Ignoring WHO call, major nations stick to vaccine booster plans | Hacker News Reader

Ignoring WHO call, major nations stick to vaccine booster plans

reuters.com

42 pointsbryan0119 comments

I suppose the surge of infections from the Delta variant have made developed world governments re-think their approach to vaxing younger citizens. In the UK a fifth of hospital admissions with covid are 18-34 years old and we're extending vaccination to 16-17 year olds.

I'm sure it's true these vaccines would save more lives in developed nations, but politically governments are still accountable to their own citizens first. It's an ugly situation. Delta has seriously thrown a spanner in the works, and I'm sure there are more variants to come. Suppose a variant pops up that's deadly to children, but the current vaccines protect against it. How would governments explain shipping vaccines abroad instead of vaxing children then?

It's tough to see any potential evolutionary path that would make SARS-CoV-2 deadly to children. There are four other endemic human coronaviruses that have been around for a long time, including HCoV-OC43 which is another betacoronavirus genetically quite similar to SARS-CoV-2. The only reason that OC43 doesn't cause many deaths today is that most of us get infected when we're young and build up protective natural immunity. It's had a long time to evolve other variants but so far none of them kill kids.

https://www.sciencedirect.com/science/article/pii/S152166162...

This seems like a misunderstanding of how evolution works. Viruses don't choose to be deadly or not based on some evolutionary path that they see ahead, the causation goes the other way around - viruses that were deadly in the past might not have an evolutionary path to the present.

We do not know how Sars-Cov-2 will end up - we cannot pre-emptively discount the potential of deaths just because it seems like a bad evolutionary strategy.

> I'm sure it's true these vaccines would save more lives in developed nations

One of the main points is that it is also in the average person's self interest to get the whole world vaccinated before a bunch of old people get boosters. It is likely even in the old person's self interest to reduce the odds of a new variant that isn't targeted by the vaccine.

> Suppose a variant pops up that's deadly to children,

Which is most likely to happen in the unvaccinated world. One of the main points is that it is also in the average person's self interest ... etc etc ad infinitum.

Not getting the whole world vaccinated as quickly as possible is potentially catastrophic. No amount of boosters will be any good against a variant that ignores the vaccine-induced immune response (or non-response, really).

How are the younger patients faring? I see the UK as a canary to the USA for the upcoming school year but have no sense of it from the news.

In Germany we vaccinate from 12 years old, to my knowledge there haven't been any newsworthy incidents.

The only thing we have is the (political) squabble if it is officially recommended by the vaccine commission, and the debate on how we are going to protect the young children - especially those at high risk - when ignorant unvaccinated adults will be spreading COVID around.

> Suppose a variant pops up that's deadly to children, but the current vaccines protect against it. How would governments explain...

All sorts of mad things could happen. But this fantasy scenario is really quite unlikely.

> But this fantasy scenario is really quite unlikely

Based on what exactly. The delta variant was unlikely. The COVID-19 was unlikely. I think I'll back governments taking precautions against the possible rather than somebody thinking it's a fantasy(def: the faculty or activity of imagining impossible or improbable things) scenario, ignoring the last 18 months of world life.

What if there's a gamma variant and drinking bleach would have protected against it? Shouldn't governments distribute bleach "just in case"?

Sure, but Delta started in India. Because of how connected we all are, if we want to protect ourselves we need to protect the world.

In Romania where I'm from, people no longer want vaccines. The authorities had to sell them before they spoil.

I say let everyone do whatever they want, including letting the doctors go home when they are tired.

Does "do whatever they want" extend even to something like doctors saying "you've declined to get vaccinated and acted like there's not to be concerned about, so we're going to not admit you to the hospital"?

Does your logic extend to "you've declined to lose weight and acted like being obese is nothing to be concerned about, so we're going to not admit you to the hospital"?

Well, it's 'danuker's logic, not my own.

I just want to know if they fully extend "do what you want" to everybody or if it's a situation of "do what you want for me, do what I want for thee."

If they do, then the answer would clearly be: yes.

As an aside, some of this is already done when resources are scarce today. The alcoholic who can't stop drinking isn't going to make it on the liver transplant recipient list. One of the biggest dangers of Covid has consistently been that it risks overwhelming hospital capacity, which so far fortunately has been minor (though has resulted in some tragic outcomes) but not something anyone should want to continue.

You can't solve obesity with two shots.

You can, in the US. /s

On one hand there's a clear pressure from governments, WHO, etc. to get vaccinated (which is still a higher pressure than from smallest groups but with a bigger voice, aka anti-sthg) for a positive outcome and on the other hand there is a strong pressure from junk food industries to eat unhealthy diet.

There's also a lot of obese people who are concerned about their weight (but I don't know the proportions).

So it's oranges to apples.

It's in very poor taste to conflate the issues of social distancing and vaccination acceptance with treatment of medical staff. If everyone social distanced and got a vaccine, there would be no issues with medical staff being overworked.

If everyone did what they wanted, what would the medical staff do? Go home and let them die on the sidewalk? Kids dying in the streets by no fault of their own wouldn't go over well.

>Kids dying in the streets...

Uh, wat? Which kids are dying from covid? This level of hyperbole is insane.

Children account for 1.3% to 4% of all US hospitalizations for COVID, depending on the US state.

What do you suggest is done when everyone throws their hands up and medical demand exceeds supply? I fail to see how being unable to admit patients is some impossible scenario.

Hospitals have been built and staffed for estimated peak capacity forever. Slack capacity is extremely expensive.

Here's an article from 2018 about LA County's makeshift flu hospital tent, which they built because the flu season was so bad then: https://www.latimes.com/local/lanow/la-me-ln-flu-demand-2018...

So, what I suggest is done, is what hospitals have always done, which is do their best to make it work.

"Two weeks to flatten the curve" was all about giving hospitals a chance and not be overwhelmed, and presumably, get better prepared. It's been 1.5 years. How long do you think it's reasonable to extend that 2 weeks to?

The last time hospitals ran during an epidemic of this intensity was in 1920. I think your confidence in the long-term viability of treating a population that has no interest in stemming the virus is completely unwarranted.

If levels stay as is, you're completely right. The issue is that they likely won't and certainly won't if "everyone does what they want."

Acceptable losses from the sounds of it. I find these conversations difficult to discuss because we all have different ideas of what is acceptable losses.

> Children account for 1.3% to 4% of all US hospitalizations for COVID, depending on the US state.

That is an acceptable price to pay for indulging in crankery. /s

We've seen what happens when restrictions are loosened. Just look at what happened in the Netherlands in the last few months.

It just doesn't work.

Sweden enters the chat.

That will lead to more variants and some of them will render the current vaccines and efforts useless.

No- designing and depending on a vaccine based on a single gene is what will (has already) lead to variants. It's no coincidence that lambda has 3 separate mutations on the spike protein targeted by the mrna vaccine.

The immune system doesn't lead to variants, randomness + time does.

Selection pressure to see what variants become dominant happens later. They aren't being actively "designed" in any sense.

That's why anything that would make real progress has to happen quickly and broadly, without large left-out pockets (not that rejecting a vaccine is any worse than not being offered one in the first place, here - that's the issue that is mostly being ignored for now, since we have no current solution).

How do antibiotic resistant infections work? I ask as a lay person.

Similar thing.

What's important to note, though, is that the mutations are blind to their environment. The virus or bacteria doesn't see an antibiotic or antibody and say "I need to adjust this aspect." It's just constantly changing as it reproduces, and some of them may end up winning a battle that the original did not. And then they spread from there as would any strain.

From the purposes of the virus, an unvaccinated person in a poor country without access to vaccines isn't better or worse than one in the US who's simply refusing. It doesn't know. They're both opportunities for the virus to keep replication and so keep (randomly, blindly) mutating.

If the odds of reproducing in a way that escapes people's current antibodies, and making your way outside the host (because a mutation the immune system adapts to before it can be spread dies there) are 1 in ten billion, say... and you leave 7 billion people in the world unvaccinated... suddenly those odds aren't so great. (Numbers entirely fake here, but basically, less likely events become more likely as more time goes by, if you keep giving them opportunities to happen.)

A key advantage of a vaccine over an antibiotic is that it can potentially stops the problem before it starts whereas antibiotics are generally given if you already have a nasty infection. So the amount of virus that's exposed to the immune system in a vaccinated person will be lower, and throttled more quickly, giving less time for it to get lucky, IIRC. But nothing about that would magically necessarily stop a virus that's still spreading like wildfire in a large unvaccinated population from coincidentally developing new traits that help it out. The goal is to vaccinate a large enough population quickly enough that this "spreading like wildfire" situation stops, so we reduce the mutation rate of the virus.

So that says right in the abstract: “When vaccine resistance has evolved, these generalities have been violated.”

So as long as mutations like the epsilon variant don’t occur (they do right?) and as long as vaccines are prophylactic against infection (not the case given need for boosters is Israel, right?), there’s nothing to worry about? Sorry if I’m being dense.

Here are very accessible peer-reviewed primary sources that will answer your question and give historical examples [1][2].

[1] Why does drug resistance readily evolve but vaccine resistance does not? https://royalsocietypublishing.org/doi/pdf/10.1098/rspb.2016...

[2] The adaptive evolution of virulence: a review of theoretical predictions and empirical tests https://www.cambridge.org/core/services/aop-cambridge-core/c...

Second link was really helpful. I found this part interesting and potentially relevant,

“reducing the risk of death for infected hosts reduces the cost of virulence, causing an evolutionary increase in virulence (Gandon et al. 2003, 2001b). Vaccines that either block infection or block transmission, on the other hand, have no effect on virulence evolution”

Especially considering Dr Fauci’s recent statements on how the COVID vaccines do not block transmission.

https://m.youtube.com/watch?v=AuO_OfjlPUI

Putting these together then it seems like we should expect the result of our vaccination efforts to be increased virulence in strains such as Delta variant. Is it possible the Delta variant itself was somehow the result of our intrepid and swift vaccination efforts? I’m having a hard time understanding why more people aren’t talking about this given the obviously well established scientific literature you’ve cited.

I'm glad you found the reference helpful.

> Is it possible the Delta variant itself was somehow the result of our intrepid and swift vaccination efforts?

The variants can arise under neutral genetic drift, ie pure random chance via naturally occurring mutation.

But the widespread dominance of these variants is very plausibly connected to the mass vaccination efforts.

Here is another good paper on the subject, in case you haven't already seen it [1].

> I’m having a hard time understanding why more people aren’t talking about this

Me too, but to be fair these are complex second and third order effects that only gained traction in the scientific literature within the past decade or so. Right now everyone is mostly focused on first order effects - eg "will the vaccination help/harm me?"

Quotes from [1]:

- "Our modeling suggests that SARS-CoV-2 mutants with one or two mildly deleterious mutations are expected to exist in high numbers due to neutral genetic variation, and consequently resistance to vaccines or other prophylactics that rely on one or two antibodies for protection can develop quickly -and repeatedly- under positive selection."

- "Our work suggests that it is likely that standing genetic variation alone has already produced a substantial population of viruses with single and double nucleotide changes that confer nAb resistance. These variants will establish quickly in the population under selection pressure. In fact, there is already a precedent for this behavior, as one such selective sweep occurred early on in the SARS-CoV-2 pandemic when the D614G mutation rose to nearly 80% frequency in under 6 months [33]."

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

So this makes it sound like we might be headed for semi-annual or even quarterly boosters.

“one possible solution to the problem of immune evasion by SARS-CoV-2 that has been proposed is to develop a new vaccine update every year, similar to influenza [42]. In practice, such a solution will only work in the face of a moderate pace of evolution of SARS-CoV-2 and a low degree of clonal diversity among various clades of SARS-CoV-2 as they evolve to evade the current crop of vaccines. Further, if within-host evolution of SARS-CoV-2 contributes to population-level immune evasion, the valley-crossing mechanism described in this paper could accelerate the emergence of vaccine-resistant strains in the months following vaccine deployment. To the extent that new strains of SARS-CoV-2 are antigenically distinct, this may also lead to increased risk of antibody-dependent enhancement (ADE), as one mechanism for ADE involves antibodies that bind to the pathogen but fail to neutralize it [43]. Finally, our work suggests that immune evasion requiring one to two mutations occurs within months, raising the prospect that this phenomenon will further shorten the duration of natural immunity, which is already limited by the relatively short duration of the humoral [44,45] and cellular [46] responses to SARS-CoV-2 infection. Further studies are required to understand the risk immune evasion poses to a strategy of annually updated vaccines.”

I wonder if this is why Dr Fauci is emphasizing the need for therapeutics as higher priority than vaccines at this point? I should say though, mathematical biological models like the ones in this study are not something I feel very well equipped to evaluate. How often are such models wrong? What are the incentives for the company associated with these authors, “Fractal Therapeutics”? Obviously Harvard is Harvard, but I just can’t understand why smart people aren’t talking about this stuff. Murti-Bing pills?

>> The immune system doesn't lead to variants, randomness + time does.

I disagree. It has been shown over many years of research that viral mutations may be driven by both antigenic drift as well as selective immunological pressures, with the question being more the degree to which these factors influence mutation in different viral species.

Not to present an argument against vaccination, rather an argument against making blanket statements that fail to accurately represent the current state of collective knowledge on the subject, to wit: We do not know with any certainty the degree to which either of these factors drive SARS-CoV-2 mutations. A naked statement that the un-vaccinated population drives the mutation rate of this virus is nothing more than speculation; issues surrounding a field of study as incredibly complex as this may not ever be definitively put to bed through analysis of (conflicting?) study outcomes- let alone through arguments made in the commons of popular science.

I don't argue that emerging SARS-CoV-2 mutations are driven more by one factor or the other, I argue that we do not know the degree to which mutations are driven by 'random' antigenic drift vs selective pressures. Unfortunately, the issue has been politicized to the point where study outcomes that suggest dominance of one over the other are likely to be attacked or even ignored, regardless of the strength of study.

Citations? Efforts to find evidence here prioritized time invested over strength- this may not represent the best arguments out there, however it took only a scant few moments to gather, and points to a much larger body of literature supporting the position that both antigenic drift and selective immunological pressures drive viral mutations (SARS-CoV-2 being no exception) and that we do not know the degree to which each is a factor... and therefore stating OR implying that the un-vaccinated population drives the viral mutation rate in this pandemic is inaccurate. Once again- we simply do not know.

"Given that the antibody response to the spike protein is so focused, could mutations in these restricted sequences lead to a less efficacious vaccine, if the human immune response is specific to the vaccine sequence? These mutations might be driven by antigenic drift, or by selection, either during natural infection or due to the vaccine itself. When a virus is grown under the selective pressure of a single monoclonal antibody that targets a single epitope on a viral protein, mutations in that protein sequence will lead to the loss of neutralisation, and the generation of escape mutants. This sequence of events has been shown in the laboratory for polio, measles, and respiratory syncytial virus,7 and in 2020 for SARS-CoV-2.8"

https://www.thelancet.com/journals/lanres/article/PIIS2213-2...

McCarthy, K. R. et al. Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape. Science 371, 1139–1142 (2021).

Plante, J. A. et al. The variant Gambit: COVID’s next move. Cell Host Microbe 29, 508–515 (2021).

Ravindra Gupta, Steven Kemp, William Harvey et al. Recurrent independent emergence and transmission of SARS-CoV-2 Spike amino acidH69/V70 deletions, PREPRINT (Version 1) available at Research Square https://doi.org/10.21203/rs.3.rs-136937/v1(2021).

> They aren't being actively "designed" in any sense

The point made by GP is that the current mRNA vaccines are actively designed to illicit a highly targeted immune response targeted towards the spike protein [1].

> That's why anything that would make real progress has to happen quickly and broadly, without large left-out pockets

Assuming you mean 100% vaccine coverage, this is the opposite conclusion that the authors of this paper came to [1].

Citing [1]:

- "The speed at which nAb resistance develops in the population increases substantially as the number of infected individuals increases, suggesting that complementary strategies to prevent SARS-CoV-2 transmission that exert specific pressure on other proteins (e.g., antiviral prophylactics) or that do not exert a specific selective pressure on the virus (e.g., high-efficiency air filtration, masking, ultraviolet air purification) are key to reducing the risk of immune escape"

- "Strategies for viral elimination should therefore be diversified across molecular targets and therapeutic modalities"

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

This is highly misleading.

All variants right now are significantly more effective at transmission in unvaccinated individuals.

The reason the mutations are on the spike protein is because it's the part of the virus that matters the most for infectivity. The more effective the spike protein, the more easily other people are affected and the faster the virus is produced.

The Delta variant itself rose in India, which has really low vaccination rates.

This is not misleading at all, GP's point is well founded and backed by peer-reviewed literature, see [1]. I have more references if you're interested.

> All variants right now are significantly more effective at transmission in unvaccinated individuals.

Please cite your primary source(s).

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

The article you linked does not say what you think it says. It says that mutation for immune escape is possible. There has been zero mutations for immune escape, so far all mutations were for higher infectivity.

Beyond that, we do know that all variants are more infective in unvaccinated individuals : http://weekly.chinacdc.cn/fileCCDCW/journal/img/cover/ffd464...

If it wasn't, it would never have out-competed the ancestral type in unvaccinated India.

The OP's point was that vaccines drove mutations. So far, that has not happened. There is no variant that is more infective in vaccinated individuals but not in unvaccinated individuals, all variants are simply more effective across the board.

> There has been zero mutations for immune escape, so far all mutations were for higher infectivity.

You're making very broad claims here that are again contradicted by the literature, see [1].

The very short paper you linked to "Transmission Dynamics of an Outbreak of the COVID-19 Delta Variant B.1.617.2" does not even discuss vaccination status. I'm inclined to believe you linked to the wrong paper - or you haven't thoroughly reviewed it yourself.

I'm not interested in arguments based on logical deductions. Show me the peer-reviewed sources backing your point and I will happily read them with an open mind.

[1] SARS-CoV-2 immune evasion by the B.1.427/B.1.429 variant of concern https://science.sciencemag.org/content/early/2021/06/30/scie...

China had around 10% vaccination rate by the time the data was collected.

You are again posting evidence that does not back your argument. Any mutation in the RBD will affect immunity. The question is whether these mutations were from selection pressure from the vaccine or for higher infectivity. Given that the evolutionary millieu had low vaccination rate and that the variants are more infective in non-vaccinated populations, we know this is not the case.

If you can find an article that shows that vaccines cause evolution of variants, then post it. Otherwise, don't, I'm not interested in non-sequiturs.

> If you can find an article that shows that vaccines cause evolution of variants, then post it

Here are several more peer-reviwed primary sources that present strong evidence & theories supporting the fact that "vaccines cause evolution of variants" [1][2][3][4].

Note that, no one is claiming that ONLY vaccines cause evolution of variants - obviously a virus will evolve naturally through random mutation as well, and that is acknowledged in the cited sources.

> You are again posting evidence that does not back your argument

If you take a few minutes to read the sources I've linked to in the this thread, you will see that they corroborate everything I have stated. These ideas are relatively new in the last decade or two, so you may not have heard of them before. That does not mean they are unfounded or based on logical fallacies as you claim.

> Given that the evolutionary millieu had low vaccination rate and that the variants are more infective in non-vaccinated populations, we know this is not the case.

You continue to use the same unsupported points and build on them with logical deduction. I have given you plenty of counter-arguments supported by peer-reviewed literature.

If you have nothing else to add to the discussion, then I will not be continuing it.

[1] Imperfect Vaccination Can Enhance the Transmission of Highly Virulent Pathogens https://journals.plos.org/plosbiology/article?id=10.1371%2Fj...

[2] The adaptive evolution of virulence: a review of theoretical predictions and empirical tests https://www.cambridge.org/core/services/aop-cambridge-core/c...

[3] Why does drug resistance readily evolve but vaccine resistance does not? https://royalsocietypublishing.org/doi/pdf/10.1098/rspb.2016...

[4] Monitor for COVID-19 vaccine resistance evolution during clinical trials https://journals.plos.org/plosbiology/article?id=10.1371/jou...

Actually, literally none of the article you linked have evidence that any of the current variants are due to vaccines.

They provide a plausible mechanism by which future variants may be cause by vaccines. But simply none have done so by now.

I'm going to stop replying because you are actively mischaracterizing your argument, ie, arguing one thing and then providing evidence and arguments from another.

Sudosysgen, while a number of your assertions would be interesting to debate, they have been very broad and without supporting evidence, which makes any meaningful discussion beyond trading opinions impossible.

Edit- added "meaningful"

Which ones exactly? It's simply true that all VOCs have originated from low vaccination environments.

If you're debating the existence of vaccine-driven VOCs, then there is data. If you are going to debate whether vaccines will cause variants, that's a fundamentally speculative assertion for which there is no hard evidence, only speculation.

Just because someone cites evidence doesn't mean it's actually evidence for what they are pushing. So far we had evidence that : Very ineffective vaccines see eventual immune escape, academic articles that link targeted therapies to immune escape but without any evidence that the current vaccines are as targeted as the examples they took, and evidence that a variant that is less neutralized by antibodies can evolve, without taking into account general reduction of infections that mass vaccine rollout necessary for it to be evolutionarily fit or other aspects to immune response, etc...

That is to say, evidence is not necessarily evidence for one's argument. There is no evidence variants will evolve because of vaccination, and I can't prove a speculative negative as a matter of logic.

>> Which ones exactly?

All of them.

>> It's simply true...

"Everyone knows..."

>> If you're debating the...

I am honestly not debating any issue with you. I was pointing out that the statements you have made in posts above are supported, in those posts, by nothing more than your assertions. They are in effect tautological, nothing more.

While you propose some good points that would otherwise be interesting to debate, without supporting evidence these points are nothing more than strongly held opinions, cleverly defended. In this case, there is nothing to be gained on either side through the debate of opinions- other than satisfaction from preening in the light of one's intellect or the presentation of a clever argument.

It seems we've been talking past each other, so as a last ditch effort to reconcile our perspectives - we are in agreement that there is no definitive evidence that vaccines are the sole origin of the current variants. In fact it's likely that neutral genetic drift was the origin.

What I provided evidence for, and what we also seem to agree on, is that "They provide a plausible mechanism by which future variants may be caused (or enhanced) by vaccines".

> But simply none have done so by now.

Time will tell - we just don't have the scientific evidence to support a conclusion either way on this yet.

Every single dominant variant has originated in a country without mass vaccination. There is data. We know that no variants of concern have been caused by vaccines.

We all know that if vaccines are not effective enough for herd immunity, then cases of variants due to vaccines are likely to happen. They haven't yet, and it is possible they never happen.

Check your timelines. Every single variant, dominant or not, originated before vaccines were available...

So why did the variants emerge from low rate vaccination areas instead of the US, Israel or Europe. If vaccines lead to immune escape (misleading term because escape sounds like an active process but it's just a passive result of natural selection) you could expect higher vaccination rate countries as the source of variants.

The timeline doesn't work in your reasoning.

Vaccines aren't a factor as they weren't available when any of the variants emerged. The emergence can't be either the vaxxed or the unvaxxed's fault. Nobody's responsible or culpable, it's entropy.

Of the current strains which are active everywhere : - Alpha emerged in the UK before vaccines - Beta in SA before vaccines - Delta and Gamma in India before vaccines.

Of the current variants of interest: - Eta and Iota come respectively from France+UK and New York City, both before vaccines. - Epsilon (not of interest anymore) came from California before vaccines. Same for theta in the Philippines. - Kappa and Lambda come respectively from India and Peru, both before vaccines.

As for who's at fault for spreading : vaxxing 60% of the population only drops Deltas R_0 from 4.6 to 4.3.

It is immaterial whether you are vaxxed. The virus is smarter.

See my comment for details : https://news.ycombinator.com/item?id=28076327

> you could expect higher vaccination rate countries as the source of variants

It does not matter where or how the variants originated - in fact it's very likely that variants arose under neutral genetic drift. What matters is the selective pressure induced by the current mRNA vaccines which illicit an immune response that is highly targeted toward the spike protein of SARS-CoV-2.

Here are some excerpts from [1], I highly suggest reading it if you're interested in these ideas:

- "The spike protein receptor-binding domain (RBD) of SARS-CoV-2 is the molecular target for many vaccines and antibody-based prophylactics aimed at bringing COVID-19 under control."

- "Such a narrow molecular focus raises the specter of viral immune evasion as a potential failure mode for these biomedical interventions. With the emergence of new strains of SARS-CoV-2 with altered transmissibility and immune evasion potential, a critical question is this: how easily can the virus escape neutralizing antibodies (nAbs) targeting the spike RBD?"

- "Strategies for viral elimination should therefore be diversified across molecular targets and therapeutic modalities"

> All variants right now are significantly more effective at transmission in unvaccinated individuals.

This is what's being said, but it's not what the data seem to show. In the recent surge in cases in Provincetown, MA, 69% of people were fully vaccinated but 74% of confirmed positive cases were among that subgroup.

Obviously there are confounding factors here but it seems readily apparent that delta isn't "significantly more effective at transmission in unvaccinated individuals".

CDC study: https://www.cdc.gov/mmwr/volumes/70/wr/mm7031e2.htm?s_cid=mm...

I don't think you understood the argument correctly.

Do you claim that the Delta variant is not more infective in non-vaccinated individuals?

Do you understand that the Delta variant outcompeted other variants in India, with a vaccination rate lower than 10%?

Beyond that, please don't cite subgroups of data when we have larger groups. By selecting specific outbreaks despite larger data you can p-hack any conclusion.

> Do you claim that the Delta variant is not more infective in non-vaccinated individuals?

In this study, there were more infections in the vaccinated group. That defies logic, though, and intuitively the infection rate of the vaccinated group cannot be higher than that of the unvaccinated. That's why I mentioned confounding factors.

From this study and others, I believe the vaccines used in the US do not provide substantial protection against infection by delta.

> Do you understand that the Delta variant outcompeted other variants in India, with a vaccination rate lower than 10%?

Yes, which means that it is more infectious. Its resistance (or lack of) to the vaccines isn't really relevant in a country with a 10% vaccination rate.

The fact that it's outcompeting other variants in countries with relatively high vaccination rates likely means that the vaccines are less effective against it.

> Beyond that, please don't cite subgroups of data when we have larger groups.

We're specifically talking about delta here, and I'm unaware of a study based upon a larger cohort where a statistically significant number of cases were sequenced, the variant determined, and the dominant variant found to be delta.

> By selecting specific outbreaks despite larger data you can p-hack any conclusion.

Again - show me the larger data here.

> In this study, there were more infections in the vaccinated group. That defies logic, though, and intuitively the infection rate of the vaccinated group cannot be higher than that of the unvaccinated. That's why I mentioned confounding factors.

> From this study and others, I believe the vaccines used in the US do not provide substantial protection against infection by delta.

This is a common error, but an error nonetheless. Take an extreme example of a population that is 100%. Any clusters of cases that pop up will thus be 100% in vaccinated folks. Of course, would would never see that and think "well, I should be unvaccinated, because 0% of infections happen for unvaccinated people."

Focus on this conflation that you are making:

> there were more infections in the vaccinated group and > and intuitively the infection rate of the vaccinated group cannot be higher than that of the unvaccinated.

You are conflating total number of infections with infection rate, which is what is leading you astray. Imagine you have 100 people. 90 are vaccinated. 10 aren't. Imagine that all 100 of those people are exposed to the Delta variant, and 10% of vaccinated folks end up testing positive, while 50% of of unvaccinated folks end up positive. In pure numbers, you end up with 9 vaccinated folks who are positive, and 5 unvaccinated folks who are positive. Voila, more infections in the vaccinated group! But, clearly, that's misleading, because comparing raw infection numbers is meaningless without also looking at percentages vaccinated.

>In this study, there were more infections in the vaccinated group. That defies logic, though, and intuitively the infection rate of the vaccinated group cannot be higher than that of the unvaccinated. That's why I mentioned confounding factors.

Unless you're going to make a rigorous statistical analysis, no, we had studies on this subject with a proper methodology and this is not what they found : https://www.nejm.org/doi/full/10.1056/NEJMoa2108891 (88% efficacy found).

>Yes, which means that it is more infectious. Its resistance (or lack of) to the vaccines isn't really relevant in a country with a 10% vaccination rate.

>The fact that it's outcompeting other variants in countries with relatively high vaccination rates likely means that the vaccines are less effective against it.

No one is disputing this. The point of contention is that the person I'm replying to had the thesis these variants arose because of vaccines, which is simply not true.

> We're specifically talking about delta here, and I'm unaware of a study based upon a larger cohort where a statistically significant number of cases were sequenced, the variant determined, and the dominant variant found to be delta.

You've not been looking then. Entire countries sample variants in the population.

If the vaccine doesn't protect from the infection but just the severity of the illness then other things could easily distort the statistics.

For example full vaccinated people could just act more careless because they feel protected. How is the severe illness and death rate in both groups is a more important aspect.

> The Delta variant itself rose in India, which has > really low vaccination rates.

Vaccines became available in India on February 1st, 2021. The delta variant was first detected during the same week.

https://www.medrxiv.org/content/10.1101/2021.07.07.21260142v...

I hardly believe it managed to both mutate and be detected within that week. Accordingly, it couldn't evolve due to either selective pressure driven by vaccines, nor a lackadaisical anti-vaxx attitude.

It just happened randomly, as such things do. Nobody's responsible, nobody's culpable.

Check your facts, and you prejudices, against whomever they may be.

> Accordingly, it couldn't evolve due to either selective pressure driven by vaccines

You seem to be missing the critical fact that - regardless of whether the mutation evolved by pure random chance or via a vaccinated individual - the selective pressure induced through mass vaccination using a highly targeted vaccine can drive further evolution of the virus. To support my statement, see the reasoning in this paper from very well respected researchers at top institutions across the country [1]. Or take a look at the historical examples of vaccine induced immune escape, for example in chickens [2], or other human viruses [3].

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

[2] Imperfect Vaccination Can Enhance the Transmission of Highly Virulent Pathogens https://journals.plos.org/plosbiology/article?id=10.1371%2Fj...

[3] Why does drug resistance readily evolve but vaccine resistance does not? https://royalsocietypublishing.org/doi/pdf/10.1098/rspb.2016...

>To support my statement, see the reasoning in this paper >from very well respected researchers at top institutions >across the country [1]. Or take a look at the historical >examples of vaccine induced immune escape, for example in >chickens [2], or other human viruses [3].

Selective pressure _can_ certainly apply, and as it has in the past, and you pointed it out correctly.

However, my point is here it _can't_ have. The timeline simply doesn't work (see https://news.ycombinator.com/item?id=28078077 for all variants).

It's literally entropy, or karma, or god, whatever you may believe : everybody was unvaxxed in India at the time. This particular Delta variant, it can't anybody's action or lack thereof in regards to vaccines.

As for the other variants, well, you might be very correct. I don't know, haven't looked into it at all.

And to be pedantic, please let me point out citing models of a natural mechanisms and suspicions by respected researchers who are probably right is not a "critical fact", it's a "well reasoned argument".

Similarly, I won't use models and past experiences projected on current unknowns when temporal logic and direct inductive reasoning gives you an unambiguous answer.

Not sure how to be any more clear about this: No one is claiming the vaccine CAUSED or ORIGINATED these variants. We are in agreement, the timeline does not support this idea.

If you read GP's comment closely, it's worded such that it acknowledges this point (though I admit it could be made even more clear).

Now consider the massive increase in dominance of these strains, not where or how they originated. That is what's relevant to the sources I've provided.

Hopefully with that cleared up, through your "temporal logic" and "direct inductive reasoning" you'll see that the timeline on which these variants came to dominate matches very closely with the mass vaccination efforts.

> The Delta variant itself rose in India, which has really low vaccination rates.

Sorry, I mixed your comment with somebody else's which used the word "emerged" and argued delta and lambda appeared because of the unvaccinated.

On the rest, not arguing on the mechanics and dynamics of the epidemic.

The only meaningful effort made to systematically track the vaccination effort effects since day one is Israel's 580K control group matched cohort. The UK is not quite at this level of details, let's say. Those two countries are not enough.

Most of the rest which I seen is "let's throw a model at the wall and see what sticks", followed "the study is under-powered but let's publish anyway", concluding with "have clueless random msm journalists and anti-covid-vaxx sleuths misquote the results".

On that account, I don't really trust anybody's observations either way quite yet. We'll have to see the post-mortem in a couple year's time.

You're making the argument that it might happen in the future.

The original argument was that it did happen.

Beyond that, the main factor for vaccine induced immune escape is incomplete vaccination or ineffective vaccination, not targeted vaccination. The existing vaccines are not even that targeted as they target the entire spike protein - the only other antigen source would be the capsid.

The original argument was:

> depending on a vaccine based on a single gene is what will (has already) lead to variants

It's the "(has already)" part that you're overly fixated on, and is not a charitable interpretation of the comment given the extraordinary amount of supporting evidence I've provided.

Listen to the feedback you're getting from others here - it doesn't seem to be getting through to you.

I agree with you, I think you may have replied to the wrong comment.

Yes I did, sorry !

Still sparks a lively debate, though ;-)

It's no coincidence the variants come from areas with lower vaccination rates. If your claim were true the variants would come from Israel , Europe or the US.

And most variants don't get a own name because they don't differ enough from known viruses, so only the variants with certain mutations get the attention and a name at all.

>If your claim were true the variants would come from Israel, >Europe or the US.

Except for the UK variant, b.1.1.7, also called Alpha, the deadliest since the beginning...

First detected in November, becoming dominant by end December. The first vaccine wasn't approved in the UK until December.

I should have been longer.

Exactly : Location of emergence of a variant has nothing to do with vaccination or not. All of the current variants raging around appeared before there were vaccines, as were all current and past variants of interest.

The UK had a full vaccination rate of approximately 0.0% when B.1.1.7 was detected, and a first dose rate of 1.5%.

Even earlier than that; it was detected in November, though it didn't become dominant til late December.

Pre vaccination and not really deadlier just faster spreading.

The vaccine elicits a response to many different sites on the virus. It's extremely unlikely that the vaccine ever becomes useless.

Some experts from highly regarded institutions across the country would disagree. See this peer-reviewed paper for introduction to their reasoning [1].

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

That's talking about 1-2 sites. The vaccine elicits a response to a dozen or more.

Did you read the paper I linked to (at least the abstract)? It directly contradicts your claims.

Please cite primary sources to support your claim, otherwise it must be regarded as uninformed opinion.

It says:

>Our modeling suggests that SARS-CoV-2 mutants with one or two mildly deleterious mutations are expected to exist in high numbers due to neutral genetic variation, and consequently resistance to vaccines or other prophylactics that rely on one or two antibodies for protection can develop quickly -and repeatedly- under positive selection.

1 or 2 mutations isn't enough. It would need an order of magnitude more. It's very unlikely for that to happen.

I don't wish to get into a cite duel with what appears to be a Covid troll account.

> 1 or 2 mutations isn't enough.

Enough for what exactly?

> It would need an order of magnitude more. It's very unlikely for that to happen.

Please cite your sources on these points. Otherwise it's just another opinion.

I am not trolling, just genuinely interested in the topic and sick of people spreading misinformation with no citations.

Unless you think trolling is sharing relevant peer-reviewed research that contradicts your unsupported claims.

Like majormajor already said, evolution is not targeted conscious process, it's randomness plus time and as long the result doesn't lead to extinction a species remains existent even if it needs very special conditions to survive.

The western greed might actually backfire. What are the chances that if we let the virus spread unchecked in the poorer countries for a few more years, the virus accumulates more mutations on the spike protein making the existing vaccines ineffective?

This has been a period of constant backfires on a global scale - starting from WHO themselves right at the start of this whole thing when dealing with the first breakout in China, especially having experience with dealing with China (SARS). They knew information was being withheld.

So will this backfire be worst then all the other backfires, or other potential backfires? Honestly we have no idea.

I'm still baffled why the leadership of WHO hasn't been renewed yet... I get that in times of crises leadership shouldn't be changed, but they are stretching it. WHO lost a lot of their soft power during this pandemic.

Every year a new flu shot is needed. Would antibiotic resistant infections evolve in the absence of antibiotics?

The antibiotic resistance most likely predates widespread pharmacological usage. We didn’t invent penicillin, it was discovered.

> The antibiotic resistance most likely predates widespread pharmacological usage

This is absolutely not true, see this very accessible peer-reviewed primary source for many historical examples of antibiotic resistance driven by modern medicine [1].

Here is an excerpt from [1]:

- "After a new drug is introduced, drug resistance can rapidly evolve, leading to treatment failures [12]. For instance, most Staphylococcus aureus isolates in British hospitals were resistant to penicillin just 6 years after the introduction of the drug [13]"

[1] Why does drug resistance readily evolve but vaccine resistance does not? https://royalsocietypublishing.org/doi/pdf/10.1098/rspb.2016...

> This is absolutely not true

I’m not saying modern medicine didn’t put a ton of evolutionary pressure on antibiotic resistance. However, there’s some evidence of AR genes being present in the microbiomes of previously isolated tribes [1]. So we didn’t promote the “invention” of AR by bacteria, but likely just accelerated the selection of AR strains.

1. 10.1126/sciadv.1500183

I see, thanks for elaborating and providing the citation - very interesting paper indeed. "This is absolutely not true" was not a charitable/informed interpretation of your comment, my apologies.

> So we didn’t promote the “invention” of AR by bacteria, but likely just accelerated the selection of AR strains

Well put, we are in agreement.

>if we let the virus spread unchecked in the poorer countries

It's spreading unchecked now in the USA because people are refusing the vaccine. The scenario you describe is absolutely going to happen, but it won't be because of poorer nations, it will be because of selfish people in rich nations.

Pretty baseless to assume where a variant is going to spread or why. It's not like every country other than USA would have 100% vaccine uptake either.

I think it's reasonable to place more of the blame on people who choose not to help (refusing the vaccine) instead of the people who don't have the means to help (unable to get a vaccine).

The original comment was laying blame on the cause of people unable to get a vaccine, not the people themselves. Incidentally that puts them in agreement with you: selfish people in richer nations

Is the bottleneck in deploying vaccine to poor countries strictly the amount of vaccine? Or is it logistics? If the former then rich countries should send more vaccine to poor countries before administering their own booster programs, but if it's logistics, then I don't see the point in holding off on booster campaigns.

My Walmart is begging people to come get vaccinated for free in my 40% fully vaccinated state. I say send the vaccines where they will be used and cherished.

Have you talked to anyone not getting vaccinated in your state to try and gather why?

Despite sort of the popular media push that there's some huge contingent of never-vaxxers, that actually appears to be a small proportion of the unvaccinated[1].

Are the remainder having doubts? Is it a transport/scheduling issue? Is there a misunderstanding about it being a multiple dose vaccine?

[1] - https://www.kff.org/coronavirus-covid-19/issue-brief/latest-...

I'll speak for myself here - I'm not interested in getting it because I've already had COVID.

I know several others who feel this way. Most of them are making the assumption that they have lasting immunity, but I'm going so far as to have my antibody levels checked. It's been several months and they are still in excess of what would be expected from having been vaccinated, so I see no benefit to getting vaccinated.

Further, there are reports of vaccine reactions being more common and more severe in people who have recovered from COVID. It's important to note that "reports of" does not mean "confirmed reports of". That said, I've not yet found anything that leads me to believe that there is a net benefit to my being vaccinated.

A quick glance at the CDC's site shows that ~35m - or ~10% of the US - have been infected to this point.

If you're talking about CDC's data tracker, which does report that 35mm figure (https://covid.cdc.gov/covid-data-tracker/#cases_casesper100k...), then this is misleading.

35mm cases have been confirmed using tests. Considering the vast majority of those who become infected with covid fail to display any symptoms whatsoever and are thus unlikely to be tested, this is very much a lower bound.

Luckily, CDC has some estimates about how many people have actually been infected at this point: https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/burd...

They estimate ~120mm Americans have been infected with coronavirus at this point.

Considering we know that those with prior infection have durable, robust immunity (https://www.cell.com/cell-reports-medicine/fulltext/S2666-37...), that means roughly 1/3rd of Americans, regardless of vaccination status, are immune to covid.

Of course, there's plenty of overlap between those vaccinated and those with natural immunity, so you can't just sum the numbers, but with ~70% vaccinated, we have to be approaching some kind of herd immunity level at this point.

Completely agree with you and parent comment, just wanted to add a few more references to peer-reviewed literature supporting these ideas [1][2].

[1] SARS-CoV-2 infection induces long-lived bone marrow plasma cells in humans https://www.nature.com/articles/s41586-021-03647-4.pdf

[2] Necessity of COVID-19 vaccination in previously infected individuals https://www.medrxiv.org/content/10.1101/2021.06.01.21258176v...

> Most of them are making the assumption that they have lasting immunity, but I'm going so far as to have my antibody levels checked. It's been several months and they are still in excess of what would be expected from having been vaccinated, so I see no benefit to getting vaccinated.

Wouldn't getting vaccinated then be comparable to vaccine + booster, giving you even better protection?

> I'm going so far as to have my antibody levels checked

I didn't know you could do this. How do you get your antibody levels checked?

I have blood drawn quarterly to keep tabs on a potential issue that runs in my family, and it’s just an added test I asked to have performed. I don’t know how much it costs off the top of my head, but I get it done through Quest Diagnostics.

The typical report is binary - you either have antibodies or you don’t. I had to specifically request additional detail, but it was available.

In my experience they are just anxious about getting something they don't understand, doing nothing is super easy/comfortable, and some media scares the last bit of uncertainty out of them.

Speaking from my own point of view, the reason I'm not getting the vaccines is in large part driven by how obvious it seems that the push is not about public health.

For one bit of the large body of evidence of this, that restrictions on those who are unvaccinated are applied even to those who have natural immunity, which is durable and robust, and almost certainly longer-lasting than vaccine immunity (https://www.cell.com/cell-reports-medicine/fulltext/S2666-37...), means to me that there is something else afoot rather than merely public health.

To boot, I am very healthy, not fat, get plenty of vitamin D and fresh air, and am thus basically more at risk from driving to the store than from covid, though it's hard to say for sure what the real numbers are--suffice to say, the risk does not meet the threshold I'd need for me to take any action beyond just getting fitter and healthier and happier every day--which I'd try to do anyway.

I understand frustration and skepticism about the politics of covid response, but I don't understand that as a motivation to decline the vaccine.

While the risk of death from the virus is low for healthy people, it's far, far higher than the risk posed by the virus. Further, many healthy people do get seriously ill (and some die) from the virus including cases of long-lasting side-effects (inability to exercise due to damage to the respiratory system which will certainly manifest in poorer health outcomes over time). Further still, even if you aren't likely to be seriously affected by the virus, taking the vaccine helps to reduce your risk of catching it in the first place and thus spreading it to others who might be less healthy--to be honest, if you were the only person who was impacted I wouldn't care, but this is solidly a case where the decisions you make affect others.

I really support people who are affected by the increasing partisanship of our institutions, but I do wish they would find a better way to vent their frustrations.

There is no reason for me to get the vaccine at all. I'm not at risk of contracting covid. That's the overriding reason. It's a pharmaceutical I do not need.

That the push is being made so insanely is just another reason to avoid it--we don't know what the actual motivations are of those pushing it, but we do know it's not primarily public health, otherwise as I stated, those 120mm Americans with robust antibodies from recovering from covid infection would never be considered any different from the vaccinated.

It's not partisanship, because as far as I can tell, public health authorities have debased themselves and lost all credibility completely in the past 1.5 years, and this is across the spectrum of global health agencies. The American political parties are in union and aside from a couple dissenters are in on the insanity.

When someone or thing hides their motivations, doing what they want seems crazy to me.

I think this probably falls to the normal debate of the balance between "but who will pay for them?" and "it costs every nation to not have all nations vaccinated"

What makes you think people want vaccines in countries that can’t afford them?

What's the guidance on booster shots? How often are we to get them?

Example: I got vaccinated in June, fairly late. Am I to get a booster shot now? Will the booster shots be the same vaccine formula as the original?

https://www.cnbc.com/2021/08/05/moderna-covid-vaccine-booste... has some details released by Moderna this morning. Important bit:

In a phase two trial, Moderna is testing a 50-microgram dose of three vaccine booster candidates in previously vaccinated individuals. The booster shots produced a promising immune response against three variants, including delta, with antibody levels approaching those seen in previously unvaccinated people who received two 100-microgram doses, the company said.

I'm interested to know if just getting another dose of the original vaccine has any effect. If so, I'd love to get it now.

Both Pfizer and Moderna have stated that boosters will be needed this Fall. Pfizer says that immunity drops from 96% to 84% at the six month point. The good news is that the vaccine continues to protect against severe disease due to its effects on T-cells and memory B-cells.

Government acting in the interest of its own people?

I think the WHO is right on this one; we really need to be thinking more about how to prevent an Omega variant that can break through our existing vaccines.

Unfortunately even complete elimination of Covid in a single country would be useless, as long as it's rampant elsewhere -- we have already shown that we're not willing or able to lock down international travel enough to prevent the spread of Covid.

Maybe this is a "yes and" situation, but I think we're not doing enough to get the rest of the world vaccinated.

All this, while the essential systems to capture vaccine safety signal appear to be apparently broken and based on "voluntary reporting", and the world does not give a single fuck about it...

https://roundingtheearth.substack.com/p/defining-away-vaccin...

https://tinyurl.com/CovidvFluReport

It's clear that a large portion of the USA will never get vaccinated, so we should be sending our vaccines to people who want them instead of letting them go to waste here.

That is happening. The US has already exported 110M vaccine doses.

https://www.wsj.com/articles/u-s-says-it-has-shared-110-mill...

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