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

Sasha said:
They judge exposure by how many of the placebo people got the virus.
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So if 10% of the placebo group contract it, they assume that 10% of the "real vaccine" group (sorry, I know there's a technical word for it, but it's late and I can't think of it) have got it but been protected, regardless of whether they've been in the same surroundings? Hm.
 
Wits_End said:
So if 10% of the placebo group contract it, they assume that 10% of the "real vaccine" group (sorry, I know there's a technical word for it, but it's late and I can't think of it) have got it but been protected, regardless of whether they've been in the same surroundings? Hm.
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That is actually the reasoning behind all trials that are analysed statistically. Vaccine studies just make it obvious.
You use statistics because you know that the end result for any oe person involves a mish mash of unknowable causal factors. So you take two groups who on a random basis ought to share an equal amount of such factors and see if your treatment affects the number of good outcomes.
 
chrisb said:
The problem comes at the next stage when you present the findings as "real" rather than statistical probability.
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I don't quite follow that. All our knowledge of reality is based on probability, nothing is more real than that. But I agree that problems arise because false assumptions are often made in calculating probabilities or the extent to which they can be extrapolated to new contexts.
 
FMMM1 said:
I'm interested in @Snow Leopard comments re adenovirus-based vaccines - can they be delivered in the short/medium term?
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Capacity to manufacture adenovirus based vaccines is actually more forthcoming and straightforward than mRNA based vaccines (due to the novel envelope technology). I suspect CSL in Australia wants the AstraZeneca vaccine to be the first to be produced for this reason...

Having said that, Russia seems to be having problems: https://www.wsj.com/articles/russia...-plans-hit-production-speed-bumps-11605026802
 
Sarah94 said:
Hancock saying that they can start vaccinating people next month. This seems hugely over-optimistic to me?? What do you all think???
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For those not in the UK, Hancock is the government Heath minister who has just done one of the weekly TV briefings.

As I understand it, one of the vaccines has completed stage 3 trials and has handed its data to the regulatory authorities in the USA and UK to ask for approval.

I think while they are waiting they have already started manufacturing the vaccines, and the UK has ordered millions of doses, so rolling out vaccination will depend on regulatory approval and manufacturers getting the doses to the NHS.

The government has presumably had some indication from them that the process will take weeks rather than months, so if this vaccine is approved, it could start being used before Christmas.
 
Sarah94 said:
Hancock saying that they can start vaccinating people next month. This seems hugely over-optimistic to me?? What do you all think???

@Jonathan Edwards
@Snow Leopard
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It sounds very plausible to me. But it will only be a limited sector of the population - maybe 1-2 million.
It might have a useful impact on health care workers, although many in the front line have already been infected.
Unfortunately there is still no sign of any meaningful strategy for keeping infection under control over the next few months. I would strongly advise not to meet up with anyone new at Xmas because the period in the New Year when everyone ends up in hospital is likely to be a level worse than anything we have seen so far.
I am guessing that things Weill begin to look sane by February-March.
 
Sarah94 said:
Hancock saying that they can start vaccinating people next month. This seems hugely over-optimistic to me?? What do you all think???

@Snow Leopard
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I suspect it will be largely symbolic, with doses given to some healthcare workers. (it may even be "preliminary approval" for front-line workers)

I doubt doses are going to be available to the general public then.
 
do we have the data from these trials ( probably not given commercial sensitivities)?
does the lack of protection against transmission in many of the vaccines reduce deaths but promote positivity rates?
given the fiasco that has been the test, trace and isolate system , the vaccination programme has a lot to live up to- and ow will this impact on the management of other acute conditions whilst the focus changes to delivery. There is only so much a system can prioritise and deliver.

it is all very well having a vaccine, it is quite another to deliver vaccinations, and there is not the realisation at large that despite having vaccine(s), life is not going to go back to normal for a significant time. It is seen as a panacea - the penny still has to drop and if this is not addressed prior to roll out we simply defer another uptick.
 
There was mention on the BBC news tonight of another vaccine - or was it treatment? - for people who had immune system problems which would prevent them from having the other vaccines. I think it was the Astra Zeneca one, but there wasn't much in the way of detail given. Does anyone know more?
 
Several of the studies coauthored by Shane Crotty (who spoke on the recent TWIV about long-term immunity post-covid19)
https://www.microbe.tv/twiv/twiv-684/

Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity
https://www.sciencedirect.com/science/article/pii/S0092867420312356
Summary
Limited knowledge is available on the relationship between antigen-specific immune responses and COVID-19 disease severity. We completed a combined examination of all three branches of adaptive immunity at the level of SARS-CoV-2-specific CD4+ and CD8+ T cell and neutralizing antibody responses in acute and convalescent subjects. SARS-CoV-2-specific CD4+ and CD8+ T cells were each associated with milder disease. Coordinated SARS-CoV-2-specific adaptive immune responses were associated with milder disease, suggesting roles for both CD4+ and CD8+ T cells in protective immunity in COVID-19. Notably, coordination of SARS-CoV-2 antigen-specific responses was disrupted in individuals ≥ 65 years old. Scarcity of naive T cells was also associated with aging and poor disease outcomes. A parsimonious explanation is that coordinated CD4+ T cell, CD8+ T cell, and antibody responses are protective, but uncoordinated responses frequently fail to control disease, with a connection between aging and impaired adaptive immune responses to SARS-CoV-2.
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Immunological memory to SARS-CoV-2 assessed for greater than six months after infection
https://www.biorxiv.org/content/10.1101/2020.11.15.383323v1

ABSTRACT
Understanding immune memory to SARS-CoV-2 is critical for improving diagnostics and vaccines, and for assessing the likely future course of the pandemic. We analyzed multiple compartments of circulating immune memory to SARS-CoV-2 in 185 COVID-19 cases, including 41 cases at ≥6 months post-infection. Spike IgG was relatively stable over 6+ months. Spike-specific memory B cells were more abundant at 6 months than at 1 month. SARS-CoV-2-specific CD4+ T cells and CD8+ T cells declined with a half-life of 3-5 months. By studying antibody, memory B cell, CD4+ T cell, and CD8+ T cell memory to SARS-CoV-2 in an integrated manner, we observed that each component of SARS-CoV-2 immune memory exhibited distinct kinetics.
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Notably, while there is significant heterogeneity at all time points, there is no cause for concern about any lack of long term immunity. One of the potentially novel findings was greater amounts of memory B-cells at 6+ months than there were at earlier time periods.

The conclusion (as I have been saying all along), there is nothing particularly unusual about the long-term adaptive immune response to SARS-2 and immunity is likely to be long term, of a similar time frame to other viral infections.
 
Wits_End said:
There was mention on the BBC news tonight of another vaccine - or was it treatment? - for people who had immune system problems which would prevent them from having the other vaccines. I think it was the Astra Zeneca one, but there wasn't much in the way of detail given. Does anyone know more?
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I think it may be the monoclonal antibody cocktail from Astrazeneca. It is not a vaccine. It is a shot of protective antibodies. A sort of high tech version of anti-tetanus serum or gamma globulin for active hepatitis. It does not produce long term immunity but provides immediate treatment for someone infected.
 
The Phase 3 international clinical trial will recruit a total of 5,000 people across countries in Europe and the United States to assess the safety and effectiveness of the antibody cocktail, known as AZD7442.

The prophylactic treatment differs from a vaccine in that it introduces antibodies, rather than prompting the body's immune system to make them. It may prove useful in people whose immune systems are weaker or compromised, and who don't respond to vaccination. Separately, AstraZeneca is developing a COVID-19 vaccine in conjunction with researchers at Oxford University.


In Britain, where the trials of the monoclonal antibody combination kicked off on Saturday, 1,000 participants will be recruited at nine sites, researchers leading the UK arm said.
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https://www.cbc.ca/news/health/astrazeneca-antibody-cocktail-1.5811763
 
@Jonathan Edwards

Professor Paul Knoepfler who is a stem cell scientist and science blogger (The Niche) recently wrote about the mRNA vaccines for Covid-19. The following excerpt got my attention....

"A possible wildcard with RNA vaccines their newness. Since we don’t know them that well, there is a remote possibility that something strange like auto-immunity to RNA could occur sometimes."

If this did end up being happening to some individuals do you think it would be within the realm of possibility that people with existing autoimmune conditions would be at increased risk of such a side effect compared to healthy individuals?

link to the post:

https://ipscell.com/2020/11/why-im-...-19-rna-vaccine-low-mostly-theoretical-risks/
 
TrixieStix said:
"A possible wildcard with RNA vaccines their newness. Since we don’t know them that well, there is a remote possibility that something strange like auto-immunity to RNA could occur sometimes."
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I don't think he is actually suggesting this as a possibility.He is just making up an example of what might be an unknown, unexpected effect.
He could have suggested all sorts of other things, none of which we actually think is a likelihood.
He is just saying that being new it might cause something we haven't thought of.
 
TrixieStix said:
Professor Paul Knoepfler who is a stem cell scientist and science blogger (The Niche) recently wrote about the mRNA vaccines for Covid-19. The following excerpt got my attention....

"A possible wildcard with RNA vaccines their newness. Since we don’t know them that well, there is a remote possibility that something strange like auto-immunity to RNA could occur sometimes."

If this did end up being happening to some individuals do you think it would be within the realm of possibility that people with existing autoimmune conditions would be at increased risk of such a side effect compared to healthy individuals?

link to the post:

https://ipscell.com/2020/11/why-im-...-19-rna-vaccine-low-mostly-theoretical-risks/
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Autoimmunity is a risk of all vaccines, but such outcomes tend to be very rare. Studies of certain existing vaccines have shown increased risk of Thrombocytopenic Purpura and Guillain Barre Syndrome for example.

"Freund's adjuvant" for example is part of the process of deliberately inducing autoimmunity in animal models for the study of autoimmune phenomena.
The key difference between this and human vaccines is the dosages are much higher.

The risk of additional autoimmunity exacerbation is unlikely, unless the autoimmune syndrome was originally triggered by similar antigens in the first place (eg. GBS that was triggered by a flu may be exacerbated by a flu immunisation).

A key point about the magnitude of risk of side effects between the new vaccine technologies (including viral vectors such as the AstraZeneca vaccine), DNA and RNA vaccines compared to inactivated virus and subunit vaccines is the dosages of the vector and nucleic acid based vaccines are typically several magnitudes of order higher, because the immune systems innate defences will prevent much of the DNA or RNA being transcribed in the first place.

The pharmaceutical companies seem to be erring on the side of high doses (because they're afraid of poor efficacy), which has had the consequence of a high rate of acute systemic reactions, eg fevers, swelling and the like.
 
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