> Pfizer’s phase 2/3 trial randomized non-hospitalized adult COVID-19 patients who were at high risk of progressing to severe illness to receive placebo or Paxlovid, a combination of the protease inhibitors PF-07321332 and ritonavir. The efficacy analysis is based on 1,219 patients.
One noteworthy feature is the newness of this drug:
> PF-07321332 was developed from scratch during the current pandemic. It’s a reversible covalent inhibitor that reacts with one of the main protease’s cysteine residues. Owen [director of medicinal chemistry at Pfizer] also discussed the chemistry involved in scaling up the compound. The first 7 mg of the compound were synthesized in late July 2020. Encouraged by the early biological data, the Pfizer team aimed to scale up the synthesis. By late October, they’d made 100 g of the compound. Just two weeks later, the chemists had scaled up the synthesis to more than 1 kg. Owen said 210 researchers had worked on the project.
Less than two years from lab to clinic is highly unusual. If approved, I believe this would be the fastest lab-to-approval for a small molecule drug in the history of the FDA.
>Less than two years from lab to clinic is highly unusual.
I assume like most other COVID vaccines/treatments, the timeline is shrunk by going straight to more expensive phases of the trial instead of having preliminary ones of escalating cost and confidence. Or at least prepping for them.
For instance, all the vaccines started setting up commercial production around the same time they started trials, because it's not worth the months delay of setting up a production line to determine if it worked first.
Also one factor slowing some studies has been the need to wait for test cases: you can't infect people with, say, Ebola so you need to wait for enough people in your study cohort to contract it naturally to get enough data to say whether a vaccine candidate is having an impact. During a pandemic, it's sadly easy to hit a statistically-significant number of infections.
Pharma companies in the US spend about twice as much on advertising as they do on R&D [1]. Recent data compiled by the House Oversight Committee shows the biggest pharma companies spent $56 billion more on stock buybacks and dividends than they did on R&D over the past five years [2]. Very little of the ridiculous prices that US citizens pay for medicine (directly or via insurance) actually goes towards R&D.
Terrible take. Your first source vaguely tries to estimate promotional spending (not advertising as you deceitfully claim). Promotional spend has a positive ROI (or you wouldn’t do it). So spending $1B in promotion gets your $1B+ in sales (it’s self funding).
Plus stock buybacks and dividends are being criticized? Returning money to investors is “bad”? Who do you think provides capital for drug development? The Grenadier Guards?
> Promotional spend has a positive ROI (or you wouldn’t do it).
That's incorrect; promotional spend on prescription drugs is the globally suboptimal result of a prisoner's dilemma where the prosecutors are going around saying "hey, that guy over there snitched, so should you". There is absolutely no guarantee that ROI is positive.
> Who do you think provides capital for drug development? The Grenadier Guards?
Most of basic drug development happens in labs e.g. at universities that are funded mainly by public sources.
Per the latest PhRMA member survey, drug companies spent about $13 billion per year on preclinical R&D, which was about 15% of their total R&D spend. Meanwhile the NIH alone provides about $40 billion per year for preclinical research. So funding for actually finding new drugs and therapies is dominated by other funding sources than drug companies.
If you look at e.g. Pfizer and J&J, more than 85% of their revenue comes from drugs that were invented elsewhere. Just to clarify, I'm not saying clinical trials isn't a necessary and expensive thing. But in large part it's not developing drugs, it's checking that there are no big side effects and that efficacy remains what you saw at small sample sizes.
For instance mRNA vaccines were invented in publically funded laboratories. Monoclonal antibodies that work against inflammation is another example. And of course CRISPR, which is very promising.
Very little drug development happens in academia. You are missing all the time, money spent in public and private markets in the biotech ecosystem that Pharma largely is the back end buyer for through off-balance sheet acquisitions/deals. VCs collectively spend tens a billions a year on biotech (~40B this year), and much more in public markets (IPOs and secondary public finances).
In the example you bring up. Moderna raised and spent billions over a decade since it was founded on the 'academic invention', and didn't have a product until their vaccine. The same is true for BioNTech. There was a large chance these companies could have folded, and before the pandemic, most were deeply skeptical.
A positive ROI in isolation for one company doesn't necessarily mean anything useful is gained across the whole industry. Consider what would happen if promotional spend was just taking market share from other pharma companies - it'd be wasted money, but everyone would have to do it to preserve market share.
Price very much depends on cost, the goal is profit maximization not maximizing revenue.
Suppose you can sell 1 million sandwiches at 5$ or 1/2 a million at 6$ which you price depends on your cost of production. If it’s costing you less than 4$ you pick the first option if it’s more than 4$ and less than 6$ you pick the second. Though in the real world costs aren’t independent of sales so it’s even more complicated.
It’s only when you get extreme markups from a guaranteed monopoly that you can approximate things as revenue maximization. Also, drug R&D numbers are extremely inflated as among other things it’s got tax advantages.
My whole post is the exception you mention in your third paragraph. Your first paragraph is what happens when you have generics, and they start treating the drug more like a sandwich that a treatment. (No bioequivalence tests, safety concerns, etc)
But does it really increase sales? We’re talking drugs that are prescribed by a doctor. Or do people not buy and take their statins unless they see a tv ad?
That should scare everyone and I’m not sure why it doesn’t. They wouldn’t be advertising them if it didn’t increase sales, which probably means oncologists aren’t always prescribing what’s best.
As far as other medications, most people don’t go to the doctor regularly. Even if they did, they would probably need to inquire about their condition to have the doctor think of updating anything.
As someone who has worked with doctors for much of my career I can assure you the quality of doctors varies just as much as other professions.
I remember having to personally call a doctor and ask them to stop prescribing a drug because it was pretty much malpractice to not use the newer approved drug from another company.
Probably because the people will name-drop that particular brand. It's up to the doctor to responsibly prescribe it, whom probably heard of the drug because of other forms of marketing or flat out kickbacks
Those free samples very much make treatment less affordable. They don’t need to hand out samples when their treatment is the only option, they need to advertise to out compete generics.
It’s shockingly effective, look at say prescriptions for patented opioids vs the vast numbers of equally effective generics. Doctors are extremely susceptible to advertising just like most people, the difference is it’s not their money being spent.
“Clinical studies comparing the response and side effects of various opioids have not been able to show robust differences between drugs.”
So, it’s not a question of which is prescribed more, it’s a question of why branded opioids are ever prescribed. We aren’t talking about a ~100 Billion dollars of accidental waste, it took a lot of work to extract that from the general public.
I mean the biggest opioid sales were OxyContin and the argument there was the time release which wasn’t available in a generic.
As a part of my job I’ve talked to insurance companies and they aren’t willing to pay for branded pain relief drugs unless there is some differentiating value.
1987 “May: MS Contin, (morphine sulfate) approved; first formulation of an opioid pain medicine that allowed dosing every 12 hours instead of every 4 to 6 hours.”
1990 “August: Duragesic (fentanyl transdermal system) approved; first formulation of an opioid pain medicine in a patch (sometimes referred to as a “skin patch”) that is changed every 3 days.”
1995 “December: OxyContin (oxycodone controlled-release) approved; first formulation of oxycodone that allowed dosing every 12 hours instead of every 4 to 6 hours.”
In the case of doctors it's more high-touch than plain old ads anyway. The representative stops by and chats them up, maybe they get some sponsored continuing education (which is of course designed to push expensive products), etc.
BS, doctors give the samples to friends and family, and some to patients. Doctors can't know a patient is poor. In private practice, the doctor assumes the patient isn't poor.
That's not how it works. The doctor prescribes the drug and gives the patient the free sample. What, did you think they were in a "take one" candy jar?
As an alternative, you could have a single payer, public health care option that would be significantly cheaper than the current shit show that the US system has (modulo the small percentage of Americans who have had a genuinely positive experience with the syst as opposed to the Kafkaesque nightmares that are the more common take.)
Your first link is from 2008, and analyzes data from 2004. I don't see how this proves anything, or even suggests much, about the industry today.
Your second link shows that the pharma companies spend almost as much on R&D as on stock dividends and buybacks. Is there any other industry that spends as much on R&D? Apple, for instance, seems to be spending ~6x as much on stock buybacks and dividends as on R&D (approximately, based on the first Google hits).
Even your own links contradict your claim that very little goes to R&D.
This is not a dick measuring contest. The comment was challenging the notion that pharmaceuticals companies spending the majority of their cash on advertising and stock buybacks is a desired outcome. The specific numbers, especially across industries, are meaningless.
R&D is actually usually done outside of the major drug companies and is funded by the government. So I doubt it really will effect it. And most price hikes lately have been in pre-existing drugs.
It's interesting to note that the Pfizer, AstroZeneca and J&J vaccines were all invented by 3rd parties.
Early stage R&D is the part that typically happens outside of big pharma, though all the big companies have their own proprietary early stage efforts/portfolios.
Even then govt funded stuff is mostly preclinical. Start ups mostly cover anything from animal studies to phase 1 / 2.
Late stage R&D, manufacturing, and marketing is extremely capital intensive and complex and is mostly done by large pharma companies, who either license the asset or enter some sort of partnership with the IP holder. And I am including regulatory approval, demonstrating value to payers, etc under marketing (e.g. it is not just advertising).
And that was due to the wisdom of operation warpspeed. Trump is under credited for this (whether his idea or not, he could claim it as such). What’s shocking to me is that he hasn’t been more pro-vax given we have the vaccines we do because of his administration.
Pfizer/BioNTech weren’t part of Warp Speed. And the Oxford/AstraZeneca vaccines were ready and had begun trials before they were part of Warp speed.
The only vaccine it might have had an impact on was potentially Moderna. But even Moderna had the vaccine ready well before the Trump administration even believed that the virus did not only affect Chinese people.
Finally, Warp Speed was not a brilliant new idea they came up with. It was part of the pandemic response plan the Obama administration had prepared many years ago. The difference is that if they had actually followed the plan warp speed would have been activated well before.
Pretty much the only thing that the Trump administration can be uniquely credited for is picking the name. Which, as we can see from the fact that the majority of current vaccine skeptics are worried about the speed at which the vaccines were created, was a terrible choice for a name.
Operation Warp Speed is, to me, an indication of the power of government "intertia". Trump changed a lot of things, and while an uncomfortable amount of the U.S. government seems to run on "tradition" that isn't actually law, after 4 years of unchecked assault it was only at the very end that it really got crazy.
Warp speed is the work of career guys. Not even Fauchi -- he was important, but these ideas are put together, presented, and executed by the unknown 9-to-5ers.
I find this whole deep state thing very strange. It's meant to sound ominous, but really it's just a bunch of career diplomates that have worked over many administrations who are the ones that make anything that works, work. We should be doing our best to preserve their knowledge and capability.
The truth is that any government needs a ton of people to operate properly and you can't change all of them upon election.
Actually, scratch that, you can sort of do that every election/change of government.
Do you know where they do that? Failed states. Failed states change most if not all the government employees upon regime change, to put people from the new regime in their place.
It's an unmitigated disaster, because you also need people other than politicians to do the heavy lifting. And those skills can't always be built up over just 4 years, you need more than that. It's dumb to throw them away. Let alone the fact that changing them with the regime means that it's super unlikely you keep the competent people, you just get new loyal folks.
It's not really a conspiracy theory though, it's just the reality that much/most of the power of the government is in the hands of unelected bureaucrats. That doesn't imply the bureaucrats are conspiring.
And that's not necessarily a bad thing (for the reasons you describe) but there's a fundamental deceit going on if the president can't actually control that bureaucracy (because people assume that he can).
Stable Western nations have career bureaucrats that continue working their office regardless of which political party is at helm. This brings expertise and continuity and has nothing to do with deep state. A new minister will assign new goals but retain the old team that has the best understanding available in their specific field.
If by “we” you mean fans of the arbitrary, irresponsible, corrupt patronage-based governance of the spoils system who use the term to denigrate the idea of a professional civil service with loyalty that extends beyond the person of the current chief executive on whom their tenure depends, then, sure, “we” do.
>What’s shocking to me is that he hasn’t been more pro-vax given we have the vaccines we do because of his administration.
He made vaccinations a partisan wedge issue to such a degree that he can't afford to walk back from it if he wants to run again in 2024, similar to the Republicans' former position on Obamacare.
That seems a bit revisionist. To my knowledge, Donald Trump was always a vocal supporter of the Covid vaccine. Kamala Harris and Joe Biden were the ones sowing doubt about it - right up until they won the election. Harris, in particular, described Trump as irresponsible for advocating for Project Warpspeed and suggesting that people should take a Covid vaccine before it had gone through the full approval process.
I think you may be getting their personal stances confused with the partisan arguments about vaccine mandates that have evolved in the year since.
Trump didn’t make the vaccine a wedge issue, he made COVID a wedge issue by repeatedly calling it a political lie (which resulted in vaccines becoming a wedge issue).
I suspect the confusion between your perspective and that of the previous commenter is a result of the difficulty Trump experienced in trying to promote a vaccine for an illness he was himself at the same time claiming does not exist.
He also clung to and promoted a bunch of other unproven treatments leading up to the vaccine… why should anyone have trusted him by this point in the pandemic?
The Latest article in BMJ about the failures in scientific integrity in the pfizer trials are a likely consequence of your last paragraph I would guess.
It's not uncommon for human tragedies to serve as a backdrop for significant scientific progress.
Wars and pandemics seem to be the testbeds for medicine, where people are desperate enough to try anything, and legislation is relaxed accordingly. The biotech companies know this all too well, and take advantage when the opportunity arises.
Development tools help accelerate software development. Better tools help you go faster. This is happening in biotech as well - they're getting some very good development tools.
Is anyone familiar how this scaling up process works? To what point can it be scaled up using lab methods, and at which point does it make sense to start making it large-scale?
Aren't we? I thought that until SARS the scientific consensus was that coronaviruses are not interesting. And SARS died out too quickly to achieve much. But I might have not paid enough attention.
I’m pretty sure the reason Moderna was able to develop a vaccine so quickly (Feb 2020?) was because they already knew the spike protein to target from the original SARS outbreak.
"horse paste" has been approved for human use for over 30 years. not sure how expecting proper testing for new medicines became some conspiracy theory thing.
If you do a liver transplant for a congestive heart failure patient, you’ll lose your license, even if liver transplants are a neat and useful procedure.
I think it’s hard to overstate what a big deal this is for science. This is a completely novel molecule that appears effective as an antiviral. This would a huge achievement for the field of drug design, and will hopefully lead to all kinds of great medicine.
> This is a completely novel molecule that appears effective as an antiviral. This would a huge achievement for the field of drug design, and will hopefully lead to all kinds of great medicine.
According to the Pfizer press release [0] Paxlovid uses Ritonavir [1], which is a known HIV antiviral, originally patented in 1989.
At the start of the covid pandemic, chinese scientists even tried Kaletra, a generic that combines Ritonavir with another HIV antiviral, and found it to not improve outcomes [2], but this might have been due to them not giving the drug early enough in the infection, but only to hospitalized patients, while Pfizer gave it to non-hospitalized patients with a risk of later hospitalization.
Yeah, as parent mentioned in another reply below, ritonavir is an antiviral, but has no effect on SARS-CoV-2 (https://pubmed.ncbi.nlm.nih.gov/34048671/). Ritonavir is just used to inhibit CYP and therefore reducing clearance of the drug.
Oh thought that was some id name for ritonavir. Seems you are right:
> PF-07321332 is designed to block the activity of the SARS-CoV-2-3CL protease, an enzyme that the coronavirus needs to replicate. Co-administration with a low dose of ritonavir helps slow the metabolism, or breakdown, of PF-07321332 in order for it to remain active in the body for longer periods of time at higher concentrations to help combat the virus.
So the main job is done by PF-07321332 even, while ritonavir is only there to keep PF-07321332 a bit longer from being destroyed by the body.
You ascribe far more rationality to the process of developing drugs than is actually applied.
Pharma mostly avoids low-profit avenues, but at least partly because that would be a good way to go out of business. However, to suggest that they intentionally suppress researchers with the goal of reducing costs seems a bit far-fetched.
I'm really not suggesting active suppression, but rather simple, Occam-compliant inaction. COVID19, for example, is not really the first of its kind - just the first that was clearly going to produce profits if addressed. And lo, magically, it was.
Mine was not a conspiracy-innuendo, but rather a simple critique of profit-driven research in health-related sciences. Humans can do wonderful things when they work together, so it's rather sad that we seem to do that only when there are riches on the line.
> but rather a simple critique of profit-driven research in health-related sciences
But as a private company they need profit to fund the science. They'd go out of business if they weren't making a profit.
It's largely the role of government to fund public goods (e.g. by providing grants to university researchers). We can't expect the scientists and engineers to work for free.
> But as a private company they need profit to fund the science.
Yes, as a private company. In my opinion, it's not like everything has to be a private profit-driven company, precisely because incentives are not necessarily aligned to the public good.
I don't understand the difference between intentionally suppressing researchers, which they are obviously not doing (that would be ghastly) and directing research towards the most profitable drugs, which they are obviously doing (to do otherwise would be bad business).
the former is an ethics violation, the latter is just a good strategy to win against the multi-armed bandit (which is how resource portfolios are managed at pharma).
many pharma do invest some of their portfolio into things that are unlikely to have short-term or any payoff, and many of them also maintain compassionate programs to get expensive drugs to people who wouldn't be able to otherwise afford them. They do this because they are highly profitable, which unfortunately is as much explained by their marketing acumen as much as it is by solid research and development.
Okay, so if I'm getting this straight, instructing researchers to not research unprofitable drugs is an ethics violation, while instructing them to research profitable ones is good strategy.
Can you provide an example of a treatment people would like that 'big pharma' wouldn't produce because they couldn't make a profit on it?
This is such a ridiculous argument, IMO. As a thought experiment consider something like cancer treatment. If some pharma company researcher found a way to 100% prevent or reverse cancer, why would the company hide that? In the best case, they could make a ton of money from it by selling it cheap to everyone. In the worse case, they could make a ton of money selling it to the ultra wealthy with an obscene price tag. If they tried to hide it, the researcher would share the information elsewhere, no?
You're saying hiding the discovery of novel, profitable, drugs because profits from the existing treatment is widespread?
I'm not saying the pharma companies pursue all possible opportunities to research/create new drugs, just that it's ridiculous to think if they did find one, they would suppress that information. It seems conspiratorial.
The Orphan drug act or incubators you link don't contradict the point I'm trying to make, but maybe that's on me.
Drugs work in economies of scale like everything else.
I like to write and publish books, but only because I know that several thousand people are going to buy them (yeah, humblebrag...). I wouldn't bother with them if my audience was two orders of magnitude smaller. It is just not worth the hassle.
Similarly, most programmers here probably work on projects used by thousands at least as well. Few people will put hours and energy into something that will only be used by, say, three users.
Rare diseases suffer from the same problem. The cost of development of drugs under current regulatory regime is high and in case of rare disease, cannot be amortized later over a huge set of patients. Moreover, most promising drugs actually fail in human trials, but the costs are already incurred.
Whilst I don't buy the malice (big pharma deliberately not curing things they could) argument, there's plenty of things they don't do 'cause they don't think they'll make a profit on them.
Novel drug research is extremely expensive and time consuming, logically speaking a for-profit pharma company will assign its resources to the research which is most likely to make a profit.
As a result rare conditions will not attract the research necessary to create drugs to treat them. To give you a concrete example, AFAIK there was never a vaccine for MERS which is a coronovirus which preceded COVID-19.
You are the head of strategy presenting to Big Pharma CEO.
You say 'Here are 5 new drugs which have potential for great impact, each will cost a billion. 4 of them are vaccines, which will be very inexpensive, and nobody will buy and we will lose money. One of them is a fairly expensive cancer treatment. Which one do you want to focus on boss?'
Supply/Demand and just Basic Economics generally work their way into the system.
Some drugs are much more profitable than others, many of them are not going to be profitable, and there's less incentive to work on them. Vaccines in particular.
It's a big part of the equation we have to deal with.
1) use of Psylocibin (mushrooms) assisted Congitive Behavioural Therapy for curing PTSD, depression, anxiety, etc. we have seen extremely good results from this and pharma companies could have likely pushed it much much sooner
2) Biofeedback/Neurofeedback has been around for more than a decade and is under-researched, under-insured, and under-prescribed for treatment of a lot of mental issues from anxiety to post-concussive syndrome to ADHD.
both of these can negate the need for a years or decades long reliance on SSRIs or stimulants.
Sandoz's original explorations into LSD were medically focused and it was marketed (and distributed for free in high purity) for psychiatric indications, but after it grew in popularity an illicit drug, all pharma got out of the business of working with highly psychoactive compounds for decades because of the negative press assocations.
I don’t think it’s pharma companies responsibility to ‘push’ psylocibin - it sounds like that sits more between doctors, public/university pharmaceutical researchers and legislators.
I can tell you from first hand experience that neurofeedback is a life changing treatment. Far superior to ADHD stimulants which is a nightmare for some.
New antibiotics for one -- if they make a new one that has no resistances in the wild yet, doctors would avoid prescribing it as long as possible, only after all older drugs are tried, so the usage would be extremely low. Nobody wants to sink a few billion into something like that.
The companies who make today's lengthy and expensive cancer treatments, are also making the mass-marketed personal care products that have carcinogens inside of them.
Found the big pharma PR guy. The people in pharma are 100% not in this for the right reasons. Not one. Look into Every Single one of these companies just a tiny bit and you'll see how absolutely evil they are and by working for them you are complicit. You don't have to agree with reality, but that's reality.
Unfortunately, it's expensive. The cost of R&D to bring a new drug to market is around $1 billion, and this doesn't include the cost of marketing (though it does include the cost of drugs that fail the approval process)(see https://jamanetwork.com/journals/jama/fullarticle/2762311). At these numbers, it's hard to raise the money unless you think the drug is gonna be profitable.
A billion is a lot of money but not for governments, it's kinda tragic when you look at what we spend on some things that we haven't figured out a more sensible way of allocating resources.
What alternative to capitalism are you implying would be better? If you have a viable alternative, just do it yourself. (I’m not saying all by yourself, team up with others to make it happen.)
I’m not being sarcastic, I’m genuinely interested in what you believe would get us from here to a Startrek-like economic system.
Startrek is amazingly devoid of status conflicts. Everybody takes for granted the the BigCaptain is BigCaptain for life and that the SeniorOfficers are SeniorOfficers for life. The crew is content to work routine boring jobs for years on end with exceedingly rare promotions (where to promote to other than a new ship?). Even in a society of small scale material affluence, there are scarce coveted goods, for example, being the captain of a starship.
That borrows heavily from the idea of just how navies works though, yeah? In a submarine, you don't wanna do a stupid. I bet you could take the script for the Hunt for Red October and make it a TNG three parter and barely anyone would notice.
Outside of the fancy starships, it does seem like it's more business as usual when it comes to the failings of people and their better wants and desires. How many plots lines dealt with trade disputes or colonies that need to do something (like leave) but don't wanna, etc.
> I’m not being sarcastic, I’m genuinely interested in what you believe would get us from here to a Startrek-like economic system.
There's gotta be fanfiction where everyone actual is a cyborg, it's only Data that's cognizant of that fact, which oddly makes him more human that everyone else.
So that's my answer: get rid of the humans.
I would also say, "let's try Anarchism" but starships are anything but lacking hierarchy. They're little benevolent fascist city-states. But Fascism isn't popular with everyone it seems.
Which I see as a problem, as world powers are very distinct, seemingly have a hard time when they don't ingrain capitalism to a large degree (China) and one is definitely required to have a robust alternative to capitalism
I don't think we've had a singular large-scale example of non-capitalism that wasn't experiencing tremendous external pressure to fail. I really wish people would stop pretending like it's impossible when it's been sabotaged at every attempt.
> The cost of R&D to bring a new drug to market is around $1 billion
This is one of the most well know, tired, scammy talking point big-pharma has used for decades.
Hint: in the very document you linked, htere is a 'costing method' section, you might want to read it a bit more carefully and you will discover the big scam: opportunity cost, not cost.
He he, does anyone remember the Software Publishers Association?
They, together with Microsoft, tried to calculate how much money Microsoft was losing in developing countries. So they went something like: 1 billion PCs x 1 copy of Windows 98 or whatever was popular at the time x $100 per copy, so Microsoft is losing $100 billion.
They just ignored a few key facts. Such as, for example, the fact that many of those 1 billion PC users in developing countries were making $100 per year. So if someone held a gun to their head they still wouldn't have been able to pay the license cost. They would have just used something else, maybe Linux.
> Hmmm.... so you're arguing that it doesn't take years of time and billions of dollars to bring a drug to market?
You just made a straw-man argument.
I posted a 2 lines comment highlighting the fact that cost and opportunity cost are two very different things, to the point that the claim that taking a drug to market costing literally billions of dollars to poor drug companies can be taken with a grain of salt.
You main take-away was that I am "arguing that it doesn't take years of time and billions of dollars to bring a drug to market".
No, I didn't make any kind of "straw man argument".
In your original post, you referred to the claim that it costs billions of dollars as a "scam", which is exactly the same thing as calling it false (indeed, it's not only calling it false, it's calling it intentionally and perhaps criminally false).
Now you're trying to walk back that claim by watering it down to "take it with a grain of salt" rather than calling it a "scam", but you did, in fact, deny that it costs billions.
If it doesn't, in fact, cost billions, why isn't someone undercutting them?
> In your original post, you referred to the claim that it costs billions of dollars as a "scam"
Yes and I still mean it, it is a scam because now people cite this study and think 'cost' where in reality they should think 'opportunity cost'.
I'm not walking back anything, this is literally a talking point coming from some lobbyists to justify the widespread practice of fake pricing of drugs in the US.
Let me just copy paste the relevant section in the document that we are referring to.
"First, we summed direct and indirect research and development spending on a therapeutic agent in each year. All sums were inflation adjusted to 2018 dollars using the US consumer price index.
Second, we accounted for failed projects by dividing total research and development expenditures on a drug in a particular year by the corresponding aggregate phase-specific probability of success, similar to what was done in previous studies of costs of drug development.3-7 For example, for each drug, we divided phase 1 costs in each year by 0.138, which accounted for spending on the other 6.2 phase 1 trials that would fail, on average, for each successful development program. We used phase 1 rates to adjust preclinical expenditures, and we used the proportion of biologics license applications and new drug applications that are approved by the FDA to adjust costs once these applications were submitted to the agency for regulatory approval. Licensing fees and milestone payments, where captured, were adjusted using the success rate for the trial phase that was ongoing when the payments were made. When a phase shift took place within the financial year, we allocated the cost proportionally to the time spent in each phase. For example, if development moved from phase 1 to phase 2 on July 1 of a given year, we divided the costs equally between each phase. Similarly, in the year of approval, we multiplied the total cost by the fraction of the year elapsed by the time of approval. Hence, if a drug was approved on July 1, we only counted 50% of the costs in the year of approval since firms often incurred postapproval costs related to pharmacovigilance or testing in other indications.
Third, we applied a real cost of capital rate of 10.5% per year (ie, weighted average cost of capital in the pharmaceutical industry), as in the DiMasi et al study.4 Cost of capital is the required rate of return for an investor and encapsulates a risk-free rate (ie, opportunity cost) and premium based on the likelihood of business failure.24"
I’m not sure you are reading this correctly. Is it the cost of capital rate you are hung up on? If so, how do you account for the time period between investment in a successful drug and when you start actually bringing in money? There’s a few years where you’ve put in several hundred million dollars and make zero back. You can split hairs about what the discount rate should be, but you need to account for that delay somehow. Spending $100 and making back $200 next year is very different than spending $100 and making back $200 in five years.
Diseases like COVID are probably some of the easier ones to cure. It’s a foreign body that is tangible. We deeply understand how the virus replicates and how it works. We know which proteins and nucleosides to target. We don’t have that luxury for diseases like cancer, autoimmune diseases, and the like.
this is where my mind was going, trying to remain positive and less conspiracy theory though. but it's really not secret that some companies (presumably pharmaceutical companies as well) have to stay in business and sometimes in order to do so, many companies build products that wear out, see how gillette razors came about for more insight on that
> PF-07321332 is designed to block the activity of [a specific] enzyme that the coronavirus needs to replicate. Co-administration with a low dose of ritonavir helps slow [the breakdown] of PF-07321332 in order for it to remain active in the body for longer periods of time at higher concentrations to help combat the virus.
It's a two-part drug. PF-07321332 is the new and shiny thing that impairs a crucial enzyme for the virus, while the pre-existing drug ritonavir lets PF-07321332 last longer, making it more clinically useful.
They can copyright it and make tons of money off of it is what it means. All of the other things that already work can't make them insane profits so, bought and paid for the news that you are fed tells you this is one of few valid ways to fight a virus you can dodge by staying in the sun for an hour each day and exercising your body.
If unvaccinated people all died or went to the hospital it would be impressive, the title is misleading or lying about it’s effectiveness. The null hypothesis would probably neutralize it’s effectiveness. They don’t use infection prevention which would be much higher for unvaccinated because in reality it’s probably not very effective against COVID. The control we also don’t know any statistics about.
This is a placebo-controlled trial. The statistical comparison shown (85% fewer hospitalizations & deaths in the treatment group) already takes into account the non-hospitalized cases in the control group.
I am thinking: if and when this is approved, we have to think about distribution.
This drug is fantastically effective at preventing hospitalisation and death, if administered within three days of symptom onset.
That gives quite a long time! But we still need to make it easy to take. Do pharmacies give it out? ER rooms? We don't want to wait until people are hospitalised; we are trying to avoid that.
So when you test positive, does the government send you out a pill with the "sorry, you have to isolate" SMS?
I highly recommend Derek Lowe's post on it for some of the details. It links to the press release which contains this information showing it was very effective still starting at 5 days from symptoms onset:
> Similar reductions in COVID-19-related hospitalization or death were observed in patients treated within five days of symptom onset; 1.0% of patients who received PAXLOVID™ were hospitalized through Day 28 following randomization (6/607 hospitalized, with no deaths), compared to 6.7% of patients who received a placebo (41/612 hospitalized with 10 subsequent deaths), with high statistical significance (p<0.0001). In the overall study population through Day 28, no deaths were reported in patients who received PAXLOVID™ as compared to 10 (1.6%) deaths in patients who received placebo.
Those extra two days (three versus five) could make a huge difference.
Who is the market for this? The assumption is that you give it ASAP and people want to take it. If people aren’t interested in vaccinations they may not want it either, and the vaccines are already very effective at preventing these issues.
I think skepticism of vaccines largely doesn't transfer to the broader medical field. The ineffective fad treatments (ivermectin and hydroxychloroquine) are still medicine, but are still "popular" with vaccine skeptics. It's not rational, but I think vaccine skepticism is largely not rational to begin with.
Anecdotally, hearing from doctors working in COVID wards, they consist almost entirely of anti-vaxxers who are now seeking (and receiving) treatments only recently approved. So while not everyone will take this, I think probably many would once they have symptoms.
That said, this does work better it seems if taken early, before the anti-vax sentiment may have worn off. Hard to say.
What it does signal is really the "end of the pandemic". We have both a vaccine (now approved for kids) and a cure. That sounds like it to me.
This. Being antivax when one has 93% if not facing the virus ≠ refusing drugs when infected. At that point, it’s worth doing everything because the risk is realized.
The first three days of symptoms for an anti-vaxxer are obviously just a flu, because covid is fake. It's not covid until they're hooked up to a machine...
There are many who won't even get a test now, to check if it's COVID. They ride it out, and won't know if they just had a flu, cold, or COVID. And thus it seems we've currently plateaued in case counts in the US :(
A lab in the UK performing PCR tests messed up big time, and returned 40 000 false positives.
40 000 people forced to work by their employers, who then spread it to colleagues and customers, because they had a respiratory disease but ‘it isn’t COVID’.
COVID is particularly bad, but employees should also be allowed to stay home and rest, to not spread the cold and flu.
The fad treatments are "still medicine," but crucially are not generally approved of by the "mainstream medical establishment." This lack of approval is the key feature of these treatments.
> This lack of approval is the key feature of these treatments.
Lack of approval + length of use as medicine. There's a narrative that drug X has been used for 50 years (despite what it's used for) and therefore the pharma industry is uninterested in its success because they can't get rich off of it.
The latter is a common thread, along the lines of "what THEY don't want you to know."
But this makes absolutely no sense. Plenty of previously approved drugs, such as anticoagulants and dexamethasone, are part of the current standard of care; and their effectiveness has unambiguously been borne out by the data with multiple independent studies / analyses that all agree.
So why are THEY for these but against ivermectin?
Of course the whole idea of THEY is nutty. The idea that there is this level of coordination / cooperation among pharma companies is ridiculous enough to be the punchline of a joke.
You only make it ridiculous, it's actually really simple. Bureaucrats in agencies have their procedures and their agenda. Very little coordination is needed to ignore some controversial medication, associated with poor countries and antivaxers, when there are other things they can appear to be working on.
Many people sick with COVID are not getting this "standard of care" you suggest exists. Just tylenol and good luck. So those other drugs are not very far from ivermectin in terms of accessibility. All effective drugs are controlled and access is not given to the broad public, only to doctors and pharmacists, and many of these gatekeepers keep them from the sick people. You have to be lucky and have a good doctor who cares about you, not just about following what government agencies tell him to do. Then he may give both "unproblematic" stuff like heparines and also more "controversial" stuff like ivermectin.
Are these patients only being given Tylenol hospitalized? Because that would strain credulity.
The FDA regulates the marketing of drugs, not the practice of medicine. Physicians can prescribe whatever they want. Treatment guidelines are determined entirely by practicing physicians.
Uptodate is a good resource to check out if you want to see for yourself what clinical guidelines look like, and the type of evidence they are supported by.
All that stuff about access to quality health care is totally true, but I don’t see how it’s relevant. Ivermectin is being described as a preventative drug comparable to the actual COVID vaccines, not merely a treatment once you’re already sick.
"fully vaccinated individuals with breakthrough infections have peak viral load similar to unvaccinated cases and can efficiently transmit infection in household settings, including to fully vaccinated contacts." [1]
This study is for household transmission in an extended setting. That's not the same as transmission e.g. in an outdoor environment or for short, casual contact.
Vaccinated people are less likely to be infected, hence "breakthrough case." Your quote is like saying that "people thrown out of windows in car crashes have the same rate of injury, despite whether the person was wearing a seatbelt or not." That may be true, but wearing a seatbelt definitely reduces the chance of getting thrown out of a window.
Only if you are looking to reinforce your beliefs. Otherwise, besides the above two strategies, you should look at which study has better methodology (though it's usually never trivial, especially not for us, bystanders), bigger sample size, stronger statistical power.
If none of these seem to suggest a clear winner then you should just think that this is still undecided. You can also ask an expert. Choosing one and believing is basically just going with your suspicion.
And, If there is uncertainty (and there always is some small amount of it) then this does not support the parent commenter's strong and confident assertion that "do not, and never have" ... produced an effect.
> in the real world, we had our biggest outbreak after vaccines were mainstream
Is that supposed to be relevant? When "we had our biggest outbreak" there were/are still sufficient unvaccinated people to transmit an outbreak.
You're clearly defending a fixed point of view here. If you want detailed responses to learn from, stop asking for people to do them yet again and look for what already exists upthread. If you're having trouble finding it, start here: https://news.ycombinator.com/item?id=29124446
Surprise: get vaccinated. And now you'll say that "but you can get it even if you are vaccinated". Which is true, but of course less likely. How much less likely is known from the experiments.
As far as I’m aware, the experiments covered symptomatic cases but didn’t look at a reduction in “getting it”.
Based on this study, vaccinated had a 25% chance vs 38% for unvaccinated to become infected if someone in their household had Covid. So a helpful reduction, but not night and day.
Once infected, from what I’ve read vaccinated folks are just as likely to spread it.
Just because you don't line an answer to a question you posted it doesn't mean that's not the right answer. But it does imply, I guess, that you'll keep posting this same question and robbing others' time.
We've banned this account because it has been using HN primarily for ideological battle. That's not allowed here, regardless of what you're battling for or against.
Please don't create accounts to break HN's guidelines with.
That is observational data confounded by reporting and inadequate testing.
Go look at Singapore. 80%+ vaccination rate (Pfizer or Moderna), with regular mass testing.
About 65% of new cases are in fully vaccinated but the new cases are still stacking up. So yes it reduces the risk, but not by 7x. This is backed up by the recent Lancet paper which showed about a ~30% decrease in risk of infection.
They provide daily updates but have been changing the detail level and categorization to get away from pure case numbers.
Go back to late August to see the breakdown of cases across fully, partially and unvaccinated individuals. The vaccines clearly work prevent serious illness, but don’t seem to be slowing the spread that much.
The MOH used to also breakdown daily deaths into vaccinated and unvaccinated, but recently stopped. I suspect (and they confirmed a few cases) where the deaths are often fully vaccinated.
Of course they don’t want to provide data for the vaccine hesitant to call out, but they have been changing their narrative so often it’s starting to be a problem.
Interesting. Last detailed report is from Sept 07. Vax rate ~90%, 2-3k new cases, ~90% in vaxed population. The vaccine seemingly had no effect on infections?! Nothing like 6.8x likelihood.
So on one hand we have detailed data from UK and Singapore with breakdown by age/date/vax status and limited VE agains infection, on the other hand opaque charts (US...) with only aggregate numbers, showing 6-10x odds in favor of vax. The lack of detailed epi USA data conspicuously continues.
I did sanity check one UK aggregate chart touted in a sibling thread claiming, absolute numbers, unvax infections >> vax infections in UK. There were egregious Simpson's issues, all age groups >18yo had (significantly) more vax infections than unvax infections. The <18yo case load was a huge outlier, dominating the aggregate numbers. Fireable offense for a data analyst.
I’ve seen some really sloppy analyses. There was one in Canada that was similar to the US. It entirely ignored factors like vaccinated people never testing positive because they are asymptomatic.
The Singapore one isn’t perfect since those at higher risk of exposure (medical workers) tend to be vaccinated so that isn’t corrected for. But that would also disappear as you start to get most of the population vaccinated.
The linked video, https://www.youtube.com/watch?v=Hc7A1bVuSJU&t=56s, is misleading. It shows that the number of unvax cases is much larger than vax cases. I hope that by know it is common knowledge that the pandemic behaves very differently between age groups. Simpson's paradox abounds. The video only breaks down vax/unvax for aggregate numbers. This is a smell.
1. In every age group, except under 18, the number of vax cases is larger than the number of unvax cases, contradicting the video on its face.
2. Under 18 has a large case number, which dominates the totals. Some issues:
2.1. Schools have strict testing and tracing policies. The large case numbers may simply an effect of higher testing rates for the respective population.
2.2. Related to 2.1., there are two ways to count cases: PCR cases and symptomatic cases. In case of large case numbers outliers, the difference between the two measures can explain a large difference, though it is impossible to independently verify that a consistent measure was applied for all age groups.
2.3. Vaccination in 12-17 was only recently introduced. VE decreases over time. Studies disagrees by how much. At six months time, for Pfizer I've seen 55%-75%, from a high of 90%. Closer to the vaccination event VE is higher, thus the number of vax cases is temporarily lower. A more realistic assessment assessment ought to a. break down under 18 in to 0-5, 5-11, 12-17, and wait 6 months post vaccination campaign. Note that VE is also a somewhat misleading metric, 90% means 9/10 case reduction, 50% merely 1/2; a small percentage drop in VE at the high values mean a large increase in cases.
3. In some age categories, e.g. 50-59, unvax share of the cases is as small as 6%. Not sure (*) what the unvax rate in UK is for that age group, the reports says somewhere in the low teens, that number has been contested. But 6% is low enough by itself. If that doesn't make you wonder about the official line "unvaccinated people were 6.8 times more likely to get COVID-19 than fully vaccinated people.", then nothing will ever do.
Can't speak about US data because US is, for some reason, very tight lipped when it comes to publishing basic epi data with breakdown by date, age and vax status. If you have a link to the equivalent of the UK PHE vaccine surveillance report for any US state, please share.
(*) Apparently UK is not sure about the vax rates either, because apparently UK doesn't know how many people of a given age live in the country. That is a story for another time.
Thanks for linking to that report, it's interesting reading, particularly the part with "We present data on COVID-19 cases, hospitalisations and deaths by vaccination status. These
raw data should not be used to estimate vaccine effectiveness" (that sentence occurs twice so tat you don't miss it)
You should not expect ZOE study data to match UK Govt data exactly, they use different methods and check different symptoms. This is that theme that Prof. Spector talks about often.
"should not be used to estimate vaccine effectiveness"
Exactly. Neither should aggregate numbers that various US states and Prof. Spector use to spread fear, acrimony and stigma should be used to estimate VE, or mislead the audiences to estimate VE by themselves. Notice how the ZOE video you linked lacks the intellectual honesty to display the same disclaimer. His own website says "Incidence estimates were updated on 21 July 2021.". He's basically fabricating numbers, for all we know just as accurate as Prof. Ferguson. This is no better than the "antivax garbage" some people are so keen on summarily calling out.
Here are some longish term studies and preprints for Pfizer's VE against infection.
* VE against infection drops over time. Sadly, I am not aware of any reliable literature for VE after 9 or 12 months. Unfortunately Pfizer killed their own critical trials, which had a solid headstart, by vaccinating the control arm after 6 months. But the trend is clear, and worrisome.
* 80% VE => 1:5 infection odds. 75% VE => 1:4 infection odds. 50% VE => 1:2 infection odds. 12% VE, it's a wash. Numbers like 1:6.8 infection odds this long after the vaccination campaign are fantasy.
> Prof. Spector use to spread fear, acrimony and stigma should be used to estimate VE, or mislead the audiences ... lacks the intellectual honesty
This is a very bold partisan claim, in fact it is insult. It comes across as another Paranoid fantasy out of US politics, irrelevant to the UK. I'm no longer interested in anything that you have to say. Good day.
This ZOE business is something else. Their website is 75% building up their credentials, 25% promoting their app and 0% substance, e.g. what the actual formulas are or a link to code and data dumps. Or at least a research publication with some details. Perhaps there is a link hidden somewhere, but neither their Home, About or FAQ point to it.
They literally changed their formula because the trends in the unvaccinated population didn't to conform to their prior biases. Though the formula details are still a mystery.
"Last week, we reported a plateau in new COVID cases based on our methods at the time, which relied on a small number of unvaccinated people in our dataset compared with the wider UK population. The number of daily new cases in the unvaccinated group appeared to be dropping which in turn resulted in our overall numbers trending down. This meant the figures were accurate to our dataset but didn’t represent the full picture in the UK."
I'd say that this will appeal to people who are covid vaccine skeptical. If you're skeptical of the mRNA vaccines, you'd probably be in favor of this treatment than the vaccines.
I had one vaccine dose with severe issues. So maybe I'm skeptical, I won't get a second or third dose. Most people in this camp will just use ivermectin. Including myself, it works and is safe.
There is no evidence ivermectin works against COVID. There is still one large study running, I think, that might show a small effect, but definitely not a big effect.
That larger study is only doing three days of doses which unfortunately isn't enough in most cases.
I had a hardened blood clot surgically removed off my scalp the other day. Was in a vein right by my temple. When the report comes back confirming I'm hoping it'll get me a proper scan.
The scientific method generally doesn't prove negatives. In this case, a trial is done where one group is given ivermectin and the other is given sugar pills (placebo). Their health outcomes are compared. If you have enough people in the trial and there is enough of a difference between the outcomes of the 2 groups then you say you have evidence that ivermectin is effective.
The well run trials to this point don't show a significant difference between the groups. The ivermectin advocates say that the trials have not been run correctly for various reasons like dosage, timing, etc. More trials can be run to try to address these concerns. This can be repeated any number of times but at some point people will give up trying if no effect is found.
The antiviral mechanism of Ivermectin involves the inhibition of nuclear transport by importin α/β1 in the host. It can and has lead to death when improperly dosed.
I suppose some people would lump me in with "anti-vaxxer" because I don't want to get the Covid vaccine.
I'm not anti-vax, btw. I have a medical condition that requires me to receive regular vaccination against several diseases, and I'm strict about doing that on time.
I've made a calculated decision in the case of this specific vaccine based on that fact that I've now had Covid twice (first time was a bit nasty, second time was very mild) and have acquired fairly robust natural immunity.
According to almost all of the research I've read, natural immunity is at least as effective as the vaccine, which makes sense to me. Our bodies (if healthy) tend to be pretty good at this stuff.
The vaccine carries risk, all medical treatments do. When I calculate my baseline risk - very healthy, fit, no cormobidities, etc..., couple it with my acquired natural immunity, my chances of a negative outcome from Covid asymptotically approach zero. This appears to me to be less risk than the vaccine introduces.
I say all this to describe my mindset, I think a lot of people share it. Lumping everyone that choses based on a risk calculation to not receive the vaccine as "anti-vaxxer" is a common thing that people do (though I believe it is wrong).
All that being said, my primary point is that if I got Covid again, I'd absolutely be receptive to a therapeutic like this.
My decision against getting the vaccine was entirely risk based. At the point where I've contracted the illness again, however unlikely, the risk has been realized and I would 100% be receptive to taking this therapeutic if my doctor recommended it.
The thing is, you're not representative of unvaccinated folks. You're an extreme outlier. Most of them haven't done this research.
In my opinion, if you're nice and wear a mask in crowded conditions, don't go around hanging especially indoors in big groups, your position is kind of ok.
Though I'd still look at the numbers to check if vaccines reduce infection rates and rate of spread. Because if that's true, it might be worth getting vaccinated to protect others a bit more.
Your priors probably need updating as natural immunity as the OP describes appears to be much more robust, esp compared to the J&J after a year. Also vaccinated people spread delta, so everyone is getting it on some time scale.
Vaccinated people? Much less so than the unvaccinated.
Double vaccinated people are 60-75% less likely to catch even asymptomatic COVID. If infected, they are 50% less likely to transmit it onwards to others. These are Delta figures.
That happens in breakthrough infections, and the goal of the vaccine is to reduce the number of breakthroughs, which it does successfully.
From the Lancet study linked in the article:
> The SAR in household contacts exposed to the delta variant was 25% (95% CI 18–33) for fully vaccinated individuals compared with 38% (24–53) in unvaccinated individuals.
That's a misleading line, referring to peak viral load. If you read the rest of the article (or probably the study abstract), you will see vaccinated people are infectious for less time.
You > Your priors probably need updating as natural immunity as the OP describes appears to be much more robust, esp compared to the J&J after a year.
Me > Though I'd still look at the numbers to check if vaccines reduce infection rates and rate of spread.
Thankfully I said that already.
> Also vaccinated people spread delta, so everyone is getting it on some time scale.
That's not guaranteed, though. Just like not everyone on the planet will ever get all the strands of flu or cold or whatever. Through natural immunity + vaccinations at some point the disease can just die down and through a simple rotation you could avoid it (i.e. everyone else gets it at a time when you're not around so you're spared).
Plus the time scale is important. In November 2019 we didn't have any vaccines, now we have 4 that are approved on a wide scale (Pfizer, Moderna, J&J, AZ) plus a bunch of others with widespread usage but a less stellar reputation (Sputnik, the Chinese ones) plus another bunch coming soon <<and>> this very topic is about a drug for curing it. And another slightly less effective drug has also been approved recently, from Merck. That's... 24 months after the initial outbreak. Who knows what 24 more months will bring?
I hear you and your argument sounds rational. I wonder what do you think about receiving it for the sake of potentially vulnerable people around you. Just to reduce the likelihood of spreading it to someone who, unlike you, might be in real danger.
I personally didn’t mind the side effects, but mainly got it because I thought: What if I get Covid and give it to someone and something happens to them? And then I thought that it still worths the risk.
Of course no one should blame you if you want to care for yourself but I’m interested to know your feelings on this.
I encourage everyone eligible to get vaccinated to protect themselves against severe symptoms, but that does little to protect vulnerable people. Vaccinated people also transmit the virus. Since the virus is endemic and can't be eradicated, everyone will be exposed multiple times throughout their lives.
But apparently vaccinated people only transmit the virus if it’s a breakthrough case. If that’s the case then the transmission is reduced in more vaccinated populations compared to unvaccinated.
It interesting that some people even when faced with such an articulate and easy to read article still resist understanding it so that their beliefs are not challenged.
It’s rational argument especially now that we know vaccinated people spread this endemic virus.
Your mindset should be: everyone is going to get this, probably multiple times in your life, vaccines reduce the symptoms, but not as effectively as having survived covid.
Maybe if they're hesitant for irrational reasons. But if they're hesitant for rational reasons, mRNA vaccines and modified adenovirus vaccines are both new for mass use.
There are some inactivated virus vaccines which would be best for people who want to avoid new vaccine types, but AFAIK they haven't even been tested in the US.
Or they'll say that the supply chain issues have forced the US to start using larger 5G spyware-mindcontrol whatevers, so they now they need people to take a pill.
Or that big pharma wasn't making enough money off ivermectin, so they invented a new pseudo-drug or something.
When you believe that core institutions are worse than inept and actively work against you, you can justify anything. I'd call it a coin toss whether they're for or against.
I have bad news for you (unless it was irony, which I can't rule out): the SARS-CoV2 virus contains its genome as RNA that is used directly (IIRC) as mRNA. Because it's needed for the protein synthesis to build new virus particles. This is true for every virus, BTW: they either contain RNA that can be used by the cell for protein synthesis (i.e. mRNA) or they do synthesize (or make the cell synthesize) the mRNA based on their genome, one way or another.
So no matter what, you'll get the viral mRNA in your body. Either through infection or through the vaccine. The vaccine just contains a small fragment and it does not proliferate. Unlike the virus.
mRNA has potential to be dangerous. There is nothing inherently dangerous in what our bodies already use as building instructions, nor is there evidence to suggest current mRNA vaccines cause any of these theoretical issues.
Yeah, plus on top of that, anything has the potential to be dangerous. Take, for example, water. Everybody knows about its positive sides, and about most of the negative ones.
But 99% of people don't know that water can kill you. I'm not talking about drowning.
> My fear is that a lot of people won't bother with a vax if they think there's a 'cure'.
Interesting. Indeed, should people bother with a vax if there's a highly effective cure? Is it worth all the teeth-gnashing and hair pulling on the part of the medical establishment, political establishment and media about people who would rather get COVID than get the vaccine? IMO this cure (once it starts rolling out ofc) is a reason to start rolling back vaccine and mask mandates rather than impose more mandates.
[Disclaimer: Fully vaxxed, will take a booster, etc]
"should people bother with a vax if there's a highly effective cure?"
Yes. COVID danger is it's virality, not it's lethality.
100% vaccinated population even at only 85% effectiveness means R0 is well below 1 and COVID cannot spread.
100% of COVID patients treated at 85% effectiveness of antiviral therapy means probably well over 1/2 the population still gets COVID, that's devastating.
If this were about a non-communicable disease, then probably the vaccine would be a slightly better idea, but due to virality there's no doubt vaxxes are better.
The best is to have both.
Finally, the vaxx is $20, antiviral is $700, which is material.
That said, if the 'cure' were 100% perfect, no side effects, cost $1 and could be given at any time after infection and prevents any further adverse effects, then we could probably just settle on that if we had to.
I don't suspect we're going to hear a lot about this in the press, because the 'narrative' still needs to be 'get vaccinated'. What will happen is the CFR will come down to to this and other measures behind the scenes so to speak.
Unless this thing comes down to $50 and is something any doctor can prescribe willy-nilly easy-peasy in which case I think there would be a big media campaign to 'inform us'.
Then you have the issue of people continuing to spread it to those who can't take a vaccine, including the immunocompromised.
There is also the worry of the effects of long covid. Just yesterday I was reading a thread on here of people complaining about experiences of their loved ones with long term covid after effects not being able to find relief from doctors because, well, we still don't even know what causes it. Better to avoid an infection that let a virus ravage through your body hoping medication can reverse all the effects on the body
> spread it to those who can't take a vaccine, including the immunocompromised.
I agree we should get vaccinated to reduce spread but, good news, this is wrong. UK clinical guidelines[1] state the immunocompromised and the immunosuppressed should get vaccinated.
In fact, they basically recommend everybody be vaccinated. Pregnant? Yes. Mild allergies? Yes. History of anaphylaxis caused by a specific ingredient in the vaccine? Speak to a a specialist who should offer (where possible) an alternative vaccine.
Moreover we know two doses of the vaccines produce an antibody response in the immunosuppressed.
That said, three doses is a good idea[2] to boost that response to a more typical level.
I think the main difference is one has to necessarily take on vaccine risk without catching covid, so you balance chance of vax complications vs chance of getting covid multiplied by chance of getting bad case of covid.
So 1 * P(bad vax) vs P(getting covid) * P(bad covid case).
While most of other proposed treatments are after you already got it.
So P(bad side effects) vs 1 * P(bad covid case).
Depending on your priors and health, those balance very differently.
Also, if the new pill ends up as effective as they say it is, there is no reason to push for 100% vax uptake anymore -- it would turn covid into a slightly more dangerous cold.
1) There really is no such thing as 'Vaccine Risk' in the material sense, any more than we would us language such as 'Flying Risk'. Esp. in the US where thee is no AZ vaccine, the risk is negligible.
'The Vaccine Risk' in the minds of many people isn't consistent with the reality, and it's a major communications problem.
Anti-vaxxers are internalizing and propagandizing a degree of risk that just isn't real, leading to bad health outcomes.
Sure, technically, it's a risk, but so is anything else.
2) 'No push for 100% Vaccine' - maybe not for '100%' but we really need to push hard on vaccines.
COVID is not scary because it's excessively deadly. It's scary because it's excessively viral, meaning, it's a community disease, less so an individual disease.
Stopping COVID means stoping the spread, not trying to cure people when they get it.
With 95% vaccination, R0 drops below 1 and so hospitalization rates are low, we can focus on the hard cases.
With 0% vaccination and a 85% effective drug, well, 'everyone' will get COVID, and a scary number of them will die.
The 'Best Answer' by far in a world where vaccines are very safe, very cheap, and very effective - is to get 'as many as we can' vaccinated. And then use the expensive drugs on the hard cases.
Most people see themselves as healthy and thus in the pool of "very unlikely to have complications from COVID-19" pool. Argue with that however you want (people being dishonest with their own perception of health), but that's how they see it.
So taking preventative measures because it is forced down their throats seems hostile. Made worse that 1) vax won't stop the spread, or we would have seen that by now, and 2) we need to boost the vax every few months? That sounds highly suspect to a lot of people.
If you were at risk, you can get vaccinated, why force a healthy person? (The answer is mostly for the folks who can't vaccinate, but those folks are screwed any way you look at this pandemic if we are honest).
No, the vaccine is fairly detrimental to the spread of COVID.
Overwhelmingly, the numbers of people in Hospitals are unvaxxed.
In BC, the last report I saw for a region had almost 100% of people below 50 in intensive care unvaxxed, almost the same numbers for seniors.
Rates of spread are actually coming down even while business activity expands, vaccines are a potent part of this. Not perfect, but a major component.
So again: COVID is a community problem, less so an individual one. 'Stopping the Dominos' from dropping is much better than trying to lift all the dominos up after they fell with drugs.
"So taking preventative measures because it is forced down their throats seems hostile."
It's not hostile to the 80-90% of people in most advanced nations who have basic civil maturity. It's a mild distraction with obvious individual and group benefits, to the point where I have a hard time understanding lack of participation (yes, it's very easy to understand hesitancy and hostility to being required to do something, but not to the level where people actually would avoid doing something obviously beneficial).
I remember when smoking was banned indoors, I get that people were a begrudged, but I think in reality most people 'got it'.
Not to mention, everyone I know knows at least one person who had a stroke within weeks of getting one of the "vaccines", I know three. Previous to this past year I've known one person in my entire life that had a stroke, and it was my wife's uncle who was in his 90s.
My friend's mom technically died in a clinical sense 5 minutes post first jab while still in the parking lot under observation. My other friend's brother dropped dead exactly 36 hours post 2nd jab. Both were zapped back to life. One of them had a pre-existing heart condition.
I know at least one ER RN that readily admits they're seeing a high increase in ER cases of young (20s) people with various neurological and cardiac issues 1-14 days post vaccine (and are almost never treating them as vaccine-caused issues hence they stay unreported). The apologists will say things like "but you don't know it was the vaccine". Sure, you're never 100% positive about anything dealing with as complex system as a human body. What you should do is start with "what has changed recently", and almost always the patients that my RN wife handles say "I've been recently vaccinated.".
You can't do stats like this. Even if it seems like a small error or being overly pedantic, it doesn't work for a pretty large number of obvious and less obvious reasons.
Vaccine side effect tracking is done pretty thoroughly, so if what you see would be a real and generic phenomenon, it would have been noticed by now.
Right. The official estimate by the CDC is that 1 in 40 vaccine injuries is reported.
None of the 3 I personally know were (suppose that's just anecdotal also). The one received the second dose 3 days before a major stroke, and massive blood clots. I'm sure it was tOtAlLy UnReLaTeD.
Nobody can tell you based on one case whether it was related or not. That's the point. And that's why they have to report every death or serious injury within 30 days of vaccination. At least here, in the EU. No matter what. If you get hit by a bus, it should be reported and recorded. Exactly because there is no other way to find rare side effects.
> The official estimate by the CDC is that 1 in 40 vaccine injuries is reported.
All risks are relative, yes. Covid risk is also negligible for some groups (like small children), it is very likely very comparable or smaller than the tiny vaccine risk. There is a lot of propagandizing degrees of risk across all tribes -- democrats wildly overestimating risk of hospitalization and republicans wildly underestimating it.
But what about 75% vaccination (lots of countries are there already or very close) and 85% effective drug? How much effort much be spent on hunting down every last antivaxxer and how many side effects of that are acceptable? (like destroying public support for vaccine mandates in general, creating nice shiny tools for the next wannabe authoritarian, etc)
For endemic viruses that also spread through domestic pets 95% becomes unobtainable unless we start going after the 100,000,000 domestic pets in the US alone.
We don't know the likelihood that it spreads through pets, pets also have owners who make up the entirety of their interactions (ie pets don't take the bus, go to restaurants, go to work or school) so of owners are vaxxed we're kosher.
As for endemic, yes, a problem, but of a different kind.
> one has to necessarily take on vaccine risk without catching covid
Thankfully that risk is tiny.
> Also, if the new pill ends up as effective as they say it is, there is no reason to push for 100% vax uptake anymore -- it would turn covid into a slightly more dangerous cold.
No, vaccination remains far cheaper. Mass vaccination also reduces the risk of mutation, and of infection others.
If everybody gets vaccinated AND this anti viral is widely available for those infected, COVID will be well and truly deranged.
> Mass vaccination also reduces the risk of mutation, and of infection others.
Only if the vaccine is effective enough. With these moderately effective vaccines, there is a danger that breakthrough cases will generate new variants.
> Moreover, no, emperical evidence shows the neutralizing antibody effect of vaccines decreases the spread of variants.
The world started vaccinating in January - 10 months ago. You won't even begin to know the true effectiveness of the vaccine and its outcomes until at least one more year goes by ey? Then you can begin to compare year over year health outcomes in highly vaccinated groups, vs unvaccinated, in the same region (same viral seasonality profile), across age groups. I can't wait to see regional all cause mortality with accurately age (and other vars) adjusted data between the vaxxed and unvaxxed.
This is true, however we are pretty certain about the numbers and they are overwhelmingly point towards getting the vaccine. (Maybe except for the very young, by witch I mean under 25 maybe under 20. But I don't know those numbers, so that might even not be a question either.)
One thing to keep in mind is that P(getting covid) is about 1. But for sure greater than 50%, especially if people don't vaccinate in large numbers (I mean others, of course) and if we do away with masks and restrictions.
When doing this kind of comparison, vaccines are tricky, because if you vaccinate close to 100%, then you'll have very few cases, so P(getting covid) will be rather small and then it will seem that the vaccines may not be worth it. But if you don't, then it will be high and that's what you should base your decision on. BTW, this is why antivaxxery could become such a phenomenon lately (even before covid): too few children died or got paralyzed in the past quite a few decades so the usual diseases somehow started to seem not such a big deal. Because people just didn't experience the other side of the equation anymore.
Also, on a side note, I'd expect that an antiviral will have more side effects than a vaccine.
This is also the same line of thinking that pushes for more knee replacements than dietician and gym trainer appointments. For some reason preventative thinking is alien.
And unfortunately the window for this closes before a skeptic will get desperate. Once people go on a vent they appear to become open minded to other treatment options.
> As a protease inhibitor, Paxlovid is free from the theoretical DNA-alteration risk tied to the mechanism of action of Merck’s molnupiravir.
This is the line I was looking for. Not that I know how protease inhibitor works, but looks more like a traditional anti-viral approach v.s. the potentially DNA altering molnupiravir.
In brief, coronaviruses make all their proteins as one long chain and then cut it up into the appropriate pieces to form the proteins (spike etc). 3CL protease is the cutting machine and Paxlovid inhibits that.
It's interesting to learn about. Other molecules are also found to inhibit replication of 3CL protease in SARS cov-2 [1].
The UK scientific advisory group SAGE published a few months ago that combination therapy might be useful to avoid 'antiviral resistant' strains of SARS cov-2 evolving. Perhaps these 3cl protease inhibitors may be used in combination.
Unfortunately in the UK there has been political pressure to do absolutely anything (no matter how questionable - e.g challenge trials) that isn't imposing even the slightest restriction.
> [...] patients who received Paxlovid within five days of symptom onset [...]
I wonder how well it will do on people who are farther along in their COVID infection?
There are a lot of people who don't get vaccinated, don't take precautions to avoid COVID, dismiss their early symptoms either because they believe COVID isn't worse than a typical cold or flu or because they think that is probably what they have, just treat it at home with vitamins and ivermectin if they do anything at all about it, and don't end up going to a doctor or hospital until they are having so much trouble breathing they have to go to the emergency room.
I wonder if having an effective oral antiviral readily available will result in someone who would have acted in the manner you suggest seeking this treatment instead.
Because theres no reason to believe it does. Firstly the study that Ivermectin-for-covid is based on in vitro(cell-in-petri-dish) studies of rhesus monkey liver cells[1]. Additionally. Rhesus monkeys have differing bodies sizes and in order to get an equivalent dose in humans would require overdosing on ivermectin, which can and has lead to death. Ivermectin targets the host nuclear transport importin α/β1 heterodimer in host tissue, exerting effects directly on cells of the human body.[2]
On top of this you refer to 'long covid' which has nothing to do with the covid virus itself. Long covid is the syndrome after a person gets over a covid infection. They're not entirely sure what causes it, but damage to internal organs and the venous system have been observed[3]. At this point there is no active viral infection in your system, inhibiting viral replication is basically irrelevant. There is absolutely zero reason, even according to the logic of ivermectin-for-covid, that ivermectin would treat that damage.
Well it felt like I never really got over it. Aside from a brief period of fever, everything else stayed until ivermectin. Headache, fatigue, sob, cough, sense of smell issues, brain fog, all kinds of erratic heart problems. There's a lot of speculation that long covid results from the virus migrating into the body and organs where it persists. This makes sense with what I experienced. Symptoms I've never had before went away within hours and cleared up completely within days of starting it.
It was three months of hoping it would get better with no movement. Then five hours later I could breathe again. So physical stuff happened. I get that placebo effect can do this but still. Coincidence would be rare and I don't think long covid resolves that way, been told it is more gradual. I've heard a lot of similar reports on a covid telegram channel I'm on, same with reddit before it got overrun with trolls. You can tell genuine discourse, especially when its the same people over several days going through the same experience.
None of this is scientific. What was is the safety on it so that made it low risk to try.
So no we have the Pfizer vaccine (which I got) who cuts the risk of both catching the virus and the risk of severe complication by a lot (forgot the number but it's big) and in addition to that we now have Pfizer oral medication that can be given to positive cases and which reduces both hospitalization and death risk by 85%.
Old normal is gone and will never come back - instead we are building a new normal, but it will take at least another year or two to solidify. It probably will be similar to what we had before. It's kind of like after 9/11 - we wanted things back to normal, too, but that old normal never returned.
It's impossible to plan anything further than 2 weeks ahead with a relative certainty that things will go through. How is that 99% normal? The uncertainties around things considered "normal" is extremely high. Wearing a mask is not normal, yet still very common (and mandated again as of today in The Netherlands).
Going through extensive testing and requiring proof of vaccinations for a thing as simple as going to the zoo is also not 99% normal. I have two trips abroad planned in the next 3 months, yet chances are high that I won't go to either due to external circumstances.
People with potentially life threatening health issues such as brain tumors are seeing their treatments postponed. Excess deaths are still very high in many countries, even with high vaccination rates.
Have you tried travelling abroad? It’s still much more complicated than it was, you have to check both countries requirements, spend money on tests, fill additional forms
I feel sorry for those in the US. You have made a miserable new normal for yourselves (and, as you say, despite everyone dutifully wearing masks and getting vaccinated, and now having the option of an effective treatment).
Edit: you've been posting like this a lot. Can you please stop that? It's not what this site is for, we ban such accounts, and I don't want to ban you. If you'd please review the guidelines and fix this, we'd appreciate it.
> Pfizer used data on patients who were treated within three days of symptom onset as the headline finding in its press release
> There were six hospitalizations and no deaths among the 607 patients who received Paxlovid within five days of symptom onset, compared to 41 hospitalizations and 10 deaths in the placebo cohort.
> Like Merck, Pfizer excluded people vaccinated against COVID-19 from its late-phase study.
No pricing information. I'm worried that "3 days after symptoms onset" is too short to be usable in real-life, but I could be wrong.
Yahoo news[0] and other news sources report significant efficacy even at the 5 day mark.
"Rates were similar for patients treated within five days of symptoms - 1% of the treatment group was hospitalized, compared with 6.7% for the placebo group, which included 10 deaths."
"The U.S. government has been in negotiations with Pfizer for enough pills for 1.7 million courses of treatment, with an additional option for 3.3 million, according to a senior administration official. That is about the same quantity that the United States has ordered from Merck. The government expects to pay about $700 per treatment course for both drugs, the official said."
Monoclonal antibody treatments are also commonly administered about 3 days after symptoms onset. They have proven to be somewhat effective in real life, although they still aren't being given to some patients who could potentially benefit.
The monoclonal therapies are also administered by IV in a clinical setting, whereas this can be taken at home and could probably even be delivered. It should be even easier to make it within the three-day window with this treatment.
If the cost is low enough and the side effects are mild enough it could work. People would take it before a test is positive so would end up taking it when they didn’t really need it.
It’s similar to the antivirals for flu where you need to take it early on so it becomes habit to test early and start early.
Home labs will help with this too. Where someone could take a test, get a prescription and pickup within a few hours.
A useful comparison. I have never taken Tamiflu because I know I’d need to haul my weak, shivering, flu-infected self through public to see a doctor to get the Rx, go to the pharmacy… all for the personally-uncertain benefit of Tamiflu.
Nowadays, this should be easier with so many virtual appointment options and delivery services. It should be, but is it?
There should be an app that does all of it for you.
1. Scan your insurance card.
2. You get notified when a doctor is ready for your virtual visit.
3. If appropriate you get the Rx written.
4. That day, some delivery service will bring you the Rx. 5. Maybe a testing service stops by as well.
Insurance companies should want to participate if it decreases Flu or Covid hospitalization for a reasonable cost.
Anyone want to make this happen? My fall classes are nearly all finished.
Edit: Pharmaceutical companies may wish to partner as well. Lots of avenues for this kind of service to find revenue.
1. You're minimizing the 2 hardest parts of doing anything medical, which is the insurance billing and state licensing requirements. The state may consider you a medical services provider even if all you do is pair people with already-certified medical professionals.
2. "That day, some delivery service will bring you the Rx." This sounds illegal or heavily licensed/regulated. It's a drug addict's dream because it's so easy to maintain multiple identities. You probably get a random doctor, so the doctor won't notice it's you with a different name. And then they even send a driver to pick up the prescription, so the pharmacy won't notice that it's you with a different name.
The pharmacy would also likely need to be in on it. I.e. in Texas, pharmacies that deliver are required to include any information that would have been given orally as a written document with the prescription. If the pharmacy doesn't know it's being delivered, they won't know to include those.
If you wanted to partner with someone, it would be CVS or Walgreens, though. They already have licensed pharmacies everywhere, and handling the pharmacy requirements are going to be the hard part. I believe they also own a lot of those tiny clinic chains that are inside grocery stores, and this would give them a way to fill in any downtime in the nurses' schedules, as well as to let them soak up excess demand in one area with slack in another.
All important questions to figure out. Definitely not minimizing either of these two points.
I have a lot more thoughts about this and everything you wrote that comes together compellingly as a nascent business strategy, and I’m not exactly naive in this domain. My first real software job focused on medical billing and insurance complexities in one of Epic’s two accounts receivables applications, but that’s really only the beginning of it. Happy to chat and discuss further. You can find my contact info in my profile.
> It’s similar to the antivirals for flu where you need to take it early on so it becomes habit to test early and start early.
Are you actually able to get tests? I've brought my kid into urgent care and they won't test for flu, so it doesn't matter that there's a drug available, because they won't test.
Patients enrolling in a clinical trial know they may get the placebo control. It wouldnt be more ethical to give it to all patients as in the case the medication does have a side effects you are only guaranteeing everyone gets hurt.
As House put it--
>Just to shortcut this discussion.. People should not be testing drugs because they're desperate. But, people won't test drugs unless they're desperate. We need drugs to save children and puppies, ergo we need desperate people, ergo welfare kills sick children.
It's almost as if we could just let people make and live by their own medical decisions. We've got one case in recent history of an argument about "you're making decisions that affect me", and it turns out that this entire argument is bunk because the "vaccines" do not prevent the spread. So it's purely a personal decision about your own health.
And pertaining to clinical trials, if I want to sign up for a clinical trial for a what might be a placebo for a great white shark bite in the midriff, that's my own choice. If I die because of this choice, that's my fault.
If you take an antiviral like this, do you still develop a good immune response to reinfection?
I wonder because almost everyone who might end up needing this isn't vaccinated (based on hospitalization rates) so I hope that at the end they also end up having some immunity to catching it again at least.
In the moment of course it is better to use than not.
You should -- protease inhibitors inhibit replication, but existing viruses should be more than enough to generate a durable response in most individuals.
Anyone taking this should still develop an immune memory to covid. As I recall, even people who took monoclonal antibodies (that is to say, an antiviral where they literally inject functional anti-covid antibodies into your veins) developed some degree of natural immunity.
No. There's a big difference between drugs and vaccines. The drug doesn't generally illicit an immune response, but the vaccine is designed to do exactly that.
With antibiotics, it is possible to kill an infection without developing a full immune response, leaving the person susceptible to reinfection. Even if that infection is symptomatic and has been going on for days, the immune response still may not be robust enough before the antibiotics kill off the infection. Not sure if that also occurs with anti-virals.
While this looks like potentially great news, Pfizer really needs a new Head of Making Up Drug Names. Paxlovid! Between this and ‘Comirnaty’ (the vaccine) it is clearly not their strong point.
trifluoroacetyl is a pretty stable substituent, as far as the fluorines go. trifluoromethyl as a substituent is a classic "medicinal chemist's favorite" and will not be labile. for example: efavirenz, fluoxetine, celecoxib all have a TFM. It's true fluorine chemistry is generally tricky, including some organofluorine chemistry, on the other hand in this case trifluoroacetic acid, trifluoroacetyl chloride etc are commercially available, affordable and common so no issue to make the trifluoroacetyl amide at some point.
anyway for me this is a really nice "medchem" friendly compound.. i like the little oddball bicyclo[3.1.0]hexane ringsystem in there (the part that looks like a pentagon fused with a triangle).
I'm fairly certain that all of those compounds derive from some fluorine gas that was incorporated into the source molecules.
The molecule I worked with in grad school, 5FU, contains a fluorine, it's a very effective anticancer drug which ultimately came from fluroacetyl which is highly toxic. In fact most of the molecules I worked with in grad school that had fluorine were toxic specifically because of fluorine. Not because they were unstable bonds, but because F is very effective in nucleoside analogs. So you can imagine why I am a bit wary of F and just in general don't think of F as being particularly compatible with life.
I think I get what you mean but I don't agree on all fronts.
1. that compounds derive from some difficult to handle gas is only a problem for the process chemists. In this case because the TFA-based precursor is available this is not a problem. Though technically, the production of that commercially available TFA will probably have involved F2.
2. Though indeed there are quite a few toxic compounds that incorporate fluorine, such as 5-fluoro-uracil, fluoroacetate etc this is not quite a general rule, as there are also plenty of non toxic medicines and materials that incorporate fluorine. It seems decently compatible with life compared, certainly compared to some other elements or classes of compounds generally.
3. specifically concerning nucleoside/-tide/-base analogs I wouldn't quite pin their cytotoxicity on fluorine, as a class these will tend to be toxic because they are similar enough to nucleosides to get where they need to be but dissimilar enough to cause problems and make systems that deal with nucleobase derivatives malfunction. Instead of 5-fluoro you can also put 5-iodo, 5-TFM, sulfur, alkynyl, etc there and get antiviral like, cytotoxic compounds
In any case, when it comes to this specific pfizer drug, I would say the presence of some fluorines is not a production problem and certainly not a toxicity red flag. For example, Derek Lowe, whose amusing post on some of the more dangerous fluorine chemistry you cite, also has the following to say about fluorine and medicinal chemistry:
"We med-chemists just love our fluorines - as long as we don't have to use, like, fluorine itself to make them - because they armor-plate parts of our molecules against being metabolized and can change the binding profiles of the parent structures like nothing else can."[0]
It's stable, but the chemistry to get there isn't trivial. https://en.wikipedia.org/wiki/Organofluorine_chemistry
(my Organic Chemistry class was more than 25 years ago, but I did research on drugs containing fluorine in grad school; we had to parameterize the force field specially, the bond has a ton of energy in it,
When I wrote my comment I knew somebody was going to come along and think I was implying CF3 was explosive.
Exactly what I was thinking, especially for an entirely novel molecule. I wonder how novel the scaffold is. Whichever med chemist led this initiative is an artist -- amazing job.
it's not hard to find other molecules with similar scaffolds. Simply train an unsupervised network (autoencoder) over SMILES strings taken from ZINC. Convert your molecule of interest to a vector using the encoder, then find N nearest neighbors and decode. Those molecules will likely have similar scaffolds.
There are other methods, graph substructure similarity is common.
More to your actual question, it was derived from a previous attempt (https://en.wikipedia.org/wiki/Lufotrelvir) which has a very similar structure, and I wasn't able to find prior information by doing a little literature searching to see if there are other similar compounds.
Right, it's not technically difficult to match a scaffold -- you can probably parallelize a big RDKit job, but it's nontrivial to scale to a gigascale set. And, like you mentioned, there's rule-based substructure matching (sometimes easier for those willing to venture a bit outside SMILES). Anyways, it was more a curiosity question -- thank you for the details on Lufotrelvir!
you wouldn't run a big rdkit job, you'd just featurize all your molecules and then do vector comparisons. lots less CPU but a big risk of false negatives.
what does 'featurize' mean here? do you mean fingerprint feature vectors? IIRC, the computation time to get a fingerprint vector vs. extracting a murcko scaffold are pretty similar, although it depends on the fingerprint.
I hope this proves to be real going forward. The vaccination route seems to be hitting a deadend as a way to end the pandemic. The pill will have to be cheap and available over the counter, it makes no sense not to subsidize this.
There is catch for antiviral drugs - like antibacterial drugs, they can lead to selection of resistant strains. Therefore, we can't just give it away to everyone without any control.
we re already doing that with vaccines which are given to more people. Besides this does not stop the virus from transmitting, but it mitigates its harmful effect
> compared to 41 hospitalizations and 10 deaths in the placebo cohort
This makes me weirdly sad. Can you imagine entering the trial for a long sought drug against a deadly disease that turn out to be working, and end up in the control group? I know that there's more to it (it's necessary, they knew, it could have not worked, plainly be nocive, etc.) but it's like being unlucky twice in a row and die out of that while having received the real thing would have saved you
It is sad and unfortunately needed. You will note they stopped this study at the first “interim analysis”. One of the really important reasons such interim analyses are done is precisely to stop a trial when it so obviously works. They then switch anyone in the placebo group to the real drug.
It is difficult to overstate just how much thought and argument has gone into clinical trial design in the last half century. It may seem detached and unfeeling, but basically every step is carefully considered compassion, ethics, and a desire for unambiguous causal truth of drug effectiveness.
Some patient next to them are not even offered to be part of this draw, and winning this draw (i.e. getting the real medicine) may lead to severe adverse effects.
It would be unethical if this placebo was given in place of a known working alternative treatment.
> It would be unethical if this placebo was given in place of a known working alternative treatment.
From what little I know of cancer treatment, that isn't how studies are generally run. When you're part of a trial, you're either given the experimental treatment, or the "standard of care", not a placebo.
So for cancer at least, you're either getting a novel treatment, or standard chemo.
This is Pfizer’s antiviral drug. Merck’s drug might be effective as well, but if seems like to be also a drug with many side affects interfering with your genome.
Getting vaccinated looks like a better option to me. Anyone know if the Pfizer one works similarly?
Note that to make the overall risk of adverse effects from covid19 lower, any treatment that is taken after the onset of symptoms must be much more effective at preventing adverse effects in symptomatic patients compared to a vaccine. This is because the vaccine greatly reduces the probabilty of symptomatic infections, while the other treatments do not.
To mention it, not necessarily directed at you. Larger test groups are required when trying to distinguish between less effective treatments.
If rabies has a 99% death rate and you try your rabies treatment on 10 people, 9 of whom live, that's much stronger evidence than a situation where 50% of people died without treatment versus 48% with treatment (sample size 100). To be confident it's not just random chance, you'll need a really large sample size for the 2nd situation.
This is a randomized clinical trial; participants are recruited into the study using methods that eliminate the biases associated with self-selected participation, like internet or TV polls. You can get statistically valid results from small samples, that apply to very broad populations, using this methodology.
Wikipedia suggests they first tried it on a lethal cat coronavirus. And the enzyme it inhibits, 3CL, is found in all coronaviriae. So one suspects this works against most coronaviruses.
Did anyone hear NPR's reporting on this? They said the early study was originally halted BECAUSE of it's positive effects at preventing hospitalization and death... very weird, I hope it is a typo or I'm understanding it wrong...
I didn't hear the NPR story, but studies can be halted when it's shown that the treatment is so clearly effective that it becomes unethical to continue administering non-treatments/weak treatments to your comparison groups. This usually indicates that research can and should advance to the next stage immediately.
I haven’t read anything about this study, but this is common for highly effective treatments.
Let’s say you have a randomized clinical trial with a control arm (placebo) and test arm (drug). If the vast majority of the test cases do significantly better (like 90% of the test cases), at some point it becomes unethical to continue. Why? Because you already have the evidence that the treatment works, so having the control arm becomes meaningless. You already know that the drug works, so there is no longer a point to collect more data AND you know that the control arm isn’t going to help half the patients. So, you stop the trial early so that you can get started with the approval process so that the drug can get to all patients faster.
Pardon my naive question, but aren't there more objectives for the clinical trial? Particularly testing for negative side effects? How are those judged if the trial is discontinued?
This was a phase 2/3 trial. So there was some side effect data collected, but enough people went through the trial to see any large/common side effects.
I generally think of the phases like this (this is just how I think of it):
Phase 1 - is it safe? If you don’t see severe toxicity then you can go to phase 2.
Phase 2 - does it work? You look for good outcomes (cures, better survival, etc). If there is significantly better outcomes relative to placebo, then go to phase 3.
Phase 3 - does it work for a large population? What is the appropriate dose? Dialing in the numbers before public release.
Phase 4 - after you’ve made the drug public, monitor the larger population for side effects or adverse events. You can’t hope to cover all patients in a phase 2/3 trial, so you keep monitoring the first waves of patients that get the drug.
Safety continues to be evaluated during Phase 3 (and after approval), but trials don't proceed to Phase 3 without establishing some reasonable baseline for safety in the earlier phases.
Data on the most obvious side effects are collected in the first phase which is a very small group of healthy patients who take the drug under medical supervision in increasing doses until the side effects are so bad they can't keep going. They use this data to establish safety limits for the rest of the clinical trial and continue monitoring the situation until well after the drug is approved.
To be cleared though, both arms or the trial are people who have COVID. The control arm is not getting the drug. If there are side effects that occur in some combination with having COVID, they will find those.
That’s correct. If a positive effect in the treatment arm of the study is found to be strong enough, it is deemed unethical to continue giving patients the placebo as control. Hence, they terminate the study and proceed to the next phase of approval
That it's unethical to continue giving half the participants a placebo makes sense.
I am curious though: do they ever continue with the trial, with the patients on the actual drug? Might that be useful for monitoring rare-ish side effects, even if the drug is highly effective?
I believe they've only halted recruiting for the trial, not the trial itself. The Pfizer CEO this morning also said they're continuing with plans for two other trials starting soon, which is in people with non-co-morbidities, and to household contacts of confirmed cases.
Presumably they're kicking the placebo participants out? As others say, it is not ethical to give them ineffective treatment (placebo), given the effectiveness of the drug has been clearly demonstrated.
Maybe they meant that further study at that level was not necessary and they were moving on to later stage trials? In order to speed up the release I mean.
When something obviously works, it's standard practice to halt the study and seek out emergency use authorization.
> There were six hospitalizations and no deaths among the 607 patients who received Paxlovid within five days of symptom onset, compared to 41 hospitalizations and 10 deaths in the placebo cohort.
> There were six hospitalizations and no deaths among the 607 patients who received Paxlovid within five days of symptom onset, compared to 41 hospitalizations and 10 deaths in the placebo cohort.
I know it shouldn't be shocking but it just hit me that being in the control group here is very close to getting a death sentence. I couldn't find it in the article OP shared or the press release, but did the control group get any other treatment?
Sometimes the experimental drug has unexpected side-effects or is less effective than the placebo. Both sides of the trial are a gamble. It is a trial because literally nobody knows for sure what the outcome will be -- only an informed guess that the new treatment is a good idea.
When trials are extremely effective, they are sometimes halted and rolled out early. That sounds like exactly what Pfizer is attempting to do here. The company thinks that they have a clear-enough signal to be worth going to the press and preparing FDA for the EUA.
Pfizer will have made an embarrassing error if the final trial-results turn out to differ with their claims, but if they don't, then Pfizer has given a several-week head start to rolling the drug out to all patients.
While I haven't read this particular study, the standard way to do a trial like this is to compare against the current standard of care, not no treatment.
10 deaths in 600 is not quite a death sentence, in my opinion. And yes, placebo group always gets current standard treatment, it would be rather wrong to do otherwise.
For sure, but in this case, not taking the chance guarantees you the "placebo", or standard care, meaning you'd be in the same boat as if you'd entered the study and received the placebo dose.
> There were six hospitalizations and no deaths among the 607 patients who received Paxlovid within five days of symptom onset, compared to 41 hospitalizations and 10 deaths in the placebo cohort.
How does this work? You sign up for the program when you're sick and you might get meds that help you? That would really suck if a loved one was in the program and died because they happened to get the placebo.
> That would really suck if a loved one was in the program and died because they happened to get the placebo.
Trials like this are performed in desperate situations, and you only ever hear about the success stories. Most such trials probably result in no measurable benefit, and run the risk of an even worse outcome than the placebo.
It's unusual but not unheard of for trials to be stopped ahead of schedule because of this - the treatment is so clearly and substantially beneficial it's considered unethical to continue depriving the control group of the treatment.
When to Stop a Clinical Trial Early for Benefit: Lessons Learned and Future Approaches:
How does it not apply here? Are you saying that no treatment (right now there are no standards of care for COVID-19) is not dangerous? If I recall correctly, that option is leading to people dying.
Standard double blind trial protocol: you sign up for the trial. You might get the actual drug or you might get placebo. It's double blind because not even the doctor knows who gets what.
Well, the other possibility is the drug could turn out to have severe side effects including death, so either way you take a risk.
If it does conclusively show effectiveness quite quickly, often they will cut the phase of the trial short and put everybody on the actual drug I think.
The alternative is what we have right now, ‘scientists’ blathering about their assumptions with the constant disclaimer that nobody really knows for real.
Part of that price is honesty on what's truly known, indicated, suggested, hypothesized, or unknown. What is "blathering" to you is intellectual integrity to others.
This is a correspondence piece, offering the opinion of a WHO working group. The opinion is also not the one you might assume: it proposes unblinding some subjects, not researchers, based on COVID-19 morbidity risk.
From a cursory search of NEJM and PubMed, I can't find evidence that any US-approved vaccines were allowed to run unblinded trials. But I could be wrong.
No, I am talking about ‘scientists’ telling others that Covid-19 is magically limited to a 1.5m or 6 feet circle (depending in which country you live). Or that they have to be really careful outside, and that it’s more safe to not go for a walk and fatten up in front of the TV. Or that ‘covid 0’ is a valid policy and that if it doesn’t work it is the fault of this week’s scapegoat. And then censoring anyone who would dare to point out the lack of logic.
Nobody, and I mean nobody, genuinely believes that COVID-19 can't be spread when social distancing measures are perfectly observed. The 1.5m/6ft distance was chosen based on both epidemiological models that show statistical decreases in contagion and the political reality that people (understandably) get very upset the more you ask them to stay away from other people.
The rest of your post doesn't reflect any government position that I'm currently aware of. Both my local government and the CDC encouraged me to go outside, while maintaining distancing, after the initial lockdown.
It's a very long read, but worth it. Basically, the social distancing measures were based on two things: That the primary spread vector was "droplets", and that they fell to the ground pretty quickly (before they could spread beyond ~6 feet).
The mistake the title refers to is that the medical definition that distinguishes "droplet" vs "aerosol" isn't the same as any other context, such as when used when determining how far the particles can travel. The cutoff between "droplet" and "aerosol" in the medical context came from a Tuberculosis study about how far different particle sizes could penetrate into the lungs. Only later were those numbers mistakenly used as the cutoff for "droplets" vs "aerosols" in general, leading to a lot of confusion over 2020: SARS-CoV-2 really does spread primarily through aerosols, not droplets, as defined in any context other than that medical mistake.
The US is not the world and really, a lot of people have made a lot of truly strange statements.
I have seen plenty of scientists with all kinds of statements, the worst being ‘oh if you got infected, it’s your own fault because you clearly didn’t stay 1.5 m from other people. Because otherwise it is impossible to get infected!’
Keep in mind, it can go the other way as well. That the drug leads to worse outcomes than a placebo. This is why there are trials. This is why they are voluntary.
They randomly assign people to the control or treatment cohort. Don’t forget there’s also the chance that the treatment gives patients liver cancer or some other yet-unknown adverse outcomes.
Sure, we survived as a species, but certainly not as individuals. We see plenty of evidence of genetic bottlenecks where the human population was reduced to small numbers, quite possibly due to disease. Just within the historical period, there are legions of plagues with extremely high mortality rates, including nearly the entire native population of North America after contact with Europeans. And let’s not forget antibiotics and near every lifesaving piece of medical knowledge we have developed over the last few thousand years. It’s your choice to refuse medical care, but don’t assume the rest of us want to go back to the caves and the hunt. Rapid drug discovery is an extremely powerful medical technology and I 100% welcome it for this disease and all futures ones.
But don't you think it's even a little suspicious other countries have been administering another infamous antiviral that happens to be a generic drug? I mean it's at least a coincidence that pfizer is somehow the one doing all the heavy lifting here... are they that good of a drug company? Aren't there other doctors, virologists, etc out there?
I just feel people are too quick to accept a for-profit mega-corporation as the defacto source of all things covid cure.
The vaccines are not 100% effective at preventing spread (nor for preventing serious illness, for that matter).
That is not even remotely the same as "not effective".
In practice, the vaccines (with the possible partial exception of the J&J single dose) provide significant reduction in both spread and serious illness.
This[1] study suggests that there a brief period of significant reduction (~three months), followed by a period modest to no risk reduction, followed by a period of increased risk.
This[2] study found no correlation between vaccination rates and viral spread.
The first study is clearly underpowered to say anything about the risk after more than around 150 days. This can be seen in figures 2 and S1, where the confidence intervals get larger than the effect size at around this point. Combining multiple age groups together also leads to a large risk of getting incorrect results due to Simpson's paradox [1]. But with so little data, the authors probably couldn't stratify for age groups without the confidence intervals exploding.
A much larger study from the US [2] shows no measurable decline in the protection against hospitalization due to COVID over more than 5 months after vaccination.
The way I see it, both studies show effectively the same result with similar confidence intervals. The US study however covers a shorter timeframe.
As far as hospitalizations go, I am not arguing with that, vaccines clearly reduce disease burden. The question was: Are vaccines effective at stopping spread? Many countries are experiencing record infection rates with a large majority of the population vaccinated. This suggests to me that vaccines are not effective in that regard.
It's not quite a binary yes-no question, but the vaccines not being effective enough for it to be possible to achieve herd immunity through vaccination alone makes a huge difference in how widely the virus ends up spreading.
More or less yes. The initial narrative of the jab as panacea has since evolved. The talking point now focuses on reducing hospitalization and death. The bit about the jab stopping transmission has been dropped as the number of so called breakthrough cases increases. Press Secretary Jen Psaki comes to mind.
People act astonished the COVID vaccines aren't perfect. You mentioning universal vaccination is such a key point. Let's look at smallpox.
We eliminated smallpox. Amazing! Yet, first, the smallpox vaccine wasn't perfect. It was 95% effective against infection. I would bet it's actually less than that. They probably mean symptomatic infection, because who was widely testing asymptomatic vaccinated people for smallpox? In contrast, symptomatic smallpox patients are pretty obviously and unambiguously infected with smallpox.
Second, what's particularly interesting is if you were the only smallpox-vaccinated person in a house of a couple others, the vaccine efficacy fell to about two thirds.
This isn't a world apart from the COVID vaccines. Two doses protects you 92-95% against severe disease. And two doses reduces the rate of transmission, if you end up infected, by 50% (this was 80%, pre Delta).
As I said, people act astonished the COVID vaccines aren't perfect. In reality, they're just focusing on COVID efficacy in ways they never have with other vaccines. The COVID vaccines are substantially more effective than your typical seasonal flu jag, or the BCG. COVID vaccines are not a world apart in efficacy than the Smallpox vaccine—and we beat smallpox! Smallpox elimination required universal vaccination, but we managed.
I'm excited to hear the results of the pill among the vaccinated. Cutting the risk of severe symptoms among high-risk vaccinated people, and the risk of long covid for everyone is very important. The vaccines are great, but not silver bullets themselves.
as someone who definitely had and suffered through long COVID, I would like to know what you think you are accomplishing by making false claims like this.
do you think you're being edgy? what possible work is your ignorant comment doing?
It took me about six months to recover from Covid post infection. I got it in the early weeks of the pandemic; it took from around mid April to October of 2020 to get back to normal. I've felt fine since. I don't know what exactly they're calling long Covid these days, but the parent comment is pretty obviously ignorant.
Like the other guy said, "long everything" exists, and so-called "long Covid" isn't any different than long complications from garden-variety colds and flus.
Attributing special powers specifically to Covid is just attention-seeking behavior.
Long-everything exists, we just don't talk about it. I've had multiple colds that lasted 2-3 months, and one that didn't completely resolve for almost 6 months.
How could I know? My lungs aren't so great, so maybe they did.
Also, the WHO definition of "Long COVID" is
“Post-COVID-19 condition occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis.”
That's any symptoms, not necessarily organ damage.
I encourage everyone eligible to get vaccinated if they can, but it does little to prevent spread. Over the long run we'll all be exposed no matter what we do. The real benefit of vaccines is in reducing the risk of severe symptoms.
I don't think either of those sources justifies "does little to prevent spread." The language used in them is considerably more hedged, eg:
"But growing evidence suggests that, with the Delta variant, fully vaccinated people can still transmit the virus."
And this:
"Unfortunately, the vaccine’s beneficial effect on Delta transmission waned to almost negligible levels over time. In people infected 2 weeks after receiving the vaccine developed by the University of Oxford and AstraZeneca, both in the UK, the chance that an unvaccinated close contact would test positive was 57%, but 3 months later, that chance rose to 67%. The latter figure is on par with the likelihood that an unvaccinated person will spread the virus."
Is also not super relevant— what most people want to know is not whether a breakthrough infection is capable of spreading it, but whether you're more likely to get a breakthrough infection. I think most vaccinated people (which is most people in rich countries now) care much more about the unvaccinated -> vaccinated transmission and the vaccinated -> vaccinated transmission than they do about vaccinated -> unvaccinated.
Vaccination slightly reduces the risk of transmission for individual interactions (at least for a while) but that just stretches the curve out a little. Since SARS-CoV-2 is now endemic throughout the worldwide human population (plus several other mammal species) we can all expect to be exposed multiple times throughout our lives no matter what we do. Fortunately the vaccines are very effective at preventing deaths.
> Vaccination slightly reduces the risk of transmission for individual interactions (at least for a while) but that just stretches the curve out a little...
That's a disingenuous statement though because vaccines also help prevent getting infected in the first place, which reduces transmission. This study seems to focus on vaccinated people who had a breakthrough infection. If you read the 'Interpretation' section:
> Vaccination reduces the risk of delta variant infection and accelerates viral clearance. Nonetheless, fully vaccinated individuals with breakthrough infections have peak viral load similar to unvaccinated cases and can efficiently transmit infection in household settings, including to fully vaccinated contacts.
The first sentence implies vaccination reduces the risk of getting infection. The second sentence is talking about vaccinated people with a breakthrough infection having similar viral load. Therefore saying "Vaccination slightly reduces the risk of transmission for individual interactions" is untrue because it ignores the infection prevention mechanism of the vaccine. It's a lot better than 'slightly'
“The most statistically significant data point is that vaccinated people certainly have a faster rate of viral decline,” said Ferguson, “so they may potentially be infectious for less time, but they don’t necessarily have any reduced peak of viral load. Most transmission probably happens around that peak of viral load, which is why we think we’re still seeing substantial transmission rates from vaccinated people, both to unvaccinated people and to other vaccinated people.”
And yet your own linked study says, right in the first paragraph, that vaccinated contacts got it 38% less often.
Is it possible that this is not enough, and “virtually everyone will eventually be exposed”? Yes. Is it possible that COVID will become endemic and many (but not all or even most) people will be exposed? Yes. Have I seen any source that makes a strong case for this? Not yet.
Time can also yield better vaccines, a policy of recurring vaccine doses (like the yearly flu shots), and milder variants that can emerge and become dominant, like some believe is what happened with the Spanish Flu.
Serious disease?
- The same/similar (though studies have shown this declines within 6 months). Op is correct.
Catching/Transmission?
- The current vaccines are systemic and not mucosal, so they don't stop it infecting the upper respiratory tract.
- A recent study shows fully-vaccinated households can spread at similar rates to unvaccinated households [1]
They're apples and oranges, really. The best course of action to get a vaccine for the preventative effects and an antiviral if one has a breakthrough infection.
If we made policy decisions based on a single paper, we'd all be taking HCQ and Ivermectin. And that study's confidence intervals are large. The upper bound looks like it could be in the same range for unvaccinated people.
Does anyone have a sense as to when US society will completely eliminate COVID measures? Is it just me or is there no clear exit criteria anymore? This will go on forever without exit criteria.
I live in Kansas and have basically forgotten COVID is a thing. The people who wanted to get vaccinated like me have and those who haven’t, haven’t. Nobody asks about it and no businesses have any sort of mask requirements. Half of the people at the grocery store wear masks and the other half don’t. Everyone seems to be getting along.
Next door in Kansas City Missouri I stopped at a gas station and an employee was shouting at a woman to put on a mask, then was yelling at the same woman to leave because she refused to comply. I’m glad she didn’t see me because I literally didn’t think to bring a mask with me and needed to run to the restroom.
I guess 5 miles difference magically makes COVID much more contagious.
Depends on your metric. It’s perfectly reasonable to think that Kansas is doing better than Missouri because more people are able to lead the life they want.
There are other metrics beside “least fatalities” to factor.
The death rate difference could be due to something as simple as a higher percentage of seniors in the state, for instance, or differing population densities. Hacker News is full of sophists.
Median age in Kansas is 36.7. Median age in Missouri is 38.6. Kansas has 4 towns with population densities >4000/sq mile. Missouri has 38 towns with population densities >4000/sq mile.
Correct. Instead it was agenda driven sarcasm, which while not forbidden on HN, adds nothing to, and always lowers the quality of discussion.
Rather than take the emotional bait and be sarcastic in return, the person who responded pointed out the misrepresentation that was behind the sarcasm, which is the most civil way to address it.
Their response was far more measured and constructive than the "take it to Reddit" response that the parent comment type usually elicits. There was absolutely nothing stunning about it - rather it was a standard civil response method in a debate whose civility has been lowered through sarcasm.
Pretty much the same story in South Carolina. Outside retail workers, mask usage in my hyper local area is about 2%. Life has been basically completely normal since June 2020.
I live in South Carolina as well, and I can confirm (I think you meant 2021 not 2020?). Most people in my city have been going about life as usual since ~ May if this year. Almost nobody wears masks. Everything is open. And guess what? We’re all good!
The sky isn’t falling. Hospitals aren’t being overrun. Life is good, and I can remember the last time I worried or had anxiety about Covid.
There seems to be a group of people who still believe we can ‘beat’ Covid. That somehow we make it go away, with endless restrictions. In reality, it is here to stay, and we will have to live with it for the rest of our lives.
South Carolina has had a pretty high number of cases since mid year [1]. Higher than the late 2020/early 2021 surge which was before vaccination.
It hasn't been doing all that great on death rates, either [2]. A bit worse than the Southern average, and quite a bit worse than the other regions of the US.
South Carolina has now reached the same death total per capita as the Northeast [3], which is quite astounding.
The Northeast got there by having a large number of people die early in the first couple of months of the pandemic as it tore through high density communities of especially vulnerable people while we were still trying to figure out basic things like how to treat it and what measures were practical and effective for limiting spread.
That should have cemented the Northeast as the US COVID death leader for the rest of the pandemic. But South Carolina in the last couple of months, despite over half the people being vaccinated, as managed to get a death rate that looks almost like an early pandemic Northeast death rate, eliminated the death gap.
Doesn’t look too bad so far as the USA goes, although if legal gun owners or Mexican cartel members were out there killing 40 people a day, you’d be screaming bloody murder about it
Being in BC, Canada sucks. I went in to an Apple store to buy the fully loaded MacBook M1 max, with 6000 dollars in my hand (literally). And was told to leave the store because my mask didn't cover my nose. I'm buying a Razer 15 now.
And I'm fully vaccinated. Not because I was scared of getting sick (i already contacted COVID twice before the vaccine, including the Delta variant), but because I was shamed into getting it (think about the immunocompromised!!!). And now I'm being told that vaccine doesn't prevent transmission? So now I'm being shamed into wearing a mask.
And now the govt is trying to bully the 10% teachers who are not vaccinated. They might lose their jobs if they don't get the shots. Think about the children!!! But wait a minute, the vaccines don't prevent transmission. So even if the teachers get vaccinated, how is it going to help the children?
If you don't understand by now that vaccines significantly reduce transmission, you just need to google "do covid vaccines reduce transmission". The top results are links to the CDC, Nature, New Scientist, the New England Journal of Medicine, The Lancet, and more, all saying that vaccines significantly reduce transmission.
Vaccines significantly reduce transmission, so if someone is telling you they don't, you need to re-evaluate whether you should trust that person and any information they're giving you.
(P.S. SARS-CoV-2 is a virus with airborne transmission that loves nasal passages, so it's probably pretty important that your mask cover your nose. So far, there's no evidence that the virus cares at all about how much money you have in your hand.)
> Individuals who have had two vaccine doses can be just as infectious as those who have not been jabbed.
You're leaving out the context: they can be just as infectious once they become infected, which is significantly less likely for those who are fully vaccinated.
Vaccines significantly reduce the transmissability of the virus by making it less likely for those vaccinated to become infected, NOT by making them less infectious if they are infected.
>I guess 5 miles difference magically makes COVID much more contagious.
In my nearest town (in the UK) there are two supermarkets. In the budget one (Aldi) nobody wears a mask, in the upmarket one (Waitrose) everybody does.
I've noticed that, Waitroses and doctor's surgeries seem to be the last bastion of English mask-wearing. I wonder what the correlation actually is fundamentally? Waitrose's clientele are wealthier and therefore older and more concious of COVID?
Odd that you have forgotten it since Kansas, if it were it's own country, would have been a top-5 world hotspot for COVID deaths only 6 weeks ago. Is your memory really that short?
I've always found it strange that some Americans focus on politeness above all.
Of all the problems in your story, the employee shouting is the least 'wrong'. You've got a woman who won't wear a mask, yourself who sneaked in without a mask, and that's just in that moment of time, but somehow the employee who has to deal with that behavior all day every day is the bad person because they lost their cool.
I mean, I saw the “masks required in this county” sign, but I really needed to pee. I knew I was going to be driving through that county for about 20 more minutes, so I checked my car for a mask. I couldn’t find one as there’s no mask mandate in my area so I’ve stopped carrying a mask around. I then held my shirt up as best I could as a “mask” and made a bee line for the bathroom. If they’d had masks at the door I’d have been perfectly fine with putting one on.
I wasn’t making any judgment about the woman yelling at people, I’d be mad if I was being threatened with fines by the local government for having maskless people in my establishment too.
> I’d be mad if I was being threatened with fines by the local government for having maskless people in my establishment too.
Ha. Perhaps she was mad because she was at risk of being exposed to Covid all day long due to boneheads who were incapable of reading, or wearing a mask, and some of them turned around and gave her grief for it?
Vaccinated people still spread the covid and vaccinated people still get covid. Most of my friend group was infected when two vaccinated friends came up to visit. They said they were feeling sick but because they were vaccinated it was fine. I think everyone in the group but 1 person was vaccinated.
The idea that once you are vaccinated you don't need to social distance or wear a mask is wrong and is getting people sick. In fact a vaccinated infection appears to have the same viral load as an unvaccinated.
https://www.ucdavis.edu/health/covid-19/news/viral-loads-sim...
If I'm out in public, I wear socks everyday (well most), I wear a shirt, I wear pants. Its not much of a stretch to wear a mask out in public too.
Your second statement is categorically false. See my comment above... you know the one you responded too. It actually links to a study showing the viral load is the same. Or here is another study:
https://www.thelancet.com/journals/laninf/article/PIIS1473-3...
Please stop spreading misinformation. Saying vaccinated people have a lower chance of getting covid is a true statement. However both of your statements are straight up misinformation.
No, they're not. You can try to split hairs and talk about how the rates are just lower, sure, but vaccinated people are not taking up beds (like the unvaccinated are).
Please take a look at the rest of the thread for sources that vaccinated individuals spread covid at lower rates than the unvaccinated.
The vaccine protects you but still allows you to carry and spread a viral load. The mask protects people around you but not yourself but limiting the viral load that you can spread.
By being a vaccinated unmasked person in a crowd of non-vaccinated people, you possibly become a super spreader.
In California, except for wearing masks in retail establishments, everything has been back to normal for months. School has been full time in person, and traffic sucks once again.
In addition to the mask mandates, which are more bothersome than you make out (e.g. it's pretty tiring to do cardio at the gym with a mask), there are other restrictions. Parents aren't allowed on our school campus, we don't have any in-person school events, kids get tested once a week, kids have to stay at 3 feet from each other at school, no wind instrument classes.
> Parents aren't allowed on our school campus, we don't have any in-person school events, kids get tested once a week, kids have to stay at 3 feet from each other at school, no wood wind instrument classes.
Not sure where you are but in my very urban CA city, except for testing which is a very good thing IMO, none of these rules are in place.
This morning, the parent community met for donuts at the elementary school campus, where kids were playing close-contact basketball. The local middle school jazz band - with plenty of wind instruments - played recently at the local street fair as a fundraiser, and it's clear they had been practicing.
Then again, around here vaccine and mask wearing rates are extremely high, so we basically had very little in the way of outbreaks and community transmission. It seems like when a critical majority of people are civically considerate and voluntarily mask and vaccinate, life can go on pretty close to normal.
Isn't the point of doing cardio work to be tired? To stress your lungs and heart? That's why extreme athletes wear masks while doing cardio... I'm sure a little surgical mask isn't as difficult as this:
Where are you in CA? Here in the Bay Area, at least East Bay, you have to wear a mask to go shopping. >90% of people at the parks are wearing masks, we can't go into the daycare to pick up our son and the nanny wears a mask all day, you can't sit in a restaurant unless you show your id and paperwork proving you have a vaccine. Heck, I see kids and adults riding their bikes or skateboarding without a helmet or any protection but they have their mask on!
Not sure what "normal" meant to you before, but it's definitely not any definition of normal to me, unless you take it that we are going to be living with all of this forever.
> Not sure what "normal" meant to you before, but it's definitely not any definition of normal to me,
I'm in the East Bay, and most of what you have described - people at the park wearing masks, riding bikes or skateboards with masks, nannies wearing masks - are voluntary behaviors not mandated by any authority.
Why does it matter to you what measures others take to protect themselves from the virus voluntarily, and which is totally within their personal liberty to do? Does it offend your sensibilities somehow? Should they not be wearing masks to make you feel like things are "normal" per your definition?
The other cases you raise -retail, restaurant, and daycare - all have very specific risks either due to density or because unvaccinated children are present.
It is "normal" now because I can go shopping or to a restaurant, have a drink at my neighborhood bar, take my kids to school, fly somewhere on vacation, have a gathering in my house, attend public events (Halloween was huge in my neighborhood) - everything I did before the pandemic - with the tiny inconvenience of getting vaccinated and wearing a mask when indoors in public.
When hospitalization rates are down. In many metro areas the ICU are still full of un-vaccinated COVID patients, which means people with normal emergencies can't get a bed.
Thus, COVID precautions are necessary to reduce the rate of infection to levels that do not overwhelm the healthcare system.
And all those areas that have "returned to normal" are sending their COVID patients to regions that are still masking because they've exhausted their local ICU capacity.
>And all those areas that have "returned to normal" are sending their COVID patients to regions that are still masking because they've exhausted their local ICU capacity.
This has been my experience as well. My state is pretty strict overall, but my area of my state is not.
Our hospital has been operating at capacity for 6 months or so, but nobody is talking about it. Because we can just ship to where they have stricter COVID control measures.
We're causing problems for other people because we can't be bothered to be part of society.
It's a joke all around. The entire world. Nihilism is almost impossible to escape right now.
It’s pretty amazing how stupid and shortsighted people are. We’re so good at overlooking the horrible situation we’re in and focusing on other things that are completely irrelevant
I used to think that one of the worst things in the USA was that 100 people per day die in preventable car accidents, but now we’re getting 10x that from a virus and people pretend that it isn’t happening
The last two years have convinced me: When the Zombie Apocalypse comes, zombies are biting and killing people in the streets, and neighborhoods are burning down, 50% of the country (world?) will whistle and just continue to go about their day, shopping, going out to eat, sending their kids to school, and looking down at all those hysterical alarmists bunkering up trying to defend themselves from the hoard. "Government, don't force me to change my life! I have the freedom to pretend everything is normal!"
Haha I've had this conversation with my wife as well. We've basically been under house arrest since early February 2020 (yes we quarantined even before there was a quarantine) and taking very conservative measures since, always 1 step ahead of the CDC the whole time with double masking and still masking when mandates were lifted here in Oregon because we knew there would be an immediate re-surge.
I told my wife I used to think we'd be one of the first to die in the Zombie Apocalypse because her and my kids are all high-anxiety people that typically crumble with too much psychological pressure. Yet covid has shown me we'd actually be one of the longest survivors given our resilience so far and how we haven't caved into the pressures of society itching to get back to normal. My dad - a self-proclaimed "survivalist" and doomsday prepper didn't make it even two months before he gave up on quarantining. He said the psychological stress was too much, he couldn't handle it lol
You survived because... most people (>99% of infected individuals) survive Covid? lol. If this was your end of the world scenario (people dining everywhere because you know... if you sit the virus goes past you) then you are up for a rude awakening if a real crisis ever arises (which I hope it doesn't)
That's the beautiful part of humans, though, we push through and live our lives no matter what. If everyone panicked every time there was something that seemed apocalypse, then we probably wouldn't be where we are today.
Maybe it's just the resilient ones that survive and keep reproducing.
I am wary of stories like this. What you’re saying is probably true true in specific cases in the most populous cities in the country, but I don’t think it’s a general policy that makes sense across the board.
I live in South Carolina & their Department of health website has great data. As of today, there are currently 551 Covid patients hospitalized statewide. 1280 ICU beds are occupied for a 76% utilization rate. Of those beds, 150 are Covid patients. That means 88% of folks in ICU are non-covid related.
This data doesn’t exactly corroborate what your saying. The way you tell it, the ICUs are still overflowing with Covid, and they just aren’t. Not in SC at least. And we’re not exactly known for our stringent Covid restrictions.
That website is very much designed to be scary. They say that hospital admins think 30% and above of Covid patients mean "extreme", but they use 20% and above for the "extreme" red. Then below that they use % "extreme", but without close reading, you think they are talking about hospital capacity. Over the whole map it's hard to find any county with over 20% of their beds being Covid patients.
The big thing is what did all of this look like before Covid? Most of the problems with capacity are due to staffing, which seems to be the real bottle-neck here.
Can you point me to a mandate anywhere with some kind of hospitalization rate cutoff? Because everywhere where there are still mask mandates, they seem to be nebulous things that will just last until it’s no longer politically popular. Oregon for example set an arbitrary date, which of course makes no sense.
Just eight Bay area counties ("San Francisco, Alameda, Santa Clara, San Mateo, Contra Costa, Marin, Sonoma and Napa" from https://www.sfgate.com/bay-area-politics/article/Bay-Area-ma... Solano is not included as they have chosen not to reinstate a mask mandate)
If they scale then the politicians won't have an excuse to maintain their mandates. They were able to get navy ships with hundreds of beds scaled up in weeks at the start of the pandemic. The cost to society of the mandates is certainly more that it would cost to scale ICUs.
ICU capacity is not that interesting to me anymore. Most hospitals don’t have row after row after row of empty ICU beds most of the time. They actually want their ICU to have just the right number of beds.
70% capacity sounds full, but it means 30% of the beds are empty. Would it ever make sense for a hospital to have 99% capacity free? Just have 99 beds empty for 1 patient? I think it’s a scare number.
Aren't the unvaccinated people in ICUs already not following COVID mandates? In areas of Southern California (e.g. Temecula) with low vaccination rates, there are virtually no restrictions. Why restrict a compliant populace that is already mostly vaccinated?
In the US the nation-wide ICU vacancy is down to pre-pandemic levels. There may be anecdotes of individual hospitals that have a lot of COVID patients in ICU, but it's simply not true that this is a wide spread problem.
It's funny that people read the same data with such different interpretations. This is why I feel like the insistence of "just look at the data" rarely leads to a clear decision, and anyone working at a company that has dealt with giving data to people to make decisions will know this intimately. People use data to make their point, and if the data doesn't agree, then they slice it or adjust it or reason their way out of using it, so they can make the decision they want.
I think Scott Adams calls it "watching the same screen, but seeing two different movies"
There are several problems, but a big one is just the way the news works. ICUs are designed to run at near capacity and are overwhelmed all the time if, for example, there's a big car accident. Right now, all eyes are on the pandemic and I'm sure it's true that there's places in the country where ICUs are full up with pandemic patients. But the way the news cycle works, "ICUs at capacity with COVID patients" gets a lot more clicks than "ICUs in this hospital are always at capacity, but now they are at capacity with COVID."
Also, there's been a couple of big hoaxes that have circulated like the one about how ERs were full of Ivermectin ODs and they were turning away car accident victims.
Here's the actual real-time-ish data of ICUs for the country:
Right now the national average for ICUs is 68% occupancy. Also from that article:
>The national average I.C.U. occupancy in 2010 was 67 percent, according to the Society of Critical Care Medicine, though the occupancy baseline changes depending on the place, time of year and size of hospital.
People have a hard time accepting that we are no longer in the early panic stage of the pandemic. Any data that suggests we can ratchet down the anxiety driven fear porn a couple points will be dismissed.
I mean, big car accidents don't happen across multiple states at the same time, it isn't that surprising that the response to something happening super-regionally is different than the response to something happening locally.
No, I didn't miss it, I was responding to the cynicism about "the news cycle", that's why I pointed out that a pandemic is a different sort of thing than a car accident.
If you are operating at your normal capacity factor but have reason to predict that you are on a trajectory to be completely overwhelmed along with every hospital within reasonable driving distance, it's different than if you are operating at your normal capacity factor and have to send a patient or two to the nearest hospital with more spare capacity.
Your response would make sense if we were still in the first months of the pandemic when there was serious risk of overrunning the hospitals.
Covid is still very real. And there are still very real risks. But this fear of overrun ICUs is irrational nonsense. We are back to pre-pandemic ICU utilization. And we have been since before the Delta variant hit.
The head internist at my local hospital participated in a news story about how everyone that works there is sick of it all just last month. This is at a small hospital that usually deals with a few patients at a time. They've had periods where they had limited space and couldn't make transfers since Delta hit.
But maybe the media called every hospital in the state to find her or something.
We are scraping by with the measures we do have in place, we can't use the fact that we are successfully scraping by as evidence that we have too many measures in place.
It's simply dishonest for you or anyone else to pretend like COVID filling up ICUs is a wide spread problem. There may be anecdotes of it being true in a particular hospital or community. But nationwide we are back to pre-pandemic occupancy levels.
I don't understand why you extrapolated that data to suggest something about how many measures we have in place. Is your position that we should lie to the public so they will do what you want?
It seems like we are experiencing a very slow and gradual offramp from the restrictions, rather than something that will have a clearly defined endpoint.
2021 is already "mostly normal", for me. I hope sometime in 2022 we will be back to "100% normal", but I'm not confident.
It really really depends on where you are. E.g. in my country it's almost like "normal". But that's not what you think. People just don't follow restrictions, people don't wear masks, abuse vaccination (simply skip or even buy fake vaccination certificate to fulfill government / employer requirements). The only difference from "normal" is increased workload on hospitals and daily news "over thousand people died today from covid-19".
When it's absolutely unbearable for healthcare system, government also introduces soft lockdown where restaurants / cafes / public places are closed. Then everything goes back to "normal".
I really don't see how it can be 100% normal next year. At least in here.
Masks became a regular fixture in Asia after original SARS. Not by regulation, but they just became an ordinary item used by people to avoid getting sick or avoid getting others sick.
Having been to many parts of Asia before Covid hit, masks were indeed not unusual, but were never worn by _everyone_ or even the majority of people, even in crowded places like subways.
Ah, yes that’s more what I meant to say. We’ll get to a place where masks aren’t required anywhere, but we may never return to a world where masks are a weird or unusual sight.
Subramanian Kumar 2021 [1] found that there is no correlation between vaccination rates and new case rates on a country-wide level, or a county-wide level in the United States.
This tracks with Dr. Vanden Bossche's assessment [2] from March of this year that mass vaccination with prophylactic vaccines will actually prolong and worsen the pandemic due to shedding of infectious variants.
Aside from islands closing their borders and implementing extremely strict testing and quarantine regimes (and even these don't hold up forever), the evidence for the effectiveness of NPIs is a lot thinner than you might intuitively expect.
It's fairly clear what the exit criteria is. Hospital capacity. When hospitals are filling up COVID measures are necessary. COVID is endemic now and will ebb and flow over the next decade. As such I would expect COVID measures to come and go based on local health department and hospital capacity needs.
Pandemics are an exponential process, so scaling capacity linearly buys you only a few days or weeks of time unless the exponential is controlled. It's not useless, but it's also decidedly not a lone solution.
That also doesn't account for the damage people contracting the virus accumulate that doesn't register on that metric.
There isn't any evidence that covid would continue to grow exponentially at this point if measures are removed. There are entire states where there are no measures, and it hasn't gone exponential there, even with low vaccination rates. The places with the strictest measures right now also have the highest vaccination rates.
I'm willing to entertain this idea, but random chance has played a big role so far. Personally, I think we should be aiming for elimination in the human population given the damaging effects of long covid in mild cases.
It was a stroke of genius for the powers that be to convince people that they have a personal responsibility to restore/protect a health infrastructure that has been looted out, and structured if not designed to act in a predatory manner. They created new emergency powers and a new moral imperative to avoid contagious respiratory disease out of whole cloth. "Only You Can Prevent Forest Fires!"
This is a good article. I'm firmly on team do-what-it-takes-to-stop-the-spread, but no one has an exit strategy. I got a booster and we have appointments for two of our three kids to get there first shot. By mid-December I'm hoping to not have to think much about it anymore.
Your children do not need it - perhaps you should evaluate whether they are in an 'at risk' category like the Nordics
https://www.nature.com/articles/d41586-021-01897-w
In the US, 340 children under 17 have died from Covid. Total. During the same period, 187 have died from the flu, and over 51,000 children have died from all causes:
Sweden halts Moderna:
https://www.cbsnews.com/news/covid-vaccine-moderna-sweden-ha...
The reason the vaccines aren't being approved for children is that there is compelling evidence that children are at greater risk from the vaccines than the virus. This is why (for example) approval for vaccination of children and teenagers is split across Europe, and the UK has restricted access to only children with known vulnerabilities:
“The low rate of severe acute disease is important news, but this does not have to mean that COVID does not matter to children,” says paediatrician Danilo Buonsenso at the Gemelli University Hospital in Rome. “Please, let’s keep attention — as much as is feasible — on immunization.”
How about 1 out of 52 children in the 5-11 test group experiencing heart inflammation as a result of the vaccine? That sounds a hell of a lot more dangerous than covid for kids.
> "according to data reviewed by the CDC's advisory panel on vaccines, as of Oct. 10, almost 2 million 5- to 11-year-olds have gotten ill from COVID-19, and 94 have died."
That's a laughably low death rate. Driving your child to school is more dangerous for them than Covid.
Can you provide a citation for that "1 out of 52" statistic? I'm seeing
>In Pfizer's clinical trial for 5- to 11-year-olds, there were no cases of myocarditis, although the company acknowledged that the trials were not big enough to pick up such rare events.
I though most of the point of vaxing children and other low-risk groups is to stop the spread, not for their own individual safety. Reducing the chance they'll infect grandma. And reducing the circulating pool of infections to prevent more virulent strains from developing. Have I got this wrong?
I thought the vaccines don't stop or even really slow spread that much, especially with Delta variants. At least that's what authorities are saying. My understanding is that the point of vaccines as now explained is to prevent hospitalizations.
They do. If you have a "breakthrough infection", you are just as likely to spread it to someone else as someone who is infected without the vaccine. But you're much less likely to get infected in the first place if you've had the vaccine, so overall much less likely to pass it to others. So the more people who get vaccinated, the slower the spread.
I think Delta is still above r0 1 in vaccinated. Delta plus is worse. So there will be spread amongst vaccinated. Not as much as unvaccinated but with vaccinated conditioned to think they are safe I don't see it solving much in the medium to longer term.
A high population of vaccinated is mathematically more likely to produce more virulent strains with a non sterile vaccine in a fast mutating virus.
That's possible but unproven. The current thinking is that new variants are mostly likely to evolve in immunocompromised patients who experience persistent infections. Vaccines are less effective in such patients because the immune system doesn't respond as it should.
But if vaccines permit asymptomatic spread, meaning the virus enters a host and begins replicating, without the host showing symptoms, by definition you’re increasing the number of opportunities for new mutations to occur. I’m not sure how that article refutes the grandparent comment’s point.
Its much more possible with a vaccine that reduces the severity of the disease and permits people to still be out and about, perhaps even unaware they might be infectious. If it puts you on your ass or worse, you aren't out spreading it.
Yes you have it wrong. That goes against medical ethics. You can't give someone a treatment that is net detrimental to them in order to benefit others.
I encourage everyone eligible to get vaccinated, but at this point there is zero possibility to stop the spread. Your "team" never had a chance. We can all expect to get infected eventually.
By "stop", I guess I really mean slow/reduce/flatten-the-curve, etc. It's all a game of probabilities, and I guess I'm on team lets-work-together-as-a-society-to-reduce-the-chances-of-getting-and-spreading-sars-cov2. But that's slightly less catchy.
Are there any other considerents in life, or reduce-the-chances-of-getting-and-spreading-sars-cov2 is the only metric of relevance? Can you conceptualize any possible anti-covid measure that has too little of a benefit for too high of a cost, such that we should not deploy (or mandate!) it?
Not what I said. I, and my whole family, get flu shots every year. I wouldn't mind also getting one for covid if it is determined to help me and my community.
You can't produce, distribute and vaccinate everyone at gun point fast enough before it mutates away from what your vax targeted. And this strategy ignores animal reservoirs where the virus can reside and come back.
not exactly sure where you live but they are completely gone in most of the country. I live in a solidly blue New England state and I havent seriously thought about Covid for months.
been going to packed bars, house parties, restaurants, music festivals, concerts all with no masks
> All 50 states (plus the District of Columbia) mandate diphtheria, tetanus, pertussis (whooping cough), polio, measles, rubella and chickenpox. In addition, every state except Iowa mandates immunization against mumps.
The comparison to mandates for children to receive well-tested and -understood vaccines, against illnesses far more threatening to them than Covid, for the narrow purpose of attending public school, is so dishonest as to be a form of gaslighting.
FWIW I believe Florida is in the process of relaxing mandates for some of the other required vaccinations -- certainly there is now political hay to be made from doing so because the concept has been so poisoned by the Covid vaccine mandaters.
> for the narrow purpose of attending public school
That doesn't seem all that narrow; 90% of the population goes through the public school system. (Side note: I'm in NY, and our vaccination mandate covers private/religious schools, too.)
> well-tested and -understood vaccines
Like the COVID vaccines, sweet.
> illnesses far more threatening to them than Covid
More gaslighting. The publications from the manufacturers themselves are chock full of unanswered questions and risks they say we must wait years for the answer to.
In what way are the COVID vaccines not well-tested or not well understood? I understand many laypeople want to declare an arbitrary length of time that they can pretend means a new drug is safe. But the professionals who have informed opinions on the matter are essentially in unanimous agreement that these vaccines have been proven safe.
The point is that if you aren't in agreement, then you can't be part of the group of people that say they are safe.
They have tried making MRNA shots for a long time with consistently negative results. Maybe they got it right this time, but still there is reason to be skeptical, as a "lay" person you have to trust the system that this shot was produced properly, tested properly, stored properly, and administered properly. Even if on a large scale there are low risks, something can go wrong on any one of those steps.
We also have never had a shot like this brought to market in such a short period of time. There is barely a year of data in the public, and that data is heavily politicized.
It's nearly impossible to ask an honest question as someone who may be worried for fear of being labeled a lunatic or a "walking bio-weapon" as someone said before in this very thread.
And then we see how much money a company like pfizer has made off of this, and their track-record in the past as well as the track record of many other pharmaceutical companies, and you have a recipe for people to be worried. Remember, public health looks at outcomes on a population level. If they push something and they think it will have a net benefit overall, they are not thinking about you and your own risk profile. You have to do that and unfortunately we're increasingly telling people that doesn't matter, that you must do what is right for the group and by-the-way, you can't possibly know what's right for you anyway.
"as a "lay" person you have to trust the system that this shot was produced properly, tested properly, stored properly, and administered properly"
Like most people, I have done this for dozens of drugs developed during my lifetime. Until it became politically charged I never saw much pushback. How many years had Cialis or Claritin or Wellbutrin been in use before people starting taking them without a second thought? And those drugs likely had much smaller trials.
The difference is that kids still get to go to school if the parents refuse these vaccines. It has never been publicized, but it's always ultimately been up to the parents.
This would be acceptable to me if the vaccinations were in any way comparable. The diseases you speak of have been known for centuries (I am comfortable being wrong on that) and the vaccines have been tested and are understood as part of being distributed for decades.
This is a common argument, and honestly it's garbage.
Actually, the vaccines they used decades ago are definitely not the same ones they use today. For starters, vaccines from centuries ago tended to have actual non-zero mortality rates.
Vaccines are never tested "for decades" either, because people kind of assume that it is highly unlikely that there are super-long-term side effects from small acute doses. I would tend to agree.
Yes, the US populace has elected to fund a public health organization which has advised on public health measures since its inception (which is not recent or coincident with Covid-19).
You are not forced to take any vaccine, though many (public and private) institutions will require you to do so to participate in their functions (e.g. attending public school, serving in the military, working in hospitals, etc...).
In any case, the will being applied is that of the people (indirectly) through its (mostly) elected representatives (who could abolish the public health organization any time it chose), not some nefarious government.
I mean, it is because you can look for another job or start your own business if that's the hill you want to die on.
But in general society has rules and we must abide by them if we want to participate. For instance I'm sure most people wouldn't appreciate if I walked around naked, which does not harm anyone unlike needlessly having an increased risk of contracting and/or spreading COVID.
Please stop spreading misinformation. I encourage everyone eligible to get vaccinated, but by your definition vaccinated people are also "walking bioweapons". The main benefit of vaccination is in preventing severe symptoms, not transmission. Since the virus is now endemic we'll all likely get infected eventually regardless of vaccination rates.
This is the trick. Force private companies to force you so that we can technically say we're not forcing you so you should shut-up you walking bio-weapon.
NYC's vaccination rate is trending towards 75%, and life is essentially back to normal with the addition of vaccine requirements for indoor dining and events (which strikes me as perfectly reasonable, given that we have a large tourism industry).
> Does anyone have a sense as to when US society will completely eliminate COVID measures?
Children are now eligible for a vaccine. It'll take a few weeks for this to trickle through the population, but we're pretty close to the point where everyone who wants a vaccination will have one.
At that point, I expect restrictions to swiftly ease up. In Massachusetts, things are already mostly back to normal. With children protected, there's definitely a light at the end of the tunnel.
Santa Clara County (aka Silicon Valley) has put out hard limits as to when the mask mandates will leave:
When hospitalization and community transmission is "low" based on the CDC definition of low, and when 80% of the total population is vaccinated or eight weeks from yesterday, whichever comes first. They also publish a dashboard with the information so anyone can see how we are progressing: https://covid19.sccgov.org/dashboards
We were at almost 80% vax rate for 12+ already and hospitalizations are currently low and have been for a while, however community transmission remains high.
So at least in our county they have specific standards as to when the restrictions leave. Other than a mask mandate, there are no other restrictions anymore, except for school kids.
Florida is essentially back to normal. Cashiers in most of the large grocery chains and ~50% of restaurant workers still wear masks, hit and miss in most other stores. Most people who come to the house don't wear them, for example, have had a contractor, electrician and cleaning crew at the house in the last week. Electrician wore a mask, no one else did. People are vaccinated who wanted it (I am), and optimally a booster will be freely available soon. Schools ended the mask requirement at least in my county a couple weeks ago.
Some businesses require their employees to all be vaccinated.
Governor appears to be fighting against that, would not be surprised if those same businesses just don't hire unvaccinated people going forward and the situation is resolved via attrition.
My guess is that the end game is when the vaccine mandate goes into effect in January. Most people will get vaccinated and those that don't wont and nothing will make them. At that point in time all that could be done has been done and life goes on. Optimally enough will be to grant some form of herd immunity or reducing the spread. I'll just get a booster when I can and go about my life. I have for all intents and purpose resumed normal life. I wear a mask in a grocery store most of the time just to give some respect to the cashiers who are wearing them but that's essentially it.
I think that will be on a state by state basis as from my understanding the individual states set the vaccine requirements for schools. I guess the federal government could try to do something along the lines of the OSHA requirement but I think that would be a political misfire in this environment. Most of what (all) politicians do is to get reelected and I think mandating child Covid vaccination would not work in the current administrations favor especially considering what a good job the republican party has done leveraging the boogey man of critical race theory. So I am doubtful that they mandate vaccines for kids. I could be wrong though.
My company is fairly standard with the state we are in. They are extremely cautious, put emphasis on safety, but did get to a point where if you are vaccinated, you can go maskless... right up until the delta variant surge started infecting and killing people at an alarming rate.
Now we're JUST starting to talk about relaxing again. If this is any barometer, not to mention the rate of which we are seeing pills/vaccines/what have you, I imagine 2022. Outside of work, things are largely "normal".
For what it's worth - I live in a dense Northern state not seeing a surge of cases.
I don't know but I haven't had a cold or any other infection in 18 months so I hope that wearing masks on trains, planes and buses stays forever. Also, shaking hands was always barbaric and I don't miss that, either.
What a horrible idea. I'm not willing to wear a mask just to avoid a cold. We cannot allow irrational germaphobes to seize control of our society in the name of "safety".
In Japan, it seems that people wear masks when they are ill as a consideration to others to avoid passing on the illness in a crowded area. Also as a red flag to others, e.g. to the elderly or immune compromised, that they may want to avoid you right now.
I frankly don’t mind that. It’s only for a limited time (while you feel ill, or suspect you are coming down with something), it’s very cheap and only mildly annoying. There is the side benefit that it makes you think twice before you go out if you think you might be infectious (is this trip really necessary?).
My personal opinion, which reasonable people may of course disagree with depending on how they weight various factors, is that forcing people to regularly hide their faces in public is too large a price to pay to avoid sometimes getting a cold.
Maybe not forcing, but if people did it as a curtesy to not get other people sick? Of course, that already happens in some places, and will never happen in others.
Pre-covid Japan had the right balance IMO. It was common to (voluntarily) wear a mask in public when you had a cold (or didn't feel like putting on make-up), but no one was going to force you to wear one.
I could see things starting to really ease up once all children have had a chance to be vaccinated and everyone else has had a chance to get their 6 month booster shot.
Children aren't at risk from Covid at all.
https://www.nature.com/articles/d41586-021-01897-w
In the US, 340 children under 17 have died from Covid. Total. During the same period, 187 have died from the flu, and over 51,000 children have died from all causes:
"at all"? What? Tons of children end up with post-acute sequelae. Where are people getting this notion that the only possible negative outcome of viral or bacterial infections is death and that that's the only stat we should look at? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927578/
Where are people getting this notion that the only possible negative outcome of unnecessary vaccination is death and that that's the only stat we should look at?
A portion of parents are very worried about Covid in their children. These parents have sway with school administrators and local governments. All I am saying is that I doubt we get total easing of Covid restrictions until these kids have had ample chance to be vaccinated. I'm not making any arguments or claims about what you are taking about.
The local pharmacies that administer the vaccines are not validating your eligibility. Those I know who are interested in the 3rd round, and beyond 6 months from their 2nd, have received it.
Sure, but I don't think people getting a booster that may not be qualified are going to prolong the pandemic, quite the opposite. There is more than enough supply.
Yes - which why I doubt we will see full "reopening" everywhere until they open up boosters to everyone and provide time for people who want them to get them.
Most COVID measures are not at the US federal level. Some mandated measures have exit criteria, at the level of government issuing them.
> This will go on forever without exit criteria.
It will go on without an exit decision, but the exit criteria that have been issued have frequently been adjusted anyway, because understanding of how current metrics project the future have evolved. Which is probably why their are fewer announced criteria and more reliance on periodic, holistic review.
It’s crazy that money is such a huge incentive. Knowing that a cure for Covid is a potentially $100B market means you throw the kitchen sink at it. Imagine being this lab. Do you think they ever had trouble hiring an assistant? Buying new equipment? Getting bonuses? This environment must be fantastically different from the typical meat grinder of bio R&D.
Money has totally failed at allocating vaccinations and treatments for COVID-19 to 95% of the global population. But it's 'succeeded' in securing boosters for people who are already vaccinated in the richest parts of the world while global supply is lacking.
No — if it was that easy, the odds are high that something else would have already done so. The two things which tend to factor into this are that there's a lot of natural variation so it means that the population will change to favor a high percentage of people who are somewhat resistant to it[1] after a few generations of recovery.
There's also an inverse relationship between deadliness and spread: if something kills at a high rate, the odds are high that it'll burn out when the outside world goes into quarantine as long as it doesn't spread to 100% of the breeding population before they start dying. Anything deadly enough to wipe out a species is going to have a LOT less resistance to lockdowns — COVID-19 is deadly but far below the rates of other diseases and that puts it in a grey area where there are a fair number of people who've had it and can say “no big deal”. Smallpox or polio were enough worse that people jumped on treatment campaigns because almost everyone with lived experience knew they didn't want it.
1. A great example appears to be Sickle Cell Anemia, where the gene responsible is thought to confer some resistance to malaria — normally this would be a disadvantage but in areas where malaria is endemic the risk of SCA is more than balanced by the risk of malaria.
Big Pharma will not invest in a research program they know will lose money, even if that money-losing situation is the successful case which saves humanity from extinction.
They will do the work, if the money comes from somewhere else.
Pharma doesn't do charity though. Drug risky is very expensive and highly risky. It's risky whether you research a drug for some disease that ten people have in the world, or for a pandemic.
Research related to the pandemic is de-risked by some margin and that alone makes it attractive.
I know people who have worked on some pretty revolutionary cardiac drugs that got laid off once their project was complete. It'll still be a meatgrinder for the talent behind these drugs. The spoils are further up the food chain.
Basically, if Trinity fizzled, they wanted to be able to recover the billion dollar plutonium core.
It didn't actually end up being used, and so it was ordered destroyed. But the thing was so tough that they essentially couldn't blow it up. Normal bombs just weren't powerful enough. So now it's just sitting there at the site.
There are still occasionally projects which approach this relative scale today. When Boeing (temporarily) shut down 737 MAX production in early 2020 it was reported that this would reduce US GDP by between 0.3% and 0.6% (depending on the economist doing the calculation), for example.
Except that this pill won't be given to people unless they're already sick with COVID. Not that this will stop the tinfoil hat brigade, but it's going to be much less controversial than universal vaccine mandates.
It won't happen, because the explicit arguments are just pretexts. After The Lancet/Wakefield and Jenny McCarthy (and other popular media figures), the word "vaccine" is now simply triggering of aggressive suspicion. That media panic combining with:
1) the 80s New Age/Self-Help/Healthy Living/Naturopathic flakes,
2) the suspicions of black people who are generally neglected and sometimes abused by the health care industry (over a very long term with sign-off from regulators),
3) and the religious fundamentalist divine punishment crowd (disease exists to punish weakness and evil), and
4) the factual observation that the healthcare industry in the US is hopelessly corrupt from top to bottom, and will not change no matter how strong the political will of the general population, or how organized it is,
...and all combinations thereof, means that this is going to be something that we have to deal with forever. It has nothing to do with whether the vaccine is new or experimental, it's that it's a vaccine. We still don't have universal vaccination for HPV, and that prevents cancer.
The media blames vaccine hesitancy on Republican hucksters, but that's just because they're centrist neolibs and that's what they're paid to do. Republican grifters take advantage of whatever's available; this week they actually became animal rights activists in order to attack Fauci:)
The anti-vax feeling is deeper than that; it's become hopelessly tangled into religion, identity, and anti-authoritarianism. It's not going away. Covid-19 was actually pretty mild when it comes down to it, when a real disease comes along, we're all dead.
I'm actually on a personal countdown until I hear the first argument that this safe, effective, experimental pill is a reason not to take the dangerous, pointless, experimental vaccine, and that big pharma wants you to take the vaccine instead of the pill because reasons.
I'm actually on a personal countdown until I hear the first argument that this safe, effective, experimental pill is a reason not to take the dangerous, pointless, experimental vaccine, and that big pharma wants you to take the vaccine instead of the pill because reasons.
That ship sailed weeks ago on the Twittersphere, once news of the new drug's development came out. According to half of the idiots, the announcement explains why horse paste had to be "suppressed," given that ivermectin was inexpensive, already approved for human use, and unpatentable. The other half maintained that no, the new Pfizer compound was unalloyed good news, because they no longer needed to worry about getting the "untested," "experimental" vaccine.
Covid-19 was actually pretty mild when it comes down to it, when a real disease comes along, we're all dead.
Exactly, SARS-CoV-2 amounts to a dress rehearsal. We know how the real thing is going to play out now, and oh, boy.
Try to understand why this viewpoint exists. We are all logical people. The difference is in the trust of public media and government. Both sides of the argument are mostly right in what they believe given the information they are consuming. My suggestion - read sources from both sides before deciding that anyone slightly against Covid hysteria is misinformed and is an anti-vaxxer. Second suggestion, anti-vaxxer is a really misleading and extremely divisive term.
That's a bold claim. In my experience the vast majority of people hardly try to think logically or apply critical thinking skills in most opportunities, and no human does so anywhere close to all the time. Humans are deeply irrational creatures, and we shouldn't pretend otherwise.
The anti-vax movement is in the uncanny valley of media trust. If they had more trust, they'd follow traditional institutional recommendations as most had done for decades. If they had less trust, they'd realize that Faceboot et al are just more media sources hijacking their sense of social proof. The path to actually rejecting "the media" isn't to just follow substitute media that promotes opposite viewpoints - you have to reason from first principles and look to falsify every single thing you read.
" A person who was fully vaccinated and then had a ‘breakthrough’ Delta infection was almost twice as likely to pass on the virus as someone who was infected with Alpha." ( and i was saying that months ago just based on obvious arithmetic on public data https://news.ycombinator.com/item?id=28081982 and was labeled as anti-vaxxer, i guess now it is me, the journal Nature and the study authors are all anti-vaxxers)
"Unfortunately, the vaccine’s beneficial effect on Delta transmission waned to almost negligible levels over time. In people infected 2 weeks after receiving the vaccine developed by the University of Oxford and AstraZeneca, both in the UK, the chance that an unvaccinated close contact would test positive was 57%, but 3 months later, that chance rose to 67%. The latter figure is on par with the likelihood that an unvaccinated person will spread the virus."
There is nothing wrong or unique about a vaccine being not effective in reducing transmission and spread. We have for example that with a flu vaccine each year. What unique and wrong is the vaccine mandate and enforcement of those failed Covid vaccines which plays right into the hands of the opposition to the vaccines in general which i think would result in a lot of damage down the road.
Non profit organizations still need money to operate. They still pay their employees with money. They still must earn revenue somehow to cover their operations, unless they are entirely funded by an endowment. The only difference from for-profit companies is that they don't earn returns for investors.
Then do we understand the risk profile of this thing? That sounds like the sort of innovation that people would want to be at the back of the queue for.
Side effects don't have to happen in the next 6 months.
Pretty sure we don't understand the long term risk of getting COVID either right? I mean it has not even been around for 2 years. Plus we do know it is possible only 1 infection would kill you.
That’s a straw man argument, when you take this drug you already have 100% covid19. Presumably that means you’ll have that risk, plus additional unknown risk. Perhaps the drug works like advertised, but we’ve seen better and more successful studies for things like ivermectin and anti-body treatments. Which have a known risk profile.
It’s the same for the vaccine. You still have the risk of what ever the vaccine risk is, PLUS covid19. Supposedly it reduces the covid19 symptoms, but doesn’t reduce risk of infection (or at least unclear), it just improves the immune response.
Hospitalisation is an acute scenario that can lead to death, negating any concerns about the long-term in the first place. The short term risk of hospitalisation in the unvaccinated versus the vaccinated is well-known. Given what we know, it still makes sense to get vaccinated, and it may make sense for those at risk of hospitalisation (vaccinated or otherwise) to take an antiviral proven to cut the risk of hospitalisation.
Actually the long term risk of the covid-19 vaccines is well understood. You will not get a side effect from the vaccines in a year from now. For all of the vaccines created for any disease, the longest recorded period between taking the vaccine and side effects presenting is 6 weeks. 3.1 billion people are fully vaccinated for covid-19, many of them have been for longer than 6 weeks.
In Norway, some children developed narcolepsy after being vaccinated with Pandemrix. The average time from vaccine (or influensa) until developing narcolepsy was 8 months.
> You will not get a side effect from the vaccines in a year from now
There are possible severe negative effects due to vaccination, even if there are zero medical side effects. Herd vulnerability could cause widespread harm - there is a monoculture of immune responses and monocultures have vulnerabilities. I agree it's unlikely to have severe long term downsides, and the short-term gains are very significant. Note that I'm mostly pro vaccination.
The technology is not brand new. It has been used in labs for decades. This is just the first time it has been used in a drug for humans. All traces of the vaccine leave your body within days of receiving the shot.
This is a strange additive error to make: proactive or reactive treatments for COVID-19 don't produce additive unknowns in the presence of a COVID-19 infection, since their entire purpose is to improve healthcare outcomes (whether by reducing infection severity or incidence altogether).
Data shows that being vaccinated divides your odds of dying and being hospitalized from covid by about 10. There's no evidence I'm aware of showing that the vaccines create additional risk anywhere close to outweighing that benefit.
There is. Because kids (basically) don’t die from COVID. The side effect risk, while small, is material in a risk calculation for them, since their entire risk from the disease is small. At a minimum, mandating it for kids (as is openly stated to be the plan in CA) is unethical.
Even if we completely ignore that some children do in fact die (being rare doesn't stop it being terrible when it happens and worth avoiding), and that even if they don't, suffering while ill is bad: when we are talking about risks of completely unknown side effects, the side effect risk of the vaccine is obviously lower than the side effect risk of COVID itself.
The vaccine is relatively simple thing specifically designed to do one task. While there is always a chance there is something we didn't understand or see coming, the chance of a virus, a hugely complex and mutating thing with broad and varied effects, having some long-term side-effect is far, far higher.
> Even if we completely ignore that some children do in fact die ... the side effect risk of the vaccine is obviously lower than the side effect risk of COVID itself.
> Dr. Marty Makary, a professor at Johns Hopkins University School of Medicine and editor in chief of MedPage Today, argues that mandating vaccines for "every living, walking American" is, as of now, not well-supported by science. ... The risk of hospitalization from COVID-19 in kids ages 5 to 17 is 0.3 per million for the week ending July 24, 2021, according to the Centers for Disease Control and Prevention. We also know that the risk of hospitalization after the second vaccine dose due to myocarditis, or inflammation of the heart muscle, is about 50 per million in that same age group.
You elided my qualifier from your quote: "when we are talking about risks of completely unknown side effects"—the argument being made was that we can't possibly know the risks of the vaccine because we can't ever know with certainty until we've tested it for a long time, and therefore we should avoid it. My point is that the virus has far more "unknowns" to it, so that argument sucks.
As to vaccinating children more generally and assessing known risks, there is no simple answer. What are the risk levels for different age groups? What is the damage to kids if they pass COVID onto their parents or grandparents and they die? I'm not saying that we should just blanket give it to everyone, but I don't think that one stat is enough to say don't give it to any child, or that no mandate could be justified.
It's obvious to you because you are following a logical train of thought. These antivax people always do the same nonsense argument. It goes, COVID has risks and vaccines have risks, therefore it's impossible to know which is worse. It's literally the dril drunk driving tweet[1].
I'm not anti-vax, the logical train of thought you are incapable of yourself is based on the very factual reality that COVID presents highly variable risk to people based on their age. This, in combination with the known risks of the vaccine, in combination with the extremely early stage of wide-scale deployment of the vaccine in children, in combination with Hippocratic principles, in combination with risk-adjusted thinking, leads to the conclusions that no, it is not completely obvious if a parent should make an appointment for their 5 year old to get a medicine EUA authorized a week ago.
Besides, if you're so smart, and it's so obvious, why do you think you're smart enough to state that Sweden, a modern country, is objectively wrong for banning mRNA vaccines for children?
In any case, my primary point was that it should be up to parents if they give their kids this vaccine, and when. Not the government mandating it.
I mostly agree with you. I think the nuance that is missing here is that the degree of risk is different.
We know the degree of risk from vaccines is low, both in the short and long term. The side effects harm few people, and are not catastrophic.
With viruses, we know that side effects in the long term are real, and can be catastrophic. It is the reason that girl are vaccinated against HPV - HPV is the leading cause of cervical cancer. This is a very big problem down the line, even though HPV itself is mostly asymptomatic.
So, it does not follow that avoiding Covid vaccine for children because the immediate likelihood of death from acute covid is the only issue. We are aware that the long term risk of viral infection can be very great with viruses. Avoiding infection is much better if the alternative is the possibility of cancer.
> So, it does not follow that avoiding Covid vaccine for children because the immediate likelihood of death from acute covid is the only issue.
I never said it was the only issue. But neither is the only choice to give your kids the current approved vaccines ASAP or never give the vaccine to them ever.
Avoiding infection is much better if the alternative is the possibility of cancer. But of course, we don't know or plausibly think something like cancer is a long term risk of a COVID infection in children. Maybe one day we will realize such outcomes happen and then it would become much more sane to rush your kids to get the vaccine that day.
I think it's important to stick to what we know, about this virus, and these vaccines: we know that it is extremely rare for children to be hospitalized from COVID, and we know that it is extremely rare for diagnosed myocarditis. But what we also know is that as time goes on, we learn more. And especially for things where are very new, like using these vaccines have on children, we stand to learn a lot, quickly. So I think it's a bad frame to presume parents are pro- or anti- vax. Hesitancy is sane on this specific issue, and that's not to mean that other positions are insane, but what is insane is to impose this on parents who are hesitant at this present time, until we understand what, exactly, is going on with heart tissue.
Can you point me in the direction of studies comparing side effect risks for young children against COVID-19 risks for children? Presumably there's such a thing that you're basing your opinion on. I would find that useful, given that I have an 8 y/o who is now vaccine-eligible and her mother and I are discussing.
CDC admits that there has been severe cardiac damage to young people from the mRNA vaccines.
This leads to an obvious series of questions: just how dangerous is COVID for children? What mechanism is causing this heart damage? Could heart damage be happening without diagnosis, and manifest later? In a year, will we be able to fix this problem with the vaccines, or have protocols to prevent it? Are the vaccines more likely to cause permanent damage in children, than COVID, as opposed to temporary health problems? Are the non-mRNA vaccines completely de-risked from the proposition from causing permanent harm to children? Will CDC guidance in a year guide parents away from mRNA vaccines and towards different ones? Is there a correlating variable we will discover so we know which specific population of children would get heart damage from this? Etc.
More questions: given this known to manifest in younger people, could it imply that age is inversely correlated with frequency? Will young children be less likely to report or articulate symptoms, even if they have increased risk? Given it seems sex coupled, is there an underlying variable correlated with sex that is a root cause we will soon understand, resulting in a vast risk reduction for parents who will be able to know if their children apply?
People claiming you can know if vaccination is a good idea or not for your kids have primitive mental models: the choice isn't to vaccinate or not vaccinate, but vaccinate now or (maybe) vaccinate later. When something is risk laden on both sides and is a dynamic system, the smart choice may be to wait if the marginal de-risking per unit time is high.
My personal view is that wrt children taking mRNA vaccines, there's basically close to free "money on the table" - wait a few months. If you've avoided COVID until now, its pretty unlikely your kids will catch it, nevermind be unlucky enough to get a severe case, which is extremely unlikely. On the other hand, it could turn out in a few months we identify the root cause of the heart issues of the vaccines, or alternative vaccines become available that de-risk it entirely. In any case, personal views aside, it's incredibly immoral to mandate this for schools, and it wouldn't surprise me if CA does this before we fully understand what is going on.
So that link you sent says there is 12.6 instances per million doses. So that is 0.00126% chance of happening. This article from March mentions around 22 per 100,000 chance from getting COVID. Much larger incidence rate.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988375/
Now obviously might not be the same age ranges or such, but I do know last year the Big-10 almost cancelled it's football season due to myocarditis risk from COVID so clearly it has been an issue for a while. Might need to weigh that in the decision you make for your children. Too many people look for one side and use that to prove their point otherwise know as confirmation bias. I would study the incidence of both sides of this before making the decision. Although my children are less than 5 so they can't get it yet anyway.
First, if this has a mechanism which is damaging heart tissue, the diagnosed cases may just be the ones which are manifesting severely enough to the point of getting to through the entire funnel of a diagnosis. The actual blast radius may be much larger, and only result in problems later in life. Especially for children whose hearts are developing, it is extremely risky to administer a drug which we know has the capacity to damage heart muscle and we do not yet understand why and have a handle on the expected distribution of that damage across the whole population.
Second, the stat you mention on COVID is misleading, because a) it is a broad age group, my concern is primarily in the very young, many of whom are now being vaccinated in the US, and b) it is conditional on a positive COVID test. Many, many young children are contracting COVID and not developing symptoms or are not getting severe enough infections to get through the funnel of being determined to be a positive case. So the incidence rate you mention is effectively a meaningless number if you account for these two elements.
Based on our current understanding, it could very well turn out that the data we have now is consistent with a situation where eg, the vaccine administered to 5-6 year olds is in fact damaging their hearts with a sizable % liklihood, and their risk of having such kinds of permanent damage to their bodies from COVID (across the entire funnel, beginning at a non-infection) is much lower. I'm not sure of the liklihood of this reality, but it's not zero. We just don't know yet.
The abstract from your linked paper seems to indicate the risk is minimal.
>According to the US Centers for Disease Control and Prevention, myocarditis/pericarditis rates are ≈12.6 cases per million doses of second-dose mRNA vaccine among individuals 12 to 39 years of age
That's a 0.0013% chance of getting something that "almost all" patients had resolution of with or without treatment:
>Almost all patients had resolution of symptoms and signs and improvement in diagnostic markers and imaging with or without treatment. Despite rare cases of myocarditis, the benefit-risk assessment for COVID-19 vaccination shows a favorable balance for all age and sex groups; therefore, COVID-19 vaccination is recommended for everyone ≥12 years of age.
There is one in the Pfizer application for FDA authorization in 5-11 age group, see Table 14, page 34. It is not a direct study, it's an extrapolation based on antigen titers in a 2000 kid 2 months clinical trial, but it's the only one I am aware of.
Don’t mistake relative risk for absolute risk. Not everyone who is vaccinated gets Covid, but everyone vaccinated is at risk of vaccine side effects.
If a 30 year old has a 0.08% chance of hospitalization, the risk drops to 0.008%. But they might stand a 1 in 5 chance of getting infected so now it’s 0.016% to 0.0016%.
But if they get injected with a vaccine, the risk of a rare side effect might be 1 in 100,000 or 0.001% which is pretty similar to Covid.
It’s the same analysis the UK did that caused them to recommend against the AZ vaccine for certain age groups.
You're comparing completely different statistics. The 3% is the infection hospitalization rate; in other words, the odds of being hospitalized once infected. The rates from your source are the total number of people per 100k who are hospitalized for covid in a given week; it does not mean they only have a .05% chance of being hospitalized once infected, it means .05% of the entire age cohort are hospitalized from covid that week.
Nope. Look at the data again. The risk of dying from an infection in the 18-49 age group is 0.06%. The risk of hospitalization from an infection in that age group is 3%; you claimed 0.08% which is wrong by two orders of magnitude.
I think 1 in 5 is very optimistic. Unless you intend to remove yourself from society, you are very likely to catch Sars-Cov-2 in the upcoming years. Probably more than once. It's endemic and easily transmittable.
Sure. We also don't know if it will give you superpowers. I mean, we have logic and the history of similar things that gives us good ideas. And the fact that the risks grow because the immune response means a shorter immune response is likely to be less severe long term. But yeah, technically there is no study there yet.
We have not seen better and more successful studies for ivermectin, we have seen a lot of studies that find it does next to nothing, and a few deeply fraudulent studies that finds that it solves world hunger.
It's a strange day when people argue against evaluating a new medicine, in favour of snake oil that doesn't work.
Given that you think that it's unclear that vaccines reduce the rate and seriousness of COVID, I am not sure that your have a good enough understanding of the ground facts to have an informed opinion on this subject.
This drug might actually save the patient from the risk of dying from covid. It would be the same for the vaccine: the vaccines reduce the risk from dying.
> Side effects don't have to happen in the next 6 months.
If this is a molecule with a short half-life that is broken down and expelled by the body, it isn't going to have random side effects that show up months in the future.
As someone who worked in toxicology, this is absolutely a false statement. This molecule is a covalent binder - it basically attaches itself permanently to proteins. It absolutely could have effects long after the free molecule is metabolized and excreted. The molecule is designed to be selective for the Covid protease but off-target effects are inevitable.
Do I think that is likely? No, because the FDA isn’t stupid and screens for obvious toxicity in cell cultures and lab animals and only then is testing humans allowed. Then those are screened before approval.
Of course the risk isn’t 0%, but it’s pretty low and if you’re at chance of dying or Covid it’s a pretty small risk relatively speaking.
Prions are "just" proteins that should get broken down by the body. But they don't, and they cause Creutzfeldt-Jakob in over 10 years after ingesting.
It's a good thing we're all here on HN to question the safety of novel pharmaceuticals. If we weren't, maybe nobody would, and we'd all just be putting prions into ourselves.
If you have something specific about this particular molecule to talk about vis a vis safety, that's an interesting comment to make. But "aspirin is a molecule but so is Mad Cow Disease so we had better be careful about new drugs" is just about the most boring, banal comment you can make. Drugs: can they be unsafe??? We'll have more at 11!
We need more Derek Lowe-type drug safety discussion here, and a lot less of whatever this is.
I'm suggesting that sometimes a very small amount of a substance can cause catastrophic effects a decade later. That's why we do testing before we release drugs.
And Pfizer isn't the hero here, they never have been.
1986: Pfizer had to withdraw an artificial heart valve from the market after defects led to it being implicated in over 300 deaths. The US Food and Drug Administration (FDA) withdrew its approval for the product in 1986 and Pfizer agreed to pay hundreds of millions of dollars in compensation after multiple lawsuits were brought against it.
2003: Pfizer has long been condemned for profiteering from AIDS drugs. In 2003 for example, it walked away from a licencing deal for its Rescriptor drug that would have made it cheaper for poorer countries.
2011: Pfizer was forced to pay compensation to families of children killed in the controversial Trovan drug trial. During the worst meningitis epidemic seen in Africa, in 1996, Pfizer ran a trial in Nigeria their new drug Trovan. Five of the 100 children who took Trovan died and it caused liver damage, while it caused lifelong disabilities in those who survived. But another group of 100 children were given the conventional “gold standard” meningitis antibiotic as a “control” group for comparison. Six of them also tragically died because, the families said, Pfizer had given them less than the recommended level of the conventional antibiotic in order to make Trovan look more effective.
2012: Pfizer had to pay around $1billion to settle lawsuits claiming its Prempro drug caused breast cancer. Prempro was used in hormone replacement therapy, usually for women going through the menopause. The settlements came after six years of trials and hardship for the women affected.
2013: Pfizer paid out $273 million to settle over 2,000 cases in the US that accused its smoking treatment drug Chantix of provoking suicidal and homicidal thoughts, self harm and severe psychological disorders. Pfizer was also accused of improperly excluding patients with a history of depression or other mental disturbances from trials for the drug. Later, in 2017, a coroner in Australia ruled that the drug had contributed to a man’s suicide. The man’s mother campaigned to change the label on the drug.
2020: Pfizer reached an agreement with thousands of customers of its depo-testosterone drug in 2018 after they sued it for increasing the likelihood of numerous issues, including heart attacks.
The total number of people affected by the use of thalidomide during the mother's pregnancy is estimated at more than 10,000, of whom approximately 40 percent died at or shortly after the time of birth. Those who survived had limb, eye, urinary tract, and heart defects [...] The severity and location of the deformities depended on how many days into the pregnancy the mother was before beginning treatment; thalidomide taken on the 20th day of pregnancy caused central brain damage, day 21 would damage the eyes, day 22 the ears and face, day 24 the arms, and leg damage would occur if taken up to day 28. Thalidomide did not damage the fetus if taken after 42 days' gestation.
So ~280 days for a pregnancy, minu 21-41 still leaves way more than half a year after taking the drug for when death occurred. And I wouldn't say the non-lethal effects are to be dismissed. If you ask me they're way up there for making sure something like that doesn't happen again. The system today (hopefully) is better than back then. And yes, personally I think it's a good thing when the approval process for drugs assumes that "every new molecule should be treated as if it were a prion".
It is perhaps worth mentioning that our ability to detect compounds that are mutagenic or teratogenic, or are likely to cause developmental abnormalities, has improved dramatically in the past 60 years, as has the stringency of drug testing. I'm not an expert, but I can certainly imagine that some of the animal testing that goes on today before a drug is approved is designed to identify problems in offspring. (The problem with thalidomide was not that its problems could not have been identified even 60 years ago; the problem was that the testing was not done or was suppressed.)
So the previous poster's question about drugs given for a short time causing long delayed effects and approved in the last 20 years stands. If a drug is not a mutagen, it is harder to imagine how it could have a long-term effect.
No idea how I missed this for three days, I'm sorry.
I absolutely agree that they could have tested for certain things but didn't. It's a product of its time in that sense:
One reason for the initially unobserved side effects of the drug and the subsequent approval in West Germany was that at that time drugs did not have to be tested for teratogenic effects. They were tested on rodents only, as was usual at the time
(side note, not to start a flame war on that, but this is a prime example of what happens thanks to regulation but not market forces)
While a lot has improved in that regard through regulation, one thing that sticks out is how similar some of this is to how things are still happening in much more recent times:
While initially considered safe, the drug was responsible for teratogenic deformities in children born after their mothers used it during pregnancies, prior to the third trimester. In November 1961, thalidomide was taken off the market due to massive pressure from the press and public
I doubly apply to medications that can potentially eff your one body/mind you have up for good what I practice in software development and try to teach my teams: assumptions make an ass out of you and me.
If a drug is not a mutagen, it is harder to imagine how it could have a long-term effect.
Harder, sure. I'm not a doctor, pharmacologist or anything like that. But I doubt that somehow doctors, pharmacologists, chemists et al are somehow immune to making assumptions. Test the hell out of this stuff. Check the "impossible" things and sometimes you will find that the "impossible" really just wasn't impossible, we just didn't think of something or didn't know about it yet. It's why general regression testing in an area can very easily find bugs. "But that's impossible, how's that related?" Well, I also can't tell you, it doesn't make immediate sense to me either but you will surely find out once you start debugging this and figure out how you broke that other downstream system, two steps removed from your change.
The OP suggested that one-off drugs rarely had long-term side effects. Thalidomide was raised as a counter example (an expectant mother might take it only once). Oxycontin is not a counter-example; the long term side effects (as opposed to short-term overdose) require dosing over an extended period.
If I’m reading this correctly, Thalidomide caused damage to fetal tissue, but didn’t actually kill the parent? This is still an awful burden for the parent, but there’s lots of drugs that are known to cause tissue damage during pregnancy. I believe this is why pregnant people are often excluded from clinical trials.
Yes, it didn't kill the parent. You might have missed the part where it killed 40% of the children at or shortly after birth.
And yes, that's (one reason) why the recommendations for the Covid vaccine were not given for pregnant women at first.
The point wasn't that there are drugs known to be dangerous to pregnant women (mainly the unborn child). The ask was for an approved drug that caused delayed death.
There were definitely so many things going wrong w/ that specific drug but it serves as a really good example for why all these precautions are taken and should be taken and any new drug should not be presumed safe but presumed dangerous and proven to not be harmful. The specific time frames and measures can of course be debated to find a good spot on the spectrum and an active pandemic can influence the choices. The discussion was going in the direction of some posters saying we should assume safe first and the Contergan case very clearly shows why assuming safety is the wrong choice.
I think the ask was actually for an approved drug, taken briefly, that caused a delayed death in the person who was taking it. If we’re going to count prenatal effects, we can come up with thousands of examples. This is why pregnant women are always studied separately.
Are there any authorized or approved drugs that are taken over a short-term (say less than a month) that have been shown to cause long-term death?
authorized or approved.
Check. Contergan was approved and used in 46 countries. Notably in East Germany there are no known cases of this, because "thalidomide was rejected by the Central Committee of Experts for the Drug Traffic in the GDR, and was never approved for use."
taken over a short-term (say less than a month)
Check. As quoted before, taking Contergan past day 42 didn't harm the fetus and deformities seem to have started on day 21. Less than a month.
cause long-term death
Check. Over the long term (>6 months) it caused death in 40% of the babies born.
Nowhere in there does it say to exclude any drugs than only cause direct death to the taker. Nor do I think should that matter. I do agree that pregnant women are studied separately precisely because the risks there are higher. To quote from the wikipedia article again:
The Society of Toxicology of Canada was formed after the effects of thalidomide were made public, focusing on toxicology as a discipline separate from pharmacology. The need for the testing and approval of the toxins in certain pharmaceutical drugs became more important after the disaster.
Sure. But that’s not what they meant. Can you name any drug that, when taken over a short course, has had long term detrimental effects to the person taking it?
It's debatable what someone meant or didn't mean, if they don't say it. I tend to go by what someone actually said. Especially on the internet (or writing in general) i.e. people you don't know, whose background you don't know, without intonation etc. There's very little to no information for interpretation.
Now you asked a new question. Fair enough. Unlike the previous question, where Contergan immediately jumped to my mind, for your question nothing jumps to mind. But google helped. I think you wanted to ask a different question, more like what I originally answered to, e.g.:
Can you name any approved drug that, that when taken over a short course, can over the long term cause the death of the person taking it?
You did ask though:
Can you name any drug that, when taken over a short course, has had long term detrimental effects to the person taking it?
Check. Heroin is a drug. It's even been prescribed as a pain killing opioid.
The UK Department of Health's Rolleston Committee Report in 1926 established the British approach to diamorphine prescription to users, which was maintained for the next 40 years: dealers were prosecuted, but doctors could prescribe diamorphine to users when withdrawing. In 1964, the Brain Committee recommended that only selected approved doctors working at approved specialized centres be allowed to prescribe diamorphine and cocaine to users. The law was made more restrictive in 1968. Beginning in the 1970s, the emphasis shifted to abstinence and the use of methadone; currently, only a small number of users in the UK are prescribed diamorphine.
taken over a short term
Check. Heroin is apparently way up there in addictiveness. After a very short period of time, you will be addicted (even if not like some people claim, after the very first use and regardless of dose or your own addiction susceptibility.
However, contrary to Bayer's advertising as a "non-addictive morphine substitute," heroin would soon have one of the highest rates of addiction among its users.
Also https://web.archive.org/web/20100213101818/http://www.drugre... which curiously notes that nicotine is even more addictive than heroin. I'll not mention nicotine further here though, because the detrimental effect come from the other substances usually taken with it when ingested via tobacco as far as I am aware (tar).
long term detrimental effects to the person taking it
Check. Detrimental effects of heroin are numerous. And given it's addictive very fast, even side effects that only turn up later, I would definitely include.
Common side effects include respiratory depression (decreased breathing), dry mouth, drowsiness, impaired mental function, constipation, and addiction.[12] Side effects of use by injection can include abscesses, infected heart valves, blood-borne infections, and pneumonia.[12] After a history of long-term use, opioid withdrawal symptoms can begin within hours of the last use.
Not to mention the constant possibility of overdosing. Meaning death. The ultimate detrimental effect.
I commend your ability to think outside the box, bringing up pregnancy and addiction as answers to the asked question.
So I’ll ask a third time, hoping that perhaps finally I can get you to the original asker’s intention:
Can you name any drug that when taken for only a short period of time, like this Covid drug surely would be, and is non addictive like this Covid drug surely is not, is harmful in the long term to the person who took it (assuming they are not pregnant as all of the people who would be allowed to take it would not be)?
While I do like this discussion I also wonder why addictive substances have to be excluded. I understand that you would like have the answer to the question be "no I don't". We can find all sorts exclusions and find a narrow path to an answer that says "no no, all drugs are always safe, see, if you only take them for a month you won't mysteriously die from exactly this 20 years from now". And while that is most probably true (and if it were true, probably hard to prove), the real answer to the question is: Yes, there medications that even if taken for a short period of time will be detrimental and harmful to you over the long term and heroin or morphine are perfect examples of this.
Remember all those war movies? I remember watching Vietnam war movies as a kid and one of the things I remember best is the use of morphine as _the_ field medicine.
Now we can argue that, especially in those times, it might be better to give a soldier that just lost a limb in the battlefield morphine than not to. It doesn't change the fact that
The VA and other reports acknowledge that physicians need better training to manage opioid treatment for veterans. Between 2001 and 2009, for example, the percentage of veterans receiving pain management with prescription narcotics increased from 17 percent to 24 percent. The number of opioid prescriptions written by military physicians more than quadrupled during that time.
Full credit to you for this. My only quibble is that "narrow" should be "wide". But all of the rest of your points have been enjoyable to think about and hold a lot of important truth. I believe at the heart of it you have a concern for humans and their welfare that is to be rejoiced and encouraged. I hope you have a good weekend!
This "how did the vaccines get approved so quickly" thing has to be one of the most asked- and- answered questions of the entire pandemic. The basic delivery platform for the vaccines had already been in human trials before the pandemic. We've also been doing rapid development of vaccines for many, many years to combat things like influenza. Coronaviruses had already been well studied, and we had dry-runs for vaccine design with SARS and MERS.
You can just do a Google search to read about 1,000 articles about how the vaccines got approved as quickly as they did. You don't need to ask your friend who works at Gilead. Not for nothing: their clinical trials would probably go a lot faster with a global pandemic lighting a fire under them.
We've administered these vaccines to almost four billion people. "COVID vaccines are dangerous" has become an extraordinary claim, demanding extraordinary evidence. There are people who sincerely believe that aspirin is dangerous, and yeast, and "mycotoxins" on coffee beans, and on and on. We're not required to take these arguments seriously on faith.
Dan, you're protecting tptacek from criticism which is absolute bullshit. I very fairly criticized his lack of reading comprehension, and the fact he's not an expert in anything except for security. What he accused me of in his comments was worse and protecting him is bullshit.
He came in attacking me twice and you do nothing to his account? He didn't even read my post and then started his rant about the vaccine when I wasn't even talking about the vaccine.
If you're going to threaten with banning, I suggest you do it to everyone fairly, even if he's one of your "favorites". You should be flagging his posts, not mine.
Plus, you flagged my perfectly accurate post on how thalidomide is safe, it's the chiral version of it that causes deformities?
That wasn't a neutral post about thalidomide, it was obviously flamewar fodder, and therefore rightly flagged.
Would you please stop posting like this now? If you keep up this flamewarry/offtopic stuff, we're going to have to ban you. Also, please stop hounding any particular user. That's not in the spirit of the site at all.
There really isn't (on HN, at least) such a thing as 'very fairly criticizing [anyone's] lack of reading comprehension' in those exact terms, it's just a slightly wordier version of 'did you read the article/comment/etc'.
So 6 out of how many other studies and drugs they've released without scandal?
If we're applying the COVID standard to Pfizer, would their failure rate be greater than or less than COVID's death rate?
If we use the 2% number I've seen around here for COVID's death rate, that means if Pfizer has over 300 drugs, these six scandals are a non-issue because they happen so rarely.
It's less defending Pfizer and questioning the poster's true motives.
Some people seem determined to do anything except take precautions laid out by infectious disease experts and take medicine specifically for this virus. And they're looking for any excuse to do so.
A diversity of people will have a diversity of risk registers, this is actually healthy for long term stability because mono cultures have associated risks.
No it's about one third of drugs according to a Yale study and it took a median of 4.2 years after the drugs were approved for safety concerns to be apparent.
Again, as someone who worked with toxicology, yeah. The default is every new molecule might be highly toxic and needs to be proven otherwise.
It’s why we don’t look at a molecule and say “oh, that’s not a carcinogen! No need to test”. And the same reason we run hERG tests to make sure drugs don’t give you a fatal arrhythmia (a surprising number of drugs do this and some are still on the market).
The post to which you are (nominally) responding was not obnoxious in the least. Your name-calling most definitely is obnoxious. I thought this was an adult forum. Eternal November?
And please show us the words where where the poster claimed that “all molecules are prions”…as you claimed. I can point to your exact words here…look forward to you doing the same.
I'm not an expert, but I think if a molecule is isolated, it is possible to determine whether or not it is a prion. IIRC, prions are basically misfolded protiens that cause other protiens to misfold, like a corrupted file that passes the corruption on to every copy or derived file until the system crashes. But you can examine them before systemic problems show up. And I believe a prion has to be a protien-like molecule. Again, not an expert.
So we shouldn't introduce any new drugs unless it's been tested for more than 10 years? Seems like a great way to put a complete halt on drug development and have more people die / suffer from preventable diseases.
There are plenty of drugs with long term effects despite not remaining in the body. Every addictive substance comes to mind, but so do chemotherapies and many other things.
What’s good about this pill is that it’s only given to people who have tested positive and likely it’ll only be prescribed to people with risk factors. In the trial, the placebo group saw a 7% hospitalization rate. That is very high, and many of the other 93% surely had a bad time as well. The risk of possible long-term side effects when weighed against a very real risk of hospitalization is an easy choice. It’s different from vaccines in that way. Vaccines are given to healthy people, so there is basically zero risk tolerance.
This isn't a chronic exposure kind of drug where you really care about those things. This is a horse pill where safety is pretty directly measurable in a short time.
(And to clarify what I am saying, even though the vaccine does prevent death, there is still considerable push back. Not sure why it will be different for this drug)
Oh I think it will be gladly accepted by unvaccinated folk. The reason being is most unvaccinated people don’t believe it isn’t effective, they don’t like being forced to protect themselves by a bunch of moral busybodies.
I just accepted as soon as we saw that covid was spreading so quickly, welp I’m gonna get that. I figured I wouldn’t be that affected by it and wasn’t.
Our parents said, well if I get it I get it, and if I die, I die, now let me see my grandkids. When the vaccine came out they were like sweet I’ll get it, can we stop these stupid mask wearing and social distancing crap. No, we can’t. So now us younger folk who aren’t afraid of covid aren’t getting vaccinated because we’re being forced to, and they’re going to keep up all the stupid rules like wearing masks everywhere anyways.
An anti viral drug that is this effective gives even less reason to have any mandates around vaccines, so unvaccinated people will cheer this.
>The reason being is most unvaccinated people don’t believe it isn’t effective, they don’t like being forced to protect themselves by a bunch of moral busybodies.
I think this is something that's very understated in public discussion around COVID-19, I got vaccinated because I weighed up the odds and thought it made sense from both a social and a personal cost/benefit perspective. I didn't get vaccinated because I was gaslit into it by the government's "nudges", nor did I get it because I was nagged or shamed into it by those who can't keep their noses out of other people's business. There's few things I dislike more in a person than a Puritan wagging finger, yet all the messaging around the pandemic was nothing but wagging fingers.
People don't like being manipulated, even if it's "for their own good" or even "for the greater good". People aren't stupid either, they know when authority figures aren't being entirely upfront with them. As well-intentioned as the measures were, the institutions who imposed them have burned up a lot of public trust in the process with the use of fear and coercion as a tool to manage the pandemic as well as being a bit economical with the truth instead of just saying "we don't know" where appropriate. I think the unfortunate persistence of the anti-vax movement is partially down to this instinct for authoritarianism and shaming people rather than extending an olive branch.
I do wonder if "vaccines mean we can permanently rid ourselves of masks, distancing, and other authoritarian restrictions" would have been more effective as a campaign than "get the vaccine or you're a horrible selfish piece of crap who probably wants to bump off grandma for her inheritence". Maybe it wouldn't have made a difference, but I think it would.
> vaccines mean we can permanently rid ourselves of masks, distancing, and other authoritarian restrictions
They said that, and it turned out to also be a lie. I got the vaccine because I was threatened with loss of employment if I didn't, and enticed by a promise that frequent testing, social distancing, and mask-wearing would not be required for the vaccinated. They pretty quickly reneged on that. To say that I am infuriated is putting it mildly. I obviously cannot undo the vaccine that I didn't want and was forced/coerced into taking.
They have destroyed any faith I had in their promises. I will most certainly now refuse any further demands along these lines, whether for flu shots, boosters, or whatever. Fool me once, shame on you.
They didn't mean that the restrictions would go away if YOU personally got vaxxed, only if a respectable number in the US did. And that still hasn't happened because people are stubborn and selfish.
The parent comment was talking about public discussion of how vax would allow a faster return to normal life. Your employer is perfectly entitled to tell you to mask or distance, or where a pink jumpsuit.
With people getting fake vax cards, etc, I can see some employers deciding to err on the side of caution. Especially since some workers can't get vaxxed at all due to medical conditions.
Except they made a big deal about the no mask, no distancing promise. It was a central theme of their "get the vaccine" campaign. Oh and also you won't get fired.
Then they reneged.
Thus, they have destroyed any credibility they may have had for future similar promises.
People are stupid. As a species, we've survived despite this, but as Carlin used to say; "“Think of how stupid the average person is, and realize half of them are stupider than that.”
People hold irrational beliefs (JFK Jr. is still alive), the earth is flat, on and on.
And America in many respects can be incredibly anti-intellectual. Being smart is often a negative in a lot of environments.
That quote never sit well with me. How about "Think of how stupid the average person is, and realize there is a 50/50 chance you are stupider than that."
> So can I live my life and worry about own family and not someone’s I don’t know?
Unfortunately, no. We live in a society where sometimes we have to take collective action to prevent collective harm. Taking personally inconvenient measures to help fight an epidemic is a prime example.
Oh so you’re the one who insists we keep taking shoes off at the airport, and throw our toothpaste that might be a bomb into the trash receptacle next to the crowd of people.
Yes there are collective actions we take, and the first two weeks of covid response might’ve been justified. But nothing since then. Maybe having to get tested to get on a plane.
Natural immunity does lower your chances, but you’re saying nope for the collective good (the good you’ve decided on) you must do xyz.
And when you give a central authority permission to dictate these "inconvenient measures" to the population, what is the recourse when those authorities act in a contradictory, dishonest, or incompetent manner?
In the two party system in the US, this isn't really a viable option. It's a strange place where you're not allowed to be both pro-choice and against intrusive government. It makes an even stronger case for reigning in the centralized power of federal and state bureaucrats because they're even less accountable.
Help me understand the limiting principle in that logic. What prevents particularly egregious abuses of personal liberty using this as a pretext?
For example, people might get struck by lightning walking by your house, so we must force you to install a lightening rod on your house to protect the collective.
Where does it stop, and how do you make that determination?
The lightning example isn't really analogous. Sure, one or two people might get struck by lightning, but they're not then going to continue spreading lightning strikes once they leave my house. Moreso, those (non-existent) spreadable lightning strikes aren't going to mutate to get worse as they propagate.
There isn't an easy or obvious answer to where it stops and how to determine that, but that goes both ways. We can't just have zero laws for fear that the laws might overextend themselves.
Unfortunately, we have to deal with nuance either way.
1. The vaccine is extraordinarily effective at mitigating risk of hospitalization and death.
2. No current COVID vaccines are sterilizing. Vaccination confers only marginal reduction in ability to carry and transmit the virus (and even this, mainly due to duration, not due to viral load).
Taken together, the "get vaccinated to protect me" canard is insane. I don't care if other people are vaccinated or not, because I am. Any other position is political, not scientific.
There is a minor argument to be had over the (tiny) immunocompromised population, but it's important to bear in mind that this population already does conduct their lives with isolation, antiviral, antibacterial, and other safety protocols regardless of COVID. They did it before the pandemic, and they will after. Nothing changes for them regardless of vaccine uptake rates.
It's better to look at excess deaths since testing is so haphazard in much of the world. Current estimates are between 10-15m excess deaths world wide.
Excess deaths are not an anomaly to begin with. Year 2000 saw excess deaths, so did 2014.
Also, when you have deliberatly forced an additional 150 million people into extreme poverty to keep them healthy ( as it were ), you are bound to see a spike in deaths.
Frankly I am surprised the death toll of the brutal restrictions toward marginalized populations is not higher.
I suspect we will soon reap the dubious benefits of undoing 35 years of 3rd world progress in 22 months.
6 months ago I still cared. Now I am just numb.
Reduced from human being with rights, to a piece of diseased flesh that must be muffled, silenced, tested, regularily injected with one experimental drug after the other and preferably locked up for eternity.
To add to it, I must feel a sende of pride in partaking in this.
Because it is the holy science.
Must be hard keeping your head up when you're swimming in such deep drama. You don't appear to understand what excess deaths mean; it means deaths over what previous trends would predict.
I would post more, but I'm sure that you're capable of using Google.
150m pushed into extreme poverty? If you mean the US, your facts are wrong. And then you pivot to the "death toll of brutal restrictions"? What is this nonsense?
You've been muffled - Oh wow, wearing a mask is just torture.
You've been silenced - Hmm, not sure what this nonsense is about.
Tested - Yup. As part of an ongoing pandemic, yup. If you can't live in civil society and agree to give up some small freedoms, buy land in Alaska and live in a cabin.
"regularily injected" - A) the drug wasn't experimental, and B) it was primarily two doses. That's not regularly...
"preferably locked up for eternity" - wow, that's exactly what my daughter said when I grounded her last week.
Do you realize how ridiculous this sounds to people? How absolutely childish and selfish? This is why a huge portion of the US is just fed up with anti-vaxxers.
From what I understand it's taken once an infection is already established. Maybe it's easier to convince the "skeptics" under those circumstances to take potentially life-saving medicine.
Sure, those same skeptics, once they're sick, happily line up for an hourlong infusion of experimental monoclonal antibodies, which have similarly unknown "long-term side effects" or whatever they're worried about.
It turns out that long-term side effects (which are a possibility with every livesaving medical intervention- what are the long-term side effects of CPR?) are a lot less scary compared to short-term death.
this drug (and all covid medicine) at this point is no longer about people hesitant to take the vaccine. this is about going back to a pre covid life. the vaccine does not protect you fully from covid 19. states in the u. s. and some eu countries have very high vaccination rates and still saw a wave of covid go through them, examples: vt, nh, de, nl. in all these places roughly 70% vaccination rate and many vaccinated people testing positive, some vaccinated dying.
when this happens governments get scared. they start doing mask and vaccine mandates. things shut down. what if you could still have these waves but nearly eliminate the chance of anyone dying? then we could start treating this like an endemic cold or flu. i think these waves in high vaccine areas show convincing “vaccine skeptics” is not the gate to get there. we could be 100% vaccinated in areas and still see covid waves. the question is can we make it less risky to the point where we can go back to where we were
Away from the debate about who will or won't take the vaccines and why, isn't this is a huge positive for the small (but not tiny) number of people for whom vaccines don't provoke immune response (severely immunocompromised, etc)? That group are also more vulnerable to bad outcomes from Covid.
There are a lot of hospital bed requests for the vaccine(1) from people who thought COVID wasn't a big deal. I'm fairly sure they'll take this drug once they experience the alternative.
1) Obviously, it's too late then. So it's only the most ignorant of people who changed their minds we have anecdotes of.
It seems to me that you're one of those not understanding COVID death rates, though.
Firstly, even though I doubt your number a bit, even a 1/200 chance of death is mighty high enough for most people to seek treatment for something.
Secondly, if you're already infected, the pill is probably less risky than those 1/200.
Thirdly, the chance of death isn't equal for everyone. A healthy young person might have a 10x reduced risk, while an older person with an existing condition a 10x increased risk. So at least for one of them the new medicine is clearly worth trying.
> A healthy young person might have a 10x reduced risk
The risk doubles every 7 years so it's going to be ~18x between generations, and much greater beyond that. Those who are old and have existing co-morbidities are really pushing the difference as severity of disease is strongly correlated with number and severity of co-morbidities.
Edit: ~18x, not ~30x. It's late here, I can't calculate 2 to the power of 4 without a calculator until I sleep, wake up, and have a strong coffee.
People think 0.5% is low, but e.g. JFK airport has about 500 takeoffs a day, if on average every day 2 or 3 planes that flew out of JFK crashed, how would they feel about air travel?
I think part of the problem is people see getting covid as something that will only happen to them once. So it is easy for them to think "well, if JFK had that many crashes, but I only had to fly once in my life, that's not so bad."
Realistically, re-infection is going to become more and more of a thing. Especially as it mutates.
GP stated that "the consequence of not taking it is death", which is demonstrably false, and specifically what I was referring to.
Also, the current mortality rate overall in the USA for Covid is less than 0.1% - in fact it's less than 0.02%. 46M confirmed cases, and 751k deaths (not all confirmed to be caused by COVID)...
The study was for patients “who were at high risk of progressing to severe illness”, where the hospitalization/death rate was 6.7% without it and 1% with. You probably wouldn’t give it out to everyone but that’s the kind of risk decision doctors make routinely.
The actual death rate for the trial cohort is close to 2%:
Pfizer said 0.8 percent of patients who got the drug combination within three days were hospitalized within four weeks — three out of 389 patients — compared to 7 percent of patients who got placebos, or 27 out of 385. And seven of those who got placebos died, Pfizer said. No one who got the treatment died within a month.
If the drug has got this far into testing, there is no chance in hell that it has >0.5% chance of death (or other awful side-effects) on ingestion. So it's an upgrade either way.
If you die of Covid, your loved ones will not care if the chance of that happening was low. You won't care either, you'll be dead. All it really takes is that one previously-undiagnosed comorbidity to put you in the front of a the line for a casket-fitting even if you're young(-ish).
If you survive but get permanent damage e.g. due to the blood clots that a lot of COVID patients develop, or due to the side effects of medications and treatment e.g. (partial) blindness from high-dose steroids or reduced mobility up to no use in your limbs especially your legs due to ECMO, then I am pretty sure you won't be running around (in the latter example because you physically cannot anymore) telling people how COVID only kills so-and-so tiny percent of the population.
Even if you escape realtively unscathed, spending a month or two in the hospital followed by some weeks of recovery or in a rehab facility (e.g. to learn how to walk again after a few weeks of coma and maybe some ECMO hoses in your legs), then that probably still would be an experience you'd like to avoid.
And that isn't even yet considering what effects you may experience in the future, "long covid" and all that.
My teenage athlete nephew mysteriously developed heart problems right around after he got vaccinated, and now he can barely walk up a flight of stairs. No one is going to say the vaccine caused it, but the timing seems pretty damning. Meanwhile, if you look at the CDC stats, the risk of injury from covid for his demographic is at least an order of magnitude lower than his risk from riding in a car.
Personally I don't believe that we are living in a rational society right now. For the fun of it, maybe I'll figure out one of those browser plugins to replace the word "science" with "propaganda".
> Meanwhile, if you look at the CDC stats, the risk of injury from covid for his demographic is at least an order of magnitude lower than his risk from riding in a car
You have to look at the CDC stats and the vehicle fatalities to make this claim. "Risk from riding in a car" is extremely low. 0.008% of teens die annually (2400 out of 30 million, age 13-19) in car accidents.
Case fatality rates from COVID are an order of magnitude higher for that age group -- 0.04-0.06%, depending on your source -- so you'd have to believe case underreporting by 100x (impossible, since cases are > 1% of population everywhere) in order for risk from "riding in a car" to be "at least an order of magnitude" higher.
Since the start of 2020, there have been 576 "All Deaths involving COVID-19" among people under 18 in the US. Compared to 60,811 deaths from all causes, that's slightly less than 1% of all child deaths.
The 576 covers almost two years, so let's call it 300 deaths/year. Not accounting for the slight difference in age ranges, that's 1/8 your number of 2400 deaths/year from car accidents. I'd call that roughly one order of magnitude lower. If you clump in children under 13 in your car accident statistic, I suspect it would fall below 1/10.
Is my math wrong or is your math wrong? If my math is wrong I would love to understand why.
I think your math doesn't distinguish between rates and amounts: indeed, if every kid in the US got COVID and only 600 died, then sure, you could make the claim that it's less risky than driving. (Also, the pandemic would be over, rendering this whole conversation moot.)
The truth is we don't know how many kids in the US have had COVID, but I'm pretty sure it's not 100% of them -- which is why the number I cite is the estimated case fatality rate and not just the total number of cases.
If you throw in an unknown scaler and fudge it, then yes you can make the statistic do whatever you want. I'd argue it's not a relevant or useful statistic, though. It's analogous to you telling me my risk of dying from a bullet to the head is near 100%. It's technically true, but I'm not going to super glue a kevlar helmet to my head.
Oh, my apologies, I originally misinterpreted one of your earlier messages when you brought up underreporting.
I understand where the 0.05% case rate number comes from (reported deaths divided by reported cases). I do personally think the reported deaths number is probably slightly over-reported and the reported cases is significantly underreported.
Even if the case fatality rate is accurate, I just don't think it's useful when assessing personal risk unless you routinely go out of your way to catch covid. If you start getting into that level of detail, you at least need to correct for comorbidities as well.
Specifically, when I say that it's an order of magnitude less likely for a teenager to die from covid than a car accident, I don't mean a teenager that caught covid or a teenager that was in a car accident. I mean a randomly sampled teenager out of the 60 million or so in the US.
I was thinking about it a bit more. Apparently the fatality rate of car accidents is 0.7%, so comparing that to a covid case rate of 0.06%, it seems like it's still an order of magnitude less fatal for a teenager to get into a car accident than to catch covid. It's been an interesting discussion, and I've enjoyed diving into the numbers more. Thanks!
Perhaps he got the vaccine in the bloodstream as opposed to muscle tissue as intended.
There are reports now of injections done without pulling back to see whether the injection site is a blood vessel. How the drug performs is seriously different in blood stream vs muscle tissue.
The primary impact of blood stream doses appears to be heart related problems.
I mean come on, if the administration of the vaccine caused it, the vaccine caused it. If he hadn't gotten the vaccine, it would not have been (as conjectured) injected into his bloodstream.
Fact is, how it gets injected appears to have a very significant influence on it's impact to the patient.
There is a clear distinction here; namely, whether the vaccine was improperly used.
Taking too much Tylonol can cause liver failure. Too much Ibuprofen can cause renal failure...
In those cases, the drug was improperly used, but the cause analysis centers on improper use, because doing that multiplies the risk and symptom severity.
See how that all works?
Saying the "vaccine caused it" simply is not enough information, which is why I linked what I did.
It is important that we get these discussions right.
Edit:
In the interest of accuracy, note I did not say the vaccine did not cause the trouble. I said it probably did not cause it, and I said improper injection probably did.
Neither is an absolute. I did not intend, nor mean to imply otherwise. What I did intend was to improve on the clarity, scope and accuracy of the discussion.
Why bother?
Better discussion means more informed people taking fewer risks and or making more good choices, all of which will improve law, costs, outcomes.
Getting back to the matter at hand, when we factor the elements down, we see one thing we can do right away, and that is we make damn sure we are administering vaccines properly.
There are risks with the vaccine. They are small by percentage, but they are there. No argument from me.
Those risks go up dramatically with improper injection; namely, it being delivered directly to the blood stream, which is entirely avoidable.
That's a fair point. It seems to me like the government is pressuring people into taking a vaccine that isn't being properly administered en masse, and all the parties involved are both protected from liability and aren't being transparent about it, all to mitigate a trivial amount of risk.
I just saw an article yesterday talking about Pfizer making $36 billion on vaccines this year.
The damn Covid is novel, meaning we get our education together, the hard way and that sucks.
And that means being smart about probabilities and potential cost and risk outcomes matters a lot! Doing that is harder than necessary too.
A small investment in proper injection can seriously reduce vaccine risks, for example. That is real news as far as I am concerned and that should be acted on STAT. And you just gotta know the optics on all that complicate and likely bias action away from optimal too.
My own first injection was not done properly. (By that I mean the person doing it did not do a blood vessel check.)
I made sure the second one was done properly.
I very seriously oppose the blanket immunity myself for similar reasons.
The profit drive on this is pretty ugly too, and it is a complicated discussion. Very generally, I must say the problem is global and allowing profit to drive policy is not doing humanity any favors.
There is a whole lot to be said... but, maybe another day.
Frankly, our current body politic is very seriously ill.
Trust is low.
Because of all that, I personally am paying close attention to how I handle my part in it and am reluctant to judge anyone else.
I am usually reluctant anyway, because what I feel should be obvious reasons! But yeah, extra care is indicated right now.
Best move, in my view as a normie out there wanting to be a good human, is to try and understand one another better, avoid judgement and the usual fear, blame and shame, talk more and hopefully more of us make smarter choices and see lower risks and better outcomes more of the time as this all plays out.
Pretty sure that is as good as it all gets right now.
That's actually the theory I developed the first time myocarditis in skinny teenagers was reported many months ago. It just makes sense that spike protein mRNA is getting shotgunned into their heart muscle cells. So, I was rather disillusioned when I saw that theory finally pop up in the news in the last month.
Saying the vaccine didn't cause the myocarditis because it was "injected wrong" isn't a compelling argument to me, or likely to anyone that's thinking rationally.
A 2% chance of death is actually very high risk for most people. Obviously with a name like dontcare007 I'm sure you've a huge appetite for risk that others don't.
If 2% of domestic flights in the US crashed, that would be about 100 plane crashes. Per day.
An accident rate of less than 1% grounded the Boeing 737 MAX. In a study of the aircraft, the FAA estimated there would have been 15 crashes over 30 years. This was seen as unacceptable.
It's much higher than that for easily identifiable subgroups -- elderly people and obese people being trivial examples.
The control arm of this study had a rate of "hospitalization or death" of 7% because they selected for subgroups at high risk.
It's fine to acknowledge that aggregate risk of Covid is low (and indeed, more people should acknowledge that fact), but we must also acknowledge that it is a serious risk for a large group of people.
That may be true, but it doesn't automatically mean that 42% of Americans are high risk. This is reflected in the aggregate statistics. Mild obesity is probably not a significant risk factor, whereas severe obesity is a big problem.
The BMI-based definition of "obesity" is a crude qualifier, and the vast majority of the affected will be in the smaller group that is both elderly and obese (esp. considering that age is, by far, the more important factor for serious outcomes.)
The trouble is that the new medications probably don't work by the time you're in the ICU with Covid. I'm not sure it was tested with this one specifically, but at least one of the recently-approved medications was previously trialled on ICU patients and showed no benefit - they had to do another study giving it to people who hadn't been hospitalized yet to get any useful reduction in deaths, and there's some reason to think this is an inherent limitation of drugs that try and reduce viral replication. This study only seems to cover patients who haven't been hospitalized at the point when they start the treatment.
I know that people can have difficulty interpreting probabilities, but given the outcome, you don't think those are really terrible odds? Of course the medicine also has a risk profile but it's clearly much, much lower.
Also it should noted that even when covid doesn't kill you it can have debilitating effects that linger or are permanent.
> Fortunately vaccination cuts that pretty close to zero.
Unfortunately as can be seen in table 5 from the link below, vaccination does not bring the fatality rate close to zero. It brings it closer to zero depending on your age. Bearing in mind this applies to hospitalized patients only(therefore not exactly IFR), the rate of death was reduced by vaccination in people over the age of 50, but not in people under the age of 50. Vaccination helps in certain cohorts.
At the start of pandemic we could have hoped that it will pass in half a year, in a year or so. Now we know that it is probably here to stay.
So eventually you will get COVID.
Depending on how long has passed after your vaccine, what variation of virus you will get, how old you are and etc will depend if it is more like 5% or 1% or so.
In my office I have 200 or so colleagues. Imagine having 4-5 funerals at the company because of this illness.
> Depending on how long has passed after your vaccine, what variation of virus you will get, how old you are and etc will depend if it is more like 5% or 1% or so.
This is fear-mongering. There is no example of a risk of death post-vaccination that gets this high. The few studies that document a decline in efficacy show a modest decline, against symptomatic illness. The vaccines remain highly effective against severe disease and death.
The article also shows that deaths-per-100k is highly dependent on age. "“Age is our top risk factor for vaccine breakthrough deaths,” said Theresa Sokol, the state epidemiologist in Louisiana, one of the jurisdictions that contributed to the C.D.C. data.". In 12-17 and 18-29, deaths-per-100k are essentially 0 for both vaccinated and unvaccinated. This is fantastic news for kids of grade school age: they can live their lives for the next 20 years without having to worry about covid medical risks.
This is meaningless without context. What percentage of the population is vaccinated? How old are the patients? What percentage of the hospitalized are extremely old/frail/comprosmised?
Remember: if 100% of your population is vaccinated, then 100% of your hospitalizations and deaths will be in vaccinated people.
When both the risks and vaccination rates are significantly different across demographic groups statistics for the whole population are often nearly useless due to Simpson's paradox.
Depending on how we define severe COVID you link is showing between 36% and 44% of the severe COVID patients at the hospital are vaccinated.
That's similar to what they have seen in Israel. As of about a month ago they were seeing about 60% of their severe cases were in vaccinated people.
Sounds pretty bad for vaccines, right? It does until you remember Simpson's paradox and take a finer look at the data [1]. It turns out that the Israel data showed in each age group efficacy against severe COVID ranging from 81.1% to 100%, with above 92% in all the 10 year age groups under 60 and still above 88% is the 10 years groups through 80.
It is very likely a similar thing is going on at the hospital whose data you linked to. That's been the case for every place I've come across in the US that published breakdowns of the stats by age group.
There is no doubt about vaccine efficacy. However it all depends. On your age, on your illnesses, on strains of virus. Who knows what you will get in 2 years.
So people who say that "pfft it is only 2% chance and only if you get" are just denying it.
You will get COVID. Hopefully you get it after a few years when there are not only vaccines but drugs widely available.
A death rate of 4-5 per 200 workers is highly unlikely. According to CDC data the infection fatality rate in a mostly unvaccinated population was 0.06% for the 18-49 age group and 0.6% for the 50-64 age group. The majority of deaths have been among older age groups, who are mostly not working at companies.
Unless you have a significant number of people working in your office over 70 years old, or if half of your colleagues are at least 60, it's more likely that nobody will die than 4-5.
I don’t think this is nearly as easy a question to answer as the other replies suggest. Pfizer will be required to make the case for safety whenever they apply for approval. It is premature to discuss this without reviewing the actual evidence they put forth.
That being said, one of the reasons that protease inhibitors are considered the way to go is that “no human proteases with a similar cleavage specificity are known, such inhibitors are unlikely to be toxic.” [1]
"Please don't talk about risk with so much at stake. Just push that code you wrote this morning to our mission-critical production system."
"We can do proper code review, unit testing, integration testing and full test cycle later on, when the pressure fades away."
We engineers all understand the risk of pushing untested code to production, but when it comes to medicine and other fields, we forget everything and rush it out. We basically act based on fear and hope.
This already went through Phase III trials. It's closer in analogy to having the entire QA team on standby at their desks to do a full test as soon as you submit a PR at 1:38am for a feature that has to go live ASAP.
The contractor that did a small percentage of the research, yes. Failures and fraud occur, and thankfully this one was small enough that it didn't matter.
Pfizer also made Celebrex, the anti-inflammatory that they knew caused health issues but they buried them and claimed it was safe.
We are living in an upside down world now. All of a sudden the drug companies are the "good" guys. Since when did the drug companies suddenly become the heroes?
1986: Pfizer had to withdraw an artificial heart valve from the market after defects led to it being implicated in over 300 deaths. The US Food and Drug Administration (FDA) withdrew its approval for the product in 1986 and Pfizer agreed to pay hundreds of millions of dollars in compensation after multiple lawsuits were brought against it.
2003: Pfizer has long been condemned for profiteering from AIDS drugs. In 2003 for example, it walked away from a licencing deal for its Rescriptor drug that would have made it cheaper for poorer countries.
2011: Pfizer was forced to pay compensation to families of children killed in the controversial Trovan drug trial. During the worst meningitis epidemic seen in Africa, in 1996, Pfizer ran a trial in Nigeria their new drug Trovan. Five of the 100 children who took Trovan died and it caused liver damage, while it caused lifelong disabilities in those who survived. But another group of 100 children were given the conventional “gold standard” meningitis antibiotic as a “control” group for comparison. Six of them also tragically died because, the families said, Pfizer had given them less than the recommended level of the conventional antibiotic in order to make Trovan look more effective.
2012: Pfizer had to pay around $1billion to settle lawsuits claiming its Prempro drug caused breast cancer. Prempro was used in hormone replacement therapy, usually for women going through the menopause. The settlements came after six years of trials and hardship for the women affected.
2013: Pfizer paid out $273 million to settle over 2,000 cases in the US that accused its smoking treatment drug Chantix of provoking suicidal and homicidal thoughts, self harm and severe psychological disorders. Pfizer was also accused of improperly excluding patients with a history of depression or other mental disturbances from trials for the drug. Later, in 2017, a coroner in Australia ruled that the drug had contributed to a man’s suicide. The man’s mother campaigned to change the label on the drug.
2020: Pfizer reached an agreement with thousands of customers of its depo-testosterone drug in 2018 after they sued it for increasing the likelihood of numerous issues, including heart attacks.
And if Pfizer fucked up the covid-19 vaccine, one of 20 other alternatives would gladly inform the public and remove a competitor from the market. That's the great thing about having so many alternatives for the covid-19 vaccine, all of them can gain an advantage by pointing out that a competitor's vaccine does not work.
The first line treatment for strep throat is penicillin or amoxicillin. Z-pack (Azithromycin) would typically only be used in case of a penicillin allergy, or maybe resistant bacteria.
'There is no relationship at all between the two drugs, said Dr. William A Petri, professor of infectious diseases at the University of Virginia.
“The only way they are alike is that they are both pills,” Petri said.
Dr. Kevin J. Downes, assistant professor of pediatrics at the Perelman School of Medicine of the University of Pennsylvania, agreed, “They are dramatically different molecules. The drugs are different in their structure and their molecular size.”
[...]
Ivermectin binds to glutamate-gated chloride channels and is used to treat parasite infections, said Joseph Glajch, a consultant in pharmaceutical and analytical chemistry.
“These two are so far apart,” he said. “If you look at how they interact with the body..., they don’t even go to the same pathways or receptors.”'
To the user who keeps getting comments deleted for bringing up this guy's funding: please look up "ad hominem fallacy". Attacking someone making a statement says nothing about the truth of their statement
Because you can't trust Pfizer, unfortunately. Here's how they run their "studies" nowadays: https://www.bmj.com/content/375/bmj.n2635. This is just one lab, nobody has come forward (yet) about others, and given that the whistleblower has been fired right away, chances of other whistleblowers coming forward are pretty low. Be that as it may, I regard whatever they say about safety or efficacy of their products the same way I did in 2019 - with extreme suspicion.
Then your criticism makes even less sense. If they tested for natural immunity, they could put the people who have natural immunity in the vaccine group.
> some assholes will use it as an excuse not to get vaxxed, completely missing the point (among others, trying to prevent something worse than Delta).
It's still quite unclear whether vaccinated or unvaccinated people pose a greater risk via viral evolution (especially w/r/t risk to people that are already vaccinated). Basically comes down to a comparison of a higher level of spread with "normal" genetic drift vs. a somewhat lower (but still fairly high) level of spread with selection for immune escape of the current vaccine versions.
It's still a good idea to get vaccinated to help your own reaction to the virus, and to keep hospitals at sustainable capacity, but the "UNVACCINATED ARE MAKING THE VIRUS MORE EVIL" claim is, at this point, more propaganda than fact.
There's no bad propaganda when it comes to persuading people to get vaccinated. The alternative is the mess we're in now because people hesitate to get vaccinated. This study uses HIV to model sars mutation. HIV is highly mutagenic :
1. PLOS study constantly uses the word "risk" and "may", i.e. the authors don't know the actual probabilities of escape and use a mathematical model based on a far more mutagenic virus, HIV.
2. even if there's a low threshold for the virus to mutate, most of the mutations are not viable
3. so far we've seen only 4 dominant strains, the rest are being outcompeted : https://www.google.com/search?q=how+many+dominant+mutations+of+covid+are+there
4. It makes more logical sense to me that if your unvaccinated body takes 10 days to mount a peak immune response (as mentioned in the PLOS study), that still gives the virus more time to mutate even if there are no pressures to mutate. There's lots of missing data in your study, particularly what exactly is the mutation rate for sars-cov-2 in vaccinated vs unvaccinated populations? But if we simply look at where the dominant mutations have come from so far, it's not from countries with high vaccination rates like Israel, New Zealand, or from asian countries that take serious measures at curbing the spread of the virus, singapore, japan, korea, china.
> There's no bad propaganda when it comes to persuading people to get vaccinated
This is a very dangerous road to go down. I strongly disagree that the government and media should have license to lie to people if it's a useful lie in the moment. All that does is erode trust in those institutions, the longer term results of which are the root cause of most of the anti-vaccine sentiment today.
> PLOS study constantly uses the word "risk" and "may", i.e. the authors don't know the actual probabilities of escape and use a mathematical model based on a far more mutagenic virus, HIV.
You're absolutely right. The experts are just guessing the odds of this stuff, and you and I are really only able to do the same, with even less certainty.
> It makes more logical sense to me that if your unvaccinated body takes 10 days to mount a peak immune response (as mentioned in the PLOS study), that still gives the virus more time to mutate even if there are no pressures to mutate
With all due respect, when dealing with probabilities like this, non-experts estimating what makes "logical sense" is completely useless.
> if we simply look at where the dominant mutations have come from so far, it's not from countries with high vaccination rates like Israel, New Zealand, or from asian countries that take serious measures at curbing the spread of the virus, singapore, japan, korea, china.
Israel and New Zealand have negligible populations on a world scale. The efficacy of social distancing in the east Asian countries you mentioned is clear, but completely unrelated to the question at hand. The delta variant came from India, a country of 1.4B people, before any of them had access to the vaccines. That tells us nothing about whether the vaccines net encourage or net discourage harmful virus evolution.
It's okay to say we don't know, and in fact far better to do so than to make up a politically convenient answer.
All those countries are small aside from China whose vaccine is not very effective and people with high East Asian ancestry have natural mutations against COVID. https://www.nature.com/articles/s41586-020-2818-3
You say vaccination or serious measure, which is the truth? Could a mutation not occur elsewhere and infect a densely populated area? There isn’t evidence that the places most affected were the origins of the virus mutations.
That article shows a clear correlation between 2 locations with large populations that are susceptible to high risk of severe covid and 2 of the main mutations delta (india) and alpha (uk).
Genuine question: is it necessary to get vaxxed if - all else held the same - the cost is not significantly higher for the antiviral? Wouldn't that cut the risk down so significantly that we can safely say, "Vaccinate if you're at-risk for your own protection, and have negligible risk otherwise"? This changes the entire risk calculation.
Vaccination is in large part about beating the epidemic, i.e. the population-scale prevalence of the pathogen, by preventing most of the infections and therefore disease transmission. This pill is about treating disease symptoms, but while doing nothing to limit disease spread.
So while on a personal level, there may not be dramatic differences in death rates etc., on a population level the differences are huge.
Incorrect, mRNA COVID vaccination is about reducing symptoms in infected patients. It does absolutely nothing to slow down or stop the spread of COVID.
This is one of the most persistent pieces of misinformation I've seen, especially in the face of clear data.
The reduction in transmission rate for the vaccinated is 89%. Even for someone with a breakthrough infection of the more contagious Delta variant being vaccinated means a 63% reduction.
It's become reflexive whenever people claim it stops transmission because all evidence for it is very very recent, while the claim of stopping transmission started to be used with authority as early as Feb 2021 with absolutely no evidence. Not even Pfizer's press release in 2020 tried to claim they even researched it, let alone had a conclusion, despite people nowadays claiming otherwise.
In my untrained eyes (from an edipemological point of view), it depends on many things. It's a slippery slope anyway ... But I sort of view it from a "practical ethics" point of view if you will ....
First thing I noticed is these result actually select people who had the antiviral administered to them within 3 days of the symptoms appearing. I have personally known people who unfortunately died in a week tops after contracting the virus (they had pre-existing conditions, namely hypertension and diabetes).
Which brings me to my next point: Suppose the antiviral exists and is viable to even beyond 85%. How much will it cost ? I'm not a US citizen, but I'm thinking insurances will rush to trying not to cover anyone who's not vaccinated or some shady shit because they always do. And how about 3rd world countries like the one I come from. We can't even get RNA vaccines, let alone an experimental drug like this.
And now my final and target point: Suppose you don't want to get the vaccine and you can afford the drug. We do have proof that even if the vaccine doesn't protect you from the virus completely, even in the unfortunate case where you do contract it, you'll end up infecting less people. Now if you choose to not get vaccinated, then you really do risk potentially contaminating more people that will either have no access to the antiviral within a reasonable effective timeframe(and that maybe not vaccinated either) or just plain infecting more people overall.
Not the cleanest reasoning, and not a mathematical proof by any means, but I believe it's one of those "mathematical" problems where the proof is finding an edge case (sorry studied in french, really don't know how they say it in english).
I'm guessing you only get this pill if you're hospitalized with severe symptoms. In which case, you're still occupying hospital beds/resources, which is the main remaining threat to rational society.
> which is the main remaining threat to rational society
What is a "rational society" and what threatens it?
My default view is Rawlsian: I'd like to live in a society which maximizes the well-being of the least well-off people, even if that's not currently me. In that framework one threat from a pandemic is that some at-risk people might die (people with some health conditions will die when infected and may not respond well to vaccination); that threat can be mitigated if people develop treatments, apply nonpharmaceutical interventions like indoor masking, and participate in community inoculation.
There are other very different notions of a "rational society". In some, the premature death of people who are elderly, medically at-risk, or choose to avoid vaccination might be preferred outcomes. Hmmm.
If your reason to not get the vaccine is to avoid yet-to-be-discovered side effects, wouldn't that apply to this drug as well though? Not to mention that the vaccines now have a year-long track record of safety despite widespread adoption, where as this one has yet to be deployed on such a large scale.
Also, the vaccines work on a principle that's somewhat well understood, accepted and deemed safe: training the immune system by giving it something that looks like the virus so it can learn. The only novel part is how this "something that looks like the virus" is created (mRNA as opposed to weakened but real virus). On the other hand this new molecule has a totally different mechanism of action and the potential for side effects may be higher.
yes vaccination 300% (i.e. single, second, and third booster dose when ready!) Drugs that have anti-biologic properties are never good for your body, neither is allowing symptoms to fully manifest before taking drugs. People should still get the vaccines. The drugs are a backup in case the virus still overwhelms your immune system or causes it to overreact.
I think that crowd will hate on this new drug. It's from Big Pharma, very expensive, it's probably full of GMOs and brain-controlling chips from Bill Gates. They'll stick with their cheap, generic ivermectin.
GMO’s is emotional, largely based on the public image around the word ”mutant” meaning a hulk like green person that was irradiated by a James Bond villain etc
> completely missing the point (among others, trying to prevent something worse than Delta)
Given that there isn’t a ton of data showing that vaccination actually reduces infection or transmission, and all of the clinical studies before approval were based on hospitals death, I don’t think you can claim that’s ‘the point’.
It would be somewhat ironic if antivaxxers latch onto this drug, because it actually has a possibility of turning out to have bad side effects that will only show up much later (increased rates of cancer), which is a major reason that is given for people not wanting to get vaccinated.
Edit: Actually I was confusing this with molnupiravir; this drug is presumably perfectly safe.
Sorry I was confusing it with Merck's molnupiravir which could potentially cause genetic errors in humans. The drug this article is about is unlikely to have side effects that appear later.
Because of its mechanism of action, which is to induce massive and deadly mutation and reproductive issues on the virus. Normally this should not have an effect on our bodies, but it's not impossible that it does lead to higher cancer rates.
> but it's not impossible that it does lead to higher cancer rates.
That is almost a non-statement that could be seemingly applied to anything with some pharmacological effect. I think you and I and every other layman are talking out of their ass when we make some kind of determination as to any side effects Paxlovid might have.
It's not a non-statement, such effects are a serious concern for nucleoside analogs. But I can't say it's an actual issue or that it's definitely not because we just don't have sufficient data.
You're correct that almost anything with a pharmacological effect has such concerns, which diminish with time. That's why prevention is superior to treatment.
Also I wasn't talking about Paxlovid, but molnupiravir, which you'd also be taking.
I don't know enough about the difference between how viral RNA polymerase and human RNA polymerase function, but my hunch is the nucleotide substitution might not apply to us. This could be wrong.
That's the hunch these drugs are based upon. But things in biochemistry are rarely black and white. There are people with serious experience in the field saying that there is a risk.
Certainly the risk is lower than untreated covid, but it's just that if you can avoid the risk then all the better.
I'm not sure that's how it works. There's a calculus to this I don't quite understand.
The group blesses and curses treatments based on contradictory criteria.
Ivermectin is blessed, supposedly because it is cheap. Molnupiravir is cursed, because it is a new drug Big Pharma wants you to pay more for. The vaccines are cursed, even though they're cheap. Monoclonal antibodies are blessed, even though they are very expensive, and are effectively just the products of vaccination.
I think it's more likely people are just doing what they are told by whoever influences them the most. None of it has to be consistent or make any kind of sense.
I'm being downvoted but in March, conservatives were screaming about how unfair it was that prisoners were getting their shots first. Things aren't always what they seem.
But just like I can trust the things I buy from the grocery stone to not poison me or to have stones embedded inside, I trust medical products taken by millions or even billions of people
People in urban areas like yourself only get food from the grocery store, so they naturally treat everything behind that as a black box. You have a learned belief in the “API of the City”, and that’s OK. The API tells you to inject yourself with random concoction that you can’t independently verify and so you do it.
People in rural areas see how food grows directly— from the ground or from livestock. They can get food from the grocery or from their backyard: sometimes the backyard food is fresher and better. These folks don’t trust the “API of the City” to provide for them. That’s OK too. The API tells them to inject themselves with a random concoction that they can’t independently verify and so they refuse.
> some assholes will use it as an excuse not to get vaxxed
Well, they've succeeded in holding out long enough, now that there's no longer a good reason to get vaxxed. Because, as most people are starting to realize, the pandemic is over (at least in the US).
It's potentially almost over thanks in large part to all the people who made the sensible society benefiting decision of taking the vaccine and/wearing a mask when in a non-dining public indoor space.
Whether it's gun violence, suicides, drug overdoses, car accidents, or now Covid -- the US has an insane threshold for what counts as an acceptable death rate.
> Ivermectin binds to glutamate-gated chloride channels and is used to treat parasite infections, said Joseph Glajch, a consultant in pharmaceutical and analytical chemistry.
> “These two are so far apart,” he said. “If you look at how they interact with the body..., they don’t even go to the same pathways or receptors.”
Almost as if after clinical evidence (sure, arguably week) and a promising mechanism of action (yeah, in silico) a widespread, double blind RCT should have been conducted a year ago...
My question/comment was not intended to spark discussion about the efficacy of ivermectin for covid-19, just confused at the classification of ivermectin as a protease inhibitor. I don't think most doctors, pharmacists, or epidemiologists would think of ivermectin as a protease inhibitor, even with a few in silica studies suggesting protease activity in certain circumstances.
There have been at least 14 RCTs, including double blinded studies. In meta-analysis, "ivermectin was not efficacious at managing COVID-19"[1]. I won't engage further in that discussion.
Yeah the big pharma were so moral they allowed any other company to copy their complex vaccines that needs special cold storage with significant investment they got free from the government also for specialized manufacturing, all this is offered patent free out of the goodness of their hearts! I wonder why smaller companies didn’t take them up on their generous offer?
There's enormous amounts of evidence that ivermectin doesn't work.
If did work, we wouldn't have over 600,000 dead here in Brazil. A sizeable portion of the population, encouraged by our goverment, made use of ivermectin as a so-called preventive treatment. It didn't work, and hundreds of thousands died despite it.
The only thing that is actually working is the advance of the vaccination campaign. While it started late, we thankfully are have a very large support for vaccination, and very few antivaxxers.
Indeed, as a Brazilian, it gets to my nerves reading those conspiracy theories about "how the media hid ${TREATMENT}'s effectiveness" or "there is no interest on using ${TREATMENT} because no money to be made! :c".
I seriously think those people are heartless. So many died because of those ineffective treatments and they keep advocating for them, with higher (and more dangerous) dosages while linking to random papers as if all of them are trustworthy (like a certain senator here). Worse, they consider those who use the right tool for the job (vaccines) the equivalent of religious nutjobs.
Most of their theories don't even make sense when you consider the wide picture: For example, even if the "evil big pharma" wasn't interested on cheap treatments, governments would have done anything to avoid lockdowns that heavily damaged their economies. It is a sick joke all the way down and a disgrace to all who died before a proper treatment was available.
I'm deadly sure that if they had lived through a collapse of public and private healthcare systems and/or had lost someone over it, they wouldn't be talking BS all the time.
And there are a frightening number of people who will say there's not enough data while Pfizer launches R&D for an entirely new drug to get it to market.
Does no one else pay mind to the fact that pharmaceutical companies have zero interest in potential treatment options if they're not under patent anymore? Why do we trust them implicitly but suspect Apple does shady things like employ slave labor and suicide nets, or that Facebook downplays psychological side effects of their products?
The real scandal would be that ivermectin worked and therefore invalidated the emergency vaccine authorization, but I doubt that will ever see the light of day given the coordinated media blitz against "horse paste".
All these quoted studies were under-powered or administered far too late and low dose and many only gave 3 does of ivermectin. It does work if you have a higher dose at .6 mg/kg, take it fairly early and as recommended by the NIH.
Teres no reason to believe ivermectin does help. Firstly the study that Ivermectin-for-covid is based on in vitro(cell-in-petri-dish) studies of rhesus monkey liver cells[1]. Additionally. Rhesus monkeys have differing bodies sizes and in order to get an equivalent dose in humans would require overdosing on ivermectin, which can and has lead to death. Ivermectin targets the host nuclear transport importin α/β1 heterodimer in host tissue, exerting effects directly on cells of the human body.[2]
As for vitamin D. That's an interesting one. Vitamin D isn't only correlated with better covid-19 outcomes, it's associated with better cancer outcomes, as well as flu outcomes. It's also associated with better outcomes in HIV, malaria, and car crashes. It's associated with a lower ALL cause mortality[A]. Impressive stuff. Now either it's the fountain of youth, or as they like to say in the sciences this is a case of "correlation does not equal causation". Now it probably won't hurt to take, but there's more to it than that. Considering about 42% of Americans are deficient in vitamin D[B] it's not a bad idea to supplement, but that also points to another correlation-- the portion on the population that has sufficient vitamin d levels either goes out often enough to synthesize it naturally, or simply is the type to go out of their way and supplement it. So two groups that will have greater physical health than the average person. This could explain why people with sufficient vitamin D do better than with covid than the average person
And what of the methodologies presented in the individual studies? Are they not sufficient?
Who are you, or anyone, to assume the curator / scientist / reporter who put this together is acting with negative intent when it presents a positive outlook for the use of other treatments that have manifested in good outcomes and healing?
Don't get me wrong, it's good to be skeptical, just not selectively.
Don't get me wrong Doc. Neither you nor I nor a random dude with a web-site has the capacity to make statements that might lead people to make medical decisions. Leave that to doctors and governments please.
It is good to be skeptical, but also important to trust the right people.
So much this. It's all too real, and happening at an alarming pace. I've stopped counting the reports and interviews from doctors and medical workers who have bravely shared their stories and fears around this.
It's unbelievable to me that people can't find the positivity in studies and results like these as long as they pose a threat to their beloved "miracle" vaccines that are objectively wrecking too many people's lives with severe adverse reactions and even death, over, and over, and over again.
At some point, the horse blinders will need to be forcibly ripped off in order to help people see and understand the people right in front of them who are suffering unnecessarily as they, and their families now fight life-long conditions and grieve their losses.
It feels impossible while people clutch their pearls at the mere mention of the possibility that something _else_ exists that's sufficiently and observably effective.
That is a valid question but another thing to note is that you wouldn’t be giving this drug to the vast majority of people who do not get any symptoms from a Covid-19 infection. Nor would you be forcing people to take this drug.
Which is a fair viewpoint from the societal level, but not as much for the individual level, which was implied in the parent message - i.e. how can "I'll take experimental treatment B instead of experimental treatment A" be an argument for not taking experimental treatments in general?
Imagine both the vaccine and the drug offer the same protection, and both come with a risk of 0.00001 that you will die from taking it.
Considering not everyone who gets infected gets symptoms, would it be illogical to not take the vaccine, just in case you get infected and get symptoms, but to take the drug once you do get infected and get symptoms?
It wouldn't be necessarily illogical but would still qualify as "taking part in an experiment trial", as put by the parent post.
To determine if this is a rational strategy or not, we'd have to get real numbers (is it really likely that 1 in 100k people die from taking the vaccine?), and compare that against the reduction in probability of dying from COVID by even combining both treatments.
It is still possible to take rational decisions in the face of unknowns. Just like you probably decided, in your opinion rationally, to take the vaccine even though there really isn’t a whole lot of data available as they are pretty new.
And please, I just made up these numbers to answer the posed question:
> how can "I'll take experimental treatment B instead of experimental treatment A" be an argument
For an individual, the antiviral is better because it means they don't need to take the vaccine with any possible risks, however small, up front. Yes once an individual become symptomatic with covid-19, they're forced to be exposed to one of the risks, but at that point the antiviral is the only choice. In short, it allows an individual to delay taking the unknown risk until there's an actual known downside to not taking it; i.e. unmitigated covid symptoms. Most people will never be exposed to that downside anyways.
From a "reducing my risk of dying" perspective, you'd have to balance the risk of dying from taking the vaccine vs the risk of dying from COVID with zero treatments, one treatment, or both treatments.
The numbers could lean either way and would be very sensitive to variations in the probabilities involved - I'm sure it would be very hard to reach any form of consensus on "probability of dying from taking the vaccine". It's also worth addressing wasn't even making the point of which (so-called) experimental treatment has a better likely outcome but rather addressing criticism at (so-called) experimental treatments in general.
From an "unknown risk" perspective, you'd also have to consider that COVID itself could have yet-unknown long-term risks.
> From an "unknown risk" perspective, you'd also have to consider that COVID itself could have yet-unknown long-term risks.
That would not factor into a correct analysis: the unknown risks of covid are the same whether or not you get vaccinated (or any other treatment) because by definition the vaccine has not been shown to mitigate the unknown risks.
mRNA treatment is now also called a vaccine. That type of treatment has never been used on the general population until c19 came along and testing standards were reduced. It is a very interesting type of new treatment, but we lack long term data to say it's truly safe.
Same can be said for any patented-molecule treatment. But that's just a new type of molecule, not a whole other type of treatment. Hence I'd say that molecule-drugs are less experimental than mRNA-vaccine jabs.
Wikipedia defines "vaccine" as "a biological preparation that provides active acquired immunity to a particular infectious disease", which in my view would fit the Pfizer/Moderna shots. Which definition of "vaccine" do you subscribe to that these "treatments" don't fit into?
Also, mRNA is not the only type of vaccine for COVID.
Finally, two more questions: would you clarify which definition of "experimental" you subscribe to? And do you have a source for "testing standards were reduced"?
Here's a link to the CDC definition from 2017: https://web.archive.org/web/20171203162427/https://www.cdc.g... ("Vaccine: A product that stimulates a person’s immune system to produce immunity to a specific disease, protecting the person from that disease.")
> It's all marketing at this point.
Definitions made prior to the pandemic would already fit the mRNA vaccines, therefore the claim that the definition was stretched for marketing/persuasion reasons don't really hold water.
> Not FDA approved in the US. "approval pending"
This FDA link claims Cominarty was approved in August 23 2021. The word "pending" is not found in this page.
Of course the actual individual version for COVID-19 is newer, but then again, so is any flu vaccine that is updated basically yearly. What matters is the age of the "vaccine platform".
The definition: mRNA does not stimulate the immune system directly. That's what's new about it. Did you know that? It tricks the cells of the body to create protein that then get hopefully a reaction from the immune sys. They typically also add some other stuff that helps to elicit this reaction (usually stuff that in large quantities is harmful to humans).
> Definitions made prior to the pandemic would already fit the mRNA vaccines, therefore the claim that the definition was stretched for marketing/persuasion reasons don't really hold water.
You you say mRNA treatment is not new? I think this is the first rollout of such medicine on humans.
See the PhaseIII trails were allowed to be skipped with the EUA.
The process by which the treatment is now pushed to kids is even more botched.
I believe we are exposing the younger (say <60) to risks bigger than the c19 poses itself. Yes we're dealing with an overly stressed healthcare system, but that's a different matter. The jab should be worth it for the person him/her self, and that should be made clear to that person, if they dont believe it they will not take it and that's their choice.
Im okay with tax being used to give people that want the free jabs. Im not okay with persuding people to to take it with anythign other than data.
This isn't meant to be a jab or insinuation about you in particular, but: what about an Adenovirus vaccine? You can still (AFAIK) get the J&J vaccine in the US, and the AZ vaccine in most of the rest of the world.
I'd argue that mRNA vaccine development represents the most rigorous that the field of vaccinology has ever been, but those (Adenovirus) vaccines use a well tested, not-previously-experimental delivery technology. Do you have an objection to them?
"Play"? :-) It's always the same play, they're making medicines to sell them.
And vaccinated people can get infected and suffer from serious symptoms. If the entire world were vaccinated and 0.1% of people would have serious symptoms, that would still be more than 8 million people looking for a cure.
yes. many people are vaccine hesitant because they dislike or are afraid of shots.
also if this can help impact the rate of hospitalization and death among unvaccinated than it also alleviates the need for actual vaccinations to do the lift of ending the overall pandemic.
Does it matter? Vaccine flows like water these days, and at least in the rich world, nearly everyone who needs this chose to be in that position. Making that choice should be incredibly costly.
Oh it matters. A drug that is not expensive, patented or is readily available surely will either never really be tried or will be tried in such a way it’ll never succeed.
Expensive drugs will enjoy trials designed and sponsored by their manufacturers.
If it's expensive - we'll have government printing more money to afford the pill, like they've been doing for the vaccine, and the general populace for the past 2 years.
Do you think there's a significant increase in government spending for paying for these pills? It's trivial compared to things like enhanced welfare benefits or military spending
Yes, by sheer volume. It’s not trivial. Monoclonal antibodies are thousands of dollars per treatment for instance and the idea of business loans or small business aid is that it’s going to investment. Of course none of this matters in 2019 a repo crisis was triggered: https://www.wikipedia.org/wiki/September_2019_events_in_the_...
They needed to inject liquidity into the economy and justified it with COVID.
> In August, DeSantis began opening the first of 21 rapid-response sites to administer Regeneron treatments, and more than 90,000 doses have been given.
>monoclonal antibodies [cost] over $2,000.
It’s about $180,000,000 just for Florida and that doesn’t include administration.
Seems since there are so many unapproved off-label therapeutics and now more and more under-patent money making ones we'll lighted the facist vaccine mandates.
Is probably just a large dose of vitamin D with other inert ingredients making it patentable. Vitamin D has already had research showing same results but you can't patent Vitamin D alone.
Read it carefully. Pfizer falsifies clinical data and covers up significant adverse effects. FDA knows about all of that and covers their asses. Whatever comes from Pfizer will be authorized without any questions being asked. It's not even a legislation, but a straight up internal arrangements between FDA and Pfizer executives.
Whatever you see in media about Pfizer is a complete crap.
I also want to remind you that Pfizer is responsible for the largest health care fraud in history. They had to pay $2.3B fine in 2009.
> The Pfizer Phase III trial involved 44,000 people and 153 locations. From August 2020 through Sept. 17, 2020 — when she was fired — Jackson told CBS 17 that Ventavia accounted for at least 1,200 of those people and accounted for three sites.
The author of the BMJ piece is quoted as saying “people are going to use this to push a political position because that’s what they’re interested in”, so congrats on demonstrating that.
1986: Pfizer had to withdraw an artificial heart valve from the market after defects led to it being implicated in over 300 deaths. The US Food and Drug Administration (FDA) withdrew its approval for the product in 1986 and Pfizer agreed to pay hundreds of millions of dollars in compensation after multiple lawsuits were brought against it.
2003: Pfizer has long been condemned for profiteering from AIDS drugs. In 2003 for example, it walked away from a licencing deal for its Rescriptor drug that would have made it cheaper for poorer countries.
2011: Pfizer was forced to pay compensation to families of children killed in the controversial Trovan drug trial. During the worst meningitis epidemic seen in Africa, in 1996, Pfizer ran a trial in Nigeria their new drug Trovan. Five of the 100 children who took Trovan died and it caused liver damage, while it caused lifelong disabilities in those who survived. But another group of 100 children were given the conventional “gold standard” meningitis antibiotic as a “control” group for comparison. Six of them also tragically died because, the families said, Pfizer had given them less than the recommended level of the conventional antibiotic in order to make Trovan look more effective.
2012: Pfizer had to pay around $1billion to settle lawsuits claiming its Prempro drug caused breast cancer. Prempro was used in hormone replacement therapy, usually for women going through the menopause. The settlements came after six years of trials and hardship for the women affected.
2013: Pfizer paid out $273 million to settle over 2,000 cases in the US that accused its smoking treatment drug Chantix of provoking suicidal and homicidal thoughts, self harm and severe psychological disorders. Pfizer was also accused of improperly excluding patients with a history of depression or other mental disturbances from trials for the drug. Later, in 2017, a coroner in Australia ruled that the drug had contributed to a man’s suicide. The man’s mother campaigned to change the label on the drug.
2020: Pfizer reached an agreement with thousands of customers of its depo-testosterone drug in 2018 after they sued it for increasing the likelihood of numerous issues, including heart attacks.
The vaccines are being widely administered by dozens of countries, each with their own regulatory authorities, and the whole process is generating enormous amounts of data, including ones outside Pfizer's control/influence.
Wait a minute. I don’t see any political position in the comment you’re replying to. I don’t even see a hint of one. I can’t even figure out what political position on what topic would be likely.
The author was obviously aware of the possibility that "one of Pfizer's vendors did a bad thing" would likely be turned into "Pfizer bad/scary!" (with the implication that doubt should be cast on the vaccines/meds) as it is here.
If a politician hired a hundred vendors to send direct mailings, and one of them used forged stamps, would it be fair to say the politician used forged stamps?
This is more like.. what if you're a food manufacturer and find out the food was contaminated. Do you keep shipping it to recoup costs and stay quiet, or do you come clean and risk the negative PR?
The worst case scenario here is ~1,200 out of 44,000 trial participants in three out of 153 trial sites may have had bad data. I would hope that Pfizer and the FDA are double-checking the data from that vendor (and I strongly suspect that one vendor with aberrant data versus the rest of them is already something they keep an eye out for).
We've subsequently given (and monitored for the same sort of issues we look for in these trials) hundreds of millions of doses of the vaccine successfully.
Which is an assertion the BMJ article doesn't support.
"Revelations of poor practices at a contract research company helping to carry out Pfizer’s pivotal covid-19 vaccine trial raise questions about data integrity and regulatory oversight. Paul D Thacker reports"
"A regional director who was employed at the research organisation Ventavia Research Group has told The BMJ that the company falsified data, unblinded patients, employed inadequately trained vaccinators, and was slow to follow up on adverse events reported in Pfizer’s pivotal phase III trial."
> Ventavia executive identified three site staff members with whom to “Go over e-diary issue/falsifying data, etc.” One of them was “verbally counseled for changing data and not noting late entry,” a note indicates.
> At several points during the late September meeting Jackson and the Ventavia executives discussed the possibility of the FDA showing up for an inspection (box 1). “We’re going to get some kind of letter of information at least, when the FDA gets here... know it,” an executive stated.
> Reports may include incomplete, inaccurate, coincidental and unverified information.
> The number of reports alone cannot be interpreted or used to reach conclusions about the existence, severity, frequency, or rates of problems associated with vaccines.
The numbers are suddenly high, in part, because of this:
> Healthcare providers are required to report to VAERS the following adverse events after COVID-19 vaccination [under Emergency Use Authorization (EUA)], and other adverse events if later revised by CDC...
There's a COVID-specific reporting requirement on a previously optional system.
Agreed. The reports that VAERS provides can hint at rare adverse outcomes for vaccines, but it simply doesn't hold any significance compared to clinical trials. Comparing them is just outright false equivalence.
There is no conspiracy theory here. Stop using that term to minimize the importance of things. VAERS is a data point. Check out similar data points from other countries. Numbers DO match.
What other data points? Can you provide peer reviewed high quality data to support your claims? Just because you want a conspiracy theory to be true does not make it so.
Can _you_ provide any other legitimate data point that tracks adverse vaccine reactions? Most likely not. Because the narrative is such that if there is anything negative comes out, people are immediately being canceled or fired.
"Due to the program's open and accessible design and its allowance of unverified reports, incomplete VAERS data is often used in false claims regarding vaccine safety."
VAERS is an unvetted database of adverse events that occur some time after a vaccine has been given. It does not mean that there is a causal link.
"CDC cautions that it is generally not possible to find out from VAERS data if a vaccine caused the adverse event, or how common the event might be.[5]"
Particularly, in the current pandemic, we vaccinated a LOT of sick and elderly patients, and we vaccinated them first, in almost unprecedented numbers. So VAERS will have a LOT of "adverse events", simply because the sick and elderly have a lot of these adverse events, vaccine or not.
Related, FDA's War on Dr. Burzynski, after Burzynski won his court cases, the FDA gave away Burzynski patents to their FDA pharma buddies. The FDA stole it after they couldn't win lawsuits against Burzynski in multiple court cases.
I'm skeptical and I wait. I'll be the last one in line to take the shot. I'm a software engineer and I know that if you deploy a system to production RIGHT AWAY, something is gonna fail.
Stop spreading disinformation. This has gone through studies showing significant positive benefits. Ivermectin has small studies with dubious methodology showing possible effects and larger studies with better methodology showing no benefit, along with substantial side-effects.
No, I’m not. You’re citing notorious disinformation sites whose anonymous creators are relying on you seeing big numbers and not noticing the problems with methodology and analysis. When actual experts look at those studies, the results have not held up.
> Different websites (such as https://ivmmeta.com/, https://c19ivermectin.com/, https://tratamientotemprano.org/estudios-ivermectina/, among others) have conducted meta-analyses with ivermectin studies, showing unpublished colourful forest plots which rapidly gained public acknowledgement and were disseminated via social media, without following any methodological or report guidelines. These websites do not include protocol registration with methods, search strategies, inclusion criteria, quality assessment of the included studies nor the certainty of the evidence of the pooled estimates. Prospective registration of systematic reviews with or without meta-analysis protocols is a key feature for providing transparency in the review process and ensuring protection against reporting biases, by revealing differences between the methods or outcomes reported in the published review and those planned in the registered protocol. These websites show pooled estimates suggesting significant benefits with ivermectin, which has resulted in confusion for clinicians, patients and even decision-makers. This is usually a problem when performing meta-analyses which are not based in rigorous systematic reviews, often leading to spread spurious or fallacious findings.
> Meta-analysis/observational studies (https://ivmmeta.com) are circulating in the scientific community and over the Internet, demonstrating the efficacy of IVM during the pandemic. However, most of the listed references fail to provide adequate methodologies, making them difficult to be validated. Major limitations include, small sample sizes, doses and frequency of IVM use, open-label studies, in which neither the participants nor the investigators were blinded to the treatments, the use of concomitant medications in addition to IVM, assuming that the efficacy resulted from IVM (https://www.covid19treatmentguidelines.nih.gov/antiviral-the...).
And clearly you haven't looked at or for well done meta-analysis of the Ivermectin studies that manage for and exclude or put less value on the poorer studies - the conclusions which show high reduction in mortality, highest if used as prophylactic.
Have you spent any time researching the opposing view that you're adamant about?
I don't know if ivermectin is efficient, but I doubt it has substantial side-effects.
Your first link states that ivermectin is "proved to be safe at the conventional dose, although severe adverse effects have occasionally been reported". Occasional is not "substantial". Your second link does not work for me.
The people pushing it as a COVID treatment are usually pushing prolonged usage at higher doses – they routinely dismiss studies showing no benefits as not using enough – and the documented side effects definitely happen at those levels. The lower doses used for parasite treatments also are balanced against high efficacy, whereas this just means you still have COVID along with new problems.
Sorry about the link - it worked earlier when I tested it. You can try this one:
Thanks for the updated link. What I read is: "Ivermectin has few unwanted effects."
I don't think (and you also seem to imply) that any of the studies conducted for Covid were using much higher doses than the standard. On the contrary, this was precisely the point of clinical studies: to determine whether a standard dose of ivermectin (with known and limited side effects) would provide benefits, even though it is lower than the dose at which ivermectin was initially shown to have antiviral properties in vitro.
> The people pushing it as a COVID treatment are usually pushing prolonged usage at higher doses – they routinely dismiss studies showing no benefits as not using enough – and the documented side effects definitely happen at those levels.
Uh, I have never seen that from them. All of them say the bad studies are the ones using too high a dosage, and the side effects from that dosage are why those studies have bad results.
No, that site is anonymous for a reason: the information presented hasn’t passed scientific review and relies on various methodological and analytic errors to show positive effects.
Do you think mentioning the site being anonymous gives any strength to your argument?
Have your links been peer reviewed by competent individuals who aren't toeing the line?
I wonder if https://mobile.twitter.com/alexandrosM has analyzed your links yet, I'll ask him. He's been debunking "long form"/poorly done "deep analysis" for awhile now - including people trying to show flaws in Ivermectin studies but where their methods are selective and showing bias; and then arrogant people like you jump in claiming they 100% know the truth.
Grand. Anything which stops the idiots stopping us from getting back on with our lives is good. Not for me thanks, but it gives people options to make decisions for themselves.
By now you should have noticed that you're not "getting back on with your lives" no matter how good a boy you are and how many freedoms you give up. You should have resisted this from the start, this is your choice.
Would you please stop posting flamewar comments and using HN for ideological battle? You've been doing it a lot and we ban that sort of account. It's not what this site is for, and it destroys what it is for.
Hey, we're all in it together. I'm not the one "staying at home" or wearing masks though, so ironically this affects me less than it does you. We don't have any vaccine-related restrictions where I live either.
You've been using HN primarily for political and ideological battle. We ban accounts that do that, regardless of what they're battling for or against, because it's destructive of everything this site is supposed to be for. Surely you know that?
I'm not going to ban you right now, but please review the site guidelines and stop breaking them.
Three different headlines, three different efficacy percentages (89%, 90%, and now 85%), all of which originate from Pfizer's own studies. Color me dubious.
The differences in these percentages are all trivially small and explained in the article. 85% is the overall view; 89% is on the sub population treated within 3 days of symptom onset; and 90% appears to be an editorialized "almost" approximation from news agencies.
I also found the article a little hard to parse, but after a close read it seems that the 85% is the whole trial, and 89% is for people who got the drug within three days.
> The rates of hospitalization or death in the Paxlovid and control arms were 1% and 6.7%, respectively, resulting in a risk reduction of 85%.
Most people that get COVID don’t go to the hospital nor do they die. How much is from a null hypothesis; people who wouldn’t have complications anyway? It’s barely significant if you use 5% as the minimum, and it can still be noise. Vaccinated people are not going to have complications like this anyway. People care about not getting infected, this treatment is inferior to monoclonal antibodies and not barely significantly different from control.
If you read past said title, the article literally includes details on the control group.
> The rates of hospitalization or death in the Paxlovid and control arms were 1% and 6.7%, respectively, resulting in a risk reduction of 85%.
> Pfizer used data on patients who were treated within three days of symptom onset as the headline finding in its press release. In that subpopulation, the rates of hospitalization or death in the Paxlovid and control groups were 0.8% and 7%, respectively, resulting in a risk reduction of 89%. Merck’s 50% reduction was seen in patients who were randomized within five days of symptom onset.
> My point was that we don’t know anything about the control. Age, BMI, health, vaccination status, sex.
This information will absolutely be part of the FDA's EUA process, and as such, it's a silly idea that Pfizer would've set up a study that doesn't account for these.
1986: Pfizer had to withdraw an artificial heart valve from the market after defects led to it being implicated in over 300 deaths. The US Food and Drug Administration (FDA) withdrew its approval for the product in 1986 and Pfizer agreed to pay hundreds of millions of dollars in compensation after multiple lawsuits were brought against it.
2003: Pfizer has long been condemned for profiteering from AIDS drugs. In 2003 for example, it walked away from a licencing deal for its Rescriptor drug that would have made it cheaper for poorer countries.
2011: Pfizer was forced to pay compensation to families of children killed in the controversial Trovan drug trial. During the worst meningitis epidemic seen in Africa, in 1996, Pfizer ran a trial in Nigeria their new drug Trovan. Five of the 100 children who took Trovan died and it caused liver damage, while it caused lifelong disabilities in those who survived. But another group of 100 children were given the conventional “gold standard” meningitis antibiotic as a “control” group for comparison. Six of them also tragically died because, the families said, Pfizer had given them less than the recommended level of the conventional antibiotic in order to make Trovan look more effective.
2012: Pfizer had to pay around $1billion to settle lawsuits claiming its Prempro drug caused breast cancer. Prempro was used in hormone replacement therapy, usually for women going through the menopause. The settlements came after six years of trials and hardship for the women affected.
2013: Pfizer paid out $273 million to settle over 2,000 cases in the US that accused its smoking treatment drug Chantix of provoking suicidal and homicidal thoughts, self harm and severe psychological disorders. Pfizer was also accused of improperly excluding patients with a history of depression or other mental disturbances from trials for the drug. Later, in 2017, a coroner in Australia ruled that the drug had contributed to a man’s suicide. The man’s mother campaigned to change the label on the drug.
2020: Pfizer reached an agreement with thousands of customers of its depo-testosterone drug in 2018 after they sued it for increasing the likelihood of numerous issues, including heart attacks.
> Pfizer’s phase 2/3 trial randomized non-hospitalized adult COVID-19 patients who were at high risk of progressing to severe illness to receive placebo or Paxlovid, a combination of the protease inhibitors
Oh, a protease inhibitor you say? I was told those were horse dewormers by the media.
This whole thing is bullshit. With this much money at stake we were never going to learn the truth.
'There is no relationship at all between the two drugs, said Dr. William A Petri, professor of infectious diseases at the University of Virginia.
“The only way they are alike is that they are both pills,” Petri said.
Dr. Kevin J. Downes, assistant professor of pediatrics at the Perelman School of Medicine of the University of Pennsylvania, agreed, “They are dramatically different molecules. The drugs are different in their structure and their molecular size.”
[...]
Ivermectin binds to glutamate-gated chloride channels and is used to treat parasite infections, said Joseph Glajch, a consultant in pharmaceutical and analytical chemistry.
“These two are so far apart,” he said. “If you look at how they interact with the body..., they don’t even go to the same pathways or receptors.”'
The difference is that this one has a double-blind study showing high effectiveness. There's no reason to think every protease inhibitor is as good as the next, drugs are weird and unpredictable, and you can only know if they work with a good study.
Except this is studied and dosed appropriately vs. tacking a bunch of Ivermectin and shitting your intestines out based on a half-truth you read about from Facebook.
I lost a family member to one of those "supposedly treats Covid" drugs. It was called Remdesivir, and it had the full blessing of the people who told you Ivermectin causes you to shit your intestines out.
It causes kidney failure. Just the thing for treating someone whose lungs are filling with fluid from viral pneumonia.
I really wish at the time they went in the hospital (in December) that I had known the WHO had withdrawn it from their recommended treatment list the month before, in November 2020. BUT that particular piece of news was not important to the people who run the big propaganda campaign against Ivermectin.
> it had the full blessing of the people who told you Ivermectin causes you to shit your intestines out...
Is this a defense of Ivermectin somehow?
> I really wish at the time... that I had known the WHO had withdrawn it from their recommended treatment list the month before
Sounds like the people who don't endorse Ivermectin did in fact say the right thing. "The people who told you" I am referring to are doctors and health professionals, not Internet mobs.
The LD50 for Ivermectin is 10mg/kg. The standard dosage range is .1-.5mg/kg. (from memory... YMMV)
So, you would have to guzzle 20 times the recommended dosage of a foul-tasting elixir to get near a lethal dose. It sticks around in your system for ~4days, so there could be a cumulative effect if you guzzle enough over a few day period.
But still, much less dangerous as Tylenol (toxic at 10g dose; typical therapeutic dose on the order of 1g):
Paracetamol poisoning was first described in the 1960s.[6] Rates of poisoning vary significantly between regions of the world.[8] In the United States more than 100,000 cases occur a year.[1] In the United Kingdom it is the medication responsible for the greatest number of overdoses.[7] Young children are most commonly affected.[1] In the United States and the United Kingdom, paracetamol is the most common cause of acute liver failure.[9][1]
And furthermore, since Ivermectin is a potent antiparasitic, many people are likely to experience Jarisch–Herxheimer reaction to the death of intestinal parasites, which indicates its working, not dangerous. So, take is slow if you also have parasites.
But, by all means, carry on believing what you're told to! ;)
Do you believe that to be some sort of counter-argument or opposing view for anything I said?
Regardless of the answer, I'm not interested in debating the wisdom of taking dog medicine in unstudied doses for an unstudied treatment with unstudied effectiveness that has a clearly documented ability to strip the lining of your intestines. You want be a trailblazer with every Facebook remedy? Be my guest.
You know IVM has been around since the 70s? People take it all of the time. It’s a very studied drug, on the list of WHO’s 100 most essential medicines. The inventor won the noble prize for it.
The cultivated animosity towards it is more of a result of propaganda. With this much money at stake, it’s easy to see who might actually be pushing that propaganda.
Let's make it explicit: I personally know people - including one direct and one extended family member - involved in this Facebook-science culture. I have seen the videos they are following, I know they are taking the medicine for an unresearched purpose in recommended dosages without any cited scientific reasoning to support.
I'm not anti-Ivermectin anymore than I'm anti-any prescribed drug. I give it to my dog. My dad has used it, under the guidance of a doctor.
One noteworthy feature is the newness of this drug:
> PF-07321332 was developed from scratch during the current pandemic. It’s a reversible covalent inhibitor that reacts with one of the main protease’s cysteine residues. Owen [director of medicinal chemistry at Pfizer] also discussed the chemistry involved in scaling up the compound. The first 7 mg of the compound were synthesized in late July 2020. Encouraged by the early biological data, the Pfizer team aimed to scale up the synthesis. By late October, they’d made 100 g of the compound. Just two weeks later, the chemists had scaled up the synthesis to more than 1 kg. Owen said 210 researchers had worked on the project.
https://cen.acs.org/acs-news/acs-meeting-news/Pfizer-unveils...
Less than two years from lab to clinic is highly unusual. If approved, I believe this would be the fastest lab-to-approval for a small molecule drug in the history of the FDA.