For what? How about for an improved vaccine. Why accept version 1 when doing so confers antibodies for a strain that has, per your recent post on lab leaks, been reengineered twice. The effectiveness of the current vaccine is also debatable. You might say that since it offers some protection its better than nothing, and if you believe that “Vaccines simply don’t have long-term effects…” then I can understand that position. But vaccines do have long term effects. The antibodies they confer stick around for a lifetime, and the first antibodies you get for a particular infection are of particular importance. There is a paper written by Thomas Francis JR, MD in the 1960s called ‘More on Original Antigenic Sin’ that describes just how consequential that first infection or vaccine is. In the paper he states that “The antibody of childhood is largely a response to the virus causing the first Type A influenza infection of the lifetime. As the group grows older and subsequent infections take place, antibodies to additional families of virus are acquired. But the antibody which is first established continues to characterize that cohort of the population throughout its life. The antibody forming mechanisms have been highly conditioned by the first stimulus, so that later infections with strains of the same type successively enhance the original antibody to maintain it at the highest level at all times in that age group. The imprint established by the original virus infection governs the antibody response thereafter. This we have called the doctrine of original antigenic sin.” Considering all of that I still support vaccines, but don’t think its fair to treat all vaccines as equal. It is possible for a vaccine to miss the mark on the imprinting of the virus, and handicap all future immune responses for that virus if it serves as the first exposure. In cases where we are seeing rapid, unexplained, and unprecedented changes in strains of SARS2, that is a real possibility. I hope that a vaccine can be developed that accounts for these things but I have a hard time believing the current vaccine has cracked the code. I was willing to take the chance personally, but I have found it hard to come to the same conclusion for my children. So I think I’m going to wait. Not because I think the vaccine is unsafe, but because I’m not convinced it’s a good candidate for original antigenic response for the rest of their lives.
The two implications of Original Antigenic Sin are:
1. Some viruses, like flu, we do not and cannot have a one-size-fits-all vaccine for, because the virus mutates faster than the vaccine can cover. So (in the case of flu) we get a new one annually.
2. Some viruses, like dengue, cause antibody-dependent enhancement from one infection to the next (or from one vaccine to a later infection, which is why a vaccine for dengue has been elusive).
#2 is a serious problem. #1 is not. #1 applies to coronaviruses. #2 does not.
So the only "problem" with the vaccine (from an antigenic original sin perspective) is that we might (might!) need an updated one later. Meanwhile, the existing vaccine is remarkably protective against severe disease, hospitalization and death.
For me, needing an updated flu vaccine has never been a problem. The flu vaccine has protected me great against flu. So for me, this concept of Original Antigenic Sin is by no means a problem when it comes to choosing the covid vaccines, especially considering that covid is a much deadlier disease than flu. In other words, if I get a flu vaccine every year at work, I'll sure as heck get a covid vaccine when I need one too.
And, we're in the midst of a pandemic that has killed 5.5 million people and is continuing to do so. We're right in the thick of it. And we have these vaccines that can protect your children from hospitalization and death -- and all the lesser things COVID can cause, like MIS-C, permanent loss of smell, and so on. It protects against all of it.
So let me understand you. You favor waiting, and rejecting for now a vaccine that is in fact effective and can protect your children (even against the highly mutated omicron), because it is turning out to be more like flu vaccine (but really, a lot better than flu vaccine, in that it's also protecting against severe outcomes against delta and omicron too).
That position doesn't make sense to me, respectfully. What on earth would you be waiting _for_? We probably will have "better" vaccines in 10 years, 20 years, 30 years. Just as we have better measles vaccines now than we had in the 60s. But these vaccines we have right now are pretty damn good at keeping you out of the hospital and dying.
Every doctor I know has had the vaccine and has made sure their kids have had the vaccine as soon as it was available. No, I don't know every doctor in the world. Some doctors, somewhere, no doubt reject the vaccine. But these people who are fairly knowledgeable, and who no doubt care about their kids as much as you care about yours, have chosen the vaccine for them. Are they all a bunch of chumps? Have they been fooled by Pharma?
Note: I'm no fan of Pharma in general nor Pfizer in particular, but when I looked at all the evidence and looked at the cost-benefit, I chose vaccination for myself and my family.
That doesn't seem like a good plan to me. So I still believe: Wait and see...for what? That's based on the (yes, imperfect) reality of the moment. Reality is always imperfect. There are no perfectly safe choices. The vaccine (_any_ vaccine) is not a perfectly safe choice. Letting your kids get covid is not a perfectly safe choice. (Of the two, letting the kid get covid is the more risky choice in my view, just as letting your kids get measles is a riskier choice than the measles vaccine.)
There is no silver bullet. There is no miracle cure. That's true for any disease. Everything has a cost-benefit. The cost-benefit comes down heavily in favor of choosing the vaccine.
Respectfully, I disagree with the statement that the mRNA vaccines are safe. The original vaccine safety papers from Pfizer and Moderna show more severe outcomes for the vaccine than the placebo group. "Severe outcomes" means "severe adverse events" or "severe COVID-19", which are both defined by the FDA who carefully standardize their terms. The trials were too small to show a statistically significant signal in any direction for more serious things like critical illness/events or death, but the signal for the weaker category "severe" shows the opposite of safety.
You are talking about the data from adults in your substack post, but OK, we can discuss that. All adverse events are not "related" adverse events. In that sense, these studies are a bit like VAERS, where if you are struck dead by lightning the next day after receiving the vaccine, it goes in VAERS.
They cast a wide net in these clinical trials. Anyway: There were more than 43,000 people in the trial you're describing, and the list of _related_ serious adverse events, all four of them, were: "Four related serious adverse events were reported among BNT162b2 recipients (shoulder injury related to vaccine administration, right axillary lymphadenopathy, paroxysmal ventricular arrhythmia, and right leg paresthesia)."
I wouldn't like any of those things, but I would take them more readily than I would take the chances of death and disability with COVID, and I would take them more readily than I would relinquish widespread vaccination at the population level, which is likely the only approach which can get this disease under control at the moment (pending better vaccines, better treatments, better drugs in the future).
No choice in life is risk-free. The dangers posed by choosing "no vaccine" are bigger than the dangers posed by choosing the vaccine.
"Related" means judged to be related by a clinician. Obviously, expert judgement can be wrong and the whole point of a randomized trial is to measure signals independently of that flawed judgement. The data show that the vaccine group had more severe outcomes than the placebo group, and the difference was too large to be a fluke.
It was not lightning or anything else like that, because the groups were randomized and nobody knew until after the trial who got the placebo and who the vaccine. How could lightening preferentially strike people in the vaccine group? If that happened, it would be proof that the vaccine attracts lightening.
Jan 7, 2022·edited Jan 7, 2022Liked by The 21st Century Salonnière
So there was a total of 162 Covid cases among the placebo group, with 9 severe cases. Thats a severity rate of around 5%. Compared to around 1% for the vaccination (one might argue that you should even deduct some base rate from it as the placebo group also had severe events without receiving a vaccine)
That makes the vaccine a much smaller risk... or what am I missing?
We are under the assumption that a large majority of non-hermits will catch covid-19 eventually, aren't we?
That assumption amounts to a huge, unwarranted, and incorrect extrapolation. The 162 in the study are symptomatic COVID cases but many others will have been asymptomatic. It is also not known if a large majority have yet to be infected. How many boosters are needed for continuing protection, and how many adverse events will they cause? That kind of risk/benefit calculation is intractable.
These shots can't be expected to convey lifelong protection so it's much more rigorous to compare vaccine benefits and harms during an observation window of several pandemic months, as was done in the study. In my calculation (linked above), I did subtract placebo events from vaccine events. The result is that not taking the vaccine is the best way to avoid severe medical outcomes.
Don't you find it weird that you come to a different conclusion than the study's authors? They conclude that the vaccine is safe. But how could they conclude that if the probability of a severe adverse events is almost doubled?
Please don't take this the wrong way -- it is obvious that you know much more about statistics than I do and I could be totally wrong here but I really DO think you misunderstood the study.
The key point is (from the Method chapter):
"Reactogenicity events among the participants who were not in the reactogenicity subgroup were reported as adverse events, which resulted in imbalances between the BNT162b2 group and the placebo group with respect to adverse events (30% vs. 14%), related adverse events (24% vs. 6%), and severe adverse events (1.2% vs. 0.7%)"
So the adverse events include fever and other typical vaccine reactions. Of course they are more likely to occur in the group who received the vaccine.
And the definition of severe you pulled from somewhere seems to differ from the author's definition.
If you check page 16 of the appendix you see examples of what they rate as a severe reaction:
* redness and swelling of >10cm in diameter,
* fatigue that prevents daily activity,
* more than 6 loose stools in 24 hours
* a fever of 38.9-40°C
So did you mean these kind of outcomes when you talked about severe reactions? Because if you did I have to tell you I would take all these severe outcomes AT ONCE if I got the protection against severe covid outcomes in return. What are some loose stools compared to a viral lung infection? I would happily shit my pants if it saved me from the ECMO!
But to end on a happy anecdote, I am vaccinated thrice and besides my arm hurting a bit I had no adverse reaction at all.
If my employer stood to make tens of billions of Dollars from the work, I could maybe also be persuaded to emphasize the positive results, and tuck the not-so-flattering data into a Supplementary Appendix that few people analyze carefully. Otherwise they would just hire someone with the required mental flexibility.
The updated NEJM paper 10.1056/NEJMoa2110345 cites the FDA definitions for adverse events as reference 12. The citation is only for Grade 4 (life threatening) events, but this is obviously the industry standard. The criteria you list correspond exactly to the FDA category "severe", so there is no disagreement about what constitutes a severe adverse event.
The FDA generally define severe for both adverse events and illness as "Prevents daily activity and requires medical intervention".
According to their more specialized definition for COVID-19, heart rate > 125 plus a positive PCR test is enough for a diagnosis of severe COVID. That is no worse than the severe reactions you listed, and in fact HR > 130 is needed to qualify as a severe adverse event. You seem to think of "severe" COVID as "critical" COVID with an ER visit or hospitalization. But that is a different category and the safety study had no cases like that.
For what? How about for an improved vaccine. Why accept version 1 when doing so confers antibodies for a strain that has, per your recent post on lab leaks, been reengineered twice. The effectiveness of the current vaccine is also debatable. You might say that since it offers some protection its better than nothing, and if you believe that “Vaccines simply don’t have long-term effects…” then I can understand that position. But vaccines do have long term effects. The antibodies they confer stick around for a lifetime, and the first antibodies you get for a particular infection are of particular importance. There is a paper written by Thomas Francis JR, MD in the 1960s called ‘More on Original Antigenic Sin’ that describes just how consequential that first infection or vaccine is. In the paper he states that “The antibody of childhood is largely a response to the virus causing the first Type A influenza infection of the lifetime. As the group grows older and subsequent infections take place, antibodies to additional families of virus are acquired. But the antibody which is first established continues to characterize that cohort of the population throughout its life. The antibody forming mechanisms have been highly conditioned by the first stimulus, so that later infections with strains of the same type successively enhance the original antibody to maintain it at the highest level at all times in that age group. The imprint established by the original virus infection governs the antibody response thereafter. This we have called the doctrine of original antigenic sin.” Considering all of that I still support vaccines, but don’t think its fair to treat all vaccines as equal. It is possible for a vaccine to miss the mark on the imprinting of the virus, and handicap all future immune responses for that virus if it serves as the first exposure. In cases where we are seeing rapid, unexplained, and unprecedented changes in strains of SARS2, that is a real possibility. I hope that a vaccine can be developed that accounts for these things but I have a hard time believing the current vaccine has cracked the code. I was willing to take the chance personally, but I have found it hard to come to the same conclusion for my children. So I think I’m going to wait. Not because I think the vaccine is unsafe, but because I’m not convinced it’s a good candidate for original antigenic response for the rest of their lives.
More on that topic can be found on another substack here: https://eugyppius.substack.com/p/more-on-original-antigenic-sin-and
Here's a more recent article on the topic. https://www.sciencedirect.com/science/article/pii/S0896841117302226?via%3Dihub
The two implications of Original Antigenic Sin are:
1. Some viruses, like flu, we do not and cannot have a one-size-fits-all vaccine for, because the virus mutates faster than the vaccine can cover. So (in the case of flu) we get a new one annually.
2. Some viruses, like dengue, cause antibody-dependent enhancement from one infection to the next (or from one vaccine to a later infection, which is why a vaccine for dengue has been elusive).
#2 is a serious problem. #1 is not. #1 applies to coronaviruses. #2 does not.
So the only "problem" with the vaccine (from an antigenic original sin perspective) is that we might (might!) need an updated one later. Meanwhile, the existing vaccine is remarkably protective against severe disease, hospitalization and death.
For me, needing an updated flu vaccine has never been a problem. The flu vaccine has protected me great against flu. So for me, this concept of Original Antigenic Sin is by no means a problem when it comes to choosing the covid vaccines, especially considering that covid is a much deadlier disease than flu. In other words, if I get a flu vaccine every year at work, I'll sure as heck get a covid vaccine when I need one too.
And, we're in the midst of a pandemic that has killed 5.5 million people and is continuing to do so. We're right in the thick of it. And we have these vaccines that can protect your children from hospitalization and death -- and all the lesser things COVID can cause, like MIS-C, permanent loss of smell, and so on. It protects against all of it.
So let me understand you. You favor waiting, and rejecting for now a vaccine that is in fact effective and can protect your children (even against the highly mutated omicron), because it is turning out to be more like flu vaccine (but really, a lot better than flu vaccine, in that it's also protecting against severe outcomes against delta and omicron too).
That position doesn't make sense to me, respectfully. What on earth would you be waiting _for_? We probably will have "better" vaccines in 10 years, 20 years, 30 years. Just as we have better measles vaccines now than we had in the 60s. But these vaccines we have right now are pretty damn good at keeping you out of the hospital and dying.
Every doctor I know has had the vaccine and has made sure their kids have had the vaccine as soon as it was available. No, I don't know every doctor in the world. Some doctors, somewhere, no doubt reject the vaccine. But these people who are fairly knowledgeable, and who no doubt care about their kids as much as you care about yours, have chosen the vaccine for them. Are they all a bunch of chumps? Have they been fooled by Pharma?
Note: I'm no fan of Pharma in general nor Pfizer in particular, but when I looked at all the evidence and looked at the cost-benefit, I chose vaccination for myself and my family.
Meanwhile, while you wait 10, 20, 30 years for a better vaccine, according to NBC news, the rates of kids being hospitalized has grown at about twice the rates of adults https://www.nbcnews.com/news/us-news/child-covid-hospitalizations-are-5-states-are-rise-rcna10089
That doesn't seem like a good plan to me. So I still believe: Wait and see...for what? That's based on the (yes, imperfect) reality of the moment. Reality is always imperfect. There are no perfectly safe choices. The vaccine (_any_ vaccine) is not a perfectly safe choice. Letting your kids get covid is not a perfectly safe choice. (Of the two, letting the kid get covid is the more risky choice in my view, just as letting your kids get measles is a riskier choice than the measles vaccine.)
There is no silver bullet. There is no miracle cure. That's true for any disease. Everything has a cost-benefit. The cost-benefit comes down heavily in favor of choosing the vaccine.
Respectfully, I disagree with the statement that the mRNA vaccines are safe. The original vaccine safety papers from Pfizer and Moderna show more severe outcomes for the vaccine than the placebo group. "Severe outcomes" means "severe adverse events" or "severe COVID-19", which are both defined by the FDA who carefully standardize their terms. The trials were too small to show a statistically significant signal in any direction for more serious things like critical illness/events or death, but the signal for the weaker category "severe" shows the opposite of safety.
More details: https://norstadt.substack.com/p/severe-adverse-events-vs-severe-covid
You are talking about the data from adults in your substack post, but OK, we can discuss that. All adverse events are not "related" adverse events. In that sense, these studies are a bit like VAERS, where if you are struck dead by lightning the next day after receiving the vaccine, it goes in VAERS.
They cast a wide net in these clinical trials. Anyway: There were more than 43,000 people in the trial you're describing, and the list of _related_ serious adverse events, all four of them, were: "Four related serious adverse events were reported among BNT162b2 recipients (shoulder injury related to vaccine administration, right axillary lymphadenopathy, paroxysmal ventricular arrhythmia, and right leg paresthesia)."
I wouldn't like any of those things, but I would take them more readily than I would take the chances of death and disability with COVID, and I would take them more readily than I would relinquish widespread vaccination at the population level, which is likely the only approach which can get this disease under control at the moment (pending better vaccines, better treatments, better drugs in the future).
No choice in life is risk-free. The dangers posed by choosing "no vaccine" are bigger than the dangers posed by choosing the vaccine.
"Related" means judged to be related by a clinician. Obviously, expert judgement can be wrong and the whole point of a randomized trial is to measure signals independently of that flawed judgement. The data show that the vaccine group had more severe outcomes than the placebo group, and the difference was too large to be a fluke.
It was not lightning or anything else like that, because the groups were randomized and nobody knew until after the trial who got the placebo and who the vaccine. How could lightening preferentially strike people in the vaccine group? If that happened, it would be proof that the vaccine attracts lightening.
So there was a total of 162 Covid cases among the placebo group, with 9 severe cases. Thats a severity rate of around 5%. Compared to around 1% for the vaccination (one might argue that you should even deduct some base rate from it as the placebo group also had severe events without receiving a vaccine)
That makes the vaccine a much smaller risk... or what am I missing?
We are under the assumption that a large majority of non-hermits will catch covid-19 eventually, aren't we?
That assumption amounts to a huge, unwarranted, and incorrect extrapolation. The 162 in the study are symptomatic COVID cases but many others will have been asymptomatic. It is also not known if a large majority have yet to be infected. How many boosters are needed for continuing protection, and how many adverse events will they cause? That kind of risk/benefit calculation is intractable.
These shots can't be expected to convey lifelong protection so it's much more rigorous to compare vaccine benefits and harms during an observation window of several pandemic months, as was done in the study. In my calculation (linked above), I did subtract placebo events from vaccine events. The result is that not taking the vaccine is the best way to avoid severe medical outcomes.
Don't you find it weird that you come to a different conclusion than the study's authors? They conclude that the vaccine is safe. But how could they conclude that if the probability of a severe adverse events is almost doubled?
Please don't take this the wrong way -- it is obvious that you know much more about statistics than I do and I could be totally wrong here but I really DO think you misunderstood the study.
The key point is (from the Method chapter):
"Reactogenicity events among the participants who were not in the reactogenicity subgroup were reported as adverse events, which resulted in imbalances between the BNT162b2 group and the placebo group with respect to adverse events (30% vs. 14%), related adverse events (24% vs. 6%), and severe adverse events (1.2% vs. 0.7%)"
So the adverse events include fever and other typical vaccine reactions. Of course they are more likely to occur in the group who received the vaccine.
And the definition of severe you pulled from somewhere seems to differ from the author's definition.
If you check page 16 of the appendix you see examples of what they rate as a severe reaction:
* redness and swelling of >10cm in diameter,
* fatigue that prevents daily activity,
* more than 6 loose stools in 24 hours
* a fever of 38.9-40°C
So did you mean these kind of outcomes when you talked about severe reactions? Because if you did I have to tell you I would take all these severe outcomes AT ONCE if I got the protection against severe covid outcomes in return. What are some loose stools compared to a viral lung infection? I would happily shit my pants if it saved me from the ECMO!
But to end on a happy anecdote, I am vaccinated thrice and besides my arm hurting a bit I had no adverse reaction at all.
Tilman, you're a champ. Thanks for your contributions here! :) Also glad to hear that you had no reaction other than a sore arm.
If my employer stood to make tens of billions of Dollars from the work, I could maybe also be persuaded to emphasize the positive results, and tuck the not-so-flattering data into a Supplementary Appendix that few people analyze carefully. Otherwise they would just hire someone with the required mental flexibility.
The updated NEJM paper 10.1056/NEJMoa2110345 cites the FDA definitions for adverse events as reference 12. The citation is only for Grade 4 (life threatening) events, but this is obviously the industry standard. The criteria you list correspond exactly to the FDA category "severe", so there is no disagreement about what constitutes a severe adverse event.
The FDA generally define severe for both adverse events and illness as "Prevents daily activity and requires medical intervention".
According to their more specialized definition for COVID-19, heart rate > 125 plus a positive PCR test is enough for a diagnosis of severe COVID. That is no worse than the severe reactions you listed, and in fact HR > 130 is needed to qualify as a severe adverse event. You seem to think of "severe" COVID as "critical" COVID with an ER visit or hospitalization. But that is a different category and the safety study had no cases like that.
It’s a Bioweapon not a vaccine.
Well, if you start with a statement like that but have no evidence to support it, where can the conversation go? I wish you well.