COVID Get Vaccinated Against the Covid Delta Variant

[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

 

[pinball1970]

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!

Hopefully it will be with people under 30 who are a lot less likely to get very sick.
We are in exponential now? BUT deaths are in v low levels. The vaccine is working.

 

[atyy]

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!

Hopefully it will be with people under 30 who are a lot less likely to get very sick.
We are in exponential now? BUT deaths are in v low levels. The vaccine is working.

https://www.bbc.com/news/health-57667987
Covid: NHS plans booster jab for those 50 and over before winter

UK looks to be in excellent shape with good plans!

 

[artis]

Well I guess being careful is wise always but for someone who has had a natural infection of the UK/other variant or the vaccine there should be no serious case even if the Delta infects you.
I am ofcourse talking about people with no serious background conditions that might otherwise affect an outcome

 

[OmCheeto]

Hopefully it will be with people under 30 who are a lot less likely to get very sick.
We are in exponential now? BUT deaths are in v low levels. The vaccine is working.

Looks exponential to me

Very nice that the case fatality rate has dropped nearly an order of magnitude, due to the vaccinations.

 

[Fra]

Well I guess being careful is wise always but for someone who has had a natural infection of the UK/other variant or the vaccine there should be no serious case even if the Delta infects you.
I am ofcourse talking about people with no serious background conditions that might otherwise affect an outcome

Given the big grey area of long COVID, which is a much larger fraction of people than those that die there are still some concerns I think? We rarely see the nice graphs on this stuff. Media mainly focuses also on death numbers and ICU occupation.

I would still opt not to get it, even if I have to drink beer at home for another year.

From one of the references ine the nice summary paper Yggdrasil recommended...

Multi-organ impairment in low-risk individuals with long COVID​

"Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection has disproportionately affected older individuals and those with underlying medical conditions. Research has focused on short-term outcomes in hospital, and single organ involvement. Consequently, impact of long COVID (persistent symptoms three months post-infection) across multiple organs in low-risk individuals is yet to be assessed.
...
In a young, low-risk population with ongoing symptoms, almost 70% of individuals have impairment in one or more organs four months after initial symptoms of SARS-CoV-2 infection. There are implications not only for burden of long COVID but also public health approaches which have assumed low risk in young people with no comorbidities."
-- https://www.medrxiv.org/content/10.1101/2020.10.14.20212555v1

/Fredrik

 

[PeroK]

Given the big grey area of long COVID, which is a much larger fraction of people than those that die there are still some concerns I think? We rarely see the nice graphs on this stuff. Media mainly focuses also on death numbers and ICU occupation.

I would still opt not to get it, even if I have to drink beer at home for another year.

From one of the references ine the nice summary paper Yggdrasil recommended...

Multi-organ impairment in low-risk individuals with long COVID​

"Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection has disproportionately affected older individuals and those with underlying medical conditions. Research has focused on short-term outcomes in hospital, and single organ involvement. Consequently, impact of long COVID (persistent symptoms three months post-infection) across multiple organs in low-risk individuals is yet to be assessed.
...
In a young, low-risk population with ongoing symptoms, almost 70% of individuals have impairment in one or more organs four months after initial symptoms of SARS-CoV-2 infection. There are implications not only for burden of long COVID but also public health approaches which have assumed low risk in young people with no comorbidities."
-- https://www.medrxiv.org/content/10.1101/2020.10.14.20212555v1

/Fredrik

And more generally, COVID is not fully understood. There must be serious risks for any country that let's the Delta variant get out of control.

We still have over 20 million people unvaccinated (mostly under 18's) and 12 million people who have had only one jab. That's just over half the population. It's impossible to predict the numbers, but we could easily have 5 million cases of the Delta in the next couple of months.

That said, the number of cases in Spain and Portugal is rising quickly. Perhaps a pan-European surge of the Delta variant will be hard to avoid.

 

[Tom.G]

In a young, low-risk population with ongoing symptoms, almost 70% of individuals have impairment in one or more organs four months after initial symptoms of SARS-CoV-2 infection.

Questionable at this point. Read the comments to the study:
(https://www.medrxiv.org/content/10.1101/2020.10.14.20212555v1)

The trials registry protocol suggests n=507 symptomatic cases would be recruited and followed up, ... . Yet the preprint appears to focus on n=201 individuals still "symptomatic after recovery" and it is therefore not surprising that nearly 100% of them report symptoms, as this appears to be the eligibility criteria for the paper.

We'd all like to know the denominator, i.e. of all young low risk patients, what percent go on to have long Covid symptoms? This paper is confusing, with regard to this question.

 

[pinball1970]

Given the big grey area of long COVID, which is a much larger fraction of people than those that die there are still some concerns I think? We rarely see the nice graphs on this stuff. Media mainly focuses also on death numbers and ICU occupation.

I would still opt not to get it, even if I have to drink beer at home for another year.

From one of the references ine the nice summary paper Yggdrasil recommended...

Multi-organ impairment in low-risk individuals with long COVID​

"Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection has disproportionately affected older individuals and those with underlying medical conditions. Research has focused on short-term outcomes in hospital, and single organ involvement. Consequently, impact of long COVID (persistent symptoms three months post-infection) across multiple organs in low-risk individuals is yet to be assessed.
...
In a young, low-risk population with ongoing symptoms, almost 70% of individuals have impairment in one or more organs four months after initial symptoms of SARS-CoV-2 infection. There are implications not only for burden of long COVID but also public health approaches which have assumed low risk in young people with no comorbidities."
-- https://www.medrxiv.org/content/10.1101/2020.10.14.20212555v1

/Fredrik

Metro UK this morning
https://metro.co.uk/2021/07/01/hund...red-long-covid-for-more-than-a-year-14857070/

 

[artis]

Well I would be cautious about the study , from all the folks I know around my age almost no one has had prolonged symptoms except me and in my case they are mostly to do with CNS and somewhat lower physical endurance.

 

[pinball1970]

And more generally, COVID is not fully understood. There must be serious risks for any country that let's the Delta variant get out of control.

We still have over 20 million people unvaccinated (mostly under 18's) and 12 million people who have had only one jab. That's just over half the population. It's impossible to predict the numbers, but we could easily have 5 million cases of the Delta in the next couple of months.

That said, the number of cases in Spain and Portugal is rising quickly. Perhaps a pan-European surge of the Delta variant will be hard to avoid.

And more generally, COVID is not fully understood. There must be serious risks for any country that let's the Delta variant get out of control.

We still have over 20 million people unvaccinated (mostly under 18's) and 12 million people who have had only one jab. That's just over half the population. It's impossible to predict the numbers, but we could easily have 5 million cases of the Delta in the next couple of months.

That said, the number of cases in Spain and Portugal is rising quickly. Perhaps a pan-European surge of the Delta variant will be hard to avoid.

Hi Perok Has this been mentioned previously?
Lambda from Peru? On another thread? A search gave me a load of mathy stuff
Its in the UK now too.

https://www.medrxiv.org/content/10.1101/2021.06.21.21259241v1

Also what happened to Epsilon?

EDIT: https://www.healthline.com/health-n...new-covid-19-variants-have-scientists-worried

I am way behind actually

Page 5

https://assets.publishing.service.g...ants_of_Concern_VOC_Technical_Briefing_17.pdf

 

[Fra]

Questionable at this point. Read the comments to the study:
(https://www.medrxiv.org/content/10.1101/2020.10.14.20212555v1)

Yes, it looks a bit hard to see the selection criteria, but I there seems to be more discussions that this sole paper. Anyway, I think the main point is the lack of knowledge of secondary effects. Beeing floored for a couple of weeks and recover is one thing, but long terms effects that may or may not involve even mild forms of local tissue scarring in organs that may go unnoticed or even brain(smell/taste) etc is unpleasant and might be as bad. Without more knowledge perhaps what is this can have implications as predispositions for future problems that show up years later? Even things that long terms loss of smell and taste is IMO quite serious. It won't kill you but will will impact quality of life.

One in ten have long-term effects 8 months following mild COVID-19​

-- https://news.ki.se/one-in-ten-have-long-term-effects-8-months-following-mild-covid-19​

Edit: as this study is behind in time, it likely refers to the original Covid-19 strain, if things is different for delta or other variants is i supposed even more unsure, we have to wait another year for next study. UK is taking the lead with delta I think, in sweden we still have i think only around 50% delta.

/Fredrik

 

[nphysics]

Preliminary data from Public Health England suggests 88% effeciveness of the Pfizer vaccine against the delta variant (B.1.617.2) vs 93% effectiveness against the alpha variant (B.1.1.7), so despite initial worries, the vaccines do still work well against this variant -- more reason to get vaccinated if you have not already.

Effectiveness of COVID-19 vaccines against the B.1.617.2 variant
https://khub.net/documents/13593956...iant.pdf/204c11a4-e02e-11f2-db19-b3664107ac42

AbstractPopular press summary: https://www.bmj.com/content/373/bmj.n1346

It's just an puzzle of no. . we just need full protection against death.

 

[pinball1970]

It's just an puzzle of no. . we just need full protection against death.

By "full" you mean 100%? No such thing.

"greatly reduce" with the published numbers as per @Ygggdrasil post is is as good as it gets.

 

[Ygggdrasil]

@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"

Regarding immunity from infection vs immunity from vaccines, one theoretical reason to think that vaccines might be more effective at inducing immunity is that viruses have evolved measures try to hide themselves from the body's immune system while vaccines are designed to stimulate strong immune responses. Furthermore, the prime-boost strategy used by most of the vaccines might be more effective at inducing long term immunity (though we don't have a lot of data on long term immunity yet).

Empirically, an observational study in Denmark identified 11k people infected during the first wave of COVID-19 and tracked whether they were infected during the second wave of infection. They found previous infection conferred 80.5% protection from reinfection (and a 93% protection against symptomatic infection). This level of protection is similar to that reported for the more effective vaccines (e.g. Pfizer, Moderna, Novavax). However, the study did find that previous infection was not as effective at protecting older adults (age > 65) from subsequent infection (~50% protection) whereas the vaccines above showed no signs of reduced efficacy in older individuals.

So, for younger individuals, it seems like there is a similar amount of protection from previous infection vs vaccination, but in older individuals, vaccination likely provides stronger protection than prior infection.

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?

I do not think that an antibody response would slow down a T-cell response. Do you have any scientific references that would support such a hypothesis?

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 ?

I also have not seen much data on this issue. Based on the studies I cited earlier showing that T-cell responses developed against the original strain are also effective against the virus and evidence that prior infection provides similar effectiveness against re-infection as the vaccines, I would guess that prior infection should provide similar effectiveness against symptomatic disease and very good protection against severe disease, hospitalization and death. However, more data would be required to fully test this hypothesis.

 

[Ygggdrasil]

Hi Perok Has this been mentioned previously?

Lambda from Peru? On another thread? A search gave me a load of mathy stuff
Its in the UK now too.

https://www.medrxiv.org/content/10.1101/2021.06.21.21259241v1

Also what happened to Epsilon?

EDIT: https://www.healthline.com/health-n...new-covid-19-variants-have-scientists-worried

I am way behind actually

Page 5

https://assets.publishing.service.g...ants_of_Concern_VOC_Technical_Briefing_17.pdf

Here's a page from the WHO that lists the variants of concern (alpha, beta, gamma and delta) as well as the variants of interest (epsilon, zeta, eta, theta, iota, kappa, and lambda): https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/

Note that widespread transmission of a new variant does not always mean that the new variant is a more transmissible form of the virus. Often, certain variants could be spread more widely by chance (e.g. they happen to get spread at a superspreader event). Here's a good example of the 20E/EU1 variant that emerged in Spain early in the summer and became widespread across Europe, yet researchers subsequently found no evidence that the variant itself had showed increased transmissibility. Rather, the researchers attribute the success of the variant to it being present in the right place at the right time (emerging just as travel and quarantine restrictions were being lifted in Europe).

Spread of a SARS-CoV-2 variant through Europe in the summer of 2020
Hodcroft et al. Nature 2021
https://www.nature.com/articles/s41586-021-03677-y

Abstract:

Following its emergence in late 2019, the spread of SARS-CoV-21,2 has been tracked by phylogenetic analysis of viral genome sequences in unprecedented detail3,4,5. Although the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, travel within Europe resumed in the summer of 2020. Here we report on a SARS-CoV-2 variant, 20E (EU1), that was identified in Spain in early summer 2020 and subsequently spread across Europe. We find no evidence that this variant has increased transmissibility, but instead demonstrate how rising incidence in Spain, resumption of travel, and lack of effective screening and containment may explain the variant’s success. Despite travel restrictions, we estimate that 20E (EU1) was introduced hundreds of times to European countries by summertime travellers, which is likely to have undermined local efforts to minimize infection with SARS-CoV-2. Our results illustrate how a variant can rapidly become dominant even in the absence of a substantial transmission advantage in favourable epidemiological settings. Genomic surveillance is critical for understanding how travel can affect transmission of SARS-CoV-2, and thus for informing future containment strategies as travel resumes.

 

[Ygggdrasil]

Here's a nice paper that estimates the transmissibility of various SARS-CoV-2 VOCs and VOIs:

Increased transmissibility and global spread of SARS-CoV-2 variants of concern as at June 2021
Campbell et al. Euro Surevill. 26: 2100509
https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2021.26.24.2100509

Abstract:

We present a global analysis of the spread of recently emerged SARS-CoV-2 variants and estimate changes in effective reproduction numbers at country-specific level using sequence data from GISAID. Nearly all investigated countries demonstrated rapid replacement of previously circulating lineages by the World Health Organization-designated variants of concern, with estimated transmissibility increases of 29% (95% CI: 24-33), 25% (95% CI: 20-30), 38% (95% CI: 29-48) and 97% (95% CI: 76-117), respectively, for B.1.1.7, B.1.351, P.1 and B.1.617.2.

 

[atyy]

Increased transmissibility and global spread of SARS-CoV-2 variants of concern as at June 2021
Campbell et al. Euro Surevill. 26: 2100509
https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2021.26.24.2100509

The estimate for delta by Campbell et al looks a lot higher than that given by Mlcochova et al. I guess it's partly because they use different definitions?

Mlcochova et al try to separate out transmissibility from immune evasion, whereas Campbell et al say "It is important to note that our analysis cannot distinguish between a genuine increase in transmissibility (i.e. the basic reproduction number) and immune evasion as explanations for higher effective reproduction numbers. For variants with relevant levels of immune evasion, as potentially observed for B.1.351 [7], the future nature of competitive growth with other variants will depend on the immune context, both infection- and vaccine-derived, of each country under consideration."

 

[atyy]

The estimate for delta by Campbell et al looks a lot higher than that given by Mlcochova et al. I guess it's partly because they use different definitions?

Mlcochova et al try to separate out transmissibility from immune evasion, whereas Campbell et al say "It is important to note that our analysis cannot distinguish between a genuine increase in transmissibility (i.e. the basic reproduction number) and immune evasion as explanations for higher effective reproduction numbers. For variants with relevant levels of immune evasion, as potentially observed for B.1.351 [7], the future nature of competitive growth with other variants will depend on the immune context, both infection- and vaccine-derived, of each country under consideration."

I guess after comparing the papers, transmissibility is defined differently in each. I'm not sure the terms in the models can be mapped exactly onto each other, but it looks like Campbell's relative reproduction number would seem be closer Mlcochova call the transmissibility increase, and if we compare those, the estimates are closer. Campbell (Fig. 3) gets about 1.5 while Mlocochova gets about 1.1 to 1.4. Campbell's number is still towards the upper end of Mlocochova's range, but that could be due to founder effects and not accounting for immune evasion, as Campbell discuss.

 

[Jonathan Scott]

Here in the UK, I'm seeing two types of numbers being used alarmingly inconsistently with one another:

a) When x% of the population is immune, due to vaccination or previous infection, the spread will finally be under control (where x% depends on the variant being discussed but is usually given as about 85%).

b) The fraction of the population who have been vaccinated is approaching x%, so we should be seeing the effects of this any day now.

This appears to completely ignore the fact that having been vaccinated is nowhere near the same as being immune due to vaccination, especially as the widely used Oxford/AstraZeneca vaccine (the one which my wife and I had) after both doses is still apparently only about 62% effective against symptomatic disease due to the delta variant, which is thought to still allow transmission, so even if everyone had been vaccinated, the immunity level would be nowhere near high enough to stop the spread. The Pfizer vaccine is better from that point of view, at around 95%, but even then the percentage of immunity is still somewhat less than the percentage vaccinated.

In the mean time, the rise in the UK over the last few weeks has been higher than exponential; the percentage increase per week has been steadily increasing, to 74.1% as of 28th June, according to the UK government web site: https://coronavirus.data.gov.uk/details/cases

Even if I'm unlikely to die of it, I really don't want to get it. Swine flu back in 2009 was horrible; fever gives me hallucinations like waking nightmares, and it took months to get back to my normal sleep patterns. I find the idea of simply letting the delta variant spread because "it is no longer expected to reach levels which could overwhelm the health service" really scary.

[Edited for typo in increase: 74.1% not 71.4%]

 

[PeroK]

Even if I'm unlikely to die of it, I really don't want to get it. Swine flu back in 2009 was horrible; fever gives me hallucinations like waking nightmares, and it took months to get back to my normal sleep patterns. I find the idea of simply letting the delta variant spread because "it is no longer expected to reach levels which could overwhelm the health service" really scary.

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

 

[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.