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

[Snow Leopard]

The latest I have heard, on Radio 4 this morning, is that the difference in efficacy for the half dose group is now being attributed to the group who had the small dose also being part of a larger group who had a 12 week interval between doses, instead of the shorter interval, and they are saying that longer interval was what boosted immunity better.

I find that very surprising, given they said the opposite in their published manuscript:

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32661-1/fulltext

Exploratory subgroup analyses included at the request of reviewers and editors also showed no significant difference in efficacy estimates when comparing those with a short time window between doses (<6 weeks) and those with longer (≥6 weeks)

I also find it very frustrating that they are doing the same thing with the Pfizer vaccine which was not tested with that interval.

I'm not convinced the reasoning behind this was based on clinical data at all.

They are also reiterating that the efficacy of the different vaccines can't be compared directly, as the trials were carried out differently, and different things were measured.

I'd consider that to be weasel-words. The trials were conducted in a broadly similar way.

I think the roll out of whatever vaccine is available and approved is largely because of the very high and rising infection, hospitalization and death rates in the uk at the moment. Anything that has a chance of helping reduce that is regarded as medically helpful.

They should be demanding more supply of the best vaccine, than accepting a second-rate vaccine.

@Snow Leopard thanks, I have some more questions:

I can't really answer these questions as I'm not the one making the decisions.

My reasoning for the 12+ months is complex, but based on supply issues and when they inevitably realise the Oxford Vaccine effiacy is not good enough to rely on to relax all COVID restrictions.

Has anyone quantified "pretty good immunity --- without the second dose"?

The figure stated in the UK regulatory document was just under 53% for one dose.

Interesting that the consider that "a 12 week interval between doses, instead of the shorter interval, and they are saying that longer interval was what boosted immunity".

It is interesting because there was no evidence of this presented in their published manuscript, in fact they claimed that the timing made no significant differnence.

 

[Barry]

That is the likely situation but it is not certain. If 90% effectiveness is defined in terms of blocking clinical symptoms then the effectiveness in preventing death may be greater roles than that.

Your person considered to have a 99% chance surviving is effectively one of a population of 1000 that cannot be told apart amongst which there are only ten who would die if exposed to the virus, for reasons we do not know. Give them all the vaccine and only 100 will get symptoms of Covid. But the ones who were going to die might still all die because they have some defect in being able to mount an adequate immune response.

On the other hand it might work the other way. Just a bit of immunity from vaccine might stop everyone dying.

I guess it's a bit like the Microsoft Windows rollout principle (tongue in cheek) - test in-house as best you can, then release to the rest of the world in the knowledge of having a much larger test population to uncover more obscure issues, and further statistics.

 

[Barry]

I also find it very frustrating that they are doing the same thing with the Pfizer vaccine which was not tested with that interval.

I'm not convinced the reasoning behind this was based on clinical data at all.

I imagine their top priority is to slow the rate of hospital admissions, as that is the main breaking point at the moment. So concentrating on getting a first dose into as many vulnerable people as possible.

 

[lunarainbows]

Pfizer released a statement saying there’s no evidence to show that a single dose of the vaccine offers any protection after 21 days. Ie so it should be done within 3 weeks. Just after after the U.K. govt announced their decision of waiting for 12 weeks for the second dose...

https://www.gponline.com/gps-hit-grossly-unfair-plan-delay-follow-up-covid-19-jabs/article/1703513

“Meanwhile, Pfizer released a statement on Wednesday saying that its vaccine was not intended to be taken 12 weeks apart. It said the vaccine's safety and efficacy had not been evaluated on any dosing schedule other than 21 days between jabs. It added that 'there are no data to demonstrate that protection after the first dose is sustained after 21 days”

 

[Barry]

But I'm not entirely sure the efficacy figure is the only valid metric, which I think only identifies those who do not develop symptoms.

In my post https://www.s4me.info/threads/the-b...vaccines-treatments.14022/page-57#post-314306 there is a link that @Snow Leopard provided, and it seems to be saying that even though more people develop symptoms test positive with the Oxford vaccine, not a single person on the trial who was administered two doses became hospitalised. Now I appreciate that this also is not the only metric of interest, but I would be far happier having this vaccine if I knew it reduced my symptoms from death to not needing hospital treatment (including being asymptomatic).

[bold showing changes]

I think my original post should have been phrased better, as above.

The efficacy against asymptomatic infection for the standard dosage (SD/SD) of the AstraZeneca vaccine was 3.8%, as published in the Lancet. (Table 2)
https://www.thelancet.com/action/showFullTableHTML?isHtml=true&tableId=tbl2&pii=S0140-6736(20)32661-1

But doesn't this still align with what I was saying? If nobody needed hospital treatment who had two doses of vaccine, then that seems encouraging. And the fact that some of those people were positive but asymptomatic, just includes them into the pool of people who did not need hospital treatment, so not sure of the relevance insofar as staying out of hospital is concerned.

I also see there was a significant cohort of older people in the UK trial.

 

[Barry]

Interesting that the consider that "a 12 week interval between doses, instead of the shorter interval, and they are saying that longer interval was what boosted immunity".

But that is a post-hoc analysis, and presumably vulnerable to various misinterpretations. At this point it is just a hypothesis surely? How can they be sure something else was not going on?

 

[Robert 1973]

In case anyone can’t access the images of letter in the above tweet here it is in full:

 

[Snow Leopard]

But doesn't this still align with what I was saying? If nobody needed hospital treatment who had two doses of vaccine, then that seems encouraging. And the fact that some of those people were positive but asymptomatic, just includes them into the pool of people who did not need hospital treatment, so not sure of the relevance insofar as staying out of hospital is concerned.

But if we're talking about keeping people out of hospitals, then Moderna and Pfizer are significantly better. But given the small numbers that were hospitalised, there is a great deal of uncertainty about claims of efficacy (against hospitalisation) based on this number.

Secondly, in case there is still any confusion, the quoted 62/70% efficacy of the AstraZeneca vaccine was for symptomatic infections - these numbers are comparable to the Moderna and Pfizer numbers.

While the sub-analysis showed that the standard dosage of the AstraZeneca vaccine only conferred 3.8% protection against asymptomatic infection, I'd still argue that these cases were only minimally infectious to others compared to the symptomatic infections which could pose risk to others.

 

[Andy]

Covid: 12-week vaccine gap defended by UK medical chiefs
https://www.bbc.co.uk/news/uk-55503739

 

[JaneL]

According to Hilda Bastian the data on preventing severe illness with the Oxford/AstraZeneca vaccine is "almost non-existent"

 

[Jonathan Edwards]

Covid: 12-week vaccine gap defended by UK medical chiefs
https://www.bbc.co.uk/news/uk-55503739

The sentence that stands out to me is:

This is the quickest way back to some degree of normality.

Everything seems to be seen in terms of a quick fix to get back to selling stuff. Having more people slightly moire immune seems to me to be a a recipe for going nowhere fast. Lots of people will assume that the vaccine makes things safe and it quite clearly won't be.

 

[lunarainbows]

Covid: 12-week vaccine gap defended by UK medical chiefs
https://www.bbc.co.uk/news/uk-55503739

But the actual people who made the vaccine are saying there’s no data on the efficacy or safety of what they’re doing. They’ve clearly looked at their own data. So where is the U.K. govt plucking this data from? It’s not like they have other information that Pfizer and others don’t? I find it hard to even fathom where this is coming from, and how they can just make up their own protocol when Pfizer have said there’s no data and no safety / efficacy proven, and give this to millions of people.

 

[Kalliope]

From an email to the NIH MECFS Information List.

News from CDC:

CDC just published a COVID-19 Broad Agency Announcement which is available at the following link:

https://beta.sam.gov/opp/0ccf2f05b7084368ad8dc3fd00b6d774/view?keywords="Centers fir disease control broad agency announcement"&sort=-relevance&index=&is_active=true&page=1

Although this announcement is not published by our ME/CFS program, we would like to raise awareness of this opportunity among partners with an interest in postinfectious fatigue, ME/CFS, or similar syndromes. Please note in particular the following topic:

Topic 12. Evaluating and Improving the Clinical Care of Individuals with Chronic Sequelae of SARS-CoV-2 and Other Infections.

12.1. Conduct implementation research to design and evaluate multi-disciplinary team approaches most effective in caring for long COVID, ME/CFS

and other post-infectious fatiguing illnesses, with the goal of improving the quality of life of those affected and supporting their recovery.

The primary point of contact for this announcement is Ronnie Williams, who can be reached through email at oga3@cdc.gov.

Here is the full text concerning Topic 12 and 12.1:


Topic # 12: Evaluating and Improving the Clinical Care of Individuals with Chronic Sequelae of SARS-CoV-2 and Other Infections. (DHCPP).

BAA 75D301-21-R-71738


Added – Amendment 0002

12.1: Conduct implementation research to design and evaluate multi-disciplinary team approaches most

effective in caring for long COVID, ME/CFS and other post-infectious fatiguing illnesses, with the goal of

improving the quality of life of those affected and supporting their recovery.

The SARS CoV-2 pandemic has highlighted the poorly understood clinical syndromes, referred to as post- infectious fatiguing syndromes, that result in significant functional impairment associated with debilitating fatigue, post-exertional malaise, dysautonomia, and cognitive difficulties. Some of these patients have evidence of organ damage and others remain ill with persistent symptoms after SARS-CoV-2 infection without obvious organ damage. The latter group, in particular, have symptoms overlapping those of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Health systems have designed clinics specifically for COVID “long haulers,” and more are cropping up as the pandemic progresses. Given numbers of people infected, even if the percentage who have persistent symptoms is small, it is possible that large numbers of patients will experience post-infectious fatiguing syndromes. Best practices for the evaluation and management of patients with this emerging condition are unclear, and an increasing demand by health care providers for information and treatment interventions is anticipated. Similarities with ME/CFS and post-infectious fatigue suggest that health care providers and patients will experience challenges in communication about the illness and in improving quality of life. The SARS-CoV-2 pandemic presents both an opportunity to apply knowledge gained from more than 30 years of studying ME/CFS, and to gain new insights about post-infectious fatiguing syndromes.

Evidence exists for the effectiveness of multi-disciplinary team approaches to the care of other complex conditions. However, consensus on how teamwork and services are optimally coordinated continues to be a work in progress.

CDC is interested in the development and evaluation of multi-disciplinary team approaches needed to care for patients with chronic sequelae of SARS-CoV-2 (long COVID), ME/CFS and other post-infectious fatiguing illnesses. All solutions should include a mechanism for the open exchange of information broadly among health care providers, including those who are experienced in the care of patients with ME/CFS and other complex post-infectious fatiguing syndromes, in the formative phase of the project and throughout the period of investigation, to facilitate information gathering about design approaches as well as the efficient dissemination of information about evidence-based practices.

 

[Amw66]

But the actual people who made the vaccine are saying there’s no data on the efficacy or safety of what they’re doing. They’ve clearly looked at their own data. So where is the U.K. govt plucking this data from? It’s not like they have other information that Pfizer and others don’t? I find it hard to even fathom where this is coming from, and how they can just make up their own protocol when Pfizer have said there’s no data and no safety / efficacy proven, and give this to millions of people.

Government have realised they have lost the plot completely and have to be seen to be doing something to reduce transmission.

Joined up thinking has never been a governmental strong point, sadly it seems that this is contagious and scientific/ medical advisors are badly affected too.

ETA medical

 

[Snow Leopard]

This is the quickest way back to some degree of normality.

Yes, the problem is that well, it won't be quick.

Normality might return after vaccinating 50 million people in the UK with a high (90+%) efficacy vaccine, but normality will not quickly return even if 90% of people are vaccinated with a 60-70% efficacy vaccine... Neither option will likely occur in less than a year, but the latter example threatens to drag on for many years.

Having said that, besides limitation on travel, things where I live are mostly back to normal, but authorities in the UK still seem to be in denial that an elimination strategy is the best.

 

[Jonathan Edwards]

Normality might return after vaccinating 50 million people in the UK with a high (90+%) efficacy vaccine, but normality will not quickly return even if 90% of people are vaccinated with a 60-70% efficacy vaccine... Neither option will likely occur in less than a year, but the latter example threatens do drag on for many years.

Yes, it begins to look as if a vaccine is really not such a magic answer. Judging by last April the UK could reduce rates tenfold in just over two months with effective social distancing measures (i.e. 'lockdown'). In another two months that could be a hundredfold. And if one factors in an assumption that by June this year testing had racked up fourfold in efficiency, which I think must be somewhere near the case then the first two months actually reduced cases by forty fold and four months would achieve 1600 fold reduction - down to 30 cases a day throughout the UK - basically one or two small clusters. Australia has shown that can be dealt with with a little patience and a sensible quarantine policy.

And of course if vaccines are being given 3 months apart we have four months before we even start getting significant population immunity.

 

[Snow Leopard]

Australia has shown that can be dealt with with a little patience and a sensible quarantine policy.

The curious part about the cluster response in Australia is there have been more than a handful of clusters of varying sizes which have been faced with a spectrum of approaches. It's not exactly science, but it is a social experiment carried out in real time with case-study level evidence.
It wasn't until the larger Melbourne cluster occurred that public opinion shifted towards acceptance towards stronger measures (lockdowns) the success of this approach and the contact-tracing-isolation approach for smaller clusters has cemented widespread faith in this approach Australian society.
It is ironic that in parts of the world where the virus is spreading rampantly, that there are more people who are resistant to the travel restriction/quarantine, and lockdown (when contact tracing is no longer feasible) approach.

I might also add that the contact tracing approach is also how isolated cases of measles have not led to outbreaks in Australia, whereas measles surveillance and contact tracing processes were either insufficient or failed in several UK and USA outbreaks. Apparently the lesson about contact tracing wasn't learned, instead people preferred to blame vaccination rates. Despite the fact that vaccination rates in the USA and UK are near historical highs for measles (MMR1 coverage at 5 years in the UK is currently at 94.5% according to the NHS and low vaccination rates are primarily in ethnic minority and low-income communities, suggesting socio-economic factors as the problem, rather than anti-vaxxers, but I digress...)

 

[Snow Leopard]

Britain Opts for Mix-and-Match Vaccinations, Confounding Experts
https://www.nytimes.com/2021/01/01/health/coronavirus-vaccines-britain.html

Cited article:
https://assets.publishing.service.g...data/file/948757/Greenbook_chapter_14a_v4.pdf

There is no evidence on the interchangeability of the COVID-19 vaccines although studies are underway. Therefore, every effort should be made to determine which vaccine the individual received and to complete with the same vaccine. For individuals who started the schedule and who attend for vaccination at a site where the same vaccine is not available, or if the first product received is unknown, it is reasonable to offer one dose of the locally available product to complete the schedule. This option is preferred if the individual is likely to be at immediate high risk or is considered unlikely to attend again.

So they will not be "reserving" a second dose, and if there are shortages, you will get whatever they have on hand.

Although no data for co-administration of COVID-19 vaccine with other vaccines exists, in the absence of such data first principles would suggest that interference between inactivated vaccines with different antigenic content is likely to be limited (see Chapter 11). Based on experience with other vaccines any potential interference is most likely to result in a slightly attenuated immune response to one of the vaccines.

So they recommend against having the COVID-19 vaccine at the same time as other vaccines, e.g. the Influenza vaccine.

 

[Amw66]

Britain Opts for Mix-and-Match Vaccinations, Confounding Experts
https://www.nytimes.com/2021/01/01/health/coronavirus-vaccines-britain.html

Cited article:
https://assets.publishing.service.g...data/file/948757/Greenbook_chapter_14a_v4.pdf



So they will not be "reserving" a second dose, and if there are shortages, you will get whatever they have on hand.



So they recommend against having the COVID-19 vaccine at the same time as other vaccines, e.g. the Influenza vaccine.

Just when you thought things could not get more confusing....
Anti vaxxers will have a field day

 

[Sean]

Australia has shown that can be dealt with with a little patience and a sensible quarantine policy.

Most of the hard work here is being done by the state/territory governments and general population, while the federal government is not adequately controlling the international borders and cases are leaking across, which have to then be dealt with by the state/territory governments and general population.

Because we are relatively clear of cases (apart from a current so far smallish outbreak in Sydney) most people are living relatively normally and even getting blasé about it in many areas, so the damn thing can get going quickly once it gets across the border.