RNA vaccines have a huge potential in treating cancer as well. Basically, you can whip up a personalized vaccine which wakes the immune system up to the fact that it has a growing tumor on its hands.
So far, the success rate is very far from 100 per cent, but the therapy sometimes works even in patients with severe late stage metastatized cancer and, in all likelihood, we will learn how to use it better in coming years.
This progress could save way more lives down the line than just those at risk with Covid.
Yes i read some interesting article aswell regarding mRNA vaccines, but from my understanting mRNA vaccine aren't yet tested in humans right? Only animals or am i mistaken?
EDIT: what my question is: is there another mRNA type vaccine out there fully developed (i'm not suggesting that they are bad!)?
EDIT2: Guys, i will never ask question again in here. Begin downvoted for a genuine question.
Don't sweat the haters, always feel free to ask legitimate questions. They're the ones who have to look in the mirror and see a person who tries to keep people from learning.
Yes, mRNA is pretty good and very promising (Moderna and BioNTech are mRNA based and they seems the most developed as for now)!
My question was not asking if they are safe or not good (they have multiple points that make them probably the next big thing in vaccines and cancer treatments), i was asking if there are already mRNA vaccine type 100% developed and used as today.
I have found that sometimes it's necessary to say "this is an honest question, I honestly don't know the answer". Otherwise people infer a negative intent
Given the desperate times, it actually seems like an ideal time. Even if there is some unknown side-effect, it only has to be less worse than the current situation to still be a net benefit.
What if it's more worse? I don't think desperate times call for throwing caution to the wind. A fundamental principle of medicine is "First, do no harm."
You say that now, but when you're part of a vast planet-wide meat computer transformed by the "vaccine" that aliens developed to turn us into their next-gen CPUs (5*10^11 neurons per sq. Kilometer!) ... Well, I'm guessing if that happened you'd feel a bit silly.
if mRNA works in anything close to a general case, i’m beginning to think that it might be as fundamentally transformative as the move from sulfa drugs to antibiotics was.
I do not know if you aware or not, but there is a similar to mRNA vaccines, yet different (actually, almost mirror reflection of what mRNA vaccine is) invention called antisense drugs. Those are actually already used as antivirals.
Antisense drugs are the same biological material, but have a very different mechanism of effect.
Specifically, mRNA vaccines require an immune response to be effective. The mRNA (vaccine) encodes a viral protein, and the host (human) immune system still has to learn to respond to that protein.
Antisense drugs are much simpler, with no immune response required. The mRNA (the drug) itself simply binds to the target mRNA.
> Antisense drugs are much simpler, with no immune response required. The mRNA (the drug) itself simply binds to the target mRNA.
Does that make them a class of "cures" rather than "immunizations"? If I get infected with the same thing a year later, will I need another dose of the antisense drug?
Vaccines have a shelf life in your body. It's good to get a titer every once in a while to make sure you don't need a booster. A year would be short though, unless you mean variants/mutations, which would really be reinfection, not with the same thing.
I know all that. Besides, one pedantic point - antisense are not the same to typical mRNA, they have thiophosphate group instead of normal phosphate in their backbone, or some other tweak to make them bind mRNA permanently.
Some of us don't know, so the extra detail is appreciated :)
Interesting re: the thiophosphate group. It sounds like it just floods your body with some mRNAs complementary to the viral mRNA that blocks it from getting turned into proteins by your cells' ribosomes?
Yes, pretty much; almost like NOPing out code in binary patches. However double check about the thiophosphates. I might be wrong. It is either Morpholinos are blockers and thios are promoting destruction of the mRNA or the opposite.
Sadly from the manufacturing process description alone, we are going to be decades away from when it's actually ...not a few million dollars per individual to treat.
An individually tailored cancer treatment is already available in the form of the CAR-T therapies, which might give an indication of how expensive it’ll be - you were pretty much right on the dot, since each treatment in a course of treatments is estimated at $375,000.
There’s a lot of reason to suspect that, once the pipeline is set up and validated, tailored RNA will be a lot cheaper than CAR-T. cell culture is hard, whereas ordering a gene length DNA construct is “only” a few hundred bucks[1]. From there, getting it to mRNA is relatively straightforward. Doing this all medical grade and at scale will be a huge challenge, but should be significantly easier than mass producing CAR-Ts.
In order to produce a personalized anti-cancer RNA vaccine, you need to
a) do a biopsy of the tumor and some healthy tissue, which is fairly cheap,
b) do genetic analysis of those samples to find the differences. This used to be prohibitively expensive, but now is fairly cheap too, the price went down six (!) orders of magnitude since 2000,
c) ask specialized software to find the optimal protein set to express. This software can be used for all the patients around, so cost of development will be split among them,
d) synthetize the correct messenger RNA and embed it in lipid nanoparticles. Not cheap, but not prohibitively expensive either, this is basically a biological equivalent of a printing job,
e) check the resulting drug and send it to the clinic where the patient is treated.
This all together is a much more straightforward and automatized process than extracting tumor-invading lymphocytes from a patient and babying them in vitro with a lot of attention from human scientists and use of fairly expensive reagents. The price tag for this process per se should be at least two orders of magnitude lower.
Then you must add the original development and testing costs, amortized equipment cost and profit. This is where the total price tag may balloon.
If a parent and child develop the same cancer, is it any more likely that the same (mRNA) drug will work for both of them? Or do cancer cells mutate so much that they're unrecognizable between patients?
It would have interesting implications if in the future a family could invest in a bank of mrna molecules for their future generations. A new form of wealth.
If the cost is $4,000 it is almost below the level that insurance is even necessary (if you're on a high-deductible plan with an HSA, you'd be out-of-pocket for it). That's less than the cost of a 10 year old car.
If it's $40,000 yeah -- still that's on par with the cost of an ER visit for a traumatic injury and a couple of days as an in-patient, exactly the sort of thing you have insurance for.
What is this money spent on? Is it a real cost per dose, or just a made-up number for something made in a research lab?
Maybe another way to ask is: On the scale from 400k of white-shoe lawyer-hours, to 400k of custom 7nm silicon-etching, where should I mentally place this? The former isn't going to budge, the latter will cost pennies in a generation's time.
Ha! The technology itself is cheap, fabricating a bunch of de novo mRNA is only a few hundred dollars these days. I’m not sure how much volume is needed for treatment, and there’s obviously much stricter QA/QC that must happen for human use, but still the actual manufacturing part is likely no more than single digit thousands per dose. At scale, per your semiconductor analogy, could likely be brought down to single-digit dollars with time.
What they charge might be made up, but the costs of developing these drugs are astronomical. My wife is a cancer research scientist in immunotherapies and she can burn through tens of thousands of dollars in materials running a single experiment. And if she makes a mistake - the money is wasted!
For sure, I don't mean to suggest it's cheap research. But whether you charge a lot or nothing for the first few doses out of the lab, it seems like this won't really make a dent in the research cost. (I don't know if this $375,000 number is in that category, or not.)
Lots of biotech-type things are rapidly getting cheaper. Most notably for this purpose, sequencing and DNA synthesis are both getting cheaper at an exponential rate (to the point that there's a term for it -- the Carlson curve -- similar to Moore's law for computing).
A treatment that costs a few million dollars now will cost a few thousand dollars in a decade or two, assuming all costs scale according to the Carlson curve. In practice, this is probably a bad assumption, if nothing else because a hospital bed alone costs a thousand dollars a night or more, but it does seem likely that mRNA-based treatments will become much cheaper to develop over time to the point where they will be cheap enough to be viable by the time they would actually finish passing through the regulatory hurdles.
Ya, I have heard virologists talking about how many can already do mrna work in their own lab. It's scaling it up that is the expensive part. But I suspect it will just be a matter of new machinery focused on individual production rather than bulk production.
Considering that no, we dont have a few million per person than no, its not really a "bargain" unless you mean in the context of a pact with the devil.
Well it depends why it costs a few million per person. If the production of the vaccine takes thousands of tons of coal and hundreds of pounds of bark of a slow-growing tree then yes, we don't have that per person. But if the current million dollar price is to enrich some pharma investors then there's nothing to say that society needs to find $100 trillion to enrich someone.
That's only true if you can use the same aspirin as many other people. If the specific substance needs to be adjusted to your specific tumor, it may remain extremely expensive for a long time - until it becomes a technician's job to find your specific cancer signature and synthesize the drug from it.
Yes, this is what I meant by it being the technician's job. But building out a new commodity specialist job out of this new technology takes a lot more time than it takes to ramp up production of a regular drug.
Back-of-envelope numbers: US GDP per capita * US life expectancy is about 5 million dollars. Healthcare is maybe 18% of GPD and climbing, call it a million a person and rising. A majority (but not a huge one) is government spending.
I don't exactly know the breakdown, but it must skew towards the old & sick -- like cancer patients. It's not inconceivable that million-dollar cancer treatments could become widespread.
Honest question here, is the mechanism in those mRNA treatments totally different? I can't imagine there is a 'spike protein' you can focus on with cancer - but perhaps I am totally wrong.
I don’t see it in the article but the majority of the work for this and other mRNA vaccines was done by a lab at the US government NIH which has been working on stabilizing coronavirus spike proteins for years now in collaboration with university labs. Moderna and other companies have supplied the platforms for distributing the mRNA coding the protein. There’s a great lecture [1] from an NIH researcher that covers this history.
Glad to see TWiV mentioned here. I just started listening a couple of weeks ago and find it fascinating and very informative. The episodes can be quite long. I usually listen while working out and it takes me 3-5 days to get through a single episode, but it's as good as anything else out there. Also highly recommend the Plenary Session podcast with oncologist Vinay Prasad, who has had several COVID-focused episodes.
I was reading about Moderna today, and I found a number of articles from 2017-18 expressing concern about their secretiveness and impatience with both safety precautions and the failures that are inevitable in drug trials, based on the experiences of former employees and science journals. I can't deny that makes me nervous. I didn't see anything about it after that time, however.
Roughly: Protein descriptions are "read" from DNA into mRNA, which is then used by ribosomes to synthesize proteins. An mRNA vaccine adds additional mRNA with instructions to synthesize the vaccine-specific protein to the cells. So it uses some of the same mechanisms that are also used to generate proteins from DNA, but does not involve DNA itself.
Like all things with the oxford vaccine - that is only if you look at one slice of the data (in which there were no elderly)... why they didn’t include elderly is beyond me but of course there aren’t going to be severe cases in vaccinated patients 18-55
I think the no serious cases includes the over 55s. The BMJ are clearer in their wording
>The analysis included 131 covid-19 cases and showed the vaccine was 62% effective when given as two standard doses (8895 participants) one month apart, but 90% effective when a half dose followed by a standard dose regime (2741) was used. No hospitalised or severe cases were found in anyone who received the vaccine. https://www.bmj.com/content/371/bmj.m4564
I think the 62% effectiveness which on the surface doesn't look that good, included basically asymptomatic people who PCR tested positive.
I'm not sure the other testing included asymptomatics so the difference between the vaccines may not be as large as it looks.
Were there no severe cases in the control group either? From my limited understanding of how these things are done, I assumed there must have been severe cases in the control group (which would have the same exclusions), and enough of them for some statistical test to show meaningful difference between the groups, for them to be trumpeting no severe cases in experimental group. No? If not, that would indeed to my non-statistician eye seem kind of sketchy. But if yes, thats how it works right?
Why is it so obvious that there wouldn't be any severe cases in vaccinated patients 18-55, when there have been severe cases in infected people 18-55 (outside this trial, I don't know enough about this trial to make a comment about that)?
Does anybody have a good link for a layman's overview of how mRNA vaccines work? Lot's of nervousness from people around this, and would love to be able to help quell some of that.
Ahh, yes, ModeRNA's vaccine is some very clever stuff.
The way that one works is a bit complex. Essentially, they still want your immune system to recognize that the virus is bad and then make antibodies against it.
Usually, you inject broken up bits of a dead virus into a person. The immune system sees the foreign objects, and makes antibodies against it.
Withe ModeRNA's vaccine, we go inside out. You have the body produce inactive parts of the virus itself. In this case, the 'spike' proteins of the viral capsid.
They do this by injecting mRNA into you. Through some complex bio-chem, the mRNA that codes for the spike protein gets into your cells and makes the ribosome complexes produce the spike protein. These then get out of the cells, again via some complex bio-chem, and the immune system sees these spike proteins. The immune system then builds antibodies to the spike proteins, just like with a regular vaccine.
Basically, you skip a few steps in the antibody creation process.
I want to stress the mRNA injection part. This method skips the DNA, meaning that you are not editing the genetic code of the cell.
The real magic here is the potential such a method has. With this method, you can have much better targeted cancer cures, much broader flu vaccines, and time limited protein production. Think time-limited genetic engineering, minus the actual gene editing. Want to glow green for a few days? No problem. Want to mitigate diseases caused by missing DNA? Just take this.
I'm wondering if you could clarify a couple things for me:
1) "Skipping steps" This appears to be doing the opposite. In an old vaccine, you'd just dump a bunch of spike proteins into the system. Here, you're adding the step of making the body produce them. Could you clarify?
2) Why not just produce those spikes in a lab? Is it just much less resource intensive to have the bodies make them?
3) As far as stressing that this doesn't alter DNA: Wouldn't it suffice to say "this does what viruses already do, but less"?
1) Yeah, besides picking the step of manufacturing virus parts, I agree, this is going a step back in the virus's life cycle.
2) It's hard to produce proteins in the lab. Our own cells are pro at it, though, including all of the post-translational modifications (like attaching sugars and careful protein folding) that can make all the difference.
3) Pretty much. Since it's just one gene being introduced, it will not produce new virions, only the spike protein that our immune system needs to recognize.
Source: Am microbiologists, although not a virologist.
I believe Moderna has a patent on their methods; it is not a property of mRNA in general.
Not all mRNA follows the path that the Moderna vaccine uses.
Someone else please chime in if I am wrong here, but their method is basically use little lipid micelles (fat micro-blobs) that cover the mRNA. Because of some biochem, these micelles can then enter a healthy cell and disgorge the mRNA. This is kinda how a virus works as well. However, these micelles seem to be very fragile, hence the very cold temperatures needed for transport.
Once in the cell the mRNA then diffuses and is translated by ribosomes into protiens
What is the process of generating mRNA in vitro at large scale?
Is it as simple as amplifying a DNA template with the spike protein sequence and any necessary promoter sequences then adding some RNA polymerase with free RNA nucleotides?
The overall video is a about vaccines in general (Hotep Jesus is rather skeptical of them), but Lupe explaining how mRNA vaccines work starts at this timestamp. There's also a place where the audio cuts out. It's only a minute or so, but they go back and finish where they left off.
Most RNA viruses are not incorporated into DNA. SARS-CoV-2 is what's called a "positive sense" RNA virus, which means that it is directly translated by cellular machinery to produce more virus copies. It should have no interaction with cellular DNA.
Retroviruses are a subset of RNA viruses that utilize the strategy you're referring to. This requires additional machinery be coded for to allow reverse transcription to DNA and then subsequent integration into host DNA. The vast majority of RNA viruses are not retroviruses.
That usually (right?) doesn't lead to staying in the host's DNA, but I understand that some of our DNA is virus DNA so it DOES happen. Viruses per se aren't exactly rare, so maybe he specifically meant this phenomenon.
But also - that's reverse transcription, not reverse translation. Maybe Lupe made this point a little too late in his description.
EDIT: Sorry, moved around the above after rethinking
I get that that's probably Lupe's shtick, but I think half (or more) of the things he's describing to Hotep Jesus are things that your average person doesn't know!
It ‘injects’ RNA into your cells that causes them to make part of a virus (parts of the outside of it, not the parts that make it reproduce).
Those parts, in turn, trigger your immune system to build up defenses against the virus so that, if it encounters the real virus, it can contain the infection.
I'm interested in this as the only pushback I've heard has been from some Christian folks on YouTube claiming that we're no longer "human" if we hack or mix our DNA. I tend to look at it more like "right to repair". If I buy an iPhone, I should be able to hack it to my heart's content.
I have no idea if that's the angle you're mentioning. I'd be really interested to hear the other potential dangers that others see.
AZD1222, the AstraZeneca covid vaccine, uses an adenoviral vector to deliver DNA to human cells that then produce the desired viral proteins to present to the immune system.
This is a bit much for me to read without the right background. I'll focus on your claim, though.
"Sending mRNA to human cells to produce viral proteins" describe how all of the other vaccines work. You're saying that this one uses DNA. I don't know if that's a typo or if that's an important difference. However from what I understand, the two other vaccines people are talking about don't change any of the genetic material in your cells. They just send other genetic material that makes use of the translation equipment in some of your cells. It sits next to your existing genetic material, and then (I'm guessing?) just goes away.
Yes, this one uses a DNA virus as a way to deposit a piece of DNA into the nucleus of a cell, so that it makes viral proteins the way cells usually do. The virus used is incapable of replication so it only has the cell entry features, not the viral propagation features.
Depositing a piece of DNA into the nucleus doesn't seem to me to be the same as changing the organism's DNA. If the cell divides, will the daughter cells each have their own copy of the DNA? It doesn't sound like it to me.
Apparently not. Wild-type adenoviruses seem to prevent cell division while they replicate their DNA on their own until they cause cell lysis to distribute the virions. Adenoviral vectors, on the other hand, leave the free DNA particle in the nucleus where it gets transcribed to RNA but it does not get replicated during mitosis.
I'm an atheist more or less and I agree with this sentiment. I'm not fond of transhumanism. But I don't think the mRNA vaccine process fits this description.
Yeah, I certainly didn't intend for it to be a faith/atheism battle. I'm simply stating that so far, all I've seen has been that one perspective. I'm interested in the potential fallout others are predicting.
Quite a bit of our DNA isn't "human" to begin with, never mind our cells themselves. In fact, most of the cells in our bodies are bacterial, as I understand it. (Edit, that's oversimplified and/or inaccurate, see below.)
That's highly debatable. Also, obviously 'most' begs the question 'most by what?' if it's just by number, then that seems unlikely but possible. But most by weight, volume, or, more importantly, functionality - not really, that's definitely human cells.
Interestingly, you're right in that the "most of your cells are bacteria" point is a myth. I'm not a specialist, and fell for the pop-sci BS. Apparently the real ratio is closer to 1:1 ( https://www.nature.com/news/scientists-bust-myth-that-our-bo... ), if we can trust Nature's summary of several recent articles.
With regard to functionality, that's a very open question. We're constantly finding that features that didn't seem useful are not just functional but important. This trend can be seen at multiple levels, from gut flora to "junk DNA."
As for what fraction of our genome is either shared with other non-human organisms or originated with them, it's tough to find a straight answer on that, but rest assured it's far from zero. See https://www.cshl.edu/the-non-human-living-inside-of-you/ . That's been well-understood by everyone other than religious fundamentalists for some time now, and there are countless legitimate sources that can be cited.
I am no religious fundemantalist (I'm actually an atheist), and care very little for the notion of purity of humanity. The idea of 'human DNA' vs 'non-human DNA' seems suspect to me, as in some trivial sense, anything that is in the genome of a human being is by definition human DNA, and on the other hand, you can find large swaths of human DNA that are identical to most mammals, and probably a few that are common to virtually all eukaryotes. I also know that viruses can leave long-lasting changes to your DNA, that may even be heritable I think.
Still, related to the importance of bacteria, while I don't doubt that, as we learn more, we will discover that they have a bigger role than even dreamed 50 years ago, you still can't compare it to the basic roles of human organs. We have actually created microorganism-free mice and other organisms, and while they are not very healthy, they are fully functional (with bad digestion and big immune problems): https://en.m.wikipedia.org/wiki/Germ-free_animal
Why aren't you fond of transhumanism? At some point medicine and technology will advance so much that we can save and improve many lives by replacing bits of ourselves with superior artificial variants. Is that so bad?
I don't even care about the risks. It's about changing the rules so much that we don't know what game we're even playing. If you stop caring what's technically a human anymore, you have to reconsider the imperative to propagate the human race. Who are you propagating and why? What's the point of any of it anyway?
Granted I'm disinclined to propagate the human race anyway, so I guess I may actually be ahead of you.
I don't consider it being ahead to be disinclined to propagate the human race. I mean, if you're just advocating that for yourself that is one thing. But advocating that as a position in general is misanthropic and in my view not a tenable or healthy position.
In any case, if you don't care about the risks and are just concerned with the meaning about why we propagate and what the point of anything is, then I must point out that I'm not super interested in discussing this. I was more getting at why someone would oppose transhumanism, but this doesn't seem tone a meaningful critique of transhumanism as much as it is a sort of pessimism about why we do anything or we should propagate at all.
As with all the progress, along with the good things transhumanism will bring, it will bring a hefty bag of bad things.
And if you entertain the thought for a while, those bad things can be really, really bad, on a number of different axis.
Right, but just because bad things have come from science and technology doesn't mean that we get rid of science and technology. It means we have to be more vigilant about doing good things with our tools.
More seriously, this is one of those situations where the short-term pluses are plain to see, but the long-term risks are vague. Why not employ the precautionary principle here?
Instead of simply alluding to long-term risks, can you be more specific about what exactly you're concerned about? What kind of precautions are you advocating? At some point medical technology will give us organs that are far superior to biological organs - should we not make these available to people?
It really depends what we're talking about here. Specific to your comments I can think of a couple things:
1) In terms of organ replacement, I agree it's a great opportunity -- but, we really won't or can't know the full spectrum of risks right away. Thalidomide, for example, was (for the most part) believed to be safe in the mid-50s, and it wasn't until the early 60s that awareness of the issues began to set in. So I am being a bit facetious when I say "you first" -- if it suits your risk tolerance or if you are in exigent circumstances, sure thing, who am I to judge? But it doesn't suit my personal risk tolerance at this point in my life. (Maybe ask me in a few years when I'm old and sick ...)
2) In terms of "transhumanism" more generally ... I see great dangers and I fear what a society of transhumans combined with humans would be capable of (if we haven't started down that road already). If transhumans really become vastly superior to humans, what will the relationship between them and the old-stock humans look like? Yuval Noah Hariri said something to the effect of, the only model for this version of the world we have is the current relationship between humans and animals -- the track record there is not exactly great ...
So, it's partially the risks from the tech itself, and partially the downstream consequences for society.
My understanding is these vaccines either inject RNA into the cell (Pfizer), where it's executed like machine code causing growth of proteins which trigger an immune response, or it injects DNA into the cell nucleus (Moderna), where it triggers creation of RNA, which does the same. So, in a sense it kind of does "hack or mix" DNA. Really strikes me as a sci-fi kind of thing.
[edit] To clarify, it doesn't alter DNA, so much as co-opt DNA/RNA replication mechanisms. Does this cross some kind of "trans-human" threshold? I think so, but I also think clothing, reading glasses, and cell phones do the same. I see no reason to draw some kind of line in the sand here.
Edit: I do plan to get the vaccine, but as a software engineer I know beta versions usually have the most “bugs” — and I have the health privilege to be in the back of the line so I will!
What's irresponsible about healthy, low risk individuals waiting until all of the high risk people get the vaccines first?
If there's autoimmune issues that pop up when the scale goes from tens of thousands to hundreds of millions, I'll know about it ahead of time and be able to take the appropriate action, such as choosing a non-mRNA vaccine such as the adenovirus type from Astrazeneca.
The irresponsible thing about healthy, low-risk people not taking vaccines is that it puts high risk individuals at higher risk of catching the virus because high risk people are the ones that can't take the vaccine.
Vaccines are not 100% effective but they don't have to be. The goal here is to reduce transmission in the population to a level where the virus can no longer spread. That is only possible if enough people take the vaccine and healthy people should absolutely be in the front of that line.
This is not a purely personal choice. You have to understand that by deciding not to immunize yourself you are making a decision for everyone else.
The risk of a vaccine having negative effects is basically nil. The biggest issues historically have been around cross-contamination, not anything to do with the vaccine itself.
"mRNA vaccines do not affect the DNA inside the cell – the synthetic mRNA fragment is a copy of the part of the virus RNA that carries the instructions to build the antigen of the virus..."
This method has been in development since 1978 (when then-young Hungarian scientist Katalin Karikó started playing with mRNA in her lab in Szolnok) until today. Hundreds of mice died during the search for bugs before anyone dared to inject a human subject.
It cannot be ruled out that the whole concept of RNA vaccines still has bugs, but it is nowhere near "it compiles, ship it now!" software betas. The process is much more risk-averse.
I'm not trying to argue that it's a "good" thing, simply that tons of things hack our DNA (there are even some studies that emotional trauma can have repercussions imprinted on our DNA) My major point is that DNA hacking/damage isn't always a life-ender. Even skin cancer is often removed without issue.
It can't fundamentally change your own DNA. The mRNA codes for a stabilized version of the sars-cov2 spike protein. Your cells then use the mRNA to build that protein. Your immune system will then build up a response. It is a terrible idea to wait for a version 2 of this vaccine. Get vaccinated or this will not go away.
I just thought of this analogy today. Others should correct me if I got this wrong.
If I want to use your printer (ribosomes) to print out some stuff (proteins), I don't need to send files (genetic instructions) to your computer (nucleus). I can just get on your wifi, send my files directly to your printer, and go home. Except I accidentally left the protein at your house. But none of the genetic material sticks around.
Relevant criteria for the question "does it it exclude old, fragile people with various common pre-existing conditions?" (not exhaustive, but indicative):
Included: Pre-existing conditions are okay as long as they are in a stable condition (defined as no significant change in therapy etc for the 3 months before enrollment).
Excluded: Immunosuppressive or immunodeficient state, asplenia, recurrent severe infections (HIV-positive participants with CD4 count ≥350 cells/mm 3 and an undetectable HIV viral load within the past year [low level variations from 50-500 viral copies which do not lead to changes in antiretroviral therapy [ART] are permitted]).
Looks fair enough to an amateur like myself.
Edit: Not sure how common a immunosuppressive or immunodeficient state is in a typical population. Perhaps it's common enough to be relevant?
Immune suppressed/deficient patients are not good candidates for vaccines in the first place, since they would be unlikely to mount an effective immune response.
I think tpmx's point is that the virus would also be less dangerous for them, so getting the vaccine has less chance of having a net benefit for the individual.
Yeah, it was, but I think the argument that the vaccine is a safer option for this crowd is also a pretty persuasive argument.
I'm not exactly in this crowd (I'm 43) but given what I now know about the prevalence of scary long term covid-19 issues ("long haulers") in young people, I would take this vaccine in a heart beat "even" if I were young.
That sounds backwards. Shouldn't those with weakened immune response be first in line for the vaccine? The vaccine would give them a boost. Those with strong immune response have a better chance of fighting off the virus.
Marjomax isn't saying that those with weakened immune responses don't need protection against the virus. They are saying vaccines do not work well in immunosuppressed people, the vaccine will not necessarily provide protection.
Vaccines work by triggering the immune system in the first place. If your immune system is not functioning normally, the vaccine may work differently or not work.
I think it's more complicated than just as a blanket "won't work". But, yeah, more complicated means more complicated -- different vaccines may be infffective, or require a higher dose, or even be harmful to immunosuppressed people. As far as the study, it would probably require a separate study focused on immunocompromised people? The fact that these are new mRNA-style vaccines is possibly relevant, maybe we know even less? Obviously we're in a rush here, there's lots of studies that would be really good to do that haven't been done yet, all that's been done is like a basic "normal people everyone" study. From which immunocompromised people were excluded because they are likely to respond to the vaccine differently, so need a different study design etc.
(And btw, THIS is what "herd immunity' is about. If enough people are immune (say from a vaccine), then there aren't enough carriers to pass it around the population, so those who AREN'T immune (possibly because they are immunocompromised and the vaccine wouldn't work on them or would be dangerous) still have much reduced chance of getting infected. Because, yeah there are people who can't take vaccines because they would be dangerous or ineffective, but may still be at high risk for complications from the virus)
Vaccines work by essentially teaching your immune system to recognize a pathogen. If your immune system is in a very weakened state, it likely will not 'learn', and even if it does, it may not be in any condition to fight the infection, even if it recognizes it as such. Of course, things are much more complicated, but in people with severe immuno-deficiency (such as advanced AIDS or people who are actively taking immune suppressants) a vaccine will not have any effect (some kinds of vaccines even risk infecting that person with the disease, though I beleiev this is not the case with any of the Covid19 vaccines).
That could exclude people who are the most likely of dying of covid (a severe case of covid doesn't mean dying, for instance I heard an ICU specialist explaining that people who are seriously obese often require ICU treatment but rarely die from it, the people who die usually have serious co-morbidities and an already reduced life expectancy).
But it's kind of secondary anyway. The main goal of the vaccine is to stop the virus from spreading in the population and getting a chance to reach vulnerable people. Even if it were to only protect people who wouldn't die of Covid in the first place, that's the vast majority of the population and enough to significantly reduce the chance of spreading.
At the condition that these studies measure the right thing. If it merely stops the symptoms but doesn't stop the spread of the virus, that may be a problem.
And autoimmune conditions, robbing a list from wikipedia: celiac disease, diabetes mellitus type 1, Graves' disease, inflammatory bowel disease, multiple sclerosis, psoriasis, rheumatoid arthritis, and systemic lupus erythematosus.
I don't know how many people with conditions take immunosuppression medication.
I take it for arthritis and alopecia and have come across many people on similar meds for diabetes or other things.
But that could be a form of confirmation bias
It means it hasn't been, and thus needs more study in that regard.
My inexpert understanding is that mRNA vaccines such as this one are unlikely to have an impact on many autoimmune cases. In many, perhaps most, others, it appears from my reading to be likely that the generated interferons are not adding anything to the likelihood of developing an autoimmune condition that wouldn't eventually already happen. (It might be the nudge over the cliff, but so might have the next common cold you catch.) But it should be tested to understand, regardless.
The first. Long lingering after effects. For some they are fairly minor, but for many they seem to be quite tough, with significant problems doing any kind of physical activity.
At the moment it's all quite nebulous, with a lot of anecdote and not enough data. But there are some studies starting up that might start to untangle what's going on.
> I think (from my parents and in-laws) that immunosuppression is normally associated with current cancer treatment.
There are other reasons a person would be considered immunosuppressed, and plenty of non-chemotherapy drugs that have immunosuppressive effects. But yes, cancer is one of them.
It would make no sense to include immunosuppressed people in the initial trials for a vaccine, the purpose of which is to determine whether a vaccine can induce an immune response.
> My selfish concern is then whether or not the vaccine will work for them.
We won't have hard data on that specific question for a very long time, but it's something your/their doctor would be better equipped to make an educated guess about, given the specifics of their situation ("immunosuppressed" can mean a range of things). In some cases, a vaccine might do nothing. In some, it might be actively dangerous. In some, it might have a weaker but still nonzero protective effect. But I wouldn't trust anything you read on HN that tries tell you anything more specific than that.
Unfortunately, vaccines can't really help immunocompromised people, as their immune system is simply unable to fight off any infection, regardless of whether it recognizes the infection or not (of course, this may be a matter of degrees). That is why, for example, people with advanced AIDS can die from essentially any pathogen.
Your answer isn't exactly wrong, but it's painting with a broad brush. "immunocompromised" is a broad term (even more so than "immunosuppressed"), so there definitely are people who are immunocompromised who could potentially benefit from a vaccine (again, we don't have hard data on that yet for any of the vaccine candidates and won't for a while).
They do help indirectly - by innoculating the 90% who can take a vaccine, the 10% who can't (for example babies when it comes to measles vaccines) are unlikely to actually catch the disease.
Oh, for sure, I wasn't trying to say vaccines shouldn't be used! They are extremely important to a healthy population overall, and it is all the more important for people with healthy immune systems to get them to help protect those that can't benefit directly.
Transplant recipients (which must be on suppressants for life) can and do take vaccines and they work. They generally can't take live virus vaccines, but that's about it AFAIK.
Also, Anybody who has received an organ transplant is immunosuppressed. They take immunosuppressive drugs so that the transplanted organ is not rejected.
It would be so nice if those people could have access to a coctail of synthetic antibodies that gave some protection to covid-19, the flu and others. Or perhaps a generic antibody that protects against most viruses(unlikely, given such an atibody does not exist in nature).
Antibodies don't themselves help fight infections; their role is simply to identify dangerous pathogens to white blood cells. In immunosuppressed patients, those cells often aren't present (or aren't responding properly), so adding antibodies wouldn't help.
That's why it's so important that all the people who can get the vaccine get it - this is the herd immunity everyone is yammering about. If the healthy people are vaccinated the virus won't be able to spread to the people who can't get vaccinated.
> Not sure how common a immunosuppressive or immunodeficient state is in a typical population.
Pregnant women are considered immunosuppressed to a certain extent. I'm a software engineer and not a doctor though, so someone could perhaps shed more light on this.
There is an additional question that opens the door to all sorts of hidden exclusions: Were study participants given medical advice prior to participation?
If I ask my doctor whether it is a "good idea" for me to participate in an investigational study like this, there are all number of reasons he may advise against. Those reasons form a defacto hidden list of exclusions. Would a doctor advise a patient with diabetes, high blood pressure, or any other chronic illness, to participate in such a study?
Why wonder? You can read in the original press release that there were ~5000 patients under the age of 65 with chronic diseases such as diabetes, severe obesity and cardiac disease. There were also ~7000 patients over the age of 65. That seems reasonable to me.
For a study to be valid and useful, the control group has to go through exactly the same criteria as the test group. Everyone is "blind" to whether they get the placebo or the real thing. So they all get the same interviews/tests and rejection criteria. Putting all the diabetics in the control/placebo group would make it pretty obvious who was and wasn't getting the real thing.
Even if it isn't blinded, you try to make sure the control group and experimental group are equally representative though, you don't "put all the X in the Y group" ever, this is true! Because the whole point is testing two groups as much alike as possible other than the thing you are testing.
As someone who volunteered for the AZD12222 trial and who has various "co-morbidities", I consulted with 2 of my doctors beforehand. Given that none of the vaccines being tested are live virus vaccines (meaning there is 100% no way to get COVID-19 from the vaccine, unlike say, the polio vaccine), and all had already passed Phase 1 safety trials, they both put it as (paraphrasing): "It's a personal choice, but if you do it, thank you for helping science."
I think COVID-19 is perhaps different than many other types of diseases in it's mainly-selective dangerousness to select groups of people. A healthy 30-something is unlikely (but possibly) to have severe, hospital-landing COVID. Someone with various co-morbidities, however is more than twice as likely to die than someone without. As such, I think that makes it much more likely that this group will volunteer, than "normal" people. It's certainly what drove me to do so.
The only issue they seemed to really care about during the intake was immunosuppression. As another comment pointed out, as long as other medical conditions were stable, you were eligible. From the vaccine makers point of view, I'd surmise this group is almost desired (my personal opinion), as you're less likely to a have asymptomatic COVID infection, which given how they are running the trial are unlikely to get noticed.
I take great solace in hearing that among the people who got COVID even when having received the vaccine (I'm talking about the AstraZeneca one, which is ~70% effective), there were no serious cases that required hospitalization. This indicates that even among the "not-effective" group, the vaccine confers some immunity. For me, that bring the personal risk factor from "possible death sentence" to "just like the flu...it'll suck for 2 weeks but I'll be fine".
Obviously I don't know if I got the vaccine or not (though given I felt crappy the next day, I'm fairly sure I did), which as another commenter points out is what makes these trials effective. Neither I, nor the doctors I met with (nor anyone at the clinic where I received it) has any idea if I got vaccine or placebo. In fact, they even had the vaccine couriered over from another hospital pharmacy using only a numeric identifier so really nobody knows what I got.
Coming back to the original question, I think many people, especially with co-morbities might seek out advice before enrolling, but at least in my case, two doctors were all for it.
I'm thankful I enrolled, and I'd encourage others, especially those who are more likely to get severe COVID to do so as well!
Because the default with chronically ill patients is no. There are also financial issues. If a patient is chronic then they are likely on ongoing treatments of some sort. If complication arise from the investigational medication then questions come up as to who will pay for what treatment. What if the complications lead to the patient having to abandon the ongoing chronic treatment? So the docs will lean towards no. And in the US there is the huge question of whether one's insurance even allows for such participation, but that is a question for one's lawyer rather than doctor. All such concerns can lead to the exclusion of certain populations, possibly the populations more relevant to the study.
Are the trial participants exposed to the virus purposefully or is the result that none of participants developed covid just from regular daily living?
There's a (blinded) control group so purely based on how deeply unethical it would be to purposefully expose them to the virus I'd wager they were 'natural' occurrences.
I understand how it could be unethical, though I'd be more confident in a study that had purposeful exposure - how can we say the vaccine really was the means of protection, and not just the current measures?
The study compares how many people in the experimental group and control group develop symptomatic COVID-19. In this case 11 people in the experimental group developed COVID-19 versus 185 in the control group. Thus the vaccine is approximately 185 / (185 + 11) = 94% effective, assuming both groups behaved similarly.
If the control group intentionally avoided exposure more than the experimental group, then the vaccine is even more effective than the study result. This is a blinded study though, so participants don't know which group they're in unless they go out of their way to find out (eg. taking an antibody test).
None of these trials have used a "challenge" design where people were deliberately exposed to the virus. Instead, they vaccinate a ton of people and then let them go about their lives.
Participants' risk of getting COVID shouldn't go up, unless participating in the trial induces them to behave more riskily.
Still, risk homeostasis is (sometimes) a thing: people reportedly ski faster when wearing a helmet, drive closer with ABS, and stuff like that. I was just trying to pre-empt that argument.
That said, if this were a factor, it would be small and would make the trial results most impressive, rather than less.
note there is not a claim this vaccine prevents infection, only lessens symptoms, meaning you are still contagious.
"We all expect an effective vaccine to prevent serious illness if infected. Three of the vaccine protocols—Moderna, Pfizer, and AstraZeneca—do not require that their vaccine prevent serious disease only that they prevent moderate symptoms which may be as mild as cough, or headache."
"Prevention of infection is not a criterion for success for any of these vaccines. In fact, their endpoints all require confirmed infections and all those they will include in the analysis for success, the only difference being the severity of symptoms between the vaccinated and unvaccinated."
It is true that for these initial protocols, they are only testing becoming symptomatic versus prevention of transmission. That said, all the trials (at least in phase 1/2) are also looking at antibody levels[1][2], which would indicate less likelihood of transmission.
Remember, all these vaccines aren't yet applying for full approval, but an EUA (Emergency Use Authorization). I fully expect that the FDA would want to see data on transmission before full approval; but that is harder to acquire, so it makes sense they wouldn't wait for that specific data.
As someone in the AZD12222 (AstraZeneca/Oxford) trial, I can confirm that they are following all participants for a full 2 years. In this time (versus the ~3 months each Phase 3
trial has run for), there will be much more time to see if these vaccines prevent transmission, not just prevent symptoms.
With all that said, many thousands of live will be saved by getting these vaccines out now, even if they are only partially effective. After all, someone who can't get sick can return to a more normal life, since they won't have issues if they were to get SARS-COV-2 infection later on.
That forbes article is quite weird.
The trials have obviously been designed to find out if the vaccine helps prevent serious illness, as fast as possible.
Questions like 'can vaccinated people still spread covid' are much harder to answer in a trial. Perhaps they'll look at that later.
Right, but are there any vaccines out there that protect against disease but don’t prevent transmission? I thought that’s what herd immunity was all about.
With this being the case, how does it even make sense for companies like Ticketmaster and Quantas to announce that they'll require their customers to be vaccinated?
Yeah, 90-95% of your customers won't have symptoms if they get infected. But they'll still have the ability to pass on that infection to someone who wasn't vaccinated, or falls into the 5-10% of people who the vaccine isn't effective for.
Obviously the vaccines have benefits, especially for high risk populations. But I see very little benefit to these corporations requiring their customers to have it, since their customers can still be infected and spread the virus.
The issue here is that there's just not data on how contagious the small percentage of vaccinated people who contract COVID may be. Realistically, all the indications we have so far are that there is some correlation between how much you experience symptoms and how likely you are to infect others. It appears that people who never get symptoms (true asymptomatic carriers) are fairly rare and also really not very likely to infect others. Most of the asymptomatic "super-spreaders" which have been reported were actually pre-symptomatic. It's theoretically possible that people who are vaccinated and become infected (which looks like only a fairly small percentage) will still be able to spread the virus, but in all likelihood that ability will be greatly diminished.
For certain meanings of making sense, it's perfectly sufficient if either a number of airline managers or a number of airline customers simply don't understand that possible limitation of a vaccine's effect. And both are very likely. And it can make sense even beyond that, because a vaccine that doesn't completely rule out infectivity can still be reasonably expected to weaken and/or shorten infectivity.
Companies want customers, as a business decision is makes sense to require vaccinations because if they check that means governments will let them open.
Ticketmaster wants to get whatever the big name acts are on stage with a full house. If they check vaccination status they can sell out a large auditoriums in February to nurses and a few lucky others. If they wait until governments allow large venues to open up they might be waiting until next fall. That is a large amount of money they are leaving on the table.
Likewise, Quantas flys international to places that lockdown as eliminated covid - if they check vaccine status they can fly anyone in without worry about restrictions.
So it makes business sense.
It is all about rates, not binary can/cannot statements. An non-symptomatic person can indeed spread the virus, but someone with a fever who is coughing constantly (ie a symptomatic case) will spread exponentially more virus. So a vaccine that prevents such symptoms can in practice reduce infection probabilities. Bring those probabilities low enough and spread stops.
For that final batch of 5-10% of people, today's headlines from the Moderna data dump shows that its vaccine is 100% effective (so far) in preventing serious disease to those that have been vaccinated. And 100% effective in preventing death (there were deaths in the placebo group).
>With this being the case, how does it even make sense for companies like Ticketmaster and Quantas to announce that they'll require their customers to be vaccinated?
This is such a weird take imo. There is no need to vaccine non-risk people afaik. I thought the whole deal with covid is how mild it is for the general population but deadly for a subset of it.
you can't completely predict who it's going to be mild for. 14-year olds with no known underlying issues have died, 25-year olds have lost their sense of smell and taste permanently or suffer from long covid months later.
Not to take away from the argument that we should vaccinate everyone (we should, at least adults. not sure if this vaccine will be approved for kids, which usually requires more stringent approvals), but your argument isn't a good one.
Covid has killed 42 people from age 5-14 in the US according to the CDC, for example. That alone is really not something we should be making huge policy decisions around. It's sad, of course, but it's extremely isolated. All it does is distract us from making good policy decisions.
If I was making policy decisions I'd order vaccine rollout as follows:
Essential workers => 80+ years old => 70+ => 60+ => etc. as we produce and distribute the vaccines.
At some point we might look at the data and say "that's good enough, we can resume normal activities while we work to vaccinate the rest of the population".
Oh, I'm with you that vaccines should be triaged by risk factors, and that reopening should be guided both by % of high-risk population vaccinated and case statistics. I was responding to OP's assertion that we shouldn't bother to vaccinate "healthy" people at all.
IIRC the IFR is ~0.2% for people in the 20-39 age bracket. I still find that risky (though I'm risk-averse), but the better argument is the lingering effects of moderate/severe cases, which I'm not sure is counted.
Also, I assume your policy decision would include younger people with risk factors like heart disease and diabetes, rather than going strictly by age. I'm chronically ill and I want my vaccine.
Sure, throw in risk factors. My lack of completeness is why I shouldn't be the one creating this policy :)
My main point is that there are sub-populations that have a small enough risk that we shouldn't stress over them too much. And talking about them is a distraction.
I would expect that reopenings wouldn't be based on vaccinated percentage, but caseloads, just as they are now. Once more people are vaccinated, however, those will decrease.
I'm not sure what you mean by x-0, but if there is no risk for young healthy people, then they don't need the vaccine? I understand there are other arguments to be had but this 100% invalidates at least on of them
EDIT: After re-reading I understood the sentence, my bad.
We don't know a priori who will have very adverse reactions. Comorbities and old age increase your chances, but those are categorically not the only variables at play.
Anything we do now to reduce the R0 of this disease will disproportionally enable people to live long enough for herd immunity to be attained, courtesy of the exponential growth curve. The amount of people that has to get sick to overwhelm hospitals is smaller than you might think. When hospitals get overwhelmed people die of other preventable cases due to reduced resources, tired physicians, lack of time to see patients at all and people being scared of even going to the hospital in the first place. Old people are not "disposable" and for younger people that happen to have the genetic (or other) predisposition to bad or fatal cases it will be hard to tell them "sucks to be you" when the preventive steps are well understood by now: interact with people as little as possible and when you do, do so outside while wearing masks.
Also, the death rate among poorer people is a multiple of that of the general population, among other reasons because they are working essential jobs to not starve. Those of us that can isolate and don't are saying that these people's lives (essential workers, including health care workers) have no value, they are just meat for the meat grinder.
You appear to have confused case fatality rate with infection fatality rate. There have been far more infections than confirmed cases because most never get tested or formally diagnosed. The actual IFR is under 1%.
That comment was meant to answer two people at once, my bad.
I was referring to the proportion of population that was not at risk. That population has an insanely small chance of having long term side effects from data I've seen. Which was the reason I'm not sure why we would force them to get these vaccines.
EDIT: To be more precise; Of course we want a vaccine and vulnerable people to get it. You'd rather risk getting whatever potential side effects of that vaccine than get covid. I'm more torn about why healthy young people should get it.
But the proportion of people who are both at risk and can't get the vaccine (and alternatives) must be small (from intuitive maths, I actually haven't looked into this).
Why would this vaccine be mandatory while plenty of other aren't? E.g. I've never got flu-tested before a concert/the flu shot, even though it could pass to other people/kill people.
I'm wondering where's the line between freedom to one own's body and other people's well being. IMO it's not as clear-cut as people make it out to be.
You've mentioned "Low risk" a few times. You're right, the risk for young people is low. That doesn't mean no-risk though. There are plenty of examples of young people suffering harm because of covid.
At the moment we think covid is at least ten times more lethal than flu. If you're comparing numbers of people killed you need to make sure you're counting death the same way, and most people aren't doing that.
It is possible, but from my understanding, a lot of diseases can have extreme cases. And even so, being free to take on that risk is what I'm refering in when I talk about one own's body.
You're missing my point. These deaths will be insanely reduced once we get the vaccine out to the people that need it. I wasn't saying they are the same; i was saying they are similar in the way they are infectuous and we don't seem to be doing much for young people for most other diseases.
It is presumably good that we will have a variety of vaccines. This way if one of them has unnoticed harmful long-term effects it will only affect a subset of the population.
Is there some sort of system like this for flu shots? Or are we injecting a large portion of the population with the exact same stuff?
You don't say? Then why are so many people here criticizing those who want to delay 4 years before testing this vaccine on themselves and on their family?
Well, presumably that's because of a lack of our ability to determine viral markers that identify spread with high certainty. If we could simply determine who we contracted COVID-19 from, we could easily sue them for damages and then you could take whatever risks you deem acceptable.
However, considering that we cannot, there is some threshold level of danger above which society will deem your personal rights forfeit and you will be forced to swallow your personal risk because others do not want to swallow the risk of your externalities. There is no objective coefficient that weights the two things, so you're pretty much subject to the wisdom of the mob.
So far, if it makes you feel happy, it is unlikely that you will be forced to take the vaccine. There will be no TB DOT-equivalent, internet comments notwithstanding.
Quite simply I'd like to internalize all externalities so that market forces can determine equilibria. So yes, I think if we could effectively determine provenance, I would like very much to enable that for all things - diseases being the obvious ones, but certainly anything else where externalities exist to some trackable degree (carbon emissions are an obvious one).
My rationale for this case is quite simple. I have very effective protocol around this disease, high risk tolerance, and I want to retain the life I had before (going out, restaurants, clubs, etc.). In exchange, I'm willing to allow you to sue me if I get you sick. I think this will create a freer society, and allow people to find their own position on the risk-benefit curve. It doesn't make sense to subject me to the conditions less-risk-tolerant people want. However, it doesn't make sense for me to subject them non-consensually to conditions I want. A good mechanism to balance these things is a near-continuous universal value measure. A good near-continuous universal value measure is money.
FWIW I've rewritten your question from "why do you feel you are entitled to sue..." to "why do you think it is a good idea for society to permit people to sue..." since I think that's more interesting. The answer to "what gives you the idea that you are entitled to sue" is "nothing, since I do not believe I can right now" which is sort of a boring (though correct) response.
Of course the whole thing is moot. Hard to prove who really caused an infection when community transmission is rampant.
> “This is a unique situation where we as a company simply cannot take the risk if in ... four years the vaccine is showing side effects,” Ruud Dobber, a member of Astra’s senior executive team, told Reuters.
Seems pretty straightforward to me. It’s an unproven method of vaccine creation and hasn’t been tested by anyone. I really can’t imagine this holding up in courts though.
The law is upheld by the people. If you damage the health of nearly an entire national via vaccine, no one will care to stay true to the letter of the law when it comes time for your retribution.
Same thing with the Nazis. Nuremberg was a kangaroo court but people stop caring about due process when you ruin the lives of everyone in their country.
In the US it's not possible to sue for damages caused by vaccines. I'm sure the courts will find a way to make it work. The concern seems to be that stifling vaccine development for the benefit of a few just isn't worth the risk of future plagues.
"benefit of a few" meaning "allow those few that were adversely affected to sue for damages" which would have the follow-on effect of hampering vaccine development
Vaccines are like 99.999% safe.. but we do give them to more than 100k people per year, so some people do suffer some unfortunate side effects including and up to seizures and brain damage. We've decided as a society that the benefits of widespread vaccination outweigh the legal rights of those harmed by their administration, so we've legislated away the ability to sue vaccine manufacturers for good-faith efforts at developing and administering vaccines.
I will gladly line up for the Covid vaccine and I'll definitely be vaccinating my children, but there is a remote risk of harm.
Why not ? I mean why would they be responsible for something they cant test ? Thats the part that makes no sense to me.
If you are (healthily) afraid of a vaccine because its not tested enough, just take your responsibility and dont take it. Or take it but dont come complain and attack other people for something that no one can do anything about now.
Is that going to be allowed? Do we seriously believe at this point that governments aren't going to make these vaccines mandatory, if not for everyone explicitly then at least in practice by making them mandatory for access to public services and spaces?
Are there serious suggestions that everyone be forced to take the vaccine? I haven’t seen that, and frankly I’m not sure that would stand up to court scrutiny.
FDA says Dec 17 meeting to discuss. This contradicts some earlier opinions that the reason the FDA was taking so long to review Pfizer (Dec 10 scheduled date) was that they were planning to review 2-3 candidates together.
For context, scheduling the meeting to review the candidates is running at 5-10% of the development time for these vaccines. 20M vaccines represent about 1/3 the elderly population in the US, there are about 1,300 deaths a day right now, and most deaths are in the high risk category. So you can estimate the cost of the delay to be quite high (depending on your assumptions, but hard not to estimate the cost to be >1000 lives). I'm unsure of any vaccine side effect or release that could be considered worse. Pendemrix caused 1 in 18,000 narcolepsy, which for the 20M at risk who could get the vaccine seems like a good trade-off (if this was as bad as that).
Moderna entered phase 1 trials in March. Vaccines entering phase 1 trials have a 33% success rate overall, 85% successful for efficacy. So this is not a case of hindsight bias, this was always reasonably likely to work. And these numbers include issues like enrollment issues, or the diesease dying out (ebola).
So lets make some assumptions to see what it would look like to "just approve things for the high risk in a pandemic":
For example, let's say that a vaccine maker instead of pushing something 85% likely to be efective pushed through pushed through something 40% likely to work. And for safety, let's just assume it's going to be 2x worse than the worst vaccine ever, so maybe 1 in 10,000 get narcolepsy. But they still push it through.
This implies taking the untested vaccine has a 40% chance of protecting you and 0.1% chance of serious side effect.
For the elderly, who at the beginning of the pandemic has a conservative IFR of >10% and let's assume a 10% chance of getting it. Not taking the vaccine has something like a 1% chance of death.
For the elderly, taking the untested vaccine would in this example would reduce your chance of death by 0.6% but increase the chance of serious disease by 0.1%. For most people, this should be an obvious decision to vaccinate, even using the most pessimistic adaptions possible.
It almost sounds like a conspiracy theory, but in the real world Moderna had a working vaccine in March, and it was always statistically likely to work with low relative downside (for some population), and it has been banned the entire time until now.
The next pandemic could be completely prevented if we focus our efforts on how to approve vaccine candidates in days not months.
Note: I think the bar for requiring a vaccination can/should definitely be higher than the bar to lift a total ban on a vaccine.
There may be other ways to reduce risk if you belong to the at risk population, though.
Those statistics all have to be taken with a grain of salt. Like if it says "x% of some population will die from some thing", it could mean "x% in the population tend to be reckless" (like "x% of people under 30 will die from base jumping", but it is easy to avoid by not doing base jumping).
In the case of Covid, perhaps not living in an old people's home (in March) could improve your odds by a lot.
There may be in general, but in this case I don't think it's a factor. Something like 40% of deaths have happened in nursing homes, where residents don't have much agency to reduce their individual risk.
But that would distort the risk for "people over 80", wouldn't it? Like if you are in a nursing home, the risk is probably higher than average for that age group, if you are not, the risk is lower than average.
>Note: I think the bar for requiring a vaccination can/should definitely be higher than the bar to lift a total ban on a vaccine.
It's unlikely in the US that the federal government could require vaccination. States maybe could but only because of very old case law that might well not stand up today. Of course, private workplaces, schools, government offices, airlines, etc. could to the degree that it might be quite difficult at some point to refuse.
To your broader point, if a roll the dice strategy backfired, you could not only have had dead people but you'd basically make vaccine development untenable both for this and probably other diseases.
> It's unlikely in the US that the federal government could require vaccination.
But the IRS could give you a tax credit for being vaccinated -- or is that crazy? :D
Indeed, it might even make sense to give a credit on social security taxes for vaccination, as it reduces the liabilities medicare is likely to incur in the future.
Personally, I doubt the US will do any such thing.. nor will it be necessary, at first we won't have enough vaccines anyways.
> States maybe could but only because of very old case law that might well not stand up today. Of course, private workplaces, schools, government offices, airlines, etc. could to the degree that it might be quite difficult at some point to refuse.
States probably can compel people to take it, considering some already require it for use of public services like schools. I’m guessing private companies can do whatever they want as long as they avoid running into disability law. I think this is a problem though - as a matter of principle, bodily autonomy is sacrosanct. Citizens who are forced to give up bodily autonomy to use basic services they can’t reasonably avoid (roads, public transportation, schools, etc) simply don’t have basic freedoms in my view.
IANAL, but the Supreme Court case I'm aware of upheld a Massachusetts law requiring smallpox vaccinations (in 1905). That said, the Supreme Court also upheld forced sterilization of the mentally defective in the early 20th Century so I'm not at all sure 100-year old court cases would be expected to be upheld today.
I don't really disagree with you in general. SWAT teams won't be holding people down and injecting people by force. But the practical effect isn't that different from a jurisdiction effectively requiring proof of vaccination to leave your house.
> States probably can compel people to take it, considering some already require it for use of public services like schools.
Public schools likely could not exist in the densities they currently exist if people didn't vaccinate. Likewise, dense urban housing, and many public venues would cease to be viable. Measles spread far faster than COVID; even with something like 95% of the population vaccinated we still have outbreaks in high anti-vaxxer communities. If we didn't require measles vaccines where we do, it would be absolutely everywhere. Likewise similarly conquered diseases like smallpox and polio.
> Citizens who are forced to give up bodily autonomy to use basic services they can’t reasonably avoid (roads, public transportation, schools, etc) simply don’t have basic freedoms in my view.
To date, no state requires vaccinations to use roads/ public transportation and I find it unlikely that they ever will. But I would support requiring proof of vaccination at the state/ national borders during an outbreak to prevent spreaders. Likewise, large gatherings (including schools) absolutely must require vaccinations. This isn't a matter of freedom/ versus not freedom. If they didn't require vaccination, they could not safely exist.
If you choose to opt out of large events, then I support that right. But schools/ colleges/ concerts/ etc, cannot exist in a vaccine optional world.
Officials have been going on about how this is the fastest vaccine ever produced and distributed. Then they backpedal slightly on that when the populace verbalizes legitimate concern that it was too fast to guarantee safety. Meanwhile, people like myself (and I assume you) are on the opposite side; this was too slow.
This virus could have been much, much worse. Not to be insensitive, we (as a species) got off easy with the transmissibility of this virus and its mortality rate. Viruses such as the measles transmit so readily that a shedding individual breathing into a room will infect people who walk through that room up-to hours later (COVID-19's r-value is somewhere around 3; measles' is closer to 15). Viruses like the smallpox, thank god now thought to be eradicated, exhibit a mortality rate higher than 30% (versus COVID's ~0.5-3%). Viruses are genetically and physically capable of extraordinary destruction, and its impossible to predict when one will make that single mutation necessary to wipe out ten percent of the human population, just due to a genetic accident.
Moderna, at least, was able to develop this COVID vaccine in literally days; the rest was testing and regulation, which was certainly sped up comparative to the severity (or relative lack-there-of) of COVID. My fear is the next one. Let's say one day we get an actual super-virus which rampages through the population. More or less, we've got some amazing development platforms out there, production is difficult but solvable, but then we hit testing and regulation. Either the government stays the course with traditional testing, and tens of millions definitely die, or they expedite traditional testing even more than we did with COVID and hundreds of millions maybe die due to an unproven vaccine.
I'm not fooled for a second by the safety claims behind these COVID vaccines. To be clear: I will still get one the moment I'm able to. But I'm going in fully aware that these companies have little idea what this vaccine is going to do to the human body in four years, in N% of patients, or how it will react with the millions of different medications people take, in different combinations, or how some weird little genetic abnormality in 0.5% of the population may affect its efficacy. There's no new safety & testing processes which enabled them to productionize this vaccine in ten months; they're just forgoing long-term studies (and getting liability waivers in the process).
Its 2020; we launch rockets to outer space every day then recover and reuse them, half the population carries in their pocket a computer capable of accessing all the world's information instantly and performing trillions of calculations per second on it, and our best-in-class state-of-the-art method of testing vaccine interactions on the human body is still "hey, uh, do you wanna come in and we're going to inject you with this thing and you tell us if you get covid, ok? we'll pay you a hundred bucks."
I believe three things very strongly: (1) the medical research community should be proud of the incredible results they've achieved in vaccine research; the speed at which Moderna and others were able to produce the first iteration of this thing is right on the money, but (2) they should also be critically ashamed of the lack of progress we've made in being able to expedite testing despite the insane and incomprehensible technology every sector around them has provided to help. (3) Fixing this needs to be humanity's number 1 priority. This is life or death for our species. Our goal should be from viral sequencing to a reasonably safe production-ready vaccine in two weeks.
Regarding #2 and #3, I don't think there is a way to speed this up. The only way they are testing these vaccines is by looking at the percentage of people who get infected who either got the vaccine or placebo. One of the reasons that these vaccines have been able to be produced so fast is that COVID is rampant, especially in the US, making it much quicker to hit the N-number of cases necessary to test.
There was talk early on about doing "challenge trials", where'd they vaccine a sub-group and the purposely infect them with the virus. There are huge ethical issues with this, especially for a virus with which we don't clearly know if someone will range from asymptotic to death. We certainly have statistics on likelihood, but there have been many reports of perfectly healthy, young, people dying from the disease. Given that unknown, I don't think it's possible for anyone to give informed consent for this kind of trial.
While I agree that we should have moved faster, even if you approved a vaccine candidate in days it's not clear who you'd vaccinate in a targeted campaign to "complete prevent" the pandemic.
Being able to produce vast quantities of this stuff rapidly is ultimately going to be at least as important as streamlining the regulatory process. After almost a year we don't have even a fraction of what we need to vaccinate the population.
They don't. But half the people got a placebo and half got the vaccine. 185 in the placebo group got covid, with 30 having severe covid, but 11 with covid and 0 severe in the vaccine group got it.
So do you really think that totally by chance, one random group of 15,000 people got a ton of exposure, and another group of 15,000 had little-to-no exposure? The probability of that is quite low.
I am curious why they didn’t test everyone. Is it just a cost/test capacity thing? Wouldn’t testing to catch asymptomatic cases increase statistical power to allow the study to yield results sooner with smaller error bars? Also, isn’t preventing asymptomatic cases an important function of the vaccine (to get to herd immunity)?
I'm in the AZD1222 (AstraZeneca) trial, and for the next two years, I need to fill out an online symptom questionnaire every single week. They also draw blood at the 6-month and 1-year mark, so presumably could test for antibodies.
You started and perpetuated multiple flamewars in this thread. That's criminal negligence if not arson. Would you please review the site guidelines and stick to the rules in the future? Note these:
"Eschew flamebait. Don't introduce flamewar topics unless you have something genuinely new to say."
"Comments should get more thoughtful and substantive, not less, as a topic gets more divisive."
"Flesh of murdered babies" is an extreme violation of these rules. The internet is flammable and we ban accounts that blow threads up in this way, so please don't do it again.
Here's what I'd like you to understand: when you're talking to a large online audience, many of whom don't share your views, blasting them with extreme rhetoric has no persuasive value and does no good for the cause you care about. Indeed, it has an anti-persuasive effect and actually hurts the cause that you care about, as well as damaging the community here.
The fact that you use the term "flesh of murdered babies" to refer to embryonic stem cells, which even the Catholic Church simply refers to as "aborted fetal cell lines", indicates that you've bought way too heavily into the right-wing American culture war.
But anyhow, to answer your question despite the terrible way it was asked, no, the Moderna vaccine did not use embryonic stem cells in its development or production. Some partners, such as NIAID, did use embryonic stem cells for in-vitro testing of the vaccine: http://phillycatholiclife.org/life-affirming-choices-3/covid..., but the Catholic church does not consider that to make the Moderna vaccine unethical, as it's its direct development and production have never involved the use of embryonic stem cells.
Flamebait and flamewar rightly get flagged. If you had something substantive and thoughtful to say on the topic, it might have been different (hard to say), but you didn't even try.
I have not flagged any of your posts, but remember that "free speech" means freedom from government interference with speech, not freedom from a particular community deciding that your speech is disruptive to that community.
I notice looking through your comment history that you spend a lot of time discussing abortion and gun control, the two primary culture war wedge issues in American politics, and which are mostly off-topic for a technology and startup focused discussion site.
I tried to answer your question in good faith, and hope that you appreciate the information, but I don't really think this is the best forum for discussing the ethics of embryonic stem cell research.
As someone who believes abortion is entirely ethical, I don’t really like the framing of your statement - but yes there are ways to obtain embryonic stem cells that don’t involve abortion - specifically the unused embryos from IVF
You’re making a choice to see fetal tissue as a baby or an unborn child - something that is not in any way inherently true.
Since there are opposing strongly held viewpoints on abortion and neither can be proven to be more correct than the other - neutral language seems like the best way forward.
You can claim the language is biased, but as a medical procedure it’s coded in all the same language as any other medical procedure - which seems to me to be the neutral thing to do. How you feel about the emotional or moral content of a medical procedure is separate from what is done.
To take a less emotional example - I think genetically modified organisms are basically a bad thing, but that doesn’t make the term wrong - calling them monsterplants would make me happy but it’s not more accurate and it linguistically enforces a viewpoint that is not “correct” just because i happen to hold it (for many nuanced reasons i won’t go into here)
Dumb people like teachers, doctors, nurses, first responders, the infirm, grocery stockers? Dumb people that have to work to pay their rent, mortgage, put food on the table? I know there are a lot of idiot anti-maskers running around, but being dumb is not a prerequisite to catching covid. Not everyone has the luxury of working from home.
The context is so simple to me, I have hard time believing the other readers can miss it. The OP means party-goers etc, not teachers, doctors and such.
No, but there have been plenty of people in the US gathering unnecessarily, not for essential work, but in large groups for Halloween parties and bars, with extended family and older relatives for Thanksgiving, and are likely to gather multiple times for Christmas once again.
Now unsurprisingly the pandemic is out of control, hospitals in many regions are overcapacity and the overworked essential healthcare workers mentioned are sending patients hundreds of miles away to the nearest available bed.
These gatherings are selfish and completely avoidable. If these multiple vaccine candidates are as promising as they are sounding, people should hold off a few more months on social events until this vaccine starts getting deployed to the highest risk crowd.
Most Americans think gathering for Thanksgiving and Christmas is both altruistic and very important. Selfishly, I would have preferred to stay home and call in, but my mom didn't want to be alone on Thanksgiving so I drove down to be with her.
They're perhaps not necessary in the strict sense of the word, but health authorities have consistently said that very important gatherings are okay as long as you try to do them safely.
This is so strange and alien to me - go visit older mother, and potentially infect her. Health authorities, meanwhile, consistenly said - if you can avoid Thanksgiving, do it.
And the opposite is strange and alien to me. I wish I knew a way to bridge the conceptual gap here, because it's been coming up a lot and I've never seen anyone successfully forge a common understanding.
I am well aware. But what is not essential are indoor weddings with hundreds or thousands of guests, a night at a packed bar, or a 30 person Thanksgiving dinner, when hospitals are overflowing and healthcare workers sick with the virus themselves are being asked to work overtime.
The virus has been around for almost a year now and people are still acting like we have no idea how it works or that uncontrolled spread can cause a disastrous collapse of healthcare systems.
I'm pretty sure I got it walking out of a grocery store. I was wearing a mask, and was walking by another older man who was also wearing a mask and standing at the exit. He was hacking and coughing so hard that the mask did nothing. I tried to hold my breath as I got until I got outside, but it was to no avail. About four days later, I developed flu like symptoms. Sometimes, it doesn't matter how smart or "dumb" you are, anyone can get it.
We may have an effective vaccine now, but it will be another six to nine months before you can go to your doctor and request the series as a normal person.
I'm not sure how much to read into it, there are so many variables to consider I doubt this study qualifies as science (like most of social science).
Incidentally, I failed the marshmallow test and I tend to behave and think with a scarcity mindset (I can't tolerate wasting food, it's hard for me to spend money).
My parents are quite well off and went to uni. Their parents started middle class and made some money.
I bet my parents wouldn't have failed the test - and they definitely always stocked the house with food and could provide resources and a stable environment.
My grandparents had a harder life (thanks to the wars, most likely) and share the same mindset I had (even though I never spent much time with them, we lived far away).
I wonder how much of that it's actually genetic, more than environmental. You could still find correlations compatible with the study, if it were.
Passing down the "poor" genes would create genealogical lines of poor families.
It does not debunk anything, the effect does not vanish, it just diminshes to 1/3 of what was originally calimed. Which means, that within a single socieconomical group, the effect will still be quite noticeable.
I have read the paper[1], and its discussion section supports the conclusions drawn by other readers, who are smarter than I am[2][3][4].
Here's one excerpt from the discussion:
> "When considering how our results might inform intervention development, recall that models with con-trols for concurrent measures of cognitive skills and behavior reduced the association between delay of gratification and age-15 achievement to nearly zero."
To put it another way, when controls for education and socioeconomic status are added, there is no significant effect.
You absolutely did not pay the attention while reading. At age 15 indeed the association diminishes to almost zero; the original experiment never claimed otherwise. The original claim was that association is strong at early childhood; nonetheless it is pretty stupid to believe that a marshmallow is a sufficient reward for 15 years old person.
Insulting me and assuming I didn't read my links doesn't make your argument stronger. It makes you sound insecure about your argument, which you should be, because you have missed basic facts about the study.
> At age 15 indeed the association diminishes to almost zero; the original experiment never claimed otherwise
The original experiment (and you, based on what you implied about people who fail to take Covid precautions) absolutely did claim an association at age 15 and beyond. That was the whole reason it became famous.
> nonetheless it is pretty stupid to believe that a marshmallow is a sufficient reward for 15 years old person
I can't tell if you're trolling or not, but I'll engage with you as though you're being sincere.
The data for 15 year olds is academic achievement, not a repeat of a marshmallow test.
From the study:
> "Academic achievement was measured using the Woodcock-Johnson Psycho-Educational Battery Revised (WJ-R) test (Woodcock, McGrew, & Mather, 2001), a commonly used measure of cognitive ability and achievement (e.g., Watts, Duncan, Siegler, & Davis-Kean, 2014). For math achievement at Grade 1 and age 15, we used the Applied Problems subtest, which measured chil-dren’s mathematical problem solving."
Personal attacks aren't allowed here, so please don't post them. Also, the site guidelines explicitly ask you not to feed egregious comments by replying, but to flag them instead. That's our polite rewording of "please don't feed the trolls".
The presumption here is that we could have been vaccinating people en masse since sometime in spring. However, I do not believe large-scale production of an mRNA vaccine was possible at that time. This does not seem to be the case. My understanding is that manufacturing this type of vaccine is significantly different than other vaccines previously produced at scale (flu vaccine, etc.) so they needed to build out their factories almost from scratch, to the exacting standards required of medical facilities, which likely took many months.
To the best of my knowledge, vaccine makers have been producing the vaccine as quick as they can, planning for hopefully good results, but knowing they could just trash it in the case of bad results, and they only just now have tens of millions of doses.
The FDA needs to make a fast-track vaccine approval process for mRNA vaccines where the pathway to deliver the mRNA has been pre-approved and the only change is in the mRNA payload. However, I don't have much faith in the FDA.
It seems obvious in hindsight, but such trials do have an important role in this process. Not to mention mRNA vaccines are new and it could possibly just have made things worse.
That's still a possibility, though "rushing" can be somewhat subjective. By strictly adhering to the scientific method/process, we can hope to eliminate uncertainty in this regard. Unfortunately... as the parent points out, that requires cooperation between geographically dispersed parties (some of whom may have priorities emphasizing social norms such as "saving face")
The null hypothesis (people with symptomatic covid are as likely to get severe symptoms, regardless of whether they received the vaccine) predicts this many cases with severe symptoms:
30 / 185 * 11 = 1.7
1.7 ~= 0, so the sample size is too small to support the headline.
If you take a Beta(1,1) distribution as your prior, then the control group's risk-of-severe-covid-given-symptoms posterior is Beta(31,156), and the experimental group's conditional risk posterior is Beta(1,12).
Drawing 100,000 samples from these distributions (`betarnd` function in matlab) gives an 87.8% sampled likelihood that the intervention reduces the conditional risk (intervention(i) < control(i)), and a 64% sampled likelihood that it reduces the risk by at least half (intervention(i) < control(i) / 2).
This is suggestive (but not yet "clearly convincing") evidence that the vaccine reduces the risk of severe covid conditional on being infected in the first place, and that comes on top of the obviously compelling evidence that the vaccine reduces the baseline risk of infection.
This conclusion makes intuitive sense since the vaccine is intended to produce an immune response. A patient who has a moderate response to the vaccine itself may not neutralize the infection before developing symptoms but would still have a primed immune system to control the disease before it becomes severe. (That is: the response to the vaccine intuitively falls on a range, rather than being "all or nothing").
I find an interesting related item to be the ~30% of people in the AZD1222 (AstraZeneca) study who got COVID after being vaccinated. They reported that in this subgroup, there were no severe infections, nor any hospital visits, confirming the parent's hypothesis that some people might not get full immunity, but still benefit from the vaccine.
As an example of un-intended side effects the vaccine trial I'm on sets off HIV tests.
This obviously means HIV will increase.
Plus other things to consider. Like conspiracies. And the fact the cheap HIV test I ordered from China can tell me if I'm on the placebo or not.
With deaths from lockdown blowing up, HIV will explode anyway after shutting do the world economy for so long. But don't think it'll be smooth sailing politically and with today's media it's a nightmare.
Two question since I dont know much about mRNA vaccines
1. The mRNA has to express the target Protein for the Anitbodies. If injected, how does this happen? It has to go somehow into the cell to be translated? Or is the delivery vehicle the magic sauce?
2. What makes mRNA vaccines so special? What is the difference of injecting the expressed protein sequence directly?
The mRNA must enter a cell to express proteins. The delivery vehicle is a "lipid nano-particle", a particle that can contain a payload and attracts surfactants to protect the payload but also allow it to penetrate cell walls. They're a bit unstable, thus the need for refrigeration. The other way this can work is using a virus, which is what the Oxford vaccine does.
You can do protein vaccines, and some are coming, but they're slower to develop as you have to figure out a way to manufacture them; with a nucleic acid you can have the body do that part for you. Additionally, the mRNA produces a more complete response; some parts of the immune system react to proteins expressed on the surface of cells, which direct protein exposure doesn't do.
I have no knowledge of this but if injecting spike proteins worked wouldn’t we just always do that? Seems like way easier than the rest of the delivery mechanism.
The AstraZeneca vaccine puts the spike protein onto a chimp cold virus.
My understanding is that the hard part is to make the body understand that it needs to produce an immune response. Just injecting spike protein doesn't work, because it isn't recognized as a threat. The AstraZeneca one uses an attenuated virus that the body is going to respond to anyway.
I believe the mRNA vaccines work by getting cells to express the spike protein themselves. You can't smuggle the protein into cells just by injecting it, but mRNA will get in there and do its thing.
I personally know people who were hospitalized due to severe COVID19. I personally know more than a couple of people who tested positive, with mild symptoms (a fever). My parents personally know people who died of it.
The main reason vaccine trials normally take years is money. Normally you wouldn't start manufacturing a vaccine before you know it at least works in animals. You also wouldn't _simultaneously_ vaccinate the 30000 people needed for phase 3 data. The Moderna study has over 100 study locations [1]. A normal vaccine trial might have 10-20. With that number, it takes much longer to get the same number of people in the study. Given the virtually unlimited financial resources coming from the government, they were able to conduct the study, as well as begin manufacturing, in record time.
All the vaccine trials are following participants for over 2 years, at which point many of the 1-in-10000 effects should be known. If you look at previous problematic vaccines [2], most rare side effects (> 1-in-100000) were only seen after MILLIONS of innoculations, meaning you only see them in Phase 4 (post-approval) studies as they are extremely rare. Given the high case fatality rate of COVID-19 [3], the risk of an unseen extremely rare reaction is much lower than the risk of dying from COVID-19, so general speaking, you should get vaccinated.
Honest question: would you wait if there was a pact to the effect that either everyone takes the vaccine, or no one does?
Because obviously not getting vaccinated when everybody else does is almost always the best choice game-theoretically speaking; it doesn't really say anything on the vaccine (it may say more on the civic sense of the individual).
Let's see... it's a calculus of death vs potential long term adverse effect:
P(death) < 0.05% for the vast majority of the population (Age < 65) vs P(unknown) long term harm in life quality, my wild estimate: P(0.1%). It's within the same order of magnitude.
I'd take the vaccine in a heartbeat, long term effects and all, if P(death) was 10% or higher.
You're correct about long term harm, I lumped them together. A better formula would be:
P(covid death or long term harm) < 0.05%
vs.
P(vaccine long term harm) = ?
since my estimate is they're about the same order of magnitude, I prefer to take the devil-I-know vs. the small-scale-tested vaccine.
I model the potential harm based on a similarly rushed vaccine of 1976 which caused a large increase in cases of Guillain-Barré Syndrome [0]. Longer trials and phase IV monitoring was instituted in response to this rushed vaccine.
What is your reason for assuming P < 0.05% for long-term harm due to COVID-19? You quite clearly assumed 0.05% for death only, therefore attributing even less to long-term health effects. But so far, there appear to be many indications that COVID-19 does have significant medium (and possibly long) term consequences even in asymptomatic cases.
I fully admit that I am not up to speed in proven COVID-19 medium- or long-term effects beyond having seen headlines, but to essentially assume none when there have been very obvious and multi-faceted indications of them implies you must have a very good basis of research to base your estimate on. Care to share?
I take the IFR (infection fatality rate) for age < 65, and multiply by 10 to get a worst case of IFR+long term harm. Note that we're talking about severe long term harm - such as autoimmune disease etc. Not "it took me 3 months to recover" stories.
For example, IFR(age<65) in geneva[0] is 0.0045%. multiply by 10 to include also long term harm, you get 0.045%.
I will note that the cited 0.0045% infection fatality rate number is quite old/outdated (June 1st). It's not easy to match different areas under the age curve (which seems to be exponential) and that it can vary a lot by region, but here is a review paper which has your number for ages 0-34 (Table 3) and (substantially) higher ones for ages above that:
What was the age profile of the trial? If you fill it with healthy people under 50 during Summer you would expect the same results with a placebo, given the profile of the virus.
Is anyone else on HN depressed by the number of people who seem to think - "AHA, based on not reading anything, I believe there is a meaningful chance that the whole medical and regulatory community just missed this extremely obvious possible flaw that just popped in my head?"
Do people really think that the most-publicized clinical trials of our times were conducted by over-reaching noobs?
Second paragraph in the article, it says there were 30 severe COVID cases in the placebo group; unless there trial was ridiculously botched the age profiles of the intervention and trial branch are going to be identical. With the reasonable caveat that definitive answer can only be given once we have read the full trial report.
They would never be that dumb to do that. In fact "The Phase 3 COVE study was designed in collaboration with the FDA and NIH to evaluate Americans at the highest risk of severe COVID-19 disease. As of today, the COVE study includes more than 7,000 Americans over the age of 65"
That would be a likely outcome even under the null hypothesis in a phase II trial, but, for a 30,000 person efficacy trial, I wouldn't be so quick to offhandedly dismiss the assertion that that's a significant result.
A 1% death rate with a disease as contagious as COVID means more than 50 million dead globally at some point (not everyone will get it but the majority will eventually).
Near universal vaccination with a vaccine that is 95% effective at preventing severe cases means saving 47.5 million lives in that scenario. Despite the disease having a 99% survival rate.
If the vaccine provides sterilizing immunity (or just reduces your ability to pass it on), it could save more, and wouldn’t even require universal vaccination to do so.
Furthermore, people are staying home voluntarily in many places. An effective vaccine will alleviate their fears and help the economy. In a way that telling people not to worry about a <1% chance or death will not.
One of the lessons I learned from Thinking, Fast and Slow, is that people who present a number as a percent scale can (but might not) have an agenda, as can people who report an absolute magnitude. What I took from this is that if you want to have a rational reaction to the data, you need to have both numbers in mind while deciding how to feel about the situation.
That means 1% aka 70 million dead. Which I interpret as the Uncanny Valley. 70 million is more than enough for vigorous response. But 1% will mean friction from - and for - policy makers.
The problem is, as virologists have told us for decades, Ebola isn't a very effective plague because it's too deadly, too fast. If we don't react to 1% mortality rate, then the end game is we select for viruses that kill 1% of us, and if the mutation rate or family for that virus is large, we get a unique variant every 5-10 years for the rest of time. If the mortality isn't selecting for the same genotype, then that's almost 10% of us overall, death by a dozen cuts.
We have to have protocols in place for reducing R. We have to have the 'pump' primed for putting out fast-track vaccines. We have to have 'red phone' protocols for world leaders to move faster when these situations are developing.
When COVID-25 comes, we'll be either repeating this experience or blaming all of our leaders for learning nothing.
That is not quite the case as the you're double counting quite a number of people.
set A = The set of all people who die from covid
set B = The set of people who were going to die that year from cancer, heart, age etc
Nearly all of set A fits inside set B. For evidence see either CDC or even the Italian health ministry data set they even published as far back as April 2020 where the median age of death was 79 and 50% had 3+ other diseases and sub 1% had no other diseases.
1. The median age of death at 79, and 50% of people have 3+ diseases doesn't imply that "Nearly all of the people who die from COVID had a life expectancy of < 1 year" as you say. Those 3+ diseases you mention include diabetes, high blood pressure, and obesity etc... Diseases that people commonly live with for decades. The median remaining lifespan of a person who dies of COVID has been estimated to be around 12 years [1,2].
2. Lets say you are correct and 90% of people who die of COVID would have died within 1 year. And let's assume that you have some magic PR method that will convince 100% of the population that this is true.
That means that COVID is still more deadly than the Flu, and some large percentage of people will still choose to remain home, stop traveling, stop eating out etc...
These people will continue to damage the economy until an effective vaccine is available. And even in your scenario a vaccine that is 95% effective will still save millions of lives.
An effective vaccine will save lives, and it will improve the economy. There is no logical reason to deny that fact.
Soooooo... If you were somewhat pragmatic, you'd acknowledge that a lot of people, maybe even a majority, actually support various social distancing measures and shutdowns. These measures certainly have a negative economic impact, irrespective of whether a negative economic impact would happen just due to the voluntary measures of these people.
And regardless, wouldn't it be a net gain to deploy a vaccine? It would certainly be more effective at placating this group of people than implying they're all idiots.
It would be a huge benefit towards resuming a relatively normal society, regardless of whether they're right or whether they're somehow all just a bunch of nervous morons. So why would you criticise it?
I agree we should have a vaccine, I do not agree with mandatory shutdowns and all the negative down stream side effects which are PROVEN to be larger than the disease itself.
Here's a source from CNBC if people are doubting the tweet, "Additionally, there was one Covid-19-related death in the study that occurred in the placebo group, according to the company (Moderna)." https://www.cnbc.com/2020/11/30/moderna-covid-vaccine-is-94p...
I don’t know about the downvotes, perhaps because it’s only tangentially related to the post? But I appreciated the thought. Talk about an unsung hero. Whoever died on the placebo died so that the rest of us can have the knowledge that we have a safe and effective vaccine. We should be grateful to them.
He would have died anyway. Without control groups, we can't test vaccines. So we would not have vaccines. It's not bad to spare a thought for him though. Just bad luck, like a person getting hit and killed by a bus, which would not have happened if he hadn't misplaced his keys and left the house later than he planned.
I think this might have flown better if you had included the first half of the tweet: Anti-vaxxers immediately jump on any report of possible adverse events in a vaccine trial (which are thoroughly investigated, of course).
I think the downvotes are from people assuming you're denouncing the placebo portion of a randomized clinical trial?
Maybe indicate otherwise? (Or explicitly state it if I'm wrong).
All of those that died during clinical trials deserve respect for signing up and helping us advance the medicine. Their death is a statistic, but not in the Stalin quote sense! It's a statistic that helped us find the treatment that will save millions.
not sure what you mean "denouncing the placebo portion of a randomized clinical trial" but I'm going to move on with my life and accept my -4 reputation :)
I meant that your original comment could have been read to imply that this placebo-recipient died a needless death. (e.g. "They should have just given him the vaccine!")
I didn't read it that way, but I could see how others would.
So far, the success rate is very far from 100 per cent, but the therapy sometimes works even in patients with severe late stage metastatized cancer and, in all likelihood, we will learn how to use it better in coming years.
This progress could save way more lives down the line than just those at risk with Covid.
https://www.nature.com/articles/d41586-019-03072-8