with Delta being the large green and blue parts at the top, and Omicron being a few red dots a little up from the bottom. If you trace back, you'll see that its nearest relative is wildtype from the spring of 2020. That's pretty weird, and there are really only three ways I can think of that it could happen:
1. human manipulation in a lab using early wildtype samples. This seems unlikely, because what would be the point and how did they let it escape?
2. chronic infection in a single immunosuppressed patient. We've seen this before (see, for example, this: https://www.nejm.org/doi/full/10.1056/NEJMc2031364 ) and southern africa has a lot of immunosuppressed people thanks to HIV. Additionally, there are some genetic markers that suggest evolution in a human.
3. spillover of wildtype in spring 2020 to some animal, evolution in that population for about 17 months, then spillback last month into humans.
I'm with the article, in that I favor 3 even though there's some evidence for 2 just because i can't quite understand how the omicron patient might have gone all that time without infecting anybody else with a proto-omicron version of the virus (which would then spread and be picked up on that chart). It's possible, I guess, that omicron got increased transmissability in a mutation in the recent past, and it could have lived in the patient with bad transmissability for a long time previous. And since delta is so amazingly transmissable, any proto-omicron could have infected a couple of people and then died out undetected. But still.
Your options are fine, but nowhere near a comprehensive set. You left out an obvious option, for example:
4. Evolution of a lineage that we didn't detect until now because it wasn't common.
We need to stop making the assumption that our surveillance systems are comprehensive. They're pretty bad, actually -- and they're generally incredibly biased in what they're looking at. Even if we were doing unbiased random sampling and sequencing, we'd have to do huge volumes of it to reliably detect rare strains.
(aside: and if we did do that, we'd be in non-stop panic mode, because we'd be finding a new strain every day.)
But we'd have to be missing a huge number of related strains to make the phylogeny look like that. The important thing isn't that we found a new strain now, it's that the strain is most closely related to very early wildtype.
> But we'd have to be missing a huge number of related strains to make the phylogeny look like that
Define "huge". There are about ~30 mutations on the spike protein from the closest known relative, and there's a fairly strong selective pressure against the wild type (both from vaccine and natural infection). I think it's quite probable that we missed a few months of evolution of a strain circulating in a single-digit percentage of people.
This is particularly true when you consider that this strain has S-gene dropout (Delta does not), and was probably dismissed as Beta and never targeted for sequencing by most labs. That's why I meant by my original comment that we're biased about what we look at.
Or the population that it evolved in is isolated, so it never escaped back into the developed world until now. Somewhat unlikely given how interconnected the world is now, but it is Africa after all.
Oh, definitely. It's fairly obvious to anyone who understands molecular clocks that this strain is already widely spread.
We're panicking and closing borders and doing untold damage because...we continue to overestimate our ability to see what nature is doing in an unbiased way.
That wouldn't happen, even with our substandard testing, unless the strain somehow had very low ability for transmission and then only evolved that in this last jump which is not likely. Since there are multiple variations from the older strain, we'd have seen at least some of the new variations along the way.
I still can't believe that US, where it's been rampant, hasn't been a place to report a new variant of concern for the first time, but UK, India, SA (and other like Peru?) have.
Re: #3, so if you go all the way back to the original strain: Potentially animal > human > animal > omicron in humans.
Like, a continuous mixing and mashing feedback loop.
If nothing else, the variants occurring in real time right before our very eyes should make the idea of evolution a lot easier for some in various communities to finally grasp.
>If nothing else, the variants occurring in real time right before our very eyes should make the idea of evolution a lot easier for some in various communities to finally grasp.
I don't think the issue of evolution has ever been a question of people grasping the science. The issue has and continues to be the resolution of its conflict with their faith. Some have found a way through that mental obstacle course, but most have not.
Scary number of people, not even of religious sort, think that it's perfectly fine to pick and choose which parts of scientific achievement they accept and which they don't. It's more on the scale of what they like or don't like. They might like their smartphones and other gadgets, not so much vaccines, fluoride, GMO, all that which isn't 'natural' or 'organic'.
So yes, it is a question of people grasping the science, not of this specifically, but as a whole. They are not on-board, they never fully confront any contradictions that they encounter or spew. Logic is not their friend, they are not inquisitive, getting to the bottom of something is not in their nature. You might think that in general people are reasonable, but margins are not that high and informed-ness is very surface-level.
There’s certainly some deeply unscientific thinking out there … but I don’t think your examples are good ones.
It’s reasonable to dislike GMOs (or some subset of them) because of who’s selling them and why, unrelated to the science. It’s reasonable to argue against fluoridated water even while accepting it’s good for dental health, because you disagree with mass medication. It’s reasonable to buy organic food if you know it to be free of certain chemicals which, knowing their scientific characteristics, you would rather avoid.
Problem is that people I'm talking about can't divorce not liking something from accepting something as a thing. They would look for 'evidence' that it doesn't exist, harmful or a product of a conspiracy. They don't use scientific method, they are not looking for facts, they are looking for confirmation of their preconceived notions using biased search engine queries or by hanging around in their bubbles. People like that don't have a habit of changing their opinions, that's who I'm talking about.
It is absolutely scientifically ok to reject GMO, since they decrease variety and after x years of abundance in a year a superbug can destroy it all.
In case of GMO it is a play with the unknown (health, stability), it is a risk against a somewhat cheaper food.
In case of vaccine it is still a play with unknown, but there the risk is against another risk not just money. If the virus would be less deadly much less people would have taken it. And the other way around as well, would be more deadly people would queue up instantly.
It is not as black and white as you describe. stupid vs smart people as you say it.
And by the way, this is called common smartness. Everybody is susceptible for different thing everybody is resistant to different things so the whole word is hard to take on.
> The issue has and continues to be the resolution of its conflict with their faith. Some have found a way through that mental obstacle course, but most have not.
This baffles me. I believe most Christian religions(definitely Catholics and most Protestants) embraced the evolution decades ago. So who is debating it and why?
Not sure if they constitute "most protestants" but the majority of so called evangelical christians are quite hostile to the scientific reality of evolution.
Ah now I see. It looks like the Fundamentalist–Modernist controversy is an US thing - it's unusual to find Protestants in Europe that would reject the evolution.
Evolution has always occurred before our eyes, e.g. antibiotic resistant bacteria. I doubt the evolution of Covid changes anyone’s opinion on evolution.
People disbelieve macro evolution. Micro evolution on the other hand is hard to disbelieve because the experiments about it can be performed in real time.
I worked with a clinical pharmacist who was an ardent young-earth creationist & anti-evolution proponent who during his day job spent his time adjusting medications and dosages for patients as part of our antimicrobial resistance stewardship team. Could never quite make that click for him.
If you were trying to make it click by citing the micro evolution you were working with it is not all that surprising it didn't work, because in fact trying to use micro evolution to prove that macro evolution is possible is not a very good approach.
In programming terms, evolution is like tweaking a program a few lines at a time, with the requirement that the program has to still run and be useful after each tweak. You can evolve a C program this way to get a faster, or smaller, or more memory efficient, or more featured C program, but you are not going to be able to evolve a C program into an APL or Haskel or LISP program that way.
That macro evolution is possible is quite amazing and astounding when you stop and really think about the constraints. It is not at all obvious that micro evolution implies the possibility of macro evolution.
It's really something that is best approached from the opposite direction. We see evidence of macro evolution, and then use micro evolution as part of the explanation of how this is happening.
Dude literally thought the world was 6,000 years old and that Adam lived to be 930 likely because "the oxygen content of the air was higher then" -- I wasn't too hung up on walking through the science of evolution with him. He also told me evolution wasn't possible because of the 2nd Law of Thermodynamics, so.. yeah.
OTOH as engineers who spend a large percentage of life pouring blood and sweat into creating things, it's not a giant leap of inference to ponder that there may be a Creator for the engineering marvel we live in.
I struggle with the speciation aspect of Evolution. Not hard to empirically verify in-species adaptations, but I'm still waiting to see coronavirus turn into influenza (etc)
Where do you think covid came from in the first place?
Covid won't change into the flu, that's like assuming a chicken might evolve into it's ancestors species or humans will evolve into apes. Evolution goes forward, not (or rarely) backwards.
It's a completely new species that, up until 2019, did not exist in the human population.
This sort of evolution happens frequently when people are in close contact with animals. Hence the reason European disease wiped out native populations but not the reverse. Also, a direct example of human evolution.
I think this is where we differ. That obnoxious spiky little ball we all now know as coronavirus(es) existed in both humans and bats long before making the "jump". Ignoring the possibility that humans are directly responsible for the new host capabilities, it's not like we watched influenza slowly morph into a coronavirus and cause a new form of havoc. All we saw was an existing "species" that had mutations inside the bounds of its genetic code that enabled it to survive elsewhere.
>I struggle with the speciation aspect of Evolution.
You might find that pondering the existence of "ring species" proves enlightening. It turns out that "species" isn't even a well defined concept when you look closely enough.
Yep, Phylogenetic boundaries and the clades are entirely arbitrary constructs. Useful, but don't treat them as though they have absolute meaning as they're essentially a discretization of a continuous process with all the limitations henceforth.
I dislike the use of the terms "macro evolution" vs. "micro evolution" because they're not really any different other than timescale. For some reason, though, people who are religious and deny evolution misrepresent "macro evolution" as "one animal changing into another" as opposed to just "micro evolution over a longer period of time".
> If nothing else, the variants occurring in real time right before our very eyes should make the idea of evolution a lot easier for some in various communities to finally grasp.
I've heard people say that hurricanes and natural disasters were God punishing us, I can easily see the same logic applied to COVID. No need to rely on science for answers when a vengeful god suffices.
Never underestimate a human's mental gymnastic ability. This is where evolution deniers draw a distinction between "micro" and "macro" evolution, arguing that "of course micro evolution happens, you can see it!" and "of course macro evolution doesn't happen, you can't see it!"
We basically guess what the US flu will be by what is “popular” in Asia or Southern Hemisphere, we figure in about 6 months or so it’ll be in the US. I have no idea how Europe or Rest Of World makes flu vaccine guesses.
Guess what though? They do the same. What is “popular” in the west MAY be popular in Asia in a few months.
The flu game is constantly a best guess of what others saw months ago.
We seem to have been increasingly getting bad at that guessing game... Thankfully coronavirus put the kaibosh on the flu at least in the short term, so if it was the flu pangenome making a meta-evolutionary play, we may have reset that clock.
False. The seasonal influenza vaccine creators haven't been increasingly getting bad at that guessing game. Vaccine effectiveness estimates have fluctuated up and down randomly with no clear trend.
are we looking at the same data? It's hovering around 40% with at least two duds, when it used to be in the high fifties, even 60%. Plus, this is a table of strictly "seasonal" flus. There is no clear definition of what constitutes a "seasonal" flu; If I'm not mistaken, "non-seasonal" is just a catch-all for flus that weren't part of the vaccine package.
Regarding #2, it's likely that Omicron did not emerge in Africa but elsewhere. South Africa has the best genetic surveillance on the planet which is why they're picking up evidence of new variants more often than other countries.
Similarly, the second case in the US was just found in here in Minnesota, probably for the same reason (at least compared to the rest of the US). MN typically has "more" cases of seasonal diseases like flu compared to other states since our Dept of Health has been reasonably functional and funded.
If this had been circulating in Europe, North America, or South America before Africa, we'd know. If it came from Asia or the Middle East, it'd be quite odd that it didn't get exported to Europe but just to Asia. It's overwhelmingly likely that it originated somewhere in Southern Africa, though the exact country will be anybody's guess right now.
Could it just be that testing was so bad in Africa that we never identified this strain as it was spreading in those communities until it had some breakthrough mutation that made it much more easy to spread?
I think it is telling that it was South Africa, probably one of the few SSA nations with the infrastructure to do this testing of a representative sample of their population, where this was found first.
it could be easy to find out. omicron has a very characteristic signature in the PCR test (a missing band) that I imagine makes it possible to do a retrospective analysis if you have good data records.
Doesn't it share that missing band with Alpha though? There's not much Alpha around these days, so it's a good signal, but if you go back in time that would confound your search.
I don't know, I wasn't aware of that (I am not an expert, just someone that reads slightly-more-scientific-than-mainstream-media dispatches, and can understand them having done a ton of molecular biology). If you can pont me to that I'd love to be enlightened.
> 2. chronic infection in a single immunosuppressed patient. We've seen this before (see, for example, this: https://www.nejm.org/doi/full/10.1056/NEJMc2031364 ) and southern africa has a lot of immunosuppressed people thanks to HIV. Additionally, there are some genetic markers that suggest evolution in a human.
I speculated about this in another post recently. Might as well try putting it up for consideration here again:
If it's in co-infection with HIV, then it isn't only the immune status that's abnormal in the physiology, and it might not even be the most significant circumstance with respect to what's happened here.
They're not particularly closely related, but both coronaviruses and retroviruses apparently pack their genome as positive-sense, single-stranded RNA, so it doesn't seem wildly implausible to me that HIV's modifications to nucleic acid metabolism would operate on coronavirus RNA, and HIV is infamous for generating plenty of variability for itself. It copying sloppily and doing it on purpose, insofar as that can be ascribed to an organism like this.
I never got particularly deep into viruses, so there may be certainly be known aspects about this I'm missing, but so far I haven't been able to find anyone to tell me a compelling reason why it wouldn't work.
What are the markers that suggest evolution in a human? I'd be interested to see a reference.
Except SARS-CoV-2 also has a proof-reading lacking RNA Polymerase, and HIV infects CD4+ T cells whilst SARS-CoV-2 infects cells which express ACE2, which are numerous, but doesn’t necessarily mean a person with both infections is at all likely to have both viruses floating in the same cytoplasm.
Basically, the mechanism you suggest is not necessary because the RNA Pol is just as shit as HIV’s
The shared cytoplasm condition is perfectly reasonable requirement, certainly, but it's also not a terribly high bar to clear. HIV does indeed prominently infect CD4+ T lymphocytes, but that is by no means the only cell type it infects.
At the very least, both species have been described to infect macrophages (and both may display tendencies to promote cell fusion, in which case I would expect many normal categorizations of what a cell type is, are off).
As for the polymerases being roughly equivalent, I have a hard time believing that.
As I've understood it, coronavirus RNA polymerase does perform proofreading, and over the course of the pandemic there has been plenty of media statements of relief and optimism about SARS-CoV-2 evolution not being such a big problem because the genome seems to be relatively stable as RNA viruses go.
Many of the people making those statements may have had more hopes than facts to back that up, by all means, but simply grabbing a few highly ranked search result on mutation rates (I don't have time to do a more proper review now, sorry) does seem to suggest SARS-CoV-2 was estimated to have a low mutation rate (https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7387429/) at least early after the introduction to human. Admittedly, it's also reported that mutations which should be suspected to reduce the proofreading effectiveness appeared early (https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8134885/).
"extremely high mutation rate of (4.1 ± 1.7) × 10^{−3} per base per cell, the highest reported for any biological entity. Sequencing of plasma-derived sequences yielded a mutation frequency 44 times lower, indicating that a large fraction of viral genomes are lethally mutated and fail to reach plasma. We show that the HIV-1 reverse transcriptase contributes only 2% of mutations, whereas 98% result from editing by host cytidine deaminases of the A3 family."
Evidently those cytidine deaminases act on viral DNA sequences as a host defense mechanism, so that source of mutations at least, would be distinguishing for an RNA dependent DNA polymerase such as HIV reverse transcriptase (which, by the way, apparently really doesn't do any proofreading), as compared to a coronavirus RNA dependent RNA polymerase.
Now I'd be curious to see if B.1.1.529 mutations appear preferentially at positions which would have cytidine after reverse transcription. I guess that would be the guanosines in RNA original?
I was under the mistaken belief that SARS-CoV-2 lacked RNA Pol proof-reading, so that is my bad there and responsible for my equivocation between it and HIV.
I completely accept that not only is it likely that there will be the viruses sharing the same cytoplasms on occasion, in large enough numbers, on long enough infections, etc etc - because one thing we know about biology is how slippery and stochastic things become, but the fact they dont generally share the same host does make this more of an interesting edge case I would imagine.
Thanks for your interesting links and thoughtful reply!
I suspected spillback for Alpha because it had a bunch of intermediate mutations that were never seen in other lineages. But no animal reservoir was found and I now think the immunocompromised single patient explanation is more likely. I can see a patient that is known to have spending 6 months in a hospital bed not infecting anyone, because they are isolated and only seen by medical staff with serious protective clothing and masking. Then at some point someone slips up and it escapes.
The article speculates that the animal reservoir could be rodents. If so, it's not sewer rats, at least not in one of the many countries that samples sewage to monitor outbreaks.
https://journals.asm.org/doi/10.1128/mBio.02703-20
By the way the transmissability of delta doesn't pose a hurdle for omicron. They are not competing, except in the sense that the severity of the delta wave makes people isolate and mask up.
Chronic infection produced many mutations, it also did that across many HIV infected individuals in South Africa.
Those infections mutated via natural selection to avoid in-host immune responses and actually transmit poorly in the population.
One of these chronically infected individuals recently came into contact with someone else that was recently infected with circulating virus.
The doubly infected individual allowed Omicron to mutate via recombination and pick up mutations that allow it to spread better and so it took off.
This is also more or less how animal spillback would happen as well. The animal type should be better animal-adapted and not better human-adapted. You probably need a recombination event to spill it back effectively.
You get the idea. If the world stage is relative, even if the net impact is bad...it's still a positive outcome if you fare substantially better than everyone else.
The only people saying China won't get Omicron are the state newspapers in China.. of course they're going to get it. Especially since they are hosting the Olympics in ~2 months and it will certainly be the dominant strain by then.
There are lot of ways we'd be easily able to tell if covid was actually common in China and being hidden. People are still traveling out of China, and they take antibody tests.
Mask adherence was already a thing in China before this pandemic, so I don't find it hard to believe compliance is very high and China doesn't have major problems with the pandemic.
> China is projected to be the single country that doesn't get Omicron
There is also zero chance that, had Omicron been first detected in China, instead of South Africa, that they would have done the responsible thing and disclosed it to the world.
You don’t actually think the Chinese border is 100% closed do you? It is not. That is like saying the border from the US to Mexico is closed no more Mexicans are coming into the US. We know that is also not true.
So far Omicron has been shown to be extremely mild with only some minor symptoms. Isn’t this the ideal situation? Finally a variant that is less lethal and may help provide immunity against more lethal variants.
Just missing the “now is the time to panic” vibe being pushed by many news outlets.
The doctor from South Africa making that claim seems to have been basing it on a couple of dozen very self-selecting patients at her private practice. The reality is that the hospitalizations are increasing rapidly in South Africa.
It might be a bit milder (though we won't know for a while, there's a lot of confounding factors and data lag). It could also be a bit more seriousl. But it seems very unlikely to be an order of magnitude milder.
GP said it hasn't been shown to be extremely mild, not that it has been shown not to be extremely mild. It's too early to tell since the first known cases were skewed towards young people.
I'm cautiously hopeful about this too, it would be ideal for a "high transmission yet benign" variant to take over. Effectively joining the common cold class of viruses.
But like everything else this pandemic, we have to wait and see. Hopefully we get the good news before the end of the year.
The governments who enact the restrictions and the majority who support them are not acting entirely on arguments based on health. For example, origin of COVID is animal reservoir (bats) which makes a bunch of the restrictions illogical (they are predicated on sterilizing immunity / eradicating it entirely - also known as zero covid).
So, it is not cut and dry case that you can present a health policy based on health, like you are making now. You probably need some kind of Girardian scapegoat or a political argument to shock the public out of it. I don't think the latter is coming because majority supports and sees the restrictions as positive.
Animal origin theory is far from settled, and there is mounting evidence that the lab leak theory was squashed early on for political reasons. This book that came out recently and it’s extremely compelling. I was fully in the “lab link is conspiracy theory” camp until I read it.
Issues like this highlight the importance of the emerging One Health (https://www.cdc.gov/onehealth/index.html) approach to tackling human, animal, and environmental health. Transdisciplinary collaboration across multiple health modalities is the only complete way to tackle large-scale health issues.
So we will get multiple competing strains that mutate quicker than we can develop the vaccine, with us trying to predict which strain will be dominant. Flue Vaccine is effectiveness estimated to be around 30% because of this.
Flu is perculiar because it reassorts - it's genome is in 8? pieces, which can interchange with other similar flu viruses within an infected cell. So a coinfection with A and B flu strains may result in C strain mixed and matched from A and B. Very hard to immunize against.
No, different virus structure. I believe there may be some possibility of gene swapping with a coinfected cell, but much less than flu - the Covid RNA genome is one long string, as opposed to 8 bundled together - it's easier to mixup separate pieces. Furthermore, Covid does have an error correction mechanism, though not perfect hence the mutations.
Unrelated question, and not to pick on you if English isn't your first language - I'm always impressed by people who speak any multiple languages with any competency:
I've seen people misspelling flu as "flue" a lot over the course of this pandemic. I thought maybe that it was a British spelling, or that it was the word in German or French or Russian or something and foreign language speakers were mistakenly using the same word in English based on the similarity, but I can't find a language where that's the case. What's up with that?
I’m not the person you’re replying to but I’ve also been wondering the same. The best I can come up with is that “flue” is an actual word (like a chimney flue) and autocorrect doesn’t alert people to the error. Kind of like there, their, and they’re.
In writing this comment though I’ve learned that my iPhone autocorrects flue to glue. Even when following the word chimney. So perhaps my pet theory is totally wrong.
InFLUEnza and the shortened version is pronounced like “blue” in English? Seems reasonable for a non-native speaker to infer it should be spelled with an e at the end.
I'm just a bad speller, and don't check what I type. But English is my second language. Though I'm sure I would be terrible speller in my original language.
Ending a virus that we have no sterilizing vaccines for and which might have an animal reservoir; don't merely need vaccine mandates but VaaS mandates.
To my knowledge no booster is approved for use within 6 months of another shot, and 6 months is overkill unless you're extremely high risk, e.g. in the "still wiping down door dash deliveries with bleach wipes" kind of high risk.
> To my knowledge no booster is approved for use within 6 months of another shot
Government recommends booster after five to six months in my country. To clarify, they do not yet recommend boosters to the end of time, just a booster after the second.
> 6 months is overkill unless you're extremely high risk
They're recommending mRNA boosters 2 months after the J&J or AZ shots, and the CDC recommendation is now 6 months for everyone who got the 2-dose mRNA.
"All adults in the United Kingdom will be able to get their booster Covid-19 vaccine doses three months after their second shot, the government indicated on Monday, in a dramatic acceleration of the country's inoculation drive that comes amid fears over the Omicron variant."
If the current state of Covid is not acceptable and it is determined that the disease needs to be eradicated, these vaccines aren't enough. We will have to start elimination of reservoir animal colonies near human civilization at a global scale. Go into bat habitats with flamethrowers. The vaccines are too leaky and another mutation in a animal population and we are back where we started.
Although, if it was a lab leak and we didn't have a animal population to worry about we could save a lot of animals. We could also accept that it's now endemic.
It's a bit weird to jump to "flamethrowers in the jungle" instead of "second-generation vaccines", isn't it?
It's definitely able to get into animals. That's been known since nearly the beginning; quite a few zoos lost animals to it. Lab leak or not doesn't really change that calculus at all.
I mean, we sorta went right to "lock down the entire economy" so I figure that's the next logical step. I personally feel both measures are a bit of a overeaction. Preparing for a endemic seasonal disease like the flu is more sensible to me, with a focus on early detection and treatment.
has anyone, i wonder, done studies of the covid waves in countries and counties vs animal activity in those areas? doesn't an animal transmission path and wild reserve have severe implications for lots of the studies we've already done on the effectiveness of our countermeasures?
It was known early that other mammals got COVID; the attitude of "there is only the Gospel and all else is Misinformation" has prevented discussion and likely prevented studies on it.
> It was known early that other mammals got COVID; the attitude of "there is only the Gospel and all else is Misinformation" has prevented discussion and likely prevented studies on it.
That is a giant strawman. I'm confused why you think that mainstream virologists are not deeply interested in discussing, researching and tracking animal reservoirs for Covid. One minor example I'm familiar with that got widespread coverage in both the scientific community and the public at large in Pennsylvania: https://www.oleantimesherald.com/news/penn-state-researchers...
One should be able to still look at what South & East Asian states have done, I don't think Vietnam or South Korea have this problem of highly politicized scientific community. Don't know if they have confirmed animal reservoir though.
We don't know, and probably never can know where it came from. If it was a lab leak they have covered their tracks enough that we cannot be sure. If it wasn't - then it is even harder to figure out where it came from.
Be careful, methicillin (and generally speaking, antibiotic) resistance are very different, both mechanistically as well as evolutionarily, from vaccine immunity evasion.
This is just introductory-level microbiology and immunology and I don’t have time to give the subject the treatment it deserves.
First, as a practical matter, small molecules like antibiotics are really difficult to develop, the repertoire is limited, and toxicity is often a big problem. The possible repertoire of antibodies against a given antigen is astronomical.
In the case of antibiotic resistance, you’re dealing with an active colony of bacteria continually reproducing within one host. In vaccine immunity, reproduction is nil or extremely limited within the host (simplifying white lie), and it is mostly at the host-population level that immune evasion evolves over time, so the population dynamics are totally different.
Edit: I recommend Lange’s Medical Microbiology and Janeway’s Immunobiology for those who are interested enough in learning more.
VAED is not specific to SARS-CoV-2 vaccines, and is the exception rather than the norm.
In fact, VAED typically occurs more often in inactivated vaccines, while in comparison, newer mRNA vaccines offer a promising way to reduce the likelihood of VAED.
To the best of my knowledge, though it cannot be ruled out as a possibility, there are no confirmed reports of VAED in humans infected with SARS-CoV-2. You're really splitting hairs and assigning excessive importance on minor details.
VAED has occurred repeatedly in mRNA vaccine trials, as well as attempts to develop a coronavirus vaccine because the vaccines provide incomplete protection, in much the same way the current COVID vaccines. It's a primary factor in why they have not made it to market for so long.
No, lol. I would strongly suggest you stop talking about things you know nothing about.
- The first 3 links have nothing to do with RNA vaccines
- The fourth link says "the ability of SARS-CoV-2 antibodies to mediate infection enhancement in vivo has never been formally demonstrated", and "the results obtained so far have been rather reassuring", which is in agreement with what I said and in direct contradiction with your point.
- The fifth link doesn't suggest in any way that VAED is a concern with mRNA vaccines. In fact it says: "Any vaccine that has been found to cause ADE has stopped being used or, more recently as described below for dengue vaccine, been recommended only for those who will not be affected by ADE. Evidence of ADE has not emerged for COVID-19 vaccines even though concerns have been raised."
Vaccinated individuals have shorter infections and a lower viral load than unvaccinated people, and therefore provide less opportunities to develop new variants. More virus = more chance for new mutations.
The more likely theory is someone immunocompromised who stayed sick for a very long time.
The theory is that it would be someone that is immunocompromised enough to just hang in there for a long time. It's a numbers game. The more people that get infected, the bigger the chance a rare event like this will happen.
This is one reason why vaccine distribution inequity may come back to bite us.
It's pretty simple. You can estimate the genetic mutation rate from the phylogenetic tree since we've been sampling the distribution of Sars-Cov2 genomes since the original Wuhan strain. If that rate is constant and if the variants all mutate at the same speed that gives you a rough timeline. Omicron has 50 mutations that are not related to other known variants. Delta has 13. We've seen delta for about 1 year right? So it's not a big leap to roughly double that estimate for Omicron.
Immunocompromised subpopulation is so small (at least in my country), especially compared to unvaccinated (abt. 30%), that it should be fairly trivial to quarantine them, don't really see an issue here if we are restricting unvaccinated life based on argument about public health.
It makes zero sense for an immunocomprised person to apply selective pressure to the virus that results in several mutations that perfectly evade the vaccines mechanism of action.
The experts interviewed in the article the OP posted all agree that a persistent infection in an imunocompromised individual is one of the leading theories. Maybe even more plausible than a reverse zoonotic event.
People with a compromised immune system are a good setting for evolving new variante of coronavirus. They stay sick for a long time (meaning more viral replication and more opportunities for mutation) and they apply a weak immune response which while not sufficient to wipe out the disease, provides selective pressure that rewards immune evasion.
There's a common antivaxxer myth that vaccines promote the creation of new variants and that we would be better off without vaccination. I think it's very important to emphasize that is not the case.
> a persistent infection in an imunocompromised individual is one of the most plausible theories
> People with a compromised immune system are a good setting for evolving new variante of coronavirus
If it turns out to be the case, should we have HIV / Cancer Patient Passports? After all, these people can be a general danger to public health as they can demonstrably incubate new dangerous strains of diseases, like Omicron.
Of course not! Please don't suggest that I would say such a heartless thing! We're talking about someone who had to be sick for months, probably inside a hospital already.
The important thing to do is get everyone vaccinated, including in Africa where there is a tremendous shortage of vaccines. The more the virus spreads, the more chances it has to mutate into new variants. Also, when everyone is vaccinated, the elderly and immunocompromised are less likely to be exposed to the disease; vaccination should be seen first as a public-health policy, not as a means for individual protection. Not to mention that, even though the vaccination is less effective individually for the immunocompromised, they are one of the groups that are at most risk from covid and therefore most benefit from being vaccinated.
> vaccination is less effective individually for the immunocompromised
> People with a compromised immune system are a good setting for evolving new variants of coronavirus
> They stay sick for a long time (meaning more viral replication and more opportunities for mutation) and they apply a weak immune response which while not sufficient to wipe out the disease, provides selective pressure that rewards immune evasion.
If what you say is true about immunocompromised people I fail to see a public health argument against their quarantine and certification via passports. We already restrict a much larger and healthier subpopulation (the unvaccinated) so restricting this smaller and disproportionately more dangerous one does seem quite obvious to me, based on public health. And as you say, these people are most likely already hospitalized so quarantine procedures should be fairly easy to implement and follow.
https://nextstrain.org/ncov/gisaid/global
with Delta being the large green and blue parts at the top, and Omicron being a few red dots a little up from the bottom. If you trace back, you'll see that its nearest relative is wildtype from the spring of 2020. That's pretty weird, and there are really only three ways I can think of that it could happen:
1. human manipulation in a lab using early wildtype samples. This seems unlikely, because what would be the point and how did they let it escape?
2. chronic infection in a single immunosuppressed patient. We've seen this before (see, for example, this: https://www.nejm.org/doi/full/10.1056/NEJMc2031364 ) and southern africa has a lot of immunosuppressed people thanks to HIV. Additionally, there are some genetic markers that suggest evolution in a human.
3. spillover of wildtype in spring 2020 to some animal, evolution in that population for about 17 months, then spillback last month into humans.
I'm with the article, in that I favor 3 even though there's some evidence for 2 just because i can't quite understand how the omicron patient might have gone all that time without infecting anybody else with a proto-omicron version of the virus (which would then spread and be picked up on that chart). It's possible, I guess, that omicron got increased transmissability in a mutation in the recent past, and it could have lived in the patient with bad transmissability for a long time previous. And since delta is so amazingly transmissable, any proto-omicron could have infected a couple of people and then died out undetected. But still.