“Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage in the UK defined by a novel set of spike mutations”
Recently a distinct phylogenetic cluster (named lineage B.1.1.7) was detected within the COG-UK surveillance dataset. This cluster has been growing rapidly over the past 4 weeks and since been observed in other UK locations, indicating further spread.
Several aspects of this cluster are noteworthy for epidemiological and biological reasons and we report preliminary findings below. In summary:• The B.1.1.7 lineage accounts for an increasing proportion of cases in parts of England.
• The number of B.1.1.7 cases, and the number of regions reporting B.1.1.7 infections, are growing.
• B.1.1.7 has an unusually large number of genetic changes, particularly in the spike protein.
> Mutation N501Y is one of six key contact residues within the receptor-binding domain (RBD) and has been identified as increasing binding affinity to human and murine ACE2.
> The spike deletion 69-70del has been described in the context of evasion to the human immune response but has also occurred a number of times in association with other RBD changes.
> Mutation P681H is immediately adjacent to the furin cleavage site, a known location of biological significance....
> nucleotide changes on this branch are predominantly amino acid-altering (14 non-synonymous mutations and 3 deletions). There are 6 synonymous mutations on the branch. This is suggestive of a process involving adaptive molecular evolution
> These include spike position 501, one of the key contact residues in the receptor binding domain (RBD), and experimental data suggests mutation N501Y can increase ACE2 receptor affinity (Starr et al. 2020) and P681H, one of 4 residues comprising the insertion that creates a furin cleavage site between S1 and S2 in spike. The S1/S2 furin cleavage site of SARS-CoV-2 is not found in closely related coronaviruses and has been shown to promote entry into respiratory epithelial cells and transmission in animal models (Hoffmann, Kleine-Weber, and Pöhlmann 2020; Peacock et al. 2020; Zhu et al. 2020). N501Y has been associated with increased infectivity and virulence in a mouse model (Gu et al. 2020). Both N501Y and P681H have been observed independently but not to our knowledge in combination before now.
> deletion of two amino acids at sites 69-70 in spike ... arose in the mink-associated outbreak in Denmark on the background of the Y453F RBD mutation
> “If allowed to go unchecked, the new variant of the virus could increase the country’s R rate, which is estimated to be between 1.1 and 1.2, by 0.4 per cent.”
Maybe they meant to say 0.4, without any qualifier - i.e. that the rate went from 0.7-0.8 to 1.1-1.2? A change from the lower end of the old range to the higher end of the new range would match the 70% increase in transmissibility.
(though that would require an increase of almost 0.5)
Something strange was happening in the UK rates in the last few weeks. Despite a second lockdown, cases in London started increasing again, and areas in 'Tier 3' (highest tier restrictions) also started increasing cases post-lockdown. This was despite other areas continuing to drop cases despite having the same measures. Apparently the areas that had started rising were correlated with percentage prevalence of this new strain, which at the moment is known to be present in the UK, but might have come from abroad, or travelled already.
As a result of this, I can see the vaccination programme getting a huge rocket, as it looks like lockdown and highest restrictions aren't decreasing cases - which is potentially disastrous for containing the virus, and stopping the hospitals get overwhelmed at a time when they normally operate at full capacity.
Christmas relaxation rules have been cancelled in the UK, which has caused much disappointment to my family and friends. Understandable, but no less disappointing.
> as it looks like lockdown and highest restrictions aren't decreasing cases
This has been apparent since the beginning. It's a highly contagious seasonal virus.
When it declined in the northeast of the US as the spring led into summer, people proclaimed their expert advice was successful...ignoring that it's seasonal virus.
Cuomo wrote even wrote a freaking book about his success.
No that has not been apparent. The first lockdown got cases down to very low levels (10s/million/day). It turned around a sky-rocketing increase in cases - it's not like the seasons changed between April and May. The second lockdown in the UK was a tiered approach, and has managed the levels (at least up to 3 weeks ago) better than France, Belgium or Spain. Not quite as good as Germany or Italy, and nowhere near the Scandinavian countries (excluding Sweden).
Are you really trying to tell me that the variation in COVID rates is only down to seasons?
You should be smart enough to know that a respiratory virus could be seasonal but still spread throughout the year.
And the further complexity of being presented with this huge US graph, which in reality is the aggregated result of so many communities with varying levels of prevalence/previous exposure.
Did you see the Hope-Simpson figure? Texas is roughly 36N to 26N. That puts it close/within the tropical zone.
That zone has a relatively diffuse outbreak curve, seems like there's some type of subtle signal though, whereas the higher latitudes get walloped in the winter months and there's not much going on the rest of the year.
Surely you understand that seasons vary geographically? What's winter in Texas at best? 50F?
New York, California And Pacific Northwest also had summer spikes. Now they are experiencing winter spikes. Any seasonality that may exist naturally is made irrelevant by pandemic fatigue. People simply start ignoring the guidance after a few months. Cases go up until things get ‘scary bad’ and then people stay home again. That is why your suggestion that we all ‘self regulate’ is not a good one. It will just lead to endless, ‘weak’ lockdowns.
Correlation, not causation. It’s also known that people simply congregated outside their homes more during the NYC summer.
This is the problem with self-regulation. Not everyone is a doctor, so many people will incorrectly gauge their own risk of severe infection and/or transmission.
Just think about it, self regulation is the easiest government intervention (basically no intervention required). If that strategy worked, we would have seen at least 1 success by now. Sweden and Brazil had few (if any) restrictions and some of the highest death rates in their regions. Developing countries with poor governance and zero public health infrastructure are also struggling.
Yes, but look at the data. There are industrialized countries with less than 1/3 the per capita death rate of the US. Maybe you can’t ‘win’ but clearly you can do a better job than others. It’s a stretch and arguably fear-mongering to equate sensible policy to reduce death with authoritarianism.
Poor people around the world have been devastated by the majority position in public health policy.
A majority of people and the health establishment thought ventilators were a good idea; it turns out mortality dropped 30% during the time period that their use was stopped.
The people deciding things have very little gauge of the disastrous costs that they themselves do not have to suffer. Their social class precludes it by nature!
Are you an essential worker? Is that below you? The least advantaged are forced to risk their lives and are bearing the brunt of all these decisions.
The Pajama Class is waging class war, convinced they're right - when in fact they've blundered their way through this - shaming everyone who disagrees with them.
Make no mistake - the public policy decisions you're advocating favor the well-off.
Clearly it's a spectrum, not a binary. I doubt you'd say we shouldn't impose more precautions during an Ebola outbreak than we would during a normal winter cold & flu season.
Precautions are generally proportional to the risks involved. Personal responsibility ceases to be the only determining factor in what precautions to take when an irresponsible person imposes the consequences of their poorly judged actions on other people. Your freedom to swing your fist ends where my nose begins. Punching me in the nose isn't justifiable simply because I will, at some point, die regardless of your actions.
That said, it is a spectrum. Which means, if you want to avoid absurd extremes then you must draw a line somewhere on that spectrum. Assuming you don't espouse political anarchism or anarcho-capitalism, approaching me & swinging your fist at my nose while we're both walking down the street is would be on the wrong side of the line for pretty much everyone. If I approach you and tell you I'll stab you if you don't hand over your wallet then swinging your fist at my nose is on the other side of that line.
COVID is clearly more complicated because in addition to the above spectrum, there is the spectrum of a probability distribution that dictates the likelihood of spreading the virus if infected, and the likelihood of serious illness or death if infected by someone spreading the virus. Drawing the line between acceptable imposition of precautions is therefore much more complicated, and absent absurd extremes is necessarily going to be drawn somewhere that some subset believes is authoritarian, and others believe is too permissive & intrudes on their own freedom from the negative consequences of other people's choices.
In all cases though, if your concept of "No one “wins” against things like death, disease, etc." were to be the guiding force behind societal decisions, then literally any action is permissible.
What's permissible now is whatever doesn't harm or constrain upper classes.
We've decided that essential workers should work and the higher classes should be sheltered and they can dispatch the expendables to sustain themselves.
Your moral analysis is pretty much in support of whatever the Pajama Class decides is right.
My post was simply a discussion on the process of determining precautions, absent going to an extreme. It was not advocacy for the specific place on the spectrum where the line should be drawn. It was, in response to your comment, an observation that no matter where the line is drawn, there will be some who view it violates their freedom as too authoritarian, and others who believe it violates their freedom by allowing irresponsible decisions by others to impact them.
I won't go into the particulars of my own opinion on where the lines should be drawn except to say that I think some decisions have been bad, some have been okay, but that in general this is not a situation that lends itself to easy answers.
NYC is a prime example of also having non-seasonal factors: Through the early Fall, there was significant opportunity for true outdoor dining. As the weather got colder, that "outdoor" dining often took on the form of fully-enclosed tents that are nearly indistinguishable from dining indoors. Even with similar social-distancing requirements handed down by the state, even assuming people did not relax their guard, following the guidelines would still result in a different models of social behavior, more in-door gatherings that still met distancing guidelines, etc.
Not quite: you're correct about seasonality but seasonality is an issue to begin with because people are spending more time inside, in closed air systems. (Other factors as well). But that still requires people to mix about with each other. Things like eating in fully enclosed "outdoor" tents instead of true outdoor settings, family get togethers like Thanksgiving, etc. If people weren't going out & seeing each other, the virus wouldn't just appear in closed social networks.
You're also ignoring the Summer spike that occured as precautions were relaxed, at the same time that it gradually began making its way off of the coasts and into land-locked states, especially those that were generally skeptical of taking precautions to begin with, so decreases & spikes are not solely attributable to seasonal factors.
Yes I just watched Boris Johnson's announcement. I know there's a lot of criticism about his leadership, but I'm still glad they are following the science.
He's had a lot of criticism, but I don't think he has done too badly. And that's coming from someone who is normally left-leaning, and not a fan of him. There were definite mistakes at the beginning, and a blase attitude resulted in a bad first wave for the UK. It's still not completely clear why the death rate was so high - may be related to the way the coronavirus ripped through care homes early on, or simply because the UK could have locked down a week or two earlier. Not to mention the mess up with ventilators and PPE.
But since then, the UK has handled the second wave reasonably well. People aren't talking about the crazy high rates in France and Spain which were exceeding the US for much for time, and with a corresponding high death rate too. I don't know what's going on with Germany, but their previously pristine record looks like it's being shattered at the moment...
I think something changed after Boris went to hospital.
One wonders if the virus is now "airborne"? Is that something viruses can actually do, ontop of being passed on through water droplets after coughing/sneezing.
>One wonders if the virus is now "airborne"? Is that something viruses can actually do, ontop of being passed on through water droplets after coughing/sneezing.
It always has been. The virus is aerosolized through exhalation, and spreads much like secondhand smoke [0].
I remember a listening to a podcast interviewing a physician from a major hospital who made sure to explain the difference between an airborne pathogen and one that is respiratory active.
Jogging my memory. Airborne meaning a virus that a person exhales in an elevator (example) will still be present and transmissible x amount of time later. Respiratory active meaning transmissible by coughing/exhaling in the presence of someone else.
These are important distinctions if true and still relevant.
As far as I understand it lives in droplets heavier than air that fall to the ground in a matter of a few seconds. The next person entering the elevator won't breathe it. Truly airborne viruses can be lifted by regular air turbulences and travel kilometers before landing on someone else.
It was already detected in May, that subsequent dominant strains (remember, the virus mutated with every single generation, every 10 days) have much more deletions than mutations, and are thus as such much less dangerous and much more transmissible, as their hosts don't detect it. This time UK got their sensationalist headline. In fact those are more dangerous, R is higher, and mortality is very low and insignificant. But reaching the vulnerable better makes it more dangerous in the end.
I'm sure this is likely. It's quite concerning, as it may mean that we need a full lock-down (as in people not going to work) until we have a majority of the population vaccinated.
I don't think that's even possible. I read somewhere that just about 40% of the population has the type of job that can be done from home. A lot of the rest is sitting at home due to restaurants, stores closing, but a fair amount of people is required to take care of the ones at home. Bringing them stuff, transporting it all.
I doubt we can win from a virus other than adapting our immune system (and some people dying). Even vaccination might just encourage the virus to evolve.
Important to note that this has been known since early summer. There are multiple strains of SARS-Cov-2, and the original Wuhan strain is almost nonexistent in the US at this point. The mutated strain, while much more infectious, is actually much less deadly at the same time.
Most of this isn’t true. This particular mutation is relatively new, only having been spreading much in the last few months. Also, there is little to no evidence that this strain is more or less deadly than any other strain, though there does seem to be indications that it is more infectious.
R number changed when that one nucleotide change increased the number of spikes on the surface by 5-8X. This modification was seen occurring in multiple locations, so maybe not a single linage change. Maybe more like an increase in probability that one nucleotide would "flip" in multiple organisms, with enough organisms at hand.
The spike itself attacks/props open ACE2 receptors, like those found on your eyes, and is mostly encoded using ~39 some odd nucleotides borrowed from a South Asian fish. Plotting the number of "words" repeated in the genome (~30K nucleotides) yields a phi-like curve, with the words/codons in the spike occurring more statistically significantly than others.
The mutation is not expected to cause more severe cases, but is more infectious due to more spikes needing to be neutralized to fend off the infection. In bloodstream plant lectins have been shown to be effective at this, as well as llama nanoparticles.
All of this is Googlable using the right key terms.
> Kawaoka and Halfmann contributed their unique coronavirus study model, which uses hamsters. The University of Wisconsin-Madison team -- including Shiho Chiba, who ran the hamster experiments -- performed replication and airborne transmission studies with both the original virus and the mutated version created by Baric and Hou.
> They found that the mutated virus not only replicates about 10 times faster -- it's also much more infectious.
> Hamsters were inoculated with one virus or the other. The next day, eight uninfected hamsters were placed into cages next to infected hamsters. There was a divider between them so they could not touch, but air could pass between the cages.
> Researchers began looking for replication of the virus in the uninfected animals on day two. Both viruses passed between animals via airborne transmission, but the timing was different.
> With the mutant virus, the researchers saw transmission to six out of eight hamsters within two days, and to all the hamsters by day four. With the original virus, they saw no transmission on day two, though all of the exposed animals were infected by day four.
> "We saw that the mutant virus transmits better airborne than the [original] virus, which may explain why this virus dominated in humans," Kawaoka said.
If some relevant mutation happens and we are forced to update the vaccines, which seems to not be so difficult for the new mRNA vaccines (pfizer and moderna ones), will it need to pass through all clinical tests again ?
I mean if the virus mutates at a speed like this it may be useful to allow mRNA as a platform (at least for this virus). So that we can get the vaccines out faster than the virus mutates. (Assuming effectiveness of the vaccine is impacted)
Highly unlikely. You overestimate our ability to genetically edit things and predict what the outcome will be. The virus is mutating at a rate of about one mutation/month - that's fairly standard.
even if, the virus was engineered, the mutation rate would incur deviation from the engineered character, at the same rate as we are seeing with this naturally occuring virus.
An engineered SARS would quickly be subject to selection.
Here’s a better one:
“Update on new SARS-CoV-2 variant and how COG-UK tracks emerging mutations” Dec 14, 2020 https://www.cogconsortium.uk/news_item/update-on-new-sars-co...
Edit: Here’s a report:
“Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage in the UK defined by a novel set of spike mutations”
Recently a distinct phylogenetic cluster (named lineage B.1.1.7) was detected within the COG-UK surveillance dataset. This cluster has been growing rapidly over the past 4 weeks and since been observed in other UK locations, indicating further spread.
Several aspects of this cluster are noteworthy for epidemiological and biological reasons and we report preliminary findings below. In summary: • The B.1.1.7 lineage accounts for an increasing proportion of cases in parts of England.
• The number of B.1.1.7 cases, and the number of regions reporting B.1.1.7 infections, are growing.
• B.1.1.7 has an unusually large number of genetic changes, particularly in the spike protein.
https://virological.org/t/preliminary-genomic-characterisati...