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!
TWIW has kind of painted themselves into the corner by insisting that anything except biological evidence is irrelevant. The evidence for B.1.1.7 being more transmissive is quite solid, and seems to be getting more so as time goes on. But no matter how strong the statistical data is, it could never be good enough for them. So their policy recommendation ends up as "do nothing at all until there is 100% certain non-circumstantial evidence".
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.
> TWIW has kind of painted themselves into the corner by insisting that anything except biological evidence is irrelevant.
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.
As a long term listener of TWIV (4 years, IIRC), I think the service they have done for the community is priceless, especially once Daniel Griffin started doing his clinical updates. That said, I remember when COVID first started hitting, and their reaction was initially "meh", then like everyone else, it started to dawn on them how bad this was going to be. So still take their voices with a grain of salt.
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.
And then there are places like Taiwan that have kept themselves COVID free and report a grand total of 7 deaths on 22M inhabitants, without any lockdown needed and thus experiencing minimal economic impact. And yet no Western country seems to want to learn from that.
1) Act immediately and aggressively at the first sign of potential virus.
2) Get your population used to wearing masks when ill with cold like viruses and thus ensure sufficient supplies and willingness to wear masks when the government mandates it.
3) Preferably be an island or have absolute control of your country (China)
There was a period when countries could've done what Taiwan did but once the virus got a hold in continental europe and usa it was over.
> 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.
I used to like TWIV, but once they aggresively and unprofessionally tried to "debunk" the lab origin hypothesis of the pandemic (which is still pretty much viable one) I kinda lost any respect to these people. I'd rather listen to UCSF podcast, way more professional.
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].
I often see "copy this country" but often, it is simply not possible, policies are usually a result of each country specificities more than the other way around. For Taiwan.
- It is an island
- It has an effective, well centralized surveillance network
- It has (presumably) an obedient population, or at least, one that don't think personal freedom includes the right to spread the disease
- They were well prepared thanks to the their experience with SARS
- A good enough welfare system to allow people to quarantine without starving or getting ruined
- A good enough police force to make sure they stay quarantined
- Enough masks and hand sanitizer, with domestic production
This is pretty much the opposite of the US. Which is highly connected, with a loosely connected government that has little control over the private sector that runs the country and a highly individualistic population.
Also, maybe there are some populations that just do better for a mix of reasons: climate, race (genetics), culture, average age, health and population density,...
Final note: closing borders is only effective if you contained the epidemic and others didn't.
I live in Taiwan.. I’m grateful to be living here during Covid.
Taiwanese people aren’t obedient. You should see how they drive.
They wear masks without flaking out about it as slavery or being against their will or whatever nonsense you guys are on about back home in the west.
Taiwanese people are couch potatoes and extremely reserved. They don’t really want to meet new people or hang out with strangers.
Also the government here didn’t play games in the early weeks. No wait and see business as usual lazy bullshit like in the
US. They check tour temperature everywhere, mall entrances, restaurants, government buildings.
All of the things you've noted are true, but the flip side is that that there seems to be a "we've tried nothing and we're all out of ideas" (or worse, flat out pandemic denialism) mentality that takes hold instead of thinking about whether it would be possible to push for some of the most obvious policies that have been shown to be the most effective (eg, enforcing testing and quarantine for all travelers, improved science communication around a respiratory pandemic). Also, it's been 10+ months, so to the degree that developed countries like the US lack sufficient PPE manufacturing, it's certainly not down to resources or capabilities (or anything besides political will in the US considering the DPA could be invoked at any time).
Also, most countries still seem to be ignoring the best/cheapest way to control spread via rapid testing and isolation. This has been not only modeled extensively at this point [1][2], but also proven to be effective by sports leagues (NBA, MLB) and Universities (look at where UIUC has kept their numbers vs the state: https://go.illinois.edu/COVIDTestingData )
[1] Larremore, Daniel B, Bryan Wilder, Evan Lester, Soraya Shehata, James M Burke, James A Hay, Milind Tambe, Michael J Mina, and Roy Parker. “Test Sensitivity Is Secondary to Frequency and Turnaround Time for COVID-19 Surveillance.” Preprint. Infectious Diseases (except HIV/AIDS), June 25, 2020. https://doi.org/10.1101/2020.06.22.20136309.
[2] Atkeson, Andrew, Michael C. Droste, Michael Mina, and James H. Stock. “Economic Benefits of COVID-19 Screening Tests.” National Bureau of Economic Research, November 2, 2020. https://doi.org/10.3386/w28031.
Consider the countries like Japan that do not actually have excess mortality despite COVID-19. Suppose they just stopped testing for it. You would not be able to tell the difference. You could then come up with any reason for this “huge success”.
This probably would have been good advice in late summer or early fall when contact tracing was still possible.
However now there seem to be so many diffuse infection events and undetected chains that the question is more about how to regain control. I'm not sure how this is achievable without contact restrictions.
One way to regain control is to mass produce cheap rapid test kits, do a couple of mass testing events where significant percentage of population is tested to identify all clusters, isolate and trace from there. See Slovakia as an example.
It's just insane how incompetent European and American governments have been in this pandemic compared to East-Asian countries. We are lucky to have some functional private institutions that bailed us out -- kept the countries running and developed a highly effective vaccine super fast.
that's because it's an island. All the islands are doing better than whole continents. You can't contain it unless you go full bore like the chinese - locking people into their homes.
I find this argument unconvincing. The UK is an island, and it's doing badly. "But it's highly connected with the rest of the world, so it makes it honorarily a non-island!" Okay, sure. How about South Korea? It isn't an island, and it's doing pretty well. "But it's de facto an island, it's not getting cases from North Korea!" Okay, sure. But by that standard the US is an island: it didn't get its cases from Mexico or Canada.
And, of course, China has more land borders than any other country in the world, and it's managed to engineer the most drastic turnaround of any country in the world.
Having a small number of entry points is useful to limit initial inoculations, but internal policy and cultural cohesion are key for preventing the explosion of any successful inoculation into national disaster, regardless of a polity's geography.
Sigh, this old canard again.
Vietnam, Thailand, Laos, Cambodia, Singapore are all doing fine without "locking people into their homes" and they're not islands.
(Ok, Singapore technically is an island but it's connected to Malaysia by the world's busiest border crossing; and Thailand's grappling with a new outbreak now but it seems to be improving.)
I feel we (US) should absolutely be closing the border to the UK, Japan, Italy and whoever else has the new strain/variant. Why would we wait on this when the evidence suggests the new version is more infectious?
If the new strain is showing up in the UK now, and you haven’t had the borders closed for the past 2-4 weeks, there is little point to starting now (in terms of stopping it from getting to the US entirely anyway).
What I’ve seen discussed is that closing borders only works if it’s done totally and immediately. Otherwise, it just slows response and causes super spreader events like we saw early this year in the US.
Makes it harder for doctors to get supplies if all the borders are closed.
The UK has an upcoming COVID vaccine (the Astra-Zeneca/Oxford one) that may prove useful in the near future. Cut off the UK from the rest of the world and the rest of the world can't benefit from it.
Also, it's almost certain that the UK strain is in the US already, and the US is shit at dealing with pandemics once they're on our soil. Border closures only work if your test/trace/isolate institutions and compliance with social distancing is good enough to eradicate the virus from within your borders; they prevent reinfection in that case. The US has shown we're completely incapable of that, so it really doesn't matter.
Any new precedent for completely closing borders between developed nations for any reason is bad. Because it creates a “we did this before.”
Even if the scale or details of circumstance are different—such as Clinton’s pardoning of his brother in minimizing Trump’s choices.
Another reason is exceptions cause outrage. And there may be many instances of diplomatic or other government travel that needs to happen or happen in the slipstream of limited public travel.
Concentrating contact tracing resources on cases of the new variant, where they'll do more good than applied randomly on all Covid cases. Targeted local shutdowns in locales where the new variant appears to have gotten a foothold. Enhanced screening of people with recent ties to the high risk areas. All the stuff we did, or should have done, for Covid itself when that pandemic was in its early stages, but with focus on the new variant.
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?
What evidence are you saying is “quite solid”. So far everything has just a been inferred from the epidemiology and the error bars are extremely wide. I wouldn’t call that solid at all.
So, when the news broke a week ago, I was wearing my skeptic hat just like for the handful of previous announcements about "new strains". And some initial reading suggested that there was nothing to worry about. But the one data point that was so eye-popping that I thought it had to be a misprint was that 60% of the cases in London were for the new variant. It wasn't a misprint, and it wasn't isolated to London.
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.
Some actual lab work? I’m not a biologist so I can’t give you specific assays. The TWiV team might, I’ll submit a question. If you look at the data behind the NERVTAG report it’s extremely noisy, and is circumstantial. Nothing in there directly measures the viruses ability to spread.
30% of people infected not able to walk a block without losing breath and being exhausted for a day — that’s enough evidence to say the risk profile has changed.
Infection rate does not change outcome of recovery (unless it’s resource constrained like vents or meds) and to that point — we’ve walked back the immediacy of vents because they were actually harmful to recovery. So technically the resource management argument should be reduced in weight by some factor.
Much as I like TWiV, they often present incorrect viewpoints.
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.
They are doing this not the first time. They are extremely aggressive against any hypothesis about the lab origin of the pandemic - and yet it is increasingly becomes acceptable by the mainstream media (BBC News tried independently verify some claims, but had literaly obstacles (physical) on their way,set by Chinese government). Racaniello (?) was big defender of GoF experimentaion on flu during 2012-2015 moratorium on this research; Osterholm AFAIR was against. TWIV are strange people, it turns out. UCSF podcasts are way more professional.
Yeah it really depends on how the numbers match up and how much risks you are willing to take given the degree of confidence in those numbers.
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.
> The problem is that action now is way more valuable than action in 1-2 months [...] If there is a substantially more transmissive variant around, that will make it much harder to buy that time.
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.
That seems like just a fancier way of expressing TWIV's "we can't possibly know anything without lab experiments that establish the exact mechanisms, so we should do nothing" philosophy.
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.
> how are we supposed to reason about something that vague? [...] I feel that anyone proposing that it's just emergent behavior should be at least a little bit more specific.
Sometimes it rains when we predicted it wouldn't, sometimes we get a full blown storm we didn't see coming... And that's using advanced techniques developed over decades on a continually available complex system for which there is demand to be able to predict on a daily basis. The very nature of these things is to have unpredictable behavior... That does not mean we necessarily do not understand the governing rules, but that the emergent behavior is not reducible into a simplified description.
> We have a simple explanation that's consistent with the known facts
It's simple and correlated, but highly suspect when a significant degree of chaos adds massive error bars to the significance of that correlation.
I think I gave arguments for all of the "No"s except for the founder effect, which I'd just discussed in another message of this thread so it seemed redundant to do that again.
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.
> 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.
Honestly, I think people are being incredibly relaxed about the fact that lockdown restrictions are incredibly expensive to the mental health of swathes of the population. I am not claiming that letting covid kill more people would be better - but I wish there was more acknowledgement of the fact that it is a trade off, and that the goal is getting society in the best shape out the other side of this. Not just the largest one.
Don’t you think this reflects a bias in the opposite direction?
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.
> 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.
Not quite. It can makes them unpredictable, not unknowable... more specifically it can make them computationally irreducible which means we cannot find a simplified description of their behavior without having to compute every step, even when we understand the underlying rules that govern them. In fact we often cannot model them very well, an easy every day example is the weather, which we desperately want to know, but our methods are a significant compromise - that may seem like an unfair analogy but it really isn't, the atoms of society may be fewer but they have far more dimensions and more complex individual interactions.
It doesn't always apply, even within the same medium, it depends on the context e.g predicting weather requires some kind of simulation of fluid and pressure, yet in a different, more narrow context it's not necessary to attempt simulating the underlying mechanisms in any way or form, instead the overall behavior can be simplified to a set of descriptive equations (Bernoulli's).
It's funny because this does touch on a core issue for science - we still mostly hold this traditional view of it based on a history of going after the more easily obtainable nuggets of behavior with nice manageable reducible descriptions, but we have been unwittingly selective.
> what other complex interactions are resulting in a new strain becoming dominant over an existing one?
It does not need to result in a new _variant_, this right here is the misunderstanding. These two things can happen and not be related.
Personally I’ve taken it to changing optimization tactics. I’m going to use pseudo-statistical language to illustrate my point so please try to be charitable. In a usual model I’d base my actions on the mean outcome for a given set of choices. For covid, I think it’s smarter to choose to minimize the maximum, worst outcome. Ie assume the absolute worst and react in the harshest way. This new strain may prove to be nothing major, but personally I’ve decided it’s wise to be even more distanced from possible disease vectors. I suspect this may be a good strategy in a universe in which an already rare occurrence has been observed, in a larger sense.
> removing the public's focus on the more evenly distributed measures we are already employing
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?
There is some other point I heard recently on Twitter - the appearance of new variants with increasingly faster speed of spread (BTW, if anyone remembers, there was a mutation in Australia, which had shorter incubation - 8 HOURS), may quite soon cause rise of true strains, and, it might potentially lead to the ADE, when suboptimal vaccines will make disease much worth instead of easing it.
Appears to be unreliable info. Anyway, this not my point. My point is ADE, which make vaccination a terrible disaster. ADE is known to happen in some diseases , including SARS-1.
A lot of COVID discussions remind me of the history of Beri-Beri in Japan. Recommend everyone to read up on that one. Clinical purists who deny any validity to field data have cost many lifes going back longer than you think.
"Takaki became navy surgeon general in 1885, yet other doctors attacked his theories and questioned his results. The sad result was that while the navy ate barley, the army ate only rice. According to Bay, the use of barley smacked of discredited traditional Japanese medicine to many Western-trained doctors. Plus, recruits were enticed into the army by promises of as much white rice as they could eat."
27 thousand deaths and a decree by the emperor later, and army doctors finally yielded to the evidence.
This is actually not-too-dissimilar to the story of scurvy in European navies in a more distant time. It took a lot of lives and most attempts to alleviate it were based on the totally false theory of humors.
Doctors can be very resistant to change of paradigma. I wonder what is our scurvy or beri-beri; given how fat and diabetic the developed world has grown, maybe nutrition.
> 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!
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?
I’m a big fan of TWiV podcast (This Week in Virology) and I understand Racaniello’s point of view. However, this thread and other info I’ve read lead me to believe that this is an important new development.
cross validation won't save you in this situation. it's a subtle point, but you can't say "omg this strain is increasing and it must therefore be more contagious" and then show that it is more contagious by showing it is increasing... this is counter-intuitive even to most scientists, in my experience. I remember when I learnt this during my PhD. I suspect many people high up in academia don't understand this point.
an observation that may help: as your stats at time t+1 are dependent on stats at time t, you cannot separate your validation set from the set you used to perform exploratory data analysis - they are highly interdependent.
Okay, but from your own explanation, this is only a hypothesis and it's possible that sanitation had nothing to do with it either. So I'm not sure what this really shows us except that we can make up any justification for anything after the fact. Correlation is easy to show, causation is hard.
> The people who tested positive with the new strain, which is said to spread more easily and was blamed for a recent spike in infections in the U.K., returned to Japan this month — two at Tokyo's Haneda airport and and three at Kansai International Airport in Osaka.
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.
That's interesting that it's an N -> Y mutation, if it's a surface mutation, that AA shift is typically associated with tighter specificity in binding to it's target, e.g. and in antibody studies.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2829252/
N501Y itself has already appeared around the world. By itself, it does look that it is not more transmissible (see Prof. Francois Balloux's Twitter for some explanations). The deletion, again by itself is not new, and also in this case it doesn't seem it has (on its own) increased fitness over the others.
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).
What happens if the world gets into a situation where the virus mutates rapidly and we find the vaccines becoming less effective?
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.
The vaccine creates broad protection against the virus’s spike protein structure. If the virus mutated enough to evade this protection, it would have to develop a structure so radically different that it would likely no longer be able to attach to the ACE2 receptor.
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.
People line up every year to get a new flu shot because seasonal influenza keeps mutating the part of its hemagglutinin protein where most neutralizing antibodies bind after exposure to a vaccine that carries the entire hemagglutinin protein (embedded in a weakened/inactivated influenza virus).
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.
The anxiety we are talking about here is exactly the kind of anxiety you _don't_ want. If there was no vaccine in the short/midterm future people would probably (and somewhat rationally) assume that everybody (or rather 60%) will get the disease at some point, which would mean that the reward for behaving cautiously now is a lot worse (at least on an individual level, it would still be necessary not to overwhelm hospitals or to protect certain high-risk-groups).
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.
>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.
Barring post-Thanksgiving spikes, cases in the US Midwest have been dropping since mid-November. And the spikes didn't even show up in all those states. Seems like places are getting past the peak already despite the temperature still dropping.
Er should avoid meaningless terms like “lokdown light” and just say that we closed bars and restaurants and told people not to meet in private, which was largely ignored.
The lockdown started on 16th December right? Shouldn't the effect become visible after 2 or 3 weeks? The current numbers are the outcome of the pre-lockdown rules?
This news started to break and fear mongering ticked up once the vaccine was out, to get people accustomed to the idea that one vaccine won’t be enough.
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.
> What happens if the world gets into a situation where the virus mutates rapidly and we find the vaccines becoming less effective?
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.
The virus mutates all of the time. Each time it enters a cell and then makes copies of itself. Sofar the consensus seem to be the mRNA vaccines should proof effective.
Most mutations aren't viable. Given the low fidelity of RNA replication (at least compared to DNA replication) it's remarkable just how close each copy is in a large population. Only a few mutations prove to be viable. Much less prove to be strong enough to overpower the current population.
People appear to be expecting there will be "weaker" variant/strains/mutations of this virus as time goes on. I am not sure why this is the mainstream thought.
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.
IANAV: So, when someone gets visibly sick, they tend to get isolated from other people. That makes it more difficult for the virus to spread. So over time there's a slight advantage to variations of a virus that don't make as many people sick.
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.
> But COVID-19 also has a _very_ large incidence of asymptomatic transmission
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%)
Asymptomatic transmission might be not very high, but presymptomatic transmission is very high. It is well established fact, that people are the most contagious right before onset of the symptoms.Keep in mind that the symptoms might be very mild.
The most-efficiently-replicating strain is likely to dominate in the long-term. As such, there is essentially no evolutionary advantage to killing or harming humans outside of the goal of replicating more efficiently. (There is also no evolutionary disadvantage).
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 incubation and transmission of the corona virus is not tightly coupled to morbidity, this virus moves to another individual before debilitating symptoms occur.
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).
I don't know much, just read a few things here and there, but viruses can get less lethal as they mutate because a virus doesn't want to kill its host, it wants to spread. Killing the host usually prevents spread.
I don't think the virus "wants" anything at all, it's just that if the host dies fast there is no time to spread, so statistically speaking it is less likely to spread and survive.
What is the evolutionary value of killing the host (potentially) before transmission can occur? I’d have thought the sweet spot is weak enough to minimise fatality/maximise accidental transmission while strong enough to ensure minimal symptoms that result in increased transmission vectors (eg coughing)
> People appear to be expecting there will be "weaker" variant/strains/mutations of this virus as time goes on. I am not sure why this is the mainstream thought.
I remember the scientists telling us early on in the pandemic that mutations typically result in less lethal viruses.
I know that some people consider it poor practice to anthropomorphise virus particles, but isn't this just an abstraction - a reasonable illustration - of what is happening?
What would you say instead, to capture these ideas, that are equally clear to everyone?
How is this news at all? The virus has been mutating and throwing off different strains all along. There are entire websites devoted to tracking these, e.g., [1]
Perhaps this is just the normal operation of American media to exaggerate the negative side of the situation? [2]
It's news if there's anything notable about the strain. More deadly, faster spreading, potentialy resistant to the vaccines.
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.
The South African variant is almost certainly not spreading faster because of the variant but because there were super spreader events like recently 1000 people tested positive after going to a night club [1]. Indoor weddings, funerals, and other big events have contributed too. While people wear masks (badly) outdoors and in shops, I think the root cause is bars, clubs, shebeens, etc. The government is also reluctant to introduce a new lockdown for fear of the damage to the economy.
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.
The title requires context - although given recent events we can infer that it is referring to the specific mutation seen in the UK. This particular mutation is of note since it has postulated as being more transmissible than other variants.
It is difficult to know what sources of information to trust. I already have antibodies, and thought I would be ok for a while. If this is a new strain, how would they know to make a vaccine for it, and how many vaccines will I need each year?
Also, the article here says "case count". I'm really interested in the count of "excess deaths".
The current vaccine is a new technology, which codifies the spike protein in mRNA. SAR-COV-2 works by using their spike protein to attach to your body's ACE2 receptors, This new vaccine time is targeting something that is invariant and integral to SAR-COV viruses (the spike protein which gives it entrance) and almost certainly covers the new variant
I already have the antibodies (from June), so it seems I won't need that vaccine. Right?
Or in other words, my antibodies would almost certainly cover the new variant.
I'm also a lay person so take this with a grain of salt. There isn't evidence that this new variant can reinfect people who previously had covid and all the expert speculation I've heard is that it probably won't break out of immunity. It's better to be cautious, but also no need to think the worst
The genomes for all three viruses have been published so it's easy enough to find the differences. But that doesn't directly tell us why the fatality rates are different.
I don’t really understand why this is a “rule.” Say there’s two viruses and it takes both 3 weeks to run their course. They are both equally contagious during the 3 weeks, however the first virus results in death for 50% of those infected (50% recover after 3 weeks and are no longer contagious), and in the second the death rate is only 1% (99% recover after 3 weeks). Is such a virus not possible to exist?
the rule being discussed doesnt apply to a virus that reproduces and transmits to another host before causing illness.
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.
It's not too surprising to anyone following the events. Retroactive blood testing of donated blood should the original strain (the phrase original variant sounds like an oxymoron) having reached places like France and NY months earlier than we realized, certainly November if not September of 2018. The magic of the virus is its ability to travel and spread undetected due to asymptomatic carriers.
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.
Just wait until it mutates and starts killing kids. Kids are currently the last to be vaccinated. I know this is morbid but this does not bode well but there is precedent. Spanish flu first only killed the elderly and then on its return killed young adults and kids disproportionately. Now the Spanish flu was influenza and this is coronavirus but this specific coronavirus should not be underestimated. I’ve said this from the beginning and I hope I’m wrong.
There’s no evidence that it’s more deadly at this time.
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.”
I have found myself concerned about this as well (and thinking about what decision-making for parents must have been like in late summer when this characteristic started to become evident).
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.
Well OC43 has been around for over a century and never mutated to start killing kids. So why would this be virus do that? Your speculation seems uninformed.
There are two important things to temper how worried you should be:
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.
You shouldn't speculate about 1. especially as this is a virus that is new. It didn't have wave after wave where the "deadly" strains would lose out in evolution.
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.
It’s not remotely clear that this strain is easier to transmit. It’s entirely hypothesis and speculation.
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.
“Hypothesis with a small prior” is a fancy way of saying “speculation”.
There are literally dozens of strains on nextstrain that have rapidly grown to be the predominant strain in a region. That alone is not a strong indication of anything other than founder effect.
yes this is a property of influenza virus, however the influenza virus is very different from corona virus, in particular the cryptic incubation period of coronavirus that occurs before symptoms can alter the hosts ability to interact with other prospecific hosts.
it is worthy of note that one single point mutation in the influenza virus corresponded to high lethality.
>> 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.<<
This is a very poor way of looking at it. H1N1 is considered a subtype rather than a strain, and there are many H1N1 strains around. It makes more sense to think of the 1918 strain going extinct and some of quasispecies descendants of it persisting.
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.
Do you know this for a fact or is that just a plausible idea you came up with? It sounds plausible enough but it also sounds plausible that if symptoms were delayed even more or failed to show up at all it might be transmissible for longer, meaning that that there would still be selective pressure towards less virulent strains.
this is fact, this is evolution. when reproduction occurs this is success, this is fitness to reproduce. if a host is killed, or inconveinienced enough to lay ill and not contact others, that is a selective factor that favours reduction of morbidity. in the case of coronavirus reproduction and transmission occurs before morbidity occurs in the index host. there is no selective pressure to become less virulent. there is selective pressure to change host, to evade recognition by the immune system.
Note that here we're not talking about a single mutation but 17 non-synonymous (they change the protein) mutations with 3-4 with known effects on the interactions of the resulting proteins
What are you talking about? Sequence is unstable due to size? Coronavirus has proofreading mechanism that corrects most mutations due to errors, the estimate for mutation speed before this variant emerged was 2 mutations per month so this variant has ~10 months of evolution in them but probably evolved much faster for some reason. This is very much a surprise
The error rate is in terms of the number of nucleotides addended to the polymerizing RNA during replication
the mutation rate is primarily a result of RNA replication, _not_ time. this means more replication events leads to more "errors", this also means longer sequence has a higher rate of error than a shorter sequence. at a length of ~29k bp the coronavirus sequence is very error prone, so error prone that this is approaching the upper limit of stability.
it seems you are mistaking DNA proofreading for an RNA proofreading mechanism, which happens to be negative selection upon nonfunctional mutant/variant. there is no recognized enzymatic [rdRNApol] error correction associated with the coronavirus.
"the RNA polymerases of RNA viruses are the kings of errors – these enzymes screw up as often as one time for every 1,000 – 100,000 nucleotides polymerized. This high rate of mutation comes from the lack of proofreading ability in RNA polymerases. These enzymes make mistakes, but they can’t correct them. Therefore the mutations remain in the newly synthesized RNA." [0]
none of these error prone generated mutations are surprising, they are to be expected espescially when the virus is given opportunity to replicate at a high cyle rate.
this is very much not a surprise, if you are aware of the properties of +ssRNA virus.
you dont seem to understand either concept. mutation is passed from individuals by vertical or horizontal transmission. variation of a gene [alleles] are mutations, mutations are the index variation. mutation is a change in the gene sequence, this is variation, this has created a mutant, also known as a variant.
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.
Not horrible or shocking, but concerning. Mutation is expected but the more strains there are the more likely one turns out to be unaffected by the vaccine and we find ourselves back at square one.
there is considerable selective pressure upon the spike protien, very large changes to this protien are not frequently viable, as the virus would need to find a new trophic target or a new host altogether.
We are tracking these changes closely and concommitantly can change the sequence of mRNA, responsively, and pre-emptively if desired.
I would hope that they could add coverage for new variants to the mRNA vaccines without having to go completely back to square one. Do they have to do full 3 phase testing on the flu vaccine every year?
first issue here is the differences in terminology regarding strains, vs variants.
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.
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!