Antiviral compound blocks SARS-CoV-2 from entering cells(medicine.wustl.edu)
medicine.wustl.edu
Antiviral compound blocks SARS-CoV-2 from entering cells
https://medicine.wustl.edu/news/antiviral-compound-blocks-sars-cov-2-from-entering-cells/
183 comments
A limiting factor for the effectiveness of anti-virals for Covid is time. Maximum viral load happens often happens before any symptoms are present, and the most severe diseases occurs weeks after infection as a result of the bodies inflammatory response instead of the virus itself. This means that by the time you know that a patient will have severe Covid-19, it is likely too late for any treatment that is based on interfering with the virus itself.
Having said that, we have a good demographic understanding of who tends to get severe Covid-19, and a large testing capacity, so a cheap anti-viral treatment with few side effects could still be effectively deployed.
Having said that, we have a good demographic understanding of who tends to get severe Covid-19, and a large testing capacity, so a cheap anti-viral treatment with few side effects could still be effectively deployed.
I imagine the willingness to get tested would also be a lot higher if the result of a positive test was a reasonably quick antiviral treatment instead of weeks of quarantine.
Sure, there will always be sceptics, but for large parts of people, organisations and governments having less perverse incentives might improve things a lot.
Sure, there will always be sceptics, but for large parts of people, organisations and governments having less perverse incentives might improve things a lot.
I feel like I'm pointing out the obvious, but another, extremely effect and quick "treatment" is vaccination. And it works great without the constant need for testing. I have to imagine that anyone willing to undergo treatment at the very start of getting covid, would have also been willing to be vaccinated.
The vaccine-hesitant aren't going to go for treatment until the outlook is dire.
Additionally, in my experience, physicians aren't terribly concerned about infections in vaccinated individuals. When I was last tested, the physician essentially just assured me that vaccinations have been shown to drastically reduce the likelihood of complications, and not to really worry about it. Granted, I could have had a less rigorous physician, or it could that I'm totally healthy.
The vaccine-hesitant aren't going to go for treatment until the outlook is dire.
Additionally, in my experience, physicians aren't terribly concerned about infections in vaccinated individuals. When I was last tested, the physician essentially just assured me that vaccinations have been shown to drastically reduce the likelihood of complications, and not to really worry about it. Granted, I could have had a less rigorous physician, or it could that I'm totally healthy.
> The vaccine-hesitant aren't going to go for treatment until the outlook is dire.
Many of them seem quite willing to get ivermectin (whether it works or not is another issue). This is a tribal thing: one tribe has determined that the vaccine isn't something their tribe gets, but many of them seem willing to try other treatments that are acceptable to the tribe. (and yes, that's not rational, but humans are often irrational)
Many of them seem quite willing to get ivermectin (whether it works or not is another issue). This is a tribal thing: one tribe has determined that the vaccine isn't something their tribe gets, but many of them seem willing to try other treatments that are acceptable to the tribe. (and yes, that's not rational, but humans are often irrational)
I distinctly remember some very prominent people saying they wouldn't get the vaccine because it came from Trump.
While some Republicans don't want to get it, it is mainly because they are told they have to get it. But there are quite a few Democrats who aren't getting it either.
The elderly typically are more conservative than the young. The elderly are also taking the vaccine at a higher rate than the young. Just based on demographics, I would assume a significant number of Republicans have taken it.
It's too bad we couldn't arrange it so that one vaccine could be the "Trump vaccine" that Republicans could get and another could be the "Fauci vaccine" for Democrats. Then people could express their political affiliations in their medical choices but still get vaccinated. There were a lot of Democratic politicians talking about not trusting rushed vaccines a year ago and if that could have focused on specific vaccines and kept going maybe we'd be in a better place today with regards to vaccinations.
Most of the vaccine hesitancy started as made up Facebook posts. Make a video, draw a contrast between the vaccines and next thing you know millions might be repeating whatever you made up. It might actually have some benefit, but furthers harmful patterns. I know people who have expressed interest in new nasal vaccines which may or may not come, I think they know they need a vaccine, but are just looking for some way to get one without admiting they've been wrong all this time.
The vaccine hesitancy started out with the entire media, Biden and Fauci saying an effective vaccine will be years away. Meanwhile Trump is out hawking the warpspeed vaccine like it will save the world. A week after the election and the narrative flips.
I don't buy the first model year of a car, very rarely take an on patent drug, and I won't inject myself with a medical device before the long term studies have been completed.
I don't buy the first model year of a car, very rarely take an on patent drug, and I won't inject myself with a medical device before the long term studies have been completed.
What are these long term studies you speak of?
I'm not aware of any currently, but that doesn't mean someone isn't doing one. At the very least, there is likely several cohort studies going on right now that will capture some useful data.
There is no substitute for time. Very few people have had the vaccine for more that 1 year. None have had it more than 5.
There is no substitute for time. Very few people have had the vaccine for more that 1 year. None have had it more than 5.
Interesting, so if you were to define quantifiable criteria for when/what would make you feel safe, what would that be?
Not trolling here, I'm genuinely interested and thank you for sharing.
Not trolling here, I'm genuinely interested and thank you for sharing.
I would need to know
- Short-term risks of taking vaccine
- Long-term risks of taking vaccine
- Short-term benefits of taking vaccine
- Long-term benefits of taking vaccine
- Risks and benefits of alternatives
The vaccine doesn't even need to be "safe" for it to be worthwhile. A person with a short enough expected lifespan (elderly or comorbid) may derive a great benefit from a drug with real long-term risks.
For long term risks, nothing can substitute for time. I'm relatively young. I have an expected lifespan of 40+ more years. Ideally, I would want 40+ years worth of long term data. Realistically, I will settle for 5 years of good data. That should give good enough information to make an informed decision.
The biggest hurdle to overcome is censorship. A large portion of the media and big tech is censoring "misinformation". Its not just social media like Facebook, Reddit, Twitter, etc. nor main stream media like CNN, Fox, MSNBC, etc. Companies like Google are removing advertisement from pages if it says something they disagree with. With this heavy handed skew, can you really trust the information that comes out?
The vaccine doesn't even need to be "safe" for it to be worthwhile. A person with a short enough expected lifespan (elderly or comorbid) may derive a great benefit from a drug with real long-term risks.
For long term risks, nothing can substitute for time. I'm relatively young. I have an expected lifespan of 40+ more years. Ideally, I would want 40+ years worth of long term data. Realistically, I will settle for 5 years of good data. That should give good enough information to make an informed decision.
The biggest hurdle to overcome is censorship. A large portion of the media and big tech is censoring "misinformation". Its not just social media like Facebook, Reddit, Twitter, etc. nor main stream media like CNN, Fox, MSNBC, etc. Companies like Google are removing advertisement from pages if it says something they disagree with. With this heavy handed skew, can you really trust the information that comes out?
My partner is ex-Christian Scientist (a faith-healing cult that doesn't believe in disease or medicine.) Zir whole family finally relented and got vaccinated, but they all got J+J. I don't know why that vaccine in particular (maybe because it's single-shot, so they only have to deal with hypocrisy once?) but that vaccine is popular with that cohort.
I wanted JJ because not mRNA and is accepted in several countries.
The JJ mechanism of action is better understood and less risky, in my view at least it is more acceptable for emergency approval.
The JJ mechanism of action is better understood and less risky, in my view at least it is more acceptable for emergency approval.
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Just out of curiosity- they used to be a christian scientist and now they’re not and go by xe/zir style pronouns? That’s quite a journey if so.
As for J&J, yes it’s generally the fact that it’s one and done so it feels less risky to people that didn’t want to get vaccinated. Then there’s the whole mRNA thing as well.
As for J&J, yes it’s generally the fact that it’s one and done so it feels less risky to people that didn’t want to get vaccinated. Then there’s the whole mRNA thing as well.
Zie grew up in CS, but was queer, and CS (at least back then) was very anti-LGBT. Principia, the CS university, would expel openly gay students and fire openly gay professors, and zir parents were homophobic too. The mom would listen to testimonials of people's "healings" of their same-sex attraction.
That made zir not fit in, and accelerated zir dropping out of CS and discovering the LGBT community, and non-binary identity.
That made zir not fit in, and accelerated zir dropping out of CS and discovering the LGBT community, and non-binary identity.
Thanks for that context. I learned a bit about something new :)
It could just be GP's preferred way of anonymizing their SO without having to resort to the dreaded singular specific "they". Call it light-weight anonymization to make it more difficult to be casually doxxed.
There's also the perceived seriousness of a treatment. A nasal spray is harmless, a capsule is more substantial, an injection is serious business. You see the same thing with placebos, with saline injections being more "effective" than sugar tablets. And a vaccine is not just an injection, it's some kind of miracle thing that cures an infection you don't even have yet.
It's not surprising people are far more willing to try out sprays and tablets than injections, even if there wasn't any misinformation and tribal politics
It's not surprising people are far more willing to try out sprays and tablets than injections, even if there wasn't any misinformation and tribal politics
There are nasal covid vaccines in development. I suspect some of the hesitant would take them, but I've talked to anti-vaxxers who still would not even take a nasal vaccine.
I agree, but vaccines in this case have their definite drawbacks as seen in vaccine-heavy Israel in that their effectiveness wears off after a few months.
I have personally heard of a number of pretty bad breakthrough cases where a person has had a fever for almost a month, another was extremely sick and there are still people who are afraid of covid for this very reason(and they are vaccinated). Having an effective anti-viral solution will bring down the fear about these scenarios and get people back to work and bring normalcy to society again.
I have personally heard of a number of pretty bad breakthrough cases where a person has had a fever for almost a month, another was extremely sick and there are still people who are afraid of covid for this very reason(and they are vaccinated). Having an effective anti-viral solution will bring down the fear about these scenarios and get people back to work and bring normalcy to society again.
Lets be careful there. While vaccines do wear off, they are not wearing off nearly as fast as most people using that line are saying.
Also, Isreal is no longer vaccine heavy. They were an early leader, but many other countries exceed their vaccine rates these days.
Also, Isreal is no longer vaccine heavy. They were an early leader, but many other countries exceed their vaccine rates these days.
Not anymore. Because it turns out mRNA vaccination efficacy drops off after 6-9 months, which is why they're rolling out booster shots in my country. I fear that soon "fully vaccinated" will mean one has had a series of 4 shots by that point. (And if you don't like that, we're taking away your job).
Well if you can't be trusted to not infect the people around you, yeah get the hell out. Its literally the only pragmatic way to deal with it.
Bad faith argument here. The current vaccines are not like the MMR vaccine, for example. Vaccinated people can still contract and spread coronaviruses. So, a vaccine subscription where everyone needs shots every 6-12 months is not the _only_ pragmatic way to deal with it; it's just the option that's being shoved down all Americans' throats right now, ostensibly for the benefit of major pharma companies and other more nefarious reasons.
SARS-CoV-2 is clearly not a death sentence, because more than 99% survive if they contract it. And there is a factor of natural immunity, which the US government is oddly trying to smokescreen/astroturf into "get vaccinated anyway".
I am not "anti-vaccination". I had my shots. I am simply against government coercion to push not the best, but the most profitable solutions.
SARS-CoV-2 is clearly not a death sentence, because more than 99% survive if they contract it. And there is a factor of natural immunity, which the US government is oddly trying to smokescreen/astroturf into "get vaccinated anyway".
I am not "anti-vaccination". I had my shots. I am simply against government coercion to push not the best, but the most profitable solutions.
It is literally the most effective way to reopen our country. Full stop. Nothing comes close. We don't have any other options currently. I wish we did, but with the tools we have, Its a purely pragmatic decision to encourage everyone to get vaccinated.
And saying it isn't a death sentence is ignorant, we've lost over 700k Americans alone to it, no idea how many people globally. I dare you to go to someone who's lost a loved one and say that its not a death sentence, because to so many it is.
And bad faith argument? There's no astroturfing. Its a good idea and way more than 50% of the US population supports it. You been drinking the kool aide.
You have a huge important point about all this that I almost missed reading your response, because its mired in 'I'm not an anti vaxer' mixed with hints of conspiracy theories. Big pharma is getting fat off this. Its a problem. It needs to be fixed for the sake of the american people.
We need intelligent people like you to fight for that.
And saying it isn't a death sentence is ignorant, we've lost over 700k Americans alone to it, no idea how many people globally. I dare you to go to someone who's lost a loved one and say that its not a death sentence, because to so many it is.
And bad faith argument? There's no astroturfing. Its a good idea and way more than 50% of the US population supports it. You been drinking the kool aide.
You have a huge important point about all this that I almost missed reading your response, because its mired in 'I'm not an anti vaxer' mixed with hints of conspiracy theories. Big pharma is getting fat off this. Its a problem. It needs to be fixed for the sake of the american people.
We need intelligent people like you to fight for that.
> push not the best, but the most profitable solutions
Don’t you think that cocktails of novel antiviral drugs are a higher profit margin solution then the vaccines that are already available? A remdesivir course costs almost two orders of magnitude more than an mRNA vaccine (in the US). Can’t really imagine these novel antiviral drugs will be much more affordable. To be clear, I do think both are important tools that we should use.
Is there some other pragmatic solution you have in mind?
Don’t you think that cocktails of novel antiviral drugs are a higher profit margin solution then the vaccines that are already available? A remdesivir course costs almost two orders of magnitude more than an mRNA vaccine (in the US). Can’t really imagine these novel antiviral drugs will be much more affordable. To be clear, I do think both are important tools that we should use.
Is there some other pragmatic solution you have in mind?
> Vaccinated people can still contract and spread coronaviruses.
This statement should always come with information about the relative rate at which it occurs.
One "can still" get pregnant despite using contraception. This is not an argument against using it, because the relative rate is far lower than if one did not use it at all.
This statement should always come with information about the relative rate at which it occurs.
One "can still" get pregnant despite using contraception. This is not an argument against using it, because the relative rate is far lower than if one did not use it at all.
> I feel like I'm pointing out the obvious, but another, extremely effect and quick "treatment" is vaccination.
Does every discussion of about post-exposure prophylaxis have to have comments about vaccination?
> And it works great without the constant need for testing.
A primary reason for testing has been to help stop the spread of the virus (test positive = isolate), not necessarily to let people with mild symptoms or no symptoms know that they're infected.
Vaccinated individuals can still spread the virus and some people are at higher risk even when vaccinated, so testing is still of value.
> I have to imagine that anyone willing to undergo treatment at the very start of getting covid, would have also been willing to be vaccinated.
That's quite an assumption. Without passing judgment about his decision not to get vaccinated and to throw the kitchen sink at COVID once he was infected, Joe Rogan is an example of a person who is willing to treat an infection but not get vaccinated. I doubt he's the only one.
> Additionally, in my experience, physicians aren't terribly concerned about infections in vaccinated individuals.
Vaccination certainly reduces the incidence of hospitalization and death, and the data to date suggests that vaccinated individuals are less likely to develop "long COVID" symptoms. But there's still a lot we don't know. Research indicates that individuals with breakthrough infections can have viral loads that are as high as unvaccinated individuals, and some percentage report courses of illness that are virtually identical to a typical course of illness in unvaccinated individuals (respiratory symptoms, extreme fatigue, etc.) so I think it's premature to make too many assumptions. Especially since in immunologically naive people, some with "mild" or even largely asymptomatic infections also report lasting issues too.
Does every discussion of about post-exposure prophylaxis have to have comments about vaccination?
> And it works great without the constant need for testing.
A primary reason for testing has been to help stop the spread of the virus (test positive = isolate), not necessarily to let people with mild symptoms or no symptoms know that they're infected.
Vaccinated individuals can still spread the virus and some people are at higher risk even when vaccinated, so testing is still of value.
> I have to imagine that anyone willing to undergo treatment at the very start of getting covid, would have also been willing to be vaccinated.
That's quite an assumption. Without passing judgment about his decision not to get vaccinated and to throw the kitchen sink at COVID once he was infected, Joe Rogan is an example of a person who is willing to treat an infection but not get vaccinated. I doubt he's the only one.
> Additionally, in my experience, physicians aren't terribly concerned about infections in vaccinated individuals.
Vaccination certainly reduces the incidence of hospitalization and death, and the data to date suggests that vaccinated individuals are less likely to develop "long COVID" symptoms. But there's still a lot we don't know. Research indicates that individuals with breakthrough infections can have viral loads that are as high as unvaccinated individuals, and some percentage report courses of illness that are virtually identical to a typical course of illness in unvaccinated individuals (respiratory symptoms, extreme fatigue, etc.) so I think it's premature to make too many assumptions. Especially since in immunologically naive people, some with "mild" or even largely asymptomatic infections also report lasting issues too.
Edit: My understanding of the science here was at least slightly wrong. Please see the reply from
LurkingPenguin and eventually my reply to them
I think results like vaccinated individuals “can” have viral loads as high as unvaccinated individuals are next to useless. I need to know how likely I am to have high viral loads and my understanding of the science there is that vaccines still do a decent job of lowering the odds. I know you aren’t really arguing against vaccination here, but it seems like it needed to be said and I think the “vaccinated individuals can have high viral loads” line is particularly bad
I think results like vaccinated individuals “can” have viral loads as high as unvaccinated individuals are next to useless. I need to know how likely I am to have high viral loads and my understanding of the science there is that vaccines still do a decent job of lowering the odds. I know you aren’t really arguing against vaccination here, but it seems like it needed to be said and I think the “vaccinated individuals can have high viral loads” line is particularly bad
> I think the “vaccinated individuals can have high viral loads” line is particularly bad
https://www.medrxiv.org/content/10.1101/2021.09.28.21264262v...
https://www.ucdavis.edu/health/covid-19/news/viral-loads-sim...
How is a statement about what some researchers are finding "particularly bad"? If vaccinated individuals routinely have viral loads as high as those seen in unvaccinated individuals, it warrants more research into how the virus affects their bodies and what, if any, risks they might face both short term and long term.
According to one study[1], vaccination reduces the risk of long COVID by 49%. Given that some studies have found the incidence of long COVID is in the double digit percentages[2], exploring this issue is not purely academic. It is pertinent to the hundreds of millions of vaccinated individuals who are still at risk of infection, even if their risk of hospitalization and death has been significantly reduced.
Science works when we ask and investigate important questions. It doesn't work when we ignore these questions because we're afraid of the optics and how they might be misconstrued by some people.
In fact, when it comes to COVID generally, it seems evident to me that shying away from difficult questions has had the opposite of the intended effect. It has probably caused more people to adopt anti-science views and reject beneficial measures like vaccination.
[1] https://www.usnews.com/news/health-news/articles/2021-09-02/...
[2] https://www.medicalnewstoday.com/articles/more-than-one-thir...
https://www.medrxiv.org/content/10.1101/2021.09.28.21264262v...
https://www.ucdavis.edu/health/covid-19/news/viral-loads-sim...
How is a statement about what some researchers are finding "particularly bad"? If vaccinated individuals routinely have viral loads as high as those seen in unvaccinated individuals, it warrants more research into how the virus affects their bodies and what, if any, risks they might face both short term and long term.
According to one study[1], vaccination reduces the risk of long COVID by 49%. Given that some studies have found the incidence of long COVID is in the double digit percentages[2], exploring this issue is not purely academic. It is pertinent to the hundreds of millions of vaccinated individuals who are still at risk of infection, even if their risk of hospitalization and death has been significantly reduced.
Science works when we ask and investigate important questions. It doesn't work when we ignore these questions because we're afraid of the optics and how they might be misconstrued by some people.
In fact, when it comes to COVID generally, it seems evident to me that shying away from difficult questions has had the opposite of the intended effect. It has probably caused more people to adopt anti-science views and reject beneficial measures like vaccination.
[1] https://www.usnews.com/news/health-news/articles/2021-09-02/...
[2] https://www.medicalnewstoday.com/articles/more-than-one-thir...
I think partly what's going on is that some people have immune systems that have a hard time generating an effective response, whether or not they area vaccinated. Vaccination gives the immune system a chance to respond and memorize, as best it can. If it can't do that effectively, there is higher likelihood of a serious outcome.
I think this is very unlikely to significantly explain what we’ve seen. It’s much more likely just the natural result of artificial immunity waning much more rapidly than naturally acquired. As well as the fact that natural immunity involves exposure to the whole virus and therefore much broader types of epitopes for the immune system to “learn”.
In addition, intramuscular vaccines only provide blood/serum antibodies, while nasal infection also provides nasal/mucosal antibodies. Those who recover from Covid infection gain sterilizing immunity (less than 1% will be reinfected) that stops future infections in the upper respiratory tract.
That's why the CDC website says Covid (leaky, non-sterilizing) vaccines only provide protection (in blood) against serious illness, not infection (in nose). A future nasal vaccine may provide sterilizing immunity (what most people assume they are getting from a "vaccine", like their personal experience with the MMR vaccine).
That's why the CDC website says Covid (leaky, non-sterilizing) vaccines only provide protection (in blood) against serious illness, not infection (in nose). A future nasal vaccine may provide sterilizing immunity (what most people assume they are getting from a "vaccine", like their personal experience with the MMR vaccine).
I think these things are hard to be sure about, but there still is good evidence that covid vaccines are sterilizing in a lot of cases. The rate of infection is still lower for vaccinated people right when controlling for other demographics?
>there still is good evidence that covid vaccines are sterilizing in a lot of cases.
What? No, there isn't. The Covid vaccines we have today are not sterilizing. Period. This isn't a conspiracy theory or anything like that, it's just a simple fact.
What? No, there isn't. The Covid vaccines we have today are not sterilizing. Period. This isn't a conspiracy theory or anything like that, it's just a simple fact.
COVID-19 vaccines aren't sterilizing to any meaningful extent. They provide only limited and temporary protection against infection. The real benefit is in protection against severe symptoms.
https://www.nature.com/articles/d41586-021-02689-y
https://www.nature.com/articles/d41586-021-02689-y
"sterilizing" seems to get a different definition every time I hear it.
There's a stable definition in textbooks.
If 2021 consumer media is offering variable definitions, Cui Bono?
If 2021 consumer media is offering variable definitions, Cui Bono?
I think also something that should be considered how the vaccine works if the immune system is already battling something. Anecdotally I know a person who's tumor had doubled in size after she took the vaccine. It could be coincidence. But at the same time, do we know how much an immune system directs it resources, and does it prioritize and immediate infection vs one that is latent.
Welp, this is making me realize I was just wrong. My understanding of the science was something like you can find asymptomatic vaccinated individuals with similar viral loads to asymptomatic unvaccinated people, which is a bit meaningless when you're choosing a threshold for "infected" and when random chance will just see some people at any level. So to be clear it's not that I think the questions shouldn't be investigated, but a statement like "some vaccinated cases have high viral loads" is meaningless to explaining what my risk of spreading covid is.
Trying to avoid the sort of bias that comes from trying to reinforce rather than question existing views, but I do still think the statement "No Significant Difference in Viral Load Between Vaccinated and Unvaccinated, Asymptomatic and Symptomatic Groups Infected with SARS-CoV-2 Delta Variant" despite being much more precise is still a bit unintuitive in it's implication. Because essentially what this means right is that they sampled people's viral loads, and then cut out everyone below a value they choose to mean "infected". It's still true that even if I had symptoms because I'm vaccinated my odds of having a high viral load are much lower. Presumably if you didn't remove all the samples with less than some concentration you'd see significant differences.
I think that something the scientists got wrong consistently with covid was not unflinchingly communicating what was likely to be true mostly out of a fear that the public would take interventions that only moderately improved their safety like wearing a mask, and start doing riskier things or because of a bias towards doing nothing when clear evidence didn't exist. It can feel like similar things are happening with vaccination where it does seem pretty clear that getting vaccinated reduces your risk of passing on covid both because you're less likely to ever get a colony of the virus sufficient to count as "infected" and because you're likely to have a shorter infection.
Trying to avoid the sort of bias that comes from trying to reinforce rather than question existing views, but I do still think the statement "No Significant Difference in Viral Load Between Vaccinated and Unvaccinated, Asymptomatic and Symptomatic Groups Infected with SARS-CoV-2 Delta Variant" despite being much more precise is still a bit unintuitive in it's implication. Because essentially what this means right is that they sampled people's viral loads, and then cut out everyone below a value they choose to mean "infected". It's still true that even if I had symptoms because I'm vaccinated my odds of having a high viral load are much lower. Presumably if you didn't remove all the samples with less than some concentration you'd see significant differences.
I think that something the scientists got wrong consistently with covid was not unflinchingly communicating what was likely to be true mostly out of a fear that the public would take interventions that only moderately improved their safety like wearing a mask, and start doing riskier things or because of a bias towards doing nothing when clear evidence didn't exist. It can feel like similar things are happening with vaccination where it does seem pretty clear that getting vaccinated reduces your risk of passing on covid both because you're less likely to ever get a colony of the virus sufficient to count as "infected" and because you're likely to have a shorter infection.
> Because essentially what this means right is that they sampled people's viral loads, and then cut out everyone below a value they choose to mean "infected".
Huh? Please cite the part of the study you're referring to to argue that the title of the study means the exact opposite of what it says.
Every manufacturer of a PCR test specifies a Ct cutoff above which the result is considered false.
> It's still true that even if I had symptoms because I'm vaccinated my odds of having a high viral load are much lower. Presumably if you didn't remove all the samples with less than some concentration you'd see significant differences.
The study says the exact opposite:
> There were no statistically significant differences in mean Ct-values of vaccinated (UeS: 23.1; HYT: 25.5) vs. unvaccinated (UeS: 23.4; HYT: 25.4) samples. In both vaccinated and unvaccinated, there was great variation among individuals, with Ct-values of <15 to >30 in both UeS and HYT data (Fig. 1A, 1B). Similarly, no statistically significant differences were found in the mean Ct-values of asymptomatic (UeS: 24.3; HYT: 25.4) vs. symptomatic (UeS: 22.7) samples, overall or stratified by vaccine status (Fig. 1B). Similar Ct-values were also found among different age groups, between genders, and vaccine types (Supplemental Figure 1).
Huh? Please cite the part of the study you're referring to to argue that the title of the study means the exact opposite of what it says.
Every manufacturer of a PCR test specifies a Ct cutoff above which the result is considered false.
> It's still true that even if I had symptoms because I'm vaccinated my odds of having a high viral load are much lower. Presumably if you didn't remove all the samples with less than some concentration you'd see significant differences.
The study says the exact opposite:
> There were no statistically significant differences in mean Ct-values of vaccinated (UeS: 23.1; HYT: 25.5) vs. unvaccinated (UeS: 23.4; HYT: 25.4) samples. In both vaccinated and unvaccinated, there was great variation among individuals, with Ct-values of <15 to >30 in both UeS and HYT data (Fig. 1A, 1B). Similarly, no statistically significant differences were found in the mean Ct-values of asymptomatic (UeS: 24.3; HYT: 25.4) vs. symptomatic (UeS: 22.7) samples, overall or stratified by vaccine status (Fig. 1B). Similar Ct-values were also found among different age groups, between genders, and vaccine types (Supplemental Figure 1).
> The study says the exact opposite:
Maybe I'm misinterpreting the study. I interpreted that as being among the fraction of people who are infected both because that's what the title says, and because they say later that "75% of the positive samples were from unvaccinated individuals" which would seem to be inconsistent with the groups having similar viral loads.
I thought we were dealing with a random variable composed something like this
VIRAL_LOAD = INFECTED ? LOAD_FOR_INFECTED : LOAD_FOR_UNINFECTED
And the study is saying that the random variable `LOAD_FOR_INFECTED` isn't correlated with vaccination status. That's indeed an interesting fact, but since `INFECTED` still was correlated (I think) overall for some random person `VIRAL_LOAD` would be too. Honestly a table would make all of this more clear.
Maybe I'm misinterpreting the study. I interpreted that as being among the fraction of people who are infected both because that's what the title says, and because they say later that "75% of the positive samples were from unvaccinated individuals" which would seem to be inconsistent with the groups having similar viral loads.
I thought we were dealing with a random variable composed something like this
VIRAL_LOAD = INFECTED ? LOAD_FOR_INFECTED : LOAD_FOR_UNINFECTED
And the study is saying that the random variable `LOAD_FOR_INFECTED` isn't correlated with vaccination status. That's indeed an interesting fact, but since `INFECTED` still was correlated (I think) overall for some random person `VIRAL_LOAD` would be too. Honestly a table would make all of this more clear.
> Maybe I'm misinterpreting the study.
With no offense intended, I think you're misunderstanding the whole concept of "viral load". If you are not infected with SARS-CoV-2, you don't have a SARS-CoV-2 "viral load".
With no offense intended, I think you're misunderstanding the whole concept of "viral load". If you are not infected with SARS-CoV-2, you don't have a SARS-CoV-2 "viral load".
I was sort of intentionally abusing the term, though I was trying to be clear that I was trying include explicitly people with a number of viral particles low enough to not be infected. My understanding is that a single covid virus infecting a cell won't result in a positive covid test and probably won't make someone sick especially if they're vaccinated. More broadly the point I'm trying to make is that vaccination lowers the expected value of covid shedding because even if they're actually infected they might spread just as well they're less likely to be infected and that phrases like vaccinated people have similar viral loads to unvaccinated individual obscures that point and helps lead people to think vaccines are useless
> Research indicates that individuals with breakthrough infections can have viral loads that are as high as unvaccinated individuals, and some percentage report courses of illness that are virtually identical to a typical course of illness in unvaccinated individuals
But that's totally expected (depending of course on how you define "some"). If the vaccine had 100% efficacy, it would be shocking. The fact that it doesn't is not a surprise.
I'm assuming the point you're trying to make is vaccines aren't as good as expected. If the point is just that there is still value in developing treatments even with vaccines, than yes i agree with you.
But that's totally expected (depending of course on how you define "some"). If the vaccine had 100% efficacy, it would be shocking. The fact that it doesn't is not a surprise.
I'm assuming the point you're trying to make is vaccines aren't as good as expected. If the point is just that there is still value in developing treatments even with vaccines, than yes i agree with you.
> I'm assuming the point you're trying to make is vaccines aren't as good as expected.
No, I was responding to "Additionally, in my experience, physicians aren't terribly concerned about infections in vaccinated individuals" and pointing out that there's still a lot we don't know about the risks associated with infection after vaccination and arguing that these things deserve additional scientific study.
No, I was responding to "Additionally, in my experience, physicians aren't terribly concerned about infections in vaccinated individuals" and pointing out that there's still a lot we don't know about the risks associated with infection after vaccination and arguing that these things deserve additional scientific study.
This isn’t about ‘95% was unaffected and the vaccine didn’t work for the other 5%’.
It’s about ‘the vaccine does not protect against getting infected and being infectious in over 50% of cases’.
It’s about ‘the vaccine does not protect against getting infected and being infectious in over 50% of cases’.
But you'd need to get tested for every minor sniffle, or if the claim about no symptoms being a time of maximum viral load, you'd have to constantly get tested even without symptoms.
Rapid antigen tests take take about 20 minutes.
[deleted]
That's a good point on the limitation, and to expand on your last point, an immediate demographic this could help is frontline healthcare workers and similar jobs who do get routine testing and are at higher risk in general.
Yup.
I'm a teacher and vaccinated. If I found out that I was exposed, and then tested positive... post-exposure prophylaxis sounds great.
Also there's my dad, who has an immune condition due to old age. He's vaccinated, but who knows how effective the vaccine was for him. The existence of PEP could make it possible for him to do more at a similar level of safety... vs. the current option of staying in a small bubble for the rest of his life despite being otherwise able-bodied and capable.
I'm a teacher and vaccinated. If I found out that I was exposed, and then tested positive... post-exposure prophylaxis sounds great.
Also there's my dad, who has an immune condition due to old age. He's vaccinated, but who knows how effective the vaccine was for him. The existence of PEP could make it possible for him to do more at a similar level of safety... vs. the current option of staying in a small bubble for the rest of his life despite being otherwise able-bodied and capable.
FYI, your dad would most likely already qualify to receive the antiviral antibody treatments that have been given emergency authorization by the FDA.
https://www.covid19treatmentguidelines.nih.gov/therapies/ant...
https://www.covid19treatmentguidelines.nih.gov/therapies/ant...
Oh sure-- if he got infected, we'd throw the kitchen sink at it-- remdesivir, monoclonals, etc. A "better remdesivir" which is supremely effective would improve the risk picture a lot.
Given that time is of the essence with antivirals, we need to give people lateral flow antigen tests they can take at home (very accurate if they come up positive) as well as some kind of pre-presciption (show the pharmacist your positive test result and get the antivirals or some such). Waiting for a doctors appointment will take too much time.
According to the founders of Ridgeback, Molnupiravir is being tested prophylacticly. They suggested that hopefully by sometime next year, if someone you’ve been in within close contact tests positive, you get on the cocktail of Molnupiravir + the upcoming Pfizer antiviral.
Molnupiravir is not a benign medication. There are serious concerns about mutagenic risks. Until more long-term safety studies are completed it certainly shouldn't be prescribed as a routine prophylactic for most patients who are at low risk anyway.
https://www.medicalnewstoday.com/articles/molnupiravir-vs-co...
https://www.medicalnewstoday.com/articles/molnupiravir-vs-co...
If the antivirals are highly effective one could really slam the immune system to stop any damaging response without the virus again going out of control.
And I'm going to hazard a guess that the likelihood of not getting early testing correlates strongly with the likelihood of not getting vaccinated.
swader999(1)
Mortality is going to be dramatically reduced once nearly everyone has T-cells+B-cells that recognize the virus. If everyone got vaccinated we'd be out of the pandemic phase and into the endemic phase with a virus that looked more like just a flu/cold.
Vaccines are a 10x or 20x improvement in death and hospitalization rates. That's just a fact. All these antivirals won't have that kind of impact and are closing the barn doors after the horse has escaped. Which is not to say we don't research both, but vaccination is the simple easy and effective answer. There's a considerable technological fetish with antivirals while boring vaccines are now treated with skepticism, which is backwards. Antivirals should be used after vaccines have failed in vulnerable populations, the major weapon against viruses is vaccines, and they work.
Vaccines are a 10x or 20x improvement in death and hospitalization rates. That's just a fact. All these antivirals won't have that kind of impact and are closing the barn doors after the horse has escaped. Which is not to say we don't research both, but vaccination is the simple easy and effective answer. There's a considerable technological fetish with antivirals while boring vaccines are now treated with skepticism, which is backwards. Antivirals should be used after vaccines have failed in vulnerable populations, the major weapon against viruses is vaccines, and they work.
mRNA vaccines look extremely promising too. It’s entirely possible that some classes of cancer will be effectively eliminated in our lifetime because of it, along with HIV and/or Malaria. The latter would probably be the biggest reduction in human death and misery since the invention of the Polio vaccine
I've been saying for roughly a year now that if nothing else good can come from Covid, we at the very least are dumping a ton of time and resources and research into mRNA vaccines.
I know basically nothing about virology, but I remember hearing a podcast a million years ago talking about mRNA vaccines, and I remember after it was over thinking "if this is even half as cool as it sounds to a lay person, the implications of this are huge". It appears that it's substantially more than half as cool as it sounded, and the fact that we are even having discussions about being able to wipe out malaria is mind-boggling to me (in a good way).
I know basically nothing about virology, but I remember hearing a podcast a million years ago talking about mRNA vaccines, and I remember after it was over thinking "if this is even half as cool as it sounds to a lay person, the implications of this are huge". It appears that it's substantially more than half as cool as it sounded, and the fact that we are even having discussions about being able to wipe out malaria is mind-boggling to me (in a good way).
We developed several working vaccines, and in record time. A triumph of scientific engineering.
I too am very hopeful for mRNA vaccines, although I don't know how much I should temper my expectations. The idea of curing certain cancers, not just preventing them, is wild.
I too am very hopeful for mRNA vaccines, although I don't know how much I should temper my expectations. The idea of curing certain cancers, not just preventing them, is wild.
I haven't even heard about the curing cancer part, that's awesome if it's true.
I think I'm going to temper my expectations to "faster and more vaccines increasingly exotic diseases" for now. I would absolutely love to be proven wrong though.
I think I'm going to temper my expectations to "faster and more vaccines increasingly exotic diseases" for now. I would absolutely love to be proven wrong though.
Chimeric antigen receptor (CAR) T-cell therapy is a way to get immune cells called T cells (a type of white blood cell) to fight cancer by changing them in the lab so they can find and destroy cancer cells. CAR T-cell therapy is also sometimes talked about as a type of cell-based gene therapy, because it involves altering the genes inside T cells to help them attack the cancer.
...
In CAR T-cell therapies, T cells are taken from the patient's blood and are changed in the lab by adding a gene for a man-made receptor (called a chimeric antigen receptor or CAR). This helps them better identify specific cancer cell antigens. The CAR T cells are then given back to the patient.
https://www.cancer.org/treatment/treatments-and-side-effects...
Right now this is done in a very personalized and labor intensive way. I think the thought is mRNA is potentially a gigafactory compared to artisanal methods.
...
In CAR T-cell therapies, T cells are taken from the patient's blood and are changed in the lab by adding a gene for a man-made receptor (called a chimeric antigen receptor or CAR). This helps them better identify specific cancer cell antigens. The CAR T cells are then given back to the patient.
https://www.cancer.org/treatment/treatments-and-side-effects...
Right now this is done in a very personalized and labor intensive way. I think the thought is mRNA is potentially a gigafactory compared to artisanal methods.
They also can only target cancers that have specific markers that are unique to the cancer and not normal cells, lest the treatment kill non cancer cells. Early experiments here did lead to patient deaths (in advanced already going to die cancer patients). Not all cancers have these unique markers so this therapy only works on a few types,m.
Fantastic podcast covering topic by interviewing the father of these therapies:
https://youtu.be/pVMl0LgdnOU
Podcast available on Apple podcasts etc. The Drive episode 177.
can't recommend enough.
Fantastic podcast covering topic by interviewing the father of these therapies:
https://youtu.be/pVMl0LgdnOU
Podcast available on Apple podcasts etc. The Drive episode 177.
can't recommend enough.
Except we had to change the definition of “working vaccine” to fit these new therapies.
Traditionally a vaccine has to keep efficacy for a year. We haven’t got a year of data but the efficacy has dropped significantly
Traditionally a vaccine has to keep efficacy for a year. We haven’t got a year of data but the efficacy has dropped significantly
I call bullshit. Antibodies wane but the memory cell response is robust and holds up over what looks to be a pretty long period (studied intensively for 6 months but with no sign of decline). Here's a new paper that shows that in detail (paper itself is dense but Twitter thread is fairly accessible):
https://twitter.com/rishirajgoel/status/1448711946010710023
By basically all measures, these vaccines work better than the flu vaccine, which for some reason doesn't attract the same sort of criticism.
https://twitter.com/rishirajgoel/status/1448711946010710023
By basically all measures, these vaccines work better than the flu vaccine, which for some reason doesn't attract the same sort of criticism.
Great link, summarizing recent research showing strong post-vaccination long-term B cell response.
Then Twitter surfaces a recent breakthrough infection study among 620k US veterans in the "More Tweets" section: https://twitter.com/EricTopol/status/1448815262522773520 After six months from initial vaccination (Mar-Aug) the J&J vaccine appears to have zero (!) VE against infection. Pfizer is holding at a modest 53% against infection. Worse, the curve has the same shape as J&J, merely 2 months delayed.
In spite of very promising cellular and molecular studies, I am left scratching my head: are the vaccines any good at preventing infection in the long term, where we define long term as a few years down the road? The question is somewhat rhetorical, as we don't have epi studies from 2025 yet.
PS. I am more than happy to make a distinction between infection and severe infection. The main reason I pay attention to VE against infection are vaccine mandates and the whole stigma buildup against unvaccinated people.
PS2. > the flu vaccine, which for some reason doesn't attract the same sort of criticism.
People are free to get or not get a flu vaccine. Not getting a covid vaccine means loss of livelihood, loss of basic liberties and social ostracism.
Then Twitter surfaces a recent breakthrough infection study among 620k US veterans in the "More Tweets" section: https://twitter.com/EricTopol/status/1448815262522773520 After six months from initial vaccination (Mar-Aug) the J&J vaccine appears to have zero (!) VE against infection. Pfizer is holding at a modest 53% against infection. Worse, the curve has the same shape as J&J, merely 2 months delayed.
In spite of very promising cellular and molecular studies, I am left scratching my head: are the vaccines any good at preventing infection in the long term, where we define long term as a few years down the road? The question is somewhat rhetorical, as we don't have epi studies from 2025 yet.
PS. I am more than happy to make a distinction between infection and severe infection. The main reason I pay attention to VE against infection are vaccine mandates and the whole stigma buildup against unvaccinated people.
PS2. > the flu vaccine, which for some reason doesn't attract the same sort of criticism.
People are free to get or not get a flu vaccine. Not getting a covid vaccine means loss of livelihood, loss of basic liberties and social ostracism.
> People are free to get or not get a flu vaccine. Not getting a covid vaccine means loss of livelihood, loss of basic liberties and social ostracism.
Gee, I wonder if something happened recently that made stopping Covid more pressing than making everyone get a flu shot? Sure seems like there’s some reason, maybe a few hundred thousand reasons, why as a society we’re taking Covid and vaccination against it more seriously than the flu.
Gee, I wonder if something happened recently that made stopping Covid more pressing than making everyone get a flu shot? Sure seems like there’s some reason, maybe a few hundred thousand reasons, why as a society we’re taking Covid and vaccination against it more seriously than the flu.
It’s weird to be so focused on infection, when efficacy against severe disease is more practically relevant. And the latter remains high, around 92% or higher, even against Delta.
Vaccine protection isn’t binary. Even if you end up infected your disease will be less severe AND you will be less contagious.
Vaccine protection isn’t binary. Even if you end up infected your disease will be less severe AND you will be less contagious.
[deleted]
COVID-19 vaccines aren't sterilizing to any meaningful extent. They provide only limited and temporary protection against infection. The real benefit is in protection against severe symptoms.
https://www.nature.com/articles/d41586-021-02689-y
https://www.businessinsider.com/delta-variant-made-herd-immu...
https://www.nature.com/articles/d41586-021-02689-y
https://www.businessinsider.com/delta-variant-made-herd-immu...
[deleted]
I call bullshit. Your source doesn’t address the efficacy decrease at all.
Yes, there are lasting changes from the vaccine, no that doesn’t indicate much about level of protection.
I definitely would never get a flu shot with its ridiculous efficacy numbers. If you forced me to get it to remain a part of society it would require my resistance by any means.
If you didn’t respond like an asshole id give you a couple sources. But, bullshit and all.
Yes, there are lasting changes from the vaccine, no that doesn’t indicate much about level of protection.
I definitely would never get a flu shot with its ridiculous efficacy numbers. If you forced me to get it to remain a part of society it would require my resistance by any means.
If you didn’t respond like an asshole id give you a couple sources. But, bullshit and all.
I don't know enough about vaccines to dispute what you're saying (though I feel like I have heard contrary data on this), but even if it's only fully effective for 8-9 months, isn't the fact that we had a vaccine that accomplished at least some of its goals safely designed and tested in record time a really cool thing?
Even if it's only effective for 6 months, that's still 6 months of slowing the spread, and conceivably we can extend the efficacy by administering booster shots.
Even if it's only effective for 6 months, that's still 6 months of slowing the spread, and conceivably we can extend the efficacy by administering booster shots.
It's not as though the concept of a vaccine booster is new, after all we get annual flu shots. It's also a question of efficacy of the vaccine versus the new predominate variant. Delta didn't exist when the vaccines were finalized.
My understanding is that all vaccines have similar "effectiveness curves", in that they are highly effective in the first weeks, and effectiveness degrades over time down to some low base level of immunity, where your body is no longer actively producing antibodies, but it has the ability to restart production quickly if necessary.
It's efficacy as measured as "chances of getting sick" declines significantly, but it's still pretty effective.
But the protection against hospitalization and death is still very robust even after almost a year.
But the protection against hospitalization and death is still very robust even after almost a year.
[deleted]
A really excellent survey on the prospects for mRNA technology from Derek Lowe: https://www.science.org/content/blog-post/what-mrna-good-and...
I wonder if the final stage will rather be direct production and injection of tailored antibodies instead of going around the corner by having ordinary cells express proteins that then trigger the immune system.
> direct production and injection of tailored antibodies instead of going around the corner by having ordinary cells express proteins that then trigger the immune system
Triggering the immune system does a lot more than produce a single wave of antibodies.
Triggering the immune system does a lot more than produce a single wave of antibodies.
Does "going around the corner," mean vaccines?
It's almost like we're emerging into a world just like the world when antibiotics were invented, but for antivirals. We basically had just a small handful of treatments for viruses, now there's a huge pipeline all of a sudden. Maybe in the future, having effective antivirals for just about any virus will be the norm, not the exception.
> Molnupiravir [interferes with] accurate replication of the virus
At first glance this sound like a really bad idea, given that the #1 concern is future covid mutations.
At first glance this sound like a really bad idea, given that the #1 concern is future covid mutations.
It specifically causes non-viable mutations. Therefore, the concern isn't currently that it'll cause mutations in the virus and create new strains, but rather that we have to be very confident that it isn't resulting in mutagenicity in mammalian cells.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136050/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136050/
Thanks, I wasn't aware of that.
Molnupiravir seems pretty good. I think in the trials eight people died in the placebo group, zero with the drug.
I wonder if they actually used human lung cells for this test; the article doesn’t seem to specify. Past tests have used Vero cells, which are apparently the norm for virology research, but aren’t a good analogue for human cells for Covid infection. This seems to be why some compounds worked well in a Petri dish, but didn’t work in actual humans.
Here's the actual paper: https://www.pnas.org/content/118/43/e2108728118
There's a lot of detailed discussion about different types of cells. Vero cells don't have TMPRSS2, but Calu-3 (human lung epithelial) cells do. To dramatically oversimplify, this compound works on the latter type but not the former.
They also did a little safety testing in a mouse model. This is early stage, as you point out there are a lot of things that work well in the lab and not so much in real humans, but still I find it promising.
There's a lot of detailed discussion about different types of cells. Vero cells don't have TMPRSS2, but Calu-3 (human lung epithelial) cells do. To dramatically oversimplify, this compound works on the latter type but not the former.
They also did a little safety testing in a mouse model. This is early stage, as you point out there are a lot of things that work well in the lab and not so much in real humans, but still I find it promising.
I’m not the best reader of scientific papers, but it looks like they used human lung cells and Vero cells. I’m not qualified to speak to the rest of the experimental design, but it looks like they’ve at least avoided that old mistake.
> We analyzed pseudotype entry driven by the spike protein of SARS-CoV-2 (SARS-2-S) or the glycoprotein of vesicular stomatitis virus (VSV-G) into the TMPRSS2-positive human lung cell line Calu-3 (7, 29). VSV-G was used as a control, as it does not depend on TMPRSS2 for host cell entry. Besides Calu-3 cells, we further used Vero cells (African green monkey, kidney) as a control, as these cells do not express TMPRSS2, and therefore any reduction in SARS-2-Sdriven entry would be related to either unspecific side effects or cytotoxicity.
> We analyzed pseudotype entry driven by the spike protein of SARS-CoV-2 (SARS-2-S) or the glycoprotein of vesicular stomatitis virus (VSV-G) into the TMPRSS2-positive human lung cell line Calu-3 (7, 29). VSV-G was used as a control, as it does not depend on TMPRSS2 for host cell entry. Besides Calu-3 cells, we further used Vero cells (African green monkey, kidney) as a control, as these cells do not express TMPRSS2, and therefore any reduction in SARS-2-Sdriven entry would be related to either unspecific side effects or cytotoxicity.
> PNAS October 26, 2021 118 (43) e2108728118; https://doi.org/10.1073/pnas.2108728118
I'm curious how was this published October 26, 2021? (Currently Oct 15)
I'm curious how was this published October 26, 2021? (Currently Oct 15)
That's the real advance! :)
PNAS recently moved to a continuous publication process so the paper comes out in the planned issue whenever ready rather than effectively coming out twice: once ahead-of-print and once in the issue.
https://www.pnas.org/page/updates#pnas-continuous-publicatio...
PNAS recently moved to a continuous publication process so the paper comes out in the planned issue whenever ready rather than effectively coming out twice: once ahead-of-print and once in the issue.
https://www.pnas.org/page/updates#pnas-continuous-publicatio...
Probably the date of the print publication.
I was reading that the flue shot also works against covid according to a study. The world will learn to live with covid. I'm more worried about the authoritarians taking advantage of the current crisis.
I remember reading in 2020 that those that have received a TB vaccine had better results with Covid. I never did find out if there was a co confounding variable that explains it. (I wouldn't be surprised if it does.)
This blocks TMPRSS2 which is the exact protein ivermectin blocks.
Some quick googling doesn’t back this up and my understanding is that ivermectin has only shown itself to be effective at doses that are higher then are remotely safe. It also just isn’t the sort of thing there would be incentive to lie about. Probably then the straightforward story is true no it’s only effective as prescribed as treatment for parasites. If you’d like to provide some sources though or more explanation that would be great.
Note that TMPRSS2 has been a potential target for treating covid basically since the beginning, so some one lying and claiming it as a mechanism of action isn’t surprising
Note that TMPRSS2 has been a potential target for treating covid basically since the beginning, so some one lying and claiming it as a mechanism of action isn’t surprising
As far as I can tell ivermectin has only been "studied" against TMPRSS2 in silico. The better-studied purported mechanism of ivermectin against SARS-CoV-2 involves something called importin [1]. On the other hand, bromhexine, which is a cough medicine used OTC around the world does inhibit TMPRSS2 and may have action against SARS-Cov-2 [2]. Bromhexine is a prodrug for ambroxol, which is also an OTC cold medicine in much of the world.
[1] https://pubmed.ncbi.nlm.nih.gov/32251768/ [2] https://pubmed.ncbi.nlm.nih.gov/32983936/
[1] https://pubmed.ncbi.nlm.nih.gov/32251768/ [2] https://pubmed.ncbi.nlm.nih.gov/32983936/
Already in 2020 (I forget just how early), __ice9 on twitter was pointing out bromhexine and stressing the importance of blocking both ACE2 and TMPRSS2 binding ("dual-entry inhibition"). This is not an area I personally know about, but it's worth bringing up for the enthusiasts for censorship.
https://twitter.com/__ice9/status/1368634545717788677
If it works, the OTC nature is important. Hard for any drug to be very effective if the get-an-appointment-see-a-doctor-get-a-prescription-get-it-filled system takes you well past peak viral load before you even start using it.
https://twitter.com/__ice9/status/1368634545717788677
If it works, the OTC nature is important. Hard for any drug to be very effective if the get-an-appointment-see-a-doctor-get-a-prescription-get-it-filled system takes you well past peak viral load before you even start using it.
I have no opinion whatsoever regarding whether or not ivermectin's purported mechanism of action against COVID is valid.
However, this:
> It also just isn’t the sort of thing there would be incentive to lie about
is not true.
There are two incentives to lie about this, if you are in any way associated with drug or vaccine manufacturers.
1.) Ivermectin is out of patent and dirt cheap; basically not profitable at all
2.) Emergency use authorization for the vaccines relied on there being no available alternative treatment
Again, I have no opinion regarding whether or not ivermectin is remotely useful for COVID. But there are plenty of incentives aimed against any older generic being repurposed.
However, this:
> It also just isn’t the sort of thing there would be incentive to lie about
is not true.
There are two incentives to lie about this, if you are in any way associated with drug or vaccine manufacturers.
1.) Ivermectin is out of patent and dirt cheap; basically not profitable at all
2.) Emergency use authorization for the vaccines relied on there being no available alternative treatment
Again, I have no opinion regarding whether or not ivermectin is remotely useful for COVID. But there are plenty of incentives aimed against any older generic being repurposed.
There are more countries in the world than the US and many of them would welcome something like ivermectin if it worked.
Sure, ivermectin is dirt cheap, but that doesn't mean somebody couldn't make a buck off of it. Not to mention that any doctor who actually proved something like that to be effective would be quickly hailed as a hero.
This is the problem with the "Covid Conspiracists"--magically everything is 100% worldwide unified action with perfect lockstep and no deviations--in spite of the fact that many of these countries have primal hatred for one another.
Sure, ivermectin is dirt cheap, but that doesn't mean somebody couldn't make a buck off of it. Not to mention that any doctor who actually proved something like that to be effective would be quickly hailed as a hero.
This is the problem with the "Covid Conspiracists"--magically everything is 100% worldwide unified action with perfect lockstep and no deviations--in spite of the fact that many of these countries have primal hatred for one another.
Many countries are using ivermectin...Mexico, India, it's even being prescribed in the US and UK. What it is missing is quality studies, but there are millions of prescriptions being written based off of clinical discretion.
So yes, there are more countries, and many ARE accepting ivermectin for treating COVID. And again, I don't know or care if it works, I'm vaccinated and wouldn't take it, nor am I a conspiracy theorist, your point is just not correct.
So yes, there are more countries, and many ARE accepting ivermectin for treating COVID. And again, I don't know or care if it works, I'm vaccinated and wouldn't take it, nor am I a conspiracy theorist, your point is just not correct.
> What it is missing is quality studies
Um, exactly? We have millions of scrips issued and still nobody can produce data.
Now, what we can posit is that there is a worldwide conspiracy to suppress the fact that ivermectin is effective OR we can posit that ivermectin doesn't actually work very well for Covid.
The problem with anecdotal medical treatments is that the human organism is highly variable. Just about any disease "treatment" will work for somebody, somewhere. But that's not enough to proclaim that something works. This is going to be especially true in countries where parasitic infestation (which ivermectin does treat) is more common. If a significant fraction of your population got their parasitic infestation cured, their Covid numbers are going to look quite a bit better, too.
If we're trading on anecdotes, then I'll say that ivermectin doesn't work. We had lots of people taking ivermectin at various level in US Red State land. Their hospitals still got overrun. If anything, ivermectin use is correlated with more hospitalization. This is, in fact, a tautology--but not because ivermectin makes Covid worse (or better) but because people were getting poisoned by ivermectin and most ivermectin users were in red state areas which had lower vaccination rates.
This is why you don't believe claims without data.
> And again, I don't know or care if it works, I'm vaccinated and wouldn't take it, nor am I a conspiracy theorist, your point is just not correct.
The problem is that your "I'm just a skeptic" ignores the fact that nobody can cough up any data. Continuing to promulgate things in the absence of data articulates your position quite clearly.
Um, exactly? We have millions of scrips issued and still nobody can produce data.
Now, what we can posit is that there is a worldwide conspiracy to suppress the fact that ivermectin is effective OR we can posit that ivermectin doesn't actually work very well for Covid.
The problem with anecdotal medical treatments is that the human organism is highly variable. Just about any disease "treatment" will work for somebody, somewhere. But that's not enough to proclaim that something works. This is going to be especially true in countries where parasitic infestation (which ivermectin does treat) is more common. If a significant fraction of your population got their parasitic infestation cured, their Covid numbers are going to look quite a bit better, too.
If we're trading on anecdotes, then I'll say that ivermectin doesn't work. We had lots of people taking ivermectin at various level in US Red State land. Their hospitals still got overrun. If anything, ivermectin use is correlated with more hospitalization. This is, in fact, a tautology--but not because ivermectin makes Covid worse (or better) but because people were getting poisoned by ivermectin and most ivermectin users were in red state areas which had lower vaccination rates.
This is why you don't believe claims without data.
> And again, I don't know or care if it works, I'm vaccinated and wouldn't take it, nor am I a conspiracy theorist, your point is just not correct.
The problem is that your "I'm just a skeptic" ignores the fact that nobody can cough up any data. Continuing to promulgate things in the absence of data articulates your position quite clearly.
I'm not saying "I'm just a skeptic." People keep putting words in my mouth or arguing against points that I didn't make.
My original argument was against the poster who said that there was no reason to lie about the utility of ivermectin. I said that there was.
In arguing against points that I didn't make, though, you keep making points that I still disagree with. Such as this false dichotomy you keep laying out:
> Now, what we can posit is that there is a worldwide conspiracy to suppress the fact that ivermectin is effective OR we can posit that ivermectin doesn't actually work very well for Covid.
Those aren't the only two options. A third option is that ivermectin does actually have some mechanism of action that has some utility in treating COVID, and that the informal clinical data which continues its usage is because of that. You're acting as if there are formal studies which indicate that it has no utility, but all of the data debunking the utility of ivermectin instead suggests that there is simply not a rigorous study formally demonstrating the utility.
For the third or fourth time, I'm not even saying that I believe that it does have utility. I actually don't care about ivermectin.
> If we're trading on anecdotes, then I'll say that ivermectin doesn't work
I don't remember laying out an anecdote saying that ivermectin does work. An argument was put forth saying that if ivermectin did work, there would be scientists and doctors all over the world studying and using it. I said that there were scientists and doctors all over the world studying and using it. I think it's entirely possible it does nothing and those things could still be true. You're the only one between us who is actually making a claim about the utility of the drug.
> This is why you don't believe claims without data.
I don't know what claim I'm purported to be believing.
My original argument was against the poster who said that there was no reason to lie about the utility of ivermectin. I said that there was.
In arguing against points that I didn't make, though, you keep making points that I still disagree with. Such as this false dichotomy you keep laying out:
> Now, what we can posit is that there is a worldwide conspiracy to suppress the fact that ivermectin is effective OR we can posit that ivermectin doesn't actually work very well for Covid.
Those aren't the only two options. A third option is that ivermectin does actually have some mechanism of action that has some utility in treating COVID, and that the informal clinical data which continues its usage is because of that. You're acting as if there are formal studies which indicate that it has no utility, but all of the data debunking the utility of ivermectin instead suggests that there is simply not a rigorous study formally demonstrating the utility.
For the third or fourth time, I'm not even saying that I believe that it does have utility. I actually don't care about ivermectin.
> If we're trading on anecdotes, then I'll say that ivermectin doesn't work
I don't remember laying out an anecdote saying that ivermectin does work. An argument was put forth saying that if ivermectin did work, there would be scientists and doctors all over the world studying and using it. I said that there were scientists and doctors all over the world studying and using it. I think it's entirely possible it does nothing and those things could still be true. You're the only one between us who is actually making a claim about the utility of the drug.
> This is why you don't believe claims without data.
I don't know what claim I'm purported to be believing.
You're discussing incentives that maybe some major drug companies might have, but they aren't the only ones around. I guess, the more accurate position is that there are strong upper bounds to how effective a secretly suppressed drug could be. Imagine that ivermectin just cured covid for a minute. The would be incredibly easy to prove in a study. I mean just observational studies would be glaringly obvious. What ambitious young scientist wouldn't want curing covid on their resume? So you have to believe, either the vast majority of scientists, the press, or government are complicit in this conspiracy and I don't see strong incentives for any of those groups.
Well that's the thing, is that there are literally millions of people in entire countries being prescribed it. India has dished out millions of doses for COVID, and there are many doctors and researchers completely convinced by clinical evidence. It's not as if there are no people picking up a signal, or that no studies are showing utility, it's that the available studies are methodologically questionable. But as you are aware, there are more formal studies taking place at the moment, and the official scientific consensus is that we don't yet know.
Again, my argument against you was that you said that there was no motivation against it, and I said that wasn't true.
Again, my argument against you was that you said that there was no motivation against it, and I said that wasn't true.
> 2.) Emergency use authorization for the vaccines relied on there being no available alternative treatment
That's simply so factually wrong it's tough to take it as serious. having a treatment that might lessen the severity of some percentage of the people that get covid has absolutely nothing to do with a prophylactic EUA for a vaccine that is wildly efficacious against mild and severe covid cases and stop you from getting it in the first place. Let's do a thought experiment even if that were true... that would mean the other vaccines that are under an EUA would have been revoked the moment Pfizer got their full approval which didn't happen. This is "there are naval insignias on the flags therefore we are not a constitutional democracy" level of conspiratorial thinking.
> 1.) Ivermectin is out of patent and dirt cheap; basically not profitable at all
that's the reason they threw it at the virus in the first place. They were looking for anything that might help.
That's simply so factually wrong it's tough to take it as serious. having a treatment that might lessen the severity of some percentage of the people that get covid has absolutely nothing to do with a prophylactic EUA for a vaccine that is wildly efficacious against mild and severe covid cases and stop you from getting it in the first place. Let's do a thought experiment even if that were true... that would mean the other vaccines that are under an EUA would have been revoked the moment Pfizer got their full approval which didn't happen. This is "there are naval insignias on the flags therefore we are not a constitutional democracy" level of conspiratorial thinking.
> 1.) Ivermectin is out of patent and dirt cheap; basically not profitable at all
that's the reason they threw it at the virus in the first place. They were looking for anything that might help.
One of the reasons it got looked at was due to a scabies outbreak at Valley View Nursing Home in Toronto that coincidentally had a Covid outbreak at the same time in early 2020. Oddly enough, the residents that had scabies did better than the residents that didn't.
From the featured article “Janetka co-founded a biotechnology startup company called ProteXase Therapeutics”
I guess you could see what their business plan is?
I guess you could see what their business plan is?
But that doesn't incentive say a PHD candidate at Harvard to agree right? They're not making any money from this new startup and they'd probably get a lot of positive news coverage if they could show a cheap cure to covid. Certainly now things are a bit locked in place so it would be harder, there would be some repetitional damage at stake, but I'm just very unconvinced a cabal of biotech startups really has the power to keep a lid on something like this
nekt(1)
"some quick googling"? Do better than this.
I mean it really isn't on me to source someone else's claim. That's why I ask them to provide a source.
Ivermectin doesn't have any legit studies with large samples to show that it's even that useful against covid.
Also, what happened to hydroxychloroquine? That was the big thing in 2020. guess 2021 is ivermectin.
Also, what happened to hydroxychloroquine? That was the big thing in 2020. guess 2021 is ivermectin.
I am not making any claims of any of these substances effectiveness in treating covid. I'm just pointing out that this substance claims to block the same human protein ivermectin does. We can all make of that what we will.
In political discussions we call this the “anti-anti” position. If you’re not making any claims that Ivermectin works, why are you wasting so much energy and karma attacking those that think it doesn’t work?
Based on what metric?
The vaccines were authorized under emergency use with trial participants comparable to samples conducted with Ivermectin.
How is it not worth considering for a drug that's already known to be safe to administer and cheap?
Beyond that, there are practicing doctors advocating that they've had good results. This should be more than enough to consider it's use, and not dismiss it as some 'thing of the year to dismiss'.
The vaccines were authorized under emergency use with trial participants comparable to samples conducted with Ivermectin.
How is it not worth considering for a drug that's already known to be safe to administer and cheap?
Beyond that, there are practicing doctors advocating that they've had good results. This should be more than enough to consider it's use, and not dismiss it as some 'thing of the year to dismiss'.
"The Phase 3 clinical trial of BNT162b2 began on July 27 and has enrolled 43,661 participants to date, 41,135 of whom have received a second dose of the vaccine candidate as of November 13, 2020."
Wow so there was an ivermectin study with 44k people? Where is it?
I agree that it should be able to be studied and probably used. But what's going on is that people are looking for an ALTERNATIVE to the vaccine... which is detrimental when the vaccine is proven to be our best tactic against death/serious illness.
Wow so there was an ivermectin study with 44k people? Where is it?
I agree that it should be able to be studied and probably used. But what's going on is that people are looking for an ALTERNATIVE to the vaccine... which is detrimental when the vaccine is proven to be our best tactic against death/serious illness.
>Wow so there was an ivermectin study with 44k people? Where is it?
Perhaps I should have spoken more precisely, but I don't get the impression you're trying to seriously consider whether ivermectin is useful.
https://ivmmeta.com/
Preemptively, if you're interested in picking apart why one RCT can't be compared in any way to a collection of studies, only some of which are RCTs, I'm not.
> But what's going on is that people are looking for an ALTERNATIVE to the vaccine
*some people
You're effectively strawmanning, and choosing not to engage with the actual doctors who don't advocate this. Which is practically all of the ones I can find. But by all means, please link me all of the doctors stating we should use ivermectin as an alternative. I'll bet I can link a lot more that aren't.
The website I linked above even explicitly states this in bold, on the front page.
>which is detrimental when the vaccine is proven to be our best tactic against death/serious illness.
The trial you're citing seems to indicate there was no observed effect on mortality.
Perhaps I should have spoken more precisely, but I don't get the impression you're trying to seriously consider whether ivermectin is useful.
https://ivmmeta.com/
Preemptively, if you're interested in picking apart why one RCT can't be compared in any way to a collection of studies, only some of which are RCTs, I'm not.
> But what's going on is that people are looking for an ALTERNATIVE to the vaccine
*some people
You're effectively strawmanning, and choosing not to engage with the actual doctors who don't advocate this. Which is practically all of the ones I can find. But by all means, please link me all of the doctors stating we should use ivermectin as an alternative. I'll bet I can link a lot more that aren't.
The website I linked above even explicitly states this in bold, on the front page.
>which is detrimental when the vaccine is proven to be our best tactic against death/serious illness.
The trial you're citing seems to indicate there was no observed effect on mortality.
> Wow so there was an ivermectin study with 44k people? Where is it?
There wasn't. Once you eliminate the studies that made up their data it is clear ivermectin doesn't work in the few studies that are left so nobody would bother doing a big study.
There wasn't. Once you eliminate the studies that made up their data it is clear ivermectin doesn't work in the few studies that are left so nobody would bother doing a big study.
Fun fact: the trial you referenced failed to show any benefit of COVID vaccination in reducing all-cause mortality in the population they studied:
https://www.medrxiv.org/content/10.1101/2021.07.28.21261159v...
> During the blinded, controlled period, 15 BNT162b2 and 14 placebo recipients died; during the open-label period, 3 BNT162b2 and 2 original placebo recipients who received BNT162b2 after unblinding died. None of these deaths were considered related to BNT162b2 by investigators.
There was actually one more death in the experimental group, albeit that's not significantly significant.
So some combination of the following must be true:
(1) The vaccination is effective at reducing COVID mortality, but COVID mortality for people in the trial was such a joke that eliminating 95% of COVID mortality doesn't actually change one's risk of dying in a non-negligible manner
(2) The vaccination is effective at reducing COVID mortality, which does spare lives, but it ends up killing just as many from adverse events / side effects
(3) The vaccine isn't effective and they doctored the numbers.
My money is mostly on (1) with a sprinkling of (2), personally.
---
And since people like to be binary thinkers, this is where I mention that I'm not an Ivermectin shill and as a medical nihilist I'm strongly skeptical of treatments in general. And while I haven't looked at the IVM data very much at all, what I have seen is incredibly weak evidence at best, as well as a bunch of really crappy associative arguments from the IVM crowd ("Africa uses IVM and Africa has less COVID mortality than the US!" as if that proves anything)
To quote (slightly paraphrased) the great Jacob Stegenga:
> If we consider the ubiquity of small effect sizes in medicine, the extent of misleading evidence in medical research, the thin theoretical basis of many interventions, and the malleability of empirical methods, then our confidence in medical interventions ought to be low.
https://www.medrxiv.org/content/10.1101/2021.07.28.21261159v...
> During the blinded, controlled period, 15 BNT162b2 and 14 placebo recipients died; during the open-label period, 3 BNT162b2 and 2 original placebo recipients who received BNT162b2 after unblinding died. None of these deaths were considered related to BNT162b2 by investigators.
There was actually one more death in the experimental group, albeit that's not significantly significant.
So some combination of the following must be true:
(1) The vaccination is effective at reducing COVID mortality, but COVID mortality for people in the trial was such a joke that eliminating 95% of COVID mortality doesn't actually change one's risk of dying in a non-negligible manner
(2) The vaccination is effective at reducing COVID mortality, which does spare lives, but it ends up killing just as many from adverse events / side effects
(3) The vaccine isn't effective and they doctored the numbers.
My money is mostly on (1) with a sprinkling of (2), personally.
---
And since people like to be binary thinkers, this is where I mention that I'm not an Ivermectin shill and as a medical nihilist I'm strongly skeptical of treatments in general. And while I haven't looked at the IVM data very much at all, what I have seen is incredibly weak evidence at best, as well as a bunch of really crappy associative arguments from the IVM crowd ("Africa uses IVM and Africa has less COVID mortality than the US!" as if that proves anything)
To quote (slightly paraphrased) the great Jacob Stegenga:
> If we consider the ubiquity of small effect sizes in medicine, the extent of misleading evidence in medical research, the thin theoretical basis of many interventions, and the malleability of empirical methods, then our confidence in medical interventions ought to be low.
>Fun fact: the trial you referenced failed to show any benefit of COVID vaccination in reducing all-cause mortality in the population they studied:
Is the implication that we should have expected it to? The study endpoints are clearly "vaccine efficacy (VE) against laboratory-confirmed COVID-19 and safety data".
Is the implication that we should have expected it to? The study endpoints are clearly "vaccine efficacy (VE) against laboratory-confirmed COVID-19 and safety data".
I think most people would have expected it to. Whether that's a reasonable expectation or not is up for debate. But yeah, many if not most people in the US were convinced that COVID was a threat so severe that it warranted completely uprooting life as we knew it. A sizeable minority of people are convinced that COVID vaccination is so important that people should be coerced into it by almost any means necessary. So I think understanding that we don't have a single randomized controlled trial that actually shows a reduction in all-cause mortality when given this intervention is pretty important.
It's a general principle of medicine (or at least, it used to be) that the important outcomes are the actually clinically relevant outcomes. Did people die less? Did they achieve a better quality of life? When you get into proxy metrics you get to this weird place where you can show that something is insanely effective for proxy metric X, and yet it makes no difference (or is even deleterious) in thing-you-actually-care-about Y.
It's a general principle of medicine (or at least, it used to be) that the important outcomes are the actually clinically relevant outcomes. Did people die less? Did they achieve a better quality of life? When you get into proxy metrics you get to this weird place where you can show that something is insanely effective for proxy metric X, and yet it makes no difference (or is even deleterious) in thing-you-actually-care-about Y.
This study not finding an effect it wasn't designed to isn't incompatible with the more hyperbolic interpretations of the threat of COVID / the importance of vaccination.
Did we need RCTs demonstrating a reduction in all-cause mortality for polio or measles vaccines before it became blindingly obvious that they were a good idea?
Did we need RCTs demonstrating a reduction in all-cause mortality for polio or measles vaccines before it became blindingly obvious that they were a good idea?
I initially skipped over this post because it appeared to be written in bad faith [1]. But I gave it another shot and read the linked paper, and I agree with the summary. Thanks for pointing this out -- your post has changed my understanding of the vaccine's effectiveness.
For skeptical readers - The linked paper is a medrxiv preprint, with authors from several locations. Many of the authors list affiliations with Pfizer, and the last author is an MD at Pfizer. This seems to be a required report from the ~6-month point of a clinical trial. There really are 14 and 15 all-cause deaths reported in the placebo and treatment groups, respectively. The causes of death for each group are in table S4 [2]. The incidence of COVID in the treatment group is much lower than in the placebo group.
I'm surprised by these results because I would have expected to see significantly lower mortality in the vaccine group.
One possible reason for this surprising result is that only a small fraction of people - even in the placebo group - caught COVID at all. I'm not sure how to account for possible missed infections but Figure 2 of the main text indicates that 0.08% of the placebo group became CASES (which I think means something like "person felt bad enough to see a medical professional, who then diagnosed them with COVID"), and the table in Figure 2 indicates that there were 1034 "occurrences" out of ~22,000 people in the placebo group (which I read as "~5% confirmed infections").
So, it's possible that the beneficial effect of the vaccine is still hidden in the statistical noise since there have been so few infections in the placebo group. It's also possible that some people _were_ harmed by receiving the vaccine (see table S4 [2]), so there's a fixed harm upfront to the vaccine group, which may eventually be surpassed once more of the placebo group gets infected.
Thanks for posting this!
[1] I really do appreciate you making this post, and it helped me learn something. I would have been more willing to read it initially if it had excluded the phrases "such a joke", "since people like to be binary thinkers", "crappy associative arguments", "to quote the great...". It seems like there's a silent majority of HN lurkers that are interested in all perspectives, and really are open to quality arguments like this, but might dismiss this post before reading it because of the choice of phrases.
[2] Link to supp material PDF is on this page: https://www.medrxiv.org/content/10.1101/2021.07.28.21261159v...
For skeptical readers - The linked paper is a medrxiv preprint, with authors from several locations. Many of the authors list affiliations with Pfizer, and the last author is an MD at Pfizer. This seems to be a required report from the ~6-month point of a clinical trial. There really are 14 and 15 all-cause deaths reported in the placebo and treatment groups, respectively. The causes of death for each group are in table S4 [2]. The incidence of COVID in the treatment group is much lower than in the placebo group.
I'm surprised by these results because I would have expected to see significantly lower mortality in the vaccine group.
One possible reason for this surprising result is that only a small fraction of people - even in the placebo group - caught COVID at all. I'm not sure how to account for possible missed infections but Figure 2 of the main text indicates that 0.08% of the placebo group became CASES (which I think means something like "person felt bad enough to see a medical professional, who then diagnosed them with COVID"), and the table in Figure 2 indicates that there were 1034 "occurrences" out of ~22,000 people in the placebo group (which I read as "~5% confirmed infections").
So, it's possible that the beneficial effect of the vaccine is still hidden in the statistical noise since there have been so few infections in the placebo group. It's also possible that some people _were_ harmed by receiving the vaccine (see table S4 [2]), so there's a fixed harm upfront to the vaccine group, which may eventually be surpassed once more of the placebo group gets infected.
Thanks for posting this!
[1] I really do appreciate you making this post, and it helped me learn something. I would have been more willing to read it initially if it had excluded the phrases "such a joke", "since people like to be binary thinkers", "crappy associative arguments", "to quote the great...". It seems like there's a silent majority of HN lurkers that are interested in all perspectives, and really are open to quality arguments like this, but might dismiss this post before reading it because of the choice of phrases.
[2] Link to supp material PDF is on this page: https://www.medrxiv.org/content/10.1101/2021.07.28.21261159v...
[meta: this was supposed to be a quick response and then I ended up getting real longwinded]
Glad you got some value out of my comment!
Thanks for the feedback on my tone. In particular the references to specific examples was very helpful to me. I’ll [try to] be mindful of its effect in the future.
Not that it's necessary but just because it's kind of interesting to psychoanalyze, I think some of the tone comes as a [maladaptive] response to past times on HN where I'd go really deep into analyzing certain studies, etc and then would get downvoted or even flagged because the conclusion was that lockdowns were deleterious or that mandates are a bad idea, etc.
The binary thinkers comment specifically (you're right that it will tend to put people off btw) was because in general (not just on HN) it happens all the time that if I point out, say, how we don't even have an RCT that shows a reduction in all-cause mortality from getting COVID-vaccinated, very often I'll get a response to the tune of "Ivermectin doesn't even work you dummy" because most people seem to only have two boxes to put people in (you're either team trump or team biden, team vaccine or team ivermectin, etc). But obviously even if I had done it in a more diplomatic way, making reference to people being binary thinkers is only going to distract from the actual points being made.
I am curious of your mentioning of being offput by "to quote the great...". Did it sound like I was being sarcastic, or was it something else about it? Because I intended it in the literal sense, i.e. indicating my respect for Stegenga and his work.
---
Back to the actual study:
> One possible reason for this surprising result is that only a small fraction of people - even in the placebo group - caught COVID at all. I'm not sure how to account for possible missed infections but Figure 2 of the main text indicates that 0.08% of the placebo group became CASES (which I think means something like "person felt bad enough to see a medical professional, who then diagnosed them with COVID"), and the table in Figure 2 indicates that there were 1034 "occurrences" out of ~22,000 people in the placebo group (which I read as "~5% confirmed infections").
Yes. I suspect that this is partially due to the fact that they actually take some steps to confirm that it really is COVID, whereas in the real world (at least in 2020, but probably still now) they'd run a PCR test with an absurdly high cycle threshold cutoff and then call that COVID even if you were completely asymptomatic (which as an aside is an oxymoron because COVID is supposed to stand for "Coronavirus Infectious Disease", and yet an asymptomatic individual is not diseased (nor are they very infectious btw)). So one interpretation is that when care is taken to actually be somewhat careful about calling something a COVID case, that the prevalence of COVID infection ends up being quite low. Whereas when that care is not taken (whether due to negligence or institutional incentives to drum up case counts / fear in general) you end up with much higher apparent case counts.
This is quite speculative, I know. I'd really like to look at a chart of reported COVID cases in the US versus the rate of cases in this trial. I'd be curious if they are similar shape / relative magnitude, or if there's dramatically more cases in the US in general than the laboratory-confirmed cases in the trial.
I couldn't actually find an actual case definition (maybe it's in the supplement?) but I found this under the Efficacy subheading in the main text:
> BNT162b2 efficacy against laboratory-confirmed COVID-19 with onset ≥7 days post-dose 2 was assessed descriptively in participants without serological or virological evidence of SARS- CoV-2 infection ≤7 days post-dose 2, and in participants with and without evidence of prior infection. Efficacy against severe COVID-19 was also assessed.
So I think that means when calculating their overall VE number, they don't "start counting" lab-confirmed COVID-19 until it's been at least a week post second dose. I do know in general in these trials they like to play that game (ignoring infections before the "fully vaccinated" cutoff to get a better-looking VE number). Although Figure 2 seems to provide numbers starting immediately after dose #1 so I suppose those numbers tell us that while VE is quite bad immediately after the first dose, its expected value doesn't seem to be negative (at least in this cohort)
As an aside, I'd note that they blew up the control arm after 6 months, so this is basically the only clean data we're ever going to get. Which should be very concerning to people considering the enormous push to mandate vaccination for an intervention that has never been shown to reduce all-cause mortality in the studied populations.
> So, it's possible that the beneficial effect of the vaccine is still hidden in the statistical noise since there have been so few infections in the placebo group. It's also possible that some people _were_ harmed by receiving the vaccine (see table S4 [2]), so there's a fixed harm upfront to the vaccine group, which may eventually be surpassed once more of the placebo group gets infected.
Unless the data is doctored or has some flaw that I'm not seeing, I agree that a much higher base rate of COVID infection would probably have shown a positive effect on mortality. Which brings us back to #1 of the 3 possible explanations I gave in my original comment. I find it very interesting that actual COVID mortality (or even bad outcomes) were so rare in this cohort of >44,000 people, that a well-over-90-percent-effective-in-reducing-COVID-mortality intervention literally did not make a detectable effect on net mortality. I think from a societal perspective it's quite interesting because during the time this trial was running, people were (and still are btw) getting bombarded by fearmongering, giant red eternally-incrementing "live" death tickers, etc.
It doesn't take some grand conspiracy to see why that might be, but I think it's something interesting to reflect on. It's a large part of why COVID took me from kind of libertarian leaning to full-blown anarchocapitalist, because I am personally so disgusted by what the media, the public health "authorities", and "polite society" at large did in terms of catalyzing such tremendous suffering on a worldwide scale (via the hysteria, global supply chain disruption, missed medical appointments, cancelled elective surgeries, and outright authoritarian/totalitarian public policy), for something that for most people, they would literally never notice if not bombarded about its existence.
Glad you got some value out of my comment!
Thanks for the feedback on my tone. In particular the references to specific examples was very helpful to me. I’ll [try to] be mindful of its effect in the future.
Not that it's necessary but just because it's kind of interesting to psychoanalyze, I think some of the tone comes as a [maladaptive] response to past times on HN where I'd go really deep into analyzing certain studies, etc and then would get downvoted or even flagged because the conclusion was that lockdowns were deleterious or that mandates are a bad idea, etc.
The binary thinkers comment specifically (you're right that it will tend to put people off btw) was because in general (not just on HN) it happens all the time that if I point out, say, how we don't even have an RCT that shows a reduction in all-cause mortality from getting COVID-vaccinated, very often I'll get a response to the tune of "Ivermectin doesn't even work you dummy" because most people seem to only have two boxes to put people in (you're either team trump or team biden, team vaccine or team ivermectin, etc). But obviously even if I had done it in a more diplomatic way, making reference to people being binary thinkers is only going to distract from the actual points being made.
I am curious of your mentioning of being offput by "to quote the great...". Did it sound like I was being sarcastic, or was it something else about it? Because I intended it in the literal sense, i.e. indicating my respect for Stegenga and his work.
---
Back to the actual study:
> One possible reason for this surprising result is that only a small fraction of people - even in the placebo group - caught COVID at all. I'm not sure how to account for possible missed infections but Figure 2 of the main text indicates that 0.08% of the placebo group became CASES (which I think means something like "person felt bad enough to see a medical professional, who then diagnosed them with COVID"), and the table in Figure 2 indicates that there were 1034 "occurrences" out of ~22,000 people in the placebo group (which I read as "~5% confirmed infections").
Yes. I suspect that this is partially due to the fact that they actually take some steps to confirm that it really is COVID, whereas in the real world (at least in 2020, but probably still now) they'd run a PCR test with an absurdly high cycle threshold cutoff and then call that COVID even if you were completely asymptomatic (which as an aside is an oxymoron because COVID is supposed to stand for "Coronavirus Infectious Disease", and yet an asymptomatic individual is not diseased (nor are they very infectious btw)). So one interpretation is that when care is taken to actually be somewhat careful about calling something a COVID case, that the prevalence of COVID infection ends up being quite low. Whereas when that care is not taken (whether due to negligence or institutional incentives to drum up case counts / fear in general) you end up with much higher apparent case counts.
This is quite speculative, I know. I'd really like to look at a chart of reported COVID cases in the US versus the rate of cases in this trial. I'd be curious if they are similar shape / relative magnitude, or if there's dramatically more cases in the US in general than the laboratory-confirmed cases in the trial.
I couldn't actually find an actual case definition (maybe it's in the supplement?) but I found this under the Efficacy subheading in the main text:
> BNT162b2 efficacy against laboratory-confirmed COVID-19 with onset ≥7 days post-dose 2 was assessed descriptively in participants without serological or virological evidence of SARS- CoV-2 infection ≤7 days post-dose 2, and in participants with and without evidence of prior infection. Efficacy against severe COVID-19 was also assessed.
So I think that means when calculating their overall VE number, they don't "start counting" lab-confirmed COVID-19 until it's been at least a week post second dose. I do know in general in these trials they like to play that game (ignoring infections before the "fully vaccinated" cutoff to get a better-looking VE number). Although Figure 2 seems to provide numbers starting immediately after dose #1 so I suppose those numbers tell us that while VE is quite bad immediately after the first dose, its expected value doesn't seem to be negative (at least in this cohort)
As an aside, I'd note that they blew up the control arm after 6 months, so this is basically the only clean data we're ever going to get. Which should be very concerning to people considering the enormous push to mandate vaccination for an intervention that has never been shown to reduce all-cause mortality in the studied populations.
> So, it's possible that the beneficial effect of the vaccine is still hidden in the statistical noise since there have been so few infections in the placebo group. It's also possible that some people _were_ harmed by receiving the vaccine (see table S4 [2]), so there's a fixed harm upfront to the vaccine group, which may eventually be surpassed once more of the placebo group gets infected.
Unless the data is doctored or has some flaw that I'm not seeing, I agree that a much higher base rate of COVID infection would probably have shown a positive effect on mortality. Which brings us back to #1 of the 3 possible explanations I gave in my original comment. I find it very interesting that actual COVID mortality (or even bad outcomes) were so rare in this cohort of >44,000 people, that a well-over-90-percent-effective-in-reducing-COVID-mortality intervention literally did not make a detectable effect on net mortality. I think from a societal perspective it's quite interesting because during the time this trial was running, people were (and still are btw) getting bombarded by fearmongering, giant red eternally-incrementing "live" death tickers, etc.
It doesn't take some grand conspiracy to see why that might be, but I think it's something interesting to reflect on. It's a large part of why COVID took me from kind of libertarian leaning to full-blown anarchocapitalist, because I am personally so disgusted by what the media, the public health "authorities", and "polite society" at large did in terms of catalyzing such tremendous suffering on a worldwide scale (via the hysteria, global supply chain disruption, missed medical appointments, cancelled elective surgeries, and outright authoritarian/totalitarian public policy), for something that for most people, they would literally never notice if not bombarded about its existence.
I can't believe it's not Ivermectin
There's a caveat, most treatments that look promising don't pan out, but there are a lot in the pipeline and it seems likely that some will. What I think will happen is a cocktail of antivirals, and together these will significantly reduce the mortality. We need that, because it looks like the virus will probably be circulating endemically. The other great thing about a cocktail (as opposed to a single antiviral) is that the virus developing resistance is both less likely and less of a problem if it does happen.