Get Vaccinated Against the Covid Delta Variant

[bob012345]

It is better to openly argue for a direct punishment, than to sick a cruel loophole on people that may condemn them to a life of poverty suffering and accelerated death, that will also affect innocent bystanders who have medical reasons not to get a vaccine, and will also set a dangerous precedent that could ruin a lot more lives in the future.

The whole purpose of my idea is not to punish people for the sake of punishment but to induce them to get the vaccine. I am open to a cap on the consequences but it should be a strong enough motivation that most unvaccinated people will choose to get the shot.

 

[Fra]

The whole purpose of my idea is not to punish people for the sake of punishment but to induce them to get the vaccine.

Maybe some people remember the narcolepsy cases, triggered from swineflue, and in Sweden there was supposed to be a insurance that pays up to the order of a million dollars or so to anyone getting sick from the vaccine. Even if no money can give your health back, as far as I know, lots of people still hasn't received it. So from the public perspective, full responsibility has not taken (and maybe cannot/should not be taken) from the governement for damages cause by a mass vaccination with a vaccine who has been developed in a rush. This makes it unreasonable to force anyone.

I hear a lot of people reason like, they want the vaccine - but don't want to be first in line. Unfortunately stressful situations forces us to take risky decisions, as not taking actions due to lack of enough evidence as per regular standards is also a risk. Each individual needs to have the freedom to make their own risk assessment, no one else can or should do that for you.

If the choice given the right information is trivial, then sharing the "wisdom" by informing people better should be the way to go.

/Fredrik

 

[atyy]

@Fra what do you think of requiring health care workers to be vaccinated?

https://www.nytimes.com/2021/04/21/health/vaccine-nursing-homes-infections.html

https://ltccovid.org/2021/05/25/nat...d-practices-in-relation-to-covid-19-no-1-may/

 

[Fra]

@Fra what do you think of requiring health care workers to be vaccinated?

https://www.nytimes.com/2021/04/21/health/vaccine-nursing-homes-infections.html

https://ltccovid.org/2021/05/25/nat...d-practices-in-relation-to-covid-19-no-1-may/

Big questions I guess, but I see two components,

1) occupational health - workers who are "forced" to take at higher risk due to their occupation, that is also of extra importance during the pandemi itself. It seems reasonable and fair that they should get priority in vaccine lines to balance the risk they are also taking.

2) Your decisions affect other people - this is more tricky and involves also psychology. I guess there is a balance. The fact that our own decisions affects our own environment in general sense is I think unavoidable, but when the effects is more directed towards certain groups, I agree a discussion is needed. If unvaccinated workes are a clear and big threat (if it is, I don't know) then one can consider saying that these workes are temporarilty not allowed to work in that area until vaccinated (they get to work in a less critical area temporarilty). OTOH, if this is a big problem it perhaps also indicates that OTHER protective equipment is insufficient during patient contact?

About the general philosophy about decisions affecting the environment, one also has to accept that the environment tries to control your decisions as that decision to influences is also their free decision and part of the "game". That is fine. I just think that too much forcing will in the long term build-in tension among everyone. Anyone feeling forced, instead of getting "help to make their own informed rational decions" can also overreact and become hostile to the environment, and it can lead to bad development. But this then turns into sociology, psycholgoy and politics I guess. Do we want a well informed population that makes rational decisions, or do we want a dictator that rules a population of fools given not incentive to make own decisions? Both systems will work, but the latter will have a large built-in tension that sooner or later will blow up.

If the people don't trust politician or government we have a problem.

The argument that "because daddy says so" is easier to come up with, than to really try to EXPLAIN at the right level, and help reasoning. And accepting "argument due to authority" shouldn't be encouraged in the first place. I think one should treat the reasons for peoples decisions with respect and instead invite for discussions.

/Fredrik

 

[Fra]

but it should be a strong enough motivation that most unvaccinated people will choose to get the shot.

If a reasonably objective (probable benefit is >> the probable damage) is not strong enough motivation?
What is the problem we have at hand?

Except for a minority which may have various religious reasons for things, maybe educating people in rational decision help? If so, forcing them will be counterproductive I think. Taking their reasoning seriously and meeting their arguments may be better, but perhaps requiring more resources.

/Fredrik

 

[atyy]

https://www.researchsquare.com/article/rs-637724/v1
SARS-CoV-2 B.1.617.2 Delta variant emergence and vaccine breakthrough
Mlcochova et al (from Ravindra K. Gupta's group)

They summarize their findings in a Twitter thread.

"While there is substantial uncertainty in our estimates, we find that 𝘪𝘯 𝘔𝘶𝘮𝘣𝘢𝘪 the Delta variant was 10% to 40% more transmissible than previously circulating lineages, and able to evade 20 to 55% of the immune protection provided by prior infection with non-Delta virus."

"Summary:The Delta variant has significant immune evasion and fitness compared to Alpha. Vaccines will prevent severe disease/death in *most* people, but special measures may be needed for those who respond poorly to vaccination. Infection in vaccinated HCWs needs to be considered"

 

[Evo]

More on the Delta variant.

Dangerous Delta COVID-19 Variant Infecting Vaccinated Adults In Israel

But half of the adults infected had been fully vaccinated with the Pfizer vaccine, Balicer said.

About 90% of the new infections in Israel were likely caused by the delta variant, the Journal reported.

The World Health Organization on Friday also warned everyone, even those fully vaccinated, to “play it safe” and continue to wear a mask and maintain social distancing in light of the large numbers of people who remain unvaccinated and the emergence of the delta variant, which it called the “most transmissible” form of the Coronavirus identified to date.

“People cannot feel safe just because they had the two doses. They still need to protect themselves,” Dr. Mariangela Simao, WHO assistant director-general for access to medicines, said at a news briefing in Geneva. “Vaccine alone won’t stop community transmission.”

“People need to continue to use masks consistently, be in ventilated spaces, [use] hand hygiene ... [practice] physical distance, avoid crowding.”

continued...

https://www.yahoo.com/huffpost/dangerous-delta-covid-19-variant-011913549.html

 

[PeroK]

This begs the question: what is the plan to get back to normal life? If mass vaccination isn't enough, then what do we do?

 

[Ygggdrasil]

Some excerpts from some articles from STAT news on the topic:

How did those pandemics end? The viruses didn’t go away; a descendent of the Spanish flu virus, the modern H1N1, circulates to this day, as does H3N2. Humans didn’t develop herd immunity to them, either. That’s a phenomenon by which a pathogen stops spreading because so many people are protected against it, because they’ve already been infected or vaccinated.

Instead, the viruses that caused these pandemics underwent a transition. Or more to the point, we did. Our immune systems learned enough about them to fend off the deadliest manifestations of infection, at least most of the time. Humans and viruses reached an immunological détente. Instead of causing tsunamis of devastating illness, over time the viruses came to trigger small surges of milder illness. Pandemic flu became seasonal flu.

The viruses became endemic.

If the pattern holds, and it is expected to, SARS-2 will at some point join a handful of human coronaviruses that cause colds, mainly in the winter, when conditions favor their transmission.

https://www.statnews.com/2021/05/19...cientists-look-to-the-past-to-see-the-future/

Functional immunity, on the other hand, may be within reach. In fact, it’s the scenario Menachery sees as most likely.

Under this scenario, people whose immune systems have been primed to recognize and fight the virus — whether through infection or vaccination — could contract it again in the future. But these infections would be cut short as the immune system’s defenses kick into gear. People infected might not develop symptoms or might have a mild, cold-like infection.

“I’m a believer that if you’ve gotten Covid-19, then your likelihood of dying from a second Covid-19 case is very low, if you maintain immunity,” Menachery said.

Peiris agreed. “It won’t have the impact it has now. … It becomes manageable.”

https://www.statnews.com/2020/08/25/four-scenarios-on-how-we-might-develop-immunity-to-covid-19/

(the full articles are worth a read if you are interested in the subject)

The problem with SARS-CoV-2 has been that it has not necessarily been that it infects people, but that it causes deadly symptoms in a large number of people (especially in certain vulnerable populations). While the new variants seem to be able to at least partially evade some antibody-based humoral immunity to infect a small fraction of vaccinated individuals, other evidence suggest that the variants (so far) are not able to evade the cellular immune response mediated by T-cells that keeps infections from spreading out of control and causing severe symptoms. For example, here are a few studies on the topic:

Negligible impact of SARS-CoV-2 variants on CD4+ and CD8+ T cell reactivity in COVID-19 exposed donors and vaccinees
https://www.biorxiv.org/content/10.1101/2021.02.27.433180v1

SARS-CoV-2 variants of concern partially escape humoral but not T-cell responses in COVID-19 convalescent donors and vaccinees
https://immunology.sciencemag.org/content/6/59/eabj1750

CD8+ T cell responses in COVID-19 convalescent individuals target conserved epitopes from multiple prominent SARS-CoV-2 circulating variants
https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofab143/6189113

Consistent with the idea that T-cell responses and cellular immunity are not affected by the variants, most studies of the vaccines suggest that the vaccines are still very effective at preventing severe disease, hospitalization and death from the coronavirus.

The recent increase in COVID-19 cases in Israel could be an interesting test case. It will be interesting to see whether the recent uptick in cases are accompanied by any uptick in hospitalizations or deaths. If not, then Israel would show that vaccination is a successful strategy to exit the pandemic: with vaccination, SARS-CoV-2 becomes something like seasonal flu—still an ever-present danger and something that can be deadly, but not to the level that it requires massive disruptions to normal life.

Pre-pandemic, people tolerated ~10-60k deaths during typical flu seasons. If COVID-19 mortality could be reduced by a factor of 10-20 (which seems reasonable given the data we have on the vaccines), this would place COVID-19 mortality in the "acceptable" range for society.

 

[Evo]

@Ygggdrasil , so do they foresee a yearly SARS-CoV-2 vaccine like the flu vaccine now? If the scenario plays out as they hope, which seems reasonable.

I get my second dose of Pfizer in a few hours.

I went to Walmart yesterday because I had to go to the post office down the street from it, NO ONE WAS WEARING A MASK! I was the only one, it was standing room only in the post office, no masks, Walmart was crowded, no masks, not even the employees. I was the ONLY ONE! And I KNOW most of these people were not vaccinated. I live in a state where only ~40% of the population are vaccinated.

 

[Ygggdrasil]

@Ygggdrasil , so do they foresee a yearly SARS-CoV-2 vaccine like the flu vaccine now? If the scenario plays out as they hope, which seems reasonable.

I get my second dose of Pfizer in a few hours.

I don't think we have enough data to know how long immunity will last. Data from other coronaviruses suggests immunity could start to wane as soon as ~1 year after infection, though re-infections are much more likely to be asymptomatic. For example, see these two studies:

The time course of the immune response to experimental Coronavirus infection of man
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2271881/

Seasonal Coronavirus protective immunity is short-lasting
https://www.nature.com/articles/s41591-020-1083-1

Current data from observational studies I have seen don't see signs of waning immunity from vaccination or infection after ~ 8-9 months, though longer term data is definitely needed.

If annual booster shots are required, there are definitely plenty of companies working on them, and IIRC Pfizer and Moderna are running clinical trials on vaccine booster shots against some of the new variants. Various companies are also creating and testing vaccines that would vaccinate against both the flu and COVID-19.

Glad to hear you are getting your second shot! Hope you don't have side effects that were too bad (I just had a mild headache the day after my second shot).

 

[Fra]

SARS-CoV-2 variants of concern partially escape humoral but not T-cell responses in COVID-19 convalescent donors and vaccinees
https://immunology.sciencemag.org/content/6/59/eabj1750
...
Consistent with the idea that T-cell responses and cellular immunity are not affected by the variants, most studies of the vaccines suggest that the vaccines are still very effective at preventing severe disease, hospitalization and death from the coronavirus.

Thanks!

It made my head spin and I found these(non-COVID specific) as well:

Cross-Reactivity of T Cells and Its Role in the Immune System​

"The ability of the T-cell receptor (TCR) to recognize more than one peptide-MHC structure defines cross-reactivity. Cross-reactivity is a documented phenomenon of the immune system whose importance is still under investigation. There are a number of rational arguments for cross-reactivity. These include the discrepancy between the theoretical high number of pathogen-derived peptides and the lower diversity of the T-cell repertoire, the need for recognition of escape variants, and the intrinsic low affinity of this receptor–ligand pair. However, quantifying the phenomenon has been difficult, and its immunological importance remains unknown. In this review, we examined the cases for and against an important role for cross reactivity. We argue that it may be an essential feature of the immune system from the point of view of biological robustness."
-- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3595599/Why must T cells be cross-reactive?
"Clonal selection theory proposed that individual T cells are specific for a single peptide–MHC antigen. However, the repertoire of αβ T cell receptors (TCRs) is dwarfed by the vast array of potential foreign peptide–MHC complexes, and a comprehensive system requires each T cell to recognize numerous peptides and thus be cross-reactive. This compromise on specificity has profound implications because the chance of any natural peptide–MHC ligand being an optimal fit for its cognate TCR is small, as there will almost always be more-potent agonists. Furthermore, any TCR raised against a specific peptide–MHC complex in vivo can only be the best available solution from the naive T cell pool and is unlikely to be the best possible solution from the substantially greater number of TCRs that could theoretically be produced. This 'systems view' of TCR recognition provides a plausible cause for autoimmune disease and substantial scope for multiple therapeutic interventions."
-- https://www.nature.com/articles/nri3279

So it seems to me from laymen perspective that T-cell defense, somehow fits in between innate and the humoral system, although it's considered part of the adaptive system? ie. The Innate system is very unspecific, but the T-cell system is more specifi, but the humoral system is even more specific? Or am I rushing into a incorrect conclusion here?

It seems to me without the humoral system, the T-cell system would have to be EVEN more cross responsive, and likely increase the chance of autoimmune reations? It's amazing to see the beauty of evolution, and how all parts seems to play a crucial role?

/Fredrik

 

[atyy]

This begs the question: what is the plan to get back to normal life? If mass vaccination isn't enough, then what do we do?

The UK is ahead of Israel in terms of having had the delta variant, and it has a high vaccination rate that it is trying to increase. So we'll have to wait and hope the UK has good results. If it isn't enough, I'd guess that probably the first thing to do would be to give a third vaccine dose to the vulnerable groups.

Edit: Israel newspaper report on the UK: https://www.haaretz.com/israel-news...-but-hospitalizations-remain-stable-1.9943803 (apparently numbers in the UK are looking ok, although it is too early to be sure?)

 

[PeroK]

The UK is ahead of Israel in terms of having had the delta variant, and it has a high vaccination rate that it is trying to increase. So we'll have to wait and hope the UK has good results. If it isn't enough, I'd guess that probably the first thing to do would be to give a third vaccine dose to the vulnerable groups.

Edit: Israel newspaper report on the UK: https://www.haaretz.com/israel-news...-but-hospitalizations-remain-stable-1.9943803 (apparently numbers in the UK are looking ok, although it is too early to be sure?)

I think it is too early to tell. One problem is that the UK schools are severely disrupted with pupils off school with COVID. If eventually we have to live with the Delta variant and its successors, then okay. But, it probably means at least another 3-6 months of disruption in the meantime.

If there is no longer an unbearable strain on the health service, then that is a big relief. The hope was that with 80%+ of the adult population vaccinated we would be back to near normality. Despite the vaccination speed and success we are still a long way from normality.

 

[Rive]

...has a high vaccination rate that it is trying to increase.

Based on the example of the major variants so far, countries with high vaccination rate should look out for further possible outbreaks (countries with low vaccination rate) instead of chasing the 100%: since any new variant possibly can (and, in case of further carelessness: sooner or later it likely will) make their high vaccination rate obsolete.

 

[atyy]

Based on the example of the major variants so far, countries with high vaccination rate should look out for further possible outbreaks (countries with low vaccination rate) instead of chasing the 100%: since any new variant possibly can (and, in case of further carelessness: sooner or later it likely will) make their high vaccination rate obsolete.

It's almost certain new variants will arise that will be able to reinfect everyone who is vaccinated. But I think it's possible that these new variants will only cause mild disease? If they only cause mild disease, then once a country reaches 100% vaccination, it can just let everyone get infected with the new variants?

 

[Rive]

It's almost certain new variants will arise that will be able to reinfect everyone who is vaccinated.

But the sped of drift depends on the 'frenzy' it's copying itself. Any widespread outbreak will come up with new variants, further away from the original.

 

[atyy]

But the sped of drift depends on the 'frenzy' it's copying itself. Any widespread outbreak will come up with new variants, further away from the original.

There are already 4 human coronaviruses that cause only mild disease, and these also are continually mutating such that any person who is infected will have immunity for only a few years. But these mutations are not of concern. Isn't it a possibility that vaccination will be sufficient to make SARS-CoV-2 like a 5th human Coronavirus that isn't of particular concern?

 

[pbuk]

I had to fix the numbers above. I forgot that only half of the recent jabs would be first timers.

By the end of April the numbers were:

For Alpha: 34.5 million protected (at least once)

For Delta: 15 million protected (twice)

And we could have had:

For Alpha: 26.5 million protected (at least once)

For Delta: 23 million protected (twice).

If we had follwed that route we could have had a maximum of 26.5m twice vaccinated by the end of June (assuming 2 months i.e. approx 8 weeks between shots); we already have 32 million.

Yes second shots are important, but you can't have a second shot until you have had a first shot so these are important too!

 

[Fra]

But I think it's possible that these new variants will only cause mild disease?

Even if the mutations themselves may be random and could be worse as well as milder, the shouldn't the selection mechanism likely to favour milder disease, as if you get strong symptoms you would isolate yourself. If you get mild symptoms, the chances is you keep interacting and spread the disease more on society, and thus such versions should be favoured in evolution.

From the virus perspective, instantly killing the host would not be a good survival strategi, as a virus is depending on it's host to reproduce.

/Fredrik

 

[Rive]

There are already 4 human coronaviruses that cause only mild disease, and these also are continually mutating such that any person who is infected will have immunity for only a few years. But these mutations are not of concern.

As long as the speed of drift is low, so there is sufficient time for every mutation to spread and renew/actualize the immunity of the population.
With the mutation rate high, it can become a very different story.

Isn't it a possibility that vaccination will be sufficient to make SARS-CoV-2 like a 5th human Coronavirus that isn't of particular concern?

It's a possibility, but right now we still have outbreaks to provide new variants at rapid speed. We may need a round of updated vaccines before it'll be settled.

shouldn't the selection mechanism likely to favour milder disease

That's a story which is easy to misunderstand. The situation needs to meet some criteria first to have those kind of selection pressures to appear. At this point what we should hope for is not a change in the virus, but a widespread change in our immune system.

 

[Fra]

That's a story which is easy to misunderstand. The situation needs to meet some criteria first to have those kind of selection pressures to appear.

What criteria? Longer timescales and high mutation rates?

/Fredrik

 

[atyy]

Even if the mutations themselves may be random and could be worse as well as milder, the shouldn't the selection mechanism likely to favour milder disease, as if you get strong symptoms you would isolate yourself. If you get mild symptoms, the chances is you keep interacting and spread the disease more on society, and thus such versions should be favoured in evolution.

From the virus perspective, instantly killing the host would not be a good survival strategi, as a virus is depending on it's host to reproduce.

But what if the virus only kills a small percentage of those it infects (0.5%)? And for the small percentage that it kills, the subject is symptomless for the first week, yet can spread the virus best in that time. By the time the subject has symptoms and isolates himself, it's already the second week. And perhaps the virus is not able to spread in the second week (because by that time the immune system has fought it off, and the subject is dying from an overactive immune system)? Will this virus be under any pressure to become milder?

Perhaps it's similar to the explanation offered for why there are many diseases that appear with age (long after the reproductive age), but are not strongly selected against, because they don't affect the subject's ability to reproduce? https://www.nature.com/scitable/knowledge/library/the-evolution-of-aging-23651151/

 

[Ygggdrasil]

Thanks!

It made my head spin and I found these(non-COVID specific) as well:

Cross-Reactivity of T Cells and Its Role in the Immune System​

"The ability of the T-cell receptor (TCR) to recognize more than one peptide-MHC structure defines cross-reactivity. Cross-reactivity is a documented phenomenon of the immune system whose importance is still under investigation. There are a number of rational arguments for cross-reactivity. These include the discrepancy between the theoretical high number of pathogen-derived peptides and the lower diversity of the T-cell repertoire, the need for recognition of escape variants, and the intrinsic low affinity of this receptor–ligand pair. However, quantifying the phenomenon has been difficult, and its immunological importance remains unknown. In this review, we examined the cases for and against an important role for cross reactivity. We argue that it may be an essential feature of the immune system from the point of view of biological robustness."
-- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3595599/Why must T cells be cross-reactive?
"Clonal selection theory proposed that individual T cells are specific for a single peptide–MHC antigen. However, the repertoire of αβ T cell receptors (TCRs) is dwarfed by the vast array of potential foreign peptide–MHC complexes, and a comprehensive system requires each T cell to recognize numerous peptides and thus be cross-reactive. This compromise on specificity has profound implications because the chance of any natural peptide–MHC ligand being an optimal fit for its cognate TCR is small, as there will almost always be more-potent agonists. Furthermore, any TCR raised against a specific peptide–MHC complex in vivo can only be the best available solution from the naive T cell pool and is unlikely to be the best possible solution from the substantially greater number of TCRs that could theoretically be produced. This 'systems view' of TCR recognition provides a plausible cause for autoimmune disease and substantial scope for multiple therapeutic interventions."
-- https://www.nature.com/articles/nri3279

So it seems to me from laymen perspective that T-cell defense, somehow fits in between innate and the humoral system, although it's considered part of the adaptive system? ie. The Innate system is very unspecific, but the T-cell system is more specifi, but the humoral system is even more specific? Or am I rushing into a incorrect conclusion here?

It seems to me without the humoral system, the T-cell system would have to be EVEN more cross responsive, and likely increase the chance of autoimmune reations? It's amazing to see the beauty of evolution, and how all parts seems to play a crucial role?

/Fredrik

The T-cell system is definitely part of the adaptive immune system even though they show more cross-reactivity than antibodies. The innate immune system is capable of recognizing broad classes of pathogens, for example, it can recognize lipopolysaccarides from all gram-negative bacteria or dsRNA from all classes of RNA viruses. The humoral (antibody) and cellular (T-cell) immune responses are typically specific to one specific virus, though they can sometimes protect against other related viruses as well (e.g. see discussing in this PF thread).

In addition to the reasons detailed in the pieces you cited detailing the reasons for the greater cross-reactivity of T-cells versus antibodies, an additional reason has to do with how the two different systems recognize their antigens. Antibodies are limited to recognizing antigens that are displayed on the surface of the pathogen and are accessible to the antibodies (many proteins of the surface of cells and viruses are glycosylated and the glycan groups can hinder antibodies from accessing certain sites on the glycoproteins). Furthermore, for an antibody to be a neutralizing antibody that can prevent viruses from infecting cells, it has to bind with specific spots on the antigen that hinder its function. Because of the limited epitopes that could act as binding sites for neutralizing antibodies, viruses can often evolve to find a small set of mutations to evade specific neutralizing antibodies.

In contrast, MHC molecules within infected cells can present a wide variety of peptides to T-cells, and these are not limited by whether the proteins are on the cell surface or even if these peptides would normally be accessible when the protein is folded. Because T-cells can recognize a variety of epitopes across the entire antigen, it is harder for viruses to evade this response by mutating specific amino acids on specific proteins.

This difference also speaks to the different functions of the two systems. The humoral immune response seeks to generate neutralizing antibodies that can prevent viruses from infecting cells in the first place. The cellular immune response cannot prevent infection from occurring; rather, once cells become infected, the cellular immune response seeks to cull the infected cells to prevent and limit the infected cells from producing more viruses.

 

[Evo]

Today.

Of those who were fully vaccinated who caught the Delta variant, 50 died, data from Public Health England that was published on Friday indicated.

The figure represents almost half of the total 117 deaths associated with the variant in the UK, where Delta now represents most cases.

But experts said this does not undermine what we know about the efficacy of the vaccines, given that the deaths come from age groups at higher risk and represent a tiny proportion of the 92,029 Delta cases analyzed

Data showed that 1,320 were sick enough to spend a night in the hospital after catching the Delta variant. Of those, 190 were fully vaccinated — that is about 14%. And 831, or a much higher 63%, were unvaccinated.

https://www.businessinsider.com/vac...eaths-but-older-relatively-few-uk-data-2021-6

 

[PeroK]

Today.
https://www.businessinsider.com/vac...eaths-but-older-relatively-few-uk-data-2021-6

At least 95% of people in the vulnerable groups have been fully vaccinated. We have approximately equal numbers of deaths from the 95% vaccinated against the 5% unvaccinated. So, it appears to be about 20 times more dangerous to be unvaccinated.

 

[Fra]

Thanks for the great explanations!

The T-cell system is definitely part of the adaptive immune system even though they show more cross-reactivity than antibodies. The innate immune system is capable of recognizing broad classes of pathogens, for example, it can recognize lipopolysaccarides from all gram-negative bacteria or dsRNA from all classes of RNA viruses.

If found this interesting stuff as well, suggesting some T-cells does not learn, and behave a bit like innate system?

Invariant natural killer T cells: bridging innate and adaptive immunity
"Invariant natural killer T (iNKT) cells are a subset of lymphocytes that bridge the innate and adaptive immune systems
...
Functionally, iNKT cells most closely resemble cells of the innate immune system, as they rapidly elicit their effector functions following activation, and fail to develop immunological memory. iNKT cells can become activated in response to a variety of stimuli and participate in the regulation of various immune responses. Activated iNKT cells produce several cytokines with the capacity to jump-start and modulate an adaptive immune response.
...
Here, we review the innate-like properties and functions of iNKT cells and discuss their interactions with other cell types of the immune system.
"
-- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3616393/

I recall also various reports that correlate severe Covid-19 disease with either underactive, or overreacting T-cell system, and that it was speculated in a tv documentary that some hospital staff that was very sick in the early panedmic might have been so beacuase they received a high dose of virus during transmission as they was treating subjects without knowing they were infected. So probably a race condition of kickstarting the immune system vs virus spread in the subject, where a high contamination dose gives the virus a lead??

Makes me wonder, although very risky to administer, would it in principe work to "vaccinate" someone by exposting them with the real virus, but perhaps a few virus molecules only; small enough so that one can presume that the immune system would beat the virus in the rac but still allow an initiation of adaptions?

/Fredrik

 

[atyy]

I recall also various reports that correlate severe Covid-19 disease with either underactive, or overreacting T-cell system, and that it was speculated in a tv documentary that some hospital staff that was very sick in the early panedmic might have been so beacuase they received a high dose of virus during transmission as they was treating subjects without knowing they were infected. So probably a race condition of kickstarting the immune system vs virus spread in the subject, where a high contamination dose gives the virus a lead??

Makes me wonder, although very risky to administer, would it in principe work to "vaccinate" someone by exposting them with the real virus, but perhaps a few virus molecules only; small enough so that one can presume that the immune system would beat the virus in the rac but still allow an initiation of adaptions?

People used try innoculation with small doses of small pox to give immunity against severe disease. It worked but was risky. Things improved after it was understood that immunity to small pox could be obtained with cow pox, with a much lower risk. https://en.wikipedia.org/wiki/Inoculation

I also came across this interesting article "Exposure to SARS-CoV-2 generates T-cell memory in the absence of a detectable viral infection". https://www.nature.com/articles/s41467-021-22036-z

 

[Ygggdrasil]

Thanks for the great explanations!
If found this interesting stuff as well, suggesting some T-cells does not learn, and behave a bit like innate system?

Invariant natural killer T cells: bridging innate and adaptive immunity
"Invariant natural killer T (iNKT) cells are a subset of lymphocytes that bridge the innate and adaptive immune systems
...
Functionally, iNKT cells most closely resemble cells of the innate immune system, as they rapidly elicit their effector functions following activation, and fail to develop immunological memory. iNKT cells can become activated in response to a variety of stimuli and participate in the regulation of various immune responses. Activated iNKT cells produce several cytokines with the capacity to jump-start and modulate an adaptive immune response.
...
Here, we review the innate-like properties and functions of iNKT cells and discuss their interactions with other cell types of the immune system.
"
-- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3616393/

Ah yes, I forgot about iNKT cells. You are correct that those do fit between innate and adaptive immunity, as you said.

I recall also various reports that correlate severe Covid-19 disease with either underactive, or overreacting T-cell system, and that it was speculated in a tv documentary that some hospital staff that was very sick in the early panedmic might have been so beacuase they received a high dose of virus during transmission as they was treating subjects without knowing they were infected. So probably a race condition of kickstarting the immune system vs virus spread in the subject, where a high contamination dose gives the virus a lead??

Yes, I've heard people hypothesize such a model for the disease, where for typical asymptomatic and mild cases, adaptive immunity is able to ramp up before viral load gets too high whereas in severe cases, viral load gets too high before the adaptive immune response can kick in either due to high initial viral load or because of impaired immune response (e.g. due to old age or underlying conditions). If you're interested in reading up more on the adaptive immune response to COVID-19, here's a good source (though it's from Feb and we've learned more since then): https://www.cell.com/cell/pdf/S0092-8674(21)00007-6.pdf

Makes me wonder, although very risky to administer, would it in principe work to "vaccinate" someone by exposting them with the real virus, but perhaps a few virus molecules only; small enough so that one can presume that the immune system would beat the virus in the rac but still allow an initiation of adaptions?

Although potentially feasible, one problem with such approach is that your vaccinated individuals are likely infectious for some period after "vaccination."

 

[artis]

@Fra brought up an interesting point here that I have also read elsewhere, maybe also @Ygggdrasil can comment.
I won't publish the source for this because it is in Russian and not from an authoritative source , nevertheless the guy saying these things is rather well known and not your typical anti vaxxer or conspirator.
So the point of argument is basically this. "It is far better to (not accounting for risk factors) develop natural immunity from the disease than to ramp up antibodies via vaccine"

The argument then goes like this. If the virus doesn't mutate or doesn't do it strongly enough then sure get a vaccine and have your antibodies and be happy , much like has been the case with tick-borne encephalitis.
But if the virus does mutate and that mutation is severe enough to transform the virus or it's function (the way it attaches and the success of it) considerably then a high antibody rate against a previous virus form like one would have from a vaccine might be detrimental in some cases as the large portion of antibodies present will tend to fight off the intruder but will be unsuccessful and spend energy in the process and slow down the capability of the naive T cells and the non-memory part of the immune system to fight off the virus. Also could a factor be the different level of antibody present for each individual after the vaccine as some develop a high level/large amount of them while others develop "just enough" to be considered "positive"What are your thoughts on this take , could it indeed be the case?Also I am searching but find it hard to get any valid information about the immune response to newer variants like the Delta from those that have had the real virus and developed natural immunity , which is my case. I wonder what are the effectiveness ratio between a natural immunity versus the best of current vaccines aka the Pfizer , Moderna etc ?

 

[pinball1970]

@Fra brought up an interesting point here that I have also read elsewhere, maybe also @Ygggdrasil can comment.
I won't publish the source for this because it is in Russian and not from an authoritative source , nevertheless the guy saying these things is rather well known and not your typical anti vaxxer or conspirator.
So the point of argument is basically this. "It is far better to (not accounting for risk factors) develop natural immunity from the disease than to ramp up antibodies via vaccine"

The argument then goes like this. If the virus doesn't mutate or doesn't do it strongly enough then sure get a vaccine and have your antibodies and be happy , much like has been the case with tick-borne encephalitis.
But if the virus does mutate and that mutation is severe enough to transform the virus or it's function (the way it attaches and the success of it) considerably then a high antibody rate against a previous virus form like one would have from a vaccine might be detrimental in some cases as the large portion of antibodies present will tend to fight off the intruder but will be unsuccessful and spend energy in the process and slow down the capability of the naive T cells and the non-memory part of the immune system to fight off the virus. Also could a factor be the different level of antibody present for each individual after the vaccine as some develop a high level/large amount of them while others develop "just enough" to be considered "positive"What are your thoughts on this take , could it indeed be the case?Also I am searching but find it hard to get any valid information about the immune response to newer variants like the Delta from those that have had the real virus and developed natural immunity , which is my case. I wonder what are the effectiveness ratio between a natural immunity versus the best of current vaccines aka the Pfizer , Moderna etc ?

High levels of natural immunity were thought to have been acquired in Brazil

https://www.bmj.com/content/372/bmj.n394

 

[engineer12]

The first is a complicated question to say the least. I will try to address it in pieces.
(1) Natural infection produces a wide range of antibodies (both to different parts of the virus, and of varying efficacy). The quicker the infection clears (if it is asymptomatic and limited to the upper airway), the less time the body has to respond...the humoral immune system (e.g. the part that develops antibodies and T-cell receptors) needs time to start producing antibodies, and then start improving them (immune cells undergo a process called somatic hypermutation to produce much higher affinity / avidity ones). If the infection is short, that doesn't happen.

There is a phenomenon called "antibody-dependent enhancement" where (in some viruses, most notably dengue) previous infection with one serotype (which is really a different virus, 65% homology with each other in dengue, subtypes 1-4) can cause severe disease (e.g. dengue hemorrhagic fever).

That phenomenon can happen in other contexts (indeed, one reason that RSV (respiratory syncitatal virus) vaccines have not been successful is that several first-generation versions (1960s) induced ADE)). It was a known phenomena that was VERY carefully tested for in the Coronavirus vaccines, and was not observed.

The Delta variant seems to be more capable to reinfect recovered people who had previous Beta or Gamma strain infections (<a href="https://www.cell.com/cell/pdf/S0092...m/retrieve/pii/S0092867421007558?showall=true">at least in pseudovirus neutralization assays</a>).

There have been documented reinfection cases in HCW in Brazil,

 

[PeroK]

It looks like the UK is all-in with the Delta variant. In the past four weeks we have gone from about 2,000 positive tests per day to over 20,000 per day (26,000 today).

The government's plan remains to open up on July the 19th and is already saying "we have to learn to live with COVID". It may turn out to be an interesting experiment!

 

[Fra]

If you're interested in reading up more on the adaptive immune response to COVID-19, here's a good source (though it's from Feb and we've learned more since then): https://www.cell.com/cell/pdf/S0092-8674(21)00007-6.pdf

Really nice and broad summary paper!
/Fredrik

 

[Fra]

There is a phenomenon called "antibody-dependent enhancement"

Wow, I never heard of this before. I read up on this and it seems to be a a trojan horse method for viruses to hide and ride on the antibodies. The level of sophistication of survival and evolution from the virus perspective is impressive.

I have in previous projects tried to understand things from the perspective of a single cell, and was amazed. But even the virus perspective seems rich.

Would it be fair to say that the emergence of mutations that employ ADE, is not exactly a coincidence?

/Fredrik