research equivalent of the “making the world a better place” SV trope.

To acquire immunity naturally you have to get sick.

In oder to acquire that immunity you have a 1% chance of dying, 2% chance of ending up in the hospital on a ventilator for a month, and a 20% chance of long haul covid.

To acquire immunity from a vaccine you have a 0.001% chance of an allergic reaction.

Which risk do you choose?

Sorry. I never said and never even meant to imply that you should try to get sick instead of getting the vaccine. Only that if you were already sick, that it greatly shifts your own risk/benefit profile in the direction of not getting the vaccine.

Currently, I think the numbers for a person in that case are then 1% chance of getting COVID again naturally vs vaccine’s 0.001% chance of allergic reaction and a reduced chance of getting COVID again of 0.5%. (Using very round numbers)

Which risk do you choose?

Source: https://www.cdc.gov/mmwr/volumes/70/wr/mm7032e1.htm

I’ll personally take the risk of being reinfected with COVID.

Either way, at a <= 1% risk of re-infection, I’m no longer a real liability to society so please just leave it for me to decide and don’t force me undergo any unnecessary medical procedures.

> while a previous infection will cause your body to produce antibodies for a much larger set of targets on the virus, which in practice leads to a more robust immunity.

That is simply not a statement you can make without supporting evidence.

Your immune systems binds to irrelevant targets all the time. People normally got measles once, but lots of people got it multiple times.

It is entirely possible that your immune system will bind to something that mutates rapidly and have worse response than the vaccine.

As someone who got the Covid19 in Original Flavor(tm), I still went and got the vaccine. I don't want to be one of the unlucky ones whose immune system didn't flag the spike protein for destruction.

> People normally got measles once, but lots of people got it multiple times

Is there a good reference for the percentage of people who did?

The vaccines also lack a specific abnormal side effect that the infection may carry: risk of death and hospitalization.

Now with death, one could argue that it does provide much longer lasting immunity....

Seriously though, for most people the severity of infection-derived immunity is preconditioned upon them surviving the disease so this looks like the classic "planes with bullet holes" image?

Not with inactivated virus. There are vaccines based on that.

… did you just respond to a statement about the reduction in morbidity and mortality from vaccines compared to infection with the virus… with a statement that says ‘use a vaccine?’

Opening argument was about robustness of immune response from exposure to the whole virus. GP implied infection was the only way to be exposed to the whole virus. I pointed out such exposure can also be achieved through inactivated virus.

> The vaccines also lack a specific abnormal side effect that the infection may carry: risk of death and hospitalization.

This is well-intentioned but false. The vaccines can send you to the hospital (side-effects). It's rare but happens. Similarly, you can be vaccinated, get infected with SARS-2, and end up in the hospital, so it's not even true that they avoid hospitalization from SARS-2 itself completely. (They help a lot with hosp/death from the virus, to be clear)

The risk associated with the vaccine (and the magnitude) are orders of magnitude lower than that of natural infection-based immunity.

The vaccine can almost certainly send a few people to the hospital in the same manner that an airbag could almost certainly cause injuries during an accident.

It's very different from a natural infectionimo.

"the risk associated.... immunity "

I know that it's a very unpopular opinion, but i'd say your statement is unfortunately still not 100% proven for every individual. A healthy 20 yo has "almost" 0 chance of having bad outcome from the covid. He also has "almost" zero chance of doing a hearth infection from RNA vaccines, and we have no idea about the long term consequences of both virus and vaccines, since both are only a few years old.

Making definitive statements in this context is hard.

Talking about these issues at the individual level when it should talked about in broader terms distorts the reality of the situation. If you try to convince "no-risk" individuals that they should get the vaccine for their own health, you're not going to get very far.

But explaining to that same 20 year old that he might unintentionally bring COVID home from college and proceed to unintentionally infect high-risk parents or grandparents? That's where the real damage would comes from.

The peace of mind knowing I'm not going to unintentionally kill off members of my family is priceless.

I'm really glad you bring this argument, because it seems to me as it would be indeed the only "real" reason to have young people vaccinated..

Unfortunately, the recent news on that front don't bring much hope. Vaccinated people can be infected, and transmit the virus to elderly people (the rate at which they do being currently debated among specialist, some claiming it is much less, other claiming it is just as much as non-vaccinated asymptomatic people).

I would like to think that getting vaccinated helped reduce viral load enough to help limit potential mutations to some degree, but who knows.

I do know I need to be able to live with myself, and if I accidentally hurt someone I loved due to being careless in the face of a real threat - it would tear me up. I'm sure others feel the same, and I hope people can keep it up through the fatigue. :)

yeah, it seems like if you're ever visiting an old relative, the better option seems to still be to get tested right before, vaccinated or not.

There's a critical point I think is getting lost in the shuffle: vaccine immunity may be different from natural immunity, but (1) it does seem to protect against severe cases, (2) precisely because the protection is imperfect, the first infection you get after being vaccinated should train the immune system in a similar way as an unvaccinated infection.

So to me, the real question is, what is your immunity like after you get vaccinated AND then infected? Because that's what is most likely to happen in the long run, as COVID becomes endemic. Everyone's going to get an infection, so does vaccine + infection give you better or worse immunity than no vaccine + infection?

It seems like the article is saying that vaccine immunity is actually more robust that natural immunity though.

For spike proteins. Not for the other targets you get with natural immunity.

> For spike proteins. Not for the other targets you get with natural immunity

From the article: "the new evidence shows that protective antibodies generated in response to an mRNA vaccine will target a broader range of SARS-CoV-2 variants carrying 'single letter' changes in a key portion of their spike protein compared to antibodies acquired from an infection." The study discussed in the article unequivocally states that vaccine-induced immunity is more robust than that from infection.

> unequivocally states that vaccine-induced immunity is more robust than that from infection.

It absolutely does not make such a strong claim - a more accurate takeaway is that vaccination using the current mRNA based formulations induces an immune response highly targeted toward the S protein RBD. This has not been conclusively proven to provide better or worse protection than immunity acquired through natural infection.

> At first glance, the RBD targeting of the vaccine sera neutralization might seem likely to increase susceptibility to viral mutations, but the rest of our results SUGGEST that this MAY not be the case.

> We found that the specificity of the mRNA-1273 vaccine-induced RBD-binding antibody response often narrows over time. In contrast, the infection-elicited RBD-binding antibody response often broadens over time

> The vaccinated individuals in our study were relatively young (18–55 years) and healthy, whereas the convalescent individuals were older (23–76 years, median 56) with a range of comorbidities (13).

> Additionally, we did not examine effects of mutations or deletions to the N-terminal domain of the spike protein, which can also affect neutralization by vaccine sera (7).

> Our experiments assayed binding of antibodies to isolated RBD expressed by yeast, and so cannot capture mutational effects on trimer conformation or antibodies with quaternary epitopes

[1] Risk of rapid evolutionary escape from biomedical interventions targeting SARS-CoV-2 spike protein https://pubmed.ncbi.nlm.nih.gov/33909660/

The quote you're highlighting is specifically referring to 'single letter' variants of the spike protein. Immunity from infection gives a wider variety of protections beyond just the narrow targeting of the spike protein.

The RDB portion of the spike protein is the part that allows the virus to latch onto your cells. We therefore expect strong limitations on how much this portion of the virus can change while still remaining infectious.

Good point, edited to clarify.

Beyond just this study, which doesn't give the whole picture of immunity, I think there is conflicting evidence. Given that vaccine effectiveness seems to be going down in Israel, I think there are legitimate concerns about the robustness of vaccine-based immunity - but the question is always "relative to what?". If it ultimately sets you up similar to or better than natural immunity from an infection (which also wanes, as we get, e.g., colds over and over throughout our lives), that's the best you can hope for.

If that's the case, then they should retract and work towards understanding why their methodology failed so miserably.

The data from Israel shows an order of magnitude better immunity from prior infection than the vaccine.

And then the question is, should you as a vaccinated healthy person mind getting infected in the sense that it can shield you maybe even more from future variants or is this a dangerous game to play?

I think it's all about timing. Right now in Oregon our hospitals are full. So the less people getting infected right now the better.

If I remember correctly, the number of vaccinated people who get infected and require hospitalization is quite low.

The number of people possibly infected by a vaccinated person as an asymptomatic or mild symptomatic carrier and who may require hospitalization is still ambiguous. I will continue to err on the side of caution, tho I have little worry for myself personally.

You remember correctly:

More than 99% of recent deaths were among the unvaccinated, infectious disease expert Dr. Anthony Fauci said earlier this month on NBC's Meet the Press, while Walensky noted on Friday that unvaccinated people accounted for over 97% of hospitalizations.

https://www.npr.org/2021/07/16/1017002907/u-s-covid-deaths-a...

As of April 2021, the CDC "unvaccinated" definition includes people who are thirteen days after their second vaccine, https://www.cms.gov/files/document/qso-20-38-nh.pdf

> Fully vaccinated” refers to a person who is ≥2 weeks following receipt of the second dose in a 2-dose series, or ≥2 weeks following receipt of one dose of a single-dose vaccine. “Unvaccinated” refers to a person who does not fit the definition of “fully vaccinated,” including people whose vaccination status is not known

That is wild. The situation in UK is nowhere near '99% unvaccinated suffer terrible outcome'.

On 20th August, Public Health England published a report that is quite a bit more balanced. From Table 5, pp 22-23, Delta cases:

    overnight inpatient admissions (inclusion#)

    all ages
    unknown                      99
    <21 days post dose 1        260
    ≥21 days post dose 1        689
    ≥14 days post dose 2      2,204
    unvaccinated              4,033

    <50 age group
    ...
    ≥14 days post dose 2        366
    unvaccinated              3,044


    deaths within 28 days of positive specimen date

    all ages
    unknown                      16
    <21 days post dose 1         14
    ≥21 days post dose 1          5
    ≥14 days post dose 2        679
    unvaccinated                390

    <50 age group
    ...
    ≥14 days post dose 2         27
    unvaccinated                 72

For all adults percent fully vaccinated is 75%, whereas for <50, percent one dose vaccinated is somewhere between 60-75%

https://assets.publishing.service.gov.uk/government/uploads/...

https://www.bbc.com/news/health-55274833

This may be explained by Simpson's Paradox. Something similar happened in Israel, if you look at the raw case numbers for the current wave, it looks like the vaccine only has a ~67% efficiency:

https://www.covid-datascience.com/post/israeli-data-how-can-...

The UK and Israel both have very high vaccination rates of older people, and lower fully vaccinated rates of younger people. Someone who is 75 most likely has a much weaker immune system than someone who is 25, to the point where someone who is 75 and fully vaccinated may have a much harder time fighting the virus than someone who is 25 and unvaccinated.

The data from Israel if broken down by under and over 50s, shows the vaccine efficiency is 92% for under 50s and 85% for over 50s. Israel mainly used Pfizer though, where as the UK mainly AstraZeneca, so there could also be differences there.

Of course Simpson's is heavily at play, of course especially when lumping <25s with >75s. Not sure I see how one can get from the (UK) data to statements like 'more than 99% of recent deaths were among the unvaccinated', which seems off by at least an order of magnitude.

It's probably still worth trying to reduce the amount of virus in circulation, even if individual risk is low. There's someone in another thread talking about being on immunosuppressants, for example.

I don't think it's a binary condition either, we can do things that are more effective and less costly (like cutting down on large, indoor, adult social gatherings) and not do things that are less effective.

That's what I've been proposing for a few months. Get the vaccine and then get the delta variant a few weeks later to crush it and then be super immune for future variants that jet off of that one.

Do you have evidence that this is the best course of action?

Well the obvious problems with it is that it's hard to tell you've been infected and you need to quarantine for the entire duration until you are sure you've been infected and have recovered.

Apart from that, if the protection from a vaccine is temporary then there's no reason to believe your immune system will learn anything from an infection it can already handle. That part of the immune response takes a while and may never succeed if the virus is long gone before then.

The whole point of my strategy would be that perhaps Delta is a precursor to a, let's say, Zeta variant that has almost complete evasion to the vaccine. Let's say in January or something.

So what you're doing is giving your body a high chance to crush the Delta and gain some cross-immunity towards the future evasive variant.

Whereas if you just relied on the vaccine, it might not even work well in January.

Obviously this is just conjecture, but I think a real possibility.

Who knows if you getbDelta while vaccinated and you crush it shortly afternentry if your immune system makes any changes or not.. this requires an immunologist to answer.

The vaccine is highly effective at preventing severe disease requiring hospitalization, but nothing is 100% (after 6 months, Pfizer is 97% effective at preventing severe disease) -- I'm not going to deliberately expose myself to something that could put me in a hospital.

And no point, really. If I'm going to force myself to have the disease to build up immunity, why not just wait until I'm accidentally exposed (which may not happen)?

The whole point of my strategy would be that perhaps Delta is a precursor to a, let's say, Zeta variant that has almost complete evasion to the vaccine.

Let's say in January or something.

So what you're doing is giving your body a high chance to crush the Delta and gain some cross-immunity towards the future evasive variant.

Whereas if you just relied on the vaccine, it might not even work well in January.

Obviously this is just conjecture, but I think a real possibility.

Unless, of course, Zeta has almost complete evasion to natural immunity too. Then you've intentionally exposed yourself to Delta for no reason.

I'll stick with my strategy of getting the vaccination (including a booster when eligible), and taking reasonable precautions against exposure.

If it comes from the lineage of the prevalent strain... there's no way that it would not have cross-immunity after 6 months.

Here's a pragmatic question - do we need large amounts of people who have natural (non-vaccine) antibodies to donate their blood? To put it more crudely, is there a way that everyone at large can benefit from their (unfortunate) suffering?

I know someone who has been donating for exactly this purpose (he's a bar owner, and apparently was told by his doctors that he had an extraordinarily high antibody count). Unfortunately, the results from all of these kinds of treatments thus far has been less than hoped for.

Individuals with a combination of history of COVID and vaccination appear to have exceptionally strong protective immunity that has been described as "bulletproof." As published in Nature [1] and analyzed by JAMA [2], individuals who had been infected (even those with mild disease) and vaccinated had over 50 times more neutralizing antibody activity than those who were unvaccinated. This level of protection was more robust even than that seen in fully vaccinated individuals.

[1] https://www.nature.com/articles/s41586-021-03696-9 [2] https://jamanetwork.com/journals/jama/fullarticle/2782139

It would be interesting to know the order of events in the population studied (vaccination first or infection first?) and whether it seems to matter for the ultimate level of immunity achieved.

Antigen targets aside, there is also a difference in the production of antibodies in the mucosal system.

Current vaccines are intra muscular and lacks a robust mucosal response while natural infection will provide mucosal immunity as well.

As one can imagine, mucosal immunity is very important in an upper respiratory track disease w.r.t. symptomatic infection and transmission.

Yeah, why aren't we putting more effort into getting an intranasal vaccine approved for emergency use? An intranasal vaccine would confer mucosal immunity and might also be more acceptable to the vaccine hesitant. They're talking about 3rd shot boosters, but I'd really like to be able to get an intranasal vaccine as the third booster.

Nasal vaccine trials are underway. We should have preliminary results in a few months.

https://www.medpagetoday.com/special-reports/exclusives/9252...

IIRC there is an intranasal expected to be approved mid next year. I can't find the source I read that in, so take the timing with a grain of salt. Another source I can't find at the moment mentioned questions about the duration of protection from that method of vaccination as well.

I would guess the push for intramuscular was driven for multiple reasons, the first being ease of development and the second to keep hospitalizations and death at a minimum.

I don't think anyone's concerned about IM vs. IN as they are mRNA vs. DNA. The boosters deliver double stranded helix straight to the nucleus like a Windows update. You'd have to pull an Apocalypse Now to roll that back. GM people nobody panics but GM organic food and everyone loses their minds.

I thought the boosters just have mRNA strands like the original mRNA vaccines do? I haven’t heard anything about them using CRISPR or otherwise editing the human genome. Would be neat but it seems like pharma companies charge a million dollars for that kind of treatment.

My source is the New York Times https://archive.is/Wk2nU

That's the current Johnson + Johnson vaccine. What does that have to do with "boosters" and what about that requires an "Apocalypse Now"?

You don’t know how vaccines or viruses work, do you?

I know how code works and that DNA is code.

Every viral vaccine works this way, though. Because every virus works this way.

Don't most viruses just deliver mRNA that tells the cell to make more viruseses? I thought only a few, like herpes, deliver dna. That's why it can't be cured. DNA vaccines used to be commonly used on dogs and livestock to prevent things like rabies iiuc. It wasn't until these jensson booster shots that I've seen them being given to people on a large scale. Also there's a big difference when the mRNA and DNA code is emerging organically and when it's being engineering in labs.

DNA viruses include chickenpox, whose massively successful vaccine is an attenuated virus which of course delivers “double strand helix right to your nucleus.”

(And of course smallpox was a DNA virus as well.)

Your appeal to nature fallacy is not worthy of a response.

So you're saying the booster shots that deliver engineered dna via viral vectors are ok because herpes and smallpox do it too?

I just learned last week that my COVID antibody count from the vaccine is zero. Since I'm on an immunosuppressing medication that wipes out the B cells in my bloodstream, this isn't really all that surprising to me. I learned about this because I'm in a medical study, and other people in the study who take the same medication also don't produce any COVID antibodies in response to the vaccine.

What's interesting is that I still get side effects from the vaccine, and they seem to be right in line with the side effects that other people generally report. I'm no immunologist, but I've taken an armchair interest in the subject since I've been managing an autoimmune disease (MS) for the past 25 years.

The immune system is an amazingly complex thing with many branches. Different types of cells interact in ways that we have yet to fully understand. In spite of having no B cells (except what's in my bone marrow), my T cell count is solidly in the normal range. And the currently-accepted catalog of types of T cells is enough to make your head swim:

https://en.wikipedia.org/wiki/T_cell#Types_of_T_cell

Three types of CD4+ Helper T cells are implicated in MS: Th1, Th17, and Th9. And yet by killing the B cells in my bloodstream, for me that seems to stop these T cells from doing MS-like activity without substantially compromising my body's ability to still fight infections.

What does all this mean for my own risk level from COVID, and in particular the Delta variant? Absolutely no clue. I've gotten my third (booster) shot and will be getting more blood drawn next week for the medical study, which I expect will again result in a zero COVID antibody count.

People on my medication have been shown to have more severe cases of COVID when they contract it. I'm a realist about COVID and realize that some day I'll contract it. The best I can do is make sure I'm otherwise in good shape by eating, sleeping, and exercising right. Another option is to go off my medication, let my B cells recover, and then try another less effective medication for a while. For people in my circumstance, there really are no good answers right now.

I know this is all at best tangential to the subject of this study, but I'm glad this research is getting done, and I hope it will lead to a better understanding of how to protect everyone.

Is it possible that your side effects are a result of your immune system reacting against the delivery mechanism (PEG or adenovirus) of the vaccine? Here's one source suggesting this may occur: https://sanchakblog.wordpress.com/2020/12/06/mrna-vaccines-b...

"I'm a realist about COVID and realize that some day I'll contract it. The best I can do is make sure I'm otherwise in good shape by eating, sleeping, and exercising right...."

My goodness, what a remarkably calm and informed attitude. It's a wonder you're allowed on the internet.

By the way, it is theoretically possible that your immune system knows how to make the antibodies, but isn't right now because of the immunosuppressing medication. One strategy might be to only pause that if you get sick, hoping that your system knows how to make the antibodies, and will do so more quickly because you've been vaccinated. But that's just a hopeful guess, of course.

Just to make sure, the bit about "remarkable calm and informed", was not mean ironically.

> What's interesting is that I still get side effects from the vaccine

What side effects? How can you know this is coming from the vaccine?

> I've been managing an autoimmune disease (MS) for the past 25 years.

Wouldn't it be more likely that this [multiple sclerosis] is the cause of your symptoms?

I assume we’re talking about the acute flu-like side effects commonly experienced in the days after getting the vaccine. Presumably this person can tell the difference between those and whatever they’ve had for the previous 25 years.

Probably means the typically vaccine side-effects that are similar to getting a cold as your body "fights off" the vaccine and develops immunity.

Wouldn't it be more likely that this [multiple sclerosis] is the cause of your symptoms?

More likely than "immunosuppressing medication that wipes out the B cells in my bloodstream"?

Which medication are you using?

Maybe one for HIV/AIDS? That disease is an eventual death sentence.

MS is autoimmune. HIV/AIDS is a viral infection. The diseases and their treatments are night and day with respect to each other. If by "that disease" you are referring to an HIV infection, then yes, complications from HIV often kill people. If you are referring to MS, not so much, relatively speaking. One study found that people with MS live to be 75.9 years old, on average, compared to 83.4 years old for those without.

Ocrelizumab.

It will be interesting to see how the immune response develops for previously covid-naive vaccinated people after their first covid infection. Specifically, does their immune system still adapt to new variants?

One of the main arguments of controversial anti-covid vaccine people like Geert vanden Bossche is that the immune response generated by the vaccine may thwart the immune system in generating an effective response to future variants after infection[0].

I don’t have enough insight into the immune system’s intricacies to evaluate whether such claims might be legit, but once variants start to emerge that really evade most of the current vaccine-induced immune response, this question will become increasingly important.

[0] https://www.geertvandenbossche.org/post/not-covid-19-vaccine...

It would be interesting to see the duration of the immunity or resistance across multiple vaccine variants. The latest data from the UK indicates that the AZ vaccine suffers less degradation over time than Pfizer, at least when it comes to the Delta variant which is now the prevalent one in the UK.

Israel has now giving boosters to 30 year olds and older in order to boost the immunity to infection and resistance to severe illness.

My understanding is that it may be due to the difference of time during the two shots. It's possible that 2 weeks between the two shots of Pfizer is too short. We're learning.

In the UK Pfizer and AZ both are on 8 weeks protocols and the UK has seen a sharper drop in Pfizer efficacy compared to AZ.

I got Pfizer in the UK, I also suspect to have had it in March (3 days of some coughing and loss of smell), I’m under 40 so no AZ for me.

In part due to immunity duration concerns and, honestly, in part due to supply issues - Canada ended up going way wide on vaccines - most people ended up with twelve weeks between vaccinations.

Canada also made the bold move of mixing different vaccines, even though there were zero clinical trials of multi-vendor vaccines.

Pfizer is 3 weeks, Moderna is 4

Moderna apparently has a 33% higher volume dosage?

It's 3x larger, at least by the amount of mRNA.

But the lower efficacy drop of Pfizer is still higher than the less degraded AZ efficacy...

This more recent Thai study shows that natural immunity is far superior for all known variants... https://www.news-medical.net/news/20210719/Thai-study-looks-...

CoronaVac vaccine? This is a much less effective vaccine than Pfizer and Moderna (https://en.wikipedia.org/wiki/CoronaVac), so it's not surprising that natural immunity would be superior.

What about the Israeli study then.. http://www.google.com/url?q=https://www.spectator.co.uk/arti...

It found that double pfizer jabbed people were 13 times more likely to be infected than those who had already recovered.

Not disputing that. Anecdotally in my household: 100% break-through rate (2 Pfizer vaxxed adults and 2 unvaxxed [ineligible] children] all recently caught what we believe to be the delta variant (confirmed via PCR). That said, the vaccine clearly reduced disease severity; all recovered within a few days.

I am glad to hear that you are all well. I am not sure that you can necessarily attribute your luck to the effectiveness of the vaccine, especially if none of you had known risk factors.

How do you know the vaccine reduced severity? My household of 3 all had it and 2 weren’t aware of it. I had minor symptoms which is the only reason we found out. This was back in 2020 so we were all unvaccinated.

The “b comes after a, so a must imply b” fallacy seems to be everywhere and nobody is calling it out.

I don't think anyone vaccinated is going to be bothered that they didn't have to risk death by COVID (UK mortality rate of 1.99%) to get superior immunity, even if you factor in J&J/AstraZeneca's clotting risk (UK mortality rate of 0.0019%).

A layman's take:

Maybe the antibodies are different because the immune system is being presented with _only_ the spike protein, rather than the whole virus?

From my understanding, the immune system breaks the viral proteins up into pieces and then starts rapidly "evolving" antibodies to target those pieces. The goal being to ultimately produce antibodies that target those pieces, and don't target the learned whitelist of proteins (from your own body). Once it's got that it begins deploying antibody producing cells, and remembers the antibodies for later infections.

What I'm curious about is the stopping criteria the body uses during the evolution stage. It sounds like it's producing an array of antibodies, not just one kind. So the stopping criteria isn't finding one working antibody. Perhaps it's more like, "Produce at least N different antibodies."

If the latter, then the difference between natural and mRNA immunity makes sense to me. If your immune system is working to produce N different antibodies for the whole viral proteome, less of those antibodies will target the spike protein. And thus it will have less resilience to changes in the spike protein. But of course more tolerance to changes in the virus as a whole. Whereas with mRNA the immune system only sees the spike proteins, and since it's still going to make N different antibodies it'll have more tolerance for changes to the spike protein.

What's most interesting to me, assuming any of the above is close to reality, is that mRNA vaccines allow us to give our immune system an inductive bias of some kind. Presumably our immune systems aren't "smart" enough to know what parts of a virus are most conserved, and thus best to target. It just targets all of it blindly. mRNA vaccines used the spike protein because we believe that to be the most conserved proteins. If those change too much the virus either won't work, or will effectively be a different species. So our mRNA vaccines are a way of telling our immune systems to focus their work on the "important" proteins, and thus, we would assume, give us better immunity.

Whether our guess about the spike proteins is correct remains to be seen I suppose.

It's not "make N antibodies". It's a bunch of cells in parallel creating cells specialized to each create a single random antibody. Cells that create antibodies that don't work don't reproduce (linear decay). Cells that create antibodies that worked reproduce (exponential growth). This process stops when the infection is gone.

For the mRNA vaccines, the antibodies only target the some protein, but on the other hand they all target the spike protein. Natural immunity products antibodies that could match want part oft the virus.

The amount of protection you get against a new variant is related to how well your existing antibodies match the new virus. With natural immunity it is likely that only some of the antibodies match (and since each antibody exists in random amounts, the matching antibodies may be the ones that you have much less of). With vaccine immunity,all of the antibodies produced will work against the new variant if the spike protein is the same, offering nearly the same immunity to the variant as the original virus (assuming the spike protein doesn't change significantly). We know that the spike protein is significantly less likely to change than other parts of the virus so that's a reasonable assumption.

Solid layman reasoning, just wanted to clear up one slight misconception:

> mRNA vaccines used the spike protein because we believe that to be the most conserved proteins

The spike protein was chosen mostly because it was well known to serve a primary role in the process of infection and subsequent immune response. Ongoing vaccine research is exploring the use of additional proteins, because they have been demonstrated to be a major factor in viral replication and protective immunity. For example, nucleocapsid (N) protein antibodies are induced by natural infection, but not by vaccination using the current solely spike protein focused mRNA vaccine formulations. N protein antibodies likely have a synergistic effect with S protein antibodies, and thus vaccine formulations incorporating both elements may result in more robust protection, especially against variants.

See my other comment on this thread for supporting excerpts and citations from the literature.

[1] https://news.ycombinator.com/item?id=28320340

Full text here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369496/

From the discussion section:

> In this study, we have shown differences in the specificity of polyclonal serum antibodies acquired by infection versus vaccination with mRNA-1273. The neutralizing activity of vaccine sera is more targeted to the RBD than for convalescent sera, with the majority of vaccine sera losing all detectable neutralization at a 1:25 cutoff after depletion of RBD-directed antibodies. (emphasis mine)

From the conclusion:

> Despite these limitations, our results in conjunction with other recent studies (19) suggest that mRNA vaccines and infection elicit somewhat distinct anti-spike antibody responses. Therefore, it is important to differentiate antibody immunity acquired by different means when assessing the impact of viral evolution. Considerable effort is being expended to identify emerging antigenic variants of SARS-CoV-2 and determine which ones might evade immunity (3, 7, 8, 35). Our findings suggest that the results could vary depending on the source of immunity. Furthermore, carefully characterizing and comparing the specificity of antibody immunity elicited by additional vaccine modalities could provide a basis for determining whether some vaccine responses will be more resistant to viral evolution.

If you are wondering whether you are sufficiently protected by having recovered from COVID, this article provides up to date answers. Get vaccinated. Get a booster if recommended.

You are being unfairly downvoted, because what you are saying runs contrary to people's gut feelings.

At this point, we have enough statistics on people getting COVID a second time with or without vaccination, to know that vaccination reduces your odds of re-infection by ~2.3. [1]

[1] https://www.cdc.gov/mmwr/volumes/70/wr/mm7032e1.htm

This is true. But given the already high baseline immunity for previously infected people, the messaging for them should be somewhere closer to “you can get the vaccine if you want” rather than “you must get the vaccine otherwise you are causing the pandemic”.

I don't know - I consider getting vaccinated to be a matter of common courtesy to those you're going to be interacting with now. I don't feel like thanking folks for only kicking - and not murdering - the adorable puppy at this point. Those who have been advised not to get vaccinated due to immune issues or other medical reasons I completely get - but everyone else is basically saying "I think preserving my pride by sticking to my misinformed opinion is more important than preventing harm to all of you." The vaccines work, get it.

My dad has survived three bouts with different forms of cancer - he's healthy and could be around for a long time. Please don't let your pride put his life in danger.

>"I think preserving my pride by sticking to my misinformed opinion is more important than preventing harm to all of you."

People who don't get vaccinated generally say it's because they don't trust the government. Probably because the government has proven time again to be untrustworthy. It's not just right wingers like the news is insinuating (another untrustworthy group), but all sides of the political spectrum and all demographics have people who are afraid to get vaccinated. No amount of scolding from you will change their mind, and COVID is probably here to stay, so you should adapt to that truth.

As to my motivations, I'm fully vaccinated.

> so you should adapt to that truth.

And they should adapt to the truth that as long as there are COVID outbreaks, there are going to be epidemic adaptations. And that as long as they are the cause of those adaptations, public sentiment will increasingly shift towards making those adaptations targeted against anti-vaxxers.

One of those adaptations should be getting COVID patients out of hospitals, where they are infecting other people, disrupting ER services and scheduled surgeries, and into field hospitals. Every bed that is currently going to deal with a trivially preventable disease is multiple life-saving surgeries that aren't getting done. It would be nice if we could end this year with a working medical system.

If people want to free-load, that's fine, but we shouldn't be throwing scheduled passengers off the plane to make room for them.

The first principle for vaccines to be administered ethically is that the benefit must be outweigh the risk. As trials have not completed and more information on vaccine side-effects is yet to be accumulated, this risk/benefit can be assessed only speculatively.

For instance, this[1] study suggests that the risk of Myocarditis from COVID in young men is six times higher from an infection than from a vaccination. If we assume a gratuitous infection risk of 100%, this may sound like a reasonable benefit. If we however consider that actual COVID infections may be undercounted by a factor of 10[2], the benefit turns negative.

[1] https://www.medrxiv.org/content/10.1101/2021.07.23.21260998v...

[2] https://journals.plos.org/plosone/article?id=10.1371/journal...

What the linked study [1] is saying is that unvaccinated people who get COVID-19 are even more likely to get Myocarditis than vaccinated people; it counters the allegation that people should not get vaccinated because of the risk of Myocarditis.

Even if the vaccine increased the risk (it doesn’t), the risk of COVID-19 is orders of magnitude higher than the risk of the Myocarditis heart condition.

There have been, from the total of 12,910,312 18-24 year-old people vaccinated, [2] about 229 cases of this rare heart disease (and, in almost all cases, the person was discharged from the hospital the same day with a clean bill of health) That means the vaccine has under a 0.002% chance of causing a very rare but not fatal heart condition. [3]

COVID-19, on the other hand, has an overall 1.66% chance of killing someone (38,043,754 cases, 629,644 deaths). [4]

I would rather take a 0.002% non-fatal risk than a 1.66% fatal risk.

Sources:

[1] i.e. https://www.medrxiv.org/content/10.1101/2021.07.23.21260998v... “Young males infected with the virus are up 6 times more likely to develop myocarditis as those who have received the vaccine.”

[2] https://usafacts.org/visualizations/covid-vaccine-tracker-st...

[3] https://www.nbcnews.com/health/health-news/evidence-grows-st...

[4] https://samiam.org/COVID-19/ derived from https://github.com/nytimes/covid-19-data/

> COVID-19, on the other hand, has an overall 1.66% chance of killing someone (38,043,754 cases, 629,644 deaths).

An honest, apples to apples statistical comparison here would compare 18-24 year old death rates to 18-24 year old heart problems risk, not lumping all deaths regardless of age together.

> I would rather take a 0.002% non-fatal risk than a 1.66% fatal risk.

Statistical problems aside, I’m happy if you take a vaccine or boosters that you feel is necessary for your health.

I think all the unvaccinated want is the same absolute right to decide the same for themselves.

The unvaccinated are volunteering themselves as breeders for the next stronger and nastier version of covid, and they pose an active danger to those who cannot be vaccinated.

And, honestly, those who have been vaccinated. Covid-19 has been observed to spread more easily in populations with large unvaccinated proportion and end up infecting (and killing) a larger number of vaccinated people.

Additionally, I am extremely concerned that their irresponsible actions are going to let Covid-19 mutate enough that it can work out a variant that the vaccine will be ineffective against.

Agreed.

The main COVID-19 mutations of concern right now are happening in other countries where the vaccine is not widely available yet. The Delta variant was first seen in India, the Beta variant was first seen in South Africa, and the Gamma variant was first seen in Brazil.

We need to make sure the entire world is vaccinated to stop these mutations from coming out of the woodwork.

(See https://en.wikipedia.org/wiki/Variants_of_SARS-CoV-2 for sources and discussion)

This is speculation. I might as well speculate that a vaccine that does not prevent infection or spread, but also puts selective pressure on the virus to escape vaccine immunity, is likely to lead to a vaccine-escape mutation when administered to a large population. This mutation then poses a risk to those who would need the vaccine that has now become ineffective.

The fact that we currently see mutations coming out populations that aren't vaccinated is a number's game. Most of the world population is not vaccinated. Vaccinating the last 30% in developed nations will not change that.

Speaking of speculation, I would strongly speculate that the vaccine will greatly increase the spread of illness.

If the vaccines dull the symptoms to the point that vaccinated people don't readily know that they're sick, then vaccinated people aren't going to be staying home when they're carriers.

In contrast, it seems far likelier that unvaccinated people will feel ill and stay home.

That is a very real danger with constant medication and vaccination - however the observed effect has been the opposite. The lowered impact of sickness leads to shorter periods of contagiousness which has lowered the spread rate. The vaccine is effectively lowering the r-value.

A large proportion of unvaccinated persons is strongly correlated with higher case rates.

> the observed effect has been the opposite

Did you really observe that? There's many highly vaccinated countries that have seen spikes with extremely high r-values.

That was a reasonable back of the envelope calculation, and I notice that the criticism of my figures was done without providing better figures.

However, I am willing to come up with more suitable figures.

https://www.statista.com/statistics/1191568/reported-deaths-... says there have been 2,630 deaths from COVID-19 for 18-29 year olds (never mind the suffering COVID-19 causes people in this age range). Something that causes 2,630 deaths is more risky than something causing 229 non-fatal hospital visits.

> I think all the unvaccinated want is the same absolute right to decide the same for themselves.

In terms of freedom of choice, I think we would be a lot better off just giving our extra vaccines to Mexico until that have a higher vaccination rate; Mexico has, last time I looked, a 25% vaccination rate compared to the 50% vaccination rate in the US. Once Latin America is well vaccinated, we can circle back to the vaccine hesitant here in the US.

There was recently a rather morbid conversation on Reddit speculating about how much vaccine hesitancy might help Democrats in future elections: https://old.reddit.com/r/politics/comments/pbeigk/desantiss_... Not to mention this graph: https://i.redd.it/4o4i7arucpj71.png (Discussion: https://old.reddit.com/r/dataisbeautiful/comments/pbzaeg/oc_... )

I have remarked upon your numbers in another comment. Why do your own math based on outdated newspaper articles and statistics websites when there are scientific publications and FDA documents to draw upon? Calculating the crude chance of death based on population averages is misleading, because those will have risk groups massively over-represented.

The CDC figure for number of COVID-19 deaths among 18-29 year olds is 2,761. https://data.cdc.gov/NCHS/Provisional-COVID-19-Deaths-by-Sex...

So, guess what, those “newspaper articles and statistics websites” have the same general numbers as more official sources like the FDA; indeed, the CDC’s own numbers are higher than the number I used for COVID-19 deaths among young adults. (And, oh, if you think the CDC’s figures are faulty, I have nothing more to say to you; you’re not looking too good after insinuating that https://doi.org/10.1101/2021.07.23.21260998 didn’t attempt to measure total COVID-19 infections, when, in fact, a cursory reading of the paper shows they did)

With something as fast moving as COVID-19, the press often times gets accurate figures before they’re formally published.

If you want to convince me the numbers I used are wrong, please give me up to date numbers from reliable sources which contradict my figures. Not estimates from a paper written a few months ago.

Finally, I need to flat out ask you: Have you gotten the COVID-19 vaccine yet? I got mine months ago. I will not respond to you again until I know your vaccination status.

> I think all the unvaccinated want is the same absolute right to decide the same for themselves.

And I, personally, refuse to grant them that courtesy. If you want to smoke twelve packs a day (while living in a country with no healthcare) then feel free buddy - but not getting vaccinated effects everyone - including those who choose to help move us past this pandemic by getting vaccinated.

This isn't a question of individual rights vs. the authoritarianism in the same way that wanting to be a thief isn't an individual decision. You can't be a thief without stealing from other people so we've agreed as a society to make it illegal - the same goes for vaccination. The US is currently tip-toeing on a knifes edge trying to avoid an open revolt of stupid people while also trying to make the vaccine mandatory - that open revolt would result in a severe jump in case count... but the government is facing facts that simply coddling people won't make the pandemic go away.

Poor analogies and collectivist arguments aside, from a medical ethics standpoint, if my personal risk from being vaccinated outweighs the personal risk of infection, you do not have a right to impose it on me. Despite this being parroted as obviously true, these analyses at this point are based on statistical modeling and conjecture with no regard to personal disposition beyond "age cohort"[1].

[1] https://www.fda.gov/media/151733/download (Page 24)

> And I, personally, refuse to grant them that courtesy.

Inalienable human rights are not a courtesy for you to grant.

Refusing vaccination is not an inalienable right in America - the Supreme Court has ruled many times that compelled vaccination is perfectly legal for the government. In fact the anti-vax crowd isn't particularly new in the US - it was present when both polio and MMR were being removed as common causes of death. The only real difference this time around is that anti-vax is considered a political tool by one of the US parties and thus has garnered a false legitimacy.

I'm talking about inalienable human rights. You're talking about legal rights. There's a distinction here.

And for what it's worth, I'm not concerned with legality: lawyers can and will legally justify anything they want to. I'm 100% sure that your claim about the law is correct. I'm sure that various inhuman authoritarian laws are going to be tried in America over Covid-19 and legally upheld. Politicians, businesses trying to make big bucks, and moral busybodies will never let a good crisis go to waste.

I'm concerned about morality. It is utterly reprehensible to force a human to inject something into his body against his will. No judge, law, legislature, vote, or disease changes that fact.

Infants receive medical care while being unable to personally consent to it and that is generally accepted - ditto for adults when they have reduced cognition for a variety of factors.

I can't disagree that compelled vaccination may be personally immoral for you - but I don't think it's in any way viewed as unethical. It is accepted at a societal level even if some individuals will reject it - and, due to the widespread effects of this pandemic, I think the society we're contemplating to derive ethics here is the global one.

> COVID-19, on the other hand, has an overall 1.66% chance of killing someone (38,043,754 cases, 629,644 deaths)

What you calculated is the case fatality rate (CFR), but the infection fatality rate (IFR) is a better representation of risk from SARS-COV-2 infection.

The global average IFR is recently estimated to be ~0.15% [1], which is extremely skewed by age.

All estimates of age stratified IFR show a gradient that decreases by orders of magnitude with age - we're talking IFRs below 0.003% for healthy young adults and children [2][3].

Furthermore, there is substantial evidence that the CFRs & IFRs are significant overestimates [5]. This completely changes the risk-reward tradeoff for many people.

I am not advocating against vaccination (it is a powerful tool that saves lives) - just spreading knowledge and illustrating the fact that everyone has a different risk-reward profile based on their age and health, and should make personal health decisions accordingly.

[1] Reconciling estimates of global spread and infection fatality rates of COVID- 19: An overview of systematic evaluations https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/eci.13...

[2] Infection fatality rate of COVID-19 inferred from seroprevalence data https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947934/

[3] COVID-19 antibody seroprevalence in Santa Clara County, California https://academic.oup.com/ije/article/50/2/410/6146069

[4] Model-informed COVID-19 vaccine prioritization strategies by age and serostatus https://science.sciencemag.org/content/sci/371/6532/916.full...

[5] Evaluating the massive underreporting and undertesting of COVID-19 cases in multiple global epicenters https://www.sciencedirect.com/science/article/pii/S253104372...

I addressed the gist of your concerns elsewhere in the thread.

There have been 2,630 deaths from COVID-19 for 18-29 year olds (never mind the suffering COVID-19 causes people in this age range) in the US. Something that causes 2,630 deaths is more risky than something causing 229 non-fatal hospital visits (the heart condition which has gotten far too much attention).

In terms of IFR vs. case fatality rate, the most comprehensive metastudy you cite, https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/eci.13... estimates that we only have 1 case per 10 infections (the Lau 2021 paper which claims we only have 1 case per 50-100 infections is obviously not true in the United States, since the cumulative COVID-19 case count is over 10% of the US population; don’t put too much faith in and do not cherry pick an individual study). Assuming an IFR 10x the CFR, we have a 0.16% IFR rate, which is still orders of magnitude larger than the 0.002% rate we are seeing with people who get that non-fatal heart condition after getting the vaccine (and there’s evidence that they are more likely to get the heart condition from an actual COVID-19 infection than from a vaccine)[1]. Before you repeat the “but young people” argument, an order of magnitude more young people have died from COVID-19 than have gotten that generally non-fatal Myocarditis heart condition after being vaccinated. So we know the risk factor of getting a vaccine is lower. [2]

Critical thinking is one thing, but there are a lot of bad faith actors in the “COVID skepticism” movement. Roughly speaking, vaccines have a near-zero chance of having averse side effects, a significant chance of reducing spread of COVID-19 (I myself am still skeptical about the studies which claim vaccinated people still spread the virus to unvaccinated people, since we’re generally seeing an exponential decrease in COVID-19 cases in places where a higher percentage of people are vaccinated), and greatly reduce hospitalizations of people who get COVID-19 [3].

It’s well known that, in the US, skepticism of vaccines and public health measures, unfortunately, have a political bias, and, lo and behold, people with a “COVID denial” (deny that masks help [4], refuse to take the vaccine, refuse to avoid large indoor social gatherings, etc.) political bent are much more likely to get a case of COVID-19 significant enough to report: https://i.redd.it/4o4i7arucpj71.png

A lot of this “skepticism” I am seeing reminds me of the young earth creationist arguments which I have seen over the years; they will take any evidence for a young earth, no matter how tenuous, and pretend it’s the one truth while ignoring all of the extensive evidence for an old earth. It’s bad faith arguing; young earth creationists and anti-vaxx “skeptics” do not argue in good faith.

This bad-faith skepticism -- which usually consists of poorly researched nonsense like claiming Myocarditis is a real concern if someone gets the vaccine -- is putting people in hospitals and bad-faith skepticism is killing people. I am having to avoid certain family members because they have drunk the kool-aid and refuse to vaccinate.

[1] https://www.medrxiv.org/content/10.1101/2021.07.23.21260998v...

[2] To address the “Rambo” argument that young people who do not have co-morbid conditions are unlikely to die from COVID-19, their chance of getting any adverse side effects from the vaccine is also very very low. See https://health.wusf.usf.edu/health-news-florida/2021-06-18/p...

[3] https://datawrapper.dwcdn.net/5Qts7/9/

[4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393808/ shows that masks do help

Please read my post again carefully, because your reply does not address my argument at all.

> There have been, from the total of 12,910,312 18-24 year-old people vaccinated, [2] about 229 cases of this rare heart disease (and, in almost all cases, the person was discharged from the hospital the same day with a clean bill of health) That means the vaccine has under a 0.002% chance of causing a very rare but not fatal heart condition.

The FDA has recorded[1] a rate of 0.0065% of Myocarditis cases and further estimates[2] a rate of up to 0.02% cases after vaccinations with the Pfizer vaccine, in the 16-17 male group. That risk appears to halve by age 25[3]. The rates with the Moderna vaccine may be higher still[4].

The common misrepresentation of Myocarditis as "mild" is concerning. In many cases, it leads to permanent heart damage, which in turn can lead to cardiac arrest later, significantly increasing mortality risk[5]. When undetected, acute Myocarditis can lead to cardiac arrest under stress, which is the leading causes of death in young athletes[6].

> I would rather take a 0.002% non-fatal risk than a 1.66% fatal risk

This is a population average, including co-morbidities, which is highly misleading. The CFR for males under 30 without co-morbidities in high-income countries has been estimated[7] at 0.0003%. At the other end, you have 80+ year males with co-morbidities at 20.08%.

[1] https://www.fda.gov/media/151733/download (Page 23)

[2] https://www.fda.gov/media/151733/download (Page 24)

[3] https://www.dicardiology.com/article/overview-myocarditis-ca...

[4] https://www.reuters.com/world/us/us-probing-moderna-vaccine-...

[5] https://jcmr-online.biomedcentral.com/articles/10.1186/1532-...

[6] https://www.mayoclinic.org/diseases-conditions/sudden-cardia...

[7] https://www.cgdev.org/sites/default/files/predicted-covid-19... (Page 6)

>your reply does not address my argument at all

Yes, it does. I pointed out that the chance of getting Myocarditis is 0.002%, i.e. near zero. I also pointed out, and I repeat myself, that there have been 2,630 deaths from COVID-19 for 18-29 year olds (never mind the suffering COVID-19 causes people in this age range) [1]. Something that causes 2,630 deaths is more risky than something causing 229 non-fatal hospital visits.

I also observe you’re quoting stuff which uses estimated risks. The 229 number is a real risk: That’s the number of people who actually got Myocarditis after being vaccinated, a fact you conveniently ignored. To argue that a theoretical risk buried in a report (which correctly felt the risk was very small and approved the vaccine) trumps a real world figure we now have is downright disingenuous bad faith arguing.

Going back to your parent post, you allege that the pre-print paper https://doi.org/10.1101/2021.07.23.21260998 doesn’t “consider that actual COVID infections may be undercounted [sic]” (your words). Did you even read the paper?? Let me quote it: “In the United States, there is no national data on infection rate by age. According to a systematic review and the working assumption of the Centers for Disease Control and Prevention, children may have infection rates similar to adults, with younger people having more mild or asymptomatic cases. Accordingly, we used the estimated 9.2% population infection rate for April 2020 - March 2021.”

In other words, no they didn’t just look at case numbers, they made a reasonable estimate of actual infection figures, and based on those estimated figures said that one is six times more likely to get Myocarditis from COVID-19 itself than from a vaccination.

Now, it’s possible that a random Ycombinator poster has a better estimate for the number of total COVID-19 infections than a team of scientists writing a paper about COVID-19 and submitting it to peer review, but I’m not holding my breath here.

[1] https://www.statista.com/statistics/1191568/reported-deaths-...

I still get the impression that you did not carefully read my reply, because it already addresses all the points you just made.

> Something that causes 2,630 deaths is more risky than something causing 229 non-fatal hospital visits.

This over-represents the risk groups. As you can see from the source[7] I posted, there's a massive difference between those with risk factors and those without.

> I also observe you’re quoting stuff which uses estimated risks. The 229 number is a real risk

The "229 number" is a number you took out of an outdated newspaper article. The FDA has recorded[2] (not estimated) a risk of 0.0065%.

> To argue that a theoretical risk buried in a report (which correctly felt the risk was very small and approved the vaccine) trumps a real world figure we now have is downright disingenuous bad faith arguing.

Let's not go down that "bad faith" route. You've been throwing around plenty of misleading numbers, but I don't think you're doing it in bad faith.

The FDA itself has found a "worst case" scenario[2] of low incidence that showed the risk/benefit ratio was not in favor of the vaccine, using efficacy estimates that may or may not reflect reality further down the road. This was then pushed aside by purported risks of longer observed hospital stays, but ignoring the long-term risk factors of Myocarditis. This is entirely speculative, at which point people risk believing whatever they want to be true, not what is actually true.

[2] https://www.fda.gov/media/151733/download (Page 24)

[7] https://www.cgdev.org/sites/default/files/predicted-covid-19... (Page 6)

As per your FDA figure 65 per million cases of Myocarditis in 12-17 year olds vaccinated:

At https://data.cdc.gov/Vaccinations/COVID-19-Vaccination-Demog... we see 11,776,463 vaccines administered to 12-17 year olds. Using math: 765 cases, which are generally non-fatal.

Using https://data.cdc.gov/NCHS/Provisional-COVID-19-Deaths-by-Sex... we get 1,131 fatalities among 15-24 year olds.

This, again, is 12-17 year olds; I was using figures for young adults before, where the chance of getting Myocarditis is smaller and the chance of dying from COVID-19 is larger.

The worst case figures for vaccine side effects you have been able to come up with is that the number of Myocarditis cases is about the same as the number of COVID-19 deaths in the adolescent age group, as as per the FDA paper you brought up “available data from short-term follow up [of Myocarditis cases] suggest that most individuals have had resolution of symptoms”. Even here, I would prefer a condition which gets resolved over something which would kill me.

I know you don’t like me making bad faith assumptions, but in the real world, people who argue against getting vaccinated usually argue in bad faith, and the results of their arguments are increased deaths because people didn’t get the vaccine. As I posted elsewhere in this thread, it’s well known that, in the US, skepticism of vaccines and public health measures, unfortunately, are bad faith arguments being made with a political bias, and, lo and behold, people with a “COVID denial” political bent are much more likely to get a case of COVID-19 significant enough to report: https://i.redd.it/4o4i7arucpj71.png [1] Also, well over 95% of COVID-19 hospitalizations are from unvaccinated people: https://datawrapper.dwcdn.net/5Qts7/9/

[1] The image is on Reddit, but the figures are from New York Times’s COVID-19 tracker and MIT Election Lab figures. My own graphs comparing COVID-19 infection rates in red states (states with right-wing governors) vs. blue states (left-wing governors) shows a much smaller COVID-19 Delta surge in places less “vaccine skeptical”; compare https://samiam.org/COVID-19/redStates.html and https://samiam.org/COVID-19/blueStates.html

So, before we talk any further, I need to know this: Did you get the COVID-19 vaccine? If not, why not? I will not reply to you until I know whether you have been vaccinated.

The mistake you keep making, despite it being pointed out to you multiple times, is to consider age groups as a homogeneous cohort, even though it has been well-established that the overwhelming majority of deaths across all ages happen in risk groups. At this point, this appears to be willfull ignorance. I'm afraid that even if I were to give you a "pledge of allegiance" regarding my vaccination status, further discussion would not lead anywhere.

You haven’t read my other replies in this thread (You’re wrong: I have addressed co-morbidity) and you refuse to disclose your vaccination status. I have nothing more to say to you; productive discussion at this point is not possible.

A significant confounding issue is a lot of people think they're "previously infected" but aren't, as the symptoms of COVID and the symptoms of flus and colds overlap, especially in milder cases. "I got it but didn't seek treatment" is impossible to verify, too.

My son had a nasty case of pneumonia early in 2020; we thought afterwards it might've been a COVID case. Later antibody testing demonstrated that it wasn't.

That's why advice is still "go get the vaccine".

‘ "I got it but didn't seek treatment" is impossible to verify’

‘Later antibody testing demonstrated that it wasn’t.’

I’m confused, can’t we antibody test people who think they had it?

Yes, we can. But from a public health perspective, many people will just short circuit to "I had the sniffles some time in the last year so I got covid. So I don't need to find a site, fill out a form, wait in line and potentially lose a couple of days of work due to symptoms. Plus, you know, those microchips - it could be true :)" One of the biggest challenges we have is picking public health messaging for a broad audience that does the most good and the least harm.

I'm still frustrated that the decision was made early on in the pandemic to say that masks don't work. And the convoluted reasoning that if you didn't have a perfect fit or if you touched the outside of the mask that was somehow more dangerous than being unmasked in a location with a sufficiently high viral load for the other stuff to matter. I also understand that the concern was that if we told the truth (masks do matter, and respirators are even better, but please don't buy them to protect yourself and your family because we didn't stockpile enough, so we need them for the doctors and nurses) we'd have had even more supply challenges.

> I’m confused, can’t we antibody test people who think they had it?

Can we? Sure.

Is it a massive waste of resources versus "just get the fucking vaccine"? Also sure.

This really is the TL;DR of all the research comparing natural and vaccinated resistance. The vaccine provides significant benefits to both folks who dodged the pandemic and those who were infected. There isn't a rational reason to avoid getting vaccinated.

Amazing this is getting downvoted when this is absolutely the conclusion of these studies in such a straightforward way. Whether or not you were naturally infected, the vaccines provide another layer of protection which can save lives.

There's no reason to get a booster. The only people pushing that are government officials who are running counter to scientific advice.

Can you provide sources?

WHO Says No Conclusive Evidence On Need For Booster Shots

https://www.axios.com/who-data-covid-booster-shots-inconclus...

nah, I'm good

Let’s look at what these articles are actually saying.. EMPHASIS is mine below:

“Also, it’s POSSIBLE that mRNA delivery may change the way antigens are presented to the immune system, leading to differences in the antibodies that get produced. A third difference is that natural infection ONLY exposes the body to the virus in the respiratory tract (unless the illness is very severe), while the vaccine is delivered to muscle, where the immune system MAY have an even better chance of seeing it and responding vigorously.”

After so many words, what has really been said? Something is possible. MAYBE injecting into a muscle is more effective for a vigorous response. But, folks, the natural infection ONLY exposes the body to the virus in the respiratory tract! (As opposed to ONLY the muscle? Neither is true.)

But hey. We already know before even writing the article… that natural immunity is ONLY this or that, while vaccines are DIFFERENT and HOPEFULLY and MAYBE will give longer lasting immunity than natural one (never mind that studies mostly show otherwise)

How do they get from vacuous statements to a firm conclusion that everyone should take the vaccine?

> antibodies elicited by the mRNA vaccine were more focused to the RBD compared to antibodies elicited by an infection, which more often targeted other portions of the spike protein.

I wonder how this might impact the design of future mRNA vaccines. For example, could vaccines target multiple proteins that both are associated with the virus?

this is referred to as a polyvalent vaccine, and it is a good thing to do once we understand enough about the antigens in question to incorporate both in one shot. There is nothing of course precluding two different vaccines of differenct valence, and we have been doing this for a short time now, when we combine single jab mRna vaccines, with adenoviral vectored vaccines, there is very slight sequence variation between adV and mRNA vaccines however by strictest interpretation this is a multivalant[bivalant] scenario.

it also generates immunity to the adenoviral vector proteins

yes and this has been the big setback for many years this is why we dont have a lot of these vector vaccines.

if someone is immune to adenovirus they typically destroy the vaccine before antigen can be presented. this reduces prophylactic opportunities regarding serial innoculation with adenovirus vector, regardless of the cassette load

i am one of those people, having worked with adenovirus, as well as coronavirus, thus i am obligated to non adenoviral vaccine, and made out quite well during my infection with SARS-1, and with SARS-2

you got infected with SARS1?

yes i did, when it was brand new, it was very concerning, i was very congested, labouring to breath and walking was starting to feel like running a marathon in 90 degree weather. when SARS-2 came around it was a case of the sniffles, with very high antibody titre, searching on a whim i discovered that i am not alone, and apparently SARS-1 convalesence related to outcome of SARS-2 infection

I don’t see why not since they already do that, both Pfizer and Moderna already have targeted multiple regions on the spike protein, presumably they also modeled them to optimize for antibody interaction and stability by taking regions that are less likely to mutate without loss of function.

If you reach out the limit of what you can encode in a single mRNA payload you can add additional payloads to a single dose or spread them across multiple doses.

Engineered viral vectors also can do similar things and also have a base pair limit so the solution would be similar.

Looks like they are trying to do something exactly like that: https://news.ycombinator.com/item?id=28319391

Intramuscular vaccinations are the most important first step and will keep hospitalization down. But intramuscular vaccination for respiratory viruses does not provide long lasting immunity to the surface mucosa tissues of the upper respiratory tract. The IgG antibodies in body serum do seep into the lower lungs and provide robust protection from serious disease, but they do not prevent infections very long in the nose, sinuses, or throat. This is the disparity many studies are now highlighting but failing to acknowledge the cause of.

The required next step is intranasal vaccination to recruit B and T cells to the upper respiratory mucosa and have the B cells produce local IgA antibodies. This would actually stop infections (infections defined from nasal swab testing).

It is up to the NIH and other large organizations in the world to get this messaging out there. There are two types of "breakthrough". There's the fact that intramuscular vaccinations don't protect the upper respiratory mucosa, and then there's the very rare cases when sars-cov-2 actually manages to infect body organs and the lower lungs. They are entirely different things.

The variants currently circulating don't play a huge role in this discrepancy. We'd be seeing the same amount of upper respiratory mucosa infections (not hospitalizations) even if there were no delta and it was just alpha/beta/gamma or even original wuhan sequence sars-cov-2.

ref: https://www.gov.uk/government/publications/long-term-evoluti... page 5, #8. "Whilst we feel that current vaccines are excellent for reducing the risk of hospital admission and disease, we propose that research be focused on vaccines that also induce high and durable levels of mucosal immunity in order to reduce infection of and transmission from vaccinated individuals. This could also reduce the possibility of variant selection in vaccinated individuals."

ref: https://science.sciencemag.org/content/373/6553/397 "the ideal vaccination strategy may use an intramuscular vaccine to elicit a long-lived systemic IgG response and a broad repertoire of central memory B and T cells, followed by an intranasal booster that recruits memory B and T cells to the nasal passages and further guides their differentiation toward mucosal protection, including IgA secretion and tissue-resident memory cells in the respiratory tract."

ref: https://www.nature.com/articles/s41577-021-00550-x

Why isn't there more of a push for emergency use of intranasal vaccines? Apparently there are some in the testing phase, but I think if they were given as much resources as the mRNA vaccines were we might have already had an intranasal vaccine in use by now. The Israelis have one in testing but it still sounds like it's a long ways off from being deployed on a large scale. The other advantage of an intransal vaccine is that we might be able to convince a portion of the vaccine hesitant to get it.

nasal mucosal immunity[IgA] is short term relative to humoral immunity[IgG; IgM]; this however would be a good prophylactic approach, as the nasal vault is a major contributor to transmission mechanisms

Yes, the neutralizing antibodies go away relatively quickly but now you have mucosal resident T cells trained on spike epitopes ready to go right at the start of the infection before things get out of hand.

Here's a good explanation of why.[1] There are several intranasal coronavirus vaccines in test. There's only one approved nasal vaccine now, for anything: FluMist. It's not recommended for people over 50. There have been previous failures. Intranasal vaccines are hard to make work.

Think of the current mRNA vaccines as a minimum viable product. The basic formulation was computed days after the virus was sequenced and they made it to market fast. They do the basic job. Serious side effects are rare. They require two doses and later, boosters. They're a pain to store and ship because of cold requirements. They're hard to manufacture because putting fragile messenger RNA into a liquid carrier envelope requires exotic equipment. They have reduced effectiveness for virus variants.

Expect later-generation products that solve some of those problems.

[1] https://www.pbs.org/newshour/health/scientists-debate-potent...

This raises an interesting question: is someone who is waiting for an effective intranasal vaccine to get something more like sterilizing immunity, and foregoing the less-effective vaccine meanwhile, anti-vax?

Yes. Refusing to get a vaccine now is harmful to yourself and others. The current vaccines are effective. A more effective intranasal vaccine may come, but you should protect yourself and others now.

If they are healthy and have survived Covid with natural immunity, that overall beats all vaccines. Antibody and T-cell tests tests are available to find out if they have already recovered from an an infection. If they have not been isolating much for the past 18 months, e.g. first responder or other essential worker, they were likely infected and already recovered.

If they are not yet infected, are healthy and take precautions to isolate at the first sign of illness, they are a lower transmission risk than a vaccinated person who gets infected but whose symptoms are suppressed by the vaccine, so they don't know they should isolate. CDC recommends that vaccinated people exposed to SARS-CoV-2 should be tested after exposure, and then wear a mask if the test is positive, https://www.webmd.com/lung/news/20210729/cdc-reverses-guidan... & https://www.cdc.gov/coronavirus/2019-ncov/vaccines/fully-vac...

> Even if they’re not showing symptoms, fully vaccinated people should “get tested 3-5 days after exposure to someone with suspected or confirmed COVID-19 and wear a mask in public indoor settings for 14 days after exposure or until they receive a negative test result,” the agency’s website says ... “Our updated guidance recommends vaccinated people get tested upon exposure regardless of symptoms,” CDC Director Rochelle Walensky, MD, told The New York Times in an email. “Testing is widely available.”

That only seems like an interesting question if you view anti-vax as some kind of ethical group.

If you choose to define it more literally as the people that are against taking any particular vaccine in common use then it's vacuously true.

Yes.

The odds of dying from covid: 1%

The odds of dying from covid after current vaccine: <0.015%

This is misleading. Your chance of dying this year is not the worlds population divided by deaths. It depends how old and/or weak you are. Do you have a source for your numbers?

It doesn't raise that question at all because both I and the references I linked say it should be used *as a booster after intramuscular vaccination*.

You raised that scenario out of the blue and it has nothing to do with what anyone suggests.

Intranasal vaccination should probably not be the only or first vaccination. It should be a booster after intramuscular vaccination so we can finally stop the spread. Additionally, since the epithelium is exposed to the outside world by definition intranasal vaccines are generally much safer and with fewer side effects.

The "failures" of Flumist (ie, ~50% efficiency) were later recapitulated by the normal intramuscular tetravalent vaccines when they mis-picked in many times in the mid-2010s (after H1N1 emerged). But for some reason people only remember the one time with Flumist. It's sort of similar to how people remember and think all seagate HDDs are faulty because of the one bad series of drives a decade and a half ago.

Informed consent disclosure to vaccine trial subjects of risk of COVID‐19 vaccines worsening clinical disease https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645850/

It seems that the new data invalidates that conclusion?

> The new evidence shows that protective antibodies generated in response to an mRNA vaccine will target a broader range of SARS-CoV-2 variants carrying “single letter” changes in a key portion of their spike protein compared to antibodies acquired from an infection.

This seems like a remarkably specific criteria. Using my naive, computer-science brain, I would think that it's unlikely that a mutation would consist of exactly one change to the RBD amino acid sequence (compared to all of the other possible mutations). What am I missing?

A variant has multiple mutations which they call "single letter changes". It's not meant to say that there will be only one mutation per variant

single letter change is refered to as a point mutation meaning one residue. it is common

there are a number of mutation types and numerous mechanisms.

https://en.wikipedia.org/wiki/Mutation

in the case of point mutations, cosmic ray ablation, and wobbly fit of the replication mechanism lead to data corruption, conflated by error prone replication or error prone proof reading

> A third difference is that natural infection only exposes the body to the virus in the respiratory tract (unless the illness is very severe), while the vaccine is delivered to muscle, where the immune system may have an even better chance of seeing it and responding vigorously.

But the respiratrory tract is constantly exposed to the external world, wheras the muscles are typically protected by the skin... Therefore I find this fact counterintuitive.

A marketing person might consider this a way of spinning a known negative into a rhetorical positive.

Unless people are being bitten by Covid-bearing mosquitoes, blood serum antibodies aren't going to be seeing virus earlier than the upper respiratory tract.

Yeah, true that.

With natural infection you get BOTH lymphocytic memory of the disease AND antibodies to the disease. With a vaccine you ONLY get the latter. And it's the lack of that balanced duality that creates the risk of ADE or Antibody Dependent Enhancement which is far more dangerous than getting the disease naturally.

I wonder low likely it is that over the course of a lifetime the vaccinated will end up with both forms of immunity. I assume we’ll be exposed to the virus regularly. Would the natural immunity be weaker if it comes from a second, very mild, infection?

I mean yeah but the point is to not get infected in the first place right?

Wouldn't this open the door to possible immune diseases in the long term?

With a much wider net for the antibodies to attack, someone with the DNA and matching proteins that are similar to the spike protein would have an increased chance of an autoimmune disease.

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