COVID Get Vaccinated Against the Covid Delta Variant

[atyy]

You're not the only one frightened by the government's plans:

https://www.theguardian.com/world/2...tm_source=esp&utm_medium=Email&CMP=GTUK_email

Might Hancock have done this differently?

 

[pinball1970]

Might Hancock have done this differently?

Probably not.
Hancock was being advised by the same group of scientific advisors as Sajid Javid is now?

 

[PeroK]

Probably not.
Hancock was being advised by the same group of scientific advisors as Sajid Javid is now?

I think that the science is definitely expected to follow the politics now!

 

[Fra]

It seems from a precaution perspective one could maybe waiting lifting recommendations or restrictions say until the fall, so one has more margin to see if there are some additional waves or new mutations giving more peaks, but at least in Sweden som argumetns for releasing recommnedations early is

1) Fatigue in public against restrictions, so when development looks brighter, its has to be balanced psychologically with release of restrictions, otherwise ppl will start ignoring the rules. Which could be bad in case it's needed to be put back in blace.

2) Legal ones, authorities say rules ensuring freedom of ppl must be well motivated. limiting peoples freedom is regulated by law and can not be done lightly, or by hunches.

3) I think the economical factors are also an issue, everyone hopes to get the wheels spinning again asap. Someone probably also makes a QALY/$ calculation of all this?

As no one KNOWS how things will develop, any kind of decision balance pros and cons, will risk getting bashed from either direction in the end.

/Fredrik

 

[Jonathan Scott]

My position has always been that the approach followed by countries such as New Zealand is best, that is to clamp down with strong rules to eliminate Covid as soon as possible, including reliable tracing, and don't let it back in. That's obviously to be followed up with vaccines when available, but got back to something similar to normal very rapidly.

It is clearly very important to make it practical for people to follow the rules; you can't just tell people to stop doing their job if that means they won't get paid. There have also been problems where events and jobs get canceled because of government guidelines which are not backed up by laws, because in that case it has been difficult to get any sort of compensation.

The damage done to the economy, mental health and so on obviously increases with time, but the half-hearted approach of removing restrictions and allowing it to run riot provided that it does not "overwhelm the health system" is clearly going to make it last a lot longer, not help any return to normal. It is therefore like doing damage at a somewhat smaller rate but for very much more time, which is clearly not a winning strategy.

Since the start of May, the Covid rate in the UK has increased by about a factor of 14, and it is currently going up by 74% per week (equivalent to trebling every two weeks). And every case creates a risk of a new even worse variant, as well as making it nearly certain that everyone will eventually end up exposed to it, and even those fully vaccinated are still at risk of serious illness.

No avoidable risks are acceptable to me. The leader (concertmaster) of my chamber orchestra caught Covid even before the first UK lockdown (in March 2020), while the government was dithering, and died shortly afterwards.

As a result of the rapid expansion of the delta variant, my son and all the other five people in his student house caught Covid three weeks ago. One person initially seemed to be getting cold-like symptoms (which are now considered to be a common characteristic of the delta variant but did not match the UK government advice for identifying Covid) but had a negative lateral flow test for several consecutive days before suddenly testing positive (just as the rest of them were getting symptoms). The government advice has now been revised to say the Covid delta variant can seem like a cold, and that if there are any symptoms of illness, even if it does not necessarily match the listed symptoms, a lateral flow test should not be used, but a PCR test should be requested immediately. Too late in this case.

My son's symptoms lasted about a week, then he came home here after another two weeks, assuming it was fine now, but he has now had a sudden relapse for the last few days. At age 20 he was not yet due for the vaccine, even though we are past the original planned date for ending restrictions. It's not clear whether my wife and I are required to self-isolate, as his positive test was around 4 weeks ago, and it seems likely that even though he has active symptoms (especially fever) the virus level should be much lower than it was initially, and he's able to live in his bedroom (with computers and TV) and use our guest bathroom, texting us if he needs anything brought to the bedroom door! Anyway, we are self-isolating voluntarily at the moment, and we have discovered that it is now possible to get stuff such as medicines delivered really quickly (within a few minutes) and surprisingly inexpensively via an online service.

 

[Rive]

You're not the only one frightened by the government's plans:

Once somebody decided not to eliminate the virus but to deal only with the first shock, releasing the preventive/protective measures is a must. The virus will drift, right. In order to have a valid and continuous protection, the population has to meet with the new variants frequently, within the timeframe while they are still protected by the previous version: otherwise a variant with accumulated changes meeting a waning protection might result higher lethality.

I too would rather opt for eliminating the virus But still, within their choice, it's logical and necessary step.

 

[Jonathan Scott]

Apparently with new figures (after the spread of the delta variant) the Pfizer vaccine is also much less effective against symptomatic disease from the delta variant. Estimates are around 64%, very similar to those for the AstraZeneca vaccine, estimated from a separate study at around 62%.

https://www.timesofisrael.com/israe...ective-against-delta-variant-eyes-third-dose/

To put it another way, if two fully vaccinated people (such as my wife and myself) are exposed to the delta variant, the probability they will both avoid symptomatic disease is about 40%, less than evens.

 

[PeroK]

And, extraordinarily, the UK is not speeding up second jabs. Last week we did only about 1 million first jabs and 1 million second jabs. That's only half the peak of 4 million per week.

It looks like we are starting to run out of people to vaccinate and the plan is to stick to the 12 week gap between first and second jabs.

The logic is to focus on the long-term benefits of the 12 week gap, but given the rise in cases, I would have thought tackling the Delta outbreak would be the priority.

 

[atyy]

Apparently with new figures (after the spread of the delta variant) the Pfizer vaccine is also much less effective against symptomatic disease from the delta variant. Estimates are around 64%, very similar to those for the AstraZeneca vaccine, estimated from a separate study at around 62%.

https://www.timesofisrael.com/israe...ective-against-delta-variant-eyes-third-dose/

To put it another way, if two fully vaccinated people (such as my wife and myself) are exposed to the delta variant, the probability they will both avoid symptomatic disease is about 40%, less than evens.

https://www.haaretz.com/israel-news...fections-in-israel-as-delta-spreads-1.9971842 gives the 64% as for infections, presumably both asymptomatic and asymptomatic - I wonder which is correct.

 

[Jonathan Scott]

I've just been checking my assumptions after spotting that I just assumed that being exposed to the delta variant was likely to cause symptomatic disease, rather than there being a significant chance of asymptomatic disease. However, it appears that this is a known feature of the delta variant.

In my son's student house, all six students (living in different flats but sharing kitchen and lounge) got symptomatic Covid. With the original Covid, many people, especially younger, had no symptoms. It's possible that those who had no symptoms had lower exposure and that therefore their immune systems were able to catch up more quickly. However, it does seem that the delta variant is significantly more likely to cause symptomatic disease.

 

[Sagittarius A-Star]

The logic is to focus on the long-term benefits of the 12 week gap, but given the rise in cases, I would have thought tackling the Delta outbreak would be the priority.

The German STIKO (Standing Committee on Vaccination) recommends now (because of the delta variant) for persons, who got the first shot with AstraZeneka-vaccine, to get the second shot minimum 4 weeks later with Biontech/Pfizer or Moderna (mRNA vaccine):
https://www.rki.de/DE/Content/Kommissionen/STIKO/Empfehlungen/PM_2021-07-01.html

Related press release of the Oxford University:

Of note is that the order of vaccines made a difference, with an Oxford-AstraZeneca/Pfizer-BioNTech schedule inducing higher antibodies and T-cell responses than Pfizer-BioNTech/Oxford-AstraZeneca, and both of these inducing higher antibodies than the licensed, and highly effective ‘standard’ two-dose Oxford-AstraZeneca schedule. The highest antibody response was seen after the two-dose Pfizer-BioNTech schedule, and the highest T cell response from Oxford-AstraZeneca followed by Pfizer-BioNTech.

Source:
https://www.ox.ac.uk/news/2021-06-2...generate-robust-immune-response-against-covid

A preliminary study shows a high number of antibodies and T-cells from the hybrid vaccination scheme.

Abstract
Adults ≥ 50 years, including those with well-controlled comorbidities, were randomised across eight groups to receive ChAd/ChAd, ChAd/BNT, BNT/BNT or BNT/ChAd, administered at 28- or 84-day intervals.
...
In conclusion, our study confirms the heterologous and homologous schedules of ChAd and BNT can induce robust immune responses with a 4-week prime boost interval.

Source:
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3874014

 

[Ygggdrasil]

Apparently with new figures (after the spread of the delta variant) the Pfizer vaccine is also much less effective against symptomatic disease from the delta variant. Estimates are around 64%, very similar to those for the AstraZeneca vaccine, estimated from a separate study at around 62%.

https://www.timesofisrael.com/israe...ective-against-delta-variant-eyes-third-dose/

To put it another way, if two fully vaccinated people (such as my wife and myself) are exposed to the delta variant, the probability they will both avoid symptomatic disease is about 40%, less than evens.

Here's a nice piece from the New York Times discussing various studies on the effectiveness of the Pfizer vaccine against the delta variant and the disagreement between the studies:

In Britain, researchers reported in May that two doses of the Pfizer-BioNTech vaccine had an effectiveness of 88 percent protecting against symptomatic disease from Delta. A June study from Scotland concluded that the vaccine was 79 percent effective against the variant. On Saturday, a team of researchers in Canada pegged its effectiveness at 87 percent.

And on Monday, Israel’s Ministry of Health announced that the effectiveness of the Pfizer-BioNTech vaccine was 64 percent against all Coronavirus infections, down from about 95 percent in May, before the Delta variant began its climb to near-total dominance in Israel.

https://www.nytimes.com/2021/07/06/science/Israel-Pfizer-covid-vaccine.html

In particular, the article notes:

One way to rule out these alternative explanations is to compare each vaccinated person in a study with a counterpart who did not get the vaccine. Researchers often go to great lengths to find an unvaccinated match, looking for people who are of a similar age and health. They can even match people within the same neighborhood.

“It takes a huge effort,” said Marc Lipsitch, an epidemiologist at the Harvard T.H. Chan School of Health.

For its new study, Israel’s Ministry of Health did not go to such great lengths to rule out other factors. “I am afraid that the current Israeli MoH analysis cannot be used to safely assess it, one way or another,” Uri Shalit, a senior lecturer at the Technion — Israel Institute of Technology, wrote on Twitter.

Given that the other much higher estimates come from published manuscripts and pre-prints where the data and methods are available, and the Israeli data showing the lower effectiveness come without any information on their data or methods, it might be prudent to wait and see the data underlying Israels' estimates.

 

[PeroK]

Given that the other much higher estimates come from published manuscripts and pre-prints where the data and methods are available, and the Israeli data showing the lower effectiveness come without any information on their data or methods, it might be prudent to wait and see the data underlying Israels' estimates.

The UK Government has based its strategy on the vaccinations being effective and the Delta variant being rendered largely harmless. We are now up to 32,500 cases today and the government's own projection is that we will be at 50,000 per day by July 19th when we open up and peak at 100,000 cases per day in August. Although, these may be optimistic figures.

It's a critical question for us is whether vaccination prevents hospitalisation and death. We'll soon find out.

What a gamble!

 

[OmCheeto]

The UK Government has based its strategy on the vaccinations being effective and the Delta variant being rendered largely harmless. We are now up to 32,500 cases today and the government's own projection is that we will be at 50,000 per day by July 19th when we open up and peak at 100,000 cases per day in August. Although, these may be optimistic figures.

It's a critical question for us is whether vaccination prevents hospitalisation and death. We'll soon find out.

What a gamble!

It is interesting watching my weekly plot for the UK. I keep waiting for a downturn. Israel seems to have joined you in the race. Note that this is a semi-log plot, so your recent growth looks quite exponential.

I finally figured out how to manually plot a linear fit with my spreadsheet. This allows me search for interesting trends around the world, without having to listen to the blather in the press.

Below I converted the 'cases/day/million(C/D/M)' for the last three weeks to log_10.
I converted the C/D/M values back to actual values, as log values are meaningless to me.
I filtered out anyone with an R^2 value less than 0.95.
Intercepts(b) less than 0.86 and slopes(m) less than 0.20 have been filtered out.
I also filtered out the US and Russia.

Kosovo has the worst growth rate.

Your Channel Islands and Israel are tied for the 2nd worst growth rate.

Scotland has the worst most recent C/D/M value.

Some of these may just be noise, so please don't read too much into this.

Created 2021.07.05	m = SP / SSx	b = My - m * Mx	R^2	C/D/M reported week #	C/D/M reported week #	C/D/M reported week #		fit	fit	fit
Date	1.00​	10​	1.001​	0​	1​	2​		0​	1​	2​
Kosovo	0.68​	1.09​	0.9999​	12​	59​	275​		12​	58​	277​
Channel Islands, United Kingdom	0.51​	2.23​	0.9999​	170​	540​	1765​		169​	545​	1756​
Israel	0.51​	1.43​	0.9516​	23​	118​	240​		27​	87​	280​
Cyprus	0.43​	2.57​	0.9988​	375​	946​	2681​		368​	984​	2629​
Malta	0.38​	1.24​	0.9937​	18​	39​	104​		17​	42​	100​
Mozambique	0.36​	1.52​	0.9848​	31​	84​	160​		33​	75​	170​
Burma	0.35​	1.64​	0.9983​	44​	94​	225​		44​	98​	221​
Baleares, Spain	0.35​	2.26​	0.9622​	199​	337​	991​		181​	405​	904​
Zimbabwe	0.32​	2.12​	0.9767​	122​	314​	540​		131​	275​	577​
Cantabria, Spain	0.32​	2.57​	0.9886​	358​	860​	1570​		374​	784​	1643​
Gilgit-Baltistan, Pakistan	0.30​	2.00​	0.9999​	100​	203​	403​		100​	201​	405​
Malawi	0.26​	1.31​	0.9948​	20​	40​	68​		21​	38​	70​
Scotland, United Kingdom	0.25​	3.17​	0.9597​	1381​	3040​	4426​		1479​	2649​	4742​
Wales, United Kingdom	0.25​	2.51​	0.9670​	307​	657​	971​		327​	581​	1033​
Belize	0.25​	2.24​	0.9825​	166​	334​	518​		173​	306​	541​
Fiji	0.24​	2.99​	0.9897​	944​	1815​	2867​		975​	1700​	2962​
Amazonas, Colombia	0.22​	2.06​	0.9940​	118​	183​	326​		115​	191​	319​
Finland	0.21​	1.95​	0.9824​	93​	135​	249​		89​	146​	240​
Michoacan, Mexico	0.21​	1.26​	0.9812​	17​	32​	46​		18​	29​	48​
Miyazaki, Japan	0.21​	0.86​	0.9916​	7​	11​	20​		7​	12​	19​
Tunisia	0.21​	3.08​	0.9949​	1188​	2036​	3098​		1212​	1957​	3160​
England, United Kingdom	0.21​	2.98​	0.9934​	978​	1469​	2523​		956​	1536​	2468​
Northern Ireland, United Kingdom	0.20​	2.71​	0.9957​	523​	794​	1340​		514​	823​	1317​

 

[Ygggdrasil]

The UK Government has based its strategy on the vaccinations being effective and the Delta variant being rendered largely harmless. We are now up to 32,500 cases today and the government's own projection is that we will be at 50,000 per day by July 19th when we open up and peak at 100,000 cases per day in August. Although, these may be optimistic figures.

Most cases likely represent cases in unvaccinated individuals, especially severe cases. In the US, >99% of COVID deaths are in unvaccinated individuals.

It's a critical question for us is whether vaccination prevents hospitalisation and death. We'll soon find out.

What a gamble!

All of the studies so far, including the data from Israel, suggest that the vaccine is very effective (>90%) at preventing severe disease, hospitalization and death. The figure I presented above (>99% of COVID deaths in the US are in unvaccinated individuals) is consistent with this idea.

 

[atyy]

All of the studies so far, including the data from Israel, suggest that the vaccine is very effective (>90%) at preventing severe disease, hospitalization and death. The figure I presented above (>99% of COVID deaths in the US are in unvaccinated individuals) is consistent with this idea.

The US data isn't for Delta. The Israel data is for Delta (>90%), but I think it's not yet released in detail.

The UK has Delta data (<90%), but I think only for first and second dose risk reduction in hospitalization.

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01358-1/fulltext
"Sequencing data from Scotland has found that for April 1 to May 28, 2021, the latest date until which data were available, 97% of S gene positive cases sequenced in Scotland were the Delta variant and that 99% of Delta variants were S gene positive. ...

Among S gene-negative cases, the effect of vaccination (at least 28 days after first or second dose) was to reduce the risk of hospital admission (HR 0·28, 95% CI 0·18–0·43) compared to unvaccinated. The corresponding hazard ratio for risk of hospital admission for S gene-positive cases was 0·38 (95% CI 0·24–0·58) ..."

 

[pinball1970]

I think that the science is definitely expected to follow the politics now!

The UK Government has based its strategy on the vaccinations being effective and the Delta variant being rendered largely harmless. We are now up to 32,500 cases today and the government's own projection is that we will be at 50,000 per day by July 19th when we open up and peak at 100,000 cases per day in August. Although, these may be optimistic figures.

It's a critical question for us is whether vaccination prevents hospitalisation and death. We'll soon find out.

What a gamble!

The September back to school wave is similar to the current wave

The only difference is September was pre DELTA and pre vaccine

We are at 32,000 per day now, similar numbers and curve to November 12th

Gradient is steeper now for this period but Delta is more infectious so that is expected?

The case rise through November led to 500-600 deaths per day whereas we are still at 35 per day.

Variant factories aside, this looks ok?

 

[Fra]

View attachment 285641

Variant factories aside, this looks ok?

Looking decent to me, but as a precaution there may an issue in the choice of measure.
Using only #death as a measure, lost QALY seems like a more relevant measure. It would be interesting to see that as well. For long-COVID or other unknowns there may be long term QALY loss which does not even involved death, and this are escaping the "death toll measure" altogether.

A model framework for projecting the prevalence and impact of Long-COVID in the UK
"The objective of this paper is to model lost Quality Adjusted Life Years (QALYs) from symptoms arising from COVID-19 in the UK population, including symptoms of ‘long-COVID’. The scope includes QALYs lost to symptoms, but not deaths, due to acute COVID-19 and long COVID...
...
we modeled 299,719 QALYs lost within 1 year of infection (90% due to symptomatic COVID-19 and 10% permanent injury) and 557,754 QALYs lost within 10 years of infection (49% due to symptomatic COVID-19 and 51% due to permanent injury)."
-- https://www.medrxiv.org/content/10.1101/2021.05.18.21252341v1.full

But another QALY paper, advocating ease of restructions (I apologize if this is posted elsewhere already)

"Stay at Home, Protect the National Health Service, Save Lives": A cost benefit analysis of the lockdown in the United Kingdom​

"This suggests that the costs of continuing severe restrictions are so great relative to likely benefits in lives saved that a rapid easing in restrictions is now warranted."
"- https://pubmed.ncbi.nlm.nih.gov/32790942/

So the antagonistic cynical statement may be?
"Go shopping, Protect the National Economy, Save Money"

/Fredrik

 

[pinball1970]

Yes I agree it is a lot more complicated than just cases/deaths.
I just noticed we have similar figures from September to Nov 2020 to the period we are in now.

Looking your references
If the vaccine reduces the ability of the virus to reproduce and do damage resulting in hospitalization and death could the vaccine reduce the risk of long Covid for instance?

In terms of a visit to A&E or an overnight stay not necessarily resulting in death, the below indicates the vaccine has had a huge impact.

We would expect those numbers to keep improving as the study starts from February when a lot less people were vaccinated or at least two doses plus 14 days.

https://assets.publishing.service.g...ants_of_Concern_VOC_Technical_Briefing_15.pdf

 

[Astronuc]

Here's a nice piece from the New York Times discussing various studies on the effectiveness of the Pfizer vaccine against the delta variant and the disagreement between the studies:

My wife was wondering about the effectiveness of Moderna against the Delta variant given a lot of news concerns the effectiveness of Pfizer vaccine.

LA Times has an article looking at the effectiveness of vaccines against Delta, but it seems to fall short without quantification.

Moderna said this week that its vaccine — which is very similar to the Pfizer shot — is also highly effective against the Delta variant.

Not much to go on.
https://www.latimes.com/science/sto...-do-covid-19-vaccines-cover-the-delta-variant

I still wear a mask going into public despite the rescinding of the 'mask mandate' for vaccinated people. The majority of the population do not wear masks, but I notice many elderly still do.

 

[atyy]

https://assets.publishing.service.g...ants_of_Concern_VOC_Technical_Briefing_15.pdf

Since I don't live in the UK, and think vaccinations should allow opening up - but don't know for sure - I'm very happy you are doing the experiment! OK, that's my bias. The one thing in the data you posted that makes me worried is that in Table 6 on p15, deaths as a proportion of cases is higher for the fully vaccinated (12/1785) than for the unvaccinated (23/19573) Perhaps not horrifying since the vaccinated were mostly old folks with a much higher risk of severe disease whereas the unvaccinated were young people not at risk, so one would need to know the age distribution ... I think

 

[Fra]

Looking your references
If the vaccine reduces the ability of the virus to reproduce and do damage resulting in hospitalization and death could the vaccine reduce the risk of long Covid for instance?

That seems like a logical expectation to me, and indeed even in Sweden we see reduced hospitalizations as well. So all looks promising. But so did it, last summer. Most was aware of a possible second wave, but NO experty I am aware of thought the second wave was going to be BIGGER than the first wave. Counterintuitive.

The major risk with the vaccine, seems to be it becomes a perfect excuse to opening up sooner. I totally understand the economical arguments though. Even early on in the pandemi, som ballpark estimates was that the cost supporting restrictions are massive, even compare to lost QALY. But that is a sensitive topic. If it wasnt for the cost of restrictions, it would seem reasonable to enjoy the effects of BOTH vaccines and some extended restrictions. But it's possible that with such strategy, we would have to keep up restrictions for years still, which may get unreasonable at some point.

I think a big nightmare outcome is that, motivated by the success of vaccines, a new mutation that perhaps makes an ADE exploit that Yggdrasil mentioned, so that those with antobodies are even MORE susceptible to a new mutation. But perhaps such an outcome is unlikely, who knows? But as per my poor understanding the risk for that would be higher if we vaccine everbody and then increase the spread of the virus because it's less harmful.

Personally I think thinks are looking decent, but I will hold my breath at least until christmas.

/Fredrik

 

[pinball1970]

I think that the science is definitely expected to follow the politics now!

Since I don't live in the UK, and think vaccinations should allow opening up - but don't know for sure - I'm very happy you are doing the experiment! OK, that's my bias. The one thing in the data you posted that makes me worried is that in Table 6 on p15, deaths as a proportion of cases is higher for the fully vaccinated (12/1785) than for the unvaccinated (23/19573) Perhaps not horrifying since the vaccinated were mostly old folks with a much higher risk of severe disease whereas the unvaccinated were young people not at risk, so one would need to know the age distribution ... I think

Yes I noticed that.
There was another report with over and under 50s vaccinated verses non vaccinated I will try and find that.

The numbers of those vaccinated who died roughly match those unvaccinated (20 and 23 resp) between 1/2/21 and 7/6/21The % of the unvaccinated for the 50+ group by June should have been very low (5% ish). They were vaccinating 50-60 years end of March.

@PeroK explained this better on another post (which I cannot find). 95% of that group (vaccinated 50+) yielded less deaths than the remaining 5% meaning being unvaccinated is 20 times more dangerous than being vaccinated.

I think we can apply that to these numbers?
Even if I have got the wrong end of the stick on that it is certain you are much more likely to end up in hospital if you are unvaccinated which means something potentially serious is going on.

Perhaps lead to some of the possible long term injuries/long Covid numbers discussed on pf.

 

[atyy]

LA Times has an article looking at the effectiveness of vaccines against Delta, but it seems to fall short without quantification.

The LA Times article is behind a paywall. I agree there aren't numbers yet for Moderna. However, Moderna used 2 tricks that Pfizer also used: (i) Kariko, Weissman and colleagues' tweak of the chemical composition of the mRNA so that the mRNA itself doesn't provoke the immune system so much (it's the protein product of the mRNA that we want to stimulate immune responses) (ii) McLellan and colleague's trick of holding the protein protein in correct pre-fusion shape, that we want the immune system to recognize and attack. So one would expect it performs very similarly to the Pfizer vaccine.

 

[atyy]

https://www.bbc.com/news/uk-england-london-57732002
Covid-19: Euro 2020 tickets offered as part of vaccine push

Mayor Sadiq Khan is offering two tickets to Sunday's final as well as 50 pairs of tickets to the Trafalgar Square Fan Zone.

 

[pinball1970]

I think a big nightmare outcome is that, motivated by the success of vaccines, a new mutation that perhaps makes an ADE exploit that Yggdrasil mentioned

/Fredrik

ADE? That is a new one to me.
I will keep my eye out for information on this relating to COVID as the paper is pre vaccine (September 2020)
With 79 million vaccinated an opportunity to see if ADE is a thing or not with COVIDThis one is post vaccine, a little harder to read (for me)
Note the mast cell reference also ( a worry for me during all this being asthmatic )
https://www.frontiersin.org/articles/10.3389/fimmu.2021.640093/full

Another search found this
https://www.news-medical.net/news/2...underlie-inflammation-in-severe-COVID-19.aspx

 

[Fra]

This is really interesting and fascinating indeed, but it seems also very complex. A broad nice T-cell immunity seems nice, but at the same time a broader immunity must be ensured not to overreat or borderling to autoimmunity. It seems evolution has taken well care of this to keep it balanced most of the time. Many papes report that severeity of disease seems linked to either a poor T-cell response, or a too strong (or incorrectly regulated) T-cell response.

Severe COVID-19 infection linked to overactive immune cells​

"Sometimes, our immune system overreacts to invaders, for example during an allergic reaction, resulting in T cells killing normal, healthy cells and causing tissue damage. However, there is a ‘brake mechanism’ that should kick in, causing T cells to reduce their activity and calming inflammation.
...
On closer inspection of the mechanism, the researchers found that the protein ‘Foxp3’, which usually induced the brake mechanism, is inhibited in lungs of severe COVID-19 patients. They are unsure why Foxp3 is inhibited, but further study could reveal this, and potentially lead to a way to put the brakes back on the T cell response, reducing the severity of the disease."
-- https://www.imperial.ac.uk/news/206173/severe-covid-19-infection-linked-overactive-immune/

I guess the more specific B-cell response seems is filling a gap here as well, in beeing "safer", with less risk of overdoing things? Marking a disarming a virus is one thing, but killing a "potentiall infected" cells is certainly more drastic unless the malign status is 100% certain.

/Fredrik

 

[Ygggdrasil]

That seems like a logical expectation to me, and indeed even in Sweden we see reduced hospitalizations as well. So all looks promising. But so did it, last summer. Most was aware of a possible second wave, but NO experty I am aware of thought the second wave was going to be BIGGER than the first wave. Counterintuitive.

It is perfectly reasonable to think that the second wave would be bigger than the first wave; that's what happened in the 1918 Influenza pandemic.

https://www.cdc.gov/flu/pandemic-resources/1918-commemoration/three-waves.htm

For example, here's an article for May 2020 of an expert with extremely prescient warnings of how the fall and winter of 2020/2021 would play out: https://www.ama-assn.org/delivering...emiologist-beware-covid-19-s-second-wave-fall

The major risk with the vaccine, seems to be it becomes a perfect excuse to opening up sooner. I totally understand the economical arguments though. Even early on in the pandemi, som ballpark estimates was that the cost supporting restrictions are massive, even compare to lost QALY. But that is a sensitive topic. If it wasnt for the cost of restrictions, it would seem reasonable to enjoy the effects of BOTH vaccines and some extended restrictions. But it's possible that with such strategy, we would have to keep up restrictions for years still, which may get unreasonable at some point.

I think a big nightmare outcome is that, motivated by the success of vaccines, a new mutation that perhaps makes an ADE exploit that Yggdrasil mentioned, so that those with antobodies are even MORE susceptible to a new mutation. But perhaps such an outcome is unlikely, who knows? But as per my poor understanding the risk for that would be higher if we vaccine everbody and then increase the spread of the virus because it's less harmful.

Many studies have looked for signs of ADE, but none have found any, even with the variants. To quote an article on the subject:

So here’s the short version: no sign of ADE during the preclinical animal studies. No sign during the human clinical trials. No sign during the initial vaccine rollouts into the population. And (so far) no sign of ADE even with the variant strains in different parts of the world. We have things to worry about in this pandemic, but as far as I can tell today, antibody-dependent enhancement does not seem to be one of them. I understand why people would worry about it, and want to avoid it. But if you’re coming across reports that say that it’s a real problem right now and that you should avoid getting vaccinated because of it, well, I just don’t see it. Some of that is well-intentioned caution, and some of it is probably flat-out anti-vaccine scaremongering.​

https://blogs.sciencemag.org/pipeli...dent-enhancement-and-the-coronavirus-vaccines (the full article is a good read if one is interested on the topic)

This is really interesting and fascinating indeed, but it seems also very complex. A broad nice T-cell immunity seems nice, but at the same time a broader immunity must be ensured not to overreat or borderling to autoimmunity. It seems evolution has taken well care of this to keep it balanced most of the time. Many papes report that severeity of disease seems linked to either a poor T-cell response, or a too strong (or incorrectly regulated) T-cell response.

Severe COVID-19 infection linked to overactive immune cells​

"Sometimes, our immune system overreacts to invaders, for example during an allergic reaction, resulting in T cells killing normal, healthy cells and causing tissue damage. However, there is a ‘brake mechanism’ that should kick in, causing T cells to reduce their activity and calming inflammation.
...
On closer inspection of the mechanism, the researchers found that the protein ‘Foxp3’, which usually induced the brake mechanism, is inhibited in lungs of severe COVID-19 patients. They are unsure why Foxp3 is inhibited, but further study could reveal this, and potentially lead to a way to put the brakes back on the T cell response, reducing the severity of the disease."
-- https://www.imperial.ac.uk/news/206173/severe-covid-19-infection-linked-overactive-immune/

I guess the more specific B-cell response seems is filling a gap here as well, in beeing "safer", with less risk of overdoing things? Marking a disarming a virus is one thing, but killing a "potentiall infected" cells is certainly more drastic unless the malign status is 100% certain.

It is well documented that severe COVID-19 is associated with dysregulation of the immune system which can result in a "cytokine storm," where at late stages of the disease, most of the damaging symptoms come from the immune response to the infection rather than the infection itself (which is why immunosuppresants like dexamethosone have been identified as effective treatments in later stage disease). However, patients progress to later-stage severe disease because their adaptive immune systems were not able to control the infection at an earlier point (see this article for a review).

Given the wide variety of clinical and observational data suggesting that both vaccination and prior infection can protect against severe disease, hospitalization and death, I don't think that having T-cell immunity is a problem for SARS-CoV-2 infection. Rather the problem is lacking immunity, getting infected, and having the virus replicate to high levels before the adaptive immune system catches up. Once the virus is widespread throughout the body, it is at this point where the immune response to the virus can trigger cytokine storms and other severe symptoms of the disease.

 

[artis]

So speaking about pandemic waves , do all virus pandemics follows a trend where the first wave is somewhat smaller, then the second wave is a killer and by each next wave the severity and numbers fall down ?
I hope this is the case for Covid, but it also seems to have been the case for the infamous and deadly "Spanish flu" and back then we did not have any vaccines but it seems that the path still resembles that of the current Covid even with us now having tons more safety gear and drugs and vaccines.
I would love some clever opinions on this one.

 

[Jonathan Scott]

There are many situations in which delayed feedback can cause increasing oscillations.