No one who got Moderna's vaccine in trial developed severe Covid-19
sciencemag.org
sciencemag.org
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.
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.
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?
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?
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.
https://acir.org/weekly-digests/2020/august/rna-vaccine-for-...
https://www.sciencedaily.com/releases/2020/11/201110102550.h...
Some of the patients would probably already be dead if it wasn't for RNA vaccines.
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.
[1] https://www.genewiz.com/Public/Services/Gene-Synthesis/Turbo...
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.
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 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.
Edit: I have no clue why people would rather something not exist than for something to exist but for it to be too expensive.
e.g. if you want to pay a chemist to synthesise Aspirin in a lab for you it will be very expensive. But it costs pennies in the store.
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.
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.
https://en.wikipedia.org/wiki/National_Vaccine_Injury_Compen...
https://www.statnews.com/2017/01/10/moderna-trouble-mrna/
https://www.statnews.com/2016/09/13/moderna-therapeutics-bio...
https://freakonomics.com/podcast/vaccine/
I don't know if it will change your mind, as he basically says that it may have been valid criticism in 2015-2016, but not anymore.
They all seem quite promising.
https://blogs.sciencemag.org/pipeline/archives/2020/11/23/ox...
>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.
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.
On the other hand, if you want to read about how software works when it actually matters, "space shuttle coding style" is fascinating.
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.
https://www.cdc.gov/vaccinesafety/concerns/concerns-history....
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.
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.
https://www.youtube.com/watch?v=e0MA48bfshw#t=2h14m3s
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.
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
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.
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.
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.
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
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?
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.
Granted I'm disinclined to propagate the human race anyway, so I guess I may actually be ahead of you.
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.
Heck, it's trying to get the body to get rid of viruses. One particular type of virus (retroviruses) do "hack or mix our DNA".
https://www.thelancet.com/journals/lancet/article/PIIS0140-6...
"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.
https://www.genetherapynet.com/viral-vector/adenoviruses.htm...
[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.
So, if we get a virus, we aren't human?
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.
mRNA degrades fairly rapidly, so this won’t keep triggering your immune system (but https://en.wikipedia.org/wiki/RNA_vaccine#Side_effects_and_r... says the mechanism used to do the ‘inject’ part may trigger its own immune reaction)
He's strongly evidence and data based and steers clear of most anything that can reasonably be considered 'political'.
I'm not sure what information beyond that will actually be received and comforting to a lay audience that is skeptical.
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.
Note: This is copied from a previous comment of mine here:https://news.ycombinator.com/item?id=25047289
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"?
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.
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?
Is this bio-chem designed by Moderna, or is it just a property of the mRNA? Does all mRNA follow the same path into the cell?
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
mRNA vaccines give the bits needed to skip to the last step in the process. Notably, there is nothing about "genetics" involved here.
Phase 2a and Phase 3 similarly listed.
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?
So, for example, it looks like this protocol would exclude people getting chemotherapy.
Happy to be proven wrong on this by someone with more information.
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.
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
People experiencing long term symptoms? I can believe that, my tinnitus after covid-19 is still there, even if I don't notice it as much.
Actual viral infection? I really doubt that, thoug perhaps it could hide like the herpes virus.
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.
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.
That's the reason why also young healthy people need to take the vaccine in order to stop the spread. It's a solidarity gesture.
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.
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.
https://immunisationhandbook.health.gov.au/vaccination-for-s...
(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)
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.
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.
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?
But looking up this one, it was blinded, indeed! https://www.henryford.com/moderna-vaccine/faqs
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.
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!
1/ take the vaccine
2/ expose himself to the virus to chekc his immunity.
We will never know before trial
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.
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).
"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."
https://www.forbes.com/sites/williamhaseltine/2020/09/23/cov...
So I guess the question is - even if not sterilizing immunity, would these vaccines significantly reduce (but not eliminate) transmission?
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.
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.
I was under the impression that vaccine + immunity will just lead to herd immunity and the disease to go away on its own.
Confirmed cases: 13.4 million people
Confirmed deaths: 267 thousand people
deaths / confirmed: ~2%
2% of the US dead (assumes homogeneous 2% death rate, which is incorrect but an upper bound): 6.6 million people
Distribution of deaths by age bracket, including population distribution: https://www.cdc.gov/nchs/nvss/vsrr/covid_weekly/index.htm
About half the population is over ~45 years old.
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.
https://www.cdc.gov/coronavirus/2019-ncov/hcp/planning-scena...
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.
So they don't infect and kill their older relatives.
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.
2017-2018 Flu 2018-2019 Flu COVID-19 as of August 27, 2020
Cases 45 million 35 million 5 million
Deaths 61,000 34,157 180,000+
A TIA at 23 isn't a trivial thing. https://twitter.com/RileyBehrens/status/1333230792206553089?...
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.
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".
I'm not sure if this is a concession for argument's sake, but imo it does take away from it. Why do you think it doesn't?
There are plenty of valid arguments to vaccinate everyone we can.
EDIT: After re-reading I understood the sentence, my bad.
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.
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.
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.
[1] https://biology.mit.edu/undergraduate/current-students/subje... [Lecture 10, with a NIH researcher who worked on the Moderna vaccine]
[2] https://www.thelancet.com/journals/lancet/article/PIIS0140-6... [Phase 2/3 study of AstraZeneca vaccine, figure shows neutralizing antibody levels]
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?
That's not what I have come to expect from a crowd of curious people carrying a scientific temper.
C'mon HN. Let's answer the questions without downvoting someone to oblivion.
https://www.newyorker.com/news/letter-from-silicon-valley/th...
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.
Why not? Liability waivers are common in other industries.
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.
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?
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.
The National Childhood Vaccine Injury Act of 1986 is the relevant law. The USSC upheld it 6-2 in a 2010 case.
The risks are low, and the benefits of the vaccine vastly outweigh them.
https://www.hrsa.gov/vaccine-compensation/index.html
Essentially the government runs the trial.
> “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,”
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.
And do you think you have this right only regarding this disease, or other similar diseases as well?
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.
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.
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.
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.
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.
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.
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.
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.
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.
I'm guessing you have excluded the "one in three kids got polio" approved vaccine?
https://en.wikipedia.org/wiki/Cutter_Laboratories#Cutter_inc...
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.
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.
I hope they at least ask subjects about exposure.
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.
https://twitter.com/tmprowell/status/1333442134553325569
I agree more testing could have been interesting, but this was a large trial with very clear results.
Sinopharm have gone ahead and vaccinated about a million people before full testing with apparently no infections and no serious side effects so it's not that outlandish. https://www.theguardian.com/world/2020/nov/20/china-has-give...
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.
30 / 185 * 11 = 1.7
1.7 ~= 0, so the sample size is too small to support the headline.
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").
Thanks for running through the math; I’m guessing we came to the same conclusion about the strength of the evidence.
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?
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.
a) the scenario when the foreign material is immediately degraded by enzymes or other mechanism, before actually accomplishing anything,
b) the scenario when the foreign material causes massive immune reaction in form of inflammation, potentially killing the host.
AFAIK navigating between those two extremes took decades during development of RNA vaccines. But now it seems that we can avoid both.
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.
> No one developed severe Covid-19
> No one developed severe adverse effects
There is a reason vaccine trials normally take several years. I'll wait until we're a few years into phase IV trials, thankyouverymuch.
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).
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.
It's an unknown vs an unknown. Novel virus, novel immunization (first mRNA or maybe first widespread modified adenovirus)
P(covid death or long term harm) < 0.05%
vs.
P(vaccine long term harm) = ?
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.
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?
For example, IFR(age<65) in geneva[0] is 0.0045%. multiply by 10 to include also long term harm, you get 0.045%.
[0] https://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099...
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:
https://www.medrxiv.org/content/10.1101/2020.07.23.20160895v...
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.
[1] https://clinicaltrials.gov/ct2/show/NCT04470427#contactlocat...
[2] https://www.cdc.gov/vaccinesafety/concerns/concerns-history....
https://investors.modernatx.com/news-releases/news-release-d...
I've found the answer starting from there. Good luck.
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?Bring on the new overlords.
I would be still cautious with that statement and not underestimate it.
* depression * suicide * poverty -> famine and disease * missed education * dependency on gov * freedoms given up and transferred to gov
I also agree that there are other side effects, just like every disease.
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?
https://www.ineteconomics.org/perspectives/blog/to-save-the-...
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.
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.
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.
[1] https://wellcomeopenresearch.org/articles/5-75 [2] https://www.medrxiv.org/content/10.1101/2020.06.08.20050559v...
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's exactly what Hans Rosling says in "Factfulness", always be wary of lonely numbers.
>>> Let’s spare a thought today for the person who signed up for the Moderna vaccine trial, received two placebo shots and died of covid19.
https://twitter.com/kakape/status/1333401133260419072
---
edit:
Please explain the downvotes.
The vaccine volunteer would be alive if he was randomly assigned the actual vaccine, and not two doses of placebo.
The tweet is from a respected journalist at Science Magazine.
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.
I didn't read it that way, but I could see how others would.
That really puts the second half in context.
* Not interesting. Placebo.
* Low quality source: personal Twitter
* Cannot find corroboration
* Unclear why you think this is interesting to us. I don't understand whether you're making a point
Hope that helps