Particularly with the mRNA vaccines there isn't much in the vaccine that isn't in the virus already.
There has to be a name for this fallacy. It is like we're living in the dark ages where contracting covid is just "God's will" and it doesn't count in risk assessments, while no matter how small the risk is over the vaccine that is all that matters.
In the case of COVID-19: you have to actively get the vaccine, meaning that people overweight its risks relative to the risks latent in not getting it.
It's good to point that out, but the first term needs to be multiplied by the chance of getting the virus.
https://newsroom.heart.org/news/myocarditis-risk-significant...
I don’t find this compelling at all. At the very least, the mRNA vaccines have the lipid nanoparticles themselves, and LNPs are quite clearly biologically active.
And the mRNA gets delivered to cells that would not be infected by the actual virus. One might imagine that such cells would be targeted to at some some extent by CD8+ T cells that learn to recognize spike protein. As far as I can tell, there is nothing published examining what actually happens, but you certainly don’t end up with massive death of muscle cells when vaccinated. See, for example, the comments here:
https://www.science.org/content/blog-post/mrna-vaccines-what...
> One might imagine that such cells would be targeted to at some some extent by CD8+ T cells that learn to recognize spike protein.
This is exactly what we want to see happen, and you're going to get CD8+ T-cells from the virus as well (and if you don't, then you're going to get very extremely ill).
The tissue distribution is a reasonably good point, but that should be considered in light of the evidence that the virus itself likes to hide out in places like the gut and that liver and gut activation after vaccination may be protective. And if that argument is wrong, that would be an argument to try to produce nasal mRNA vaccines.
And at this point we do have a really massive amount of data on the safety and efficacy of the mRNA vaccines and we're having to sift the data very closely to find effects lower than one in million. Other vaccines perform worse. I think it probably is because we're getting closer and closer to minimalism.
The LNPs are most certainly active in the quantities used:
https://www.news-medical.net/news/20221109/Empty-lipid-nanop...
(Also, you don’t have cell walls.)
> This is exactly what we want to see happen, and you're going to get CD8+ T-cells from the virus as well (and if you don't, then you're going to get very extremely ill).
No. What you want to see is protection from the virus, hopefully prevention of infection entirely, hopefully long lasting, hopefully in a form that the virus can’t easily evolve its way out of. And you want this with as little in the way of side effects as practical.
You might think this would happen with an appropriate antibody response or an appropriate CD8+ response or some combination or something else. That’s a hypothesis that may or may not be correct.
But saying that you want your T cells attacking your muscle cells after a vaccine seems absurd. Maybe you can tolerate that (as people apparently can), but I can’t imagine it’s desirable. As far as I can tell, the actual desired means to get CD8+ T cells is for antigen-presenting cells to present pieces of the protein in question attached to MHC1 on their surface, along with the appropriate signals to nearby T cells to encourage them to develop into the right kind of T cell. Your muscle cells are not those antigen presenting cells!
> And at this point we do have a really massive amount of data on the safety and efficacy of the mRNA vaccines … Other vaccines perform worse.
I’m a fan of Covid vaccines too, but this feels like drinking the Kool-Aid. The chickenpox vaccine is effective. The measles vaccine is effective. The tetanus vaccine is pretty effective.
The current crop of monovalent Covid mRNA were highly effective from a week or so after the second dose out to quite a few months against variants closely enough related to the original. [0] Otherwise they are, frankly, far from highly effective. The bivalent vaccines, as far as I can tell, look decent in terms of immunogenicity, but haven’t really been studied well for efficacy against actual infection.
So maybe these mRNA vaccines achieve a form of minimalism, and maybe they’re better than other Covid vaccines, but on the scale of vaccines overall, they’re not great.
[0] Compare to the chickenpox vaccine. In actual randomized trials, they were nearly completely effective even in patients exposed to chickenpox a few days before vaccination. The two-dose series appears to protect recipients for life, or at least decades, strongly enough that epidemic chickenpox is gone in the US. And that continues to work despite chickenpox surely being reintroduced by visitors from abroad on a regular basis and from older infectious shingles patients. That is an effective vaccine.
There's several studies that have shown myocarditis from the virus is indistinguishable from previously-measured myocarditis in the population in general - that the virus isn't actually causing any. At least one of them included vaccine-caused myocarditis and showed it's several times higher.
https://newsroom.heart.org/news/myocarditis-risk-significant...
> Post COVID-19 infection was not associated with either myocarditis (aHR 1.08; 95% CI 0.45 to 2.56) or pericarditis (aHR 0.53; 95% CI 0.25 to 1.13). We did not observe an increased incidence of neither pericarditis nor myocarditis in adult patients recovering from COVID-19 infection.
https://pubmed.ncbi.nlm.nih.gov/35456309/
But also your source is kind of bad. It doesn't have an unvaccinated control group, so from that research there's no way to know if what they found was virus or vaccine related. But they did find an age and sex based correlation which lines up with other sources saying the vaccines are bad for young men:
> The risk of COVID-19 vaccine-associated myocarditis was higher in men younger than age 40 after a first dose of an mRNA vaccine or after a second dose of any of the 3 vaccines.
There's also a useful metric for the "chance of dying" - it's known as a micromort. Each micromort is a one in a million chance of dying https://en.wikipedia.org/wiki/Micromort
A fair bit of statistical work has been done on COVID-19 and it is summarized in the wikipedia article.
AstraZeneca vaccination against COVID-19 – 2.9 micromorts[31]
COVID-19 infection at age 10 – 20 micromorts
COVID-19 infection at age 25 – 100 micromorts
COVID-19 infection at age 55 – 4,000 micromorts
COVID-19 infection at age 65 – 14,000 micromorts
COVID-19 infection at age 75 – 46,000 micromorts
COVID-19 infection at age 85 – 150,000 micromorts [32]
NYT - Putting the Risk of Covid-19 in Perspective Is the risk of dying from Covid-19 comparable to driving to work every day, skydiving or being a soldier in a war?
https://www.nytimes.com/2020/05/22/well/live/putting-the-ris...
> Converting this to micromort language, an individual living in New York City has experienced roughly 50 additional micromorts of risk per day because of Covid-19. That means you were roughly twice as likely to die as you would have been if you were serving in the U.S. armed forces in Afghanistan throughout 2010, a particularly deadly year.
Rare is not zero - but if you are risk adverse, then avoiding things that are fairly high up on the risk counter would be reasonable. Likewise, if there are two options (driving in a car vs driving in a motor cycle), taking the one that adds the least amount of additional risk is reasonable.
For example, according to "Challenges in Inferring Intrinsic Severity of the SARS-CoV-2 Omicron Variant" (https://www.nejm.org/doi/full/10.1056/NEJMp2119682?query=fea...): "This meaningful but fairly small difference [vs Delta] implies that omicron, alpha, and wild-type SARS-CoV-2 have similar intrinsic severity."
Consider "traveling 230 miles by car is 1 micromort"... but that doesn't account for impaired driving or any of the other factors known to influence likelihood or survival of a car crash.
The numbers would likely change if you further specified them, but they are useful for the broad comparisons and risk analysis.
If you've got someone going skydiving every weekend, what does that do to their life insurance rates? Well, skydiving is 8 micromorts per jump. So that's 400 micromorts per year. And that goes into some insurance premium cost calculations.
From Wikipedia:
> Micromorts for future activities can only be rough assessments, as specific circumstances will always have an impact. However, past historical rates of events can be used to provide a ball park, average figure.
Another part of this is a study about risk acceptance.
> An application of micromorts is measuring the value that humans place on risk. For example, a person can consider the amount of money they would be willing to pay to avoid a one-in-a-million chance of death (or conversely, the amount of money they would receive to accept a one-in-a-million chance of death). When offered this situation, people claim a high number. However, when looking at their day-to-day actions (e.g., how much they are willing to pay for safety features on cars), a typical value for a micromort is around $50 (in 2009). This is not to say the $50 valuation should be taken to mean that a human life (1 million micromorts) is valued at $50,000,000. Rather, people are less inclined to spend money after a certain point to increase their safety. This means that analyzing risk using the micromort is more useful when using small risks, not necessarily large ones.
That last sentence is an important one when looking at this.
Would you be willing to be paid $150 to get vaccinated?
As always, xkcd explains it best: https://www.explainxkcd.com/wiki/index.php/882:_Significant
Your link is not relevant to this issue so I don't know what point you're trying to make.
To be clear I support vaccination. But patients should make their own decisions free of coercion based on informed consent with full knowledge of the risks on both sides. Don't presume to patronize them with spurious, bad faith comments about "P-hacking". Let's see the actual data.
And FWIW, if you want a more complete (but much less amusing) explainer on the subject, wikipedia always comes through: https://en.wikipedia.org/wiki/Data_dredging
For example, peanut allergies don't exist because most people don't have reactions to them. You absolutely can ask the question for if peanuts are good or bad for a subpopulation.
The alternative is just sticking your head in the sand.
I'm not sure why you're trying to derail the discussion by bringing up data dredging. That would only potentially be relevant as a possible criticism of the methodology in a particular study. So what's your point?
It isn’t p-hacking for a dude to inquire what the chances are for the male subgroup.
For example, we know that a dubious methodology was used for counting deaths in Toronto (Canada's most populous city, and the fourth most populous city in North America).
This was publicly admitted to by Toronto Public Health itself, as early as June 2020:
"Individuals who have died with COVID-19, but not as a result of COVID-19 are included in the case counts for COVID-19 deaths in Toronto."
https://twitter.com/TOPublicHealth/status/127588839006028596...
I can't see how that significant city's death stats could be considered reliable or usable for analytic purposes, after considering how the counting was done. The provincial and national stats would also be affected to some extent.
This makes me quite doubtful about the stats coming out of other regions, too.
The meta-analysis is looking at that question that you are asking.
It also has all the papers that it cites for analysis and an analysis of its own limitations.
> The systematic review encompassed 113 studies, of which 27 studies (covering 34 geographical locations) satisfied the inclusion criteria and were included in the meta-analysis.
The closest I've seen to an answer is to remove accidental deaths (eg, hit by a car, firearms fatality, etc) but there's a huge range of arguable cases like stroke which is plausibly covid-affected. Second, you have the problem of comparing stats between locations that used different definitions, so it's harder to do post-hoc correlations.
The decisions seems to have been avoiding false-negative mistakes by increasing false positives in the first wave of analysis: "Let's include everything under a simple rule for covid stats so that we at least have some kind of worst-case baseline modelling with similar datasets, and we can figure out afterwards which are real and which aren't"
Anyway, just wanted to see if you actually have a better answer to the problem than the standard that was used.
The recent Paxlovid study supports this. It reduces deaths days 30-90. Deaths that would not be counted as Covid deaths. But they clearly are if paxlovid reduces them.
> "Individuals who have died with COVID-19, but not as a result of COVID-19 are included in the case counts for COVID-19 deaths in Toronto."
I don't know the particulars of Toronto Public Health, but this wasn't uncommon for immediate reporting vs death record reporting. Since, in many places, comprehensive death records can take a few weeks (or longer!) to go through the pipeline before ending up on finalized reports, it's useful to have more immediate death reporting during a pandemic. Such immediate reporting is necessarily going to be a little rougher around the edges, but it generally gets you pretty close to the real numbers.
But, it's absolutely true that this immediate reporting isn't perfect. Still, it's very useful, and usually close enough for near term needs. Taking the Toronto example, the main tradeoffs are that a) you include some deaths where Covid wasn't actually a contributing factor and b) you miss deaths where the person was never tested for Covid (especially applicable to deaths that occurred at home). Often, these two somewhat balanced themselves out, but only in places with fairly high levels of testing.
Then, in the medium to longer term, you can switch over to relying on more comprehensive death records. This helps to filter out non-causal scenarios (e.g. the "hit by bus, tested positive for covid, died" scenarios). It also helps add in cases that were initially missed (had symptoms of covid, never went to hospital, died at home, etc).
Finally, to validate numbers, we can also look at excess deaths. This helps ensure that we're not wildly off base with reported numbers. Excess deaths isn't a perfect metric to compare to, but it's still a great benchmark.
To wrap up this comment, let me respond to this:
> We have to be extremely cautious when considering any of the death-related statistics for this particular situation.
I fully agree, but.. I would suggest that your comment missed a lot of the accuracy refinement that happens in practice over the medium to longer term. Additionally, it's very much worth pointing out that, with additional analysis (from death records, from excess death analysis, etc), we've found that very few places were likely over-reporting Covid deaths, but that a significant number of places were under-reporting Covid deaths. So, yes, take shorter term Covid death stats with a grain of salt, but know that we've generally ended up reporting too low, not too high.
This is highly misleading. The average individual may be at such risk, just like humans have ~1.9 legs on average, but that doesn't mean that everyone walks around with their 1.9 legs.
So those statistics are based on the risk to the general population and therefore have approximately zero relevance to any single person.
Almost by definition, the disease will claim those most vulnerable first, so questioning whether vaccination is worth it for those less vulnerable is valid.
What're the risks of vaccination vs covid for a healthy 25 year old who works from home?
I don't believe that comparing those two is unreasonable.
However, to your last question that is what micomorts can answer.
The risk of death from a vaccination is 2.9 micromorts. The risk of death from contracting Covid-19 for a 25 year old is 100 micromorts. So 30x greater risk.. and those are directly comparable numbers.
The other point to consider - you're not always going to be 25. I'm much closer to the 55 bracket than the 25 bracket, and that represents a 40x increase in risk... so about 1200x greater risk than vaccination.
Assuming you remain a hermit for some number of years (and Covid-19 remains endemic), is there a point where you would change your mind on the value proposition of a vaccination? And if the answer is yes - why not do it now?
Yea, currently you're comparing 2.9 micromorts vs 100 micromorts. At 25, that comparison doesn't have too much to it. 100 micromorts is not something that I think too much about either (comparable to the risk of death while giving birth for the women out there). I've done road trips that racked up 100 micromorts cumulative (more if you add in the hiking and skiing micromorts on that trip).
I'll also note I'm older now than when I was when I did that roadtrip... and there are things that I would do now to further mitigate the risks that I took back then.
It's not wrong for your age, but it is something that should be said "yes, its a risk and it is a lot riskier."
That said, there's a number even beyond that 100 micromorts to consider.
New data shows long Covid is keeping as many as 4 million people out of work - https://www.brookings.edu/research/new-data-shows-long-covid...
> 1.6 million full-time equivalent workers could be out of work due to long Covid. With 10.6 million unfilled jobs at the time, long Covid potentially accounted for 15% of the labor shortage.
That 4M number is not part that I want to be part of. While I have better than average health insurance, the not-dying also has a significant risk to it too. It is harder to quantify as it isn't an accurate cause of mortality - but it is not something that should be ignored.
Many people here enjoy better than average salaries - consider the risk of going on long term disability for the next 40 to 60 years with the corresponding reduction in compensation. And yes, I know people who are no longer able to work on anything that has a deadline or expectations of attendance in meetings; their lifestyle has changed significantly from three years ago.
So in other words it's pretty inflated.
1) Putting covid-positive patients in nursing homes instead of isolating them
2) Excess use of ventilators set to maximum
3) Omicron
4) I feel like I'm forgetting something...
https://www.cdc.gov/mmwr/volumes/69/wr/mm6919e5.htm was a initial report on the excess deaths in NYC in the spring of 2020.
The by age micromorts are based on a paper that was published in December of 2020. Delta was first detected in the US in Feb of 2021 and named in May of 2021 - again, those numbers are before Delta and Omicron (and vaccination).
The numbers may not be current, but they are not inflated. They are an accurate representation of the excess deaths at that time.
> The numbers may not be current, but they are not inflated. They are an accurate representation of the excess deaths at that time.
That is exactly my point for mentioning Omicron: When you introduced them above you were using them for current risk.
I'd add to this the fact that it was especially true earlier in the pandemic, and at that time COVID was significantly more likely to be fatal. Even if someone rejects the idea of getting a fourth dose of the vaccine (rightly or wrongly), it's possible to think that the first two doses were an entirely reasonable one-time intervention into an ongoing pandemic that saved many thousands of lives.
I've read conflicting accounts of whether that's true or false, but even if it is - what difference does it make? We're not going to reach heard immunity here. Everybody's going to get it, several times throughout their lives, no matter what we do at this point.
Choosing not to take Advil affects nobody but you. Choosing not to get vaccinated against a highly-contagious virus affects society.
I agree with your general point, but to be clear, it likely reduces your chances of doing that, to some extent. It does not prevent you from spreading COVID.
If the vaccine prevents one case of spread while not preventing another, it has still prevented COVID spread.
No? If they were the best form of contraception we had (which is the relevant comparison w.r.t. vaccines), of course people would use them! It would make abstinence marginally more appealing, of course, but there are already people who don't want or can't afford a pregnancy who unwisely choose to forgo contraception. There would certainly be an enormous number of people who would choose to use condoms rather than forgo sex entirely.
If vaccination causes you to experience an early immune response, versus several asymptomatic days while unknowingly contagious, then it has prevented you from spreading covid to some of those you would have otherwise.
If vaccination results in a less severe infection with lower viral load, then it has prevented you from spreading covid to some of those you would have otherwise.
My reply was intentionally simple in order to drive home a point about selfish versus societal viewpoints.
Depends on what you mean by "covid" here. If you're referring to the virus, then no - this is a misconception. The vaccines at best only reduce symptoms, they don't stop infection or transmission.
> versus several asymptomatic days while unknowingly contagious
This was also an early guess that turned out to be wrong. We've known this wasn't a thing for years, at least before these vaccines.
> My reply was intentionally simple in order to drive home a point about selfish versus societal viewpoints.
Right now, getting vaccinated is the selfish action because it's likely to turn you into an asymptomatic spreader. At least when unvaccinated you'll know to stay home.
This is a) insane and b) directly contradicts the point you tried to make above it.
If I remember the timeline right it was mid/late 2020 we realized that assumption was wrong, then about a year later it was apparent the vaccines weren't stopping the spread. So yeah, my statements are entirely consistent: There wasn't before the vaccines, there was after.
Even before the COVID-19 pandemic, it was routine for medical institutions to be overwhelmed by respiratory viruses. We didn't halt society, we just accepted the consequences and moved on.
https://time.com/5107984/hospitals-handling-burden-flu-patie...
There's no non sequitur here: getting vaccinated reduces every demographic's risk of serious illness (even when serious illness is not especially likely!), which in turn reduces the burden on healthcare institutions. That is a good civic reason to get vaccinated that has nothing to do with transmission.
[1]: https://www.cdc.gov/nchs/nvss/vsrr/covid19/excess_deaths.htm
Look whatever you think about anything full hospitals everywhere and people in Spain being left for dead in old folks homes were definitely real things - I am not sure about your definition of "halt society" here but policy choices that reduced social contact in indoor spaces was absolutely required. You just can't rewrite history if that is what you are trying to imply.
Is it? No. It is not. Not even for the best protected youngest cohort. Get your shot. You're being misled by politics and tiny, difficult numbers.
In my case i vaccinated because i knew i was a transmission node in case of being infected and not noticing, potetially endangering multitude of vulnerable people.
I don't even take OTC pain killers like advil unless I absolutely feel like I have to.