From 60 Minutes an Epidemiological View Of What Vaccination Level Is Needed

[Ygggdrasil]

Here's a section from a niece Perspective piece published in Nature outlining some scenarios for what SARS-CoV-2 looks like going into the future:

The first – and most worrisome – scenario is that we will not gain rapid control of this pandemic and thus will face a future with ongoing severe disease manifestations combined with high levels of infected individuals which, in turn, might foster further evolution of the virus. Vaccinations and prior infection might achieve long term herd immunity, but we will need a very broad application of vaccines worldwide combined with comprehensive disease surveillance by accurate and readily available diagnostic assays or devices76.

A second and more likely scenario is the transition to an epidemic seasonal disease like influenza. Effective therapies that prevent progression of COVID-19 disease (e.g., monoclonal antibodies reduce hospitalization and death by 70-85%) may bring the burden of SARS-CoV-2 infection to levels that are equivalent or even lower than influenza. However, we should remember that the annual mortality burden of influenza, in non-pandemic years, is estimated to be 250,000 to 500,000, with up to 650,000 all-cause deaths globally, comprising ~2% of all annual respiratory deaths (two thirds among people 65 years and older)77. This is an extremely significant health burden and equates to a relatively ‘optimistic’ view of the future of the SARS-CoV-2 pandemic.

A third scenario is the transition to an endemic disease similar to other human Coronavirus infection that have a much lower disease impact than influenza or SARS-CoV-2. There is, however, limited data on the global burden of disease by common human coronaviruses78 and as noted in earlier sections, it is not possible to predict with confidence whether further adaptations of SARS-CoV-2 to humans will increase or decrease its intrinsic virulence.

https://www.nature.com/articles/s41586-021-03792-w

The full article is relevant to the discussion as it talks about how the virus can persist as an endemic virus through pockets of susceptible individuals and waning immunity after infection or vaccination, changes in the virus through antigenic drift that diminish protection, and reentries from zoonotic reservoirs, pulling upon our experiences with other similar viruses like influenza.

 

[anorlunda]

For 60 years or so, Western Society has enjoyed very low rates of serious sickness and deaths due to infectious diseases. But diseases continue to evolve. COVID is related to other viruses. Some bacteria are evolving resistance to antibiotics.

My point is that we should not be too surprised if we enter some decades where the death rates because of infections diseases are higher than they have been the past 60 years. We certainly can't expect only monotonic decreases forever.

Would it be wrong to use the term Brownian noise when describing long term evolution of death rates?

 

[Laroxe]

This seem to imply that the R0 number tells you something about how infectious the virus actually is and provides some sort of stable metric. The problem here is that the R0 number can only tell us what is happening within a specific population, at a specific time, in a certain culture and with other variables that might affect transmission. Within a week of the first estimate, 5 other research groups published estimates on the same population, each estimate being different, falling somewhere between 1.4 and 4, depending on the mathematical method they used and type of data they input. All of these figures were based on the disease behaving in a similar way to SARS and MERS, however, the transmission of SARS-CoV-2 turned out to be markedly different. MERS and SARS patients typically shed coronaviruses while symptomatic, we now know that SARS-CoV-2 can be contagious even before patients know they’re sick. Estimates made early on did not take into account the possibly quite high level of asymptomatic individuals,” and therefore likely underestimated R0. Some researchers have argued that R0 values as high as 13 best explain the virus’ rapid spread across the world.

There are even problems in estimating the average number of people a single individual can infect, actually the real number is 0, patterns of spread are rarely consistent, but Covid has taken this to a new level. Early in the course of this pandemic, most infections are caused by relatively few individuals, so called super spreading. Typically, these events occur when an infected person, comes into contact with a lot of others, this might be because of restricted environments, like cruise ships or care homes. It's even suggested that some people might have some phenotype that causes them to shed more virus than others. All of these issues degrade the value and accuracy of the R0, and it's always a variable number, a snapshot in time.

I did wonder about the stated goal of stopping community transmission, this strikes me as totally unrealistic, the effects on specific populations means reducing serious disease and deaths is much more achievable. The current vaccines are already doing this, so there is no real pressure to produce a new vaccine. Like the R0 number, the concept of herd immunity is also a bit confusing, but its likely that the R0 for the delta variant is simply a reflection of a level of antibody escape. Virologists appear to be getting a lot more interested in the B and T cell responses, which they feel underpin the protection against severe disease and do so for quite a prolonged period of time. Booster shots might only be recommended for specific at risk populations. There is currently an ongoing debate about the ethics of immunising children when they are at low risk from the disease and the vaccines carry some risk. This is compounded by the global supply issues. I suspect that while some countries have been able to isolate themselves, they still simply represent populations with low levels of immunity, an ideal target for the virus until they get vaccinated.

 

[Vanadium 50]

How do you define under control?

Very good question.

In the US over the last 12 months, Covid is the #3 cause of death, making up about 20%. Assuming we stay exactly where we are for the next 12 months, it will make up about 2% of total deaths, and move down to #7 or #8 near kidney disease and seasonal influenza. Is that success? Or do we need to move even lower?

Another factor of 2 takes it to #14 and near Parkinson's. Is that success? Or do we need to move even lower?

 

[bhobba]

Interesting to contrast Covid to a virus most are not aware of - RSV:
https://www.mayoclinic.org/diseases...-syncytial-virus/symptoms-causes/syc-20353098

It is so infectious virtually everyone gets it by 2. It is usually not a problem, but it can be dangerous and cause death in some children. You develop antibodies, so when you get it later in life, you either fight it off, or the symptoms are mild, so mild it is generally thought to be the common cold. I seem to recall reading somewhere, but do not hold me to it; the RSV virus causes about 20% of 'cold' cases. Of course, our immune system is not as good as we age, and for aged care residents is can be a big problem:
https://pubmed.ncbi.nlm.nih.gov/16038573/

I think this has lessons for what may eventually happen with Covid. We all may get it when young (so far, it has not proved to have much of a fatality rate in the very young), develop antibodies that give us the sniffles as we age. It becomes a problem when immunity wanes.

Just a possibility. I think the most likely outcome is as Yggdrasil posted. It will be like the Flu, and we will get, along with our Flu shot each year, a Covid shot. If the pandemic has shocked people into getting vaccinated against the Flu, we may even be overall better of than we were before. Only time will tell.

BTW I have found a youtube video for the original video I posted and will change it to that, so hopefully, everyone can see it.

Thanks
Bill

 

[bhobba]

I did wonder about the stated goal of stopping community transmission, this strikes me as totally unrealistic, the effects on specific populations means reducing serious disease and deaths is much more achievable. The current vaccines are already doing this, so there is no real pressure to produce a new vaccine.

I agree it is unrealistic to stop community transmission entirely. You only have to look at the Sydney outbreak. It is made worse by population pockets with high numbers of immigrants. To many of them, limiting contact to family members in the same household also means their extended family in different physical households. It is cultural. The same thing happened with the Melbourne outbreak. Some communities were not getting the message for cultural reasons. A good friend of mine when young moved from Canberra to Perth, where his family was. He was second generation Australian. When I visited for a few weeks to watch America's Cup, I was shocked at just, culturally, how different his parents were to their sons and daughters. They had to still explain many things to them, and their English was poor. They even had to ask me about things.

The current vaccines are good, but the rate variants keep popping up, new vaccine development is needed. We also would like to eliminate the minimal risk they have of thrombosis, heart issues etc.

But we need to be careful. We tinkered with the Whooping Cough vaccine to reduce rare side effects. That worked, but it is now not as effective, meaning here in Aus, we have this no jab no pay rule. If no vaccination against Whooping Cough, then no government supplements, tax concessions, or even enrolling in a government school.

Thanks
Bill

 

[StoneTemplePython]

some red flags in this thread
1.) (including the title): talking about herd immunity purely in terms of vaccination and not natural immunity(/prior infections)
2.) talking about antibodies and not T and B memory cells

in short, with a few exceptions, much of this thread feels like political talking points

 

[Laroxe]

I agree it is unrealistic to stop community transmission entirely. You only have to look at the Sydney outbreak. It is made worse by population pockets with high numbers of immigrants. To many of them, limiting contact to family members in the same household also means their extended family in different physical households. It is cultural. The same thing happened with the Melbourne outbreak. Some communities were not getting the message for cultural reasons. A good friend of mine when young moved from Canberra to Perth, where his family was. He was second generation Australian. When I visited for a few weeks to watch America's Cup, I was shocked at just, culturally, how different his parents were to their sons and daughters. They had to still explain many things to them, and their English was poor. They even had to ask me about things.

The current vaccines are good, but the rate variants keep popping up, new vaccine development is needed. We also would like to eliminate the minimal risk they have of thrombosis, heart issues etc.

But we need to be careful. We tinkered with the Whooping Cough vaccine to reduce rare side effects. That worked, but it is now not as effective, meaning here in Aus, we have this no jab no pay rule. If no vaccination against Whooping Cough, then no government supplements, tax concessions, or even enrolling in a government school.

Thanks
Bill

One of the reasons I thought that elimination was unlikely was based on the 4 Coronaviruses that infect humans that lead to mild, cold like illness. All of these made a successful transition from animals to humans, and they can estimate when this occurred. The ARCoV2 between 1190 and 1449 and the 229E Coronavirus between 1686 and 1800, both from bats. Then we have the OC43 which originated in rodents, spread to cattle and then to humans in the 1890S and the latest HKU1 identified in 2004 also from rodents. Generally we know little about the history of these events because the diseases they cause were new and there were no test, but it may be that the first 3 followed a similar course to the current Covid-19 pandemic, and these events were certainly followed by pandemics, these viruses are common across the whole world. The OC43 has been the source of considerable speculation, as the crossover event was followed by a recorded pandemic in the late 1890. This pandemic seems to have caused around a million deaths and was referred to as Russian flu though the symptoms were unlike those caused by flu, the virus currently causes cold like symptoms.

These viruses have not disappeared and are in fact very common causes of infection, but it seems that humans and these viruses have “learned to live” with each other. There may have been many more but like SARS and MERS they might never have made the transition effectively, SARS in fact has disappeared and each cluster of infections with MERS represents a new crossover event.
The reproductive rate and its general inefficiency in viruses means there are always variants arising, the more widespread the rate of infection is, the greater the number of variants. A number of these variants may be able to avoid the actions of some antibodies, It's actually very difficult to evolve resistance to all the antibodies produced and the T cell response still speeds up our ability to refine specific antibodies to new variants. This is why that even though some antibody responses are blunted by the delta variant, giving it a selective advantage, many people can continue to be infected but following previous exposure or vaccination the speed of the antibody response limits the seriousness of the disease.
To justify the development of new vaccines a new variant would need to arise that largely escaped our immune response due to previous exposure, and if such a variant was generally more dangerous it would in fact be at a selective disadvantage. When people become very ill they automatically self-isolate and if people die, the virus dies with them. We would need to be at the stage of this new variant spreading in the population, simply to recognise it as a serious threat, remember we will in effect be dealing with hundreds of variants.
There are several alternatives to developing new vaccines, the first is in the use of vaccines that present a wider range of antigens to the immune system, some of which might stimulate antibodies to conserved parts of the virus and therefore more difficult to evade. The second would be in developing delivery systems that produce different types of responses, for example in the tissues in which the virus starts to replicate. These ideas are already present in some vaccines already in development, as are new delivery systems.
Developing booster vaccines that target particular variants is at best a short term and ultimately expensive option, and would then be faced with the distribution issues we see now. There is already work looking at identifying conserved parts of the virus that may even help prevent other Coronavirus disease. However, this might be quite difficult, we are already aware of the fact that following infection we produce antibodies to a wide range of antigens, they can potentially attack virtually all parts of the virus. It does seem that this virus has ways of hiding parts of its envelope from the immune system and/or antibodies, a lot of antibodies appear to have no protective effect, that's why researchers focussed on the spike proteins in developing the vaccines. Similar work is being done to try and broaden the effectiveness of vaccines to other diseases, most notably flu, but I wouldn't hold my breath.
Because some vaccines in development are likely to be available soon, I suspect it makes more sense to wait and see how effective they are against variants, even though vaccine producers already have blueprints for new formulations that are variant specific.

 

[Laroxe]

I agree it is unrealistic to stop community transmission entirely. You only have to look at the Sydney outbreak. It is made worse by population pockets with high numbers of immigrants. To many of them, limiting contact to family members in the same household also means their extended family in different physical households. It is cultural. The same thing happened with the Melbourne outbreak. Some communities were not getting the message for cultural reasons. A good friend of mine when young moved from Canberra to Perth, where his family was. He was second generation Australian. When I visited for a few weeks to watch America's Cup, I was shocked at just, culturally, how different his parents were to their sons and daughters. They had to still explain many things to them, and their English was poor. They even had to ask me about things.

The current vaccines are good, but the rate variants keep popping up, new vaccine development is needed. We also would like to eliminate the minimal risk they have of thrombosis, heart issues etc.

But we need to be careful. We tinkered with the Whooping Cough vaccine to reduce rare side effects. That worked, but it is now not as effective, meaning here in Aus, we have this no jab no pay rule. If no vaccination against Whooping Cough, then no government supplements, tax concessions, or even enrolling in a government school.

Thanks
Bill

Actually, you have just reminded me of a very important effect of vaccination with the mention of Whooping cough. The original vaccine was produced using killed cells of the whole pertussis bacterium. While this process introduced a very wide range of antigens some of which induced adverse reactions it was decided to produce a vaccine from selected 1–5 purified pertussis proteins, this was shown to be just as immunogenic while causing fewer problems. The preliminary clinical trials in the 1990s comparing the two suggested comparable efficacy and immunogenicity.

However, more recent data have shown that the disease is not adequately controlled and outbreaks have occurred, even in countries with extensive vaccine coverage. The higher antigenic load of the whole cell vaccine may explain the epidemiological evidence that supports the longer lasting protection induced by these vaccines, the purified protein vaccines may also lack some potentially protective antigens in the whole cell formulations.

There is now evidence that B. pertussis and B. parapertussis have adapted to the restricted niches of hosts, in highly vaccinated populations. It seems that circulating strains of B. pertussis are evolving to evade the vaccine-conferred immunity, in this it is the vaccine itself which acts as the selective force.

So far I haven't seen any comments that explicitly address the effects of the vaccination program, and there is a continuing debate as to the relevance of the new variants. It is for example suggested that the delta variant is more infectious / transmissible, and this reflects some new quality of the virus. In fact, the delta variant has become much more widespread as the vaccination program has been developing, and this virus has shown itself to be resistant to the effects of at least 1 monoclonal antibodies, an antibody that all the current vaccines stimulate. Evolutionary theory suggests that over time, a relatively small selective advantage can have a massive effect on the overall population.

As the delta variant finds it easier to become established in populations with relatively low levels
of immunity, that's all that is needed to provide the selective advantage over the current strain in rates of infection. However, this variant has no additional tools to counter the T cell response induced by all the current vaccines, so it still runs a course that is time limited and therefore milder.
This would suggest that the delta variant has no adaptations that make it more transmissible or deadly, what we are seeing is a fitness advantage because of changes in the host population, induced by vaccination. In non-immune populations, it would still predominate if this was the first variant the population was exposed to, it is likely to have all the abilities of the first variant, which wasn't of course the original variant identified in people.

When we talk about the evolution of changes in the way an organism interacts with its environment the first consideration should be issues of fitness, we tend to apply our own human biases to explanations of changes. We tend to think of the changes in the number of infections as synonymous with increased virulence, so we see the increase in the delta variant as more dangerous. In fact we can only get an estimate by comparing the spread of two variants in a non-immune population, so really we don't know. While it has become more common in immune or partially immune populations, in terms of the numbers of associated deaths, it seems to have made little if any difference. For a virus, causing serious disease or death actually limits its fitness and evolution if nothing else almost guarantees things will change. The most successful pathogens tend to be associated with a long period in which they can infect others, be asymptomatic or at least have mild symptom's so that the victim maintains social contacts, can avoid at least some of the bodies defences and if it does kill someone it takes a long time to do it. SARS had a very short incubation period, during which it couldn't spread, it caused profound illness, people automatically isolated themselves and rapidly lead to the deaths of many it infected. It no longer infects anyone, the virus is, in effect, extinct.

 

[morrobay]

some red flags in this thread
1.) (including the title): talking about herd immunity purely in terms of vaccination and not natural immunity(/prior infections)
2.) talking about antibodies and not T and B memory cells

in short, with a few exceptions, much of this thread feels like political talking points

Indeed , So let's talk about 1. and 2. It's high time. You should start a new topic. Regarding 1. Do past infections with the 4 coronaviruses confer some immunity ? I for one cannot remember getting a flu vaccination or the last time I had a flu. And yes why not more discussion regarding 2. ?

 

[atyy]

some red flags in this thread
1.) (including the title): talking about herd immunity purely in terms of vaccination and not natural immunity(/prior infections)
2.) talking about antibodies and not T and B memory cells

in short, with a few exceptions, much of this thread feels like political talking points

Regarding your point about herd immunity, the OP is in the context of Australia.