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Oxford-AstraZeneca Vaccine Less Effective Than the Two MRNA Vaccines
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From AstraZeneca’s press release:

This announcement contains inside information

Not anymore.

23 November 2020 07:00 GMT

Two different dosing regimens demonstrated efficacy with one showing a better profile

No hospitalisations or severe cases of COVID-19 in participants treated with AZD1222

Positive high-level results from an interim analysis of clinical trials of AZD1222 in the UK and Brazil showed the vaccine was highly effective in preventing COVID-19, the primary endpoint, and no hospitalisations or severe cases of the disease were reported in participants receiving the vaccine. There were a total of 131 COVID-19 cases in the interim analysis.

131 is a pretty sizable number of cases, but one reason they got that high is because it’s less effective in the treatment arm than the Pfizer-BioNTech and Moderna vaccines.

One dosing regimen (n=2,741) showed vaccine efficacy of 90% when AZD1222 was given as a half dose, followed by a full dose at least one month apart, and another dosing regimen (n=8,895) showed 62% efficacy when given as two full doses at least one month apart.

Is there a good reason to think the 1.5 dose regimen is more effective than the 2.0 dose regimen? Or is it just the smaller sample size?

The combined analysis from both dosing regimens (n=11,636) resulted in an average efficacy of 70%. All results were statistically significant (p<=0.0001).

Three weeks ago this would have been exciting, upbeat news. But the Messenger RNA vaccines came out in the 94-95% efficacy range. On the other hand, they are trickier to keep cold enough, so this one might have some use in regions without good electricity.

The vaccine can be stored, transported and handled at normal refrigerated conditions (2-8 degrees Celsius/ 36-46 degrees Fahrenheit) for at least six months and administered within existing healthcare settings.

 
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  1. OT:
    World War Hair escalation.

    • Replies: @Mike Pierson, Davenport Rector, Midfielder
    @Altai

    John Cleese is hanging tough in WWT

    https://t.co/lMAn4U6cht

    https://t.co/oGPwEWJM9a

    https://www.rt.com/news/507517-john-cleese-transphonic-rowling/

    The joys of being old and rich. You don't have to GAF.

    , @AndrewR
    @Altai

    When Serena threw her "sh3boon" temper tantrum, I felt bad for Naomi, who seemed like a sweet girl. Now I want to send both of them, together with Serena's girl Meghan Markle, to the Islamic State (is that still a thing?)

    In related news, Serena's hubby, reddit co-founder Alexis Ohanian, responded to me on Twitter once. Someone else had insulted him and Serena, so Alexis tweeted to him something like "why don't you say that to my face?"

    I pointed out the absurdity of a man in a "power couple" like his to get so angry at low status trolls on the internet like Scott Greer. He responded right before my account got permanently suspended.

    I think on some level he's well aware she is unattractive and manly, and he feels bad that he married her for her money, especially since he is wealthy in his own right.

    https://mobile.twitter.com/alexisohanian/status/1137443418739752960

    Replies: @Barnard, @Anonymous

  2. Three weeks ago this would have been exciting, upbeat news.

    Tlump out of office now! Ret a hundled vaccines broom!

    On the other hand, they are trickier to keep cold enough, so this one might have some use in regions without good electricity.

    Like much of the USA in a few years.

  3. Less effective but can be stored at refrigerator temperature and 1.5 doses mean more can be treated.

  4. @Altai
    OT:
    World War Hair escalation.

    https://twitter.com/WokeCapital/status/1330645467810684929

    Replies: @Mike Pierson, Davenport Rector, Midfielder, @AndrewR

    John Cleese is hanging tough in WWT

    https://t.co/lMAn4U6cht

    https://t.co/oGPwEWJM9a

    https://www.rt.com/news/507517-john-cleese-transphonic-rowling/

    The joys of being old and rich. You don’t have to GAF.

  5. @Altai
    OT:
    World War Hair escalation.

    https://twitter.com/WokeCapital/status/1330645467810684929

    Replies: @Mike Pierson, Davenport Rector, Midfielder, @AndrewR

    When Serena threw her “sh3boon” temper tantrum, I felt bad for Naomi, who seemed like a sweet girl. Now I want to send both of them, together with Serena’s girl Meghan Markle, to the Islamic State (is that still a thing?)

    In related news, Serena’s hubby, reddit co-founder Alexis Ohanian, responded to me on Twitter once. Someone else had insulted him and Serena, so Alexis tweeted to him something like “why don’t you say that to my face?”

    I pointed out the absurdity of a man in a “power couple” like his to get so angry at low status trolls on the internet like Scott Greer. He responded right before my account got permanently suspended.

    I think on some level he’s well aware she is unattractive and manly, and he feels bad that he married her for her money, especially since he is wealthy in his own right.

    https://mobile.twitter.com/alexisohanian/status/1137443418739752960

    • Replies: @Barnard
    @AndrewR

    Even more bizarre to me was that Bulgarian tennis player Grigor Dimitrov had briefly dated Serena. Did Ohanian marry Serena for money? Unless he squandered most of his he should be worth more than her. He sounds like a woke true believer who somehow thinks he has a personal responsibility for the repression of American blacks. He gave up his seat on the Reddit board so a "person of color" could be represented on it. Is it some sort of, "blacks are oppressed just like we Armenians are oppressed" mentality?

    , @Anonymous
    @AndrewR


    I pointed out the absurdity of a man in a “power couple” like his to get so angry at low status trolls on the internet like Scott Greer.

     

    Plus he has a girl’s name. That’s gotta sting.

    Replies: @Reg Cæsar

  6. Anonymous[137] • Disclaimer says:

    I suspect the Oxford scientists are just being more honest, corporate Yanks lie through their teeth so I wouldn’t trust their stats particularly. Same with Russians, Putin almost immediately announced the Sputnik V vaccine had a 90% efficacy rate after Pfizer had announced theirs did.

    The British academic establishment is too honest, and lacks the “Chutzpah” of the Yanks and Russians I think.

    • Replies: @Anon
    @Anonymous

    You can bet that any information released by a publicly traded American pharmaceutical company has been legally vetted and is precisely accurate. On the other hand, and I don't know about the U.K., but any information about funded research released via the public relations office at an American university will be inaccurate and exaggerated. Look at the incentives and disincentives.

    The thing with corporate news releases, however, is that you have to read the original release very closely. THAT is what is accurate, not news reports about what it says. This is analogous to the law that anything printed by the National Enquirer is true, when closely read, but the innuendos may not be.

    Replies: @Bill

    , @Herald
    @Anonymous


    The British academic establishment is too honest, and lacks the “Chutzpah” of the Yanks and Russians I think.


     

    The above bears little relation to fact. The British Pharmaceutical company GSK, gets top marks, when it comes to paying fines and penalties for business malpractice.

    https://www.painnewsnetwork.org/stories/2020/11/17/glaxosmithkline-most-heavily-fined-drug-company

  7. The drug appears highly effective in preventing severe cases.

    No hospitalisations or severe cases of COVID-19 in participants treated with AZD1222

    • Replies: @Hypnotoad666
    @anon


    The drug appears highly effective in preventing severe cases.
     
    You would have to compare the outcome to the placebo side. And there's the rub. Covid itself is so innocuous that hardly anyone gets seriously sick in the placebo group.

    In fact, since they can't use the fakey death and hospitalization rates that the media does, these controlled studies would be the perfect vehicle for testing the hypothesis that covid is simply not dangerous.

    Put another way, if the "end point" of efficacy was prevention of death, they would have to say the vaccines had no statistical efficacy. The virus itself is pretty efficacious in not killing people.

    Replies: @anon

  8. On the other hand, they are trickier to keep cold enough, so this one might have some use in regions without good electricity.

    You have learned nothing.

  9. The headline in the Washington Post reads “AstraZeneca vaccine up to 90% effective and easily transportable, says company.”

    It seems to me, at those sample size magnitudes, that that sample size difference isn’t going to make very much difference in the reliability of the conclusions one can draw, about efficacy though I really haven’t worked through the math.

    n is greater than 2000 in both types of dosing regimens— a number that is a multiple of the sample sizes for the mRNA vaccine tests.

    I wonder what the medical, immunological reason is for testing out a two-stage ramped up dosage regimen against a two-stage, equally split dose.

    • Replies: @candid_observer
    @PiltdownMan

    The relevant sample sizes are the number of cases in which the subject caught Covid, which is 132, combined between the two dosage regimens. The 1.5 dose case, at 90%, would comprise, say, 1/4 of these, or in the neighborhood of 30. This is roughly the same number as in the originally proposed initial testing point for the Pfizer vaccine. This would have a fairly wide confidence interval, but I don't see how the difference between the efficacy of the two dosage regimes, which is 28%, would be accountable to chance.

    Replies: @Jack D

    , @Occasional lurker
    @PiltdownMan

    Cant't tell you with certainty, but in the clinical 1 and ii trials of some of the other vaccines, they tried several different dosing regimes (and time lags), trying to balance immunogenicity with side effects. You attempt to use the lowest dose possible. Maybe they were dissatisfied with the immune response after the smaller dose and decided to see what happens if the same people get a double dose the second tine around, and were satisfied with the results.
    Using a single shot without second dose was already discarded in the preclinical studies.

  10. That 1.5 doses is better than 2 doses is very fishy. Inconsistent batches of vaccine? Problems with methodology? Then 1.5 dose group was smaller – perhaps just by luck not a lot of folks in that group caught the ‘rona.

    • Replies: @candid_observer
    @Jack D

    Since it's a randomized trial, it's not important whether by chance the overall number of people in the 1.5 group who caught the virus is larger or smaller. The relevant finding is that of those who did, 90% came from the control group. But, as I said in another comment, the number who got covid in the 1.5 dose group must have been roughly 30. That's going to have a fairly wide confidence interval, but not, I'm pretty sure, enough to render the difference between the two groups as accountable to chance.

    Figuring out the confidence interval in these cases is a little messy -- it presumably involves sampling from a stratified population, one component of which is the placebo, the other the experimental. I'm sure that there's R code lying around to do that, but I'll leave that to others.

    As fishy as the result is, it's very likely real and important. It will make for some interesting science to figure out what's going on. Counterintuitive results are good that way.

    Replies: @Dr. DoomNGloom

  11. @PiltdownMan
    The headline in the Washington Post reads "AstraZeneca vaccine up to 90% effective and easily transportable, says company."

    It seems to me, at those sample size magnitudes, that that sample size difference isn't going to make very much difference in the reliability of the conclusions one can draw, about efficacy though I really haven't worked through the math.

    n is greater than 2000 in both types of dosing regimens— a number that is a multiple of the sample sizes for the mRNA vaccine tests.

    I wonder what the medical, immunological reason is for testing out a two-stage ramped up dosage regimen against a two-stage, equally split dose.

    Replies: @candid_observer, @Occasional lurker

    The relevant sample sizes are the number of cases in which the subject caught Covid, which is 132, combined between the two dosage regimens. The 1.5 dose case, at 90%, would comprise, say, 1/4 of these, or in the neighborhood of 30. This is roughly the same number as in the originally proposed initial testing point for the Pfizer vaccine. This would have a fairly wide confidence interval, but I don’t see how the difference between the efficacy of the two dosage regimes, which is 28%, would be accountable to chance.

    • Thanks: PiltdownMan, Hangnail Hans
    • Replies: @Jack D
    @candid_observer


    I don’t see how the difference between the efficacy of the two dosage regimes, which is 28%, would be accountable to chance.
     
    Statistically no, but the result makes no sense. It would not surprise me if it failed to replicate. Some of the study was done in Brazil, maybe with Brazilian quality data collection/ handling of the vaccine. Sometimes drugs behave in a counterintuitive way, where more is not better but not usually vaccines - you usually want the highest dose that will not cause side effects.

    These results are not confidence inspiring. This vaccine will be great for 3rd world countries because it requires only refrigeration, not even freezing and is cheaper. Right now, if I had the choice, I would take the Moderna vaccine as #1, Pfizer as #2 and Oxford as a distant 3rd.

    Replies: @candid_observer

  12. For those worried that them newfangled mRNA vaccines might impede your acceptance into heaven on the grounds that you are no longer fully human, the Oxford vaccine is based on a different technology.

    I am not qualified to pronounce on whether such a vaccine would endanger your immortal soul, but the way that it works is that it is made from a virus that is a weakened version of a common cold virus (adenovirus) that causes infections in chimpanzees, but which has been genetically modified so that it is impossible for it to grow in humans. The virus is live but sterile – it will only live for one generation. Genetic material has been added to this virus that causes it to make the Covid spike protein. Your body detects the spike protein and makes antibodies for it so the next time it sees the spike protein (attached to a real live ‘rona virus) it is ready to attack it.

    So arguably, taking this vaccine does not turn you into Frankenstein because it is no different than catching a cold. There is genetic alteration going on, but the alteration is made in the cold virus, not you. Maybe the cold virus is no longer eligible for cold virus heaven?

    • Thanks: AnotherDad
    • Replies: @That Would Be Telling
    @Jack D


    For those worried that them newfangled mRNA vaccines might impede your acceptance into heaven on the grounds that you are no longer fully human, the Oxford vaccine is based on a different technology.
     
    Except they work on the same exact principle, hijacking some of your cells to produce the SARS-CoV-2 spike protein that the adaptive, antibody producing part of immune system recognizes as alien and thus replies with a thorough response. The mRNA ones are much more precise, since they contain only the mRNA for the spike protein (in at least one case, slightly modified to make it better targeted by the immune system). The adenovirus virus vector vaccines are a complete virus, with one part replaced by DNA coding for the spike protein, and their ability to reproduce gimped. I assume they also force the cells they hijack to produce other adenovirus proteins.

    This is supposed to be standard vaccine technology nowadays, whereas the mRNA vaccines are brand new, never before tried at this scale on humans. But in theory, the precision of the mRNA vaccines will make them the safest ones ever (but maybe not immediately, since no one is taking the time to precisely fine tune the dosing, this being a genuine emergency). The only really new thing they bring to the table is the lipid blob that protects the mRNA from getting zapped before it gets inserted into cells. That's akin, but not exactly like the lipid envelope stolen from real virus hijacked cells of "enveloped" viruses like the coronaviruses and the flu.

    My guess, which so far is backed up by the trials, is that's a no or very low risk thing due to the very small quantities of these somewhat novel lipids. And your body of course has a zillion mechanisms for dealing with lipids (fats), our cell's walls are for example made of a lipid bilayer, which is why these vaccines use lipids in the first place.

    Replies: @Anonymous, @Jack D

    , @kpkinusnnyphiladelphia
    @Jack D

    Outstanding explanation. That's exactly how the AZ vaccine is created and works.

    FYI, Moderna's vaccine just needs to be refrigerated.

    https://www.supplychaindive.com/news/moderna-vaccine-coronavirus-distribution-supply-chain-cold-refrigerated/589086/

    , @Anonymous
    @Jack D


    it is no different than catching a cold
     
    Except it's the chimp cold and you catch it in your muscles :-)

    Sputnik V and upcoming J&J vaccine (which is simply a first stage Sputnik V, based on the human Ad26 serotype) are looking slightly more promising.

    Replies: @That Would Be Telling

    , @Macumazahn
    @Jack D

    "There is genetic alteration going on, but the alteration is made in the cold virus, not you."
    Quite. And it's disingenuous to suggest that any concern about this difference must perforce be irrational.

  13. @Jack D
    That 1.5 doses is better than 2 doses is very fishy. Inconsistent batches of vaccine? Problems with methodology? Then 1.5 dose group was smaller - perhaps just by luck not a lot of folks in that group caught the 'rona.

    Replies: @candid_observer

    Since it’s a randomized trial, it’s not important whether by chance the overall number of people in the 1.5 group who caught the virus is larger or smaller. The relevant finding is that of those who did, 90% came from the control group. But, as I said in another comment, the number who got covid in the 1.5 dose group must have been roughly 30. That’s going to have a fairly wide confidence interval, but not, I’m pretty sure, enough to render the difference between the two groups as accountable to chance.

    Figuring out the confidence interval in these cases is a little messy — it presumably involves sampling from a stratified population, one component of which is the placebo, the other the experimental. I’m sure that there’s R code lying around to do that, but I’ll leave that to others.

    As fishy as the result is, it’s very likely real and important. It will make for some interesting science to figure out what’s going on. Counterintuitive results are good that way.

    • Thanks: Hangnail Hans
    • Replies: @Dr. DoomNGloom
    @candid_observer

    I think they are using Bayesian, so they would compute a "credible interval" rather than a "confidence interval".
    The question then becomes "what efficacy maximizes the probability of the observed data?" the credible interval will most likely be the efficacy ranges that include 90% of the possible outcomes based on some prior.

    I could also estimate this non-parametrically using combinatorial analysis, but getting that right in a spreadsheet binomial distribution is not for the faint of heart and I can't do that in my head anymore.

  14. @candid_observer
    @PiltdownMan

    The relevant sample sizes are the number of cases in which the subject caught Covid, which is 132, combined between the two dosage regimens. The 1.5 dose case, at 90%, would comprise, say, 1/4 of these, or in the neighborhood of 30. This is roughly the same number as in the originally proposed initial testing point for the Pfizer vaccine. This would have a fairly wide confidence interval, but I don't see how the difference between the efficacy of the two dosage regimes, which is 28%, would be accountable to chance.

    Replies: @Jack D

    I don’t see how the difference between the efficacy of the two dosage regimes, which is 28%, would be accountable to chance.

    Statistically no, but the result makes no sense. It would not surprise me if it failed to replicate. Some of the study was done in Brazil, maybe with Brazilian quality data collection/ handling of the vaccine. Sometimes drugs behave in a counterintuitive way, where more is not better but not usually vaccines – you usually want the highest dose that will not cause side effects.

    These results are not confidence inspiring. This vaccine will be great for 3rd world countries because it requires only refrigeration, not even freezing and is cheaper. Right now, if I had the choice, I would take the Moderna vaccine as #1, Pfizer as #2 and Oxford as a distant 3rd.

    • Agree: AnotherDad
    • Replies: @candid_observer
    @Jack D

    Well, I guess it could be something other than actual differences in efficacy, but I'm having a little difficulty seeing what these alternatives could be, assuming that it really was a randomized, double blinded trial. Why would some form of incompetence result in a much better result?

    Again, I'm just not seeing how that would work.

    Replies: @candid_observer

  15. @Jack D
    @candid_observer


    I don’t see how the difference between the efficacy of the two dosage regimes, which is 28%, would be accountable to chance.
     
    Statistically no, but the result makes no sense. It would not surprise me if it failed to replicate. Some of the study was done in Brazil, maybe with Brazilian quality data collection/ handling of the vaccine. Sometimes drugs behave in a counterintuitive way, where more is not better but not usually vaccines - you usually want the highest dose that will not cause side effects.

    These results are not confidence inspiring. This vaccine will be great for 3rd world countries because it requires only refrigeration, not even freezing and is cheaper. Right now, if I had the choice, I would take the Moderna vaccine as #1, Pfizer as #2 and Oxford as a distant 3rd.

    Replies: @candid_observer

    Well, I guess it could be something other than actual differences in efficacy, but I’m having a little difficulty seeing what these alternatives could be, assuming that it really was a randomized, double blinded trial. Why would some form of incompetence result in a much better result?

    Again, I’m just not seeing how that would work.

    • Replies: @candid_observer
    @candid_observer

    An important question is whether the use of the 1.5 vs 2.0 protocols were likewise randomized and blinded. That is, was the exact same group of people given, at random, and blinded, either the 1.5 dose or the 2.0 dose regime. This would eliminate a lot of concerns about how the two protocols were handled, and any potential differences between the groups targeted. If the two protocols were given to two different groups, then of course differences between these groups might account for the differences in efficacy.

    One final caveat, though. All of this presumes that the company is giving accurate results, and that no one in this process has fudged things so that the stock price doesn't crash. I hate to think that that might have happened, but people do do a lot of awful things under great pressure.

    Replies: @kpkinusnnyphiladelphia

  16. @Jack D
    For those worried that them newfangled mRNA vaccines might impede your acceptance into heaven on the grounds that you are no longer fully human, the Oxford vaccine is based on a different technology.

    I am not qualified to pronounce on whether such a vaccine would endanger your immortal soul, but the way that it works is that it is made from a virus that is a weakened version of a common cold virus (adenovirus) that causes infections in chimpanzees, but which has been genetically modified so that it is impossible for it to grow in humans. The virus is live but sterile - it will only live for one generation. Genetic material has been added to this virus that causes it to make the Covid spike protein. Your body detects the spike protein and makes antibodies for it so the next time it sees the spike protein (attached to a real live 'rona virus) it is ready to attack it.

    So arguably, taking this vaccine does not turn you into Frankenstein because it is no different than catching a cold. There is genetic alteration going on, but the alteration is made in the cold virus, not you. Maybe the cold virus is no longer eligible for cold virus heaven?

    Replies: @That Would Be Telling, @kpkinusnnyphiladelphia, @Anonymous, @Macumazahn

    For those worried that them newfangled mRNA vaccines might impede your acceptance into heaven on the grounds that you are no longer fully human, the Oxford vaccine is based on a different technology.

    Except they work on the same exact principle, hijacking some of your cells to produce the SARS-CoV-2 spike protein that the adaptive, antibody producing part of immune system recognizes as alien and thus replies with a thorough response. The mRNA ones are much more precise, since they contain only the mRNA for the spike protein (in at least one case, slightly modified to make it better targeted by the immune system). The adenovirus virus vector vaccines are a complete virus, with one part replaced by DNA coding for the spike protein, and their ability to reproduce gimped. I assume they also force the cells they hijack to produce other adenovirus proteins.

    This is supposed to be standard vaccine technology nowadays, whereas the mRNA vaccines are brand new, never before tried at this scale on humans. But in theory, the precision of the mRNA vaccines will make them the safest ones ever (but maybe not immediately, since no one is taking the time to precisely fine tune the dosing, this being a genuine emergency). The only really new thing they bring to the table is the lipid blob that protects the mRNA from getting zapped before it gets inserted into cells. That’s akin, but not exactly like the lipid envelope stolen from real virus hijacked cells of “enveloped” viruses like the coronaviruses and the flu.

    My guess, which so far is backed up by the trials, is that’s a no or very low risk thing due to the very small quantities of these somewhat novel lipids. And your body of course has a zillion mechanisms for dealing with lipids (fats), our cell’s walls are for example made of a lipid bilayer, which is why these vaccines use lipids in the first place.

    • Replies: @Anonymous
    @That Would Be Telling


    I assume they also force the cells they hijack to produce other adenovirus proteins.
     
    No. The vector is replication-deficient. The only role for all of the viral parts is to deliver DNA into cells and produce mRNA encoding spike protein.

    Replies: @That Would Be Telling

    , @Jack D
    @That Would Be Telling

    I agree with everything you said. But (arguably) hijacking your cells by means of an (attenuated) viral infection is more "natural" than injecting you with mRNA. AFAIK, catching a cold does not prevent your soul from entering heaven. As I said before, people were voicing various (admittedly insane) objections to mRNA vaccines but they might not have the same objections to the Oxford vaccine.

    Then again, given that these objections were not really rational to begin with, they will surely invent other objections to the Oxford vaccine too. My experience with folks like this is that if you bat away their current excuses they just come up with other ones and that you are never going to satisfy them or produce a vaccine that they are actually willing to take.

  17. Three weeks ago this would have been exciting, upbeat news.

    And it is now, IMO. The more, the merrier. Three companies will produce more vaccine than two. This isn’t all just abstraction, or lab work; it’s about manufacturing, too. We also have no idea whatsoever about the duration of efficacy for any of these vaccines.

    Etc.

    • Thanks: AnotherDad
    • Replies: @AnotherDad
    @Svigor


    This isn’t all just abstraction, or lab work; it’s about manufacturing, too.
     
    Well said Svigor.

    Smart "idea people" like many commenters on this blog--myself included--have a tendency to mistake a "solution"--an idea, a model, more so a successful demo--as a solution. Problem solved.

    But real solutions in the real world have to actually roll out through all these logistical barriers of production and distribution.

    As you said ... the more the merrier. Another vaccine that seems to work, great! Let's get their production lines humming as well.

    We've got critical issues of racism and hair style discrimination to deal with, it's time to put this crappy Xi virus in the rearview!

    Replies: @Hypnotoad666

    , @vhrm
    @Svigor


    This isn’t all just abstraction, or lab work; it’s about manufacturing, too.
     
    It's also shamanism. We'll do the vaccine dance and the miasma will be lifted from the land. At this point, the sooner the better.

    I'm not disputing the existence of the virus or the efficacy of the vaccine, I'm just intensely annoyed by the autoimmune disease that SarsCov-2 has triggered in our society. We already have chronic fatigue syndrome, some muscle wasting, and are bed ridden two days a week.
    Naturally acquired herd immunity is actually doing the heavy lifting in actually dealing with Covid, (helped by better treatment protocols), but if the vaccines are the antihistamine that prevent Biden, newsom and Cuomo from driving is into anaphylactic shock, then I'm all for them.

    /soapbox

    Replies: @Jack D

  18. @candid_observer
    @Jack D

    Well, I guess it could be something other than actual differences in efficacy, but I'm having a little difficulty seeing what these alternatives could be, assuming that it really was a randomized, double blinded trial. Why would some form of incompetence result in a much better result?

    Again, I'm just not seeing how that would work.

    Replies: @candid_observer

    An important question is whether the use of the 1.5 vs 2.0 protocols were likewise randomized and blinded. That is, was the exact same group of people given, at random, and blinded, either the 1.5 dose or the 2.0 dose regime. This would eliminate a lot of concerns about how the two protocols were handled, and any potential differences between the groups targeted. If the two protocols were given to two different groups, then of course differences between these groups might account for the differences in efficacy.

    One final caveat, though. All of this presumes that the company is giving accurate results, and that no one in this process has fudged things so that the stock price doesn’t crash. I hate to think that that might have happened, but people do do a lot of awful things under great pressure.

    • Replies: @kpkinusnnyphiladelphia
    @candid_observer


    One final caveat, though. All of this presumes that the company is giving accurate results, and that no one in this process has fudged things so that the stock price doesn’t crash. I hate to think that that might have happened, but people do do a lot of awful things under great pressure.
     
    I think the probability of fraudulent data maneuvering is very very low.

    Mistakes? Sure, though the data review process in pharma companies goes through so many layers and approval cycles, that silly mistakes are extremely rare.

    AstraZeneca is a huge company, and has lots more going on than this vaccine. Besides, it's already cashed the check for this, so there's low risk to the stock.

    I have said this elsewhere, but it is worth repeating. Operation Warp Speed will be one of Trump's greatest legacies. Vaccines against non-blood borne viruses in many ways are the simplest of pharma products -- get a non-infection piece of the virus into you somehow and then let the immune system kick in. Compare the vaccine "mechanism of action" to, say, that of antibody drug conjugates or CAR-T therapy, and it is orders of magnitude simpler.

    There is no reason for vaccine creation to take two years or more. Remember the little Napoleonic squirt Fauci pontificating about how it's going to take 18 to 24 months or more? That's because (a) he's a fucking worrywart and (b) his entire vaccine creation experience made him incapable of seeing what could be done by compressing the research AND production timeline.

    This "expert" basically reads papers and hangs out in the lab for a living. He's the most annoying little goombah shit on the planet, and that's in a world that includes Andrew Cuomo. He needs to be taken out into the NIH parking lot and bullied as if he were still in middle school.

    Replies: @candid_observer

  19. @PiltdownMan
    The headline in the Washington Post reads "AstraZeneca vaccine up to 90% effective and easily transportable, says company."

    It seems to me, at those sample size magnitudes, that that sample size difference isn't going to make very much difference in the reliability of the conclusions one can draw, about efficacy though I really haven't worked through the math.

    n is greater than 2000 in both types of dosing regimens— a number that is a multiple of the sample sizes for the mRNA vaccine tests.

    I wonder what the medical, immunological reason is for testing out a two-stage ramped up dosage regimen against a two-stage, equally split dose.

    Replies: @candid_observer, @Occasional lurker

    Cant’t tell you with certainty, but in the clinical 1 and ii trials of some of the other vaccines, they tried several different dosing regimes (and time lags), trying to balance immunogenicity with side effects. You attempt to use the lowest dose possible. Maybe they were dissatisfied with the immune response after the smaller dose and decided to see what happens if the same people get a double dose the second tine around, and were satisfied with the results.
    Using a single shot without second dose was already discarded in the preclinical studies.

    • Thanks: PiltdownMan
  20. @Jack D
    For those worried that them newfangled mRNA vaccines might impede your acceptance into heaven on the grounds that you are no longer fully human, the Oxford vaccine is based on a different technology.

    I am not qualified to pronounce on whether such a vaccine would endanger your immortal soul, but the way that it works is that it is made from a virus that is a weakened version of a common cold virus (adenovirus) that causes infections in chimpanzees, but which has been genetically modified so that it is impossible for it to grow in humans. The virus is live but sterile - it will only live for one generation. Genetic material has been added to this virus that causes it to make the Covid spike protein. Your body detects the spike protein and makes antibodies for it so the next time it sees the spike protein (attached to a real live 'rona virus) it is ready to attack it.

    So arguably, taking this vaccine does not turn you into Frankenstein because it is no different than catching a cold. There is genetic alteration going on, but the alteration is made in the cold virus, not you. Maybe the cold virus is no longer eligible for cold virus heaven?

    Replies: @That Would Be Telling, @kpkinusnnyphiladelphia, @Anonymous, @Macumazahn

    Outstanding explanation. That’s exactly how the AZ vaccine is created and works.

    FYI, Moderna’s vaccine just needs to be refrigerated.

    https://www.supplychaindive.com/news/moderna-vaccine-coronavirus-distribution-supply-chain-cold-refrigerated/589086/

  21. @That Would Be Telling
    @Jack D


    For those worried that them newfangled mRNA vaccines might impede your acceptance into heaven on the grounds that you are no longer fully human, the Oxford vaccine is based on a different technology.
     
    Except they work on the same exact principle, hijacking some of your cells to produce the SARS-CoV-2 spike protein that the adaptive, antibody producing part of immune system recognizes as alien and thus replies with a thorough response. The mRNA ones are much more precise, since they contain only the mRNA for the spike protein (in at least one case, slightly modified to make it better targeted by the immune system). The adenovirus virus vector vaccines are a complete virus, with one part replaced by DNA coding for the spike protein, and their ability to reproduce gimped. I assume they also force the cells they hijack to produce other adenovirus proteins.

    This is supposed to be standard vaccine technology nowadays, whereas the mRNA vaccines are brand new, never before tried at this scale on humans. But in theory, the precision of the mRNA vaccines will make them the safest ones ever (but maybe not immediately, since no one is taking the time to precisely fine tune the dosing, this being a genuine emergency). The only really new thing they bring to the table is the lipid blob that protects the mRNA from getting zapped before it gets inserted into cells. That's akin, but not exactly like the lipid envelope stolen from real virus hijacked cells of "enveloped" viruses like the coronaviruses and the flu.

    My guess, which so far is backed up by the trials, is that's a no or very low risk thing due to the very small quantities of these somewhat novel lipids. And your body of course has a zillion mechanisms for dealing with lipids (fats), our cell's walls are for example made of a lipid bilayer, which is why these vaccines use lipids in the first place.

    Replies: @Anonymous, @Jack D

    I assume they also force the cells they hijack to produce other adenovirus proteins.

    No. The vector is replication-deficient. The only role for all of the viral parts is to deliver DNA into cells and produce mRNA encoding spike protein.

    • Replies: @That Would Be Telling
    @Anonymous



    I assume they also force the cells they hijack to produce other adenovirus proteins.
     
    No. The vector is replication-deficient. The only role for all of the viral parts is to deliver DNA into cells and produce mRNA encoding spike protein.
     
    That's their only role from the viewpoint of us humans wanting protection from COVID-19, but tell me how the virus is gimped so that the cells it hijacks only make the spike protein? It might even be producing the whole set of viral proteins, with some of them needed for replication being gimped. Plus of course whatever protein or proteins it had that were replaced in part or whole by the coronavirus spike protein.

    This requires some research from one of us, but IMHO not until there's better results from a adenovirus vector vaccine , either from more data from this one, or one of the others. Ad5-nCoV from the PRC and Russia, assuming they can be trusted, Gam-COVID-Vac AKA Sputnik V, which might be OK but was prematurely championed and thus the following Phase 3 trial is likely going to be too political, or Janssen (Johnson & Johnson)/BIDMC, which is testing their's on up to 60,000 participants. Of the viral vector type that's all I could find on Wikipedia, plus I had to do some digging or work from memory for Sputnik V to confirm they all use an adenovirus vector, someone has been deleting information from the table.
  22. @Jack D
    For those worried that them newfangled mRNA vaccines might impede your acceptance into heaven on the grounds that you are no longer fully human, the Oxford vaccine is based on a different technology.

    I am not qualified to pronounce on whether such a vaccine would endanger your immortal soul, but the way that it works is that it is made from a virus that is a weakened version of a common cold virus (adenovirus) that causes infections in chimpanzees, but which has been genetically modified so that it is impossible for it to grow in humans. The virus is live but sterile - it will only live for one generation. Genetic material has been added to this virus that causes it to make the Covid spike protein. Your body detects the spike protein and makes antibodies for it so the next time it sees the spike protein (attached to a real live 'rona virus) it is ready to attack it.

    So arguably, taking this vaccine does not turn you into Frankenstein because it is no different than catching a cold. There is genetic alteration going on, but the alteration is made in the cold virus, not you. Maybe the cold virus is no longer eligible for cold virus heaven?

    Replies: @That Would Be Telling, @kpkinusnnyphiladelphia, @Anonymous, @Macumazahn

    it is no different than catching a cold

    Except it’s the chimp cold and you catch it in your muscles 🙂

    Sputnik V and upcoming J&J vaccine (which is simply a first stage Sputnik V, based on the human Ad26 serotype) are looking slightly more promising.

    • Replies: @That Would Be Telling
    @Anonymous


    Except it’s the chimp cold and you catch it in your muscles
     
    Heh, but the use of (gimped) non-human adenovirus vectors is because too many of us already have immunity to too many of the human ones, so you have to get around that one way or another. With it being gimped to not be able to replicate, it's probably no more dangerous than a human one that's been tweaked in the lab to evade the immune system, except for the spike protein.

    Or maybe using this one was a mistake; we're told this is a now common vaccine technology, so I would hope there is data from other vaccines available. Just looked at Ebola vaccines, the two approved ones use different vectors, one a human adenovirus, GSK has a chimp adenovirus vector in Phase 3 since 2016, you have to get an Ebola outbreak in the populations you administered a vaccine to to really test these :-(....

    One other related issue is that once you have "enough" vaccines for a lethal pathogen, finishing the sequence of trials for new ones is not ethical using a placebo. Instead, the control arm has to be one of the best alternatives, and you see if your's is as good or better. Which will be a tough row to hoe if the mRNA ones continue to show such high efficacy rates, tempered by their inherently higher costs for now (new technology not up on the learning curve of manufacturing) and perhaps more intense storage requirements.

    Replies: @Jack D

  23. @candid_observer
    @candid_observer

    An important question is whether the use of the 1.5 vs 2.0 protocols were likewise randomized and blinded. That is, was the exact same group of people given, at random, and blinded, either the 1.5 dose or the 2.0 dose regime. This would eliminate a lot of concerns about how the two protocols were handled, and any potential differences between the groups targeted. If the two protocols were given to two different groups, then of course differences between these groups might account for the differences in efficacy.

    One final caveat, though. All of this presumes that the company is giving accurate results, and that no one in this process has fudged things so that the stock price doesn't crash. I hate to think that that might have happened, but people do do a lot of awful things under great pressure.

    Replies: @kpkinusnnyphiladelphia

    One final caveat, though. All of this presumes that the company is giving accurate results, and that no one in this process has fudged things so that the stock price doesn’t crash. I hate to think that that might have happened, but people do do a lot of awful things under great pressure.

    I think the probability of fraudulent data maneuvering is very very low.

    Mistakes? Sure, though the data review process in pharma companies goes through so many layers and approval cycles, that silly mistakes are extremely rare.

    AstraZeneca is a huge company, and has lots more going on than this vaccine. Besides, it’s already cashed the check for this, so there’s low risk to the stock.

    I have said this elsewhere, but it is worth repeating. Operation Warp Speed will be one of Trump’s greatest legacies. Vaccines against non-blood borne viruses in many ways are the simplest of pharma products — get a non-infection piece of the virus into you somehow and then let the immune system kick in. Compare the vaccine “mechanism of action” to, say, that of antibody drug conjugates or CAR-T therapy, and it is orders of magnitude simpler.

    There is no reason for vaccine creation to take two years or more. Remember the little Napoleonic squirt Fauci pontificating about how it’s going to take 18 to 24 months or more? That’s because (a) he’s a fucking worrywart and (b) his entire vaccine creation experience made him incapable of seeing what could be done by compressing the research AND production timeline.

    This “expert” basically reads papers and hangs out in the lab for a living. He’s the most annoying little goombah shit on the planet, and that’s in a world that includes Andrew Cuomo. He needs to be taken out into the NIH parking lot and bullied as if he were still in middle school.

    • Replies: @candid_observer
    @kpkinusnnyphiladelphia

    My supposition is that if there were a possibility of fraudulent data, it wouldn't be as a result of any company wide conspiracy, but an individual or two at a critical stage in producing the data who, say, didn't want to lose their job or see their stock tank.

    I guess I do really doubt that this would take place, because it would be quickly caught, and would be self destructive. But, you know, think of Theranos.

    In any case, we need to keep our eyes out for further results from the vaccine. As the number of cases of covid grow in the recipients, we should get a much better idea as to the precise efficacy rates of the two dosage regimes.

    Also, I do wonder it there might not be a mechanism that would explain the lower efficacy rate for the 2.0 dose approach. Perhaps the first dose of 1.0 doesn't do enough to fully combat the disease as it is ordinarily contracted, but is enough to enable the body to destroy immediately the spike proteins introduced by the second dose, before they can induce changes in the antibody (or T-cell?) levels? A lower first dose, though, might allow the second dose to add onto the first. mRNA approaches, though, wouldn't seem to have that problem, because they introduce the spike protein indirectly, and cells have no reason or method to destroy the mRNA.

    Probably this speculation makes no sense for reasons obvious to those who understand such things. But I am not such a person.

    Replies: @kpkinusnnyphiladelphia, @Bill

  24. @candid_observer
    @Jack D

    Since it's a randomized trial, it's not important whether by chance the overall number of people in the 1.5 group who caught the virus is larger or smaller. The relevant finding is that of those who did, 90% came from the control group. But, as I said in another comment, the number who got covid in the 1.5 dose group must have been roughly 30. That's going to have a fairly wide confidence interval, but not, I'm pretty sure, enough to render the difference between the two groups as accountable to chance.

    Figuring out the confidence interval in these cases is a little messy -- it presumably involves sampling from a stratified population, one component of which is the placebo, the other the experimental. I'm sure that there's R code lying around to do that, but I'll leave that to others.

    As fishy as the result is, it's very likely real and important. It will make for some interesting science to figure out what's going on. Counterintuitive results are good that way.

    Replies: @Dr. DoomNGloom

    I think they are using Bayesian, so they would compute a “credible interval” rather than a “confidence interval”.
    The question then becomes “what efficacy maximizes the probability of the observed data?” the credible interval will most likely be the efficacy ranges that include 90% of the possible outcomes based on some prior.

    I could also estimate this non-parametrically using combinatorial analysis, but getting that right in a spreadsheet binomial distribution is not for the faint of heart and I can’t do that in my head anymore.

  25. If you live in a nation with an authoritarian government that can make everyone take it, you would have a 70% less chance of exposure, combined with a 70% less chance of becoming infected if you were exposed, for a total efficacy of 91%

  26. @anon
    The drug appears highly effective in preventing severe cases.

    No hospitalisations or severe cases of COVID-19 in participants treated with AZD1222
     

    Replies: @Hypnotoad666

    The drug appears highly effective in preventing severe cases.

    You would have to compare the outcome to the placebo side. And there’s the rub. Covid itself is so innocuous that hardly anyone gets seriously sick in the placebo group.

    In fact, since they can’t use the fakey death and hospitalization rates that the media does, these controlled studies would be the perfect vehicle for testing the hypothesis that covid is simply not dangerous.

    Put another way, if the “end point” of efficacy was prevention of death, they would have to say the vaccines had no statistical efficacy. The virus itself is pretty efficacious in not killing people.

    • Replies: @anon
    @Hypnotoad666


    these controlled studies would be the perfect vehicle for testing the hypothesis that covid is simply not dangerous.
     

    Put another way, if the “end point” of efficacy was prevention of death, they would have to say the vaccines had no statistical efficacy. The virus itself is pretty efficacious in not killing people.

     

    I've given this a fair amount of thought. First, I look at the graphs in the WSJ, paying attention to the ratio of reported deaths to reported cases. Which is 1-2%.

    If a symptomatic reported case in the placebo group has a 1% chance of dying of covid, it is plausible in the control group that out of 90 reported cases, there will 0 deaths. Especially since they go to considerable effort to reject candidates with co-morbidities.

    And, it is logical that all covid deaths will (1) display symptoms (2) have a positive test (3) have a serious case and then (4) die. And since there were maybe 10% serious cases in the control group, if they kept running the trials, they would eventually start generating some deaths.

    So, in my opinion, the announced test results aren't substantially at odds with the announced/believed rates of death and serious cases.

    However, it is also striking that the virus, as you noticed, isn't very efficacious at killing people. Especially people who don't have serious co-morbidities or aren't close to dying of old age.

    But this virus is quite efficacious at triggering the leadership of moderately developed countries with modern medical systems to panic. Starting with Red China and much of the rest of the world including Russia.

    Replies: @Jack D, @epebble, @Jonathan Silber

  27. Are there potential dangers in taking more than one vaccine at the same time for the same disease?

    • Replies: @Jack D
    @Henry's Cat

    Probably not a good idea to take them all at once but for example with flu there are a number of different flu vaccines on the market and it is common for people to take different ones each year - maybe 1 year you get the nasal vaccine and another year the injectable and in the 3rd year you get the high dose version because you are over 65, etc.

    No one really knows yet how long the protection from the vaccine will last. Also at this point with the shortage of vaccines it would be unethical to take more than 1 while other people have not yet had any. If it becomes common to get the vaccine annually or at some other interval, it might not be a bad idea to hedge your bets by rotating which one you get (as long as they are all highly effective).

    As of now, all the existing and planned vaccines have focused on getting your body to produce (one way or another) antibodies to the spike protein so as long as you are producing a sufficient level of antibodies it really shouldn't matter which one you take. It's not impossible that someday there will be a vaccine that targets some other feature of the coronavirus and there would probably be benefits to getting that vaccine in addition to a spike protein vaccine but as of now all the planned vaccines are aiming for the same target and I see little benefit (and possibly risk) in getting more than 1 at the same time.

  28. @That Would Be Telling
    @Jack D


    For those worried that them newfangled mRNA vaccines might impede your acceptance into heaven on the grounds that you are no longer fully human, the Oxford vaccine is based on a different technology.
     
    Except they work on the same exact principle, hijacking some of your cells to produce the SARS-CoV-2 spike protein that the adaptive, antibody producing part of immune system recognizes as alien and thus replies with a thorough response. The mRNA ones are much more precise, since they contain only the mRNA for the spike protein (in at least one case, slightly modified to make it better targeted by the immune system). The adenovirus virus vector vaccines are a complete virus, with one part replaced by DNA coding for the spike protein, and their ability to reproduce gimped. I assume they also force the cells they hijack to produce other adenovirus proteins.

    This is supposed to be standard vaccine technology nowadays, whereas the mRNA vaccines are brand new, never before tried at this scale on humans. But in theory, the precision of the mRNA vaccines will make them the safest ones ever (but maybe not immediately, since no one is taking the time to precisely fine tune the dosing, this being a genuine emergency). The only really new thing they bring to the table is the lipid blob that protects the mRNA from getting zapped before it gets inserted into cells. That's akin, but not exactly like the lipid envelope stolen from real virus hijacked cells of "enveloped" viruses like the coronaviruses and the flu.

    My guess, which so far is backed up by the trials, is that's a no or very low risk thing due to the very small quantities of these somewhat novel lipids. And your body of course has a zillion mechanisms for dealing with lipids (fats), our cell's walls are for example made of a lipid bilayer, which is why these vaccines use lipids in the first place.

    Replies: @Anonymous, @Jack D

    I agree with everything you said. But (arguably) hijacking your cells by means of an (attenuated) viral infection is more “natural” than injecting you with mRNA. AFAIK, catching a cold does not prevent your soul from entering heaven. As I said before, people were voicing various (admittedly insane) objections to mRNA vaccines but they might not have the same objections to the Oxford vaccine.

    Then again, given that these objections were not really rational to begin with, they will surely invent other objections to the Oxford vaccine too. My experience with folks like this is that if you bat away their current excuses they just come up with other ones and that you are never going to satisfy them or produce a vaccine that they are actually willing to take.

  29. I dug into the details on this vaccine, and unfortunately it requires that it be baked in an 800-degree pizza oven for ten minutes just prior to the injection. Very few doctor’s offices are equiped with these, not to mention Walgreens locations.

  30. @Henry's Cat
    Are there potential dangers in taking more than one vaccine at the same time for the same disease?

    Replies: @Jack D

    Probably not a good idea to take them all at once but for example with flu there are a number of different flu vaccines on the market and it is common for people to take different ones each year – maybe 1 year you get the nasal vaccine and another year the injectable and in the 3rd year you get the high dose version because you are over 65, etc.

    No one really knows yet how long the protection from the vaccine will last. Also at this point with the shortage of vaccines it would be unethical to take more than 1 while other people have not yet had any. If it becomes common to get the vaccine annually or at some other interval, it might not be a bad idea to hedge your bets by rotating which one you get (as long as they are all highly effective).

    As of now, all the existing and planned vaccines have focused on getting your body to produce (one way or another) antibodies to the spike protein so as long as you are producing a sufficient level of antibodies it really shouldn’t matter which one you take. It’s not impossible that someday there will be a vaccine that targets some other feature of the coronavirus and there would probably be benefits to getting that vaccine in addition to a spike protein vaccine but as of now all the planned vaccines are aiming for the same target and I see little benefit (and possibly risk) in getting more than 1 at the same time.

  31. @kpkinusnnyphiladelphia
    @candid_observer


    One final caveat, though. All of this presumes that the company is giving accurate results, and that no one in this process has fudged things so that the stock price doesn’t crash. I hate to think that that might have happened, but people do do a lot of awful things under great pressure.
     
    I think the probability of fraudulent data maneuvering is very very low.

    Mistakes? Sure, though the data review process in pharma companies goes through so many layers and approval cycles, that silly mistakes are extremely rare.

    AstraZeneca is a huge company, and has lots more going on than this vaccine. Besides, it's already cashed the check for this, so there's low risk to the stock.

    I have said this elsewhere, but it is worth repeating. Operation Warp Speed will be one of Trump's greatest legacies. Vaccines against non-blood borne viruses in many ways are the simplest of pharma products -- get a non-infection piece of the virus into you somehow and then let the immune system kick in. Compare the vaccine "mechanism of action" to, say, that of antibody drug conjugates or CAR-T therapy, and it is orders of magnitude simpler.

    There is no reason for vaccine creation to take two years or more. Remember the little Napoleonic squirt Fauci pontificating about how it's going to take 18 to 24 months or more? That's because (a) he's a fucking worrywart and (b) his entire vaccine creation experience made him incapable of seeing what could be done by compressing the research AND production timeline.

    This "expert" basically reads papers and hangs out in the lab for a living. He's the most annoying little goombah shit on the planet, and that's in a world that includes Andrew Cuomo. He needs to be taken out into the NIH parking lot and bullied as if he were still in middle school.

    Replies: @candid_observer

    My supposition is that if there were a possibility of fraudulent data, it wouldn’t be as a result of any company wide conspiracy, but an individual or two at a critical stage in producing the data who, say, didn’t want to lose their job or see their stock tank.

    I guess I do really doubt that this would take place, because it would be quickly caught, and would be self destructive. But, you know, think of Theranos.

    In any case, we need to keep our eyes out for further results from the vaccine. As the number of cases of covid grow in the recipients, we should get a much better idea as to the precise efficacy rates of the two dosage regimes.

    Also, I do wonder it there might not be a mechanism that would explain the lower efficacy rate for the 2.0 dose approach. Perhaps the first dose of 1.0 doesn’t do enough to fully combat the disease as it is ordinarily contracted, but is enough to enable the body to destroy immediately the spike proteins introduced by the second dose, before they can induce changes in the antibody (or T-cell?) levels? A lower first dose, though, might allow the second dose to add onto the first. mRNA approaches, though, wouldn’t seem to have that problem, because they introduce the spike protein indirectly, and cells have no reason or method to destroy the mRNA.

    Probably this speculation makes no sense for reasons obvious to those who understand such things. But I am not such a person.

    • Replies: @kpkinusnnyphiladelphia
    @candid_observer

    You know more than most!!

    The key is part two of the immune response: memory T-cells. Antibodies degrade, but memory T-cells hang around, sometimes for many years.

    By the way, if you know of any smart college kids interested in biology, the field to go into is immunology. There's gold in them thar' hills.

    Researchers have made huge strides, but there's still plenty to figure out. Future cancer cures will almost certainly come from either immunological treatments or inducing cell apoptosis with nanotechnology.

    Twenty, thirty years from now. chemo and radiation will be relegated to the leeches category.

    Replies: @That Would Be Telling

    , @Bill
    @candid_observer


    I guess I do really doubt that this would take place, because it would be quickly caught,
     
    I'm curious what mechanism you think would quickly catch it.
  32. @Anonymous
    @That Would Be Telling


    I assume they also force the cells they hijack to produce other adenovirus proteins.
     
    No. The vector is replication-deficient. The only role for all of the viral parts is to deliver DNA into cells and produce mRNA encoding spike protein.

    Replies: @That Would Be Telling

    I assume they also force the cells they hijack to produce other adenovirus proteins.

    No. The vector is replication-deficient. The only role for all of the viral parts is to deliver DNA into cells and produce mRNA encoding spike protein.

    That’s their only role from the viewpoint of us humans wanting protection from COVID-19, but tell me how the virus is gimped so that the cells it hijacks only make the spike protein? It might even be producing the whole set of viral proteins, with some of them needed for replication being gimped. Plus of course whatever protein or proteins it had that were replaced in part or whole by the coronavirus spike protein.

    This requires some research from one of us, but IMHO not until there’s better results from a adenovirus vector vaccine , either from more data from this one, or one of the others. Ad5-nCoV from the PRC and Russia, assuming they can be trusted, Gam-COVID-Vac AKA Sputnik V, which might be OK but was prematurely championed and thus the following Phase 3 trial is likely going to be too political, or Janssen (Johnson & Johnson)/BIDMC, which is testing their’s on up to 60,000 participants. Of the viral vector type that’s all I could find on Wikipedia, plus I had to do some digging or work from memory for Sputnik V to confirm they all use an adenovirus vector, someone has been deleting information from the table.

  33. @Svigor

    Three weeks ago this would have been exciting, upbeat news.
     
    And it is now, IMO. The more, the merrier. Three companies will produce more vaccine than two. This isn't all just abstraction, or lab work; it's about manufacturing, too. We also have no idea whatsoever about the duration of efficacy for any of these vaccines.

    Etc.

    Replies: @AnotherDad, @vhrm

    This isn’t all just abstraction, or lab work; it’s about manufacturing, too.

    Well said Svigor.

    Smart “idea people” like many commenters on this blog–myself included–have a tendency to mistake a “solution”–an idea, a model, more so a successful demo–as a solution. Problem solved.

    But real solutions in the real world have to actually roll out through all these logistical barriers of production and distribution.

    As you said … the more the merrier. Another vaccine that seems to work, great! Let’s get their production lines humming as well.

    We’ve got critical issues of racism and hair style discrimination to deal with, it’s time to put this crappy Xi virus in the rearview!

    • Agree: ic1000
    • Replies: @Hypnotoad666
    @AnotherDad


    We’ve got critical issues of racism and hair style discrimination to deal with, it’s time to put this crappy Xi virus in the rearview!
     
    The problem of course is that the "no crisis should go to waste" people don't want it to go away.

    Conventional wisdom claims that a thousand people are dying per day in the U.S. At the same time, tens of millions of doses of (just proven) safe and effective vaccine are just sitting in refrigerated warehouses. What is the official explanation for this seeming stupidity? Serious question.

    Can't we just ship the vaccine, declare victory and have a parade or something.

    Replies: @That Would Be Telling, @James B. Shearer, @epebble, @anon

  34. @Anonymous
    @Jack D


    it is no different than catching a cold
     
    Except it's the chimp cold and you catch it in your muscles :-)

    Sputnik V and upcoming J&J vaccine (which is simply a first stage Sputnik V, based on the human Ad26 serotype) are looking slightly more promising.

    Replies: @That Would Be Telling

    Except it’s the chimp cold and you catch it in your muscles

    Heh, but the use of (gimped) non-human adenovirus vectors is because too many of us already have immunity to too many of the human ones, so you have to get around that one way or another. With it being gimped to not be able to replicate, it’s probably no more dangerous than a human one that’s been tweaked in the lab to evade the immune system, except for the spike protein.

    Or maybe using this one was a mistake; we’re told this is a now common vaccine technology, so I would hope there is data from other vaccines available. Just looked at Ebola vaccines, the two approved ones use different vectors, one a human adenovirus, GSK has a chimp adenovirus vector in Phase 3 since 2016, you have to get an Ebola outbreak in the populations you administered a vaccine to to really test these :-(….

    One other related issue is that once you have “enough” vaccines for a lethal pathogen, finishing the sequence of trials for new ones is not ethical using a placebo. Instead, the control arm has to be one of the best alternatives, and you see if your’s is as good or better. Which will be a tough row to hoe if the mRNA ones continue to show such high efficacy rates, tempered by their inherently higher costs for now (new technology not up on the learning curve of manufacturing) and perhaps more intense storage requirements.

    • Replies: @Jack D
    @That Would Be Telling


    One other related issue is that once you have “enough” vaccines for a lethal pathogen, finishing the sequence of trials for new ones is not ethical using a placebo.
     
    Not in the US it's not, but the Chinese and the Russians and the Indians can do whatever the hell they want. Remember that this is a worldwide pandemic and that the US has less than 5% of the world population, so there is going to be a really big market for this vaccine outside of the US. 3rd world countries are not going to be willing or able to pay $70/head for a Covid vaccine and they are not going to be able to create a -70 degree cold chain so something that is $3/head and that you can keep in a household fridge or a cooler is going to be more up their alley.
  35. https://edition.cnn.com/2020/11/23/europe/astrazeneca-oxford-coronavirus-vaccine-intl/index.html

    AstraZeneca’s Oxford coronavirus vaccine is 70% effective on average, data shows, with no safety concerns

  36. @candid_observer
    @kpkinusnnyphiladelphia

    My supposition is that if there were a possibility of fraudulent data, it wouldn't be as a result of any company wide conspiracy, but an individual or two at a critical stage in producing the data who, say, didn't want to lose their job or see their stock tank.

    I guess I do really doubt that this would take place, because it would be quickly caught, and would be self destructive. But, you know, think of Theranos.

    In any case, we need to keep our eyes out for further results from the vaccine. As the number of cases of covid grow in the recipients, we should get a much better idea as to the precise efficacy rates of the two dosage regimes.

    Also, I do wonder it there might not be a mechanism that would explain the lower efficacy rate for the 2.0 dose approach. Perhaps the first dose of 1.0 doesn't do enough to fully combat the disease as it is ordinarily contracted, but is enough to enable the body to destroy immediately the spike proteins introduced by the second dose, before they can induce changes in the antibody (or T-cell?) levels? A lower first dose, though, might allow the second dose to add onto the first. mRNA approaches, though, wouldn't seem to have that problem, because they introduce the spike protein indirectly, and cells have no reason or method to destroy the mRNA.

    Probably this speculation makes no sense for reasons obvious to those who understand such things. But I am not such a person.

    Replies: @kpkinusnnyphiladelphia, @Bill

    You know more than most!!

    The key is part two of the immune response: memory T-cells. Antibodies degrade, but memory T-cells hang around, sometimes for many years.

    By the way, if you know of any smart college kids interested in biology, the field to go into is immunology. There’s gold in them thar’ hills.

    Researchers have made huge strides, but there’s still plenty to figure out. Future cancer cures will almost certainly come from either immunological treatments or inducing cell apoptosis with nanotechnology.

    Twenty, thirty years from now. chemo and radiation will be relegated to the leeches category.

    • Replies: @That Would Be Telling
    @kpkinusnnyphiladelphia


    By the way, if you know of any smart college kids interested in biology, the field to go into is immunology. There’s gold in them thar’ hills.
     
    Only if they are willing to become shitlibs, or already are.
  37. @AnotherDad
    @Svigor


    This isn’t all just abstraction, or lab work; it’s about manufacturing, too.
     
    Well said Svigor.

    Smart "idea people" like many commenters on this blog--myself included--have a tendency to mistake a "solution"--an idea, a model, more so a successful demo--as a solution. Problem solved.

    But real solutions in the real world have to actually roll out through all these logistical barriers of production and distribution.

    As you said ... the more the merrier. Another vaccine that seems to work, great! Let's get their production lines humming as well.

    We've got critical issues of racism and hair style discrimination to deal with, it's time to put this crappy Xi virus in the rearview!

    Replies: @Hypnotoad666

    We’ve got critical issues of racism and hair style discrimination to deal with, it’s time to put this crappy Xi virus in the rearview!

    The problem of course is that the “no crisis should go to waste” people don’t want it to go away.

    Conventional wisdom claims that a thousand people are dying per day in the U.S. At the same time, tens of millions of doses of (just proven) safe and effective vaccine are just sitting in refrigerated warehouses. What is the official explanation for this seeming stupidity? Serious question.

    Can’t we just ship the vaccine, declare victory and have a parade or something.

    • Replies: @That Would Be Telling
    @Hypnotoad666


    Conventional wisdom claims that a thousand people are dying per day in the U.S. At the same time, tens of millions of doses of (just proven) safe and effective vaccine are just sitting in refrigerated warehouses. What is the official explanation for this seeming stupidity? Serious question.
     
    The FDA has to double check the companies' work? Also note the data collected so far is just enough for an Emergency Use Authorization, more time must pass for more data to be collected before the FDA can sign off on it for the general population.

    Replies: @Hypnotoad666

    , @James B. Shearer
    @Hypnotoad666

    "Conventional wisdom claims that a thousand people are dying per day in the U.S. At the same time, tens of millions of doses of (just proven) safe and effective vaccine are just sitting in refrigerated warehouses. What is the official explanation for this seeming stupidity? Serious question."

    You want to be very sure a vaccine is safe before you start giving it to millions of people. Suppose the vaccine kills (or has some very bad side effect) one in a hundred thousand of the people who take it.
    You might not see even one example in a trial on 60000 people but give it to one hundred million people and that's a thousand dead. Plus the indirect deaths caused by people being more scared to take other vaccines.

    , @epebble
    @Hypnotoad666

    Suppose they give 20 million vaccines to the first group, and 20,000 develop paralysis. Won't this derail the whole vaccine project? Approving a new vaccine/drug that will be given to billions has to be done carefully so that even the slightest side effects are well analyzed and understood. For example, I have a question: In none of the vaccine trials they have disclosed How many people died in the placebo group? If no one died in the placebo groups in the trials, I am not impressed with the success of the vaccine. What good is a vaccine if the persons who were not vaccinated did not die when 1.4 million people have already died due to the disease?

    Replies: @That Would Be Telling

    , @anon
    @Hypnotoad666


    Conventional wisdom claims that a thousand people are dying per day in the U.S. At the same time, tens of millions of doses of (just proven) safe and effective vaccine are just sitting in refrigerated warehouses. What is the official explanation for this seeming stupidity? Serious question.
     
    No one actually considers this that sort of emergency. And 1,000 averages to 20 per state. More like the announced influenza deaths of say 80,000. Most of whom are old people dying of natural causes.

    And because Trump. They haven't switched gears very quickly since the election. And people get tripped up, maybe because they weren't clued in to the fact that the Democrat anti vax stance was just politics.
    Or they are waiting for a committee of outside experts — known as the Vaccines and Related Biological Products Advisory Committee, or VRBPAC, which I think meets December 11. But can't they move the meeting up? The members are so busy, they can't spare a few hours for Zoom videoconferences?

    They did act like Ebola was an emergency. And dusted off a vaccine that had been studied for years, put together an ad hoc test. And based on 16 infections in a control group, approved and started using it, even though the p value was only .84. Of course, Ebola is very very fatal -- about 1/2 die a plague like death.

    It isn't for safety reasons, because those were carefully considered before Phase 3 trials

    Put your mask on, social distance, and STFU. They will get to it when they get to it.

    Replies: @That Would Be Telling

  38. @Hypnotoad666
    @AnotherDad


    We’ve got critical issues of racism and hair style discrimination to deal with, it’s time to put this crappy Xi virus in the rearview!
     
    The problem of course is that the "no crisis should go to waste" people don't want it to go away.

    Conventional wisdom claims that a thousand people are dying per day in the U.S. At the same time, tens of millions of doses of (just proven) safe and effective vaccine are just sitting in refrigerated warehouses. What is the official explanation for this seeming stupidity? Serious question.

    Can't we just ship the vaccine, declare victory and have a parade or something.

    Replies: @That Would Be Telling, @James B. Shearer, @epebble, @anon

    Conventional wisdom claims that a thousand people are dying per day in the U.S. At the same time, tens of millions of doses of (just proven) safe and effective vaccine are just sitting in refrigerated warehouses. What is the official explanation for this seeming stupidity? Serious question.

    The FDA has to double check the companies’ work? Also note the data collected so far is just enough for an Emergency Use Authorization, more time must pass for more data to be collected before the FDA can sign off on it for the general population.

    • Replies: @Hypnotoad666
    @That Would Be Telling

    "the data collected so far is just enough for an Emergency Use Authorization . . . "

    I thought this was an emergency. Newsome, Whitmer, Cuomo, et al., have certainly claimed as much by seizing "emergency powers."

  39. AstraZeneca had 3 times smaller sample (11k) than Moderna (30k) yet they had similar number of infected. The infection rate of Moderna volunteers was about 4 times (rough approx) lower than in the general population in the US in 3 months period. Are British volunteers more risk taking?

    • Replies: @That Would Be Telling
    @utu

    Per this source AZ/Oxford's Phase 3 trial has ~24,000 so far, of course half vaccine and half placebo. Moderna is indeed 30,000 so far, and as I remember Pfizer/BioNTech is over 43,000. Just read from that article that Janssen (Johnson & Johnson)/BIDMC is going for 60,000, or that total through the end of the study, these run for a couple of years.

  40. @That Would Be Telling
    @Anonymous


    Except it’s the chimp cold and you catch it in your muscles
     
    Heh, but the use of (gimped) non-human adenovirus vectors is because too many of us already have immunity to too many of the human ones, so you have to get around that one way or another. With it being gimped to not be able to replicate, it's probably no more dangerous than a human one that's been tweaked in the lab to evade the immune system, except for the spike protein.

    Or maybe using this one was a mistake; we're told this is a now common vaccine technology, so I would hope there is data from other vaccines available. Just looked at Ebola vaccines, the two approved ones use different vectors, one a human adenovirus, GSK has a chimp adenovirus vector in Phase 3 since 2016, you have to get an Ebola outbreak in the populations you administered a vaccine to to really test these :-(....

    One other related issue is that once you have "enough" vaccines for a lethal pathogen, finishing the sequence of trials for new ones is not ethical using a placebo. Instead, the control arm has to be one of the best alternatives, and you see if your's is as good or better. Which will be a tough row to hoe if the mRNA ones continue to show such high efficacy rates, tempered by their inherently higher costs for now (new technology not up on the learning curve of manufacturing) and perhaps more intense storage requirements.

    Replies: @Jack D

    One other related issue is that once you have “enough” vaccines for a lethal pathogen, finishing the sequence of trials for new ones is not ethical using a placebo.

    Not in the US it’s not, but the Chinese and the Russians and the Indians can do whatever the hell they want. Remember that this is a worldwide pandemic and that the US has less than 5% of the world population, so there is going to be a really big market for this vaccine outside of the US. 3rd world countries are not going to be willing or able to pay $70/head for a Covid vaccine and they are not going to be able to create a -70 degree cold chain so something that is $3/head and that you can keep in a household fridge or a cooler is going to be more up their alley.

  41. All of them requiring two doses weeks apart means that the average American will probably fail to be immunized. Making the effort to get the first shot will happen for many Americans but if any Americans get an immune response (run a fever) then they will not get the second shot. All three vaccine are built for the institutional world where there are corporate minders (occupational health, human resources) that will hunt employees down and make sure they get both shots. The general public needs a one dose shot that can be shipped and stored at-20 C or higher.

    • Replies: @Jack D
    @guest007

    Most vaccine recipients had few side effects and most of those were after the 2nd shot. I realize there are a lot of stupid people but if you have enough sense to get 1 shot then you can come back in 2 weeks. Sheesh, it's not that hard.

    Replies: @guest007

  42. @Svigor

    Three weeks ago this would have been exciting, upbeat news.
     
    And it is now, IMO. The more, the merrier. Three companies will produce more vaccine than two. This isn't all just abstraction, or lab work; it's about manufacturing, too. We also have no idea whatsoever about the duration of efficacy for any of these vaccines.

    Etc.

    Replies: @AnotherDad, @vhrm

    This isn’t all just abstraction, or lab work; it’s about manufacturing, too.

    It’s also shamanism. We’ll do the vaccine dance and the miasma will be lifted from the land. At this point, the sooner the better.

    I’m not disputing the existence of the virus or the efficacy of the vaccine, I’m just intensely annoyed by the autoimmune disease that SarsCov-2 has triggered in our society. We already have chronic fatigue syndrome, some muscle wasting, and are bed ridden two days a week.
    Naturally acquired herd immunity is actually doing the heavy lifting in actually dealing with Covid, (helped by better treatment protocols), but if the vaccines are the antihistamine that prevent Biden, newsom and Cuomo from driving is into anaphylactic shock, then I’m all for them.

    /soapbox

    • Replies: @Jack D
    @vhrm


    Naturally acquired herd immunity is actually doing the heavy lifting in actually dealing with Covid,
     
    Unfortunately, some of the heavy lifting is being done by pall bearers. Acquiring immunity thru infection is doing it the hard way. And even now with 200,000+ dead, we are less than 10% of the way thru the population. By the time herd immunity is acquired without vaccines, you are probably talking 2 million dead. That's not chopped liver.

    Replies: @That Would Be Telling, @vhrm

  43. @AndrewR
    @Altai

    When Serena threw her "sh3boon" temper tantrum, I felt bad for Naomi, who seemed like a sweet girl. Now I want to send both of them, together with Serena's girl Meghan Markle, to the Islamic State (is that still a thing?)

    In related news, Serena's hubby, reddit co-founder Alexis Ohanian, responded to me on Twitter once. Someone else had insulted him and Serena, so Alexis tweeted to him something like "why don't you say that to my face?"

    I pointed out the absurdity of a man in a "power couple" like his to get so angry at low status trolls on the internet like Scott Greer. He responded right before my account got permanently suspended.

    I think on some level he's well aware she is unattractive and manly, and he feels bad that he married her for her money, especially since he is wealthy in his own right.

    https://mobile.twitter.com/alexisohanian/status/1137443418739752960

    Replies: @Barnard, @Anonymous

    Even more bizarre to me was that Bulgarian tennis player Grigor Dimitrov had briefly dated Serena. Did Ohanian marry Serena for money? Unless he squandered most of his he should be worth more than her. He sounds like a woke true believer who somehow thinks he has a personal responsibility for the repression of American blacks. He gave up his seat on the Reddit board so a “person of color” could be represented on it. Is it some sort of, “blacks are oppressed just like we Armenians are oppressed” mentality?

  44. Whatever a pharmaceutical company asserts is the efficacy, in a study, of its new drug, will exactly be its effectiveness, in clinical setting, when taken by the general public: the history of pharmaceuticals, and vaccines in particular, demonstrates that beyond a shadow of a doubt.

  45. Meanwhile, back on planet Earth, the average immune system of a person under age fifty is 300 times more effective than the Oxford vax and 50 times more effective than any RNA vax at conquering the Coronasniffles.

    Imagine, if you will, a virus so deadly that it increases average human life expectancy.

    Covidiots.

    • Replies: @Jack D
    @Je Suis Omar Mateen

    There are some sad cases now involving people who have Covid but are Covid deniers so they keep calling it a hoax, Coronasniffles, etc. until their last breath and they miss out on the chance to say goodbye to their families. Even as they are literally dying from the disease they continue to deny that it even exists.

    Replies: @clyde, @The Last Real Calvinist

  46. @vhrm
    @Svigor


    This isn’t all just abstraction, or lab work; it’s about manufacturing, too.
     
    It's also shamanism. We'll do the vaccine dance and the miasma will be lifted from the land. At this point, the sooner the better.

    I'm not disputing the existence of the virus or the efficacy of the vaccine, I'm just intensely annoyed by the autoimmune disease that SarsCov-2 has triggered in our society. We already have chronic fatigue syndrome, some muscle wasting, and are bed ridden two days a week.
    Naturally acquired herd immunity is actually doing the heavy lifting in actually dealing with Covid, (helped by better treatment protocols), but if the vaccines are the antihistamine that prevent Biden, newsom and Cuomo from driving is into anaphylactic shock, then I'm all for them.

    /soapbox

    Replies: @Jack D

    Naturally acquired herd immunity is actually doing the heavy lifting in actually dealing with Covid,

    Unfortunately, some of the heavy lifting is being done by pall bearers. Acquiring immunity thru infection is doing it the hard way. And even now with 200,000+ dead, we are less than 10% of the way thru the population. By the time herd immunity is acquired without vaccines, you are probably talking 2 million dead. That’s not chopped liver.

    • Replies: @That Would Be Telling
    @Jack D


    Acquiring immunity thru infection is doing it the hard way.
     
    It's not even clear it'll work for the normal meaning of the term, protecting those in the "herd" who can't achieve immunity through a vaccine. Look at Wikipedia's table on R0, the "basic reproduction number" for pathogens attacking a naive population, as is mostly the case now with COVID-19, but will change sooner or later. I look at smallpox and rubella as severity bookends with roughly comparable R0s and transmission through respiratory droplets. Both require vaccination to control, and we managed to eradicate smallpox as well as rinderpest through that method.
    , @vhrm
    @Jack D


    we are less than 10% of the way thru the population. By the time herd immunity is acquired without vaccines, you are probably talking 2 million dead.
     
    There's virtually no reason to believe we're that far inaway. The "confirmed cases" are a severe undercount. The first several months it was by a factor of 20x, now it's probably less due to increased testing but still most cases ate probably not detected.

    The serosurveys that were supposed to tell us the actual incidence (which also somewhat undercount a little considering the time lag of development of antibodies etc but can be statistically corrected) basically haven't materialized. I have no idea why. There was some excitement in March... then not much. We just mindlessly and swab hundreds of thousands of people for RPCR tests with little rhyme or reason instead.

    Also due to the heterogeneity of succeptibility on the network ( Tom Hanks / boho / Trump disease because they have many connections) the threshold for naturally acquired immunity to stop the spread of much lower than that for uniform vaccination. k prob on the 30% to 40%.

    Clearly we were already below the threshold for non flu season. That's why or was dying out. Now it's flu season and we'll get to the higher threshold and it'll start dying out well before the vaccine gets large distribution (is my guess. we'll see how it goes)


    More importantly about those pall bearers:


    Those under age 50 who get infected with the coronavirus lose less than one day of discounted quality-adjusted life expectancy; seniors age 70 or older lose nearly 90 days.

     

    https://www.forbes.com/sites/theapothecary/2020/10/06/what-is-your-risk-of-dying-from-covid-19/?sh=37af8bb46159

    Yes that's on average, (and I'm not in a position to vouch for the methodology but it seems plausible, though they are probably high since they don't take into account, I believe, that the people who died were overall sicker and thus had lower expected life than avg people of their age)
    but at the scales of a whole society we have to look at since average impacts, we can't just say "every life is infinitely precious".

    Put in those terms, the government imposed lockdowns and trampling of civil liberties is nowhere near worth it, imo.

    BTW are you ready for the "reparations for essential workers" social justice movement that we'll probably be dealing with for the next 2 decades?

    Replies: @Jack D

  47. @guest007
    All of them requiring two doses weeks apart means that the average American will probably fail to be immunized. Making the effort to get the first shot will happen for many Americans but if any Americans get an immune response (run a fever) then they will not get the second shot. All three vaccine are built for the institutional world where there are corporate minders (occupational health, human resources) that will hunt employees down and make sure they get both shots. The general public needs a one dose shot that can be shipped and stored at-20 C or higher.

    Replies: @Jack D

    Most vaccine recipients had few side effects and most of those were after the 2nd shot. I realize there are a lot of stupid people but if you have enough sense to get 1 shot then you can come back in 2 weeks. Sheesh, it’s not that hard.

    • Replies: @guest007
    @Jack D

    Ask any occupational health or public health nurse abou having to hunt people down to have their TB test read. That is why many health departments have gone to using blood tests for TB since it is a single interaction with the individual of interest.

    There is probably good data on the Shingles VAccine that requires to doses to see who comes back.

  48. @Jack D
    @vhrm


    Naturally acquired herd immunity is actually doing the heavy lifting in actually dealing with Covid,
     
    Unfortunately, some of the heavy lifting is being done by pall bearers. Acquiring immunity thru infection is doing it the hard way. And even now with 200,000+ dead, we are less than 10% of the way thru the population. By the time herd immunity is acquired without vaccines, you are probably talking 2 million dead. That's not chopped liver.

    Replies: @That Would Be Telling, @vhrm

    Acquiring immunity thru infection is doing it the hard way.

    It’s not even clear it’ll work for the normal meaning of the term, protecting those in the “herd” who can’t achieve immunity through a vaccine. Look at Wikipedia’s table on R0, the “basic reproduction number” for pathogens attacking a naive population, as is mostly the case now with COVID-19, but will change sooner or later. I look at smallpox and rubella as severity bookends with roughly comparable R0s and transmission through respiratory droplets. Both require vaccination to control, and we managed to eradicate smallpox as well as rinderpest through that method.

  49. @That Would Be Telling
    @Hypnotoad666


    Conventional wisdom claims that a thousand people are dying per day in the U.S. At the same time, tens of millions of doses of (just proven) safe and effective vaccine are just sitting in refrigerated warehouses. What is the official explanation for this seeming stupidity? Serious question.
     
    The FDA has to double check the companies' work? Also note the data collected so far is just enough for an Emergency Use Authorization, more time must pass for more data to be collected before the FDA can sign off on it for the general population.

    Replies: @Hypnotoad666

    “the data collected so far is just enough for an Emergency Use Authorization . . . ”

    I thought this was an emergency. Newsome, Whitmer, Cuomo, et al., have certainly claimed as much by seizing “emergency powers.”

  50. And now for some details, mostly from Dr. “Things I Won’t Work With” AKA Derek Lowe, in “Oxford/AZ Vaccine Efficacy Data“. Anchored by the sentence “Immunology strikes again!“, one guess is that giving a full dose first primes the immune system to zap too much of the second dose before it can do its job. This could explain the Sputnik V approach, which uses different adenovirus vectors for its two doses.

    This was a serendipitous discovery through an accident in the U.K. where number of subjects being dosed by Oxford (vs. AZ I think) were accidentally given an initial half dose. They had lower side effects on the second dose, which resulted in an investigation that discovered the dosing error, and they decided to continue with this dosing pattern for some of Phase 3. Low numbers though, 2,741 with the 1/2 initial and full booster, 8,895 with full for both. Low numbers compared to the mRNA trials, only 24,000 so far. The US based trial was halted for a month due to safety concerns, as I recall for a shorter period elsewhere, this due to a neurological problem one of the U.K. participants had.

    I would point you to a linked Nature article, but it fails the Gell-Man Amnesia Effect test (or maybe a nationalist one), claiming both mRNA tests require the much lower temperatures of the Pfizer/BioNTech. But it also claims two things with probably more reliability, that AZ is going to ask the US regulators if they can switch to the 1/2 then full dosing pattern in the ongoing US trial, and that AZ has cooked up a lot of doses (perhaps not (all) bottled, though), and can produce them at much higher rates than I remember from the mRNA companies. It’s also a cheaper, as previously mentioned uses existing vaccine technology.

    Safety info is limited for now, “The Oxford release says just that ‘No serious safety events related to the vaccine have been identified’, and the AZ one says ‘No serious safety events related to the vaccine have been confirmed’.” but the FDA standard is 1/2 your participants for 2 months after the last dose, and as the mRNA trials showed, you can get efficacy data before that. Of course you don’t really know when you’ll have enough people coming down with symptomatic COVID-19 for efficacy, whereas the period required for safety is deterministic.

  51. @AndrewR
    @Altai

    When Serena threw her "sh3boon" temper tantrum, I felt bad for Naomi, who seemed like a sweet girl. Now I want to send both of them, together with Serena's girl Meghan Markle, to the Islamic State (is that still a thing?)

    In related news, Serena's hubby, reddit co-founder Alexis Ohanian, responded to me on Twitter once. Someone else had insulted him and Serena, so Alexis tweeted to him something like "why don't you say that to my face?"

    I pointed out the absurdity of a man in a "power couple" like his to get so angry at low status trolls on the internet like Scott Greer. He responded right before my account got permanently suspended.

    I think on some level he's well aware she is unattractive and manly, and he feels bad that he married her for her money, especially since he is wealthy in his own right.

    https://mobile.twitter.com/alexisohanian/status/1137443418739752960

    Replies: @Barnard, @Anonymous

    I pointed out the absurdity of a man in a “power couple” like his to get so angry at low status trolls on the internet like Scott Greer.

    Plus he has a girl’s name. That’s gotta sting.

    • Replies: @Reg Cæsar
    @Anonymous


    Plus he has a girl’s name. That’s gotta sting.

     

    https://images-na.ssl-images-amazon.com/images/I/51STE5MVZPL._SY445_.jpg

    https://s3-us-west-2.amazonaws.com/courses-images-archive-read-only/wp-content/uploads/sites/883/2015/08/23202442/CNX_History_10_05_Tocquevill.jpg


    https://thumbs.dreamstime.com/b/helsinki-finland-april-statue-finnish-author-aleksis-kivi-helsinki-finland-statue-finnish-author-aleksis-kivi-110441154.jpg

    https://c8.alamy.com/comp/DD3G68/alexis-getafe-august-23-2013-football-soccer-alexis-ruano-delgado-DD3G68.jpg

    https://www.idolbirthdays.net/images/7/7e/alexis-minotis.jpg

    Replies: @SimpleSong, @clyde

  52. @kpkinusnnyphiladelphia
    @candid_observer

    You know more than most!!

    The key is part two of the immune response: memory T-cells. Antibodies degrade, but memory T-cells hang around, sometimes for many years.

    By the way, if you know of any smart college kids interested in biology, the field to go into is immunology. There's gold in them thar' hills.

    Researchers have made huge strides, but there's still plenty to figure out. Future cancer cures will almost certainly come from either immunological treatments or inducing cell apoptosis with nanotechnology.

    Twenty, thirty years from now. chemo and radiation will be relegated to the leeches category.

    Replies: @That Would Be Telling

    By the way, if you know of any smart college kids interested in biology, the field to go into is immunology. There’s gold in them thar’ hills.

    Only if they are willing to become shitlibs, or already are.

  53. @utu
    AstraZeneca had 3 times smaller sample (11k) than Moderna (30k) yet they had similar number of infected. The infection rate of Moderna volunteers was about 4 times (rough approx) lower than in the general population in the US in 3 months period. Are British volunteers more risk taking?

    Replies: @That Would Be Telling

    Per this source AZ/Oxford’s Phase 3 trial has ~24,000 so far, of course half vaccine and half placebo. Moderna is indeed 30,000 so far, and as I remember Pfizer/BioNTech is over 43,000. Just read from that article that Janssen (Johnson & Johnson)/BIDMC is going for 60,000, or that total through the end of the study, these run for a couple of years.

  54. @Hypnotoad666
    @AnotherDad


    We’ve got critical issues of racism and hair style discrimination to deal with, it’s time to put this crappy Xi virus in the rearview!
     
    The problem of course is that the "no crisis should go to waste" people don't want it to go away.

    Conventional wisdom claims that a thousand people are dying per day in the U.S. At the same time, tens of millions of doses of (just proven) safe and effective vaccine are just sitting in refrigerated warehouses. What is the official explanation for this seeming stupidity? Serious question.

    Can't we just ship the vaccine, declare victory and have a parade or something.

    Replies: @That Would Be Telling, @James B. Shearer, @epebble, @anon

    “Conventional wisdom claims that a thousand people are dying per day in the U.S. At the same time, tens of millions of doses of (just proven) safe and effective vaccine are just sitting in refrigerated warehouses. What is the official explanation for this seeming stupidity? Serious question.”

    You want to be very sure a vaccine is safe before you start giving it to millions of people. Suppose the vaccine kills (or has some very bad side effect) one in a hundred thousand of the people who take it.
    You might not see even one example in a trial on 60000 people but give it to one hundred million people and that’s a thousand dead. Plus the indirect deaths caused by people being more scared to take other vaccines.

  55. @Je Suis Omar Mateen
    Meanwhile, back on planet Earth, the average immune system of a person under age fifty is 300 times more effective than the Oxford vax and 50 times more effective than any RNA vax at conquering the Coronasniffles.

    Imagine, if you will, a virus so deadly that it increases average human life expectancy.

    Covidiots.

    Replies: @Jack D

    There are some sad cases now involving people who have Covid but are Covid deniers so they keep calling it a hoax, Coronasniffles, etc. until their last breath and they miss out on the chance to say goodbye to their families. Even as they are literally dying from the disease they continue to deny that it even exists.

    • Replies: @clyde
    @Jack D

    I have nothing against The Jews but they are the biggest hypochondriacs and Israel has the most psychiatrists per X population. And by all means get that anti-CovX19 jab asap. I am not rushing out for it if ever.

    Quercetin -Zinc -D

    , @The Last Real Calvinist
    @Jack D

    Are you thinking of the 'sad cases' as related by that nurse from South Dakota? Her 'testimonial' has been blasted out across the world in the past few days.

    She was making it up:

    https://www.foxnews.com/media/cnn-silent-nurses-viral-patients-denying-coronavirus-deathbed-falls-apart

  56. @Anonymous
    @AndrewR


    I pointed out the absurdity of a man in a “power couple” like his to get so angry at low status trolls on the internet like Scott Greer.

     

    Plus he has a girl’s name. That’s gotta sting.

    Replies: @Reg Cæsar

    Plus he has a girl’s name. That’s gotta sting.


    • Replies: @SimpleSong
    @Reg Cæsar

    Off topic but I've always really enjoyed reading de Tocqueville. A man ahead of his time; he seems to write in the style of an internet comment.

    , @clyde
    @Reg Cæsar

    The first photo--
    Running jumping standing still and back when Zimmerman was still Zimmerman and a nobody strumming n humming abandoned Woodie Guthrie tunes in university adjacent coffee houses. Dens of folkie iniquity - depravity- pot smoking and innocent hetero hook ups. But all in good fun back then, 50-60 years before idiots could stare-star gaze into their personal flat screens and alone phones. Trying to divine their future and fates.

  57. @Hypnotoad666
    @AnotherDad


    We’ve got critical issues of racism and hair style discrimination to deal with, it’s time to put this crappy Xi virus in the rearview!
     
    The problem of course is that the "no crisis should go to waste" people don't want it to go away.

    Conventional wisdom claims that a thousand people are dying per day in the U.S. At the same time, tens of millions of doses of (just proven) safe and effective vaccine are just sitting in refrigerated warehouses. What is the official explanation for this seeming stupidity? Serious question.

    Can't we just ship the vaccine, declare victory and have a parade or something.

    Replies: @That Would Be Telling, @James B. Shearer, @epebble, @anon

    Suppose they give 20 million vaccines to the first group, and 20,000 develop paralysis. Won’t this derail the whole vaccine project? Approving a new vaccine/drug that will be given to billions has to be done carefully so that even the slightest side effects are well analyzed and understood. For example, I have a question: In none of the vaccine trials they have disclosed How many people died in the placebo group? If no one died in the placebo groups in the trials, I am not impressed with the success of the vaccine. What good is a vaccine if the persons who were not vaccinated did not die when 1.4 million people have already died due to the disease?

    • Replies: @That Would Be Telling
    @epebble


    In none of the vaccine trials they have disclosed How many people died in the placebo group? If no one died in the placebo groups in the trials, I am not impressed with the success of the vaccine. What good is a vaccine if the persons who were not vaccinated did not die when 1.4 million people have already died due to the disease?
     
    anon[255] in the comment currently numbered 59 covers this pretty well. The number of people in the placebo groups are small as these things go, and there hasn't been much time for them to contract a fatal case; for the most recently enrolled, time measured in days and weeks (the hard rule for safety is that have the vaccine arm of the trials must be at 2 months after the 2nd inoculation). We could assume right now there might be a few serious cases in the placebo arms of the trials that might proceed to death.

    Replies: @Hernan Pizzaro del Blanco

  58. anon[255] • Disclaimer says:
    @Hypnotoad666
    @anon


    The drug appears highly effective in preventing severe cases.
     
    You would have to compare the outcome to the placebo side. And there's the rub. Covid itself is so innocuous that hardly anyone gets seriously sick in the placebo group.

    In fact, since they can't use the fakey death and hospitalization rates that the media does, these controlled studies would be the perfect vehicle for testing the hypothesis that covid is simply not dangerous.

    Put another way, if the "end point" of efficacy was prevention of death, they would have to say the vaccines had no statistical efficacy. The virus itself is pretty efficacious in not killing people.

    Replies: @anon

    these controlled studies would be the perfect vehicle for testing the hypothesis that covid is simply not dangerous.

    Put another way, if the “end point” of efficacy was prevention of death, they would have to say the vaccines had no statistical efficacy. The virus itself is pretty efficacious in not killing people.

    I’ve given this a fair amount of thought. First, I look at the graphs in the WSJ, paying attention to the ratio of reported deaths to reported cases. Which is 1-2%.

    If a symptomatic reported case in the placebo group has a 1% chance of dying of covid, it is plausible in the control group that out of 90 reported cases, there will 0 deaths. Especially since they go to considerable effort to reject candidates with co-morbidities.

    And, it is logical that all covid deaths will (1) display symptoms (2) have a positive test (3) have a serious case and then (4) die. And since there were maybe 10% serious cases in the control group, if they kept running the trials, they would eventually start generating some deaths.

    So, in my opinion, the announced test results aren’t substantially at odds with the announced/believed rates of death and serious cases.

    However, it is also striking that the virus, as you noticed, isn’t very efficacious at killing people. Especially people who don’t have serious co-morbidities or aren’t close to dying of old age.

    But this virus is quite efficacious at triggering the leadership of moderately developed countries with modern medical systems to panic. Starting with Red China and much of the rest of the world including Russia.

    • Replies: @Jack D
    @anon


    However, it is also striking that the virus, as you noticed, isn’t very efficacious at killing people. Especially people who don’t have serious co-morbidities or aren’t close to dying of old age.
     
    It really depends what "very efficacious" means. If the IFR is even 1%, that means 3.5 million deaths when applied to the entire US population. And yes these are disproportionately people not in perfect health - older, fatter, etc. But that describes a lot of us. Our medical system has gotten pretty good at keeping people with chronic conditions alive and most of them had a good few years left in them before Covid hit.

    Replies: @anon, @Hypnotoad666, @Bill

    , @epebble
    @anon

    they go to considerable effort to reject candidates with co-morbidities.

    That seems like a bad design of experiment to leave out the primary victims of the disease. If they had selected, say, 10,000 people with comorbidities each for vaccination and placebo, and after 2 months announced, 100 people have died in the placebo group but only 5 in vaccinated group, the impact of the vaccine would have been far more impressive in public mind and there would be far fewer people unwilling to get vaccinations.

    , @Jonathan Silber
    @anon

    ...they [designers of the drug study] go to considerable effort to reject candidates with co-morbidities.

    The effectiveness of vaccines against the flu in the group of persons elderly, weak, and sickly has in recent years been estimated to be as low as 20%.

  59. @Reg Cæsar
    @Anonymous


    Plus he has a girl’s name. That’s gotta sting.

     

    https://images-na.ssl-images-amazon.com/images/I/51STE5MVZPL._SY445_.jpg

    https://s3-us-west-2.amazonaws.com/courses-images-archive-read-only/wp-content/uploads/sites/883/2015/08/23202442/CNX_History_10_05_Tocquevill.jpg


    https://thumbs.dreamstime.com/b/helsinki-finland-april-statue-finnish-author-aleksis-kivi-helsinki-finland-statue-finnish-author-aleksis-kivi-110441154.jpg

    https://c8.alamy.com/comp/DD3G68/alexis-getafe-august-23-2013-football-soccer-alexis-ruano-delgado-DD3G68.jpg

    https://www.idolbirthdays.net/images/7/7e/alexis-minotis.jpg

    Replies: @SimpleSong, @clyde

    Off topic but I’ve always really enjoyed reading de Tocqueville. A man ahead of his time; he seems to write in the style of an internet comment.

  60. anon[255] • Disclaimer says:
    @Hypnotoad666
    @AnotherDad


    We’ve got critical issues of racism and hair style discrimination to deal with, it’s time to put this crappy Xi virus in the rearview!
     
    The problem of course is that the "no crisis should go to waste" people don't want it to go away.

    Conventional wisdom claims that a thousand people are dying per day in the U.S. At the same time, tens of millions of doses of (just proven) safe and effective vaccine are just sitting in refrigerated warehouses. What is the official explanation for this seeming stupidity? Serious question.

    Can't we just ship the vaccine, declare victory and have a parade or something.

    Replies: @That Would Be Telling, @James B. Shearer, @epebble, @anon

    Conventional wisdom claims that a thousand people are dying per day in the U.S. At the same time, tens of millions of doses of (just proven) safe and effective vaccine are just sitting in refrigerated warehouses. What is the official explanation for this seeming stupidity? Serious question.

    No one actually considers this that sort of emergency. And 1,000 averages to 20 per state. More like the announced influenza deaths of say 80,000. Most of whom are old people dying of natural causes.

    And because Trump. They haven’t switched gears very quickly since the election. And people get tripped up, maybe because they weren’t clued in to the fact that the Democrat anti vax stance was just politics.
    Or they are waiting for a committee of outside experts — known as the Vaccines and Related Biological Products Advisory Committee, or VRBPAC, which I think meets December 11. But can’t they move the meeting up? The members are so busy, they can’t spare a few hours for Zoom videoconferences?

    They did act like Ebola was an emergency. And dusted off a vaccine that had been studied for years, put together an ad hoc test. And based on 16 infections in a control group, approved and started using it, even though the p value was only .84. Of course, Ebola is very very fatal — about 1/2 die a plague like death.

    It isn’t for safety reasons, because those were carefully considered before Phase 3 trials

    Put your mask on, social distance, and STFU. They will get to it when they get to it.

    • Replies: @That Would Be Telling
    @anon


    Or they are waiting for a committee of outside experts — known as the Vaccines and Related Biological Products Advisory Committee, or VRBPAC, which I think meets December 11. But can’t they move the meeting up? The members are so busy, they can’t spare a few hours for Zoom videoconferences?
     
    I mostly agree with what you're saying, even referenced you as having a good answer to another's questions, but this is not a fair criticism. If the FDA isn't going to just be a rubber stamp, they're first going to read and analyze both Pfizer/BioNTech's and the anticipated any day now Moderna Emergency Use Authorization (EUA) applications (really helps that they both use the same basic technology), then discuss them at that meeting, and then hopefully approve one or both of them for EUA uses.
  61. Anon[130] • Disclaimer says:
    @Anonymous
    I suspect the Oxford scientists are just being more honest, corporate Yanks lie through their teeth so I wouldn't trust their stats particularly. Same with Russians, Putin almost immediately announced the Sputnik V vaccine had a 90% efficacy rate after Pfizer had announced theirs did.

    The British academic establishment is too honest, and lacks the "Chutzpah" of the Yanks and Russians I think.

    Replies: @Anon, @Herald

    You can bet that any information released by a publicly traded American pharmaceutical company has been legally vetted and is precisely accurate. On the other hand, and I don’t know about the U.K., but any information about funded research released via the public relations office at an American university will be inaccurate and exaggerated. Look at the incentives and disincentives.

    The thing with corporate news releases, however, is that you have to read the original release very closely. THAT is what is accurate, not news reports about what it says. This is analogous to the law that anything printed by the National Enquirer is true, when closely read, but the innuendos may not be.

    • Replies: @Bill
    @Anon


    You can bet that any information released by a publicly traded American pharmaceutical company has been legally vetted and is precisely accurate.
     
    Right. Any lying going on has been outsourced to the academic and contract labs who actually do the research.
  62. Inactivated and attenuated vaccines at least don’t have Frankenstein cooties in them.

    What about Sputnik V and the Sinovac vaccines?

    Provincial as ever, ain’t you?

    • Replies: @That Would Be Telling
    @obwandiyag


    Inactivated and attenuated vaccines at least don’t have Frankenstein cooties in them.

    What about Sputnik V and the Sinovac vaccines?

    Provincial as ever, ain’t you?
     

    Don't be a jerk, especially an ignorant jerk. Sputnik V has "Frankenstein cooties," while Sinovac's CoronaVac is a killed/inactivated whole virus vaccine. As I read its Wikipedia page, it's only just now, like maybe last week, possibly getting the numbers needed for FDA level standards, 30,000 total Phase 3 participants. And maybe only enough for efficacy, not sure where it is on half of the vaccine arm having two months of experience after the second inoculation, which so far is taking longer than efficacy for the 3 most advanced in testing Western vaccines.

    Sputnik V is more than a month behind CoronaVac in starting its Phase 3 trials, and I guess you don't know the withering criticism it came under was due to it getting official approval in Russia a full month before its Phase 3 trial started on ~September 10th? I.e. we don't have any idea about its safety and efficacy based on large numbers of trial participants.

    But in theory it could be as good or better than the AZ/Oxford one, from the beginning they tried to sidestep the "react in dose two to the virus vector in dose one" known problem by using different human adenovirus vector for the first and second doses. But with it being as much or more a political stunt than a real vaccine effort, it's going to be hard for it to gain trust, probably harder than CoronaVac which is at least officially following the standard processes.

    Replies: @obwandiyag

  63. @Reg Cæsar
    @Anonymous


    Plus he has a girl’s name. That’s gotta sting.

     

    https://images-na.ssl-images-amazon.com/images/I/51STE5MVZPL._SY445_.jpg

    https://s3-us-west-2.amazonaws.com/courses-images-archive-read-only/wp-content/uploads/sites/883/2015/08/23202442/CNX_History_10_05_Tocquevill.jpg


    https://thumbs.dreamstime.com/b/helsinki-finland-april-statue-finnish-author-aleksis-kivi-helsinki-finland-statue-finnish-author-aleksis-kivi-110441154.jpg

    https://c8.alamy.com/comp/DD3G68/alexis-getafe-august-23-2013-football-soccer-alexis-ruano-delgado-DD3G68.jpg

    https://www.idolbirthdays.net/images/7/7e/alexis-minotis.jpg

    Replies: @SimpleSong, @clyde

    The first photo–
    Running jumping standing still and back when Zimmerman was still Zimmerman and a nobody strumming n humming abandoned Woodie Guthrie tunes in university adjacent coffee houses. Dens of folkie iniquity – depravity- pot smoking and innocent hetero hook ups. But all in good fun back then, 50-60 years before idiots could stare-star gaze into their personal flat screens and alone phones. Trying to divine their future and fates.

  64. @Jack D
    @Je Suis Omar Mateen

    There are some sad cases now involving people who have Covid but are Covid deniers so they keep calling it a hoax, Coronasniffles, etc. until their last breath and they miss out on the chance to say goodbye to their families. Even as they are literally dying from the disease they continue to deny that it even exists.

    Replies: @clyde, @The Last Real Calvinist

    I have nothing against The Jews but they are the biggest hypochondriacs and Israel has the most psychiatrists per X population. And by all means get that anti-CovX19 jab asap. I am not rushing out for it if ever.

    Quercetin -Zinc -D

  65. @epebble
    @Hypnotoad666

    Suppose they give 20 million vaccines to the first group, and 20,000 develop paralysis. Won't this derail the whole vaccine project? Approving a new vaccine/drug that will be given to billions has to be done carefully so that even the slightest side effects are well analyzed and understood. For example, I have a question: In none of the vaccine trials they have disclosed How many people died in the placebo group? If no one died in the placebo groups in the trials, I am not impressed with the success of the vaccine. What good is a vaccine if the persons who were not vaccinated did not die when 1.4 million people have already died due to the disease?

    Replies: @That Would Be Telling

    In none of the vaccine trials they have disclosed How many people died in the placebo group? If no one died in the placebo groups in the trials, I am not impressed with the success of the vaccine. What good is a vaccine if the persons who were not vaccinated did not die when 1.4 million people have already died due to the disease?

    anon[255] in the comment currently numbered 59 covers this pretty well. The number of people in the placebo groups are small as these things go, and there hasn’t been much time for them to contract a fatal case; for the most recently enrolled, time measured in days and weeks (the hard rule for safety is that have the vaccine arm of the trials must be at 2 months after the 2nd inoculation). We could assume right now there might be a few serious cases in the placebo arms of the trials that might proceed to death.

    • Replies: @Hernan Pizzaro del Blanco
    @That Would Be Telling

    Most of the most in the trial are under the age of 45, and very few are over the age of 65. So the fatality rate should be about 1 in 900 of those infected. Thus far among the 3 studies less than 225 have been infected.

    Replies: @That Would Be Telling

  66. My money is on the Oxford-AstraZeneca vaccine being the international vaccine of choice in 12 months time .
    I just have a natural caution about the claims of American Big Pharma

  67. @obwandiyag
    Inactivated and attenuated vaccines at least don't have Frankenstein cooties in them.

    What about Sputnik V and the Sinovac vaccines?

    Provincial as ever, ain't you?

    Replies: @That Would Be Telling

    Inactivated and attenuated vaccines at least don’t have Frankenstein cooties in them.

    What about Sputnik V and the Sinovac vaccines?

    Provincial as ever, ain’t you?

    Don’t be a jerk, especially an ignorant jerk. Sputnik V has “Frankenstein cooties,” while Sinovac’s CoronaVac is a killed/inactivated whole virus vaccine. As I read its Wikipedia page, it’s only just now, like maybe last week, possibly getting the numbers needed for FDA level standards, 30,000 total Phase 3 participants. And maybe only enough for efficacy, not sure where it is on half of the vaccine arm having two months of experience after the second inoculation, which so far is taking longer than efficacy for the 3 most advanced in testing Western vaccines.

    Sputnik V is more than a month behind CoronaVac in starting its Phase 3 trials, and I guess you don’t know the withering criticism it came under was due to it getting official approval in Russia a full month before its Phase 3 trial started on ~September 10th? I.e. we don’t have any idea about its safety and efficacy based on large numbers of trial participants.

    But in theory it could be as good or better than the AZ/Oxford one, from the beginning they tried to sidestep the “react in dose two to the virus vector in dose one” known problem by using different human adenovirus vector for the first and second doses. But with it being as much or more a political stunt than a real vaccine effort, it’s going to be hard for it to gain trust, probably harder than CoronaVac which is at least officially following the standard processes.

    • Replies: @obwandiyag
    @That Would Be Telling

    Troll Russia-basher.

    A lot of likely-sounding pseudo-academic babble. From the talking points memo.

    Got your number.

  68. @anon
    @Hypnotoad666


    Conventional wisdom claims that a thousand people are dying per day in the U.S. At the same time, tens of millions of doses of (just proven) safe and effective vaccine are just sitting in refrigerated warehouses. What is the official explanation for this seeming stupidity? Serious question.
     
    No one actually considers this that sort of emergency. And 1,000 averages to 20 per state. More like the announced influenza deaths of say 80,000. Most of whom are old people dying of natural causes.

    And because Trump. They haven't switched gears very quickly since the election. And people get tripped up, maybe because they weren't clued in to the fact that the Democrat anti vax stance was just politics.
    Or they are waiting for a committee of outside experts — known as the Vaccines and Related Biological Products Advisory Committee, or VRBPAC, which I think meets December 11. But can't they move the meeting up? The members are so busy, they can't spare a few hours for Zoom videoconferences?

    They did act like Ebola was an emergency. And dusted off a vaccine that had been studied for years, put together an ad hoc test. And based on 16 infections in a control group, approved and started using it, even though the p value was only .84. Of course, Ebola is very very fatal -- about 1/2 die a plague like death.

    It isn't for safety reasons, because those were carefully considered before Phase 3 trials

    Put your mask on, social distance, and STFU. They will get to it when they get to it.

    Replies: @That Would Be Telling

    Or they are waiting for a committee of outside experts — known as the Vaccines and Related Biological Products Advisory Committee, or VRBPAC, which I think meets December 11. But can’t they move the meeting up? The members are so busy, they can’t spare a few hours for Zoom videoconferences?

    I mostly agree with what you’re saying, even referenced you as having a good answer to another’s questions, but this is not a fair criticism. If the FDA isn’t going to just be a rubber stamp, they’re first going to read and analyze both Pfizer/BioNTech’s and the anticipated any day now Moderna Emergency Use Authorization (EUA) applications (really helps that they both use the same basic technology), then discuss them at that meeting, and then hopefully approve one or both of them for EUA uses.

  69. @Jack D
    @guest007

    Most vaccine recipients had few side effects and most of those were after the 2nd shot. I realize there are a lot of stupid people but if you have enough sense to get 1 shot then you can come back in 2 weeks. Sheesh, it's not that hard.

    Replies: @guest007

    Ask any occupational health or public health nurse abou having to hunt people down to have their TB test read. That is why many health departments have gone to using blood tests for TB since it is a single interaction with the individual of interest.

    There is probably good data on the Shingles VAccine that requires to doses to see who comes back.

  70. @anon
    @Hypnotoad666


    these controlled studies would be the perfect vehicle for testing the hypothesis that covid is simply not dangerous.
     

    Put another way, if the “end point” of efficacy was prevention of death, they would have to say the vaccines had no statistical efficacy. The virus itself is pretty efficacious in not killing people.

     

    I've given this a fair amount of thought. First, I look at the graphs in the WSJ, paying attention to the ratio of reported deaths to reported cases. Which is 1-2%.

    If a symptomatic reported case in the placebo group has a 1% chance of dying of covid, it is plausible in the control group that out of 90 reported cases, there will 0 deaths. Especially since they go to considerable effort to reject candidates with co-morbidities.

    And, it is logical that all covid deaths will (1) display symptoms (2) have a positive test (3) have a serious case and then (4) die. And since there were maybe 10% serious cases in the control group, if they kept running the trials, they would eventually start generating some deaths.

    So, in my opinion, the announced test results aren't substantially at odds with the announced/believed rates of death and serious cases.

    However, it is also striking that the virus, as you noticed, isn't very efficacious at killing people. Especially people who don't have serious co-morbidities or aren't close to dying of old age.

    But this virus is quite efficacious at triggering the leadership of moderately developed countries with modern medical systems to panic. Starting with Red China and much of the rest of the world including Russia.

    Replies: @Jack D, @epebble, @Jonathan Silber

    However, it is also striking that the virus, as you noticed, isn’t very efficacious at killing people. Especially people who don’t have serious co-morbidities or aren’t close to dying of old age.

    It really depends what “very efficacious” means. If the IFR is even 1%, that means 3.5 million deaths when applied to the entire US population. And yes these are disproportionately people not in perfect health – older, fatter, etc. But that describes a lot of us. Our medical system has gotten pretty good at keeping people with chronic conditions alive and most of them had a good few years left in them before Covid hit.

    • Agree: Johann Ricke
    • Replies: @anon
    @Jack D

    @Jack

    Your argument is reasonable enough. But the result, less so.


    In 2018, a total of 2,839,205 resident deaths were registered in the United States
     
    But it is not obvious where it is flawed. Even if we had done absolutely nothing, it doesn't seem plausible that the total number of deaths would have more than doubled from a typical year.

    Maybe because asymptomatic cases might be 40%-50%, so half the country would start out immune to death. Or maybe because you need to stratify the population before applying severity estimates. Which amount to similar sorts of adjustments.

    It may also be that the reported cases and deaths that we are looking at are too biased (unrepresentative) to be of much use.

    The number of officially reported cases is about 3% of the population.

    Replies: @Jack D

    , @Hypnotoad666
    @Jack D


    If the IFR is even 1%, that means 3.5 million deaths when applied to the entire US population.
     
    The CDC's latest IFR estimate by age group is: 0-49 (effectively zero); 50-69 (.5% IFR); 70+ (5.4% IFR -- Yikes!). https://www.cdc.gov/coronavirus/2019-ncov/hcp/planning-scenarios.html

    Taking the CDC death count data at face value, it's hard to overstate how overwhelmingly this is a disease of the 70+ cohort, who apparently comprise about 15% of the overall population. https://www.infoplease.com/us/population/population-65-years-and-over-age-1990-2000-and-2010

    It's like people have been saying from the beginning, why are we messing around with closing schools and restaurants instead of quarantining the 70+ people who are actually at risk.

    Replies: @That Would Be Telling

    , @Bill
    @Jack D

    IFR is lower than 1%. Estimates have been drifting lower consistently. 0.6% recently for the US. https://www.nature.com/articles/s41586-020-2918-0 figure 2, panel C.

    The early R0 estimates of 3ish are also looking pretty ridiculous at this point, given that Rt has been only modestly above 1 even though the US has done very little to arrest the spread of the virus.

    To get millions of deaths, you need an IFR near 1 and an R0 above 2 or something like that.

  71. @That Would Be Telling
    @epebble


    In none of the vaccine trials they have disclosed How many people died in the placebo group? If no one died in the placebo groups in the trials, I am not impressed with the success of the vaccine. What good is a vaccine if the persons who were not vaccinated did not die when 1.4 million people have already died due to the disease?
     
    anon[255] in the comment currently numbered 59 covers this pretty well. The number of people in the placebo groups are small as these things go, and there hasn't been much time for them to contract a fatal case; for the most recently enrolled, time measured in days and weeks (the hard rule for safety is that have the vaccine arm of the trials must be at 2 months after the 2nd inoculation). We could assume right now there might be a few serious cases in the placebo arms of the trials that might proceed to death.

    Replies: @Hernan Pizzaro del Blanco

    Most of the most in the trial are under the age of 45, and very few are over the age of 65. So the fatality rate should be about 1 in 900 of those infected. Thus far among the 3 studies less than 225 have been infected.

    • Replies: @That Would Be Telling
    @Hernan Pizzaro del Blanco


    Most of the most in the trial are under the age of 45, and very few are over the age of 65.
     
    "The" trial? Maybe this AZ/Oxford one, but at least one other has gone to the trouble of enroll a great many participants over 65, I believe Moderna has based on participant self-reporting in the media. We've also seen reporting that the older set have less side effects and less of an immune system response, the former likely because of the latter, but that the response is judged as "good enough." I bring that up because you can't have that data without "enough" elderly as test subjects.

    Thus far among the 3 studies less than 225 have been infected.
     
    OK, you now acknowledge there are multiple trials, but your total number is way off, it's more like ~170 each for the mRNA ones, plus whatever are in this AZ/Oxford one which is less far along by FDA standards. Given all the data we have, including how unlikely it is to kill even the elderly, the numbers are low enough over a very few months to reasonably expect no one will have died from COVID-19. Yet.
  72. @anon
    @Hypnotoad666


    these controlled studies would be the perfect vehicle for testing the hypothesis that covid is simply not dangerous.
     

    Put another way, if the “end point” of efficacy was prevention of death, they would have to say the vaccines had no statistical efficacy. The virus itself is pretty efficacious in not killing people.

     

    I've given this a fair amount of thought. First, I look at the graphs in the WSJ, paying attention to the ratio of reported deaths to reported cases. Which is 1-2%.

    If a symptomatic reported case in the placebo group has a 1% chance of dying of covid, it is plausible in the control group that out of 90 reported cases, there will 0 deaths. Especially since they go to considerable effort to reject candidates with co-morbidities.

    And, it is logical that all covid deaths will (1) display symptoms (2) have a positive test (3) have a serious case and then (4) die. And since there were maybe 10% serious cases in the control group, if they kept running the trials, they would eventually start generating some deaths.

    So, in my opinion, the announced test results aren't substantially at odds with the announced/believed rates of death and serious cases.

    However, it is also striking that the virus, as you noticed, isn't very efficacious at killing people. Especially people who don't have serious co-morbidities or aren't close to dying of old age.

    But this virus is quite efficacious at triggering the leadership of moderately developed countries with modern medical systems to panic. Starting with Red China and much of the rest of the world including Russia.

    Replies: @Jack D, @epebble, @Jonathan Silber

    they go to considerable effort to reject candidates with co-morbidities.

    That seems like a bad design of experiment to leave out the primary victims of the disease. If they had selected, say, 10,000 people with comorbidities each for vaccination and placebo, and after 2 months announced, 100 people have died in the placebo group but only 5 in vaccinated group, the impact of the vaccine would have been far more impressive in public mind and there would be far fewer people unwilling to get vaccinations.

  73. @Hernan Pizzaro del Blanco
    @That Would Be Telling

    Most of the most in the trial are under the age of 45, and very few are over the age of 65. So the fatality rate should be about 1 in 900 of those infected. Thus far among the 3 studies less than 225 have been infected.

    Replies: @That Would Be Telling

    Most of the most in the trial are under the age of 45, and very few are over the age of 65.

    “The” trial? Maybe this AZ/Oxford one, but at least one other has gone to the trouble of enroll a great many participants over 65, I believe Moderna has based on participant self-reporting in the media. We’ve also seen reporting that the older set have less side effects and less of an immune system response, the former likely because of the latter, but that the response is judged as “good enough.” I bring that up because you can’t have that data without “enough” elderly as test subjects.

    Thus far among the 3 studies less than 225 have been infected.

    OK, you now acknowledge there are multiple trials, but your total number is way off, it’s more like ~170 each for the mRNA ones, plus whatever are in this AZ/Oxford one which is less far along by FDA standards. Given all the data we have, including how unlikely it is to kill even the elderly, the numbers are low enough over a very few months to reasonably expect no one will have died from COVID-19. Yet.

  74. @anon
    @Hypnotoad666


    these controlled studies would be the perfect vehicle for testing the hypothesis that covid is simply not dangerous.
     

    Put another way, if the “end point” of efficacy was prevention of death, they would have to say the vaccines had no statistical efficacy. The virus itself is pretty efficacious in not killing people.

     

    I've given this a fair amount of thought. First, I look at the graphs in the WSJ, paying attention to the ratio of reported deaths to reported cases. Which is 1-2%.

    If a symptomatic reported case in the placebo group has a 1% chance of dying of covid, it is plausible in the control group that out of 90 reported cases, there will 0 deaths. Especially since they go to considerable effort to reject candidates with co-morbidities.

    And, it is logical that all covid deaths will (1) display symptoms (2) have a positive test (3) have a serious case and then (4) die. And since there were maybe 10% serious cases in the control group, if they kept running the trials, they would eventually start generating some deaths.

    So, in my opinion, the announced test results aren't substantially at odds with the announced/believed rates of death and serious cases.

    However, it is also striking that the virus, as you noticed, isn't very efficacious at killing people. Especially people who don't have serious co-morbidities or aren't close to dying of old age.

    But this virus is quite efficacious at triggering the leadership of moderately developed countries with modern medical systems to panic. Starting with Red China and much of the rest of the world including Russia.

    Replies: @Jack D, @epebble, @Jonathan Silber

    …they [designers of the drug study] go to considerable effort to reject candidates with co-morbidities.

    The effectiveness of vaccines against the flu in the group of persons elderly, weak, and sickly has in recent years been estimated to be as low as 20%.

  75. anon[255] • Disclaimer says:
    @Jack D
    @anon


    However, it is also striking that the virus, as you noticed, isn’t very efficacious at killing people. Especially people who don’t have serious co-morbidities or aren’t close to dying of old age.
     
    It really depends what "very efficacious" means. If the IFR is even 1%, that means 3.5 million deaths when applied to the entire US population. And yes these are disproportionately people not in perfect health - older, fatter, etc. But that describes a lot of us. Our medical system has gotten pretty good at keeping people with chronic conditions alive and most of them had a good few years left in them before Covid hit.

    Replies: @anon, @Hypnotoad666, @Bill

    @Jack

    Your argument is reasonable enough. But the result, less so.

    In 2018, a total of 2,839,205 resident deaths were registered in the United States

    But it is not obvious where it is flawed. Even if we had done absolutely nothing, it doesn’t seem plausible that the total number of deaths would have more than doubled from a typical year.

    Maybe because asymptomatic cases might be 40%-50%, so half the country would start out immune to death. Or maybe because you need to stratify the population before applying severity estimates. Which amount to similar sorts of adjustments.

    It may also be that the reported cases and deaths that we are looking at are too biased (unrepresentative) to be of much use.

    The number of officially reported cases is about 3% of the population.

    • Replies: @Jack D
    @anon

    The 1918 flu killed 50 million people worldwide including 675k out of 100 million in the US. The US now has 3.5x the population so 2.5 million US deaths would not be out of the question for an uncontrolled pandemic. For various reasons the pandemic has not raged in all states and cities simultaneously so the death toll is getting spread out over more than 1 year - it might take several years to get to 2.5 million. If the vaccines arrive and are taken by enough people this should cut the eventual toll considerably.

    Replies: @Hypnotoad666, @anon

  76. @That Would Be Telling
    @obwandiyag


    Inactivated and attenuated vaccines at least don’t have Frankenstein cooties in them.

    What about Sputnik V and the Sinovac vaccines?

    Provincial as ever, ain’t you?
     

    Don't be a jerk, especially an ignorant jerk. Sputnik V has "Frankenstein cooties," while Sinovac's CoronaVac is a killed/inactivated whole virus vaccine. As I read its Wikipedia page, it's only just now, like maybe last week, possibly getting the numbers needed for FDA level standards, 30,000 total Phase 3 participants. And maybe only enough for efficacy, not sure where it is on half of the vaccine arm having two months of experience after the second inoculation, which so far is taking longer than efficacy for the 3 most advanced in testing Western vaccines.

    Sputnik V is more than a month behind CoronaVac in starting its Phase 3 trials, and I guess you don't know the withering criticism it came under was due to it getting official approval in Russia a full month before its Phase 3 trial started on ~September 10th? I.e. we don't have any idea about its safety and efficacy based on large numbers of trial participants.

    But in theory it could be as good or better than the AZ/Oxford one, from the beginning they tried to sidestep the "react in dose two to the virus vector in dose one" known problem by using different human adenovirus vector for the first and second doses. But with it being as much or more a political stunt than a real vaccine effort, it's going to be hard for it to gain trust, probably harder than CoronaVac which is at least officially following the standard processes.

    Replies: @obwandiyag

    Troll Russia-basher.

    A lot of likely-sounding pseudo-academic babble. From the talking points memo.

    Got your number.

  77. @Jack D
    @vhrm


    Naturally acquired herd immunity is actually doing the heavy lifting in actually dealing with Covid,
     
    Unfortunately, some of the heavy lifting is being done by pall bearers. Acquiring immunity thru infection is doing it the hard way. And even now with 200,000+ dead, we are less than 10% of the way thru the population. By the time herd immunity is acquired without vaccines, you are probably talking 2 million dead. That's not chopped liver.

    Replies: @That Would Be Telling, @vhrm

    we are less than 10% of the way thru the population. By the time herd immunity is acquired without vaccines, you are probably talking 2 million dead.

    There’s virtually no reason to believe we’re that far inaway. The “confirmed cases” are a severe undercount. The first several months it was by a factor of 20x, now it’s probably less due to increased testing but still most cases ate probably not detected.

    The serosurveys that were supposed to tell us the actual incidence (which also somewhat undercount a little considering the time lag of development of antibodies etc but can be statistically corrected) basically haven’t materialized. I have no idea why. There was some excitement in March… then not much. We just mindlessly and swab hundreds of thousands of people for RPCR tests with little rhyme or reason instead.

    Also due to the heterogeneity of succeptibility on the network ( Tom Hanks / boho / Trump disease because they have many connections) the threshold for naturally acquired immunity to stop the spread of much lower than that for uniform vaccination. k prob on the 30% to 40%.

    Clearly we were already below the threshold for non flu season. That’s why or was dying out. Now it’s flu season and we’ll get to the higher threshold and it’ll start dying out well before the vaccine gets large distribution (is my guess. we’ll see how it goes)

    More importantly about those pall bearers:

    Those under age 50 who get infected with the coronavirus lose less than one day of discounted quality-adjusted life expectancy; seniors age 70 or older lose nearly 90 days.

    https://www.forbes.com/sites/theapothecary/2020/10/06/what-is-your-risk-of-dying-from-covid-19/?sh=37af8bb46159

    Yes that’s on average, (and I’m not in a position to vouch for the methodology but it seems plausible, though they are probably high since they don’t take into account, I believe, that the people who died were overall sicker and thus had lower expected life than avg people of their age)
    but at the scales of a whole society we have to look at since average impacts, we can’t just say “every life is infinitely precious”.

    Put in those terms, the government imposed lockdowns and trampling of civil liberties is nowhere near worth it, imo.

    BTW are you ready for the “reparations for essential workers” social justice movement that we’ll probably be dealing with for the next 2 decades?

    • Replies: @Jack D
    @vhrm

    These numbers were based on the assumption that Covid-19 deaths would not exceed 225,000. We've already passed 250,000 and are running at 1,500 deaths/day. Even if it abates at the end of flu season (end of February), just from now until then is probably another 150,000 deaths.

    To put it in perspective, the article also says: "For seniors age 70 and older, getting Covid-19 is riskier than climbing Mt. Everest." I don't know about you, but that sounds like a pretty serious risk to me. There's no way I would voluntarily undertake an Everest climb. And with Covid you don't even get a photo at the summit.

    Replies: @Herald

  78. @anon
    @Jack D

    @Jack

    Your argument is reasonable enough. But the result, less so.


    In 2018, a total of 2,839,205 resident deaths were registered in the United States
     
    But it is not obvious where it is flawed. Even if we had done absolutely nothing, it doesn't seem plausible that the total number of deaths would have more than doubled from a typical year.

    Maybe because asymptomatic cases might be 40%-50%, so half the country would start out immune to death. Or maybe because you need to stratify the population before applying severity estimates. Which amount to similar sorts of adjustments.

    It may also be that the reported cases and deaths that we are looking at are too biased (unrepresentative) to be of much use.

    The number of officially reported cases is about 3% of the population.

    Replies: @Jack D

    The 1918 flu killed 50 million people worldwide including 675k out of 100 million in the US. The US now has 3.5x the population so 2.5 million US deaths would not be out of the question for an uncontrolled pandemic. For various reasons the pandemic has not raged in all states and cities simultaneously so the death toll is getting spread out over more than 1 year – it might take several years to get to 2.5 million. If the vaccines arrive and are taken by enough people this should cut the eventual toll considerably.

    • Replies: @Hypnotoad666
    @Jack D


    For various reasons the pandemic has not raged in all states and cities simultaneously so the death toll is getting spread out over more than 1 year – it might take several years to get to 2.5 million.
     
    It seems hard to square some the CDC data and estimates with the idea that we are far from herd immunity.

    For example, the CDC officially estimates that: (a) R0 is about 2.5; (b) "Time from exposure to symptom onset*~6 days (mean); (c) "Time from symptom onset in an individual and symptom onset of a second person infected by that individual†~6 days (mean); and (d) Mean ratio of estimated infections to reported case counts, Overall (range)§ 11 (6, 24). https://www.cdc.gov/coronavirus/2019-ncov/hcp/planning-scenarios.html

    Oddly, the CDC doesn't list duration of infectiousness, but other sources say: "Most people with coronavirus who have symptoms will no longer be contagious by 10 days after symptoms resolve." https://www.health.harvard.edu/diseases-and-conditions/if-youve-been-exposed-to-the-coronavirus#:~:text=Most%20people%20with%20coronavirus%20who,there%20are%20documented%20exceptions.

    The CDC also says that 3.77% of Americans qualify as "reported case counts." https://covid.cdc.gov/covid-data-tracker/?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fcases-updates%2Fcases-in-us.html#cases_casesper100k

    If you put all this together, then supposedly 41.47% of Americans have already contracted covid. (3.77% case counts x ratio of 11:1 infections to case counts in (d), above).

    Moreover, each infected person supposedly infects 2.5 other people in ten days, who each infect another 2.5 people in ten days. That's like a 250% interest rate compounding every ten days. At that hyper-geometric rate the other 68.53% of Americans would all be infected in no time. And we would be hitting herd immunity before a vaccine could even be rolled out.

    Replies: @Bill

    , @anon
    @Jack D


    2.5 million US deaths would not be out of the question for an uncontrolled pandemic.
     
    Not out of the question, but I would say unlikely, if not implausible. And the 1918 flu killed 675k out of 100 million, so the population fatality rate was 2/3 of a percent. And that influenza was known for it's lethality. Which means that a lot of people either didn't get it or were partially immune. One of the distinguishing characteristics of corvid is that the oldest and least healthy victims still take 20 days to succumb, clogging up our critical care facilities.

    I agree with most of your larger points and have argued that the crisis should be handled with a greater sense of urgency. And the government is still not behaving like it is killing 1500 people a day. If 7 jetliners were crashing every single day, the Transportation Safety Board wouldn't be waiting around until a December 11 meeting to get recommendations from a public advisory board.

  79. @vhrm
    @Jack D


    we are less than 10% of the way thru the population. By the time herd immunity is acquired without vaccines, you are probably talking 2 million dead.
     
    There's virtually no reason to believe we're that far inaway. The "confirmed cases" are a severe undercount. The first several months it was by a factor of 20x, now it's probably less due to increased testing but still most cases ate probably not detected.

    The serosurveys that were supposed to tell us the actual incidence (which also somewhat undercount a little considering the time lag of development of antibodies etc but can be statistically corrected) basically haven't materialized. I have no idea why. There was some excitement in March... then not much. We just mindlessly and swab hundreds of thousands of people for RPCR tests with little rhyme or reason instead.

    Also due to the heterogeneity of succeptibility on the network ( Tom Hanks / boho / Trump disease because they have many connections) the threshold for naturally acquired immunity to stop the spread of much lower than that for uniform vaccination. k prob on the 30% to 40%.

    Clearly we were already below the threshold for non flu season. That's why or was dying out. Now it's flu season and we'll get to the higher threshold and it'll start dying out well before the vaccine gets large distribution (is my guess. we'll see how it goes)


    More importantly about those pall bearers:


    Those under age 50 who get infected with the coronavirus lose less than one day of discounted quality-adjusted life expectancy; seniors age 70 or older lose nearly 90 days.

     

    https://www.forbes.com/sites/theapothecary/2020/10/06/what-is-your-risk-of-dying-from-covid-19/?sh=37af8bb46159

    Yes that's on average, (and I'm not in a position to vouch for the methodology but it seems plausible, though they are probably high since they don't take into account, I believe, that the people who died were overall sicker and thus had lower expected life than avg people of their age)
    but at the scales of a whole society we have to look at since average impacts, we can't just say "every life is infinitely precious".

    Put in those terms, the government imposed lockdowns and trampling of civil liberties is nowhere near worth it, imo.

    BTW are you ready for the "reparations for essential workers" social justice movement that we'll probably be dealing with for the next 2 decades?

    Replies: @Jack D

    These numbers were based on the assumption that Covid-19 deaths would not exceed 225,000. We’ve already passed 250,000 and are running at 1,500 deaths/day. Even if it abates at the end of flu season (end of February), just from now until then is probably another 150,000 deaths.

    To put it in perspective, the article also says: “For seniors age 70 and older, getting Covid-19 is riskier than climbing Mt. Everest.” I don’t know about you, but that sounds like a pretty serious risk to me. There’s no way I would voluntarily undertake an Everest climb. And with Covid you don’t even get a photo at the summit.

    • Thanks: Johann Ricke
    • Replies: @Herald
    @Jack D


    “For seniors age 70 and older, getting Covid-19 is riskier than climbing Mt. Everest.”
     
    Not many over 70 seniors will be attempting Everest, so the Covid-19 death risk, on that basis, is negligible. In any event it is no worse than a normal seasonal flu.

    Those, that want to risk the hastily assembled hardly tested liability free vaccines, are simply playing a new form of Russian Roulette.

  80. @Anonymous
    I suspect the Oxford scientists are just being more honest, corporate Yanks lie through their teeth so I wouldn't trust their stats particularly. Same with Russians, Putin almost immediately announced the Sputnik V vaccine had a 90% efficacy rate after Pfizer had announced theirs did.

    The British academic establishment is too honest, and lacks the "Chutzpah" of the Yanks and Russians I think.

    Replies: @Anon, @Herald

    The British academic establishment is too honest, and lacks the “Chutzpah” of the Yanks and Russians I think.

    The above bears little relation to fact. The British Pharmaceutical company GSK, gets top marks, when it comes to paying fines and penalties for business malpractice.

    https://www.painnewsnetwork.org/stories/2020/11/17/glaxosmithkline-most-heavily-fined-drug-company

  81. @Jack D
    @vhrm

    These numbers were based on the assumption that Covid-19 deaths would not exceed 225,000. We've already passed 250,000 and are running at 1,500 deaths/day. Even if it abates at the end of flu season (end of February), just from now until then is probably another 150,000 deaths.

    To put it in perspective, the article also says: "For seniors age 70 and older, getting Covid-19 is riskier than climbing Mt. Everest." I don't know about you, but that sounds like a pretty serious risk to me. There's no way I would voluntarily undertake an Everest climb. And with Covid you don't even get a photo at the summit.

    Replies: @Herald

    “For seniors age 70 and older, getting Covid-19 is riskier than climbing Mt. Everest.”

    Not many over 70 seniors will be attempting Everest, so the Covid-19 death risk, on that basis, is negligible. In any event it is no worse than a normal seasonal flu.

    Those, that want to risk the hastily assembled hardly tested liability free vaccines, are simply playing a new form of Russian Roulette.

  82. @Jack D
    @anon


    However, it is also striking that the virus, as you noticed, isn’t very efficacious at killing people. Especially people who don’t have serious co-morbidities or aren’t close to dying of old age.
     
    It really depends what "very efficacious" means. If the IFR is even 1%, that means 3.5 million deaths when applied to the entire US population. And yes these are disproportionately people not in perfect health - older, fatter, etc. But that describes a lot of us. Our medical system has gotten pretty good at keeping people with chronic conditions alive and most of them had a good few years left in them before Covid hit.

    Replies: @anon, @Hypnotoad666, @Bill

    If the IFR is even 1%, that means 3.5 million deaths when applied to the entire US population.

    The CDC’s latest IFR estimate by age group is: 0-49 (effectively zero); 50-69 (.5% IFR); 70+ (5.4% IFR — Yikes!). https://www.cdc.gov/coronavirus/2019-ncov/hcp/planning-scenarios.html

    Taking the CDC death count data at face value, it’s hard to overstate how overwhelmingly this is a disease of the 70+ cohort, who apparently comprise about 15% of the overall population. https://www.infoplease.com/us/population/population-65-years-and-over-age-1990-2000-and-2010

    It’s like people have been saying from the beginning, why are we messing around with closing schools and restaurants instead of quarantining the 70+ people who are actually at risk.

    • Replies: @That Would Be Telling
    @Hypnotoad666

    In this and your following comment, you're putting a lot of trust in the CDC, which has been grossly incompetent at infectious disease control for a long time, part of a general problem with our public health establishment, that's no longer fashionable, they're rather be banning Big Gulps and guns. So I personally take all their data with large grains of salt, except for that which comes from death certificates, which requires its own set of considerations in interpreting.

    That said, you're not figuring morbidity into the picture, and we know it's a thing, see for example "long COVID", but I have no idea how bad for the population. I'm also not sure how you would quarantine 70+ old people, a lot of them are still in fairly good health, ambulatory, able to drive etc., oh, yeah, and lots are stubborn, even ornery.

    Yes, the vast majority of COVID-19 deaths in my area are from the 70+ cohort, and I think most of those were living in long term care facilities, but you should also do the numbers vs. time for all ages compared to hospital capacity, the ones that get seriously sick take up isolation beds, normal and ICU. Exceed that capacity, as for example is happening right now in my whole region out to 150+ miles in all directions, and patient outcomes get worse as they get parked in ER, plus there's the minor detail of people who need care for the "normal" things. Exceed it too much and death rates go way up, that's what "bending the curve" is about. Which my region is abjectly failing to do.

  83. @Jack D
    @anon

    The 1918 flu killed 50 million people worldwide including 675k out of 100 million in the US. The US now has 3.5x the population so 2.5 million US deaths would not be out of the question for an uncontrolled pandemic. For various reasons the pandemic has not raged in all states and cities simultaneously so the death toll is getting spread out over more than 1 year - it might take several years to get to 2.5 million. If the vaccines arrive and are taken by enough people this should cut the eventual toll considerably.

    Replies: @Hypnotoad666, @anon

    For various reasons the pandemic has not raged in all states and cities simultaneously so the death toll is getting spread out over more than 1 year – it might take several years to get to 2.5 million.

    It seems hard to square some the CDC data and estimates with the idea that we are far from herd immunity.

    For example, the CDC officially estimates that: (a) R0 is about 2.5; (b) “Time from exposure to symptom onset*~6 days (mean); (c) “Time from symptom onset in an individual and symptom onset of a second person infected by that individual†~6 days (mean); and (d) Mean ratio of estimated infections to reported case counts, Overall (range)§ 11 (6, 24). https://www.cdc.gov/coronavirus/2019-ncov/hcp/planning-scenarios.html

    Oddly, the CDC doesn’t list duration of infectiousness, but other sources say: “Most people with coronavirus who have symptoms will no longer be contagious by 10 days after symptoms resolve.” https://www.health.harvard.edu/diseases-and-conditions/if-youve-been-exposed-to-the-coronavirus#:~:text=Most%20people%20with%20coronavirus%20who,there%20are%20documented%20exceptions.

    The CDC also says that 3.77% of Americans qualify as “reported case counts.” https://covid.cdc.gov/covid-data-tracker/?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fcases-updates%2Fcases-in-us.html#cases_casesper100k

    If you put all this together, then supposedly 41.47% of Americans have already contracted covid. (3.77% case counts x ratio of 11:1 infections to case counts in (d), above).

    Moreover, each infected person supposedly infects 2.5 other people in ten days, who each infect another 2.5 people in ten days. That’s like a 250% interest rate compounding every ten days. At that hyper-geometric rate the other 68.53% of Americans would all be infected in no time. And we would be hitting herd immunity before a vaccine could even be rolled out.

    • Replies: @Bill
    @Hypnotoad666

    The ratio of cases to infections you use is much higher than recent data show. Your number, if you follow it back, is very old. You can find more recent stuff in the supplement, table e2, to this article: https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/10.1001/jamainternmed.2020.7976, which, btw, is cited on the CDC's seroprevalence page.

    They tabulate the data by state without a national average (and I am too lazy to do the calculation myself), but 2 or 2.5 looks like about the right number. This makes a pretty big difference.

    If you just look through the CDC's seroprevalence page, you'll see that, as of mid-September, seroprevalence in the US was below 10% overall. Even in New York, it was around 20%.

  84. @Hypnotoad666
    @Jack D


    If the IFR is even 1%, that means 3.5 million deaths when applied to the entire US population.
     
    The CDC's latest IFR estimate by age group is: 0-49 (effectively zero); 50-69 (.5% IFR); 70+ (5.4% IFR -- Yikes!). https://www.cdc.gov/coronavirus/2019-ncov/hcp/planning-scenarios.html

    Taking the CDC death count data at face value, it's hard to overstate how overwhelmingly this is a disease of the 70+ cohort, who apparently comprise about 15% of the overall population. https://www.infoplease.com/us/population/population-65-years-and-over-age-1990-2000-and-2010

    It's like people have been saying from the beginning, why are we messing around with closing schools and restaurants instead of quarantining the 70+ people who are actually at risk.

    Replies: @That Would Be Telling

    In this and your following comment, you’re putting a lot of trust in the CDC, which has been grossly incompetent at infectious disease control for a long time, part of a general problem with our public health establishment, that’s no longer fashionable, they’re rather be banning Big Gulps and guns. So I personally take all their data with large grains of salt, except for that which comes from death certificates, which requires its own set of considerations in interpreting.

    That said, you’re not figuring morbidity into the picture, and we know it’s a thing, see for example “long COVID”, but I have no idea how bad for the population. I’m also not sure how you would quarantine 70+ old people, a lot of them are still in fairly good health, ambulatory, able to drive etc., oh, yeah, and lots are stubborn, even ornery.

    Yes, the vast majority of COVID-19 deaths in my area are from the 70+ cohort, and I think most of those were living in long term care facilities, but you should also do the numbers vs. time for all ages compared to hospital capacity, the ones that get seriously sick take up isolation beds, normal and ICU. Exceed that capacity, as for example is happening right now in my whole region out to 150+ miles in all directions, and patient outcomes get worse as they get parked in ER, plus there’s the minor detail of people who need care for the “normal” things. Exceed it too much and death rates go way up, that’s what “bending the curve” is about. Which my region is abjectly failing to do.

  85. @candid_observer
    @kpkinusnnyphiladelphia

    My supposition is that if there were a possibility of fraudulent data, it wouldn't be as a result of any company wide conspiracy, but an individual or two at a critical stage in producing the data who, say, didn't want to lose their job or see their stock tank.

    I guess I do really doubt that this would take place, because it would be quickly caught, and would be self destructive. But, you know, think of Theranos.

    In any case, we need to keep our eyes out for further results from the vaccine. As the number of cases of covid grow in the recipients, we should get a much better idea as to the precise efficacy rates of the two dosage regimes.

    Also, I do wonder it there might not be a mechanism that would explain the lower efficacy rate for the 2.0 dose approach. Perhaps the first dose of 1.0 doesn't do enough to fully combat the disease as it is ordinarily contracted, but is enough to enable the body to destroy immediately the spike proteins introduced by the second dose, before they can induce changes in the antibody (or T-cell?) levels? A lower first dose, though, might allow the second dose to add onto the first. mRNA approaches, though, wouldn't seem to have that problem, because they introduce the spike protein indirectly, and cells have no reason or method to destroy the mRNA.

    Probably this speculation makes no sense for reasons obvious to those who understand such things. But I am not such a person.

    Replies: @kpkinusnnyphiladelphia, @Bill

    I guess I do really doubt that this would take place, because it would be quickly caught,

    I’m curious what mechanism you think would quickly catch it.

  86. @Jack D
    @Je Suis Omar Mateen

    There are some sad cases now involving people who have Covid but are Covid deniers so they keep calling it a hoax, Coronasniffles, etc. until their last breath and they miss out on the chance to say goodbye to their families. Even as they are literally dying from the disease they continue to deny that it even exists.

    Replies: @clyde, @The Last Real Calvinist

    Are you thinking of the ‘sad cases’ as related by that nurse from South Dakota? Her ‘testimonial’ has been blasted out across the world in the past few days.

    She was making it up:

    https://www.foxnews.com/media/cnn-silent-nurses-viral-patients-denying-coronavirus-deathbed-falls-apart

  87. @Anon
    @Anonymous

    You can bet that any information released by a publicly traded American pharmaceutical company has been legally vetted and is precisely accurate. On the other hand, and I don't know about the U.K., but any information about funded research released via the public relations office at an American university will be inaccurate and exaggerated. Look at the incentives and disincentives.

    The thing with corporate news releases, however, is that you have to read the original release very closely. THAT is what is accurate, not news reports about what it says. This is analogous to the law that anything printed by the National Enquirer is true, when closely read, but the innuendos may not be.

    Replies: @Bill

    You can bet that any information released by a publicly traded American pharmaceutical company has been legally vetted and is precisely accurate.

    Right. Any lying going on has been outsourced to the academic and contract labs who actually do the research.

  88. @Jack D
    @anon


    However, it is also striking that the virus, as you noticed, isn’t very efficacious at killing people. Especially people who don’t have serious co-morbidities or aren’t close to dying of old age.
     
    It really depends what "very efficacious" means. If the IFR is even 1%, that means 3.5 million deaths when applied to the entire US population. And yes these are disproportionately people not in perfect health - older, fatter, etc. But that describes a lot of us. Our medical system has gotten pretty good at keeping people with chronic conditions alive and most of them had a good few years left in them before Covid hit.

    Replies: @anon, @Hypnotoad666, @Bill

    IFR is lower than 1%. Estimates have been drifting lower consistently. 0.6% recently for the US. https://www.nature.com/articles/s41586-020-2918-0 figure 2, panel C.

    The early R0 estimates of 3ish are also looking pretty ridiculous at this point, given that Rt has been only modestly above 1 even though the US has done very little to arrest the spread of the virus.

    To get millions of deaths, you need an IFR near 1 and an R0 above 2 or something like that.

  89. @Hypnotoad666
    @Jack D


    For various reasons the pandemic has not raged in all states and cities simultaneously so the death toll is getting spread out over more than 1 year – it might take several years to get to 2.5 million.
     
    It seems hard to square some the CDC data and estimates with the idea that we are far from herd immunity.

    For example, the CDC officially estimates that: (a) R0 is about 2.5; (b) "Time from exposure to symptom onset*~6 days (mean); (c) "Time from symptom onset in an individual and symptom onset of a second person infected by that individual†~6 days (mean); and (d) Mean ratio of estimated infections to reported case counts, Overall (range)§ 11 (6, 24). https://www.cdc.gov/coronavirus/2019-ncov/hcp/planning-scenarios.html

    Oddly, the CDC doesn't list duration of infectiousness, but other sources say: "Most people with coronavirus who have symptoms will no longer be contagious by 10 days after symptoms resolve." https://www.health.harvard.edu/diseases-and-conditions/if-youve-been-exposed-to-the-coronavirus#:~:text=Most%20people%20with%20coronavirus%20who,there%20are%20documented%20exceptions.

    The CDC also says that 3.77% of Americans qualify as "reported case counts." https://covid.cdc.gov/covid-data-tracker/?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fcases-updates%2Fcases-in-us.html#cases_casesper100k

    If you put all this together, then supposedly 41.47% of Americans have already contracted covid. (3.77% case counts x ratio of 11:1 infections to case counts in (d), above).

    Moreover, each infected person supposedly infects 2.5 other people in ten days, who each infect another 2.5 people in ten days. That's like a 250% interest rate compounding every ten days. At that hyper-geometric rate the other 68.53% of Americans would all be infected in no time. And we would be hitting herd immunity before a vaccine could even be rolled out.

    Replies: @Bill

    The ratio of cases to infections you use is much higher than recent data show. Your number, if you follow it back, is very old. You can find more recent stuff in the supplement, table e2, to this article: https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/10.1001/jamainternmed.2020.7976, which, btw, is cited on the CDC’s seroprevalence page.

    They tabulate the data by state without a national average (and I am too lazy to do the calculation myself), but 2 or 2.5 looks like about the right number. This makes a pretty big difference.

    If you just look through the CDC’s seroprevalence page, you’ll see that, as of mid-September, seroprevalence in the US was below 10% overall. Even in New York, it was around 20%.

  90. In the meantime, Mr. Sailer, one of your fellow unz.com contributors is going off the rails. Too bad you don’t punch to the right to address her nonsense.

    https://www.unz.com/mmalkin/covidgate-part-two-clinical-trials-and-crusader-bias/#comment-4305178

  91. anon[320] • Disclaimer says:
    @Jack D
    @anon

    The 1918 flu killed 50 million people worldwide including 675k out of 100 million in the US. The US now has 3.5x the population so 2.5 million US deaths would not be out of the question for an uncontrolled pandemic. For various reasons the pandemic has not raged in all states and cities simultaneously so the death toll is getting spread out over more than 1 year - it might take several years to get to 2.5 million. If the vaccines arrive and are taken by enough people this should cut the eventual toll considerably.

    Replies: @Hypnotoad666, @anon

    2.5 million US deaths would not be out of the question for an uncontrolled pandemic.

    Not out of the question, but I would say unlikely, if not implausible. And the 1918 flu killed 675k out of 100 million, so the population fatality rate was 2/3 of a percent. And that influenza was known for it’s lethality. Which means that a lot of people either didn’t get it or were partially immune. One of the distinguishing characteristics of corvid is that the oldest and least healthy victims still take 20 days to succumb, clogging up our critical care facilities.

    I agree with most of your larger points and have argued that the crisis should be handled with a greater sense of urgency. And the government is still not behaving like it is killing 1500 people a day. If 7 jetliners were crashing every single day, the Transportation Safety Board wouldn’t be waiting around until a December 11 meeting to get recommendations from a public advisory board.

  92. @Jack D
    For those worried that them newfangled mRNA vaccines might impede your acceptance into heaven on the grounds that you are no longer fully human, the Oxford vaccine is based on a different technology.

    I am not qualified to pronounce on whether such a vaccine would endanger your immortal soul, but the way that it works is that it is made from a virus that is a weakened version of a common cold virus (adenovirus) that causes infections in chimpanzees, but which has been genetically modified so that it is impossible for it to grow in humans. The virus is live but sterile - it will only live for one generation. Genetic material has been added to this virus that causes it to make the Covid spike protein. Your body detects the spike protein and makes antibodies for it so the next time it sees the spike protein (attached to a real live 'rona virus) it is ready to attack it.

    So arguably, taking this vaccine does not turn you into Frankenstein because it is no different than catching a cold. There is genetic alteration going on, but the alteration is made in the cold virus, not you. Maybe the cold virus is no longer eligible for cold virus heaven?

    Replies: @That Would Be Telling, @kpkinusnnyphiladelphia, @Anonymous, @Macumazahn

    “There is genetic alteration going on, but the alteration is made in the cold virus, not you.”
    Quite. And it’s disingenuous to suggest that any concern about this difference must perforce be irrational.

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