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Covid Mutations

UK variant (B.1.1.7) detected in Switzerland (2 imported cases):
and in Germany (one import from the UK):
 
Separate new variant detected in Nigeria - has the P681H mutation (potentially biologically important) in common with the B.1.1.7 lineage (missing the N501Y and 69/70 deletion). Either (more likely) arose independently or (less likely) may possibly be an early branch from B.1.1.7 arising from travel import as the samples were taken in August and October. Not possible to characterise impact on transmissibility yet but this variation may be helpful in helping characterise individual roles of particular mutations.
 
Five imports of B.1.1.7 from returning travellers from the UK to Japan (age range 10-60, one symptomatic) arriving in the last week at Haneda and Kansai airports.
Minister of Health, Labor and Welfare Tamura announced at a press conference after 9 pm on the 25th that five people who returned from the United Kingdom were confirmed to be infected with the mutated new coronavirus. This is the first time that a person infected with a mutated virus has been confirmed in Japan.
 
2hats do you know if there is any work ongoing to find patient zero of the UK variant? Europe seems to be comfortable that the variant originated here but I am not so sure. We detected it first but that does not mean it originated here.

It's impossible to find patient zero and probably not fair on the individual. There are multiple separate developments which are the same or similar anyway.
 
Would be a struggle because, though we have sequenced more than other country by far, it's a small fraction of cases.
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Yeah I wouldnt expect to find patient zero but I suppose my mind leaves open the possibility that if first cases were picked up via genomic surveillance of a hospital outbreak then there is a chance of getting an origin story thats a bit more concrete than is normally managed. But since I dont have access to everything authorities know about individual cases, there are too many holes in the picture I have, and I would assume a very low chance of getting much more on this front, meaning we are more likely to have to put up with a vague hypothesis or two instead.

For example here are some quotes from that ECDC document I linked to the other day.

Phylogenetic analysis (Figure 4) reveals that there are very few intermediary forms between this variant and other circulating viruses reported to GISAID. The cluster differs by 29 nucleotide substitutions from the original Wuhan strain, which is higher than current molecular clock estimates of around two substitutions per genome per month [10]. The fraction of non-synonymous mutations in the spike protein for the variant is much higher than expected from random mutations (27% of the 22 substitutions acquired since the Nextstrain clade 20B common ancestor are located in the S-gene, which comprises 13% of the viral genome, and all of these substitutions are non- synonymous).

The unusually high number of spike protein mutations, other genomic properties of the variant, and the high sequencing coverage in the UK suggest that the variant has not emerged through gradual accumulation of mutations in the UK. It is also unlikely that the variant could have arisen through selection pressure from ongoing vaccination programmes as the observed increase does not match the timing of such activities.
One possible explanation for the emergence of the variant is prolonged SARS-CoV-2 infection in a single patient, potentially with reduced immunocompetence, similar to what has previously been described [17,18]. Such prolonged infection can lead to accumulation of immune escape mutations at an elevated rate.
Another possible explanation could be adaptation processes in a virus that occur in a different susceptible animal species and is then transmitted back to humans from the animal hosts. This led to the emergence of a variant with multiple spike protein mutations (including RBD mutation Y453F and deletion 69-70) in Denmark during transmission among mink [19]. Several different spike protein mutations associated with mink have also been described in the Netherlands [20]. The UK has reported to ECDC and the WHO Regional Office for Europe that there is no clear epidemiological link to animals for VUI 202012/01, so this explanation is less likely for this variant [1].
Lastly, it is also possible that the variant has emerged through circulation in countries with no or very low sequencing coverage. This hypothesis is less plausible, however, as random mutations acquired during circulation of the virus would not explain the unusually high proportion of spike protein mutations, and undetected circulation for a long enough time for the high number of mutations to accumulate (around 10 months according to current molecular clock estimates) is also not very likely due to global travel patterns.
South Africa reports through the GISAID EpiCoV database [11] and a public press release [21,22] a similar rapid increase since October of a variant with the spike protein mutation N501Y, two additional RBD mutations and multiple additional spike protein mutations. This variant has no close evolutionary relation to VUI 202012/01 but demonstrates that the emergence of successful variants with similar properties may not be rare.

 
First case of B.1.1.7 now sequenced in France.

e2a: Confirmed. Sample taken a week ago from an individual in their 30's in western France.
 
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B.1.1.7 also now confirmed in one case in Israel and two cases in Hong Kong, samples collected over the last 1-3 weeks.

Also just noticed one case in Gibraltar.
 
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An uptick in S gene dropouts in recent US SARS-CoV-2 RT-PCR testing has been noted which may well indicate the H69/V70 double deletion is on the march there. This in turn might be indicative (in the absence of more extensive genomic sequencing) that B.1.1.7 is starting to take a hold.
 
Preprint on the details of the PCR S-gene dropout associated with B.1.1.7/VOC 202012/01. That a cluster of such observations correspond "to a conservative estimate of a significantly larger population of infectious subjects that have an increased viral load up to 10,000-fold higher" than the previous dominant UK variant.
DOI: 10.1101/2020.12.24.20248834
 
Two important new preprints concerning B.1.1.7. Both essentially confirm the new variant as around 50% more transmissible than previous variants and that recent 'lockdowns' have been insufficient to curb it. Indeed, B.1.1.7 flourished whilst other variants were suppressed.

New Imperial report. All regression models, at all spatial resolutions, with different target combinations, suggest an increase in R of ~0.5.

Second, a preprint from EMBL using a Bayesian approach to model positivity rates amongst lineages. Their findings were very similar in that the best model fit indicates that, during the recent 'lockdown', the new variant had R~1.25 whilst previous variants had R~0.85.
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Two important new preprints concerning B.1.1.7. Both essentially confirm the new variant as around 50% more transmissible than previous variants and that recent 'lockdowns' have been insufficient to curb it. Indeed, B.1.1.7 flourished whilst other variants were suppressed.
..
This is what concerns me, that current "hands face space" and 15 minutes at 2m might not be sufficient defence against B.1.1.7
 
Quick question 2hats or anyone qualified.

The virus mutated, somewhere, to B.1.1.7. This then gets spread about by travel and contact.

But is it possible the virus mutated to B.1.1.7 in more than one place? Thus negating the need for say a traveller from the UK to spread it to Canada, for example.

Is that clear? I'm asking does the mutation, for a particular mutation, only ever take place once and then get spread? Or can this same mutation happen in two totally separate places in the world?

TIA.
 
Quick question 2hats or anyone qualified.

The virus mutated, somewhere, to B.1.1.7. This then gets spread about by travel and contact.

But is it possible the virus mutated to B.1.1.7 in more than one place? Thus negating the need for say a traveller from the UK to spread it to Canada, for example.

Is that clear? I'm asking does the mutation, for a particular mutation, only ever take place once and then get spread? Or can this same mutation happen in two totally separate places in the world?

TIA.

A mutation can happen independently in a number of places, absolutely. Some mutations are more likely to occur than others (due to details about how the RNA is transcribed), and those are very likely to occur multiple times. The variant under examination though I think has 17(?) mutations, which makes the chances of all 17 occurring independently significantly lower - I don’t know if they are tracking all 17 though (I think some are thought to be biologically neutral).

Techniques of molecular phylogenetics and biogeography will be used to decide whether a particular variant cropping up in a particular geographical location is more likely to have evolved from a local strain, or been imported, by the number (and sometimes type) of changes needed to get to it from the previous local strains. One assumes the more likely set of events is the one that happened. It’s important to remember that this is just probabilistic though - it’s not always what actually happened (the principle of parsimony is what it’s called).
 
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23 mutations. Perhaps statistically unlikely to have risen in multiple locations by pure chance than if there were the same selection pressures/circumstances in disparate locations with large case populations, some high viral load and extended duration.
 
Exactly, the number of mutations that are involved in this strain is one of the red flags that made them sit up and take notice, and its also useful when trying to construct some reasonable assumptions about the histoery of this strain. Its also one of the reasons why they think this strain may have arisen in an immunocompromised patient who remained infectious for a long period, since the number of mutations involved exceeds that mutation rate they'd normally expect to see with this sort of virus.

As for whether they are tracking all the mutations, yes, all this detail is, like all the rest of the genomic info, available in the worldwide databases of different samples and strains genomes. So they are part of the fingerprint that is now used to look for this strain. This is separate to any analysis of what effect each mutation has, where some of them are indeed assumed to be of much less relevance. And then there is the other form of tracking which is quicker/easier than proper genomic analysis - one where the inability of some common tests to detect the S part of the new strain virus due to some spike mutations enables this s-dropout to be used as a proxy for the new strain being involved. This is the method being used to quickly build a rough picture of the extent of the spread of the new strain in different places. That method also reveals something about the nature of individual mutations having popped up lots of times independently in the past in versions of the virus that arent changed in all the other ways that allows them to be labelled as the new variant. In other words, they have long seen some percentage of their samples that didnt trigger the spike part of their test, as a result of a mutation. It was only when this phenomenon was associated with the new variant and crucially when levels of prevalence of the new variant rose dramatically to a level that showed up at high levels well beyond all the other s-dropout causing mutations that they were able to use the s-dropout rate as a proxy indicator of the new variant.

That was a bit of a mouthful so here is some text from an early ONS analysis. It indicates that there are other reasons why S-gene dropout can be picked up other than the new variant, and it was only after a certain date that they think it becomes a reliable indicator, because the signals at that point had risen far above the previously seen stuff that can be written off as background noise.

The new variant of COVID-19 has genetic changes in the S gene. This means the S-gene is no longer detected in the current test, and cases that would have previously been positive on all three genes are now positive only on the ORF1ab and the N gene (not the S gene).

There are also other reasons why a swab may be positive for only these two genes, including lower viral load in the sample, which is why we have always seen a small percentage of this type of positive result. We have been advised that the dropping of the S-gene became a reliable indicator of the new variation in COVID-19 from mid-November (18th November in the attached Table). Prior to that, the data should not be read as being an indicator of the variant. However, we have published a fuller series for transparency.

From the results tab of the spreadsheet at Percentage of COVID-19 cases that are positive for ORF1ab and N genes - Office for National Statistics
 
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