New Variant Covid-19 VUI 202012/01

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Re: New Variant Covid-19 VUI 202012/01

Post by Woodchopper » Wed Jan 20, 2021 5:56 am

Woodchopper wrote:
Wed Jan 20, 2021 5:39 am
mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants
https://www.biorxiv.org/content/10.1101 ... 5.426911v1

Loss of efficacy of RNA vaccines seems relatively mild. Paper concludes that: “Taken together the results suggest that the monoclonal antibodies in clinical use should be tested against newly arising variants, and that mRNA vaccines may need to be updated periodically to avoid potential loss of clinical efficacy.”
Doesn’t look like this covers the 501NYv2 variant mentioned in earlier posts.

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Re: New Variant Covid-19 VUI 202012/01

Post by Woodchopper » Wed Jan 20, 2021 9:09 pm


Neutralization of SARS-CoV-2 lineage B.1.1.7 pseudovirus by BNT162b2 vaccine-elicited human sera

Here, we investigated SARS-CoV-2-S pseudoviruses bearing either the Wuhan reference strain or the B.1.1.7 lineage spike protein with sera of 16 participants in a previously reported trial with the mRNA-based COVID-19 vaccine BNT162b2. The immune sera had equivalent neutralizing titers to both variants. These data, together with the combined immunity involving humoral and cellular effectors induced by this vaccine, make it unlikely that the B.1.1.7 lineage will escape BNT162b2-mediated protection.
https://www.biorxiv.org/content/10.1101 ... 8.426984v1

Which is good news.

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Re: New Variant Covid-19 VUI 202012/01

Post by Woodchopper » Wed Jan 20, 2021 9:34 pm

Israel new UK variant
We currently estimate over 50% in the ultra Orthodox population and 40% nationwide, and growing in its overlall fraction of cases
https://twitter.com/segal_eran/status/1 ... 32864?s=21

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Re: New Variant Covid-19 VUI 202012/01

Post by raven » Wed Jan 20, 2021 11:16 pm

Woodchopper wrote:
Sat Jan 16, 2021 8:23 pm
The lethal triad: SARS-CoV-2 Spike, ACE2 and TMPRSS2. Mutations in host and pathogen may affect the course of pandemic
“ dynamics of pandemics are strongly influenced not only by virus variation but also by host genetic background.”
https://www.biorxiv.org/content/10.1101 ... 2.426365v1
Thanks for that link. I'd assumed variation in the ACE2 receptor would have an effect so it's good to see something on that. Even if I didn't understand most of it.

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Re: New Variant Covid-19 VUI 202012/01

Post by Woodchopper » Thu Jan 21, 2021 9:23 am

Woodchopper wrote:
Tue Jan 19, 2021 5:29 pm
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).

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.
https://twitter.com/guptar_lab/status/1 ... 36675?s=21

Not very bad in its self. This was after the first dose, so a second dose should help. But bad in that it shows what can happen.
Here's the preprint:

Impact of SARS-CoV-2 B.1.1.7 Spike variant on neutralisation potency of sera from individuals vaccinated with Pfizer vaccine BNT162b2
https://www.medrxiv.org/content/10.1101 ... le-metrics

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Re: New Variant Covid-19 VUI 202012/01

Post by Woodchopper » Thu Jan 21, 2021 8:15 pm

Tracking SARS-CoV-2 VOC 202012/01 (lineage B.1.1.7) dissemination in Portugal: insights from nationwide RT-PCR Spike gene drop out data

https://virological.org/t/tracking-sars ... t-data/600

Over six weeks S gene dropout has gone from 0.9% to 13.3%.

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Re: New Variant Covid-19 VUI 202012/01

Post by Woodchopper » Thu Jan 21, 2021 8:26 pm

Escape of SARS-CoV-2 501Y.V2 variants from neutralization by convalescent plasma

“ We observed that neutralization of the 501Y.V2 variants was strongly attenuated, with IC50 6 to 200-fold higher relative to first wave virus. The degree of attenuation varied between participants and included a knockout of neutralization activity. This observation indicates that 501Y.V2 may escape the neutralizing antibody response elicited by prior natural infection. It raises a concern of potential reduced protection against re-infection and by vaccines designed to target the spike protein of earlier SARS-CoV-2 variants.”
https://www.krisp.org.za/publications.php?pubid=316

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Re: New Variant Covid-19 VUI 202012/01

Post by Woodchopper » Thu Jan 21, 2021 9:15 pm

When the number of COVID-19 cases began to rise again in Manaus, Brazil, in December 2020, Nuno Faria was stunned. The virologist at Imperial College London had just co-authored a paper in Science estimating that three-quarters of the city's inhabitants had already been infected with SARS-CoV-2, the pandemic coronavirus—more than enough, it seemed, for herd immunity to develop. The virus should be done with Manaus. Yet hospitals were filling up again. “It was hard to reconcile these two things,” Faria says. He started to hunt for samples he could sequence to find out whether changes in the virus could explain the resurgence.

On 12 January, Faria and his colleagues posted their initial conclusions on the website virological.org. Thirteen of 31 samples collected in mid-December in Manaus turned out to be part of a new viral lineage they called P.1. Much more research is needed, but they say one possibility is that in some people, P.1 eludes the human immune response triggered by the lineage that ravaged the city earlier in 2020.

[...]

P.1 adds to the concerns because it appears to have hit on a similar constellation of mutations and has emerged in a place with a high level of immunity. “Anytime you see the same mutations arising and starting to spread multiple times, in different viral strains across the world, that's really strong evidence that there's some evolutionary advantage to those mutations,” Bloom says.

Like B.1.1.7, the Brazilian variant is already on the move. Just as Faria was finishing his analysis of the Brazilian genomes, a report was published of a variant detected in travelers arriving in Japan from Brazil—and it turned out to be P.1. (As Science went to press, U.S. researchers also reported several new variants, but their importance remained unclear.)

HOW THESE NEW variants are affecting the course of the pandemic is unclear. In Manaus, for example, P.1 might have nothing to do with the new surge in infections; people's immunity might simply be waning, says University of Oxford epidemiologist Oliver Pybus. Or it might be driving the boost because it is transmitted more easily, like B.1.1.7, not because it can evade the immune response. “Of course it could be a combination of these factors, too,” Pybus says.

Similarly, in a recent modeling study, researchers at the London School of Hygiene & Tropical Medicine calculated that South Africa's 501Y.V2 variant could be 50% more transmissible but no better at evading immunity, or just as transmissible as previous variants but able to evade immunity in one in five people previously infected. “Reality may lie between these extremes,” the authors wrote.

Ester Sabino, a molecular biologist at the University of São Paulo, São Paulo, has launched a study to find reinfections in Manaus that could help decide between these hypotheses for P.1. Lab studies investigating the variants are also underway. The United Kingdom on 15 January launched a new consortium, G2P-UK (for “genotype to phenotype-UK”), headed by Wendy Barclay of Imperial College London, to study the effects of emerging mutations in SARS-CoV-2. One idea discussed at the 12 January WHO meeting is to set up a biobank that would aid studies by housing virus samples, as well as plasma from vaccine recipients and recovered patients.

Interactions between the new mutations may make it harder to tease out their effects. The variants from the United Kingdom, South Africa, and Manaus all share a mutation named N501Y, for instance, or Nelly, as some researchers call it. But the mutation, which affects the spike protein, also occurs in some variants that do not spread faster, suggesting N501Y does not operate alone, says Kristian Andersen of Scripps Research: “Nelly might be innocent, except maybe when she's hanging with her bad friends.”

Bloom thinks none of the changes is likely to let the virus escape the immune response entirely. “But I would expect that those viruses have some advantage when a lot of the population has immunity”—which might help explain the surge in Manaus.
https://science.sciencemag.org/content/ ... 7/329.full

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Re: New Variant Covid-19 VUI 202012/01

Post by Woodchopper » Fri Jan 22, 2021 9:56 am

Woodchopper wrote:
Fri Jan 08, 2021 4:18 pm
Genomic tests on the 24 December 2020 confirmed the presence of the UK variant in Ireland. Further analysis to date has indicated the following cases of the UK variant:
• Week 51 (to 20th Dec): 6 variants in 70 samples or 8.6%
• Week 52 (to 27th Dec): 18 variants in 141 samples or 12.8%
• Week 53/Week 1 (to 3rd Jan): 47 variants in 189 or 24.9%
https://assets.gov.ie/118212/b00522b8-7 ... 185a00.pdf
Now up to 60% according to this press report: https://www.independent.ie/irish-news/i ... 97794.html

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Re: New Variant Covid-19 VUI 202012/01

Post by Woodchopper » Fri Jan 22, 2021 5:00 pm

Possible that the UK variant is more lethal: https://twitter.com/peston/status/13526 ... 49633?s=21

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Re: New Variant Covid-19 VUI 202012/01

Post by lpm » Fri Jan 22, 2021 5:02 pm

Johnson announcing that right now.
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Re: New Variant Covid-19 VUI 202012/01

Post by lpm » Fri Jan 22, 2021 5:12 pm

Sir Patrick Vallance

- confident new variant spreads more easily
- increase in deaths from 10/1,000 to 13/1,000 for sixty year olds - will be different for different ages
- vaccines still work
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Re: New Variant Covid-19 VUI 202012/01

Post by lpm » Fri Jan 22, 2021 5:14 pm

A bit "meh", surely?

The exponential impact of higher transmission is far worse for deaths than this sort of increase in fatality rates.
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Re: New Variant Covid-19 VUI 202012/01

Post by Woodchopper » Fri Jan 22, 2021 6:35 pm

lpm wrote:
Fri Jan 22, 2021 5:14 pm
A bit "meh", surely?

The exponential impact of higher transmission is far worse for deaths than this sort of increase in fatality rates.
Yes, but still bad news. That’s presumably also more people in hospital and more on ventilators.

A few weeks ago there was an apparent anomaly that the UK variant had a higher viral load but didn’t appear to make people sicker. Looks like it does after all.

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Re: New Variant Covid-19 VUI 202012/01

Post by Woodchopper » Fri Jan 22, 2021 6:48 pm

NERVTAG paper on COVID-19 variant of concern B.1.1.7

Summary
1. The variant of concern (VOC) B.1.1.7 appears to have substantially increased transmissibility compared to other variants and has grown quickly to become the dominant variant in much of the UK.

2. Initial assessment by PHE of disease severity through a matched case-control study reported no significant difference in the risk of hospitalisation or death in people infected with confirmed B.1.1.7 infection versus infection with other variants. [1]

3. Several new analyses are however consistent in reporting increased disease severity in people infected with VOC B.1.1.7 compared to people infected with non-VOC virus variants.

4. There have been several independent analyses of SGTF and non-SGTF cases identified through Pillar 2 testing linked to the PHE COVID-19 deaths line list:
a. LSHTM: reported that the relative hazard of death within 28 days of test for VOC-infected individuals compared to non-VOC was 1.35 (95%CI 1.08-1.68).
b. Imperial College London: mean ratio of CFR for VOC-infected individuals compared to non-VOC was 1.36 (95%CI 1.18-1.56) by a case-control weighting method, 1.29 (95%CI 1.07-1.54) by a standardised CFR method.
c. University of Exeter: mortality hazard ratio for VOC-infected individuals compared to non-VOC was 1.91 (1.35 - 2.71).
d. These analyses were all adjusted in various ways for age,location,timeand other variables.

5. An updated PHE matched cohort analysis has reported a death risk ratio for VOC- infected individuals compared to non-VOC of 1.65 (95%CI 1.21-2.25).

6. There are several limitations to these datasets including representativeness of death data (<10% of all deaths are included in some datasets), power, potential biases in case ascertainment and transmission setting.

7. Based on these analyses, there is a realistic possibility that infection with VOC B.1.1.7 is associated with an increased risk of death compared to infection with non-VOC viruses.

8. It should be noted that the absolute risk of death per infection remains low.

9. An analysis of CO-CIN data has not identified an increased risk of death in hospitalised VOC B.1.1.7 cases. However, increased severity may not necessarily be reflected by increased in-hospital death risk.

10. Since the time lag from infection to hospitalisation and death is relatively long, data will accrue in coming weeks, at which time the analyses will become more definitive.

https://assets.publishing.service.gov.u ... .1.1.7.pdf

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Re: New Variant Covid-19 VUI 202012/01

Post by lpm » Fri Jan 22, 2021 9:01 pm

Woodchopper wrote:
Fri Jan 22, 2021 6:48 pm

9. An analysis of CO-CIN data has not identified an increased risk of death in hospitalised VOC B.1.1.7 cases. However, increased severity may not necessarily be reflected by increased in-hospital death risk.
I don't understand this bit. It kills more people overall, but doesn't kill extra people in hospital?
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Re: New Variant Covid-19 VUI 202012/01

Post by shpalman » Fri Jan 22, 2021 9:04 pm

lpm wrote:
Fri Jan 22, 2021 9:01 pm
Woodchopper wrote:
Fri Jan 22, 2021 6:48 pm

9. An analysis of CO-CIN data has not identified an increased risk of death in hospitalised VOC B.1.1.7 cases. However, increased severity may not necessarily be reflected by increased in-hospital death risk.
I don't understand this bit. It kills more people overall, but doesn't kill extra people in hospital?
Well, doctors have gotten better and figuring out who would benefit from hospital and who... wouldn't.
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Re: New Variant Covid-19 VUI 202012/01

Post by OffTheRock » Fri Jan 22, 2021 9:15 pm

Might also be increased risk of being admitted to hospital, but if you are sick enough to be admitted then your risk of dying is about the same as people admitted with any other strain of Covid 19.

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Re: New Variant Covid-19 VUI 202012/01

Post by Woodchopper » Fri Jan 22, 2021 10:35 pm

lpm wrote:
Fri Jan 22, 2021 9:01 pm
Woodchopper wrote:
Fri Jan 22, 2021 6:48 pm

9. An analysis of CO-CIN data has not identified an increased risk of death in hospitalised VOC B.1.1.7 cases. However, increased severity may not necessarily be reflected by increased in-hospital death risk.
I don't understand this bit. It kills more people overall, but doesn't kill extra people in hospital?
See paragraph 18 in the document. First there are data issues. Second, it suggests that the variant is causing more people to go to hospital overall. So the proportion of deaths in hospital is unchanged as there are both more fatal cases and more non-fatal cases.

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Re: New Variant Covid-19 VUI 202012/01

Post by dyqik » Fri Jan 22, 2021 10:59 pm

OffTheRock wrote:
Fri Jan 22, 2021 9:15 pm
Might also be increased risk of being admitted to hospital, but if you are sick enough to be admitted then your risk of dying is about the same as people admitted with any other strain of Covid 19.
A (probably in the future) option raised by this Washington Post article based on Danish data is that it makes healthcare system overload more likely, as it spreads faster.

https://www.washingtonpost.com/world/eu ... story.html

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Re: New Variant Covid-19 VUI 202012/01

Post by Woodchopper » Sat Jan 23, 2021 4:29 pm

Thread on the new variant and greater severity: https://twitter.com/billhanage/status/1 ... 67363?s=21

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Re: New Variant Covid-19 VUI 202012/01

Post by Woodchopper » Sat Jan 23, 2021 5:42 pm

Südafrikanische CoV-Mutation in Tirol entdeckt
https://tirol.orf.at/stories/3086491/

21 cases of the SA variant found in Tyrol in Austria.

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Re: New Variant Covid-19 VUI 202012/01

Post by Millennie Al » Sun Jan 24, 2021 3:08 am

lpm wrote:
Fri Jan 22, 2021 9:01 pm
Woodchopper wrote:
Fri Jan 22, 2021 6:48 pm

9. An analysis of CO-CIN data has not identified an increased risk of death in hospitalised VOC B.1.1.7 cases. However, increased severity may not necessarily be reflected by increased in-hospital death risk.
I don't understand this bit. It kills more people overall, but doesn't kill extra people in hospital?
Using made up figures, 100 people catch each variant. With the old one, 10 get hospitalised of whom 5 die. With the new variant 20 get hospitalised of whom 10 die. In hospital deaths are 50% for both, but the new variant is twice as deadly. It's very plausible if we assume that hospitalisation is a measure of how seriously ill you are, so once you're that ill the chance of death could easily be the same for many diseases of greatly varying severity - what metters instead is how treatable they are.

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Re: New Variant Covid-19 VUI 202012/01

Post by Woodchopper » Tue Jan 26, 2021 11:11 am

Prospective mapping of viral mutations that escape antibodies used to treat COVID-19

Antibodies are a potential therapy for SARS-CoV-2, but the risk of the virus evolving to escape them remains unclear. Here we map how all mutations to SARS-CoV-2’s receptor-binding domain (RBD) affect binding by the antibodies in the REGN-COV2 cocktail and the antibody LY-CoV016. These complete maps uncover a single amino-acid mutation that fully escapes the REGN-COV2 cocktail, which consists of two antibodies targeting distinct structural epitopes. The maps also identify viral mutations that are selected in a persistently infected patient treated with REGN-COV2, as well as during in vitro viral escape selections. Finally, the maps reveal that mutations escaping the individual antibodies are already present in circulating SARS-CoV-2 strains. Overall, these complete escape maps enable interpretation of the consequences of mutations observed during viral surveillance.
https://science.sciencemag.org/content/ ... f9302.full

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Re: New Variant Covid-19 VUI 202012/01

Post by shpalman » Wed Jan 27, 2021 10:34 pm

Cough and sore throat more common with UK Covid variant
Coughs, sore throats and fatigue are more common in people who test positive for the new variant of coronavirus, but a loss of taste or smell is less likely
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