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Comment by ethbr0 | Hacker News Reader

Here's the link on CoVariants (aka 21K): https://covariants.org/variants/21K

Gives a better breakdown of what we're actually talking about.

Also known as B.1.1.529
Variant21K appears to have arisen in November 2021, possibly in South Africa. Early sequences are predominantly from South Africa, though also detected in Botswana and Hong Kong.

21K is primarily of concern due to the large number of mutations it has in the Spike gene. Many of these variants are in the receptor binding domain and N-terminal domain, and thus may play key roles in ACE2 binding and antibody recognition.

This literally reads like post apocalyptic fan fiction.

>This literally reads like post apocalyptic fan fiction.

I find it incredibly fascinating how fast this virus can mutate in order to throw curveballs around our natural and engineered defenses and become more efficient at killing us.

How is this even possible in such a short amount of time? I thought evolution takes tens of thousands of years. It's not like viruses have giant brains with massive IQs to come up with all this so fast.

Would be cool if someone could ELI5.

Given a population of almost 8 billion and a six months head start you are now looking at a reservoir of many millions of people infected at any given time. Each of these will provide 1 to 100 billion new virions, and each of those is an opportunity for the virus to undergo a mutation, which RNA viruses are particularly receptive to because they lack the same level of error correction that DNA based viruses enjoy.

Edit: fixed bit about error correction, thanks somewhereoutth!

With that said, then a one sise fits all vacinne is highly unlikely, correct? That there will be variants and mutations that will out pace (so to speak) the protection a given jab is engineered to offer?

Long to short, if death prevention is the objective then we need to shift to finding solution that are less specific but still effective. For example, anti virals.

The various vaccines have different ways of acting, some will be less specific but also less effective from the start, some will be more specific but run a higher chance of being outdated by future mutations, all of them can only be tested for efficacy against the known strains. So yes, this probably will remain.

>That there will be variants and mutations that will out pace (so to speak) the protection a given jab is engineered to offer?

Flu vaccines are also updated on a yearly basis to reflect the strains currently in circultion, so why would the covid vaccines not do the same?

This sounds like an anti-viral subscription service. :)

It's like the ideal scenario if you are a multinational pharmaceutical company.

The immune system (and vaccines) operate mostly on the external bits of a viral particle.

These bits perform several critical functions: hiding from the immune system, attaching to cells the virus needs to replicate in, etc.

Changing any of these things results in two questions.

(1) Does the change make the virus better or worse at X? (where X is something related to what that bit was doing)

(2) Does the change make the virus more or less visible / resistant to the immune system?

The answer to both of these are independent, and for any one particular change, depends all the way down to chemistry and physics.

It's possible that a given virus design cannot mutate external features without rendering itself ineffective. It's also possible that relatively minor mutations can make it more effective and/or able to avoid antibodies and the immune system.

The mutation space has been studied for SARS-CoV-2, but to put it simply, it's a very complicated problem that involves (among other things) protein folding and molecular simulation. Not easy stuff to brute force.

Interestingly, SARS-CoV-2 does have error correction - but the essence of your comment is correct.

Fair enough, I should have been more precise.

Well, isn't the common cold the result of an endless stream of "curveballs" and thus why there's no prevention for it? That is, the virus that causes the common cold is actually numerous variants (not the exact same version of the virus).

The diversity of the virus species causing the common cold is actually much higher. There are rhinoviruses, adenoviruses, enteroviruses, and coronaviruses, among many others. It seems this symptom and transmission pattern is just very evolutionally successful.

It has a much shorter lifespan thus in one human lifecycle it has a much more time to evolve. Humans (or other higher animals) are not powerless. They have sex. The random recombination of genes when reproducing can create an environment hostile to parasites/viruses in its offspring. See https://en.m.wikipedia.org/wiki/Red_Queen_hypothesis for details.

Evolution takes tens of thousands of tries, not years.

Sometimes far fewer tries than that, of course, but viruses certainly get a lot of iterations in any given population in any given month.

The probable cause for many variants of concern has been multi-month long infections in one immunocompromised person (obviously a different one each time), often treated with convalescent plasma or monoclonal antibodies to keep the disease in check but not cure it. This provided the virus a perfect optimization platform, and for it to quickly collect a group of mutually beneficial changes.

In the normal case the selective pressure isn't really there, since the virus will get beat back after a week or two anyway and just 1-2 point mutations probably didn't give it any significant advantage is infecting more hosts.

Given how many mutations this variant has compared to its most direct known ancestor, the former is almost certainly what happened in this case too.

See for example: https://www.scientificamerican.com/article/covid-variants-ma...

> How is this even possible in such a short amount of time? I

Mutations on organisms such as viruses depend on the raw amount of virus duplication which happens, not per se "time", if you have a large amount of hosts, and therefore high amounts of duplication that increases the duplication rate making it more likely that mutations will occur, therefore speeding up the mutation rate, and as it happens with large countries still not taking strong measures against covid there's ample amount of hosts which can incubate new mutations....

Also, ought be noted that mutation is entirely random, this is *not* "a consequence to vaccines existing", most mutations will be neutral, others negative to the virus itself, but few might have positive effects on its vitality, or incubation period or others

> and become more efficient at killing us.

This is not actually a "goal" of the virus, since dead people cannot move and therefore spread much less of the virus. They seek to become more infectious so they can spread more, and in this process sometimes they also accidentally kill the host.

> Viruses don’t always become attenuated (less virulent). When they do, it’s because there is an evolutionary selection pressure driving it. No such pressure exists for SARS-CoV-2. An example of this type of selection pressure would be a virus that is so virulent, it kills its host before it can be transmitted to another one. A virus is essentially a machine programmed to make more viruses. To do that, it needs to be spread to new hosts. So variants that are so virulent they kill a host before that host can pass it along, that is under negative selection pressure. The more virulent viruses won’t be passed on. But attenuated variants will. They are under positive selection. For SARS-CoV-2, this has never been an issue. This virus can be transmitted to a new host before an infected person develops symptoms. Even those who die from COVID are most contagious before they become severely ill.

https://mobile.twitter.com/angie_rasmussen/status/1441416013...

Viruses select only for transmissibility, nothing else. They do not select for virulence any more than any other number of factors that may or may not overall have an impact on transmissibility. To think a virus naturally becomes less virulent to become more transmissible ignores a raft of other factors such as its ability to generate viral load that the host spreads, its ability to evade host defenses, presymptomatic/asymptomatic capability of spread, etc. etc.

Numerous viruses throughout history have not become less virulent even over the course of thousands of years.

It speaks to the more serious problem with vaccine hesitancy - the more virions (individual virus 'particles') that exist, the greater the chance of a mutation that finds a way around our defenses. It's just basic evolution.

The variants arise randomly and proliferate with the current major strains. The infected population adapts to reduce the transmission of the most virulent/contagious strains. Selective pressure (tug of war between infecting people and people fighting off the infection) increases on the new variants until one or a few maintain or exceed the transmission of the progenitor strain.

That's the problem with the, "I'll get over it/I'm not worried/My segment of the population doesn't die from it" mentality. The more infections - subclinical, asymptomatic, severe, fatal, undetected - the more rolls of the dice. We (humans) are selecting variants that are worse for us, hoping we can snuff out the infection before some key mutation that eludes our immune system and/or testing develops.

Two other thoughts with internal conflicts/points worth mentioning - First, recovered patients should be more resistant to new strains. Their immune systems threw everything at the virus to defeat it, so their response will be more diversified than those with mRNA vaccines targeting a specific protein sequence. (The magnitude and usefulness of the variations in immune response can negate that advantage.) Second, the reasons that a 'novel' virus is dangerous are that we, as a species, don't know if we can (naturally/innately), and we don't know how much the virus can change in protein sequence (to evade our defenses) or our response to infection.

Anyways, I'm rambling. Not a virologist, but a PhD (and as such, I think I know more about stuff than a really do) and that's how I think about it. :)

On the other hand the vaccines could be causing more stress on the virus as they generally aren't very good. I'm saying this as someone who had the virus then the vaccine.

> That's the problem with the, "I'll get over it/I'm not worried/My segment of the population doesn't die from it" mentality. The more infections - subclinical, asymptomatic, severe, fatal, undetected - the more rolls of the dice.

The vaccines we're currently using don't prevent infection as they do not provide sterilising immunity. To quote[1] Sunetra Gupta[2], infectious disease epidemiologist and a professor of theoretical epidemiology at the Department of Zoology, University of Oxford:

> The vaccines that we currently employ appear to be highly effective in preventing life-threatening illness but do not meaningfully contribute to the maintenance of herd immunity.

> …we find ourselves trapped by the superannuated conviction that vaccines must block infection as well as disease.

Given that, how is contrasting those who've had vaccines with those who haven't of any relevance? We have other comments in the thread (like this one[3]) pointing out that it could be immuno-compromised people that are the main source of new variants. Right now, they're among the least likely people to have been vaccinated.

[1] https://www.telegraph.co.uk/news/2021/11/24/vaccines-never-r...

[2] https://en.wikipedia.org/wiki/Sunetra_Gupta

[3] https://news.ycombinator.com/item?id=29354300

> We (humans) are selecting variants that are worse for us

I believe this to be a very common misconception. Evolution selects variants that are better at replicating. It does not follow that those are the worse for our health.

Imagine a variant that would effectively be very lethal to us: wouldn't it go extinct if the bearers die or even stay home sick before it can spread?

Successful viruses fly below the radar, I guess.

Other posters have addressed the other questions so I'll focus on your comment concerning "massive IQs to come up with all this so fast".

Evolution does not work that way. It is not a conscious decision or process on the part of the organism. It is the result of mutations due to imperfect copying of genetic material. Very likely most of the mutations are useless or harmful to the organism. But once in a while the mutation gives the organism an advantage and allows it and it's progeny to outcompete the other, unmutated organisms.

Even the process of evolution does not make decisions or have a particular direction or goal. It's all randomness and depends on the large number of chances.

As far as becoming more efficient at killing is, most viruses mutate to a state of being less deadly. Not killing the host is an advantage for a virus.

Here is a nice video showing the evolution of microorganisms in action:

"The Evolution of Bacteria on a “Mega-Plate” Petri Dish" https://vimeo.com/180908160

The original paper about the experiment:

"Spatiotemporal microbial evolution on antibiotic landscapes" https://www.science.org/doi/10.1126/science.aag0822

NOT a ELI5 but this should give you a reasonable understanding. Why are RNA virus mutation rates so damn high? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6107253/ "RNA viruses have high mutation rates—up to a million times higher than their hosts—and these high rates are correlated with enhanced virulence and evolvability, traits considered beneficial for viruses. However, their mutation rates are almost disastrously high, and a small increase in mutation rate can cause RNA viruses to go locally extinct"

Some bloke who was the head of Porton Down aka Public Health England when commenting on the London Plague pits found when digging the tunnel for Cross Rail suggested RNA viruses have a single helix so are prone to high levels of mutations unlike DNA which has the double helix checksum to reduce mutations. This is probably the episode. https://www.bbc.co.uk/programmes/b04cnps9

How Messenger RNA vaccines work. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different...

mRNA is not the only solution, some dietary changes can create a chemical based attack vector as your body has evolved to cope with extremes. This just one example of many different chemical attack vectors. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413200/

There is also this https://news.ycombinator.com/item?id=12451198

But I cant find the hacker news link on a paper from MIT which also suggested a 3 day fast reset the immune systems "memory" which was a novel way of wiping vaccine triggered immune system responses and probably isnt what you want to do if you believe in the covid vaccines, but if you are an anti-vaxxer forced into having a vaccine, then it could be a way of wiping its effect from your body if the study was accurate.

Now before you go out fasting, just bear in mind you will be depleting your body of many things like the vampire chemical glutathione (NAC, Glutamine & Glycin) which depletes as you age. Its called the vampire chemical because it whitens skin and makes you sensitive to light amongst other things so there might have been some truth to those vampire legends!

I know Vit D is mentioned alot, the Welcome Trust in Cambridge reversed engineered the human genome back a few years back and suggested there were 2776 Vit D receptors, most concentrated around the immune system genes, but the VDR has a zinc finger so you need to take zinc and both A & D will get you closer to hypercalcemia so that brings its risks, but in 1959 the scientific community did work out if you take A & D you need to take K to mitigate the risk of hypercalcemia. And if you are elderly, you should consider taking taurine as this helps the body manage the fats in your diet (bile) amongst other things, which explains why the elderly generally absorb A & D less easily or respond less to supplementation compared to young people. You'll find taurine in some wacky places in the body.

sarscov2 is already over the size threshold where it would mutate too much to survive and spread, so it has an error correcting mechanism, and as a result a much lower mutation rate than many other RNA viruses including the more prevalent smaller coronaviruses.

"This literally reads like post apocalyptic fan fiction."

That's a huge part of the pandemic, people are not used to being exposed to that kind of language, so their imagination runs wild.

Even the word “coronavirus” sounds scary and exotic.

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