Covid Mutations

[elbows]

As anticipated, and now if verified, potentially the real fun begins.

Exclusive: Two variants have merged into heavily mutated coronavirus

The UK and California variants of coronavirus appear to have combined into a heavily mutated hybrid, sparking concern that we may be entering a new phase of the covid-19 pandemic

www.newscientist.com

I wonder how much public awareness of recombination there is. Its something I mostly only heard about when researching flu and pandemics a long time ago, and I used to find it a bit annoying that some scientists thought they spotted its fingerprints all over the place, whilst others were rather dismissive and tended to downplay how much of a role it had. But my knowledge on that is rather old and very incomplete, so I can at least look forward to the opportunity for humanity to understand it better and form some consensuses on its role with this pandemic virus and related coronaviruses.

 

[yield]

Depressing.

Very

 

[Flavour]

Yeah this is potentially a massive disaster but the lesson needs to be learned and super hardcore lockdowns need to be enforced where the new recombinant is present to prevent its spread otherwise this thing will just never ever end

 

[prunus]

Yeah this is potentially a massive disaster but the lesson needs to be learned and super hardcore lockdowns need to be enforced where the new recombinant is present to prevent its spread otherwise this thing will just never ever end

Hang on hang on - all this is saying is that recombination, as expected, has now been demonstrated happening. There’s nothing in this to panic about - the particular new recombinant isn’t associated with any worse outcomes, and is in fact similar to other variants that are out there (in terms of the selection of mutations it exhibits).

Recombination just allows mutations to spread faster, it doesn’t make them intrinsically worse. It’s very likely that several of the mutations already observed are the result of recombination events of one type or another - it’s just now that we have seen it with the required level of evidence to be able to say “yes it’s definitely happening [as expected]”.

 

[elbows]

I'm also far from convinced that variant surveillance is timely enough to be able to react in a way that could hope to suppress the strains. I'd be more confident about other approaches that gives the virus less opportunities for so many variations to pop up in the first place.

 

[2hats]

A study (preprint here) of 65 individuals investigating the evolution of their viral trajectories, in particular focussing on B.1.1.7 versus non-B.1.1.7 variants, through repeated daily testing. It found that B.1.1.7 has a longer duration of infection and clearance compared to other variants (overall viral load broadly similar). That is perhaps contributing to transmission. For B.1.1.7 you would need significantly more than 10 days of isolation to limit spread (~17 days to isolate just over 90% of cases).

 

[2hats]

By constructing ancestral recombination graphs likely multiple recombination events, in recently taken samples (November 2020) of B.1.1.7 and B.1.351, are identified. This and prior work suggest ongoing recombination in SARS-CoV-2 variants.

Due to the high level of homogeneity between sequences, the effects of recombination will be either undetectable or indistinguishable from recurrent mutation in the majority of cases. However, as genetic diversity builds up over longer timescales, the effects of recombination may become more pronounced. Particularly in light of the recent emergence of new variants, the rapid evolution of the virus through recombination between strains with different pathogenic properties is a crucial risk factor to consider.

DOI: 10.1101/2021.01.21.427579.

 

[Supine]

I like the names for the changes

 

[2hats]

The Economist has an overview article on recent variants:

The same covid-19 mutations are appearing in different places

Convergent evolution may make travel restrictions redundant

www.economist.com

which includes a nice graphic of the 'family tree' illustrating PANGO lineages.

Accessible article link.

And a preprint focussed on the appearance of the E484K variant B.1.526 in New York, mentioned above, the incidence of which has been growing in recent weeks.
DOI: 10.1101/2021.02.23.21252259.

 

[2hats]

PHE reports 3 cases of P.1 (Manaus, Brazil) identified in the UK (south Gloucestershire). Three more have been identified in Scotland.

Confirmed cases of COVID-19 variants identified in UK

Latest updates on SARS-CoV-2 variants detected in UK.

www.gov.uk

 

[2hats]

From modelling of Brazilian genomic and mortality data, the P.1 variant is estimated to be around 1.4-2.2x more transmissible than, and able to evade 25-61% of protective immunity elicited by infection with, previous non-P.1 SARS-CoV-2 lineages.


Preprint here.

 

[elbows]

PHE reports 3 cases of P.1 (Manaus, Brazil) identified in the UK (south Gloucestershire). Three more have been identified in Scotland.

Confirmed cases of COVID-19 variants identified in UK

Latest updates on SARS-CoV-2 variants detected in UK.

www.gov.uk

They dont know where one of the England cases is.

The third case identified in England is not linked to the other two cases and the whereabouts of that person are still not known.

PHE said the person did not complete their test registration card so follow-up details are unavailable.

Officials are asking anyone who took a test on 12 or 13 February and who has not received a result or has an uncompleted test registration card to come forward immediately by calling 119.

Covid-19: Brazil 'variant of concern' detected in UK

Six cases of the variant first detected in Brazil have now been found in England and Scotland.

www.bbc.co.uk

 

[elbows]

Something I feel like quoting from a 10th February SAAGE modelling group consensus statement:

Likely impact of more transmissible or immune escape variants

As immunity accumulates in a population, the potential for the virus to evolve to overcome it increases. The higher the prevalence, the greater the probability that any new variant might escape the current immunity; this evolution of immune evasion can happen in the absence of vaccine-induced selection pressure (for example the substitution E484K seen in SARS-CoV-2).

As more people are vaccinated, the relative advantage of any such escape mutant increases.

Any period of high prevalence combined with accumulating immunity (either through infection or vaccination) provides both the selection pressure and the opportunity for escape mutants. A strategy of high prevalence with R around 1, where reducing transmission relies on vaccination to allow loosening of measures, is a more dangerous approach, with respect to vaccine escape.

The UK, however, is not a closed system and the relative risk of an escape mutant arising from local transmission versus it being introduced from other countries needs to be considered, as there may be repeated introductions from elsewhere, despite improved quarantine. The UK is a world leader in sequencing and so is likely to identify any new variants quickly; this may not be the case in other countries.

It is highly likely more variants (both homegrown and imported) will evolve; if prevalence is low, it will be considerably easier to manage these.

https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/963368/S1096_SPI-M-O_Consensus_Statement_on_COVID-19.pdf

 

[purenarcotic]

Christ this is just never going to end is it.

 

[elbows]

Christ this is just never going to end is it.

I wouldnt like to predict either way. I dont want to spend too much of my energy fretting at times when I could be taking a happier view, but I also dont want giant setback to sneak up on me or anyone else, I'd rather bake them in to my future expectations without going so far as to consider them inevitable.

 

[Riklet]

How the fucking fuck are they still letting people in from countries with P1 variant... or indeed, bloody Brazil.

Insane.

 

[weltweit]

How the fucking fuck are they still letting people in from countries with P1 variant... or indeed, bloody Brazil.

Insane.

I gather they are letting British nationals return from Brazil and have recently required they [1] quarantine in hotels local to the airport.

[1] I don't know when exactly that rule came into force.

 

[William of Walworth]

Are people being subject to quarantine when they travel to the UK from all world nations?? Or just from some?

That question is surely relevant, as the 'Brazil variant' is present in a good few nations, or so I read today ...

 

[zahir]

Interview with Deepti Gurdasani about variants.

A scientist’s opinion: Interview with Dr Deepti Gurdasani about SARS-CoV-2 mutations - ESMH

Dr Deepti Gurdasani ’s background is as a clinical epidemiologist and statistical geneticist. After completing her clinical training in internal medicine

sciencemediahub.eu

 

[2hats]

In some areas of France B.1.351 and P.1 variants constituted in excess of 30% of recorded cases last week.

 

[elbows]

16 cases of B.1.1.318 identified and made a Variant Under Investigation with the tag VUI-202102/04.

Confirmed cases of COVID-19 variants identified in UK

Latest updates on SARS-CoV-2 variants detected in UK.

www.gov.uk

Cases of this variant, understood to have originated in the UK, were first identified on 15 February through genomic horizon scanning. All individuals who tested positive and their contacts have been traced and advised to isolate.

Following assessments, the variant was designated a VUI on 24 February. It contains the E484K mutation, which is also found in 2 existing VUIs present in the UK, but does not feature the N501Y mutation, present in all variants of concern (VOCs).

The addition of this variant as a VUI means there are now a total of 4 VUIs and 4 VOCs currently being tracked in the UK.

Also from the same update:

Cases with no travel links
As of 3 March:

• a total of 59 cases of the variant VOC-202012/02, first detected in South Africa, have been found in England where no travel links could be established
• a total of 26 cases of the variant VUI-202101/01, the P2 variant first detected in Brazil, have been found in England where no travel links could be established

 

[2hats]

16 cases of B.1.1.318 identified and made a Variant Under Investigation with the tag VUI-202102/04.

Previously also seen in the US, Nigeria, Norway, Japan, Switzerland and Finland. Features spike mutations D614G, D796H, E484K, P681H, T95I, and Y144 deletion.

 

[2hats]

Immune response to B.1.351 found to be cross-reactive to both earlier variants and P.1 suggesting the B.1.351 spike might be a good choice as a foundation for vaccines moving forward (response to B.1.1.7 previously found to be poorly cross-reactive).

DOI: 10.1101/2021.03.06.434193.

 

[2hats]

On the role and importance of T cell response, in particular with respect to variants.

First, an important paper: T cell response across variants demonstrated to be maintained and broadly similar, suggesting T cell response to any given variant should also provide a degree of protection against severe disease that could be provoked by any other variant. This is based on a comprehensive analysis of SARS-CoV-2-specific CD4+ and CD8+ T cell responses from seropositives (11 individuals, 21-57 years) who had been variously infected with an earlier variant or B.1.1.7, B.1.351, P.1, or B.1.429, as well as recipients of mRNA-1273 and BNT162b2 vaccines (sampled around 2 weeks after second dose; 19 individuals, 22-67 years). It was found that the vast majority of SARS-CoV-2 T cell epitopes are not affected by the mutations across the variants, demonstrating that CD4+ and CD8+ T cell responses in seropositives and vaccinees are not substantially evaded by those variants. Seropositive (left) and vaccinee (right) responses:

DOI: 10.1101/2021.02.27.433180.

Second, related, SARS-CoV-2 isolates demonstrate (in vitro) the ability to escape CD8+ T cell surveillance through point mutations. This highlights the potential capacity of this virus to, given sufficient time (for example, in chronic episodes), evade adaptive immune responses.
DOI: 10.1126/sciimmunol.abg6461.

 

[weltweit]

It's no good 2hats I still don't understand what those charts mean.

 

[2hats]

Essentially the responses are broadly consistent across the variants (keyed by colour). (Horizontal in upper panels, similar across lower panels).

 

[2hats]

The latest PHE technical briefing (number 7) on SARS-CoV-2 variants of concern has been released. It covers
VOC 202012/01 (B.1.1.7), VOC 202102/02 (B.1.1.7 cluster with E484K), B.1.1.7 with S494P Clade, VOC 202012/02 (B.1.351), VOC 202101/02 (P.1), VUI 202101/01 (P2), VUI 202102/01 (A.23.1 with E484K), VUI 202102/03 (B.1.525), VUI 202102/04 (B.1.1.318), VUI 202103/01 (B.1.324.1 with E484K). Small numbers (107 cases) but notably the case fatality rate for B.1.525 reported as 3.7% (cf 2.6% for B.1.1.7, 2.3% for B.1.351).

 

[elbows]

The latest PHE technical briefing (number 7) on SARS-CoV-2 variants of concern has been released. It covers
VOC 202012/01 (B.1.1.7), VOC 202102/02 (B.1.1.7 cluster with E484K), B.1.1.7 with S494P Clade, VOC 202012/02 (B.1.351), VOC 202101/02 (P.1), VUI 202101/01 (P2), VUI 202102/01 (A.23.1 with E484K), VUI 202102/03 (B.1.525), VUI 202102/04 (B.1.1.318), VUI 202103/01 (B.1.324.1 with E484K). Small numbers (107 cases) but notably the case fatality rate for B.1.525 reported as 3.7% (cf 2.6% for B.1.1.7, 2.3% for B.1.351).

That document may contain traces of copy & paste errors. As if trying to read documents where all the names are numbers is not already hard enough.

VUI 202102/03 (B.1.525) is lineage B.1.525 (first sequence detected in the UK in February 2021). The complete mutation profile of VUI 202102/01 (A.23.1 with E484K) is shown in Table 12 and genomic case definitions in Table 13.

Table 12. VUI 202102/03 (B.1.525) Variant defining mutations

 

[elbows]

At least they didnt mess around with obfuscating this bit:

Δ144 is an antigenic escape mutant and is highly associated with virus replication in immunocompromised patients.

 

[2hats]

A variant previously identified (DOI: 10.1101/2021.03.03.21252812) in the Philippines, P.3 (also known as PHL-B.1.1.28) has been spotted in the UK. PHE report two cases. It features E484K, N501Y, and P681H mutations in the spike (plus a number of other amino acid replacements and deletions). May be biologically significant so PHE have provisionally labelled it VUI-21MAR-02.

Meanwhile, in Brittany, the French authorities report several cases of a new variant (9 mutations in the spike) belonging to clade 20C (previously predominately seen in North America).