23 ms·

Evidence for a mouse origin of the SARS-CoV-2 Omicron variant

230 points by mynameismon 5y ago

vlovich123 5y ago
I guess it’s not unreasonable for it to jump to mice if it started in bats, right? Still, the jumping back and forth seems weird, no? Is this a previously observed and well understood behavior or something new we’re hypothesizing from a sample size of one utilizing new techniques?
- colechristensen 5y ago
  Plenty of diseases, coronaviruses included infect several species. Sometimes one variant freely infects many species, sometimes a novel mutation enables a jump from one to the other, often somewhere in the middle where something will spread easily in one and not so much in the other until it evolves to change. This is pretty basic infectious disease stuff.
- lifeplusplus 5y ago
  - abacadaba 5y ago
    ya but those here humanized gmo mice
    - lifeplusplus 5y ago
      yummy
  - gsk22 5y ago
    Did you read the article? The link to mice was for the Omicron variant, not the original strain that emerged in Wuhan. Stop spreading FUD.
    - kafkaIncarnate 5y ago
      He didn't even really need to read the article, it's in the title!
- avl999 5y ago
  Many viruses with animal reservoirs jump between animals and humans all the time. The Flu virus does that all the time.
  - AstralStorm 5y ago
    Not that often and as influenza is a relatively simple virus in comparison with coronaviruses, predicting the cross-reacting variant is reasonably easy. Apparently not so much with this one.
- kafkaIncarnate 5y ago
- jtdev 5y ago
- rossdavidh 5y ago
  I don't think we know how often it happens naturally, since there's no particular funding source for monitoring it (up until recently, anyway, hopefully more now).
- defaultprimate 5y ago
  No evidence has been found in bats, just speculation
temporalparts 5y ago
Exciting! Now only if they can find the origins of the original virus.
- jessaustin 5y ago
  It's possible that several scientists in the relevant fields already have well-founded suspicions regarding this. As soon as political developments allow them to share their knowledge without endangering their funding, we might hear about it.
  - wesleywt 5y ago
    Comments like these are frustrating. This pandemic was predicted for many years by scientist. I don't understand why the public wants to believe in the fantasy that this was deliberate action. No, this pandemic was caused by deliberate inaction.
    - todd3834 5y ago
      If it came from a lab then it was caused by overaction. If it came from the wild then you are right. That’s the reason people want to know
      - petre 5y ago
        It could have come from guano miners just as easily, but bringing it to a 50M population center was a recipe for disaster. Ebola and AIDS did not come from a lab but from tampering with wild animals.
    - halpert 5y ago
      How can you be so sure. The first outbreak was literally a few feet from a lab studying this exact virus. Biden called for U.S. intelligence to figure out if the original virus came from a lab: https://www.nytimes.com/2021/05/27/briefing/lab-leak-theory-covid-origins.html https://www.nytimes.com/2021/05/27/briefing/lab-leak-theory-... What do you know that the U.S. president and U.S. intelligence doesn't?
deleted 5y ago
[deleted]
baskethead 5y ago
criticaltinker 5y ago
> Intermediate versions have gone largely undetected, thus resulting in an exceptionally long branch leading to the most recent common ancestor (MRCA) of Omicron in the phylogenetic tree. We hereafter refer to this long branch as Branch O. > We found that mutations accumulated in ORF S at a rate of ∼0.45 mutations per month on average. In sharp contrast, 27 mutations accumulated in ORF S in Branch O during the 18 months spanning May 2020–November 2021, equivalent to ∼1.5 mutations per month, or ∼3.3 times faster than the average rate of other variants > We found that the Omicron spike protein sequence was subjected to stronger positive selection than that of any reported SARS-CoV-2 variants known to evolve persistently in human hosts, suggesting a possibility of host-jumping Although host jumping is undoubtedly occurring (eg infection has been serologically observed in white-tailed deer and other animals), I’m skeptical that it is the primary factor as this paper suggests. Another possibility is that viral mutation rates are underestimated, and/or infections are systematically underestimated. There is evidence of both in the literature. Combined with enhanced selective pressure on the spike protein RBD due to mass vaccination campaigns, these are scientifically supported alternative explanations for the observations in OP.
- Scoundreller 5y ago
  > Combined with enhanced selective pressure on the spike protein RBD due to mass vaccination campaigns Depends on the campaign. The major Chinese vaccines are “inactivated” and might pressure things differently than our spike-protein focussed viruses in the west. https://covid19.trackvaccines.org/country/china/ https://covid19.trackvaccines.org/country/china/
- bunnie 5y ago
  The science in the paper is fairly interesting. It observes that: 1) Certain types of mutations are favored by different host biologies. In other words, in humans, you would tend to see one type of coding substitution, in mice, pigs, bats, etc. you'd see another type of coding substitution. The paper gives specific mechanisms that underly this biases; I'm not an expert in these, so I can't say for sure if they are correct, but it the mechanisms as proposed make sense on a first read-through. 2) The early omicron variants have a set of mutations that would be consistent with evolution in a non-human host, overlapping most strongly with mice biology. 3) Perhaps even more significantly, _later_ omicron variants that have spread through human populations have picked up mutations that are once again more consistent with human biology. So the paper manages to show both positive and negative data toward their hypothesis, which makes it stronger. For the TL;DR crowd, figure 3 summarizes this pretty well. To analogize this in computer terms, it's as if someone was tracing the evolution of memes by observing the types of compression artifacts introduced in various re-compressions of the meme. For example, JPEG might introduce artifacts related to DCT math, whereas JPEG-2000 would introduce artifacts related to wavelet math. The analysis shows that the artifacts of this new Omicron meme has compression artifacts consistent with, say, Wavelet compression up until it jumped to being shared by JPEG-users, at which point newer modifications to the Omicron 'meme' show JPEG-consistent artifacts. That's basically the scientific core of the paper. So, to contest the validity of the paper, I think it would be helpful to find citations that dispute the observation that mutations accumulate with a certain bias based on the host biology, rather than whattaboutism pointing to other hypotheses and leaving it at "there are other alternative explanations" therefore this paper is not interesting. So, while I don't dispute your statement that there are other alternative explanations, what I would really like to see are comments addressing the core scientific thesis of the paper, which is that certain mutations appear more frequently in other host biologies; and that the first omicron cases showed a preponderance of these differently-biased mutations; and that since it has been circulating in humans, the later mutations are once again consistent with a human host. At the very least, I thought it was a very interesting analysis, as I had never seen the molecular bias of mutations used as a proxy for host biology before. If this is true, then viruses that can spread through alternate host biologies would gain a diversity of mutations that would be less available co-evolving with a single host, which could lead to evolutionary advantages over viruses that are unable to hop between hosts.
todd3834 5y ago
I’ve never seen such a large ratio of downvoted comments on a thread. I guess I’m not surprised by how polarizing the subject is. I guess I just thought this was a safe place to be contrarian and not just downvote ideas that are not on your team.
- jpgvm 5y ago
  It's all a bit ironic. Something that should be purely a matter of science and health got morphed into this crazy political beast upon hitting Western shores. COVID-19 isn't that drastically different from SARS, MERS, etc. The main difference is transmissibility of asymptomatic carriers that allowed it to leave Asia undetected. So while the rest of these viruses had been handled in a mature and efficient fashion by the countries affected the very idea of a modern viral pandemic was new to the Western world and it showed, boy did it show. Instead of just focussing on the issue at hand it was immediately the "Chinese virus" and the American political machine was in full swing to capitalise on the situation. Most of the Western world followed suit with political lines being drawn around responses (or lack there of) and assignment of "blame". In the UK and USA this resulted in probably hundreds of thousands of needless deaths off the back of delayed and then ham-fisted action by Boris Johnson and Donald Trump's administrations. Meanwhile in Asia it remained apolitical for the most part (I say most part because aspects of pandemic control did become quite political of late). I was in Thailand for the entire duration of the pandemic and despite having access to less resources, late access to the vaccine and being one of the first nations to be exposed outside of China Thailand actually performed very well. Lots of insinuations were made this was due to climate and other factors, anything that shifted the blame away from politicisation of the pandemic as the root cause of performance differences. However as time has wore on and countries with more facts based approaches have continued to out-perform it's obvious - politics is the only real difference among the developed nations, hell it's so strong that it overcomes better access to vaccines and higher ICU bed/capita which should both dominate.
  - crate_barre 5y ago
    This all happened because Trump dubbed it the China virus at the beginning and brought up specific treatments like Hydroxychloroquine. The political climate in America was such that just those two stances coming from Trump established the dividing line. We had no chance from the beginning to discuss this without the political shadow. The accessory to all of this was the vaccine/lab origin censorship by big tech, who are kind of seen as over-woke liberal bastions. To lockdown or not lockdown, to mask or not mask, to vaxx or not vaxx, to Ivermectin or not Ivermectin, lab leak or no lab leak … why so binary? Ah, because we went political with this a long time ago. If there was one person we needed to literally not say anything about this, it was Trump. But alas, he was the fucking president and we also needed him to say something. The Pandemic histrionics are an age old Shakespearean play. A tragedy. History is something else when you have the primary sources right before you. I would never need to read a book on all the nuances of everything that happened. Makes you wonder how easily historians can spin history in all those books, when in reality those events could have been as simple and silly as this one.
indigodaddy 5y ago
- jpgvm 5y ago
  A group of intelligent people downvoting a set of arguments that rely mostly on logical fallacy isn't bias, it's self-moderation. If lab-leak arguments had literature to stand on and didn't instead just invoke false-dichotomy to justify their existence I am sure they would find more fertile ground here.
  - indigodaddy 5y ago
    There is no actual evidence for either, so both should be vigorously explored.
    - jpgvm 5y ago
      Sure. My problem isn't with the direction of the arguments but their lack of substance.
    - convolvatron 5y ago
      is there a point in 'exploring' these ideas on HN where its very unlikely someone is going to show up with any actual evidence? what is the value in repetitive circular uninformed speculation?
    - evv555 5y ago
      There's evidence that the lab was doing gain of function research on coronaviruses. That's not exactly a smoking gun but it's extremely compelling evidence. NIH admits that Fauci lied about funding gain of function research in Wuhan.[1] 1. https://youtu.be/lRCowOPL5Vc?t=229 https://youtu.be/lRCowOPL5Vc?t=229 2. https://www.youtube.com/watch?v=pAIsK9tosck https://www.youtube.com/watch?v=pAIsK9tosck
- civilized 5y ago
  Meanwhile, I've noticed there are plenty of people who will downvote my comments if they are even mildly, vaguely skeptical of "lab leak", "vaccines/lockdowns cause more deaths than they prevent", or the other anti-establishment narratives that have become culture war memes. These meme narratives seem to be cherished as sacred by a significant percentage of HN. Sorry guys, but I call 'em like I see 'em, and sometimes -- definitely not all the time, but sometimes -- I think the establishment happens to be right. And HN is supposed to be a place for that kind of genuinely independent thinking. If you want to fight the culture war, you can do that on the other 99.99999% of the internet where it's everybody's favorite thing to do.
gorgoiler 5y ago
Before anyone gets too excited, this is a paper from a third party (six authors from various state funded science and technology institutes in Beijing.) It is being hosted on the NIH’s mirror of an Elsevier journal. Specifically, the URL decodes as: * PMC: PubMed Central, an information portal hosted by * NCBI: The National Centre for Biotechnology Information, part of * NLM: The National Library of Medicine, brought to you by the letters * NIH: The United States National Institutes (more than 1!) for or-is-it-of Health. (The hyphenated part is silent.) As for the paper itself, it’s just too bad that their Data Availability Statement is basically “yes” without linking to it. Googling the file names in their R scripts found them easily enough.
- bawolff 5y ago
  Why would that alter my level of excitement? I know different journals are of differing levels of quality, and im not in the know enough to assess which is which, but i would never assume that the NIH is the only group that knows how to do science.
  - gorgoiler 5y ago
    For me, HN putting the paper’s title next to “TLA.gov” gave the former the weight of the latter, suggesting this was a US government finding. But, with respect to the original authors, it’s more like “Mice did this!” alongside “www3.docs.nih.gov/~jeff45/theories/drafts/mice.htm?”
- ImaCake 5y ago
  It is routine for basically all papers in medicine research to be hosted on PMC. Often they host the entire article, not just the index and abstract. The reasons for this open access are complicated but boil down to certain rules from funding bodies. I have no idea if the particular Elsevier journal (in the banner at top of the page) is reputable, but the science here seems at least robust. If I wanted to discredit this paper, I would point out the authors developed an analysis technique they want to apply to other diseases/models. COVID is a nail and they have a specific hammer, no matter if it’s the right kind of hammer.
ta8645 5y ago
Is there any chance we could vaccinate mice? Perhaps developing an edible version that we could use to help stop them from generating future variants? I can just see anti-vaxxers using this development as proof that 100% vaccination isn't a useful goal.
- nzmsv 5y ago
  Not an anti-vaxxer, but comments like this are even better antivaxx fodder :) I understand where you are coming from, but the ultimate goal is to stop COVID, not get everyone a jab in the arm. If the jabs (legitimately) stop working we should stop the jabs. Compliance with COVID rules isn't a goal unto itself. Vacccinating mice is a fun idea to think about, but you'd have to develop vaccines for squirrels, raccoons, and pigeons shortly after the mouse one. Also think about all the unintended consequences (your food vaccine getting into waterways, for example). So yeah, this is the kind of idea that makes antivaxxers look sane.
  - inter_netuser 5y ago
    Please, let's not try doing Marek's disease in humans. https://en.wikipedia.org/wiki/Marek%27s_disease https://en.wikipedia.org/wiki/Marek%27s_disease "The evolution of Marek's disease due to vaccination has had a profound effect on the poultry industry. All chickens across the globe are now vaccinated against Marek's disease (birds hatched in private flocks for laying or exhibition are rarely vaccinated). Highly virulent strains have been selected to the point that any chicken that is unvaccinated will die if infected.[14] Other leaky vaccines are commonly used in agriculture. One vaccine in particular is the vaccine for avian influenza. Leaky vaccine use for avian influenza can select for virulent strains.[15]"
    - nzmsv 5y ago
      OK, I'm probably going to burn a bunch of karma on this comment, but this is very interesting. For example, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4516275/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4516275/ looks like a legitimate piece of research. Isn't this exactly what we are doing with the current COVID vaccines? How does one explore this question without being labeled a crazy antivaxxer?
underdeserver 5y ago
doingtheiroming 5y ago
The odd thing about opposition to lab-leak hypotheses is precisely that it defines itself by that opposition. If the wet markets were the source surely vigorous campaigning against wet markets would be of more utility that vigorously scouring the internet for alternative ideas to downvote. Given we know that lab leaks happen continually we should all perhaps be campaigning vigorously for an end to wet markets, protection for cave habitats, better controls in labs in general and a complete moratorium with gain of function research. We don’t know where this pandemic came from but we know enough to say that it’s likely all those things could be sources in the future. So perhaps leave the debate alone and focus on stopping the next pandemic.
- forgotmyoldacc 5y ago
  The term "wet market" just means a market that sells non-dry goods, like meat or vegetables. Most farmers markets are wet markets. See https://www.youtube.com/watch?v=whbyuy2nHBg https://www.youtube.com/watch?v=whbyuy2nHBg for an example. Perhaps you mean campaigning against eating exotic animals?
  - XorNot 5y ago
    Live animal markets have been a historically common origin for new diseases - cities were an absolute disaster disease-mortality wise until the hygiene initiatives started cleaning them up. Extended, concentrated exposure to animals has always been a breeding ground for new plagues.
    - q1w2 5y ago
      I think you are unnecessarily conflating hygiene with wild animal contact. Even a perfectly hygienic butcher shop and wet market can transmit a new disease. Keeping it clean is good to reduce the transmission of common illnesses - but the genesis of a new disease can easily be passed in a clean market.
  - josefx 5y ago
    I think the issue would be less the "exotic" and more the wild animals sold in unhygienic conditions, which at least was the picture some media painted when describing Chinese wet markets.
fredestine 5y ago
Could it be that some researcher gave this variant to mice so that it will be easy to test and spread it later to human to counter more agressive variant and help that way bring up natural immunity?
- kennywinker 5y ago
  > Could it be that some researcher gave this variant to mice so that it will be easy to test Yes, that is technically possible. Mice and humans also come into contact fairly often, so natural transmission from humans to mice (and back) wouldn't be that rare an event. > and spread it later to human to counter more agressive variant I think you might be giving too much credit to virologists - I don't think anybody could know from observing a virus in mice if it was going to be more or less aggressive in humans. > and help that way bring up natural immunity? Natural immunity doesn't seem to be very useful against covid. Or, at least, not more useful than the vaccines we already have. Stories of people getting covid twice, even three times, are getting more and more common. This doesn't seem to be a "get it once and you're set for life" virus.
  - ppod 5y ago
    >Natural immunity doesn't seem to be very useful against covid. Or, at least, not more useful than the vaccines we already have Do you have any evidence for that? The question has obviously become politicised. Experts figure out what information they think might make people more relaxed or careless about covid, and heavily push the reverse line. It's no wonder people's trust in experts is failing. https://www.theguardian.com/commentisfree/2021/oct/24/which-protects-you-more-vaccination-or-prior-infection https://www.theguardian.com/commentisfree/2021/oct/24/which-... https://www.medrxiv.org/content/10.1101/2021.08.24.21262415v1 https://www.medrxiv.org/content/10.1101/2021.08.24.21262415v...
    - rsfern 5y ago
      The recent flurry of papers on omicron trying to decouple the effect of its intrinsic virulence from prior immunity have been finding that prior infection (with delta) and unboosted vaccination have comparable risk reduction file hospitalization from Covid It’s been a couple weeks so maybe there is better, less preliminary analysis available now On hospitalization risk in the UK: https://www.imperial.ac.uk/mrc-global-infectious-disease-analysis/covid-19/report-49-Omicron/ https://www.imperial.ac.uk/mrc-global-infectious-disease-ana... On reinfection/breakthrough risk: https://www.medrxiv.org/content/10.1101/2021.12.27.21268278v1 https://www.medrxiv.org/content/10.1101/2021.12.27.21268278v...
londons_explore 5y ago
To summarize this paper in a less technical way than the abstract does: This paper finds very strong evidence that omicron jumped to infecting mice in May 2020, then jumped back to humans again in Nov 2021. * Mutations in the spike protein, which are likely to depend on which animal is best infected, were a far closer match in mice than any of 20 other species tested (P<1.6x10^-11 ) * The types of genetic changes (ie. transitions from one base to another) were not those expected to be found in human cells, but were those expected to be found in mouse cells (P<0.008) * Omicron binds far better to mouse cells receptors than any other animal or human tested (P<1x10^-5 ) * The genetic changes seen happened at a rate far 3.3x faster than expected in humans. (my summarization here has traded scientific accuracy for simplicity) Any of those fist 3 bullet points I would consider pretty decisive evidence. To have found all three is amazing.
- jonathanstrange 5y ago
  Wow, those P values are very low. Is this normal in this type of research? Are they calculated directly based on combinatorial arguments?
  - londons_explore 5y ago
    No. P values this low are very rare. I haven't checked any of the analysis with my own data, but the approach seems pretty legitimate. Each is calculated in a different way, using mostly-non-overlapping evidence, so it's almost legitimate to multiply them together to get P<1.3x10^-18... Not that there's any need - each alone is very convincing. The whole lot really should have been written as three separate papers, with better written abstracts, and a metapaper, written by different authors, combining the evidence and comparing to the evidence for other hypothesis.
  - deleted 5y ago
    [deleted]
  - MontyCarloHall 5y ago
    > Are they calculated directly based on combinatorial arguments? Yes. Most of the extremely low p-values come from binomial tests with a very low binomial probability p_bin relative to the fraction of positive outcomes. For example, > We identified 45 point mutations that were introduced in Branch O (hereafter referred to as “pre-outbreak mutations.”) We observed that the pre-outbreak mutations were over-represented in ORF S (P = 1.2 × 10−13, binomial test with the expected probability equal to the length of ORF S relative to the SARS-CoV-2 genome). So p_bin = len(ORF S)/len(genome). The spike protein sequence (ORF S) is roughly 1300 bases and the entire SARS-CoV-2 genome is roughly 30 kilobases long, yielding p_bin ≈ 0.04. If there are 45 total pre-outbreak mutations, and assuming they ought to be uniformly distributed across the genome (big assumption, BTW!), then seeing 17 of them occur in the spike protein sequence would yield a binomial p-value (one-sided test) on the order of 1e-13. The other low p-values either also come from binomial tests with similarly low binomial probabilities relative to positive outcomes, or from Fisher exact tests with gross imbalances between categories (and high counts to back those up).
eraad 5y ago
Mouse as in lab mouse?
- tim333 5y ago
  Who knows.
NicoJuicy 5y ago
I'm not sure, but instead of vaccines. Would it be possible to increase mutations that benefit us by using a large population of mice untill a variant pops it that is more beneficial than the one in a pandemic? Eg. - severely reduce severity - replace previous variant - more transmittable I'm just wondering. Since even Lions in the zoo in Belgium had COVID.
- p_l 5y ago
  Those result in more deaths, thanks to higher rate of infection, and ultimately you don't know what way it will mutate again.
- yosito 5y ago
  Seems possible, but risky. You could end up with mutations that go the other way too. Imagine something super contagious and virulent escaping the lab by accident and killing millions of people.
dr_dshiv 5y ago
If one thought that a more infectious but less severe coronavirus was economically advantageous, how long would it take to breed in laboratory mice? Obvious you couldn't announce making it, but if it happened to spread, that's good for the world, right?
- p_l 5y ago
  No, because more infectious but less severe virus is actually going to kill more people and cause more disruption economically even without deaths. For the former, essentially you're dealing with multiplying lower chance of death with much higher infection rate, resulting in bigger count of deaths (and other events like hospitalisations, isolation, etc., which increase economic disruption).
  - trenchgun 5y ago
    But if it's really mild though, then it can be a Christmas gift.
  - saalweachter 5y ago
    Also you could really only develop a strain that was more infectious/less deadly in mice, using mice. Once you jump it back to humans it's a new roll of the dice on whether it's more or less deadly and infectious.
    - dr_dshiv 5y ago
      I generally agree. But it seems possible to know a priori that it wouldn't adversely affect the lungs, which is the primary cause of death/damage.
      - p_l 5y ago
        Except lungs are, arguably, a minor (just most visible) issue with COVID. We're going to deal with long history of disablement caused by how COVID attacks neural tissue, for example, something I think might be more disastrous long term (1918 flu was similar, with some historic effects like Aktion T-4)
hoseja 5y ago
bikamonki 5y ago
Reading this thread I can see that finally HN has turn into another Twitter. That is sad. I thought we were a different crowd: objective, respectful, inquisitive, non-political. Is this the endgame for all social nets?
lngnmn2 5y ago
There is nothing with amounts to an evidence, only speculations. Evidences require at least an reproducible experiment. Nothing based on estimated probabilities and correlations is an evidence by definition. Again, this is nothing but hypothetical speculations with too many assumptions.
- thehappypm 5y ago
  So, is researching the Big Bang futile since we’ll never be able to reproduce it?
orbifold 5y ago
Wild conspiracy: What if the omicron variant was created by the same process as is used in GoF research more generally. Use humanised mice with human ACE2 receptors and pass it through them over many generations selecting for infectiousness / immune escape wrt the existing vaccines. Maybe they even observed anti-body dependent enhancement (ADE) in mice. I don't think this is entirely implausible because current research is doing things along those lines: There is an established "mouse" model now and people are actively working on chimeric vaccines, engineering virus variants with different spike proteins (for chimeric vaccines see e.g. https://www.science.org/doi/10.1126/science.abi4506 https://www.science.org/doi/10.1126/science.abi4506). They engineered several COVID variants in that paper, some which antagonise the innate immune response. > To confirm that scrambled coronavirus spikes are biologically functional, we also designed and recovered several high-titer recombinant live viruses of RsSHC014/SARS-CoV-2 NTD, RBD, and S2 domain chimeras that included deletions in nonessential, accessory open reading frame 7 (ORF7) and ORF8 that encoded nanoluciferase (fig. S1C). SARS-CoV-2 ORF7 and -8 antagonize innate immune signaling pathways (25, 26), and deletions in these ORFs are associated with attenuated disease in humans (27, 28). and made sure that the "single" spike vaccine was ineffective vs. the chimeric vaccines, which gave broad protection.
Projectiboga 5y ago
We all saw South Park: Pandemic Special, the whole thing can be blamed on Mickey Mouse and his whoring around and luring Randy into debauchery.
- tim333 5y ago
  I hadn't so I had to find the clip https://www.youtube.com/watch?v=KNMRD9nCASw https://www.youtube.com/watch?v=KNMRD9nCASw

230 points by mynameismon 5y ago

I guess it’s not unreasonable for it to jump to mice if it started in bats, right? Still, the jumping back and forth seems weird, no? Is this a previously observed and well understood behavior or something new we’re hypothesizing from a sample size of one utilizing new techniques?

colechristensen 5y ago
Plenty of diseases, coronaviruses included infect several species. Sometimes one variant freely infects many species, sometimes a novel mutation enables a jump from one to the other, often somewhere in the middle where something will spread easily in one and not so much in the other until it evolves to change. This is pretty basic infectious disease stuff.
lifeplusplus 5y ago
- abacadaba 5y ago
  ya but those here humanized gmo mice
  - lifeplusplus 5y ago
    yummy
- gsk22 5y ago
  Did you read the article? The link to mice was for the Omicron variant, not the original strain that emerged in Wuhan. Stop spreading FUD.
  - kafkaIncarnate 5y ago
    He didn't even really need to read the article, it's in the title!
avl999 5y ago
Many viruses with animal reservoirs jump between animals and humans all the time. The Flu virus does that all the time.
- AstralStorm 5y ago
  Not that often and as influenza is a relatively simple virus in comparison with coronaviruses, predicting the cross-reacting variant is reasonably easy. Apparently not so much with this one.
kafkaIncarnate 5y ago
jtdev 5y ago
rossdavidh 5y ago
I don't think we know how often it happens naturally, since there's no particular funding source for monitoring it (up until recently, anyway, hopefully more now).
defaultprimate 5y ago
No evidence has been found in bats, just speculation

temporalparts 5y ago

Exciting! Now only if they can find the origins of the original virus.

jessaustin 5y ago
It's possible that several scientists in the relevant fields already have well-founded suspicions regarding this. As soon as political developments allow them to share their knowledge without endangering their funding, we might hear about it.
- wesleywt 5y ago
  Comments like these are frustrating. This pandemic was predicted for many years by scientist. I don't understand why the public wants to believe in the fantasy that this was deliberate action. No, this pandemic was caused by deliberate inaction.
  - todd3834 5y ago
    If it came from a lab then it was caused by overaction. If it came from the wild then you are right. That’s the reason people want to know
    - petre 5y ago
      It could have come from guano miners just as easily, but bringing it to a 50M population center was a recipe for disaster. Ebola and AIDS did not come from a lab but from tampering with wild animals.
  - halpert 5y ago
    How can you be so sure. The first outbreak was literally a few feet from a lab studying this exact virus. Biden called for U.S. intelligence to figure out if the original virus came from a lab: https://www.nytimes.com/2021/05/27/briefing/lab-leak-theory-covid-origins.html https://www.nytimes.com/2021/05/27/briefing/lab-leak-theory-... What do you know that the U.S. president and U.S. intelligence doesn't?

deleted 5y ago

[deleted]

baskethead 5y ago

criticaltinker 5y ago

> Intermediate versions have gone largely undetected, thus resulting in an exceptionally long branch leading to the most recent common ancestor (MRCA) of Omicron in the phylogenetic tree. We hereafter refer to this long branch as Branch O. > We found that mutations accumulated in ORF S at a rate of ∼0.45 mutations per month on average. In sharp contrast, 27 mutations accumulated in ORF S in Branch O during the 18 months spanning May 2020–November 2021, equivalent to ∼1.5 mutations per month, or ∼3.3 times faster than the average rate of other variants > We found that the Omicron spike protein sequence was subjected to stronger positive selection than that of any reported SARS-CoV-2 variants known to evolve persistently in human hosts, suggesting a possibility of host-jumping Although host jumping is undoubtedly occurring (eg infection has been serologically observed in white-tailed deer and other animals), I’m skeptical that it is the primary factor as this paper suggests. Another possibility is that viral mutation rates are underestimated, and/or infections are systematically underestimated. There is evidence of both in the literature. Combined with enhanced selective pressure on the spike protein RBD due to mass vaccination campaigns, these are scientifically supported alternative explanations for the observations in OP.

Scoundreller 5y ago
> Combined with enhanced selective pressure on the spike protein RBD due to mass vaccination campaigns Depends on the campaign. The major Chinese vaccines are “inactivated” and might pressure things differently than our spike-protein focussed viruses in the west. https://covid19.trackvaccines.org/country/china/ https://covid19.trackvaccines.org/country/china/
bunnie 5y ago
The science in the paper is fairly interesting. It observes that: 1) Certain types of mutations are favored by different host biologies. In other words, in humans, you would tend to see one type of coding substitution, in mice, pigs, bats, etc. you'd see another type of coding substitution. The paper gives specific mechanisms that underly this biases; I'm not an expert in these, so I can't say for sure if they are correct, but it the mechanisms as proposed make sense on a first read-through. 2) The early omicron variants have a set of mutations that would be consistent with evolution in a non-human host, overlapping most strongly with mice biology. 3) Perhaps even more significantly, _later_ omicron variants that have spread through human populations have picked up mutations that are once again more consistent with human biology. So the paper manages to show both positive and negative data toward their hypothesis, which makes it stronger. For the TL;DR crowd, figure 3 summarizes this pretty well. To analogize this in computer terms, it's as if someone was tracing the evolution of memes by observing the types of compression artifacts introduced in various re-compressions of the meme. For example, JPEG might introduce artifacts related to DCT math, whereas JPEG-2000 would introduce artifacts related to wavelet math. The analysis shows that the artifacts of this new Omicron meme has compression artifacts consistent with, say, Wavelet compression up until it jumped to being shared by JPEG-users, at which point newer modifications to the Omicron 'meme' show JPEG-consistent artifacts. That's basically the scientific core of the paper. So, to contest the validity of the paper, I think it would be helpful to find citations that dispute the observation that mutations accumulate with a certain bias based on the host biology, rather than whattaboutism pointing to other hypotheses and leaving it at "there are other alternative explanations" therefore this paper is not interesting. So, while I don't dispute your statement that there are other alternative explanations, what I would really like to see are comments addressing the core scientific thesis of the paper, which is that certain mutations appear more frequently in other host biologies; and that the first omicron cases showed a preponderance of these differently-biased mutations; and that since it has been circulating in humans, the later mutations are once again consistent with a human host. At the very least, I thought it was a very interesting analysis, as I had never seen the molecular bias of mutations used as a proxy for host biology before. If this is true, then viruses that can spread through alternate host biologies would gain a diversity of mutations that would be less available co-evolving with a single host, which could lead to evolutionary advantages over viruses that are unable to hop between hosts.

todd3834 5y ago

I’ve never seen such a large ratio of downvoted comments on a thread. I guess I’m not surprised by how polarizing the subject is. I guess I just thought this was a safe place to be contrarian and not just downvote ideas that are not on your team.

jpgvm 5y ago
It's all a bit ironic. Something that should be purely a matter of science and health got morphed into this crazy political beast upon hitting Western shores. COVID-19 isn't that drastically different from SARS, MERS, etc. The main difference is transmissibility of asymptomatic carriers that allowed it to leave Asia undetected. So while the rest of these viruses had been handled in a mature and efficient fashion by the countries affected the very idea of a modern viral pandemic was new to the Western world and it showed, boy did it show. Instead of just focussing on the issue at hand it was immediately the "Chinese virus" and the American political machine was in full swing to capitalise on the situation. Most of the Western world followed suit with political lines being drawn around responses (or lack there of) and assignment of "blame". In the UK and USA this resulted in probably hundreds of thousands of needless deaths off the back of delayed and then ham-fisted action by Boris Johnson and Donald Trump's administrations. Meanwhile in Asia it remained apolitical for the most part (I say most part because aspects of pandemic control did become quite political of late). I was in Thailand for the entire duration of the pandemic and despite having access to less resources, late access to the vaccine and being one of the first nations to be exposed outside of China Thailand actually performed very well. Lots of insinuations were made this was due to climate and other factors, anything that shifted the blame away from politicisation of the pandemic as the root cause of performance differences. However as time has wore on and countries with more facts based approaches have continued to out-perform it's obvious - politics is the only real difference among the developed nations, hell it's so strong that it overcomes better access to vaccines and higher ICU bed/capita which should both dominate.
- crate_barre 5y ago
  This all happened because Trump dubbed it the China virus at the beginning and brought up specific treatments like Hydroxychloroquine. The political climate in America was such that just those two stances coming from Trump established the dividing line. We had no chance from the beginning to discuss this without the political shadow. The accessory to all of this was the vaccine/lab origin censorship by big tech, who are kind of seen as over-woke liberal bastions. To lockdown or not lockdown, to mask or not mask, to vaxx or not vaxx, to Ivermectin or not Ivermectin, lab leak or no lab leak … why so binary? Ah, because we went political with this a long time ago. If there was one person we needed to literally not say anything about this, it was Trump. But alas, he was the fucking president and we also needed him to say something. The Pandemic histrionics are an age old Shakespearean play. A tragedy. History is something else when you have the primary sources right before you. I would never need to read a book on all the nuances of everything that happened. Makes you wonder how easily historians can spin history in all those books, when in reality those events could have been as simple and silly as this one.

indigodaddy 5y ago

jpgvm 5y ago
A group of intelligent people downvoting a set of arguments that rely mostly on logical fallacy isn't bias, it's self-moderation. If lab-leak arguments had literature to stand on and didn't instead just invoke false-dichotomy to justify their existence I am sure they would find more fertile ground here.
- indigodaddy 5y ago
  There is no actual evidence for either, so both should be vigorously explored.
  - jpgvm 5y ago
    Sure. My problem isn't with the direction of the arguments but their lack of substance.
  - convolvatron 5y ago
    is there a point in 'exploring' these ideas on HN where its very unlikely someone is going to show up with any actual evidence? what is the value in repetitive circular uninformed speculation?
  - evv555 5y ago
    There's evidence that the lab was doing gain of function research on coronaviruses. That's not exactly a smoking gun but it's extremely compelling evidence. NIH admits that Fauci lied about funding gain of function research in Wuhan.[1] 1. https://youtu.be/lRCowOPL5Vc?t=229 https://youtu.be/lRCowOPL5Vc?t=229 2. https://www.youtube.com/watch?v=pAIsK9tosck https://www.youtube.com/watch?v=pAIsK9tosck
civilized 5y ago
Meanwhile, I've noticed there are plenty of people who will downvote my comments if they are even mildly, vaguely skeptical of "lab leak", "vaccines/lockdowns cause more deaths than they prevent", or the other anti-establishment narratives that have become culture war memes. These meme narratives seem to be cherished as sacred by a significant percentage of HN. Sorry guys, but I call 'em like I see 'em, and sometimes -- definitely not all the time, but sometimes -- I think the establishment happens to be right. And HN is supposed to be a place for that kind of genuinely independent thinking. If you want to fight the culture war, you can do that on the other 99.99999% of the internet where it's everybody's favorite thing to do.

gorgoiler 5y ago

Before anyone gets too excited, this is a paper from a third party (six authors from various state funded science and technology institutes in Beijing.) It is being hosted on the NIH’s mirror of an Elsevier journal. Specifically, the URL decodes as: * PMC: PubMed Central, an information portal hosted by * NCBI: The National Centre for Biotechnology Information, part of * NLM: The National Library of Medicine, brought to you by the letters * NIH: The United States National Institutes (more than 1!) for or-is-it-of Health. (The hyphenated part is silent.) As for the paper itself, it’s just too bad that their Data Availability Statement is basically “yes” without linking to it. Googling the file names in their R scripts found them easily enough.

bawolff 5y ago
Why would that alter my level of excitement? I know different journals are of differing levels of quality, and im not in the know enough to assess which is which, but i would never assume that the NIH is the only group that knows how to do science.
- gorgoiler 5y ago
  For me, HN putting the paper’s title next to “TLA.gov” gave the former the weight of the latter, suggesting this was a US government finding. But, with respect to the original authors, it’s more like “Mice did this!” alongside “www3.docs.nih.gov/~jeff45/theories/drafts/mice.htm?”
ImaCake 5y ago
It is routine for basically all papers in medicine research to be hosted on PMC. Often they host the entire article, not just the index and abstract. The reasons for this open access are complicated but boil down to certain rules from funding bodies. I have no idea if the particular Elsevier journal (in the banner at top of the page) is reputable, but the science here seems at least robust. If I wanted to discredit this paper, I would point out the authors developed an analysis technique they want to apply to other diseases/models. COVID is a nail and they have a specific hammer, no matter if it’s the right kind of hammer.

ta8645 5y ago

Is there any chance we could vaccinate mice? Perhaps developing an edible version that we could use to help stop them from generating future variants? I can just see anti-vaxxers using this development as proof that 100% vaccination isn't a useful goal.

nzmsv 5y ago
Not an anti-vaxxer, but comments like this are even better antivaxx fodder :) I understand where you are coming from, but the ultimate goal is to stop COVID, not get everyone a jab in the arm. If the jabs (legitimately) stop working we should stop the jabs. Compliance with COVID rules isn't a goal unto itself. Vacccinating mice is a fun idea to think about, but you'd have to develop vaccines for squirrels, raccoons, and pigeons shortly after the mouse one. Also think about all the unintended consequences (your food vaccine getting into waterways, for example). So yeah, this is the kind of idea that makes antivaxxers look sane.
- inter_netuser 5y ago
  Please, let's not try doing Marek's disease in humans. https://en.wikipedia.org/wiki/Marek%27s_disease https://en.wikipedia.org/wiki/Marek%27s_disease "The evolution of Marek's disease due to vaccination has had a profound effect on the poultry industry. All chickens across the globe are now vaccinated against Marek's disease (birds hatched in private flocks for laying or exhibition are rarely vaccinated). Highly virulent strains have been selected to the point that any chicken that is unvaccinated will die if infected.[14] Other leaky vaccines are commonly used in agriculture. One vaccine in particular is the vaccine for avian influenza. Leaky vaccine use for avian influenza can select for virulent strains.[15]"
  - nzmsv 5y ago
    OK, I'm probably going to burn a bunch of karma on this comment, but this is very interesting. For example, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4516275/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4516275/ looks like a legitimate piece of research. Isn't this exactly what we are doing with the current COVID vaccines? How does one explore this question without being labeled a crazy antivaxxer?

underdeserver 5y ago

doingtheiroming 5y ago

The odd thing about opposition to lab-leak hypotheses is precisely that it defines itself by that opposition. If the wet markets were the source surely vigorous campaigning against wet markets would be of more utility that vigorously scouring the internet for alternative ideas to downvote. Given we know that lab leaks happen continually we should all perhaps be campaigning vigorously for an end to wet markets, protection for cave habitats, better controls in labs in general and a complete moratorium with gain of function research. We don’t know where this pandemic came from but we know enough to say that it’s likely all those things could be sources in the future. So perhaps leave the debate alone and focus on stopping the next pandemic.

forgotmyoldacc 5y ago
The term "wet market" just means a market that sells non-dry goods, like meat or vegetables. Most farmers markets are wet markets. See https://www.youtube.com/watch?v=whbyuy2nHBg https://www.youtube.com/watch?v=whbyuy2nHBg for an example. Perhaps you mean campaigning against eating exotic animals?
- XorNot 5y ago
  Live animal markets have been a historically common origin for new diseases - cities were an absolute disaster disease-mortality wise until the hygiene initiatives started cleaning them up. Extended, concentrated exposure to animals has always been a breeding ground for new plagues.
  - q1w2 5y ago
    I think you are unnecessarily conflating hygiene with wild animal contact. Even a perfectly hygienic butcher shop and wet market can transmit a new disease. Keeping it clean is good to reduce the transmission of common illnesses - but the genesis of a new disease can easily be passed in a clean market.
- josefx 5y ago
  I think the issue would be less the "exotic" and more the wild animals sold in unhygienic conditions, which at least was the picture some media painted when describing Chinese wet markets.

fredestine 5y ago

Could it be that some researcher gave this variant to mice so that it will be easy to test and spread it later to human to counter more agressive variant and help that way bring up natural immunity?

kennywinker 5y ago
> Could it be that some researcher gave this variant to mice so that it will be easy to test Yes, that is technically possible. Mice and humans also come into contact fairly often, so natural transmission from humans to mice (and back) wouldn't be that rare an event. > and spread it later to human to counter more agressive variant I think you might be giving too much credit to virologists - I don't think anybody could know from observing a virus in mice if it was going to be more or less aggressive in humans. > and help that way bring up natural immunity? Natural immunity doesn't seem to be very useful against covid. Or, at least, not more useful than the vaccines we already have. Stories of people getting covid twice, even three times, are getting more and more common. This doesn't seem to be a "get it once and you're set for life" virus.
- ppod 5y ago
  >Natural immunity doesn't seem to be very useful against covid. Or, at least, not more useful than the vaccines we already have Do you have any evidence for that? The question has obviously become politicised. Experts figure out what information they think might make people more relaxed or careless about covid, and heavily push the reverse line. It's no wonder people's trust in experts is failing. https://www.theguardian.com/commentisfree/2021/oct/24/which-protects-you-more-vaccination-or-prior-infection https://www.theguardian.com/commentisfree/2021/oct/24/which-... https://www.medrxiv.org/content/10.1101/2021.08.24.21262415v1 https://www.medrxiv.org/content/10.1101/2021.08.24.21262415v...
  - rsfern 5y ago
    The recent flurry of papers on omicron trying to decouple the effect of its intrinsic virulence from prior immunity have been finding that prior infection (with delta) and unboosted vaccination have comparable risk reduction file hospitalization from Covid It’s been a couple weeks so maybe there is better, less preliminary analysis available now On hospitalization risk in the UK: https://www.imperial.ac.uk/mrc-global-infectious-disease-analysis/covid-19/report-49-Omicron/ https://www.imperial.ac.uk/mrc-global-infectious-disease-ana... On reinfection/breakthrough risk: https://www.medrxiv.org/content/10.1101/2021.12.27.21268278v1 https://www.medrxiv.org/content/10.1101/2021.12.27.21268278v...

londons_explore 5y ago

To summarize this paper in a less technical way than the abstract does: This paper finds very strong evidence that omicron jumped to infecting mice in May 2020, then jumped back to humans again in Nov 2021. * Mutations in the spike protein, which are likely to depend on which animal is best infected, were a far closer match in mice than any of 20 other species tested (P<1.6x10^-11 ) * The types of genetic changes (ie. transitions from one base to another) were not those expected to be found in human cells, but were those expected to be found in mouse cells (P<0.008) * Omicron binds far better to mouse cells receptors than any other animal or human tested (P<1x10^-5 ) * The genetic changes seen happened at a rate far 3.3x faster than expected in humans. (my summarization here has traded scientific accuracy for simplicity) Any of those fist 3 bullet points I would consider pretty decisive evidence. To have found all three is amazing.

jonathanstrange 5y ago
Wow, those P values are very low. Is this normal in this type of research? Are they calculated directly based on combinatorial arguments?
- londons_explore 5y ago
  No. P values this low are very rare. I haven't checked any of the analysis with my own data, but the approach seems pretty legitimate. Each is calculated in a different way, using mostly-non-overlapping evidence, so it's almost legitimate to multiply them together to get P<1.3x10^-18... Not that there's any need - each alone is very convincing. The whole lot really should have been written as three separate papers, with better written abstracts, and a metapaper, written by different authors, combining the evidence and comparing to the evidence for other hypothesis.
- deleted 5y ago
  [deleted]
- MontyCarloHall 5y ago
  > Are they calculated directly based on combinatorial arguments? Yes. Most of the extremely low p-values come from binomial tests with a very low binomial probability p_bin relative to the fraction of positive outcomes. For example, > We identified 45 point mutations that were introduced in Branch O (hereafter referred to as “pre-outbreak mutations.”) We observed that the pre-outbreak mutations were over-represented in ORF S (P = 1.2 × 10−13, binomial test with the expected probability equal to the length of ORF S relative to the SARS-CoV-2 genome). So p_bin = len(ORF S)/len(genome). The spike protein sequence (ORF S) is roughly 1300 bases and the entire SARS-CoV-2 genome is roughly 30 kilobases long, yielding p_bin ≈ 0.04. If there are 45 total pre-outbreak mutations, and assuming they ought to be uniformly distributed across the genome (big assumption, BTW!), then seeing 17 of them occur in the spike protein sequence would yield a binomial p-value (one-sided test) on the order of 1e-13. The other low p-values either also come from binomial tests with similarly low binomial probabilities relative to positive outcomes, or from Fisher exact tests with gross imbalances between categories (and high counts to back those up).

eraad 5y ago

Mouse as in lab mouse?

tim333 5y ago
Who knows.

NicoJuicy 5y ago

I'm not sure, but instead of vaccines. Would it be possible to increase mutations that benefit us by using a large population of mice untill a variant pops it that is more beneficial than the one in a pandemic? Eg. - severely reduce severity - replace previous variant - more transmittable I'm just wondering. Since even Lions in the zoo in Belgium had COVID.

p_l 5y ago
Those result in more deaths, thanks to higher rate of infection, and ultimately you don't know what way it will mutate again.
yosito 5y ago
Seems possible, but risky. You could end up with mutations that go the other way too. Imagine something super contagious and virulent escaping the lab by accident and killing millions of people.

dr_dshiv 5y ago

If one thought that a more infectious but less severe coronavirus was economically advantageous, how long would it take to breed in laboratory mice? Obvious you couldn't announce making it, but if it happened to spread, that's good for the world, right?

p_l 5y ago
No, because more infectious but less severe virus is actually going to kill more people and cause more disruption economically even without deaths. For the former, essentially you're dealing with multiplying lower chance of death with much higher infection rate, resulting in bigger count of deaths (and other events like hospitalisations, isolation, etc., which increase economic disruption).
- trenchgun 5y ago
  But if it's really mild though, then it can be a Christmas gift.
- saalweachter 5y ago
  Also you could really only develop a strain that was more infectious/less deadly in mice, using mice. Once you jump it back to humans it's a new roll of the dice on whether it's more or less deadly and infectious.
  - dr_dshiv 5y ago
    I generally agree. But it seems possible to know a priori that it wouldn't adversely affect the lungs, which is the primary cause of death/damage.
    - p_l 5y ago
      Except lungs are, arguably, a minor (just most visible) issue with COVID. We're going to deal with long history of disablement caused by how COVID attacks neural tissue, for example, something I think might be more disastrous long term (1918 flu was similar, with some historic effects like Aktion T-4)

hoseja 5y ago

bikamonki 5y ago

Reading this thread I can see that finally HN has turn into another Twitter. That is sad. I thought we were a different crowd: objective, respectful, inquisitive, non-political. Is this the endgame for all social nets?

lngnmn2 5y ago

There is nothing with amounts to an evidence, only speculations. Evidences require at least an reproducible experiment. Nothing based on estimated probabilities and correlations is an evidence by definition. Again, this is nothing but hypothetical speculations with too many assumptions.

thehappypm 5y ago
So, is researching the Big Bang futile since we’ll never be able to reproduce it?

orbifold 5y ago

Wild conspiracy: What if the omicron variant was created by the same process as is used in GoF research more generally. Use humanised mice with human ACE2 receptors and pass it through them over many generations selecting for infectiousness / immune escape wrt the existing vaccines. Maybe they even observed anti-body dependent enhancement (ADE) in mice. I don't think this is entirely implausible because current research is doing things along those lines: There is an established "mouse" model now and people are actively working on chimeric vaccines, engineering virus variants with different spike proteins (for chimeric vaccines see e.g. https://www.science.org/doi/10.1126/science.abi4506 https://www.science.org/doi/10.1126/science.abi4506). They engineered several COVID variants in that paper, some which antagonise the innate immune response. > To confirm that scrambled coronavirus spikes are biologically functional, we also designed and recovered several high-titer recombinant live viruses of RsSHC014/SARS-CoV-2 NTD, RBD, and S2 domain chimeras that included deletions in nonessential, accessory open reading frame 7 (ORF7) and ORF8 that encoded nanoluciferase (fig. S1C). SARS-CoV-2 ORF7 and -8 antagonize innate immune signaling pathways (25, 26), and deletions in these ORFs are associated with attenuated disease in humans (27, 28). and made sure that the "single" spike vaccine was ineffective vs. the chimeric vaccines, which gave broad protection.

Projectiboga 5y ago

We all saw South Park: Pandemic Special, the whole thing can be blamed on Mickey Mouse and his whoring around and luring Randy into debauchery.

tim333 5y ago
I hadn't so I had to find the clip https://www.youtube.com/watch?v=KNMRD9nCASw https://www.youtube.com/watch?v=KNMRD9nCASw