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Delta variant, breakthrough infections and related consequences


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Throughout the COVID-19 pandemic there have been key findings that have altered our understanding or required responses to this disease. For example, the realization that pre- or asymptomatic persons might be infectious has required a different approach to masking and social distancing. While we have several threads discussing the pandemic, I feel that recent developments justify a new topic, especially as it could be used to clarify potential misunderstandings.

With the delta variant (B.1.617.2) gaining dominance we are seeing yet another change that requires us to re-think the trajectory of the pandemic. First of all, the transmission rate of this variant is much higher than estimates for the original strain. The CDC has compared it to chicken pox, which has a basic reproduction number (R0) of >10.

What does it mean? First of all, this might indicate that vaccine-based herd immunity is entirely out of the picture. With a R0 of 10 you would need to have a total protection of >92% of the population. Since the effectiveness of the best vaccines against the delta variant are a bit lower than 90%, it means that even with no vaccine hesitation and even if we could vaccinate children with it, we won't hit the required target for herd immunity. This has been assumed to happen for a while now, and might be the least surprising bit of news.

However, there are a few recent findings that have prompted changes in messaging, for example with regard to masking. The key issue here are the finding that folks with breakthrough infections have similar viral loads as unvaccinated folks.

What does it mean? Fundamentally there some vaccinated folks that get infected with SARS-CoV-2. That in itself is not surprising. Historically, breakthrough infections happen for most vaccinations at low frequencies. Most of the time the focus is on illness, i.e. symptomatic manifestations of infections. However, as mentioned, the possibility of asymptomatic spread has changed that. The fact that vaccinated folks still have high titers means that folks with breakthrough infections could infect others and especially unvaccinated folks are at risk of becoming seriously ill. Vaccinated folks, for the most part do not seem to develop serious symptoms anymore, but it means that vaccinated folks could unwittingly infect and endanger un-or undervaccinated folks. This has prompted a reversal in the masking recommendation. Moreover, it has made many infectious disease experts nervous as in many countries mask mandates are being lifted.

Unknowns: There are still many open questions. For example, in the US, the delta variant is causing more illness in younger folks, including children. It is not clear whether this is really a property of the virus, or just because younger folks tend not to be vaccinated. It is not certain whether the vaccine effectively protect from long-haul COVID symptoms. The rate of breakthrough infections is unclear, we know the lower end of the estimate based on detected cases, but since folks without symptoms typically do not get tested, we do not know exact numbers. Even in a highly vaccinated community it is possible that there is a large enough reservoir to allow new variants to develop.

 

https://www.cdc.gov/mmwr/volumes/70/wr/mm7031e2.htm?s_cid=mm7031e2_w

https://www.medrxiv.org/content/10.1101/2021.07.31.21261387v1

 

Discussion points:

As a whole it means that we are heading into new territory during fall and winter. The big question is whether the current vaccination rates are good enough to prevent mass hospitalization or will easing of restrictions make folks forget that the disease is still there and cause a new surge. Vaccine hesitancy will add fuel to this potential fire.

The communication in many countries/states/provinces have been confusing to say the least and quite a few folks I have talked to seem under the impression that there is little danger left, despite the fact that even in highly vaccinated countries, especially younger folks are barely hitting 50% of full vaccinations. Moreover, most folks in the world are still unvaccinated, meaning that we will need to prepare for more variants. 

Everyone is being sick and tired of the situation, yet undoubtedly the world has changed yet again (and will continue to do so). A big decision at some point is to establish how many deaths we are comfortable with. With regard to flue, for example, the number is surprisingly high across countries and by any estimate, COVID-19 is going to eclipse it, unless very high vaccination rates are maintained, which is notoriously difficult.

 

Edit Aug, 19, 2021:

A new preprint has come out indicating that with the Delta variant Pfizer might only be 42% effective at preventing infections (not disease!) and Moderna was about 76%.

https://www.medrxiv.org/content/10.1101/2021.08.06.21261707v1

This seem to highlight that behavioral prevention is still going to be important.

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57 minutes ago, CharonY said:

Throughout the COVID-19 pandemic there have been key findings that have altered our understanding or required responses to this disease. For example, the realization that pre- or asymptomatic persons might be infectious has required a different approach to masking and social distancing. While we have several threads discussing the pandemic, I feel that recent developments justify a new topic, especially as it could be used to clarify potential misunderstandings.

With the delta variant (B.1.617.2) gaining dominance we are seeing yet another change that requires us to re-think the trajectory of the pandemic. First of all, the transmission rate of this variant is much higher than estimates for the original strain. The CDC has compared it to chicken pox, which has a basic reproduction number (R0) of >10.

What does it mean? First of all, this might indicate that vaccine-based herd immunity is entirely out of the picture. With a R0 of 10 you would need to have a total protection of >92% of the population. Since the effectiveness of the best vaccines against the delta variant are a bit lower than 90%, it means that even with no vaccine hesitation and even if we could vaccinate children with it, we won't hit the required target for herd immunity. This has been assumed to happen for a while now, and might be the least surprising bit of news.

However, there are a few recent findings that have prompted changes in messaging, for example with regard to masking. The key issue here are the finding that folks with breakthrough infections have similar viral loads as unvaccinated folks.

What does it mean? Fundamentally there some vaccinated folks that get infected with SARS-CoV-2. That in itself is not surprising. Historically, breakthrough infections happen for most vaccinations at low frequencies. Most of the time the focus is on illness, i.e. symptomatic manifestations of infections. However, as mentioned, the possibility of asymptomatic spread has changed that. The fact that vaccinated folks still have high titers means that folks with breakthrough infections could infect others and especially unvaccinated folks are at risk of becoming seriously ill. Vaccinated folks, for the most part do not seem to develop serious symptoms anymore, but it means that vaccinated folks could unwittingly infect and endanger un-or undervaccinated folks. This has prompted a reversal in the masking recommendation. Moreover, it has made many infectious disease experts nervous as in many countries mask mandates are being lifted.

Unknowns: There are still many open questions. For example, in the US, the delta variant is causing more illness in younger folks, including children. It is not clear whether this is really a property of the virus, or just because younger folks tend not to be vaccinated. It is not certain whether the vaccine effectively protect from long-haul COVID symptoms. The rate of breakthrough infections is unclear, we know the lower end of the estimate based on detected cases, but since folks without symptoms typically do not get tested, we do not know exact numbers. Even in a highly vaccinated community it is possible that there is a large enough reservoir to allow new variants to develop.

 

https://www.cdc.gov/mmwr/volumes/70/wr/mm7031e2.htm?s_cid=mm7031e2_w

https://www.medrxiv.org/content/10.1101/2021.07.31.21261387v1

 

Discussion points:

As a whole it means that we are heading into new territory during fall and winter. The big question is whether the current vaccination rates are good enough to prevent mass hospitalization or will easing of restrictions make folks forget that the disease is still there and cause a new surge. Vaccine hesitancy will add fuel to this potential fire.

The communication in many countries/states/provinces have been confusing to say the least and quite a few folks I have talked to seem under the impression that there is little danger left, despite the fact that even in highly vaccinated countries, especially younger folks are barely hitting 50% of full vaccinations. Moreover, most folks in the world are still unvaccinated, meaning that we will need to prepare for more variants. 

Everyone is being sick and tired of the situation, yet undoubtedly the world has changed yet again (and will continue to do so). A big decision at some point is to establish how many deaths we are comfortable with. With regard to flue, for example, the number is surprisingly high across countries and by any estimate, COVID-19 is going to eclipse it, unless very high vaccination rates are maintained, which is notoriously difficult.

Very informative. Thanks. 

I read in today's FT that the Imperial College React-1 survey has found that vaccination (in the UK a mix of Pfizer and Astra/Zeneca) seems to cut transmission of the Delta variant by half, ie. vaccinated individuals are half as infectious as unvaccinated. So they can still infect a lot of people.

It also cuts symptomatic infection: 40% of vaccinated people with a +ve test were asymptomatic, while many others had only mild symptoms. This is consistent with the hospitalisation data in the UK.

The vaccines seem to be ~90% effective at preventing disease serious enough to require hospitalisation. 

So it looks as if the virus will be endemic, though we can hope the incidence of serious disease can be managed through vaccination. However, from your information, and this from the UK, it very much looks to me as if some public health countermeasures to reduce transmission may be needed long term, on top of vaccination.

I don't think I'll be throwing away my mask and I think a lot of people will be well advised to continue to work from home as much as they can.

  

 

Edited by exchemist
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48 minutes ago, exchemist said:

Very informative. Thanks. 

I read in today's FT that the Imperial College React-1 survey has found that vaccination (in the UK a mix of Pfizer and Astra/Zeneca) seems to cut transmission of the Delta variant by half, ie. vaccinated individuals are half as infectious as unvaccinated. So they can still infect a lot of people.

It also cuts symptomatic infection: 40% of vaccinated people with a +ve test were asymptomatic, while many others had only mild symptoms. This is consistent with the hospitalisation data in the UK.

The vaccines seem to be ~90% effective at preventing disease serious enough to require hospitalisation. 

So it looks as if the virus will be endemic, though we can hope the incidence of serious disease can be managed through vaccination. However, from your information, and this from the UK, it very much looks to me as if some public health countermeasures to reduce transmission may be needed long term, on top of vaccination.

I don't think I'll be throwing away my mask and I think a lot of people will be well advised to continue to work from home as much as they can.

  

 

I have not been following the REACT releases as frequently as I should, but I have seen a recent release indicating that the viral load in vaccinated folks was lower, which seems to be different than the CDC report. However, the report did not (in my memory) separate out delta infections, so it could still have been a mix of alpha/delta infections.

I also think that masks are a good measure at this point. Even ignoring COVID-19, these measures have prevented the influenza season and thereby prevented thousands of deaths. A change in our behaviour could have overall significant public health impact, even if we just follow customs (such as mask wearing when having a cough) that are common elsewhere.

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46 minutes ago, CharonY said:

I have not been following the REACT releases as frequently as I should, but I have seen a recent release indicating that the viral load in vaccinated folks was lower, which seems to be different than the CDC report. However, the report did not (in my memory) separate out delta infections, so it could still have been a mix of alpha/delta infections.

I also think that masks are a good measure at this point. Even ignoring COVID-19, these measures have prevented the influenza season and thereby prevented thousands of deaths. A change in our behaviour could have overall significant public health impact, even if we just follow customs (such as mask wearing when having a cough) that are common elsewhere.

The UK has been pretty well 100% Delta for the last few months, as far as I understand. So I think the significance of the latest figures is that they can be taken to be indicative of Delta, specifically. But admittedly I'm just going on a newspaper report (albeit our most reliable newspaper).  

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From memory I think delta became dominant end of May in the UK and was reported about 90% by mid-June or so. Assuming all the Ct values are from May to now one would expect a substantial if not most numbers coming from the delta variant. That being said I am not sure where the abundance information was precisely derived from. 

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12 hours ago, iNow said:

image.thumb.png.bc20cbc3420069c8e9ded409ae1ac078.png

While this should be a great incentive to get vaccinated,  I fear that some assume that after  getting vaccinated there is no need for any precautions anymore.  Yet, there is still a lot we need to understand for proper risk assessment.

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I have heard very mixed messages from health officials on that matter. Those I work closely with are for the most part nervous due to the unknowns. The highest priority in their mind is whether hospital beds will become limiting. Higher up on the food chain folks seem already start to transition. I.e. the focus there is how to live with the new reality of COVID-19 as an endemic (and potentially seasonal) disease. Yet for the latter science has, in my mind, not sufficient answers to make it clear how such a life would need to be in order to keep health burden at an acceptable (whatever it may be) level.

For some, the living with COVID-19 appears to translate as pretend it is not there. Especially among young folks the attitude is a bit concerning.

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16 minutes ago, CharonY said:

For some, the living with COVID-19 appears to translate as pretend it is not there. Especially among young folks the attitude is a bit concerning.

People don't seem to realize that not getting vaccinated means that there's close to 100% probability that you will eventually catch the disease. Unless you die from something else.

High vaccination levels would make the latter more of an important part of the equation, and includes "old age." In the US we're already at >10% having had the disease. 

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6 minutes ago, swansont said:

People don't seem to realize that not getting vaccinated means that there's close to 100% probability that you will eventually catch the disease. Unless you die from something else.

High vaccination levels would make the latter more of an important part of the equation, and includes "old age." In the US we're already at >10% having had the disease. 

Yes, and on top being asymptomatic does not equate to no health burden. But I think you are right. Folks still do not seem to realize how effective the virus is spreading, in part precisely because it does not immediately cause severe disease. By comparison, SARS caused maybe around 10k infections and 1k deaths. But if you talk to folks (even biology students) they do not seem to know the vast difference impact of the respective diseases. 

But also from the political side of things I am worried that folks in several areas are winding down tracing (even it it seemed to be done only halfheartedly in the first place) and testing. So we are going to run blind into a new situation, which is rather incomprehensible to me.

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23 minutes ago, CharonY said:

from the political side of things I am worried that folks in several areas are winding down tracing (even it it seemed to be done only halfheartedly in the first place) and testing. So we are going to run blind into a new situation,

My home state was super smart and decided to address Covid by no longer reporting the numbers and making it illegal for schools to mandate masks. The numbers can’t go up if you’re not counting them! 

Super duper smart. Reminds me of government reports and military planning docs being required to strip the words “climate change” out every publication. 

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50 minutes ago, iNow said:

My home state was super smart and decided to address Covid by no longer reporting the numbers and making it illegal for schools to mandate masks. The numbers can’t go up if you’re not counting them! 

Super duper smart. Reminds me of government reports and military planning docs being required to strip the words “climate change” out every publication. 

Unfortunately not an isolated case, nor even specific to the US. In quite a few areas folks are not getting tested unless they have symptoms, are not required to isolate when positive, making mask mandates impossible and so on. The argument is that now that it is endemic we need to to treat it like other endemic diseases, which translates to we are not going to monitor it closely anymore and are not asking you to take extra precautions.

This is a huge gamble and unfortunately the vulnerable are going to carry the risk.

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It is a world problem, not just an American one.
The inept roll-out of vaccines means that although some countries can be fully vaccinated ( and mistakenly feel secure ), in others, where vaccines aren't even available yet, the virus is spreading, and mutating as the host reproduces it, possibly rendering the vaccinations in the former countries, ineffective, if not useless.
The rapid spread of Covid in India, when they were selling all their vaccine production abroad, resulted in the mutation that is Delta.
Who knows how contagious, or deadly, the next mutation from the Southern US, India or Brazil, might be.

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3 hours ago, MigL said:

It is a world problem, not just an American one.
The inept roll-out of vaccines means that although some countries can be fully vaccinated ( and mistakenly feel secure ), in others, where vaccines aren't even available yet, the virus is spreading, and mutating as the host reproduces it, possibly rendering the vaccinations in the former countries, ineffective, if not useless.
The rapid spread of Covid in India, when they were selling all their vaccine production abroad, resulted in the mutation that is Delta.
Who knows how contagious, or deadly, the next mutation from the Southern US, India or Brazil, might be.

Absolutely, and it is the bit that the richer nations have forgotten in their race to obtain vaccines for themselves. Together with the fact that they are also opposed to a patent waiver, things are likely going to get uglier for a while yet. It is one of the reasons why the WHO is trying to get more support for distribution of first doses of vaccines before looking at booster shots. 

Also one thing of note, if breakthrough infections resulting in a certain baseline level of transmission and reproduction, even high(ish) vaccination rates may not prevent the rise of new variants. So far we have variations coming from basically all corners of the world, it is just mostly random where more transmissible variants arise. Before delta, alpha (from the UK) was quickly replacing the original variant. In short it is dangerous to assume where new variants may come from. As you said, it is global problem.

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I have a question about the mRNA vaccines. As far as I understand, one of the advantages of the mRNA vaccines is that the RNA can be synthesised pretty easily. So what is the problem to change the RNA, so that it produces better immunisation against the newer COVID strains? E.g. base it on the RNA that is responsible for the spike protein of the Delta variant.

Is this organisational (new RNA, so new vaccine, so new process of approval), or are there more technical problems?

 

And another question: why base the mRNA vaccine on the spike protein? The only requirement for a vaccine is that the virus cannot multiply in the human body, not that no single body cell can be infected by the virus. Wouldn't there be parts of the virus that have a slower tendency to mutate? The immediate possible advantage of mutations that effect the spike protein might stand under heavier evolutionary pressure as other mutations, e.g. of the envelope of the virus.

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8 hours ago, Eise said:

I have a question about the mRNA vaccines. As far as I understand, one of the advantages of the mRNA vaccines is that the RNA can be synthesised pretty easily. So what is the problem to change the RNA, so that it produces better immunisation against the newer COVID strains? E.g. base it on the RNA that is responsible for the spike protein of the Delta variant.

Is this organisational (new RNA, so new vaccine, so new process of approval), or are there more technical problems?

It would be trivial to have RNA synthesized, and I am pretty sure that folks are doing it. The big issue though is that it is necessary to test safety or efficacy for the new mRNA. While the process is likely going to be faster, it would still require time and money. Meanwhile, the current vaccine has been surprisingly effective in preventing disease so the incentive to invest that is a bit lower. That being said, there is no fundamental guarantee that an adapted vaccine would be more effective. Predicting what works and what doesn't (or what is safe) is a bit difficult to predict when it comes to the immune system and mostly relies on empirical data.

 

8 hours ago, Eise said:

And another question: why base the mRNA vaccine on the spike protein? The only requirement for a vaccine is that the virus cannot multiply in the human body, not that no single body cell can be infected by the virus. Wouldn't there be parts of the virus that have a slower tendency to mutate? The immediate possible advantage of mutations that effect the spike protein might stand under heavier evolutionary pressure as other mutations, e.g. of the envelope of the virus.

The thought is correct, but based on these and other consideration actually make the spike protein an attractive target. The spike protein (or rather a specific domain of the protein) needs to interact with the human ACE receptor. Thus there is some selective pressure to maintain the receptor binding domain, as larger mutations could weaken the interaction. Of course some mutations could enhance binding, but there is only a limited space where such mutations could occur. Because of the way they work, they are also readily accessible by the immune system and are very immunogenic.

The envelope (E) and membrane (M) proteins have been studied on SARS-CoV-1 and have the fundamental problem of being fairly small and only have a relatively small domain exposed to the outside. As a consequence they were found to be only weakly immunogenic. 

The N protein (part of the nucleocapsid) has a number of other issues comparatively speaking. The biggest during the decision-making process was based on research on SARS-CoV-1, where it was found that using parts of the N protein elicited quite different responses. Some appeared to be protective, but then they also observed ADE (a phenomenon discussed in another thread in this forum). Thus figuring out a safe epitope for SARS-CoV-2 would have been risky. In addition, the N gene has exhibited about 2-3x the number of mutations compared to the S-gene (which was not really known at the time of vaccine development) and together it makes it a rather unattractive target. 

 

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  • 2 weeks later...
Officials at the World Health Organization said Wednesday that it strongly opposes booster shots for all adults in rich countries because the boosters will not help slow down the pandemic. By diverting doses away from unvaccinated people, booster shots will help drive the emergence of more dangerous mutants, say the WHO doctors.

"I'm afraid that this [booster recommendation] will only lead to more variants.... And perhaps we're heading into an even more dire situation," says WHO chief scientist Dr. Soumya Swaninathan.

The problem with a call for boosters, she says, is that the virus is primarily circulating in unvaccinated people — not in the fully vaccinated.   
 
I imagine if I was in that tiny percentage of the populace that is most vulnerable and would benefit from the booster,  I might not want a third shot at the cost of dire global consequences.   In any case,  I'm skeptical of Biden's assertion that the US can do this without diverting doses away from the unvaxxed. 
 
Report to moderator   http://forums.escapefromelba.com/Themes/core/images/ip.gif 75.76.164.18
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1 hour ago, TheVat said:
Officials at the World Health Organization said Wednesday that it strongly opposes booster shots for all adults in rich countries because the boosters will not help slow down the pandemic. By diverting doses away from unvaccinated people, booster shots will help drive the emergence of more dangerous mutants, say the WHO doctors.

"I'm afraid that this [booster recommendation] will only lead to more variants.... And perhaps we're heading into an even more dire situation," says WHO chief scientist Dr. Soumya Swaninathan.

The problem with a call for boosters, she says, is that the virus is primarily circulating in unvaccinated people — not in the fully vaccinated.   
 
I imagine if I was in that tiny percentage of the populace that is most vulnerable and would benefit from the booster,  I might not want a third shot at the cost of dire global consequences.   In any case,  I'm skeptical of Biden's assertion that the US can do this without diverting doses away from the unvaxxed. 

The big issue I think is that much of the world is hang out to dry, whereas in some countries the unvaccinated population is mostly so by choice. I do not understand why those countries are not putting more effort in to get vaccines into those that want it, globally. Just thinking in terms of national consequences is, as the pandemic has demonstrated, incredibly short-sighted.

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Recent article from The Guardian:  Jabbed adults infected with Delta ‘can match virus levels of unvaccinated’

https://www.theguardian.com/world/2021/aug/19/jabbed-adults-infected-with-delta-can-match-virus-levels-of-unvaccinated

"Fully vaccinated adults can harbour virus levels as high as unvaccinated people if infected with the Delta variant, according to a sweeping analysis of UK data, which supports the idea that hitting the threshold for herd immunity is unlikely."

-----

To me this news just stresses the importance of developing a wide range of treatment options in addition to vaccines.  Vaccines shouldn't be viewed as the only remedy.

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4 hours ago, TheVat said:

I'm skeptical of Biden's assertion that the US can do this without diverting doses away from the unvaxxed. 

What’s the evidence that doses already bought and paid for by the US would be shipped to other countries if not used for dose #3 on US citizens?

The US has already sent 110 Million doses to other countries and committed to providing 600 Million (over half a billion) doses to the world. That’s quite a bit more than every single other country… combined. 

Is the suggestion here that this number would automatically inflate to 700 Million if we had instead decided to wait on boosters… and that this would meaningfully alter the outcome?

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2 hours ago, Alex_Krycek said:

 

 

Recent article from The Guardian:  Jabbed adults infected with Delta ‘can match virus levels of unvaccinated’

https://www.theguardian.com/world/2021/aug/19/jabbed-adults-infected-with-delta-can-match-virus-levels-of-unvaccinated

"Fully vaccinated adults can harbour virus levels as high as unvaccinated people if infected with the Delta variant, according to a sweeping analysis of UK data, which supports the idea that hitting the threshold for herd immunity is unlikely."

-----

To me this news just stresses the importance of developing a wide range of treatment options in addition to vaccines.  Vaccines shouldn't be viewed as the only remedy.

There are a wide range of treatment options that have been developed. However, except for vaccine there is none that prevents getting sick.

 

29 minutes ago, iNow said:

The US has already sent 110 Million doses to other countries and committed to providing 600 Million (over half a billion) doses to the world. That’s quite a bit more than every single other country… combined. 

Is the suggestion here that this number would automatically inflate to 700 Million if we had instead decided to wait on boosters… and that this would meaningfully alter the outcome?

The issue here is that all vaccinated countries will continue to hoard the supply. Regardless how much the US has committed, (and obviously other wealthy nations should do more) much of the world do not even have their frontline workers fully (or even partially) vaccinated. There is also a financial incentive for Pfizer and Moderna to prioritize booster shot deliveries to countries who pay a premium on it.  However, whole continent of Africa is about 5% vaccinated, for example and even those countries which managed to control the spread to some degree are struggling. 

The idea is that looking at the whole planet (which we should) a booster shot has diminishing return compared to giving first or second shots in entirely unvaccinated and/or high-risk areas such as hospitals, for example.

The ability to reduce or even prevent outbreak or death as well as spread are vastly magnified in those areas over protection of potential loss of vaccination efficacy in a mostly vaccinated population.

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1 hour ago, CharonY said:

The idea is that looking at the whole planet (which we should) a booster shot has diminishing return compared to giving first or second shots in entirely unvaccinated and/or high-risk areas

To be clear, we’re in violent agreement around the logic of this one. We need the whole world vaccinated or we all suffer collectively. No quarrel. 

I’ve also watched politics and economics long enough to know that avoiding a 3rd shot booster in the US isn’t going to magically send extra doses to those areas most in need of their 1st.

Those countries are lacking shot number 1 due to issues unrelated to the US deciding to offer shot #3 to its citizens (damned near half of whom haven’t even bothered taking shot 1 despite the absolute lack of cost, complexity, or obstacle in doing so).

I also want the world vaccinated. I don’t think lack of vaccine supply is the driver of it not happening. I’m essentially struggling with the idea that boosters in the US are the primary barrier to achieving that global vaccination we both agree is desperately needed, especially given all of the vaccines being produced in China, Russia, and elsewhere.  

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