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Covid Mutations

A case of P.1 (B.1.1.28.1, Manaus, Brazil) raising the question of whether that variant (mutations S:K417T, S:E484K, and S:N501Y) might be demonstrating immune escape (as has recently been suggested elsewhere based on modelling and laboratory studies of the E484K mutation in the presence of N501Y). Here an immunocompetent 29 year old female was reinfected with P.1 (experienced worse symptoms) nine months after previous confirmed infection with a B.1 (earlier D614G variant). She had tested positive for IgG antibodies to the first SARS-CoV-2 infection just 8 days prior to the second infection. More research is urgently required to identify and sequence P.1 (and other S:E484K) reinfections of such seropositive individuals.
virological.org

SARS-CoV-2 reinfection by the new Variant of Concern (VOC) P.1 in Amazonas, Brazil

SARS-CoV-2 reinfection by the new Variant of Concern (VOC) P.1 in Amazonas, Brazil Felipe Naveca 1,2,3, Cristiano da Costa 2,4, Valdinete Nascimento 1,2,3, Victor Souza 1,2,3, André Corado 1,2,3, Fernanda Nascimento 1,2,3, Ágatha Costa 1,2,3, Débora Duarte 1,2,3, George Silva 1,2,3, Matilde...
virological.org virological.org
 
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From Ravi K Gupta / Gupta Lab on twitter -https://twitter.com/GuptaR_lab

Further data on immune responses following the Pfizer mRNA vaccine against pseudo virus bearing Spike protein with mutations in the B.1.1.7 variant (del69/70, del 144/145, N501Y, A570D, P681H, T716I, S982A, D1118H). There is a modest reduction in efficacy of vaccine sera.

Among 15 individuals with neutralisation activity three weeks after the Pfizer mRNA vaccine, 10 showed evidence of reduction in efficacy of antibodies against the B.1.1.7 mutant (Fold change >3). The highest fold change was 6. Median fold change was 3.85 (IQR 2.68-5.28).
1610984604837.png

These modest changes are what we expected to see given the mutational profiles, esp del 144/145 which is a target region for our antibodies. Vaccines should be highly effective and vaccine coverage is a priority. Full results and methods on Medrxiv in the coming days.
 
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Indeliblelink said:
These modest changes are what we expected to see given the mutational profiles, esp del 144/145 which is a target region for our antibodies. Vaccines should be highly effective and vaccine coverage is a priority. Full results and methods on Medrxiv in the coming days.
Click to expand...
But also note, from the same research study, single dose vaccine acquired immunity, not unsurprisingly, appeared to be significantly less effective in 80+ cohorts.


Of course, the study is a very small one. Elderly may need a much longer time to produce a strong immune response, and then perhaps only after a second dose, though a small number will inevitably produce poor immune responses. Not dissimilar results have been seen in Moderna data.
 
South African based scientific panel discussion on the new variant 501Y.V2 that was held yesterday. I haven't watched it all yet but the point most people seem to be talking about is evidence of reinfection/immune escape with 501Y.V2.
Prelim data from psuedo virus assays shows 21 out of 44 convalescent serum samples from patients infected from the first wave had complete immune escape from new variant 501Y.V2, >90% of the 44 samples showed reduced immunity. Evidence from clinical studies needed.
 
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New COG-UK report (41 pages) on SARS-CoV-2 Spike mutations of interest in the UK - 15th January 2021

COVID-19 Genomics UK Consortium

www.cogconsortium.uk

A brief summary of the latest COG-UK mutational surveillance report, which explores SARS-CoV-2 spike gene mutations of potential or known importance.
On the 15th January 2021, a research report was released by the COVID-19 Genomics UK (COG-UK) consortium. This provides information on mutations and associated variants of interest in the gene encoding the SARS-CoV-2 spike protein that have been identified from sequence data generated by the consortium. We focus on SARS-CoV-2 spike gene mutations of potential or known importance based on epidemiological, clinical and/or experimental observations.

We also include information on several variants first identified elsewhere that are of current concern in the UK, but not all of these are in the UK dataset at the time of writing (as in the case of the lineage P.1 recently detected in Brazil). Frequency numbers are as of the 29th December 2020, but for the global variants of interest, updated numbers and reports of the geographic distribution can be found here.

The report is structured in four parts:

1) a list of high frequency individual mutations, a subset of which may be important;

2) highlighted mutations of potential or known clinical and public health importance based on current evidence;

3) a list of mutations known to lead to weaker neutralisation of the virus by convalescent plasma from people who have been infected with SARS-CoV-2, and/or some monoclonal antibodies (mAbs) that may be given to patients with COVID-19;

4) structural analyses of mutations and variants described in 2) above.

At the time of writing, we are not aware of any evidence that the mutations or combination of mutations detected to date will reduce vaccine efficacy.

We also highlight open access websites that provide updated information on circulating lineages, variants of special interest, and amino acid replacement, insertion and deletion counts for all SARS-CoV-2 genes

Read the full report here.
Click to expand...
 
So from the video above the 484 mutation in the SA variant confers escape from natural immunity generated by infection in normal UK virus. People who have recovered from the UK virus will be able to be infected by this SA variant. That isn't good. No news yet on escape from vaccine though.
 
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I've got behind with some of the detail, is there actually interesting evidence along the lines of what Merkel is quoted as saying in this news item?

Most schools will remain closed, despite opposition, given evidence that some new variants are more transmissible among children, Merkel said.

“If we had a situation like London, then we wouldn’t be talking about schools anymore but about ambulances and overflowing hospitals,” she said.
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www.reuters.com

Germany warns of border closures amid fear of COVID-19 mutations

German Chancellor Angela Merkel warned that Germany may need to consider border crossing curbs if other European countries do not act to halt the spread of the coronavirus, particularly its new, more transmissible variants.
www.reuters.com www.reuters.com
 
Spike dropout proxy data suggest B.1.1.7 appears to be rapidly growing in Portugal. The geographic spread of these samples implies that variant is widely spread across the country and under active community transmission.
a525134570d9237cd330ce7f6695f212490b471b.png

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The NERVTAG document about B.1.1.7 severity that has generated todays headlines about the new strain possibly being more deadly.

I note that the language used in the paper is to describe their initial assesment as a 'realistic possibility' and there is also a yardstick included that enables us to decode what that phrase means.

There is a realistic possibility that VOC B.1.1.7 is associated with an increased risk of death compared to non-VOC viruses.
Click to expand...

Screenshot 2021-01-22 at 19.41.11.png


And this is the summary table from the end of the document showing the different papers that have looked into the question so far and what effect each has so far estimated.

Screenshot 2021-01-22 at 19.44.42.png
 
"California" variant CAL.20C [B.1.429 / L452 Variant] may be driving surge around LA
www.medrxiv.org

Emergence of a novel SARS-CoV-2 strain in Southern California, USA

Since October 2020, novel strains of SARS-CoV-2 including B.1.1.7, have been identified to be of global significance from an infection and surveillance perspective. While this strain (B.1.1.7) may play an important role in increased COVID rates in the UK, there are still no reported strains to...
www.medrxiv.org www.medrxiv.org
: We detected a novel strain descended from cluster 20C and defined by five mutations (ORF1a: I4205V, ORF1b: D1183Y, S: S13I;W152C;L452R). This strain, CAL.20C, was first observed in July 2020 in 1/1230 samples from LA county and not detected in Southern California again until October. Since then, this strain’s prevalence has increased absolutely and relatively in Southern California, where by December it accounted for 24% of all samples and 36.4% (66/181) of our local Los Angeles cohort.
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www.reuters.com

California virus variant driving surge around LA; smell training advised for lingering problem

The following is a roundup of some of the latest scientific studies on the novel coronavirus and efforts to find treatments and vaccines for COVID-19, the illness caused by the virus.
www.reuters.com www.reuters.com

In LA there's also been an increase in death rates of those hospitalized in the last few months (from a 1 in 8 chance in Sept to a 1 in 4 chance from November to present)
However it seems this is down to the hospitals being so overcrowded that only the sickest patients are being admitted.
 
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There were statements from some medical experts in the media several months ago that Covid-19 was unlikely to mutate to become significantly more transmissible and that it was more likely than not to become less lethal over time (though pretty sure no one person made both these claims at once). Was there any real theoretical basis to these predictions or was it just wishful thinking at work?
 
Doodler said:
There were statements from some medical experts in the media several months ago that Covid-19 was unlikely to mutate to become significantly more transmissible and that it was more likely than not to become less lethal over time (though pretty sure no one person made both these claims at once). Was there any real theoretical basis to these predictions or was it just wishful thinking at work?
Click to expand...

I'd want to see the statements. Broadly speaking, I do not think much of anyone who claimed that increased transmissibility over time was unlikely. Its not a given that transmissibility will increase over time, but it is widely considered to be the sort of thing we might expect. The idea that it could become less lethal over time often goes hand in hand with the expectation of increased transmissibility. I wouldnt call these completely safe assumptions, but they have become established for a reason. Assumptions are there to be reinforced or destroyed, and I wouldnt bet too much money on what direction a particular pandemic might lead them.

Also have to keep in mind that some of those statements would have been made when trying to bust a simplified, cliched view about pandemic virus evolution which the public had been repeatedly introduced to by documentaries etc about the deadly 2nd wave of thew 1918 pandemic.

Also need to consider that an evolved virus that carries no greater risk of death for each individual who catches it, can still kill more people than the old version if it is much more transmissible, because more people overall would be expected to catch it.
 
Doodler said:
There were statements from some medical experts in the media several months ago that Covid-19 was unlikely to mutate to become significantly more transmissible and that it was more likely than not to become less lethal over time (though pretty sure no one person made both these claims at once). Was there any real theoretical basis to these predictions or was it just wishful thinking at work?
Click to expand...

Yes, it's quiet well understood theory. If it becomes more lethal it would likely get transmitted less. See ebola for that kind of thing.
 
elbows said:
I'd want to see the statements. Broadly speaking, I do not think much of anyone who claimed that increased transmissibility over time was unlikely. Its not a given that transmissibility will increase over time, but it is widely considered to be the sort of thing we might expect. The idea that it could become less lethal over time often goes hand in hand with the expectation of increased transmissibility. I wouldnt call these completely safe assumptions, but they have become established for a reason. Assumptions are there to be reinforced or destroyed, and I wouldnt bet too much money on what direction a particular pandemic might lead them.
Click to expand...

There were some statements last Spring that haven't aged well. For example, this NPR feature from March 2020 takes a reassuring line:

But it's not as if the coronavirus needs to become more potent to survive and thrive. It's already replicating itself around the world very successfully, says Justin Bahl, an evolutionary biologist at the University of Georgia. "The viruses themselves are not actually under much pressure to change."
Click to expand...

Also from March 2020, a different set of researchers quoted on the Popular Science website under the title Yes, the new coronavirus is mutating - but that's not a bad thing. Sample claim:

So the odds of the virus mutating in such a way that it actually becomes more lethal or contagious over the timescale of weeks, months or even a couple of years aren't very high.
Click to expand...

One of the researchers quoted above, Nathan Grubaugh, appears as a co-author of the article We shouldn't worry when a virus mutates during disease outbreaks in Nature Microbiology, February 2020. This takes a more nuanced line: mutations may or may not affect virulence and ease of transmission, it depends.

They make a sort-of prediction: "Will adaptation [in SARS-CoV-2 to humans] precipitate more deaths? Unlikely."

This and simillar stuff was going around then, I remember it.
 
Supine said:
Yes, it's quiet well understood theory. If it becomes more lethal it would likely get transmitted less. See ebola for that kind of thing.
Click to expand...

This 2013 article Evolution of Virulence in Emerging Epidemics from PLOS Pathogens may be of interest. In brief: evolutionary theory predicts high virulence will be selected for in the early stages of an epidemic but may be selected against later on when susceptible hosts become less common. Are we still in the early stages of the pandemic, and how would we know?

I've seen smallpox cited as evidence against declining virulence theory, and this is mentioned in passing in Will the Coronavirus Evolve to be Less Deadly? in Undark, November 2020, along with the theory of the trade-off between virulence and transmissibillity. In short: so far, scientists have observed increased transmissibility of SARS-CoV-2 with no corresponding decline in virulence. There is still no way to be sure how it will develop.
 
Doodler said:
There were some statements last Spring that haven't aged well. For example, this NPR feature from March 2020 takes a reassuring line:



Also from March 2020, a different set of researchers quoted on the Popular Science website under the title Yes, the new coronavirus is mutating - but that's not a bad thing. Sample claim:



One of the researchers quoted above, Nathan Grubaugh, appears as a co-author of the article We shouldn't worry when a virus mutates during disease outbreaks in Nature Microbiology, February 2020. This takes a more nuanced line: mutations may or may not affect virulence and ease of transmission, it depends.

They make a sort-of prediction: "Will adaptation [in SARS-CoV-2 to humans] precipitate more deaths? Unlikely."

This and simillar stuff was going around then, I remember it.
Click to expand...

I have a bit of sympathy for parts of those stances because I suspect I probably made some vaguely similar mistakes myself when discussing the subject for much of 2020, before the UK new variant news emerged.

The context that needs to be considered is the vast amount of sloppy hogwash that the media etc are prepared to pump out when it comes to pandemics and virus mutations at the best of times. The stuff I go on about like lazy cliches that were enabled by simplistic and widespread views of the 1918 pandemic. I'm pretty confident that some of those articles were an attempt to respond to that shit early in the pandemic, in a reassuring way. But then it becomes all too easy to make the opposite mistake.
 
A separate variant featuring E484K (with potential for natural immunity/vaccine escape) may have independently arisen in Liverpool, where PHE are investigating a cluster. Lacking in detail somewhat right now.
www.liverpoolecho.co.uk

Covid mutation cluster traced back to Liverpool

Cluster of cases involving mutation located among staff from Liverpool Women's Hospital
www.liverpoolecho.co.uk www.liverpoolecho.co.uk
 
elbows said:
Just saw this on twitter, havent read yet.

Click to expand...


So looks like 501Y.V2 has at least some ability to escape neutralising antibodies generates by at least some first wave variant infections. Not ideal; exactly what that will mean for overall immune response (neutralising antibodies are only one part of the response) either naturally or vaccine derived remains to be seen from reinfection studies.

I still think we are likely to end up with a stable cocktail vaccine covering the major variants over the next few years, given the functional constraints on the S protein, which isn’t a dreadful outcome. Hopefully.
 
elbows said:
An ONS study on any differences in reported symptoms with the new variant. Percentage differences arent really dramatic but maybe still worth a look.

www.bbc.co.uk

Covid-19: Cough, fatigue, sore throat 'more common' with new variant

But loss of taste and smell may be less likely to affect those with the new strain, a study suggests.
www.bbc.co.uk
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Journalists trying to crowbar differences from small amounts of data without knowledge of basic statistics. That's my guess before actually reading the article ;)
 
Co-infections associated with P.2 being reported from Brazil (Rio Grande do Sul area): P.2 with B.1.1.248 and another of P.2 with B.1.91. The potential exists for accelerating mutations.
www.reuters.com

Brazil researchers find people infected with two different coronavirus strains

Researchers in southern Brazil said they have discovered patients infected with two different strains of the new coronavirus simultaneously, reflecting concerns about the growing number of variants in the country.
www.reuters.com www.reuters.com
Also noted is a new variant, preliminary name VUI-NP13L (descendant of B.1.1.248 with 12 mutations including P13L in the nucleocapsid).
Preprint - DOI: 10.1101/2021.01.21.21249764.
 
2hats said:
But also note, from the same research study, single dose vaccine acquired immunity, not unsurprisingly, appeared to be significantly less effective in 80+ cohorts.


Of course, the study is a very small one. Elderly may need a much longer time to produce a strong immune response, and then perhaps only after a second dose, though a small number will inevitably produce poor immune responses. Not dissimilar results have been seen in Moderna data.
Click to expand...

I put this in the other thread but it makes more sense as a a reply here


Let's hope gaps longer than three weeks give similar results.
 
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