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Covid Mutations

Turns out to have been speculation by Birx, apparently.

Its not good for credibility when authorities that failed to control their outbreaks and are suffering badly in the middle of winter tries to explain their nasty curves by blaming a new variant without any proper evidence. The curve simply looking much worse than they'd have liked to see is entirely insufficient, but apparently its just too tempting for them to resist seeding such narratives.

I'm hoping my own thoughts on the UK side of things are helped along by the s gene dropout figures over the next few weeks. So far I consider that there are a few compelling nuggets in such data, but also some contrary indicators, especially recently.
 
New mutation, related to B.1.1.248 lineage, identified in Japan, apparently an import from Brazil (4 cases). Features N501Y and E484K mutations in common with 'SA' variant but with other mutations ('UK' variant doesn't feature E484K).
Somewhat related preprint - a case of a B.1.1.248 reinfection (after 5 months) in Brazil - DOI: 10.20944/preprints202101.0132.v1
 
Confirmed reinfection in the UK by a different variant (B.2 first, then B.1.1.7), after just over 8 months. Patient was a 78 year old with type 2 diabetes, no immunosuppression. First episode mild, second critical/life threatening. The patient's antibody levels were regularly monitored after the first infection and antibodies to SARS-CoV-2 were present shortly before the onset of the second infection. Raises questions about immune and vaccine escape and possibility of reinfection.

DOI: 10.1093/cid/ciab014
 
LSHTM analysis (not yet peer reviewed) of the 501Y.V2/B.1.351 variant through modelling the South African pandemic. Either it is 1.50 (95%CI: 1.20-2.13) times as transmissible as previously circulating variants, or if it is as equally transmissible as previous variants then it evades 21% (95%CI: 11-36%) of previously acquired immunity. Fairly likely the reality lies somewhere between these (somewhat increased transmission and somewhat increased immune escape) and it represents an additional public health problem. There is some evidence for increased severity but the uncertainty in that is substantial.
 
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A new variant identified in Brazil (Manaus) which has turned up in 46% of samples collected over two weeks in December. With biologically significant mutations E484K, K417T, and N501Y it has been declared as a new lineage P.1 (descendent of B.1.1.28). Extensive local transmission points to an independent evolution, but some key commonalities in spike mutations with B.1.1.7 and B.1.351 "raises concern about convergent evolution to a new phenotype, potentially associated with an increased propensity for re-infection of individuals".
 
Looks like naming strategies are evolving to improve communication in how mutations are evolving:

 
A new preprint investigates the effect of recently seen mutations on ACE2 affinity.

501Y seen in the B.1.1.7 (UK) variant exhibits 2.5x affinity compared to previous variants. The 501Y plus E484K mutations seen in B.1.351 and B.1.1.248, P.1 (SA and new Brazilian variants) exhibit 13x affinity.

But it is not yet clear as to the implications of this for transmissibility/pathogenesis, as a tighter binding and other mutations in those variants, in tandem with E484K, might even inhibit transmission (this has been seen in some other combinations of mutations).
DOI: 10.1101/2021.01.06.425392
B.1.1.248, P.1 are clearly variants to keep an eye on and require further analysis.
 
... potentially associated with an increased propensity for re-infection of individuals".

Some evidence of that in this paper.
A 37-years-old healthcare worker resident in Northeast Brazil presented two clinical episodes of COVID-19 in June and October 2020, that were confirmed by RT-PCR in samples collected 116 days apart. Whole-genome sequencing revealed that the two infections were caused, respectively, by the two most prevalent SARS-CoV-2 Brazilian lineages B.1.1.33 (primo-infection) and B.1.1.28 (reinfection).

I'm guessing this is the same case/patient and someone's got the age wrong. ?
A 45-year-old female healthcare executive, resident in Salvador, Bahia state, Northeast Brazil, with no comorbidities, presenting symptoms of viral infection on two occasions (May 26, 2020 and October 26, 2020).
In both occasions, results of RT-PCR tests targeting 3 genes (N, E and RdR) were positive for SARS-CoV-2 in nasopharyngeal samples.
Sequencing was conducted on the two nasopharyngeal swabs, sample A was identified as B.1.1.33 lineage and sample B as B.1.1.248, a lineage derived from B.1.1.28, recently identified in Brazil. Phylogenetic analysis, of the two newly whole genome sequences compared with contemporaneous sequences from Brazil clearly demonstrated that the two COVID-19 episodes, separated by a 147-day interval, were indeed caused by different SARS-CoV-2 lineages, confirming reinfection.
 
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Some evidence of that in this paper.
See previously second reference in post #159. E484K has demonstrated degrees of immune escape in this and the "SA" variant and in the lab.
 
Some evidence of that in this paper.
Doesn't look good that you can be infected by one strain and then later by another.
 
Its pretty consistent with pre-pandemic knowledge. Whats different this time is that we will get much more research into the underlying factors that contribute to waning coronavirus immunity. ie will will learn more about how much mutations contribute to that picture, and how much waning immunity within an individuals body contributes.
 
Two new US variants reported, identified in Columbus, Ohio. One, COH.20G/501Y, includes the N501Y mutation seen in 20B/501Y.V1 aka VOC 202012/01 (B.1.1.7, the "UK" variant) and 20C/501Y.V2 (B.1.351, the "SA" variant). The other is reported as having three mutations in the spike. No details yet.
e2a: One of these variants looks like it has mutations Q677H (spike), A85S (matrix), D377Y (nucleocapsid).
 
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A new preprint investigates the effect of recently seen mutations on ACE2 affinity.

501Y seen in the B.1.1.7 (UK) variant exhibits 2.5x affinity compared to previous variants. The 501Y plus E484K mutations seen in B.1.351 and B.1.1.248, P.1 (SA and new Brazilian variants) exhibit 13x affinity.

But it is not yet clear as to the implications of this for transmissibility/pathogenesis, as a tighter binding and other mutations in those variants, in tandem with E484K, might even inhibit transmission (this has been seen in some other combinations of mutations).
DOI: 10.1101/2021.01.06.425392
B.1.1.248, P.1 are clearly variants to keep an eye on and require further analysis.
One of the "Brazilian" variants already circulating in the UK.


e2a: analysis of the phylogenetic tree indicates the variant now found in the UK is not the B.1.1.248 lineage.
 
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Two new US variants reported, identified in Columbus, Ohio. One, COH.20G/501Y, includes the N501Y mutation seen in 20B/501Y.V1 aka VOC 202012/01 (B.1.1.7, the "UK" variant) and 20C/501Y.V2 (B.1.351, the "SA" variant). The other is reported as having three mutations in the spike. No details yet.
e2a: One of these variants looks like it has mutations Q677H (spike), A85S (matrix), D377Y (nucleocapsid).
The preprint is now up
 
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The "Brazilian" variant in the UK, mentioned earlier Friday, is the P.2 variant (a descendant of B.1.1.28), with an E484K mutation. 7 cases were detected amongst samples taken in December. It has been spreading in Rio de Janeiro State and has been associated with reinfections.
 
2hats what are the chances of a variant which could defeat the immunity afforded by the 3 current UK vaccines?

I understand the Pfizer vaccine can be changed quickly, what about the Oxford/Astra Zeneca one?
 
2hats what are the chances of a variant which could defeat the immunity afforded by the 3 current UK vaccines?
Quite possible it will happen sooner or later, though likely in degrees of reduction of efficacy rather than all out failure. More likely to happen the longer the virus is left to circulate in large populations unchecked.
I understand the Pfizer vaccine can be changed quickly, what about the Oxford/Astra Zeneca one?
Similar timeframe - synthesise new DNA, just like RNA for Pfizer, Moderna. But then they all need to convince the regulatory bodies that they work and are safe. Maybe some will eventually produce polyvalent vaccines to better target a number of variants of concern as determined by sequencing. Likely manufacturing and distribution of new versions and demands for such in preference to previous are going to throw up issues.
 
This article is a good summary of where we are up to with recent, key variants. In particular the P.1 variant which appears to be spreading rapidly around Manaus, Brazil, where a high level of seropositives have previously been recorded. Whether this is happening because it escapes previously acquired immunity or that immunity is now on the wane is very much an active area of investigation.
 
Confirmed reinfection in the UK by a different variant (B.2 first, then B.1.1.7), after just over 8 months. Patient was a 78 year old with type 2 diabetes, no immunosuppression. First episode mild, second critical/life threatening. The patient's antibody levels were regularly monitored after the first infection and antibodies to SARS-CoV-2 were present shortly before the onset of the second infection. Raises questions about immune and vaccine escape and possibility of reinfection.

DOI: 10.1093/cid/ciab014
Daniel Griffin who does a weekly clinical report talked about a similar suspected reinfection a while ago (about June) where the second infection was a lot more serious (fatal iirc) than the first one. Any idea how frequent this could be? With undetected asymptomatic first infections these could easily sneak under the radar.
 
This article is a good summary of where we are up to with recent, key variants. In particular the P.1 variant which appears to be spreading rapidly around Manaus, Brazil, where a high level of seropositives have previously been recorded. Whether this is happening because it escapes previously acquired immunity or that immunity is now on the wane is very much an active area of investigation.

IMO, that was a really clearly written article -- easy to understand for non-scientists, and covering a lot of ground :)
 
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