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You chopped off a crucial part of the sentence that completely changes its meaning. The real sentence is:

> By aggregating VOC-associated and antibody-selected spike substitutions into a single polymutant spike protein, we show that 20 naturally occurring mutations

Aggregating ... into a polymutant spike. That means they put all 20 mutations together, each of them carefully selected from variants of concern or antibody attachment sites, into one single spike protein. Basically they created the most crazy supermutant resistent spike they could. The chance of which would be astronomically small in nature. And their conclusion is that even then a good dose of vaccine allows the body to eliminate it.

Thanks, you're right and I've updated it to clarify.

> And their conclusion is that even then a good dose of vaccine allows the body to eliminate it.

That's not the same thing I got from the conclusion, it sounded like you needed to have a previous infection + the vaccine to clear it. What am I missing?

Did I misread? This super spike protein defeats merely the vaccinated, but not the naturally infected and then vaccinated, AFAIU.

Additionally, could that even happen naturally? Since viruses only reproduce asexually, there's no way for multiple strain's mutations to somehow be combined together, right?

I think it's more of an emergent pattern.

Mutant ABC is the target. First Mutant A becomes the predominant strain. There might be some Mutant AB or AC in the population, but the controlling factor is currently Mutant A.

Eventually, Mutant A therapies/vaccines are introduced and Mutant A starts to lose its hold. Mutant AB isn't treated by the new treatments (or they're less effective, or Mutant AB goes undetected longer, etc.). Mutant AB becomes king of the hill. Repeat with Mutant ABC.

All this would assume that there's no Mutant B or Mutant BC or Mutant AC that increases in prevalence. All the mutations would have to build up over time or occur simultaneously by coincidence (or you could get a combination).

It's just basic evolution - organism follows the niche. We have a hard time recognizing it because generation turnover is so rapid. Instead of taking ~30 years for 2.5 offspring, it's a few days for millions of offspring.

I don't think mode of reproduction matters much when we're talking at this scale. While the virus creates stable clones across generations, I would think they're more susceptible to mutations and any viable mutation is quickly amplified exponentially. Just like the old high school bio experiment to demonstrate antibiotic resistance, only your respiratory mucus membranes are the medium. Those bacteria reproduced asexually.

I'd say it's misleading to say viruses reproduce asexually. Viruses are produced by infected cells.

If the cell is infected by multiple viruses, sometimes there's crossover where the instructions for one get mixed with the instructions for another. So, yes, multiple mutations can end up being combined of they infect a single individual.

It actually doesn't even have to be the same virus. This is how many zoonotic diseases develop -- take a piece of a virus that can attack humans and combine it with a different virus that doesn't attack humans.

Most positive strand RNA viruses, including SARS-COV2, are capable to undergo recombination.

Polymutant just means it has multiple mutations, right? I'm not sure what crazy supermutant resistant is. Does it say anywhere that this was the most crazy supermutant resistant spike they could possibly create, or just that they combined some natural mutations?

No, their engineered mutant completely evaded normal immunity, but that was the purpose of the study, to find a virus that would, then test it against the super immunity discovered in some individuals. This super immunity was able to neutralize the virus, helping to support the idea that there is a special immunity in certain infected then vaccinated people that we should strive to replicate in future vaccines.

But this was only based on the spike protein.

Natural immunity targets far more locations than just the spike. Whereas the Pfizer vaccine only targets that spike.

So it presents a scenario with crippled natural immunity vs the full capabilities of the mRNA vaccine.

Which means in this "super mutant" scenario, the mRNA will always need natural immunity be effective, but natural immunity will only need vaccination if both the spike is mutated as described, and if non-spike targets are also mutated to be resistant.

Which is far more unlikely than the already unlikely "super mutant" spike.

They only tested the plasma from people who were infected, people vaccinated with Pfizer, and people who were infected, then vaccinated.

The 20 mutations they mention was a set of 20 mutations to a single spike protein that they then attached to a carrier virus to test plasma neutralization. It's not the full space of possible mutations that could cause immunity escape, but it is one that they found with a plausibly low number of mutations that it could occur in the wild that would result is almost total escape for vaccinated or previously infected.

An interesting result was that the infected then vaccinated individuals developed antibodies that targeted a very broad range of coronaviruses, including their engineered virus, delta, many other variants, and the original SARS.

It's suggested that future vaccines could be engineered to produce this broad immunity.

The immune system is almost terrifyingly complex.

> An interesting result was that the infected then vaccinated individuals developed antibodies that targeted a very broad range of coronaviruses, including their engineered virus, delta, many other variants, and the original SARS.

Glad you brought this up, but from what I understand this isn't actually all that interesting (read: surprising). mRNA vaccines target the spike protein because it's functional and well-conserved. Natural infection means your immune system sees many more proteins.

Yes, but natural infection did not produce this broad immunity in their samples, only infected then vaccinated developed this special kind of broad immunity. That is supprising in a way, that we could coax the immune system into producing a special kind of immunity that wouldn't otherwise be likely to occur naturally. It opens an area of research into what mRNA sequence or dosing regimen could reproduce this immunity for a future super vaccine.

Natural infection was one event vs. natural infection + vaccine being two events separated by a time interval. It may be that we are stumbling upon a natural mechanism that makes recurring infections almost impossible past 2nd event.

It's possible, but I am not aware of any evidence for or against that theory at this point.

I mean it kind of makes sense if viewed like deep learning. If we train a system on one set of data, the virus itself, it will probably learn to recognize similar data. If we then highlight one specific part that's very special in this data, the spike protein, then the system will recognize the pattern much more easily. Dataset I or II alone would both let the system recognize the pattern, but not be as effective, since it's harder to tell what's important and what's not.

I think we need the denominator here to put '20' into context. 20 out of 100 million possible mutations is, meh, I'll take those odds. 20 out of 100, well, that's something else entirely, isn't it.

Edited because a correction by another user helps to clarify - it is not about the 20 mutations (which they created a mutant spike will all 20 of them!) though, it is more about what was and was not effective in defendening against the mutant spike.

Coronaviruses are RNA viruses, so there's only a single copy of the genetic material, vs DNA with two copies. The result of RNA viruses is that they typically mutate at a much higher rate than DNA viruses. There are viruses that mutate faster than Coronaviruses, though.

>So, perhaps unsurprisingly, if you've had the virus and then received a vaccine, it appears that you have a very high level of immunity

Why would someone get vaccinated post infection?

For more robust immunity, many people do this.

it is in fact recommended.

But apparently not effective in all cases. A friend of mine in their early 20s has Covid a second time, having been vaccinated after their first infection.

(To catch it once is unfortunate...)

But these are outliers, right?

I don't know why your comment bothers me so much, but...

No, your friend didn't have COVID a second time after being vaccinated after their first infection. Especially lacking any clarification that they were in fact tested positive both times, you are merely contributing to noise on the internet.

1) "a friend of yours" is not a data point on which others should base their worldview (unless their testicles got huge and their fiance called it off, why even share?)

2) reinfection is rare

3) it is likely the first time they think they had covid, they weren't tested, and actually had the flu.

Here is the CDC information on reinfection: https://www.cdc.gov/coronavirus/2019-ncov/your-health/reinfe...

As of August 6, 2021, the CDC has nothing conclusive to say on the matter: "Cases of reinfection with COVID-19 have been reported, but remain rare . "

Anecdotes are noise, and I would encourage you to do no further research.

> No, your friend didn't have COVID a second time after being vaccinated after their first infection.

PCR tested positive both times, double jabbed in-between. You might not like the fact that it's possible, but that doesn't make it impossible.

1) You seem to be the one projecting a world view based off an anecdote. Chill.

2) Law of large numbers. A small percentage of a very large number is still a large number.

3) Here you go again with made up "facts" that aren't even anecdata.

> Cases of reinfection with COVID-19 have been reported

Seems pretty conclusive. They're referred to as "breakthrough cases", and not as rare as you seem to believe. What's more important is that the risk of hospitalization and death in breakthrough cases is considerably reduced.

> I would encourage you to do no further research

I would encourage you to do more. Making up "facts" to make a point does nothing to strengthen your position (whatever that may be – seems more like you just wanted to rant).

A vaccine doesn't prevent you from catching a virus again--especially if you get a big bolus.

It does mean that your body is prepared to sweep the virus out faster and prevent it from spreading as far in your body.

In computer terms, a vaccine reduces the latency between when your body gets a virus and when it reaches critical immune response to get the virus under control.

So, for example, while you may get Covid in your nose, being vaccinated means that it doesn't get down into your lungs and heart and cause damage down there (the issues that cause most people to be hospitalized).

Why wouldn't they?

there are of course unknown risks associated with putting anything into your body. But it's probably still a good idea.

For the same reason most vaccines require two doses. And for the same reason some countries are planning or doing booster shots.

Antibody levels drop rapidly after an infection, if they persist at all.

Getting a vaccination after infection re-triggers the immune system and makes antibodies more likely to persist for longer.

Reading up on this many months ago it seemed likely that natural infection plus a single vaccination would be equivalent to two vaccine shots.

There was research about only needing to give one shot of vaccines like AstraZeneca to people with previous infection. It was considered too complex to manage, and the research as to efficacy wasn’t finalised, so they stuck with two.

Having had Covid, plus two shots of something like AstraZeneca is presumably somewhere in the region of a standard two-shot-plus-booster campaign.

I don’t really understand much of this paper, but given other comments it seems to be a reasonable idea.

Because your immune system isn't guaranteed to pick up on the most relevant part of a pathogen.

While lots of people got diseases like smallpox and measles only once, others would get them several times. The difference is what part of the virus your antibodies selected to attack.

The spike protein seems to be both extremely important to SARS-CoV-2 and relatively unchanging.

If your body creates antibodies to it, you will have immunity on par with the vaccines.

If your body doesn't create antibodies to it, you have a mixed bag of immunity. Getting a vaccine buffs that up.

Immune systems are very buggy learning systems. This is good from a species survival perspective, but not always for a specific individual.

It is currently recommend, and studies, such as this one, show that you will be highly protecting yourself from future variants you would have otherwise had low immunity against.

Given the... possible... origins of this virus, I hope they are being exceedingly careful about actually synthesizing a virus with all of these mutations at once.

Or they stand a very high risk of creating and releasing the doomsday variant they are worried about in the first place...

I think they only synthesized the spike proteins, not the whole virus. You don't need a whole virus to check if a protein is neutralized or not.

(For the record, if spike proteins were themselves in any way harmful to life on their own, Moderna and Pfizer wouldn't be the primary vaccine vendors for the US right now.)

> in any way harmful to life on their own

I think it's fairly well accepted that they can cause myocarditis [1], which has killed some [2]. Better than getting the virus, but they appear to be capable of harm. I've naively wondered if the young men are getting jabbed in veins, rather than muscle tissue.

1. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/my...

2. https://www.bbc.com/news/world-asia-58380867

No need to downvote. I'm not anti-vax, but I'm also not anti-science. The virologist, Vincent Racaniello, has a great podcast on YouTube. He has talked about this a few times. From my understanding of what he said, the spike protein created by infection, and with the vaccines, can "bind" proteins together, causing the myocarditis. There's speculation that this might be related to some of the cognitive problems of coronavirus, also.

Approval doesn't mean absolute safety, since that's absolutely impossible to achieve. This is considered acceptable (as shown by the CDC page listing it as a risk), since an actual infection is worse, for most.