The biology of coronavirus COVID-19 - including research and treatments

Sarah94 said:
https://amp.theguardian.com/world/2...dy?CMP=share_btn_tw&__twitter_impression=true

Thoughts on this @Snow Leopard ? It's really scary stuff!
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The UK is in deep trouble, due to the sheer number of active cases.

But I wouldn't go blaming all of this on a new variant. The modelling is quite weak as it is based on a lot of unproven assumptions about transmissibility.
I suspect the model and the rest of the hype is partly being used as a tool to try and scare people into doing the right thing (and perhaps partly used to deflect blame as well).
These models don't tend to take into account dynamic changes in behaviour that people naturally take when increasingly afraid (independent of government laws) of transmission. This is one of the reasons why we don't actually see the true "exponential" spread that would predict that everyone in society is infected in a matter of 1-2 months. But they also don't consider that while the general population might be doing the right thing, substantial transmission can occur due to a minority of people doing the wrong thing.

Davies et al. 2020 said:
To understand possible biological mechanisms for the observed dynamics associated with VOC 202012/01, we considered four alternative hypotheses for why the new variant might be spreading more efficiently: increased infectiousness; immune escape; increased susceptibility among children; and shorter generation time.
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The model (Fig S1) which is used for their future projections, given use of vaccines also had several notable assumptions. The first that the vaccine model they used only assumes 60% efficacy against infection (95% efficacy against disease). This is not enough to achieve "herd immunity" even if 100% of the population was vaccinated. I am not 100% certain, but the model also assumes that if a vaccinated individual is infected, then they have similar infectiousness as someone who was not vaccinated.
The second is that they assume a zero "waning rate of vaccination" (which is reasonable for the short time period modelled), and they also modelled several different assumptions about (less than 100%) "cross-protection" between earlier variants and the new VOC 202012/01 variant.

"Estimation of change in mobility over time" was based on Google Community Mobility data and "Estimation of social contacts over time" was based on "CoMix survey" data (weekly survey of face-to-face contact patterns, taken from a sample of approximately 2500 individuals). So their model is susceptible to a variety of biases, including social desirability bias (people lying on the Comix survey, claiming less face-to-face contact during the lockdown) and statistical limitations where those surveyed are in limited numbers for the areas being modelled. These surveys are used as a proxy to imply how the general population is behaving.

So to be quite clear, the conclusion that the increased transmission of the variant is not due to differences in population behaviour is based on the assumption that the people who are spreading the virus are behaving in exactly the same way as those included in the surveys (with respect to number of face to face contacts and mobility). (and this applies to other factors like mask wearing etc).

General discussion (not related to the paper):
Other nations have shown that the pandemic can be controlled without using "tier 4" style lockdowns or vaccines. The principle is simple: quarantine.

Forced isolation of all of those who are at risk until the virus is eliminated from the community and force all travellers to isolate until there is no risk that they are infected. Of course this isn't foolproof as people don't always obey the rules (and it is difficult to achieve 100% isolation), so a layer of contact tracing to make sure that all local spread is tracked and traced and close contacts at high risk are forced to isolate until confirmed that they are not infectious. If there is significant untraceable community transmission, then this is a trigger for lockdown-type measures, until contact tracing is effective again.

So there is an alarming alternative conclusion to that of increased transmissibility, namely a subset of people who are taking much less care than the general population!
 
The Times today

Fauci has changed his view. To achieve herd immunity vaccination rates could require vaccinations to be 90% rather than 70% as he believed previously. US has vaccinated more than million, about 0.3% of population since Dec 14th.
It doesn't say which vaccine this figure is based on, but I think US has been using Moderna and Pfizer.

Looking back to post #1050, @shak8 noted Vincent Racaniello
giving a figure of 75% to reach HI with Pfizer and Moderna.

Why the changing estimates?
 
chrisb said:
That may depend on the amount of wastage. There have already been two reports that I have seen of refrigeration failure leading to loss of product.
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Seems the Moderna vaccine is stable*; however, I wonder if this will come down to cost - Moderna $25 - Oxford $2.5 -- 10X. Also, apparently they can tweak these RNA vaccines to make them more (temperature) stable.

*"Refrigeration Storage: After thawing, to facilitate storage at points of administration, Moderna expects that mRNA-1273 will remain stable at standard refrigerated conditions of 2° to 8°C (36° to 46°F) for up to 30 days within the 6-month shelf life. The stability at refrigerated conditions allows for storage at most pharmacies, hospitals, or physicians’ offices.
https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-longer-shelf-life-its-covid-19-vaccine#:~:text=Refrigeration Storage: After thawing, to,the 6-month shelf life.
Shipping & Long-term Storage: For shipping and longer-term storage, Moderna expects that mRNA-1273 will be maintained at -20°C (-4°F), equal to most home or medical freezer temperatures, for up to 6 months. Using standard freezer temperatures of -20°C (range of -25° to -15°C or -13° to 5°F) is an easier and more established method of distribution and storage than deep freezing and most pharmaceutical distribution companies have the capability to store and ship products at -20°C (-4°F) worldwide.
 
Binkie4 said:
The Times today

Fauci has changed his view. To achieve herd immunity vaccination rates could require vaccinations to be 90% rather than 70% as he believed previously.
Why the changing estimates?
Click to expand...

Herd immunity is as long as a piece of string - there is no magic figure. However, a useful figure would be one which is likely to be a watershed between infection fizzling out and infection spreading. That is going to be dependent on the circumstances at the time as well - just as the R number depends on social habits.

It may be that with the new variants that may spread faster and the high saturation of the population with active infection act present that you need more people immune to turn the tap off.

Of course it may be partly driven by a desire to encourage vaccination, although Fauci tends to tell things straight I think.
 
Jonathan Edwards said:
My reaction would be that this was obviously the situation anyway, even if there was no new variant. The level of spread has been allowed to rise such that we are bound to have more deaths next year than this unless there is complete lockdown for a couple of months.

Everyone seems to have been living a fantasy watching the figures rise.

The relevance of the new strain is just that people will have to do things properly to get levels down like last May. All flights need to be cancelled. There need to be bans on moving from county to county except for food delivery and so on. Schools must stay closed. It can be done but people need to get real.
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Particularly true when the vaccine is already being rolled out; i.e. reduce the level of transmission and get on with vaccinating people/ending the pandemic.
 
Binkie4 said:
The Times today

Fauci has changed his view. To achieve herd immunity vaccination rates could require vaccinations to be 90% rather than 70% as he believed previously. US has vaccinated more than million, about 0.3% of population since Dec 14th.
It doesn't say which vaccine this figure is based on, but I think US has been using Moderna and Pfizer.

Looking back to post #1050, @shak8 noted Vincent Racaniello
giving a figure of 75% to reach HI with Pfizer and Moderna.

Why the changing estimates?
Click to expand...

Maybe linked to the point @Snow Leopard made i.e. the Oxford vaccine might not be effective enough to achieve herd immunity (RNA vaccines are)
 
Snow Leopard said:
Loss of product has nothing to do with number needed to vaccinate for a given threshold of "herd immunity".



In the long run, they'd be worse off. There are going to be more vaccines available next year that may also have superior efficacy. All the claims that poor countries deserve an inferior vaccine because it is a little cheaper just make me feel quite angry.

If anyone wants to use the AZD1222 vaccine, they'd have to have a good reason to do it right now, e.g. vaccinating healthcare workers right now, or selective ring-vaccination. I don't think the general population should be vaccinated with a clearly inferior vaccine.
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Are there any more (cheaper) RNA vaccines reporting in the near future?
 
FMMM1 said:
Maybe linked to the point @Snow Leopard made i.e. the Oxford vaccine might not be effective enough to achieve herd immunity (RNA vaccines are)
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This will be interesting. My GP told me in a phone consult last week that I would be offered Oxford in March . I queried the 62% VE and the lack of data on the elderly. He said they will be using half a dose then full dose.

This was at the back of my mind when I read the Times snippet. I don't think we are to be given a choice in U.K. as far as I know. @Jonathan Edwards - do you have more information.

edit: sentence removed for personal reasons
 
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Binkie4 said:
This will be interesting. My GP told me in a phone consult last week that I would be offered Oxford in March. I queried the 62% VE and the lack of data on the elderly. He said they will be using half a dose then full dose.

This was at the back of my mind when I read the Times snippet. I don't think we are to be given a choice in U.K. as far as I know. @Jonathan Edwards - do you have more information.
Click to expand...

Binkie4 said:
The Times today

Fauci has changed his view. To achieve herd immunity vaccination rates could require vaccinations to be 90% rather than 70% as he believed previously. US has vaccinated more than million, about 0.3% of population since Dec 14th.
It doesn't say which vaccine this figure is based on, but I think US has been using Moderna and Pfizer.

Looking back to post #1050, @shak8 noted Vincent Racaniello
giving a figure of 75% to reach HI with Pfizer and Moderna.

Why the changing estimates?
Click to expand...

Could you post a link to the (New York?) Times article - thanks.
 
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Binkie4 said:
This will be interesting. My GP told me in a phone consult last week that I would be offered Oxford in March. I queried the 62% VE and the lack of data on the elderly. He said they will be using half a dose then full dose.

This was at the back of my mind when I read the Times snippet. I don't think we are to be given a choice in U.K. as far as I know. @Jonathan Edwards - do you have more information.
Click to expand...

Heard the same, from a neighbour who is a GP, i.e. the UK is about to start vaccinating with the Oxford vaccine (January). Not surprised about the "no choice" who would choose Oxford over the other 2?
 
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FMMM1 said:
Are there any more (cheaper) RNA vaccines reporting in the near future?
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There is a Chinese Academy of Sciences candidate, "Covidvax" but no phase 3 data provided and no idea on price or availability though.
https://www.researchsquare.com/article/rs-89633/v1

The other possibilities:

CvnCoV (CureVac, Germany) - currently phase 2 trials
LUNAR-COV19 (Arcturus/Duke-NUS, Singapore) - phase 1–2 trials
COVAC1 (Imperial College, UK) - phase 1 trials
 
Binkie4 said:
This will be interesting. My GP told me in a phone consult last week that I would be offered Oxford in March. I queried the 62% VE and the lack of data on the elderly. He said they will be using half a dose then full dose.

This was at the back of my mind when I read the Times snippet. I don't think we are to be given a choice in U.K. as far as I know. @Jonathan Edwards - do you have more information.
Click to expand...
FMMM1 said:
Could you post a link to the (New York?) Times article - thanks.
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It's not actually a news article. It's a news column in the UK Times headed " Strains tell as vaccine offers hope of way out" on the R hand side of page 14, today 26/12/20.
We don't have a subscription to the online Times, only the hard copy so I can't post you a link. Just half a dozen lines about US gives the info about Fauci.

edit:" today 26/12/20"added.
 
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Binkie4 said:
This will be interesting. My GP told me in a phone consult last week that I would be offered Oxford in March . I queried the 62% VE and the lack of data on the elderly. He said they will be using half a dose then full dose.
Click to expand...

The study published in The Lancet:
https://www.sciencedirect.com/science/article/pii/S0140673620326611

Note that the pooled data for symptomatic infections was 70·4% (54·8 to 80·6) (95% CI in brackets)

The data for the LD/SD was 90·0% (67·4 to 97·0), for symptomatic infections with an notably small sample size of ~1370 vaccinated and a wide confidence interval.

But also note that the overall efficacy of the LD/SD group was (including those with positive swabs who did not report additional COVID symptoms described as incl) was 58·9% (1·0 to 82·9). Which again, is an extremely wide confidence interval.
Oh and the result for the LD/LD group was a woeful 3·8% (−72·4 to 46·3) group.

I do not find these numbers very confidence inspiring, even when you look at the cherry picked LD/SD result.

I find the dismissal of your queries by the GP quite concerning actually, as it suggests that they have not read, or do not understand the statistics in the manuscript (and the dangers of cherry picking data) and are simply believing the questionable claims in the media that the "half dose then full dose" of the Oxford vaccine is as good as the approved mRNA vaccines.

I'm once again going to plug this paper as a good argument as to why the ChAdOx1 vaccine should be avoided in favour of the mRNA alternatives (at least until other vaccines with high efficacy are approved).
https://www.medrxiv.org/content/10.1101/2020.12.15.20248278v2.full-text
 
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@Snow Leopard . I can't pretend to understand the stats but am waiting for the UK regulatory results to be published. I presume that more data on Oxford will be released? Will need reading carefully.
Link to last article looks interesting.
 
Binkie4 said:
@Snow Leopard . I can't pretend to understand the stats but am waiting for the UK regulatory results to be published. I presume that more data on Oxford will be released? Will need reading carefully.
Link to last article looks interesting.
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What new data, other than perhaps the data from the modestly sized India trial?

Notably, India's Central Drugs Standard Control Organization rejected AstraZeneca's application on the 9th of December, due to "inadequate safety and efficacy data" but there are claims/rumors in the media that they have submitted extra data and that it will be approved shortly.

AztraZeneca and some media commentators keep talking about how the trial data meets the "minimum" efficacy of 50%, but since when is the bare minimum good enough when there are better alternatives?

Also, an aside, AstraZeneca is starting phase 1/2 trials of AZD1222 / rAd26-S ("Sputnik") combination trials.
https://clinicaltrials.gov/ct2/show/NCT04684446
 
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