https://www.microbe.tv/twiv/twiv-697/
Any biological differences are theorized solely from the genome at this point. In the episode, Racaniello is at pains to point out that genomic differences alone don't imply biological differences in say transmission, and things like founder effects might also explain the variant's prevalance. We simply don't know yet.
There's a neat cautionary example at 35:10 which I'll try to summarize here. Polio was endemic, with low incidence, for thousands of years. Around 1900 it went from endemic to epidemic. Why? Did it suddenly mutate into a deadlier or more transmissable strain? While we don't have polio sequences from before and after 1900 to compare, we do know that rapid improvements in sanitation delayed exposure to the polio virus. Babies were now encountering the virus after maternal antibodies to it had waned! And it turns out this adequately explains the spike in polio a century ago.
Goes to show how complex the dynamics of these systems can be!
The problem is that action now is way more valuable than action in 1-2 months. Mass vaccination is right around the corner, we just need to buy time to get there. If there is a substantially more transmissive variant around, that will make it much harder to buy that time. You need to be able to act on the balance of probabilities, not wait for perfect information.
(And their claim that there's nothing we can do differently is just total bunk.)
And because they run a popular podcast, their view gets massively amplified by being parroted in internet discussion.
I definitely don't know enough about this topic to say you're right, but as an avid layman listener of TWIV for 8+ months now, I've recently started thinking along the same lines.
With the greatest of respect, Vincent Racaniello, while being clearly a true expert in the field, tends to take a very quick and polarised view to newly presented evidence, and can often sound like he's being overly dismissive to my layman's ears. To the degree where I end up thinking, "it can't be that black and white".
I get the sense that sometimes the co-hosts would likely go for a more nuanced perspective, and often they do try to soften the edges around some of his opinions, but the podcast is very much his domain.
By the same token, I've often heard him admit that he was wrong. The sign of a good scientist! So there's that.
Being in the UK, and having received head-on the full barrage of "communication" from our Government during COVID, I have learnt to be sceptical of the messages they put out, and defaulted to "cynical" when first hearing their report of the new variant at the end of a recent press conference. The more time goes on though, the evidence does seem to be mounting that we should be looking at this very closely and not dismissing it out of hand.
> The problem is that action now is way more valuable than action in 1-2 months.
Completely agree. We have to use a balance here of scientific evidence, but also strategic thinking - which may not be 100% scientific - and the strategy may be that it's safer to assume this variant is more easily transmissible, and act accordingly, rather than wait for the science to catch up and prove it 100%.
All of that said, re. TWIV - it has been a game-changer of a podcast for me during this pandemic. I thoroughly enjoy listening to the hosts, all of whom are generally good natured, clearly very experienced, and doing a good job overall of science communication. No view on COVID is going to be perfect, and in my view their output is a net positive (by far) even despite the above.
In the latest TWIV, their comment was that the things you would do to prevent COVID are the same no matter if it is a new Strain or not. That's true - but we also have to deal with a increasingly uncomfortable truth - in many places, the COVID incident and death rate are pretty much the same, despite dramatically different legal and social dictates around masking, etc. Italy, France, USA, UK, Spain, Belgium, etc are all within 10% of the total death per million population, for example.
There is a weird cycle around COVID. Everyone reports on how awful it is somewhere, people draw a over-broad conclusion about the moral or scientific failures of the continent / state / country / red state / blue state, then that wave of covid waxes in one place, and wanes is another, and the cycle repeats again.
This pattern continues despite different travel restrictions, different masking policies (way less then my state in the USA, for example), etc.
SO I think the answer is not - we couldn't change anything - but rather - what is really the science behind this - and do we truly understand what is going on? I get that Vincent is burned out and has a knee jerk reaction, if I had to deal with all the insanity around the Hydrochloroquine crap I would be too.
No country has been dealing better with Covid than Taiwan. No lockdown, and > 200 days without new Covid case [1]. Taipei had daily direct flights from Wuhan, and the Diamond Princess mooring near Taipei. They told the world early on [2] how they did it. Summary: Border closure, contract tracing, testing and controlled quarantine for those testing positive. It's worth reading [2] to realise how swiftly, decisively and rationally Taiwan reacted, and compare it with other countries. It probably helped having had an epidemiologist as vice-president [3].
[1] https://www.theguardian.com/world/2020/oct/29/taiwan-domesti...
[2] C. Y. Wang, C. Y. Ng, R. H. Brook, Response to COVID-19 in Taiwan: Big Data Analytics, New Technology, and Proactive Testing, https://jamanetwork.com/journals/jama/fullarticle/2762689
And sure, border closures too. They're late in that the new variant is probably present at some level in most of Europe. But the fewer cases you have to start with, the longer it'll stay contained at low levels. You might even be able to contain it entirely for a while. All the cases of B.1.1.7 in Denmark (0.4% of their sequencing) appear to be part of the same cluster. They should be able to manage that much better than if the variant was being constantly reintroduced by travelers.
For the UK specifically, they're doing a bunch of things differently for their Tier 4 level vs. Tier 3, which was introduced specifically in response to B.1.1.7. Are you suggesting that all of those measures should have been done everywhere anyway?
That is the single strongest set of data here. In the areas where both the new variant and the older ones can be distinguished (via sequencing or via the fortuitous FN from the commonly used PCR test), the new one is spreading substantially faster. This measurement is not sensitive to confounding factors such as environmental or behavioral changes, because those would affect all variants equally.
The thing that the TWIV guys seem to love repeating is that this is just a founder effect. I just don't understand where they're getting that idea from. Yes, that's almost certainly been the explanation in the earlier cases we had where one variant become predominant. But that happened in low prevalence environments. It's basically inevitable that if there are few cases, one variant or the other will become predominant just by random chance. That was not the case in the UK. In mid-October, when this variant was still basically non-existent, they were at 15k confirmed cases / day. This variant is not a founder, it was a very successful invader.
The other evidence is weaker, because it's less direct and the data is noisier. (Increased viral loads, many of the changes happening in parts of the genome that were already expected to be of biological interest, correlation studies showing that areas where the new variant is predominant have higher growth rates when controlling for other factors). That data would not be conclusive by itself. But all of it is directionally consistent with the main data point of concern, and strengthens the case.
What you describe is one such example. TWiV suggests that anything short of convincing proof should be ignored. However, every bit of evidence updates our individual confidence to some extent. It's quite silly to draw an arbitrary line at a certain "quality" of evidence, and treat anything below that line as useless.
I suspect that in an effort to debunk unreasonable and sensational stories in the media, TWiV got carried away, and started to sweep the subtleties under the carpet.
It seems these days, it's really hard to find highly nuanced, carefully balanced, sources of information.
By current accounts the vaccines will still work against this variant. So the last thing you want to happen is for the virus to catch the vulnerables in the last moment before they are vaccinated and essentially renders the whole vaccination program ineffective.
Of course there's the debate of this whole pandemic about the harm to economy and people's lives etc. To me the majority of the damage has already been done and can't be undone. So I'd like the measures to be taken to end this ASAP, even if they are even stricter, and to mitigate the harm as much as possible. But I highly doubt that's what's going to happen. The actual policy effects may be neither here nor there.
This isn't surprising because the variant hasn't really encountered the vaccines yet, so it's not an adaptation to them.
But which action? I can see two class of possible cause that do not entirely overlap in response: A singular cause such as a strain; or fluctuations as the emergent behavior of a complex dynamic system. If incorrectly attributed to a localised strain, efforts may be ineffectively focused on creating division between larger populations while removing the public's focus on the more evenly distributed measures we are already employing.
> You need to be able to act on the balance of probabilities, not wait for perfect information.
How about the probabilities between the two class of above cause? We seem to have an innate bias towards inferring 1:1 causal relationships which makes a strain feel like a simple and attractive explanation. This bias fails miserably in the face of dynamic systems where behavior cannot usually be attributed to a single variable... IANAV, but the spread of infectious disease is without a doubt a complex dynamic system from which a significant degree of unpredictable behavior must emerge.
To be honest this problem is not even particularly unique to this situation... The world is vast and complex, yet people usually want simple explanations - particularly for undesirable situations, something tangible to blame, a villain... The media continually exploit this desire and I cannot help but feel this is another example. A strain (real or not) makes for an excellent villain and story VS "chaos" which is extremely difficult for any reporter to spin an accessible narrative into.
The undeniable fact is that this variant has successfully replaced other already highly prevalent variants. That needs to be explained somehow.
Could it be a founder effect? No.
Could it be random chance? No. Of course a stochastic process could converge like this even with no selective advantage eventually. But the change has been too fast and too consistent in this case.
Could it be a super-spreading event? No. The change has been continuous, and a single event would cause just a step-change in relative prevalance.
Could it be the new variant being more transmissive, or having another similar selective advantage? Yes.
Could it be an unspecified emergent behavior? I guess it could. But how are we supposed to reason about something that vague? We have a simple explanation that's consistent with the known facts, I feel that anyone proposing that it's just emergent behavior should be at least a little bit more specific.
In the UK, my view is the action to take was very clearly to dial back the public's expectations of having a 5 day "free for all" period of relaxation of our restrictions over Christmas.
This 5 day period, as originally planned, was going to lead to massive cross-country travel, plenty of it being completely unnecessary, with no doubt a lot of risk taking in the spirit of "it's Christmas" and an inevitable huge spike of cases and deaths in the weeks that followed.
I mean I love Christmas, but I can cope with not having 5 days of partying for just one year... *
As it happens, the government did take action to dial this back at the very last minute to allow just 1 day of relaxed rules (Christmas Day) rather than the week that was originally on the table. In my view they should have been planning for this right from the start and they unnecessarily screwed up a lot of people's Christmas plans by leaving it until the very last minute to make this change.
Now even if the variant turns out to be a "non issue" (and we still have rising numbers anyway), I think it's better that they took this action to further limit Christmas (as tough as it is for everyone) rather than take the "wait and see" or "hope for the best" approach, both of which seem to have been UK govnt strategies at one time or another during 2020.
* I'm being slightly flippant here. This is clearly a tough time for a lot of people, and many families will be spending Christmas apart and will find this very hard for all sorts of reasons.
Systems are dynamic and complex, but that doesn’t make them unknowable. If complex systems were impossible to model science wouldn’t be a thing.
Sure, the “new variant” narrative is an easy one to pick up because it’s superficially understandable; but what other complex interactions are resulting in a new strain becoming dominant over an existing one?
Do we just sit on our hands and go, well gee, better do nothing? Guess it’s just too hard to know what to do at this point...
There is a typical government fallacy that to be seen doing something is better than nothing, even when it’s the wrong thing... I get it, that’s bad.
...but this is a case where doing nothing has been a colossal disaster so far; and it’s extremely clear what the result of doing nothing different will be if the new variant hypothesis is correct.
So it’s a risk game. Is the cost * probability of A vs B a better choice?
You’re saying the probability is not known at this point because systems are complicated.
So what? It’s still clear to me that it’s very likely that something is happening, even if exactly what it is, is unclear.
You can still build a risk matrix taking that into account.
How is this focus "removed" and why is there any reason to think that evenly distributed measures along with targeted ones would be a problem for the public?
What is the source for this? I've read another explanation: the overuse of pesticides like Paris Green, DDT (see pictures of kids literally sprayed with it on their clothing), and the use of "medical metals" to treat any kinds of diseases - giving mercury, arsenic etc. All of these (pesticides, metals) can weaken the bowels and allow the polio virus (which resides in the bowels) to enter into the spine where it then causes paralysis.
Maternal transfer of antibodies is one of my favorite immunity topics - it is far overlooked in usefulness lately, largely seen as impractical due to changes in lifestyle (not many mothers breastfeed)
Dear downvoters: what do you find does not contribute to conversation about sharing this theory?
https://twitter.com/billhanage/status/1341857733633581063?s=...
I share your opinion.
https://khub.net/documents/135939561/338928724/SARS-CoV-2+va...
and have a newer one where they're more confident: https://app.box.com/s/3lkcbxepqixkg4mv640dpvvg978ixjtf/file/...
I haven’t seen any work on this variant that doesn’t fall into that trap.
Any adjective like "strain" implies a binary distinction, but that doesn't mean you should round off "don't know" to false.
This is talking about the SARS-CoV-2 VOC 202012/01 variant [0], aka B.1.1.7., aka carrying the N501Y mutation.
No news here, other than confirmed spread to Japan.
[0] https://www.cdc.gov/coronavirus/2019-ncov/more/scientific-br...
https://nextstrain.org/groups/neherlab/ncov/S.N501?animate=2...
N50Y has also a similar antibody neutralization profile as the non-mutated version.
Of course, these data refer to the mutations on their own, not together.
More on the deletion (on its own, again): while it is supposedly tied to a faster entry into the cells (twice as efficient in experimental assays), it look like it has lower fitness in absence of an ongoing immune response (it would lower in presence - but not disappear - in the immunocompromised patient it was first found into between treatments with convalescent serum).
We assume the drug companies will be able to adapt the vaccine quickly to the new variants. If this happens then it creates a few problems..
One problem is having to continuously distribute a new vaccine to people indefinitely.
Another problem is only certain countries are capable of manufacturing the vaccine. So you have a kind of supply chain scarcity develop where only certain people in certain countries will be able to get one.
I've seen mixed reports about whether the current vaccine will hold up as variants appear.
What is going on right now is mass anxiety. The vaccine is out, so humanity is imagining how things could still go wrong. The easiest thing to imagine is a version of the virus that doesn’t respond to antibodies. Luckily, they imagine this because they don’t understand how the vaccine works. It’s fantasy, and it is highly unlikely that any of this would play out.
Sure, spike ain't hemagglutinin and corona ain't no influenza, but let's not pretend there's no precedent at all for proteins mutating to the point that vaccines become ineffective.
Perhaps the new mRNA technique could lead to better flu vaccines as well.
Not enough anxiety, in my opinion. Tons and tons of people are still behaving as if everything is normal, or that they are somehow special.
You might be inducing a "so-what" mentality where people don't want to refrain from going to bars and restaurants just to not catch a virus that's going to get them at some point.
In Spain alone they have 3 different vaccines that are not even in phase 1, but will be next year.
There will be at least 5 totally different technologies against it. There are "slower to market" technologies than RNA but stronger and proven.
Also the weather is going to get better in the North Hemisphere soon.
January is colder than December usually. We're not even over the peak. February should be roughly similar to December, March is when it gets better again usually. But that's still 2 months of people staying indoors a lot.
I came across the nextstrain site [1] in March, where they showed multiple variants in the wild, concentrated to certain regions.
The media is turning this into a bigger deal than it is, else they’ll lose control over the population. Imagine what would happen if there wasn’t constant coverage of the est. case count...life would go back to normal.
This is precisely the world we're in, and which we've been in since the dawn of infectious disease.
Some viruses (in fact, some entire realms of virus) exhibit this phenomenon; they're sharp as hell for things that aren't even a full-fledged organism. But we're sharper, and we make vaccines to account for subtle mutations. Often times, we get it right, which is incredible.
We already do this for influenza.
In virological warfare "that's a feature, not a bug".
Shouldn't these viruses get selectively better at fighting human immune systems? And we're throwing 750.000 new hosts to this virus worldwide every day.
I'm sure there are other factors, but that's a big one. So most viruses tend to harm the host less over time.
We saw the opposite effect during the Spanish Flu. As I recall at least one theory: because there was a war on, only severely sick soldiers would get sent away from the front lines, where they could come into contact with the general population. Less severe cases were kept on the front lines. This behavior created an inverse effect, applying selective pressure on more _severe_ strains of the virus. Hence, the second more deadly wave.
Once the Spanish Flu pandemic was "over" and the war was over, that pressure wore off and the Spanish Flu slowly evolved into various common cold strains that we still see today (AFAIK).
My guess is that it's hard to speculate what will happen with COVID-19. Several common cold viruses are coronaviruses, so from that one might conclude that COVID-19 will follow the same path of becoming less severe over time. But COVID-19 also has a _very_ large incidence of asymptomatic transmission. So isolating people who are very sick is unlikely to provide much selective pressure to this virus.
If COVID-19 _does_ become less severe over time, it will occur only because of different selective pressures or for different reasons. For example, maybe the mutations that result in higher transmission also, by some genetic necessity, lower severity.
The asymptomatic nature of COVID-19 gives it a big question mark, and we should _not_ assume anything about it becoming less severe over time. We should keep up aggressive measures to control its spread and lean on our vaccines to squash it before it has a chance to get worse. The quicker we get the vaccine out, and the more aggressive we are about controlling the virus's spread, the higher our chance of getting out of this mess.
Does it? Meta-analysis concluding secondary attack rate in households from asymptomatic transmission around 0.7%.
> Household secondary attack rates were increased from symptomatic index cases (18.0%; 95% CI, 14.2%-22.1%) than from asymptomatic index cases (0.7%; 95% CI, 0%-4.9%)
https://jamanetwork.com/journals/jamanetworkopen/fullarticle...
> The asymptomatic nature of COVID-19 gives it a big question mark
Also the mass, un-targeted lockdowns have probably screwed with the selective pressure as well.
So, there are two suggestions within viral genetics:
1. Mutations which are kinder to the immune system might be able to spread relatively easier. As noted in the other comments, this is likely dependent on human behaviour and ritual around illness and death.
2. Significant mutations which spread more efficiently are perhaps more likely to knock-out genes causing harm (lost to 'evolutionary cost') than to enhance those genes.
Neither of these are completely guaranteed, but they are generally seen as likely.
the virus will not become weaker as time goes on, it will have less variation to call upon for evasion of host defenses.
the major selective pressure on this virus appears to be exhaustion of variant production bringing the cat and mouse game of new viral antigen sequence vs antibody respecification to a stalemate, and the virus must move on [spillover] to a new host species. The ability to occur in many novel variations, and eventually spillover from a host species to a conspecific host is how this virus persists.
> Trade-offs between different components of parasite fitness provide the dominant conceptual framework for understanding the adaptive evolution of virulence (Alizon et al. 2009).
...
> By far, the most widely studied trade-off involves transmission and virulence (Anderson and May, 1982; Frank, 1996; Alizon et al. 2009).
But. I have no training.
I remember the scientists telling us early on in the pandemic that mutations typically result in less lethal viruses.
Is this not the case?
If any (will), it shouldn’t be killing its host.
These are anthropomorphic reasoning and antagonisms.
What would you say instead, to capture these ideas, that are equally clear to everyone?
In general, a "weaker" virus has an evolutionary advantage. Killing or disabling the host means fewer opportunities to spread.
Perhaps this is just the normal operation of American media to exaggerate the negative side of the situation? [2]
[1] https://nextstrain.org/sars-cov-2/
[2] PDF link: https://www.nber.org/system/files/working_papers/w28110/w281...
So far UK and South Africa have two strains that are faster spreading (and hopefully that's the only difference). If there's nothing special about the one from Japan, I bet that this is just getting attention because the other two are in the news. Either news orgs jumping on a bandwagon or HN readers expecting that it's similar when it's not.
But maybe this one actually is notable too, I don't know.
Well, then it's news because it means that Japan is now going to face, or has been facing, much faster spread than before.
I’ve just come from the UK, and while rules were less strict for a while, and people weren’t wearing masks as much, I’m less certain if people were social distancing. We certainly were in preparation for travel, but I imagine schools, college holidays, etc contributed just as much as any variant.
[1] https://www.timeslive.co.za/news/south-africa/2020-12-08-130...
1) This is from a Japanese website.
2) Could you point me in the direction of a nation which has media that doesn't over exaggerate things?
Also, the article here says "case count". I'm really interested in the count of "excess deaths".
the basis of the lethality and transmissibility are inversely related is dependent upon dead or ill hosts having down time and not interacting with other hosts. thus if you are sick and febrile, you contact fewer individuals thus less opportunity for virus transmission between individuals.
in the case of the coronavirus the dynamic is different. you contact the virus, virus replicates, and becomes transmissible, you still feel fine and behave as always transmitting the virus to other individuals, Then you begin to feel ill and bedridden. the virus has reproduced, transmitted and even if it kills you, it has escaped the selection pressure of the first case, where lethality or morbidity must be decreased for maximization of transmission.
here is a slightly difficult read but is is a classic example of the rule you are asking about.
NYT article on paper: [2]
[1] https://cmmid.github.io/topics/covid19/reports/uk-novel-vari...
[2] https://www.nytimes.com/2020/12/23/health/coronavirus-uk-var...
At least now widespread testing is available and we're able to track new variants in geography and time. Looks like the mutated one mentioned just hit France a couple of days ago.
Presumably you mean 2019?
Assuming we ever get out of them...
In the words of Derek Lowe...
“Many infectious pathogens, in fact, gradually evolve versus a given animal host to be more infectious and less virulent over time. Remember, it’s not the job of a virus to make people deathly ill: it’s the job of a virus to make more virus.”
Ask yourself: if you're that parent, do you wish that your kid had already been exposed and run a complete course of the virus prior to this mutation?
It seems obvious that the answer is 'yes', and, at least to my way of thinking, is an indictment of the purely horizontal approach to pandemic control so far displayed by states.
Is that relevant and who are you?
1. Many times there is an inverse relationship between ease of transmission, and severity of symptoms. There is a good chance that this new more transmissible mutant is likely to make people less sick.
2. So far all the available evidence seems to indicate that the vaccines will be effects against this strain as well.
Death rate in London and Kent didn't seem very different to other affected areas which would imply that the virus has same severity of symptoms but it is easier to transmit/contract.
We have seen strains quickly accelerate because of founder effect several times in 2020, and particular strains dominate in particular regions. The experimental studies that are needed to confirm a claim of evolutionary advantage have not been done, and the observational evidence is weak.
Those who would panic about this should be just as circumspect in their their claims as those who would dismiss it.
But when considering the data - that the strain has grown faster than all others in the UK at the time - the likelihood becomes significant. Not certain, but not worthy of your casual dismissal.
You dismiss their observational evidence as weak, but offer no further analysis. Please do so.
it is worthy of note that one single point mutation in the influenza virus corresponded to high lethality.
https://journals.plos.org/plospathogens/article?id=10.1371/j...
>> The 1918 pandemic strain A/Brevig Mission/18 was reconstructed with a pathogenicity-reducing mutation in PB1-F2 (S66N). The resultant 1918 S66N virus was attenuated in mice having a 3-log lower 50% lethal dose and caused less morbidity and mortality in mice than the wild-type virus. Viral lung titers were also decreased in 1918 S66N–infected mice compared with wild-type 1918 virus–infected mice. In addition, both viruses with an S at position 66 (WH N66S and wt 1918) induced elevated levels of cytokines in the lungs of infected mice. Together, these data show that a single amino acid substitution in PB1-F2 can result in increased viral pathogenicity and could be one of the factors contributing to the high lethality seen with the 1918 pandemic virus.<<
https://en.wikipedia.org/wiki/Myxomatosis
the coronavirus breaks past this dynamic as there is disjunction between transmission and onset of symptoms. thus morbidity is not a selective pressure upon transmisibility of the coronavirus.
Mutation and variation are different concepts.
Mutations affect the single organisms. Variations happens between individuals, groups or populations of an organism.
mutation is also a term loaded with connotations due to popular depictions.
sexual reproduction is the mechanism of verticall transmission of variation of genetic sequence through a population. genetic drift is also a mechanism of variation of a population.
the long and short of it is that mutation and variation, are tied together, they are the same thing.
you also seem to have overlooked the abuse of the term mutation, by the original article title, the use of mutation is slicker, than the use of error prone generated variant.
the use of the term strain is also erroneous in this context.
We are tracking these changes closely and concommitantly can change the sequence of mRNA, responsively, and pre-emptively if desired.strains are signifigantly different from each other, variants are a nuance on the same theme.
the virus strain that infects small mammals is separate from the trans specific strain that spilled over to humans.
the virus with small changes to the spike sequence altering spike structure or function is a variant.
under emergency conditions a 3phase trial is not mandatory , and would likely be a quick deliberation under normal conditions for small adjustments to the sequence, similar to seasonal influenza vaccines.