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AstraZeneca’s US Vaccine Trial Data

Update: this has turned into a stupid, needless, mess. Which frankly seems to be AstraZeneca’s pandemic brand so far. It turns out that the company’s press release (as discussed below) is apparently more of an interim read than reflective of the final data. The NIH took the extraordinary step of stating its concerns about this late last night, and there’s all sorts of fallout today – see this article at the Washington Post for more. It seems clear that the final efficacy figure will be lower than the 79% quoted from the initial press release, and it seems clear – at least to me, and to a lot of other people – that handling the data in this way was a deliberate attempt to make that number look better. Anyone should know better than to try this, but especially a large, experienced, multinational drug company whose data handling during this vaccine’s development has already been the subject of a lot of (justified) criticism. I can’t think of a benign explanation, so unless we would like to assume that the company is so breathtakingly incompetent than they did this bizarre move for no reason at all, we’re left with bad ones. This is the sort of thing that gets high-level people submitting resignations and “pursuing other interests”. Isn’t it?

This morning brings news of new trial results of the AZ/Oxford vaccine, with results from the US, Chile, and Peru. This one has been a much more complicated and difficult story than it really should have been – at least, I think that’s how it’s going to look years from now. As you’ll likely remember, the initial trial results (from the trials in the UK, South Africa, and Brazil) were. . .well, they were a mess, and a good part of that mess was the way that they were presented to the world. Later results in a smaller group that had a longer dosing interval cleared things up a bit, but in recent weeks the focus (rightly or wrongly) has shifted from the efficacy numbers to the safety ones.

Now the new trial has shown 79% efficacy against symptomatic disease, and says that the vaccines showed 100% efficacy against severe disease and hospitalization. There’s always room to argue about that latter number, because the number of such cases is not large and the statistical power involved is invariably going to throw up a wide confidence interval on that 100% number. There were over 32,000 participants, with one-third of them in the placebo group. In this case, the press release mentioned 141 total symptomatic cases, and it’s come out this morning that there were 5 severe cases in the 10,000+ placebo group, versus zero in the roughly 21,000-patient treatment group. It’s worth remembering that the 95% confidence interval for the both-doses-completed group in the original trial data was 41% to 75% efficacy, so these new numbers are higher than people were expected based on that. But as mentioned, I would be careful about trumpeting a solid 100% protection in severe disease, for this or for the other vaccine trials – that said, that protection is obviously very strong, and that of course is good news.

What about safety? The review board specifically looked for thrombotic events of all kinds (as well they might after the recent reports from Europe), and saw no vaccine-related signals. But remember, this was about 21,000 people, so you’re not going to pick up something that’s real but happens at a very low level. And that’s where the arguing is, how many such events there have been in the vaccinated population, what different sorts of cardiovascular problems have been seen, whether they are above the levels you would expect to see in a general unvaccinated population, and (finally) just what those background levels really are. The dust is still in the air about all this, but I would not have expected this trial to help resolve these issues, which are down in the per-million-patients level.

If only the original trial data could have been as clear a readout as this one has been! Instead we had questions about overall efficacy, questions about subgroup analysis, about single doses versus two, half-doses versus full, intervals between doses, etc. All that is on AZ and Oxford. Now, they’ve had help muddying things since then, for sure. For example, a German bureaucrat misread the trial data and based on that a newspaper report spread the idea that the vaccine was only 8% effective in patients over 65, which was completely wrong. The latest arguments about safety have not always been conducted at the most honorable level, either, with accusations of nationalism and favoritism flying around. And back out in the world of real data, it appears that the vaccine is significantly less effective against the B.1.351 variant (although to be sure, the other vaccines are also less effective to some degree against it as well).

No, the going never would have been smooth, but it didn’t have to be like this. There will be books about the way vaccines were developed and launched during this pandemic, and there’s enough material for one just on this vaccine in particular. But the latter chapters are still being formed: this vaccine should continue having a big role in knocking down this pandemic around the world. Today’s data give more confidence that it can do so.

 

255 comments on “AstraZeneca’s US Vaccine Trial Data”

  1. Andy K says:

    I’d maybe argue that the original results (essentially phase 2s) were Oxford’s fault, and the conclusive data was AZN’s – the benefits of big pharma’s experience designing registration trials and dealing with regulators, and not trying to answer 15 questions at the same time…

    Still – great news, assuming people can be persueded to take the thing.

    1. luysii says:

      Andy K — “”Still – great news, assuming people can be persueded to take the thing.”

      You can say that in spades. The readership is all in its own little world where the evidence is overwhelming that the vaccine should be taken when available.

      The problem is that the most vulnerable who need vaccines the most: e.g. minorities, the working class etc. etc. isn’t buying this and isn’t getting vaccinated. For more on this and a possible way to break through to them see

      https://luysii.wordpress.com/2021/02/23/600000-pandemic-deaths-in-the-united-kingdom/

      1. Shannon says:

        > evidence is overwhelming that the vaccine should be taken when available.

        This is unquestionably false light of the confirmed thrombosis issue in Germany and Norway.
        The risk from the virus is exponential with age so it makes sense to take it anyway if you are elderly but the 5 : 120k incident rate in Norway is alarming. They are still finding cases in Germany, last count was 13 : 1.6M.
        For all of these vaccinations there will be some age at which the risk from the vaccination exceeds the risk from the virus. This is why there is no currently approved vaccinations for children and there might never be and the crossover age could be as high as 45 or so – especially looking at the high incident rate in Norway.

        1. luysii says:

          An example of the unintended consequences of reducing the risk of an infrequent complication — [ Nature vol. 354 p. 255 ’91 ]. An amazing article places the blame for the cholera epidemic sweeping South America starting in Peru on a misguided application of an Environmental Protection Agency study implicating water chlorination as a cause of cancer. During the 80’s Peruvian officials, citing the EPA study, stopped chlorinating many of the wells in Lima. However, others say that the decision might have been based on economics than data.

          It’s comforting to know that the 3,516 who have died so far have been spared a long bout with cancer.

        2. Chris Phillips says:

          “For all of these vaccinations there will be some age at which the risk from the vaccination exceeds the risk from the virus.”

          If you’re trying to persuade people not to protect themselves from dying of COVID-19, you really need to show some evidence, rather than this kind of airy assertion.

          Because as far as I can see there are several orders of magnitude between the COVID-19 fatality rate at any age, and any hypothetical risk of fatality from vaccination.

          1. Adrian says:

            > If you’re trying to persuade people not to protect themselves from dying of COVID-19, you really need to show some evidence, rather than this kind of airy assertion.
            > Because as far as I can see there are several orders of magnitude between the COVID-19 fatality rate at any age, and any hypothetical risk of fatality from vaccination.

            Assuming no obesity or other preexisting conditions:
            1. What is the risk for a woman in her 20s to die of COVID-19 if infected?
            2. What is the risk for a woman in her 20s to die of COVID-19?
            3. What is the risk for a woman in her 20s to die of the Oxford/AZ vaccine?

            1. is very low, and 2. can be even lower than that by an order of magnitude by practicing social distancing and using proper FFP2 masks (mine are made in the UK).

            What are the sources for your bold claim that 3. would be “several orders of magnitude” lower than 2.?

          2. Chris Phillips says:

            Adrian

            I don’t think you read my comment properly. (Not that that’s surprising, based on past experience.)

            My whole point was that if anti-vaccine propagandists are claiming the vaccine is more dangerous than the disease and trying to frighten people into staying unvaccinated it is up to them to provide evidence for their claims.

            Give it a try for once.

          3. Adrian says:

            Chris Phillips, noone is eroding the trust in vaccines more than people like you.
            You are the evil antagonist to Frances Oldham Kelsey.

            If you frighten people into no longer trusting that approval ensures safety, the rational reaction by most people will be to reject vaccines unless convinced otherwise for a specific vaccine.

        3. WST says:

          Well, why not compare 1:1,000,000 event with similar probability of death per age group and tested positive. Here are official Swedish statistics, the important thing is the order of magnitude.
          Read it as: “in age group 0-9 years, 1 in 2,031 tested positive dies”

          Age group Positive/Death CFR
          Ålder_0_9 2 031 0,05%
          Ålder_10_19 20 475 0,00%
          Ålder_20_29 6 503 0,02%
          Ålder_30_39 3 891 0,03%
          Ålder_40_49 1 594 0,06%
          Ålder_50_59 426 0,23%
          Ålder_60_69 82 1,23%
          Ålder_70_79 11 9,17%
          Ålder_80_89 4 25,08%
          Ålder_90_plus 3 35,01%

          conclusions are obvious

          1. Stefano Franchi says:

            These are very weird statistics. Only 4 cases in the 80-89 yrs bracket in Sweden? And only 11 in the 70-79 bracket, compared to 20,400 in the 10-19 yrs bracket? Either Covid-19 infection in Sweden followed a very strange pattern or these data are deeply wrong. Either way, no conclusion can be drawn from these

          2. Marko says:

            Stefano, the first figure is not cases, it’s the ratio of positive cases per death , i.e., the reciprocal of the CFR.

          3. Alberto J. Villena says:

            That is a wrong question.
            The correct one is: what is the probability that a healthy 20-year-old woman will infect and transmit, directly or through others, the virus to an elderly person, who has a very high risk of dying from Covid-19?

          4. luysii says:

            Alberto J. Villena — exactly. My father, whose parents were immigrants, told be about ‘schloff schnellen must haben de bed’ — or sleep faster we need the bed, as immigrants back then as now packed themselves like sardines into tiny apartments to economically survive. This is exactly the case where I live now (45% Puerto Rican).

            Also, even though a 20 year old has a 1/2,000 chance of dying if she gets COVID19 — that’s still FIFTY times the one in a million chance of getting some hematologic complication from the vaccine.

          5. Andy Cooke says:

            Re the question: “ 1. What is the risk for a woman in her 20s to die of COVID-19 if infected?
            2. What is the risk for a woman in her 20s to die of COVID-19?
            3. What is the risk for a woman in her 20s to die of the Oxford/AZ vaccine?

            1. is very low, and 2. can be even lower than that by an order of magnitude by practicing social distancing and using proper FFP2 masks (mine are made in the UK).”

            Using https://www.medrxiv.org/content/10.1101/2020.07.23.20160895v7.full-text, and the 1.5:1 ration between male and female deaths, and the rate of hospitalisation in the UK, and the rates of Long Covid, then for a 25-year-old woman

            Deaths per million: 90
            Hospitalisations per million: 1,500
            Long Covid per million (exceeding 3 months) c.70,000-100,000

            As to whether they can avoid infection: unless herd immunity is reached, then when restrictions are dropped, sooner or later, the strong majority of us will be exposed. Either with vaccine protection or without. Maintaining masking and social distancing forever is not plausible.

            The risk of death from the AZ vaccine would be, IF there is a causal connection, around 1-2 per million, with maybe 5 per million risk of hospitalisation. Ergo the position points strongly to a woman in her twenties being orders of magnitude more at risk from covid seems strongly supported

        4. Roland says:

          “For all of these vaccinations there will be some age at which the risk from the vaccination exceeds the risk from the virus. This is why there is no currently approved vaccinations for children and there might never be”

          There’s currently no approved Covid vaccinations for children because none have been sufficiently trialled in children. That is, the risk is almost completely unknown, which is very different from knowing it exceeds the risk of the virus. For that matter the risk profile from long Covid in children is under-explored too.

          All the major vaccines are currently undergoing trials in children – some as young as 6 months – so there’s at least some expectation vaccinating them will make sense.

      2. stewart says:

        With regards to your previous blog post, I thought it was obvious by last April that the major source of introduction of SARS-COV-2 into the Americas was from Europe, especially Italy and Spain.

  2. Steve Scott says:

    It may not be needed in U.S.: NY Times: ” the vaccine is unlikely to become available before May, when federal officials predict that three manufacturers that already have authorization will be producing enough doses for all the nation’s adults.”
    Washington Post: “The one-shot Johnson & Johnson efficacy rate is 66 percent overall and 72 percent in the United States in preventing moderate to severe cases of covid-19, according to data presented to the FDA.”

    Some people may conclude, rightly or wrongly, that AZ is better than J&J in preventing severe illness. So there may be some pressure to use AZ. But it seems that the U.S. will soon have an oversupply. I suspect we might sell off or donate unneeded shots to third world countries.

  3. Duncan says:

    My Auntie had AZ a couple of weeks ago.

    Maybe things could and should have been different. This trial always had the feel of being a (very impressive) academic exercise rather than a big pharma job.

    But I don’t care to be honest. I’m going to be taking this soon enough in all probability. Let the academic community fight the rest out. I’m going to take it and be happy

  4. johnnyboy says:

    Getting a bit tired of the repeated bashing of the Oxford/AZ initial trial data release, it’s becoming a bit of a tedious trope. It could bear reminding all the armchair virologists/epidemiologists/clinical trial analysts that there was a pandemic going on, with litterally thousands dying every day, so the honus was on speed rather than having a neatly polished package with all the Ts neatly crossed. Yes errors were made, it’s been said hundreds of times – can we move on now ? Could also bear stressing that AZ had very little vaccine development experience, that they had to work with an academic outfit with little clinical trial experience, that they were dependent on outsourcing for a lot of the material production, that AZ in general is a little fish in the Big Pharma pond, with rather limited resources compared to behemoths like Pfizer or J&J. And despite that they managed to produce a decent vaccine in record time, while giants with a lot more vaccine experience (GSK, Sanofi) just floundered. And all this for little to no profit, which means this vaccine will contribute to immunising most of the world, while Moderna’s Bancel and his VC chums are raking in the dough , and Pfizer’s Albert Bourla is now the highest paid CEO in Big Pharma (and will likely be even more next year when revenue for their $40 vaccine kicks in). So perhaps mention that next time, along with all the bad bits?

    1. rab says:

      Well said on all counts.

    2. Med Chem says:

      Well said.

      1. Eric says:

        Agree wholeheartedly with that except the bit about the size of AZ. It is definitely “Big Pharma” although mostly small molecule.
        A large part of the problem with the data was, I believe, because their phase 2 kind of morphed into phase 3 as the good results rolled in and speed was of the essence.

    3. Adrian says:

      The University of Oxford administering half the intended dose to many volunteers in a trial was a shocking display of gross incompetence.

      Throughout summer last year the team at the University of Oxford did have the time to generate constant press coverage in Europe how fast and good their vaccine would save the world, so let’s not accept stress or time pressure as excuse.

      1. Roland says:

        It wasn’t actually incompetence. It was limitations of measuring equipment which gave conflicting readings and while they cleared up the discrepancy they trialled doses which they knew were either half or all of the intended dose out of caution, rather than a) risking giving full or double doses, or b) holding up the entire trial for months when every single day wasted meant dozens of extra Covid deaths. I cannot see a more competent decision to make in that circumstance.

        Obviously they had a lack of some precise vaccine manufacturing equipment. Again, that wasn’t incompetence but down to the fact they were, pre-pandemic, a university research department with very limited budget involved in methodical long-term vaccine research, not a big pharmaceutical company ready to push out a large-scale commercial vaccine at short notice (if there were even any of those).

        1. Adrian says:

          > when every single day wasted meant dozens of extra Covid deaths

          COVID-19 has already taught us many times that trying to do things fast instead of doing them right often makes them take longer while delivering worse results.

          I work in IT where attempts to speed things up by doing them fast instead of properly are a common cause of project failures, so I’ve seen this lesson being learnt the hard way many times in my life.

        2. WST says:

          “It wasn’t actually incompetence.”
          Nope, did not account for absorption of a solvent .

          “Oxford ran its own analysis for good measure. The university had been using a different method known as spectrophotometry, which measures viral material in liquids based on how much ultraviolet light the viral matter absorbs.”
          “The documents published in The Lancet confirm that the error lay with the Oxford researchers. A common emulsifier, polysorbate 80, used in vaccines to facilitate mixing, had interfered with the ultraviolet-light meter that measures the quantity of viral material, according to the documents. As a result, the vaccine’s viral concentration was overstated and Oxford ended up administering half doses of vaccine, believing they were full doses.”

          https://www.reuters.com/article/health-coronavirus-britain-vaccine/special-report-how-a-british-covid-19-vaccine-went-from-pole-position-to-troubled-start-idINKBN28Y0XQ

        3. Not-an-epidemiologist says:

          I’d argue that the bigger issue with the dosing mix-up was the way they sold this “serendipitous” error because their small post-hoc sub-group analysis gave them a golden 90% efficacy figure to sell to the media. The emphasis that they initially placed on that sub-group analysis was … unwise, at best. And it’s downright embarrassing in the light of what we know about all the other confounders for that sub-group.

          I’m grateful that they’ve made a cheap and safe vaccine, and will gladly take it when I get the chance (although of course I’d prefer Pfizer or Moderna in my arm if given the choice, as I think most people who’ve looked at the data would). The AZ vaccine is immeasurably better than no vaccine.

          But the way the trials were carried out hasn’t been very helpful, from anyone’s perspective.

          1. Mariner says:

            I’d certainly agree with this.

            Initially, it was the less than scrupulous British politicians who were all promoting the 90% figure with a bit of ‘vaccine nationalism’ but I was disappointed that those commenting from Oxford/AZ weren’t more circumspect with their claims. Their PR actions are at least in part to blame for some of the slings and arrows against the vaccine which seem to be coming from all sides at present.

    4. Danish vikingj says:

      1)
      Is it really fair to say that GSK and Sanofi “just floundered”?
      As I recall nobody knew if any of the vaccines would even work a year ago, or how much protection they would provide. Some were hoping for at least 50% protection. There are many more vaccines in the pipeline for COVID-19, and some will fail in trails some will not, and do we honestly know why?
      2)
      At the risk of upsetting a lot of scientist, it seems to me that the impressive part of the vaccine story is the large clinical studies and the fast ramping up of production. Whereas the actual “invention/development” of the vaccines is not really that big of a deal? Isnt it all well-established methods?

      1. Academologist says:

        To the second point: As Derek has pointed out before, this is the first time we’ve seen a purely RNA-based vaccine, and getting to that has taken decades of funding and several lifetimes of FTEs. The ongoing basic research into immunology, virology, and coronaviruses in particular shouldn’t be ignored. We’re fortunate that people had the foresight to do much of the research that was needed to develop these vaccines long before Covid-19 was even a thing. Think about that you see a clip of John McCain (RIP) criticizing the $1million funding to study the DNA of bears. From one angle, it sure sounds silly, but I think many obese individuals would like to know how to ‘activate’ their brown adipose during the winter. If only I could get three months off to hibernate and sleep the weight away…

        Back to your point though, one might argue that manufacturing is mostly standard plumbing and clinical trials are mostly just box checking. I certainly wouldn’t. Given the production timeline and the consequences of failure, I can only imagine how little sleep the production people have gotten this past year. I know enough clinicians that I’m familiar with how much sleep they’ve been getting. If anybody deserves a few months hibernation it’s them.

        1. Ian Malone says:

          Yes, AZ, Pfizer, Moderna, Novavax, Sputnik V. All platform technologies, intended in part for “plug-and-play” application (although as Derek’s past posts highlight even then it’s not truly “just take the sequence and hey presto”). Years in development to get to the point where it can be done reliably, and the technology to scale them up is also the result of research. Also the earlier work on coronaviruses after SARS and then MERS which allowed understanding where to go after in this one. The traditional routes to a vaccine are dead or attenuated virus, a process of trial and error. Sinovax is one, and if you think the earlier Oxford trial data was patchy then try to find good trial data on it.

          As for Ox/AZ, this is being seen in the context of the go-for-broke trial designs of Pfizer and Moderna, which has certainly delivered a clearly working vaccine, but also left us in the scenario where we may be unnecessarily vaccinating more slowly than we could because we don’t have a clear idea about dosing. That’s the real loss of the compressed time scale for development; the earlier phase work to refine ideal doses. The Oxford study tried to do the kind of subgroups and dose analysis that is often done, it just didn’t suit the race. The results were not flawed, just hard for people to understand.

    5. Lintonlad says:

      Couldn’t agree more!
      I do wish they’d charged a bit more though and put it to better trials, better production and MUCH better comms/PR/marketing!

    6. D says:

      I’m sure we’ll discover in the end the mysterious reason why the companies who sold their vaccines for profit got a consistently better US press than those who sold it at cost.

  5. D L Reid says:

    I had my first jab of the AZ vaccine last week. As a medical professional I made a point of insisting on it. Apart from a very sore arm I suffered no adverse affects.

    1. Charles H says:

      It’s the second injection that causes the intense reaction, though for me that just meant a sore arm for a week. … Well, sore, and I think the arm was running a fever, though the rest of me was fine.

      1. Jonas says:

        Not so for the AZ vaccine. Any reactions to the second shot will be much milder.
        It is interesting that it’s different from the mRNA vaccines -where you only seem to get some reaction after the 1st shot if you have had Covid.

  6. M says:

    The main reason, IMHO, to take any vaccine is because it’s very likely that it will keep you out of the hospital should you (unfortunately) develop a symptomatic case of COVID after being vaccinated. It’s a truth that some people are still going to get COVID even after they are vaccinated (all the clinical trial data and data from Israel show this), but the severity and need for hospitalization is proving to be greatly reduced for those that are vaccinated.

    Stay safe, everyone, and encourage people to get vaccinated if they are unsure.

  7. urb says:

    Well said.

  8. Patrick says:

    I’m a little surprised by the relative insouciance here (not from Derek, in the comments) over the B.1.351 (first found in SA) data. It’s limited data, but it’s *very bad*. I don’t think that I’ve seen the AZ vaccine induced neutralizing ABs lab tested against it, which seems weird since we’ve seen that for Pfizer and Moderna (and J&J and Novavax have significant real world trial data).

    Has anyone seen that analysis? Because what little we know is suggestive that it may offer very little protection – and given that, doesn’t it seem likely that places which use the AZ vaccine will A) still be vulnerable, and B) have to re-vaccinate everyone later anyway? There are worse problems to have, of course, and it will do great good despite that possibility.

    1. A Nonny Mouse says:

      They are already working on the booster shot for that variant.

    2. Oudeis says:

      Yeah, I’m definitely in wait-and-see mode with that. There’s definitely a possibility of bad things happening, but my reasonable hope is that among the vaccinated population, B.1.351 will not spread very quickly or cause severe illness, even if it isn’t largely shut down like we expect the previous variants to be. Fingers crossed, and fingers crossed that everything goes right with the boosters in the works.

    3. Jonas says:

      It’s not all about antibodies. It will be T cell and B cells preventing severe infection.
      NAb is all very well, but they will wane over time anyway on all vaccines -so the longer term protection is important too!

    4. Roland says:

      “Has anyone seen that analysis?”

      Yes, it’s carefully hidden in a pre-print ostensibly about the Brazil variant:
      ‘Antibody evasion by the Brazilian P.1 strain of SARS-CoV-2’
      https://www.biorxiv.org/content/10.1101/2021.03.12.435194v1

      “Neutralization titres against P.1 were similar to those against B.1.1.7 and only a minority of samples failed to reach 100% neutralization at 1:20 dilution of serum, considerably better than neutralization of B.1.351, where titres were reduced 7.6-fold and 9-fold for the BNT162b2 Pfizer and ChAdOx1 nCoV-19 AstraZeneca vaccines respectively.”

      (Note that this is with 3 week dose interval for Pfizer and 8-14 week dose interval for AZ, and N=25 in both cases). It’s roughly the same reduction seen in other tests of Pfizer and Moderna serum against the actual variants (not the artificial single mutation viruses Pfizer tried to fool people with).

      Despite Moderna and Pfizer’s claims otherwise I think it’s clear all vaccines are struggling similarly with the SA variant, at least relative to the high bar of efficacy they have against the other variants.

      1. Adrian says:

        > I think it’s clear all vaccines are struggling similarly with the SA variant

        All vaccines are struggling with the SA variant, but the Oxford vaccine has such a low protection left that the government of South Africa has already sold 1 million doses it had of that vaccine since it wouldn’t have made much sense to use that vaccine in their country.

        1. Mariner says:

          Based on that preprint, perhaps South Africa should sell their doses to Brazil. I’m sure you’d agree, Adrian?

        2. Chris Phillips says:

          Adrian

          Obviously the information just posted shows very similar reductions for AZ and Pfizer in respect of the South African variant.

          The trouble with the AZ trial data for South Africa isn’t that it demonstrates the minimal headline figure for efficacy, but that its statistical power is too low to allow efficacy to be estimated in any meaningful way. The confidence interval is huge, and largely overlaps with the UK/Brazil interval for the same dosing regimen.

          But God forbid you should let facts get in the way of your obsessive posting of any anti-vaccine propaganda you can think of.

      2. donjoe says:

        That wasn’t hidden so much as it was quoted from another study, which maybe doesn’t show quite what your excerpt says it shows:

        “The Pfizer-BioNTech vaccine serum induced 3.6-fold higher neutralization titers against the Victoria strain than the Oxford-AstraZeneca vaccine (p < 0.0001). Although the overall reduction of titers was quite similar, 7.6-fold versus 9-fold, respectively, because the AstraZeneca titers started from a lower base more of the samples failed to reach 50% FRNT titers against B.1.351 (9/25) than for the Pfizer vaccine (2/25)"
        https://www.cell.com/cell/fulltext/S0092-8674(21)00226-9?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867421002269%3Fshowall%3Dtrue

  9. bob says:

    do we know how long immunity lasts with any of the vaccines ? so we will have to re-vaccinate everyone later anyway ?

    1. PastTense says:

      A number of experts think we will be ending up with annual booster shots–partly because of decline in efficacy and partly to deal with new variants.

      1. x says:

        I don’t believe I’ve seen any experts claiming falling efficacy; that’s all come from the internet peanut gallery with no knowledge of immunology, reading articles written by “journalists” with no knowledge of immunology about falling antibody titers.

        But maybe I just missed it.

  10. Chris Phillips says:

    “Now the new trial has shown 79% efficacy against symptomatic disease, and says that the vaccines showed 100% efficacy against severe disease and hospitalization. There’s always room to argue about that latter number, because the number of such cases is not large and the statistical power involved is invariably going to throw up a wide confidence interval on that 100% number.”

    Yes, I think this is true of all the phase III trials, because of the small number of severe cases. I reckon that figure of 5 in the placebo arm and none in the vaccine arm would translate to an expected efficacy against severe disease of 90%, but with a huge confidence interval of 58-100%.

    1. Oudeis says:

      Thanks for crunching those numbers. I need to learn statistics again.

      That said, it’s not just one study of one vaccine. I believe none of the vaccine trials have had a severe case of COVID. Obviously you can’t just add them all together because they’re different vaccines, but five vaccines (Pfizer/BioNTech, Moderna, J&J, Oxford/AZ, and Novavax) all show apparent 100% effectiveness against severe disease. That seems improbable to me if the vaccines’ real effectiveness levels were down toward the bottom of the confidence interval you identify.

      Corrections on any of this are, as always, welcome.

      1. Tom Maguire says:

        A follow-up on the Pfizer experience in Israel tracked nearly 600,000 newly vaccinated.

        As you (we?) expect, there were some severe cases among the vaccinated even after their “fully vaccinated” cutoff of 7 days after the 2nd dose.

        They came up with a 92% efficacy for reducing severe disease. Like the Mandalorian, I like those odds.

        “The results show that in fully vaccinated individuals (7 or more days after the second dose), the risk of symptomatic COVID-19 decreased by 94% compared with the unvaccinated, while the risk of severe disease decreased by 92%. In the period immediately preceding the second dose (days 14-20 after the first dose), vaccine effectiveness was lower, but still substantial — the risk of symptomatic COVID-19 decreased by 57% in vaccinated individuals, and the risk of severe disease by 62%. While there was insufficient data to provide an estimate on the reduction in mortality in those who received two doses, data from 21-27 days after the first dose points to a substantial reduction in mortality as well.”

        https://www.eurekalert.org/pub_releases/2021-02/cri-reo022421.php

        1. Oudeis says:

          Thanks for the news. Agreed–I’ll take those odds. It’s astonishing how successful the vaccine work has been. The medicine Nobels for the next five years should just go to these teams, one at a time.

  11. petros says:

    I think some of the comments have reinforced my perceptions of the trial design, that these related more to the academics’ input. However, given the laudable aim of providing a novel vaccine at cost, such issues are of less import than efficacy and safety.
    The new study results clearly confirm efficacy, although the emergence of new variants may prove to be a problem for all the vaccines.

    The safety issues raising issues in Europe but not apparently the UK do prompt speculation that the issues may relate to batches from different sites. I would comment that I experienced no effects at all when I had my jab last month but do have friends who have had typical vaccination reactions.

    1. Adrian says:

      It is more likely the difference are different groups who got the vaccine in the UK and many EU countries.

      In many EU countries like Germany the Oxford/AZ vaccine was or is not even approved for elderly and was mainly given to care personnel and school/kindergarten teachers, other vaccines were used for elderly people.

      Data for the Oxford/AZ vaccine from the UK is mostly on elderly people who did not receive this vaccine at all in Germany, while German data for the Oxford/AZ vaccine is mostly on young women.

      1. Chris Phillips says:

        Adrian

        If you didn’t realise that wasn’t true when you first posted it, you certainly do now. The statistics were quoted to you only a few days ago.

        Seven million people under 60 have been vaccinated in the UK. . Only 1.6 people of any age have been vaccinated with AZ in Germany.

        1. Adrian says:

          Chris Phillips, comparing apples with oranges does not make your claims true.
          You imply the Oxford vaccine would have been the only vaccine used in the UK, which is not true.

          Half the vaccinations in the UK were with the Pfizer vaccine, which is the more common vaccine given to healthcare personnel in a hospital setup there.

          1. Chris Phillips says:

            “You imply the Oxford vaccine would have been the only vaccine used in the UK, which is not true.”

            Desperate stuff. Of course I’m implying no such thing.

            But AstraZeneca has certainly been used in more than half the vaccinations in the UK.

            Given a total of 7 million under-60s vaccinated in the UK, compared with 1.6 million of all ages vaccinated with AZ in the UK, it’s clear that many more people of that age group will have been vaccinated with AZ in the UK than in Germany.

            Why are you trying to mislead people?

    2. Charles H says:

      Well, I’ve also heard that the baseline value for deep vein thrombosis is underestimated, and based on old data, with a method of detection that is currently considered too insensitive. I find this highly believable, but I can’t think of a way to systematically correct for this kind of error.

  12. Dr. Victor Frankenstein says:

    I am wondering what is going on with adapting the existing vaccines to the new mutants. Technically, that should be easy to do. But will these need new mass trials before they can be rolled out? Are they already in production?

    1. A Nonny Mouse says:

      At least in the UK, they have said that a full trial will not be necessary.

      1. JS says:

        Both the FDA and EMA issued guidance for vaccines targeting variants a while back:

        http://www.fda.gov/regulatory-information/search-fda-guidance-documents/emergency-use-authorization-vaccines-prevent-covid-19

        http://www.ema.europa.eu/en/news/adapting-covid-19-vaccines-sars-cov-2-variants-guidance-vaccine-manufacturers

        No mass trials. Mainly tests for geometric mean titers and seroconversion rates. The former quite conservative.

  13. Bill says:

    So is there any more light shed on the suggested benefits of half-dose, or increased period between shots?

    1. Jonathan B says:

      I haven’t heard that there is trial of any sort on that. The US trial used a consistent protocol on all patients I believe, unlike the original UK one where various Phase 2 trials aimed at exploring dosing issues got incorporated into the Phase 3 trial.

      However the UK may eventually provide some real world information. Although back in January the government said it would use a 12-week dosing interval as part of the strategy to maximise coverage, in practice it seems that there will be a mix of intervals. When I got my first dose (AZ) I was given the appointment for my second shot at 9 weeks later. Friends report other intervals. Of course to get data it will need enough new infections after the summer to track the vaccination records of those that get a positive test despite previous immunisation.

      Nothing on dose size though, all UK patients are being given the standard full dose. However there is reportedly a trial exploring a mix-and-match approach of different vaccines for first and second dose, which some suggest might create higher efficacy.

      1. Mariner says:

        Any mention of the half dose situation was quickly dropped. It turned out that there was in general a longer delay between the doses with the group mistakenly given the half dose initially (probably as they tried to work out what had gone wrong and what should be done). It was the longer gap between doses which seemed to lead to improved immune response. Something which we’ve seen elsewhere with the J&J single dose vaccine so that might be something to do with adenovirus vectors. I do also recall reading that the Oxford team initially hoped it might be a one dose vaccine. Perhaps it could have been if they’d waited longer to test for the immune response in the early trials?

        Incidentally, I had my first dose of the AZ vaccine 9 days ago. I’m male and in my late 40s and have had a mild but persistent headache since shortly after the jab. In fact, I went to the doc at the weekend who checked my eyes, blood pressure, calves (for DVT) and so forth. He indicated it was highly unlikely to be CVST with just a mild headache but no other symptoms. If the headache remains at the end of the week, I’ll perhaps get a second opinion…

        1. A Nonny Mouse says:

          Interestingly, my daughter was on the Imperial trial. They followed up with a call after the second dose the day after. She said that she had a headache still which certainly set alarm bells going with several more calls over the next few days though she felt fine by day 3.

      2. stewart says:

        There have been announcements of a 11-12 week dosing interval. My appointment is for 11 weeks after the first jab.

        1. A Nonny Mouse says:

          16th Feb –> 4th May for me. Had to book the second dose at the time of booking the first though I am told that is not the case in Scotland (always have to be different).

          1. Mariner says:

            My second dose was booked at the same time as the first was booked. 12 weeks between the two doses – to the minute! My second dose will be at 10.06am on a Saturday morning in June.

  14. Alia says:

    Got my AZ shot a month ago, the next morning was pretty bad (like a bad hangover, really) but by the late afternoon I was ok. The second dose is scheduled for mid-May, hope I’ll get it then. And I do hope it will protect me at least from going into hospital, as right now we are in the middle of another wave and hospitals are bursting at the seams.

  15. Jonas says:

    Efficacy was clear from the beginning, even if the subgrouping, designed or accidental made it all have wider confidence intervals. Having a high proportion of healthcare volunteers also made them be exposed to higher viral loads than other trials -and critiques did not even acknowledge this. There nasty coverage it received by certain commentators even in the NYT, some blatantly anti-British in Wired, and playing straight into anti-vaxxers hands.

    On safety, I have to say that I am slightly concerned for AZ and J&J in that the signal for CVST could be real on a certain subset of the population (genetic factors? if indeed Norway and Germany is affected, but apparently not the UK)

    J&J recorded a case of CVST (specifically transversal sinus thrombosis) in healthy 25 year old male. FDA’s briefing calls for vigilance to be kept on thrombotic events given that there was an unbalance in this regard, with 2 cases being in the placebo group, and 6 in the vaccine group.

    AZ and J&J are similar vaccines.

    1. FrankN says:

      Jonas: I am not certain that the UK situation is so different. It might just be that UK practitioners didn’t know what to look out for, and thus reported cases differently.

      Here is some comparison of the Vaccine Analysis Reports annexed to the latest UK reporting. Both vaccines, AZ and BNTX, were given in similar number, so you would also expect incidence numbers to be similar. Maybe somewhat higher for BNTX, vaccination with which started earlier and allowed for longer observation.
      https://www.gov.uk/government/publications/coronavirus-covid-19-vaccine-adverse-reactions/coronavirus-vaccine-summary-of-yellow-card-reporting

      But, actually:

      – Thrombocytopenia: AZ 43, BNTX 24
      (that’s the key diagnosis discussed in Germany and Norway).

      Digging deeper – here some of the stuff that could be associated to (undiagnosed) bleeding in the brain:

      – Eye disorders (Total): AZ 2.499, BNTX 1.489
      including
      – Photophobia AZ 298, BNTX 107
      – Vision blurred AZ 333, BNTX 240
      – Vision Impairment/ blindness AZ 140, BNTX 96

      – Nervous system disorders (Total) AZ 49.655 BNTX 19.142
      including
      – Coordination and balance disturbances AZ 288 BNTX 125
      – Disturbances in consciousness NEC AZ 2.931 BNTX 1.471
      – Headaches NEC AZ 27.296 BNTX 9.404
      – Memory loss (excl dementia) AZ 93 BNTX 52
      – Mental impairment (excl dementia and memory loss) AZ 156 BNTX 95
      – Speech and language abnormalities AZ 72 BNTX 48

      – Psychriatic disorders AZ 4.046 BNTX 1.499
      including
      – Hallucinations AZ 335, BNTX 70
      – Depressive disorders & symptoms AZ 248 BNTX 122
      – Panic attacks and disorders AZ 59 BNTX 35
      – Suicidal and self-injurious behaviour AZ 15 BNTX 4

      Then, we have
      – Death and sudden death AZ 154, BNTX 117

      And, finally:
      – Vascular disorders (Total) AZ 1.843 BNTX 1.205
      including
      – Peripheral vasoconstriction, necrosis and vascular insufficiency
      AZ 362 BNTX 103
      – Peripheral vascular disorders NEC AZ 838 BNTX 538

      Any of the a/m symptoms has been 1.5-2.5 times more frequently reported in the UK for AZ than for BNTX. This looks like a pattern that at least deserves in-depth analysis by UK authorities.

      1. sgcox says:

        Can not find the exact numbers how many shots in UK are AZ or Pfizer, only numbers “ordered”.
        Ursula von der Leyen claimed last Friday that EU exported 10M vaccine doses to UK. It is AZ and Pfizer combined. As all Pfizer are made in Belgium, the Pfizer number administered in UK is much less than 10M.
        UK vaccinated 28M. That surely means at least 2>1 for AZ doses as a very conservative estimate.
        So your numbers are exactly as they should be if both vaccines are identical in terms of AE.

        1. FrankN says:

          UK vaccination statistics are not broken down by vaccine. The only figures you get are from the MHRA reports as the one linked above (Section 2, below Table 2). It says

          “As of 7 March, an estimated 10.9 million first doses of the Pfizer/BioNTech vaccine and 11.7 million doses of the Oxford University/AstraZeneca vaccine, had been administered, and around one million second doses, mostly the Pfizer/BioNTech vaccine, had been administered.

          The estimated number of doses administered differs from the estimated number of people vaccinated due to the different data sources used.”

          My impression, after reading the full report, was that MHRA isn’t particular happy with information availability on UK vaccinations.

          1. Jonas says:

            The figures you quote on how millions of vaccine have been given up to the report date seem reasonable, no?
            or are you talking about stating how many people vaccinated with which vaccine by age group?

          2. Jonas says:

            MHRA weekly report’s latest update is available now.
            It lists 5 sinus thrombosis for AZ and 2 for Pfizer.
            Incidentally, traverse myelitis -which was another scare story of the pandemic is 10 for one vaccine, 11 for the other.

        2. Chris Phillips says:

          “Ursula von der Leyen claimed last Friday that EU exported 10M vaccine doses to UK. It is AZ and Pfizer combined.”

          It’s perhaps worth noting that in response to Ms von der Leyen’s latest not-very-veiled threats against the UK, it was stated by AstraZeneca that only one small batch of their vaccine had been exported from the EU to the UK, and that had not yet been quality tested (and therefore not yet used).

        3. Jonas says:

          No, as of the last report available the number of vaccines by each of Pfizer an AZ given in the UK are very similar 10 /11 million of each. It is trie that in the last weeks AZ has been given more and that trend is likely to continue.
          The mild adverse effects are definitely worse for AZ after dose 1. As people get second doses of Pfizer those side effects are likely to be more pronounced on that booster (whereas it will be much milder for AZ booster).

          I don’t buy the “British doctors are incompetent and can’t diagnose CVST” argument. If there is something it maybe a genetic factor, worsened by younger people having been prioritised to have AZ in most EU countries and Norway. In itself a stupid decision as one dose of AZ is better than 1 dose of Pfizer -which paradoxically leaves many oldies without apparent antibodies until the booster .

          1. FrankN says:

            My point was not “British doctors are incompetent and can’t diagnose CVST”. My point was and is that it is much easier to find something, if you know what to potentially look out for.

            Ten days ago, there had been “six plus one” German CVST cases reported to PEI. Yesterday evening, it were sixteen. Not because there had been nine new incidences over the last week. But because some German doctors, with the CVST theory out, took the time to review their files (and possibly check available blood samples more thoroughly) and came up with a CVST diagnosis for their cases.

            British doctors are compentent, and will most likely do the same. In fact, they already seem to do it, if I interprete the MHRA note on “two additional cases reported after the report had been finalised” correctly.

  16. Philip says:

    Four vaccines and three different spike proteins. This is from memory, so please forgive me if I am wrong. The Pfizer and Moderna mRNA vaccines produce a spike protein that has been modified to stay in the prefusion state. The J&J vaccine produces a spike protein that has the same modifications as the mRNA vaccines and has the fearon cleavage site deleted. The AZ vaccine uses the wild type spike protein.

    My WAG is that if there is a very rare thrombotic problem with the AZ vaccine, it is because of the differences in the spike protein.

    1. Jonas says:

      yet there was an actual case of transverse sinus thrombosis (a manifestation of CVST) in a 25 y/o participant in the J&J trial (see FDA briefing). Could have been coincidental of course -but overall number of thromboembolic events in the vaccine group was higher (6) than placebo (2) so FDA raised this so a potential signal.

  17. PastTense says:

    raps.org shows 13 Covid-19 vaccines authorized somewhere in the world and 58 vaccine candidates in development (with 3 of these no longer being studied). I had been expecting a lot of these candidates to stop being developed, but it hasn’t been happening so far. Any thoughts as to how many vaccines the world will end up with?

  18. FUanon says:

    Plenty of evidence that people that have had the virus and get the vaccine have more side effects. Covering this up means you are s$$$ leadership.

  19. Marko says:

    This is getting ridiculous :

    “Late Monday, the Data and Safety Monitoring Board (DSMB) notified NIAID, BARDA, and AstraZeneca that it was concerned by information released by AstraZeneca on initial data from its COVID-19 vaccine clinical trial. The DSMB expressed concern that AstraZeneca may have included outdated information from that trial, which may have provided an incomplete view of the efficacy data. We urge the company to work with the DSMB to review the efficacy data and ensure the most accurate, up-to-date efficacy data be made public as quickly as possible.”

    https://www.nih.gov/news-events/news-releases/niaid-statement-astrazeneca-vaccine

    1. PastTense says:

      The New York Times has an article about this press release, but it still is not clear exactly what problem the monitoring board has:

      https://www.nytimes.com/live/2021/03/22/world/covid-vaccine-coronavirus-cases

    2. A Nonny Mouse says:

      It was someone on this blog a while ago that said the AZ vaccine would never be approved in the US as the not for profit model is an anathema to their healthcare system. Seems that they are trying hard to make it so.

      At least the vaccine can go to Canada and Mexico.

      1. sgcox says:

        It was me and unfortunately current events only reinforce my view.
        This dangerous socialist idea that human life should not be commercialised is anathema and should be exterminated before it gets any hold in US.
        Even if FDA approves Oxford/AZ vaccine, the negative campaign in the media will make sure that people will refuse to take it and hospitals to administer. It does not matter how safe and effective it is. It just has to be stopped.

        1. Oudeis says:

          There’s an enormous amount of healthcare provided in the U.S. by not-for-profit hospitals. Some quick Googling suggests that a majority of large U.S. health insurers are not-for-profit entities, and of course tons of U.S. medical research occurs at not-for-profit universities.

          And I fail to see how supposed U.S. suspicion of not-for-profit medical research forced the Oxford/AZ team to release the wrong data, which they admit to.

          Please get your facts straight and stop slandering my country. There are plenty of bad things you can say about us that are actually true, so if you want to badmouth us, please stick to those.

          1. Don't kid yourself says:

            “Not for Profit” describes the tax status of a legal entity, not it’s ethics or behavior. Many of these large institutions are at least as concerned with perpetuating and growing themselves as they are with any sort of public service.

          2. Oudeis says:

            Don’t kid yourself either. The same is just as true of Oxford and AZ.

          3. Marko says:

            Ox/Az selling their vaccine for a fifth of what Pfizer and Moderna charge. That’s how you distinguish the real non-profits from the posers.

          4. Oudeis says:

            Pfizer and Moderna ran competent trials and reported their full results. Ox/AZ ran a crappy trial and then, after running a new one, announced misleading interim data, apparently to make their vaccine look more effective than it really is. Did they do that for altruistic reasons? Why isn’t that the way you separate the good guys from the posers?

            Plus, the small differences in price–large in relative terms, maybe, but small in absolute per-dose terms–are small potatoes compared to the brand goodwill and intellectual property all these firms are trying to get out of this. All of them are trying to do good, and all of them are trying to take advantage. From where I sit, Pfizer and Moderna are succeeding better at the “doing good” part, and I do not mind at all if they succeed better at taking advantage.

          5. Marko says:

            “Plus, the small differences in price–large in relative terms, maybe, but small in absolute per-dose terms…”

            Haha. Show me the math on that one. I’m sure it’ll be “priceless”.

            The idea of a non-profit vaccine is to prioritize getting a shot into billions of arms at an affordable cost, rather than prioritizing the enrichment of shareholders and company execs.

        2. ab says:

          sgcox, I’m gonna guess you’re not from the US, or if you are, you don’t read the news much. The US main stream media absolutely loves anything non-profit, anything European, and especially anything that makes US pharma companies look bad. Single-payer/socialized medicine would have been here a long time ago if the NYT writers were senators. As far as I can tell, they’re a bit confused about how to handle the apparent success of the US vaccine effort so far. If there’s a way to spin it to make bigevilpharma into a pariah again, they’ll find a way.

          1. Marko says:

            “Single-payer/socialized medicine would have been here a long time ago if the NYT writers were senators. As far as I can tell, they’re a bit confused about how to handle the apparent success of the US vaccine effort so far.”

            How much does an individual pay for a vaccine in the US? Zero, zip, nada. How does that happen? The US gov’t picks up the tab , using the single payer/socialized medicine model, as do other civilized countries. The difference between those other countries and the US is that once the pandemic is over, the US will go back to being uncivilized

          2. AVS-600 says:

            Do you mind pointing out some examples of the “confusion” here? As far as I’m aware, the vaccine is available freely (though maybe that’s not true in all 50 states). When I got my first dose, I didn’t even have to present health insurance information, I just signed up, went to a community center, and showed my ID.

            In general, I think anyone trying to apply the circumstances of the pandemic to ANY long-term political position is going to be pretty tough. But, without making a judgment on the absolute veracity of either statement: “our system of giving away the vaccine for free has been very effective” isn’t in any contradiction to “socialized medicine delivers acceptable health outcomes”.

      2. WST says:

        “the not for profit model ” – the terms of AZ agreement with Oxford U and governments are secret so the business model’s details are not known. It seems that “not for profit” has a time limit.
        Most likely AZ issues have compromised their future profits model, but it’s bit naive to think AZ is a socialist charity that the evil capitalists have to annihilate by all means.

        https://www.ft.com/content/c474f9e1-8807-4e57-9c79-6f4af145b686

        1. stewart says:

          The reports I saw said “for the duration of the pandemic”.

          1. WST says:

            “for the duration of the pandemic”.

            The FT article says that AZ decides when the pandemic is over…could be as early as 1/7/2021.

      3. Jack says:

        AstraZeneca received $1.2 billion from the U.S. government for testing, manufacturing, and supply of their vaccine. The government ordered 300 million doses. The vaccine is likely to be approved, and if it is approved, it will be used.

    3. debinski says:

      AZ seems determined to shoot themselves in the feet repeatedly. Hard to imagine what the “outdated information might” be.

      1. debinski says:

        OK, not so hard to imagine after some googling:
        Fauci told ABC News’ “Good Morning America” on Tuesday that the Oxford-AstraZeneca shot is “likely a very good vaccine.” However, he added, the DSMB became concerned that the data in AstraZeneca’s public statement “were somewhat outdated and might, in fact, be misleading a bit.”

        In response, AstraZeneca said that the figures published Monday “were based on a pre-specified interim analysis with a data cut-off of 17 February.”

        Apparently the most recent data don’t look as good. Not a great way to start the EUA review process.
        https://www.cnbc.com/2021/03/23/covid-us-health-agency-casts-doubt-over-astrazeneca-vaccine-data.html

        1. bud says:

          these reports should be done behind closed doors ,
          AstraZeneca today announced interim results of their phase 3 US study, notice the words interim results

        2. hob says:

          As the trial is continuing, there will be more data available already, which could alter the results at least slightly.

          AstraZeneca said it did not expect that to be the case. The data since 17 February was consistent with the interim analysis it had outlined on Monday. “We will immediately engage with the [DSMB] to share our primary analysis with the most up-to-date efficacy data. We intend to issue results of the primary analysis within 48 hours,” the company said.

        3. Doug H MD says:

          let me just say that the real problems with their data are not even being mentioned.

          1. Marko says:

            Don’t leave us hangin’ , doc. Enlighten us !

          2. bud says:

            https://www.statnews.com/2021/03/23/mishaps-miscommunications-overshadowing-astrazenecas-covid-vaccine/

            suggests updated data vaccine efficacy of 69 -74 rather than 79 does it really matter?

        4. Chris Phillips says:

          The Washington Post article linked in Derek’s update gives a fullish picture of what happened. Apparently the “headline” efficacy figure was 79% for data up to February 17, which was the figure released by AstraZeneca. But the monitoring board had considered that figure “unstable” because a large number of possible and probable cases remained to be adjudicated. (The implication seems to be that these data were not released to the company by the board.)

          The data to March 16 showed efficacy of 75% and the board advised these should be released to the company, but strongly recommended 33 remaining possible and probable cases should be examined, as these decisions could potentially reduce the efficacy to 69%.

          So if the company has gone ahead and released the 79% figure the board’s frustration is understandable (though it wasn’t the board that went public; it wrote to the company and copied the letter to the NIH, which went public).

          It’s puzzling that the company is saying the full data are consistent with the press release. Obviously the change from 79% to 75% over a month won’t be statistically significant, but that’s scarcely the point.

          https://www.washingtonpost.com/world/astrazeneca-oxford-vaccine-concerns/2021/03/23/2f931d34-8bc3-11eb-a33e-da28941cb9ac_story.html

          1. Not-an-epidemiologist says:

            That’s very interesting context.

            The fact that AZ has managed to run out the full analysis in only three days suggests that they probably could have waited — and they were clearly being encouraged to do so. Three days of extra analysis, only a 3% drop in overall efficacy, and an increase in the efficacy for elderly participants … whoever made the decision to release the interim analysis must be looking pretty foolish at this point.

  20. Adrian says:

    Chris Phillips, noone is eroding the trust in vaccines more than people like you.
    You are the evil antagonist to Frances Oldham Kelsey.

    If you frighten people into no longer trusting that approval ensures safety, the rational reaction by most people will be to reject vaccines unless convinced otherwise for a specific vaccine.

    1. Chris Phillips says:

      Adrian

      You’re pathetic.

  21. idiotraptor says:

    I’d like to digress for a moment from the contentious comments that now all too often follow Derek’s excellent posts. Is any one else struck by the unending display of graphic, macro-lens enhanced, fear-inducing photos showing needles partially inserted into people’s arms? As a life-long diabetic well-acquainted with injections, I am convinced that many media outlets employ stock photos showing large-gauge needles, unlike those used for COVID-19 vaccine injection, being filled from content vials. Just wondering.

  22. David Cockburn says:

    No doubt some of the negativity about the AZ vaccine is driven by the mediocre quality of the initial studies and by the political spillover from Brexit but I can’t help suspecting that much is due to price. The AZ vaccine is so much less expensive than it’s competitors that there’s a huge temptation to disparage it as interfering in their making a great deal of money from the pandemic. Ill advised decision driven by Oxford university.

      1. Chris Phillips says:

        That’s very good, but is it really feasible to screen everyone before they are vaccinated?

        Does anyone who understands these things see anything in that press release to indicate whether the mechanism they have identified will apply only to the AstraZeneca vaccine? Or only to viral vector vaccines?

  23. sgcox says:

    This is the last thing we need :
    https://www.bbc.co.uk/news/health-56483445
    Now the antimaskers can run around sneezing and coughing and saying “we are protecting people!”

  24. MTK says:

    The main problem here is not a scientific or technical one, but a trust issue.

    AZ has screwed things up so badly and repeatedly it’s now hard to take anything they say or report at face value. I think (don’t know) the vaccine to be safe and effective. To what degree on both counts I have no idea because AZ has used up any credibility currency they had.

  25. JeffC says:

    I am reliably informed that the terms of the AZ-Oxford deal contain a defect veto on all PR from Oxford. Every press release contains their fingerprints. The Jenner Institute is filled with great scientists, but egos are….substantial. And they want it to be clear that is they who are saving the world…..

    1. sgcox says:

      Oh, yes. Despite my adamant support of Oxford/AZ vaccine I sometimes cringe reading or listening.

  26. Danish vikingj says:

    This is my understanding of the situation regarding the AZ vaccine. There are two possibilities:

    i) There are no side effect with the AZ vaccine and there was never any justification for pausing the roll out (sure, there might be some very rare and minor side effects, as can never be completely ruled out with any drug ever.)

    ii) There are likely serious, but very, very rare side effects (thrombotic events) that may justify pausing the roll out in certain situations. For example, in countries with very good control of the virus and where fatalities are generally very low it could be argued that a slower roll out may theoretically result in only a very few additional fatalities among older people, whereas there is a real risk that not pausing may result in few fatalities among possibly middle aged individuals?

    Comments?

    1. Some idiot says:

      Hmmm… my thoughts (I also live in Denmark):

      (i) I think this has unfortunately been ruled out now. Sounds like the effect is real, although there are a lot of very important questions that it raises…

      (ii) From the Danish perspective, given that the AZ vaccine is not the main one being used here, this sounds about right. This is also probably one of the reasons why the health authorities here did not reduce their original 2 week pause (speaking of which, I will be very interested to see what Søren Brostrøm says in the next few days…). Another reason for that decision was probably the generally excellent job people have been doing here in terms of keeping infection rates flat, despite the fact that the UK variant is now >95% of the cases. For countries which are very reliant on the AZ vaccine, the maths here would probably point in a different direction.

      From the link an earlier poster put in to the diagnostic work that was performed by a German team (I can’t remember who), it seems now to be settled that the vaccine can cause activation of platelets in a very, very small group of patients, who are therefore would probably need to be treated after vaccination. But this, to me, gives rise to a number of other important questions:

      1) is there a similar effect with the Pfizer/BioNtech vaccine? Moderna? J&J?

      2) why on earth do we see such an apparent difference between patients vaccinated in the UK vs EU?

      3) Is it different reporting in the UK? I doubt it, particularly since we have seen vaguely similar results from a heterogeneous EU, and I have confidence in the NHS. For that matter, I have great confidence in the Danish health authorities, but that is another matter.

      4) is the effect due to differences in the vaccine produced in UK vs EU? I really, really doubt this, but I would be interested to know if anyone has a more informed view on this. In related news, the AZ vaccine produced in Australia has just been approved, so it will be interesting to see what happens there.

      5) If 2 is real, but 3 and 4 are false, then what is the cause of the discrepancy? If I was grasping for straws before, then I really start now… Genetics? No, the UK is pretty heterogeneous, so that wouldn’t make sense…

      1. Danish vikingj says:

        Maybe differences in production batches is the best guess right now?

        Early in trails, there was one instance of an adverse reaction to the AZ vaccine, but it was not revealed if it was thrombosis?:
        https://www.statnews.com/2020/09/08/astrazeneca-covid-19-vaccine-study-put-on-hold-due-to-suspected-adverse-reaction-in-participant-in-the-u-k/

        Btw: Here is a link to the German study on how the AZ vaccine may trigger thrombosis:
        https://www.dw.com/en/astrazeneca-german-team-discovers-thrombosis-trigger/a-56925550

      2. Another Idiot says:

        OK, Some Idiot,

        I’m going to purely speculate here and just throw out some ideas with no basis in anything real. (That’s my way of saying I’m talking out my a** here because I really have very little knowledge in biology.)

        In response to your questions 1 and 4.

        1. Very interested if there are any differences between the mRNA vs the adenovirus vaccines in this regard.

        4. If the adenoviruses show some increase in clotting, then are there differences in the sources of the chimp adenoviruses used in the UK and EU and are there differences in those batches? Just asking because of all the things in the vaccines I’m guessing that the actual adenoviruses may be the most difficult to fully and completely spec, but I don’t really know if that’s true. You must be able to genotype it to try and ensure its the same, but since I’m not a biologist I don’t know how much variance there is in that, meaning how representative is the genotyping of the actual batch and does PCR amplification result in starter bias.

        1. sgcox says:

          The AZ virus vector is absolutely identical in all production sites. It is not a live actual virus which can somehow mutate in a wild but a specific construct manufactured for vaccine production in specifically engineered cell line. The reported problems in Belgium is the sluggish growth and yield which hampers the volume produced, not the product.

          1. Another Idiot says:

            Once again, not my area of expertise, but the very fact that there’s some variance in growth and yield, does not give me a great deal of confidence. Something is out of control as a process chemist would say.

            Not saying that may be the source of whatever we may be seeing, just saying it’s a difference.

          2. Some idiot says:

            @sgcox, yes, I agree that the vector is identical. However, it is clear that the process is _not_ identical, due to the problems observed. I am a scale-up process chemist (albeit small molecule, not biologics), and the bane of my existence is small site-to-site (or, indeed, reactor-to-reactor) differences that lead to differences in process efficiency that are difficult to impossible to predict beforehand. Yes, all the software that is available these days to predict/optimise mixing/stirring from one reactor to another makes an absolutely huge difference. But still things slip through. I can understand from discussions from colleagues in biologics that small differences in mixing in tanks used for (eg) fermentation can have an enormous effect on the the process (mass-transfer of the cells themselves, nutrients and gas phases is extremely complex and can be critical).

            So my heart really, seriously goes out there to all those trying to get the system to function correctly, under incredible pressure and (essentially impossible) time constraints. I know what that pressure is like (for small molecules), and I wouldn’t wish it on my worst enemy.

            But the simple fact is that there _are_ differences in the way the process operates, simply because it _is_ sluggish (compared to the UK site), and the filtration _is_ problematic (compared to the UK site). Those factors being the case, it is inevitable that the “soup” at the end differs compared to that from the UK site. The really interesting question is as to what sort of an effect this difference will make to the end product. My very strong feeling is “not much”, because I believe that the people working on it have done a good job. I really do doubt (very strongly, actually) that this is the case. The only reason I still entertain the idea at all is that I find it difficult to reconcile the differences between the EU and UK experiences with the vaccine.

            I should also put on record that I believe that the AZ vaccine is both safe (with a very low level of side effects) and an incredibly important one for fighting the pandemic. I am just really, seriously curious as to why we see this UK/EU difference…

          3. sgcox says:

            UK also uses vaccine made in India. 5M doses have been delivered and further 5M delayed as India joined “vaccine wars”. 5M is a large enough number to pick up rare events and data certainly recorded and exist in NHS. Would be interesting to see but very unlikely right now unless someone on top pushes for it.

          4. Some idiot says:

            I didn’t know that, and I agree completely that it could be very interesting to see whether or not there are differences, particularly since it would be “different production sites, same population.” Having said that, I think you are right in that it is unlikely to be made available…

      3. sgcox says:

        Actually, 5) can make sense if we assume it is a some rare genetic predisposition in a relatively more homogenous Denmark population as compared to heterogeneous UK.

        1. Some idiot says:

          Very true, if the observations were confined to Denmark (Denmark is certainly very genetically homogeneous compared to other EU countries, and especially UK). Also, Norway can be seen to be genetically pretty similar to Denmark. But given that it has been seen in other EU countries as well, this suggests not… Unless there is some scandinavian genetic factor that is present in the cases outside the nordic countries. Would be interesting if anyone does such a check…!

          1. A Nonny Mouse says:

            Wasn’t there a high incidence of narcolepsy in the Scandanavian countries with a certain vaccine?

          2. Some idiot says:

            Hmmm I hadn’t heard about that… Do you remember what vaccine that was? Could be very interesting to look into…

          3. sgcox says:

            Pandemrix

      4. jule s says:

        I’m going for 4) and specifically contaminated production batches….

        The Greifswald team have likened the AZ vaccine induced immune thrombocytopenia (VITP) to heparin induced thrombocytopenia (HIT), where negatively charged heparin activates the platelets by binding to PF4, which then triggers an autoimmune response against the platelets.

        So what could trigger the autoimmune response in the case of the AZ vaccine? People have proposed the spike protein, the adenovirus vector,…
        But, how about Gram- bacterial lipopolysaccharides (LPS)?
        1) LPS are negatively charged polyanions that form immunogenic complexes with the positively charged chemokine platelet factor 4 (PF4) resulting antibodies can trigger ITP (DOI: 10.1182/blood-2012-06-434985).
        2) AZ (or more accurately their motley crew of subcontractors) have had a lot of problems with getting acceptable yields for their adenovirus vector cultures, especially for the batches produced in the EU.
        It is well known that low-level bacterial contamination reduces yields in cell cultures. Low-level bacterial contamination leads to low level LPS contamination, which is very difficult to get rid off later in the purification and difficult to check for during (non-biological) quality control.

        I do not have access to the QC tests done for the different batches of the AZ vaccine, so the above hypothesis might be easy to refute….

        1. Marko says:

          The QC checks for LPS, which are very sensitive (LAL and/or ELISA) should preclude this, but at a time of such vaccine scarcity, there might be pressure to release borderline batches that otherwise wouldn’t pass muster. It seems to me that they could check the final product to see if any lots are contaminated, in which case we should hear about it eventually. I agree that it’s a possibility that should be investigated.

          Evidence of substandard QC would probably be the straw that broke the camel’s back for AZ. They can’t afford any more mistakes.

          1. jule s says:

            The Brits are doing “stability tests” on a batch of 1.7 million doses. I would really like to know what those tests are. Unfortunately, everything to do with the vaccination in the
            UK cannot be made public under “national security” grounds.

      5. A different idiot says:

        (i) I think this has unfortunately been ruled out now. Sounds like the effect is real

        I don’t believe this has been ruled out. The EMA did not find a causal link in their investigation. The problem here is that the underlying statistics are uncertain – this is a rare disease, possibly under-reported (until people start looking very closely, for example at those who have recently been vaccinated). Also I believe Covid infection can also cause these clotting problems, so it’s not as if we can rely on historical baselines.

        Finally there are a LOT of very rare diseases out there. It’s not unexpected that one or two of them show an elevated occurrence in a small population of vaccine recipients just by chance. Those will disappear when you look at a bigger group, which is what might have happened here.

  27. sgcox says:

    Exiting news from Pfizer
    https://www.pfizer.com/news/press-release/press-release-detail/pfizer-initiates-phase-1-study-novel-oral-antiviral
    This is a first proper oral anti-Covid drug in clinical trials. Not the HCQ/Zinc/whatever nonsense.
    And yes, yes, profits from vaccine helps to finance such projects. 🙂

  28. Kaleberg says:

    The thing to compare is the overall death rate in the two arms of the study. There are all sorts of dangerous things I do that can sometimes make me safer, for example, riding in an automobile to be seen by a doctor when I am seriously ill. Thousands of people die every year riding in automobiles, but serious illness can be fatal. Life is full of tradeoffs. I probably wouldn’t parachute jump to my local clinic when seriously ill, as there are all sorts of reasons that is a bad idea.

    1. Marko says:

      “The thing to compare is the overall death rate in the two arms of the study.”

      That would be nice to know for all of the vaccines, but you’d have to use the post-rollout data to get a read on it, as there are too few deaths in the trials to say much. You can use severe disease or hospitalizations as a proxy :

      https://pbs.twimg.com/media/ExGonlbVkAA8lqk?format=png&name=small

      1. Rob Sutherland says:

        Thanks Marco!
        That is a a great graphic!
        And thanks to all the other folks that put reasonable discussion of the science ahead of all the BS!

        I apologize for any naivety, but leaving aside all the issues with the trial data AZ have likely f….d up, how important is it at this point?
        The AZ vaccine has been EUA’d in a lot of places (in some cases literally months ago) and has been administered to tens of million folks in the UK and EU and beyond.
        Arguing about the last dot and comma from Phase III data collected on the fly is so ‘last year’ right now.
        Real world data show that this vaccine is about as safe as any other and as about effective as any other wrt dealing with the bad stuff (serious disease, hospitalizations and death).
        Dealing with the ‘bad stuff’, although largely forgotten in the ludicrous ‘efficacy sweepstakes’ is entirely why we initially developed these medicines. Absent the latter, there is no reason for all the lockdowns etc., that the Pandemic has imposed on us all.

        Links provided initially elsewhere on this excellent blog:
        1. https://onlinelibrary.wiley.com/doi/10.1002/ajh.26132?af=R
        2. https://ashpublications.org/blood/article/109/7/2832/125650/Adenovirus-induced-thrombocytopenia-the-role-of
        3. https://nltimes.nl/2021/03/21/experts-found-astrazeneca-vaccine-may-cause-blood-clotting-disorders
        4.https://www.medizin.uni-greifswald.de/fileadmin/user_upload/Aktuelles/2021/Corona/Therapie_Thrombosen/PI-16-2021-Universitätsmedizin-Greifswald.pdf

        suggest that the very rare clotting issues that have dominated recent media coverage:
        1. Are not limited to the AZ vaccine.
        2. Not even limited to covid-19 vaccines.
        3. Are beginning to be properly understood by good science as it gets a handle on the likely cause(s) of these rare adverse events.
        3. There are well-established clinical protocols out there that can obviate the worst effects of this HIT-like thrombocytopenia phenomenon.

        Comments?
        best
        r

  29. Peter says:

    I wonder when the shareholders will demand changes in the top management. AstraZeneca was in a great position to get a stellar reputation, but they keep messing things up, and Soriot himself has contributed to that too. Their shares could have soared, yet they’re crumbling.

  30. bob says:

    https://www.scribd.com/document/498427839/Janssen-Ad26-COV2-S-Vaccine-EUA-Critical-Review
    Relates to the JNJ EUA data…. hardly instils confidence in how any of these vaccines have made their way into people.
    Just reported in Spain is another death associated with AZ vaccination in a 26 year old med student – resulting in tragic and severe loss of life years. Was this caused by the AZ vaccine? (vaccine death deniers will say there is no established link, that these things happen all the time – common sense calls absolute BS on that and now the deniers will also have to disregard the science behind an elucidated MOA for these events occurring – beyond belief!). We will unfortunately probably see many more of these events in the coming months.
    The basic tenet of approving a medicine is based on risk – benefit – now lets look at both sides. Benefit is questionable in younger age cohorts, the length that any benefit lasts is unknown and any the proven absolute reduction in risk of death is fractional and based on clearly twisted numbers in trial data. Let’s not forget that the virus is mutating and variants cannot be contained so vaccination really shows nothing to remove any practical real world benefit. Current impressive efficacy data in locked down populations is not the real/old world. The risks both short and long term safety and efficacy of these vaccines are not understood, it wouldn’t take nostradamus to predict that the efficacy figures will not hold up as variants inevitably spread and continue to emerge.
    Vaccine lunacy and hysteria has infected the world, let’s pray a real catastrophe of disease enhancement doesn’t happen in the future. It’s all we can do now as the literature has shown this happening with other corona viruses (but Covid-19 is somehow special so it couldn’t possibly happen? If it does, it will happen on a massive scale).
    In the JNJ EUA there is a report of death in the vaccine cohort – one looks suspiciously like it could have been caused by a PE but this wasn’t deemed a COVID death but could it have been due to the vaccine? Why wasn’t this properly investigated?
    “Two deaths in the vaccine group were secondary to respiratory infections not due to COVID-19. A 61-year-old participant died of pneumonia on Day 24 following onset of symptoms on Day 13. A 42-year-old participant with HIV died on Day 59 following diagnosis of a lung abscess on Day 33. A 66-year-old participant died of unknown causes after waking up with shortness of breath on Day 45.”
    If the virus mutates to become much more lethal from a vaccine resistant (or vaccine enhanced?) zoonotic jump we have no defence

    1. Trurl says:

      From the linked “paper”:

      [quote]We have made it clear on many occasions that we are NOT anti-vaxxers.[/quote]

      This is the anti-vaxxer equivalent of “I’m not a racist, but…”, isn’t it?

      1. Some idiot says:

        The phrase “vaccine death deniers” doesn’t exactly inspire confidence either…

      2. JDK says:

        Took a quick look at the ‘paper’ too. Ugh. bob owes me some brain cells (but not his!)

    2. WST says:

      From the linked pdf “Janssen Ad26.COV2.S Vaccine EUA (Critical Review)”
      In the review table there is delicious attempt to scientific humour:
      several of:
      “benefit not proven, >99.97% effective”

      1. bob says:

        Bob says beware the black swan – precognition not required just common sense – those who look only at retrospective data will never imagine or see the future, plenty of those ilk on here. The self proclaimed cognoscenti laughed at those who forecast the recent financial disaster. This idiotic and completely futile attempt to beat a rapidly mutating, highly transmissible coronavirus is the biggest example I have ever seen of collective stupidity from seemingly educated people – our educational systems may be to blame for churning out sheeple who question not and swallow whole the fallacies that are fed to us. These vaccines just can’t and won’t work in the medium to long term and there’s clearly massive potential for this idiocy to completely backfire.

        1. Chris Phillips says:

          “sheeple”

          A bit of a giveaway.

  31. sgcox says:

    Updates from Vaccine War fronts:
    Italian police raided the factory near Rome and discovered 29 million doses of AZ vaccine allegedly to be shipped to UK. Hours later EU officials revealed that 16M were to be shipped to Belgium to distribute in EU and 13M are reserved for Covax initiative. This is getting ridiculous.

    1. Danish vikingj says:

      Sounds very strange. Who allegedly said they were going to be send to the UK?! The EU?

      1. sgcox says:

        Italian newspapers and other media.
        https://www.politico.eu/article/italian-authorities-discover-29m-oxford-astrazeneca-vaccine-doses-la-stampa/
        Yes, likely to be exaggeration/speculation but why send police in he first place ?

      2. sgcox says:

        OK, I read the story again and still can not believe my eyes.

        “This discovery comes as AstraZeneca comes under harsh criticism from the European Commission over shortfalls of vaccine deliveries, having widely missed its original delivery targets set in the EU’s advance purchase agreement. Its most recent promise is to deliver in the first quarter of the year 30 million doses — nearly equal to the amount found at the Catalent site.”

        So basically EU was sitting on the amount promised and actually delivered and still threatens to impose vaccine export restrictions.
        It is ether gross incompetence or malign intent by EU. Any other explanations ?

        1. Chris Phillips says:

          “It is ether gross incompetence or malign intent by EU. Any other explanations ?”

          A desperate attempt to deflect attention from the mess they’ve made of vaccine procurement?

          Not that that is exclusive of either of the other two.

    2. A Nonny Mouse says:

      The mad thing is that the UK only has 2m/week capacity for the AZ vaccine and the EU is wanting stocks from that as well.

      Prior to the outbreak, we only had one vaccine plant in Speke (Liverpool) making flu vaccine. All others were sourced from EU based producers. It was only with vast inputs of government money that we have anything at all (UK has put 10.6 billion into vaccines- for 65m people- and the EU about 3.5 billion for 400m people).

    3. jule s says:

      Could you please limit your posts to scientific discussions and avoid contaminating this board with your anti-EU conspiracy theories.
      Thanks.

  32. exGlaxoid says:

    Anyone know what PF-07321332 is? They are claiming it is a novel SARS-CoV2-3CL protease inhibitor in a press release, with pretty much no information in the release. I can find nothing on it.

  33. Rob Sutherland says:

    Last night I tried to respond to Marco re a nice graphic he linked to but Marco’s post and my response have been ‘disappeared’.
    So here is my second attempt:
    “Thanks Marco! That is a great graphic!
    And thanks to all the other folks that put reasonable discussion of the science ahead of all the BS!
    I apologize for any naivety, but leaving aside all the issues with the trial data AZ have likely messed up, how important is it at this point?
    The AZ vaccine has been EUA’d in a lot of places (in some cases literally months ago) and has been administered to tens of million folks in the UK and EU and beyond. Arguing about the last dot and comma from Phase III data collected on the fly is so ‘last year’ right now.
    Real world data show that the AZ vaccine is about as safe as any other and as about effective as any other wrt dealing with the bad stuff (serious disease, hospitalizations and death). Dealing with the ‘bad stuff’, although largely forgotten in the ludicrous ‘efficacy sweepstakes’ is entirely why we initially developed these medicines. Absent the latter, there is no reason for all the lockdowns etc., that the Pandemic has imposed on us all.

    Links provided initially elsewhere on this excellent blog:

    1. https://onlinelibrary.wiley.com/doi/10.1002/ajh.26132?af=R
    2. https://ashpublications.org/blood/article/109/7/2832/125650/Adenovirus-induced-thrombocytopenia-the-role-of
    3. https://nltimes.nl/2021/03/21/experts-found-astrazeneca-vaccine-may-cause-blood-clotting-disorders
    4.https://www.medizin.uni-greifswald.de/fileadmin/user_upload/Aktuelles/2021/Corona/Therapie_Thrombosen/PI-16-2021-Universitätsmedizin-Greifswald.pdf

    suggest that the very rare clotting issues that have dominated recent media coverage:
    1. Are not limited to the AZ vaccine.
    2. Are not even limited to covid-19 vaccines.
    3. Are beginning to be properly understood by good science as it gets a handle on the likely cause(s) of these rare adverse events.
    3. There are well-established clinical protocols out there that can obviate the worst effects of this HIT-like thrombocytopenia phenomenon.

    Comments?

    1. buddy says:

      you could argue the efficacy data for the AZ Oxford vaccine in the US trial are outdated anyway regardless of numbers since a longer interval between doses gives much improved efficacy

    2. Jonas says:

      Some evidence of vaccine effect, but such a low apparent incidence that it’s difficult to tell. More vigilance and data clearly needed.
      mRNA vaccines don’t seem to give the body as much of a “shock” as AdV ones. Could it be that the thrombocytopenemia is somehow milder with Pfizer and Moderna? Though worth checking if the more pronounced yet mild adverse effects post booster doses also mean a worse effect in rarer effects.

  34. Dan says:

    So I would like an honest thought as to which vaccine is safest for the following two scenarios:

    88 yr old women with a chronic flare condition from RA, unable to go off methotrexate. High Blood Pressure/High Cholesterol. (BMI within high normal)

    62 yr old male with an idiopathic heart condition of Bradycardia and Tachycardia along with Hemochromatosis/Hypothyroidism/Raynaurds syndrome/Essential Tremors/Intrinsic Blocking Factor. Only taking supplements/no prescriptions (BMI within high normal)

    I have talked to Doctors on both situations but would like an honest thought?

  35. exGlaxoid says:

    Pfizer vaccine appears safest and quite effective in almost every case, so if it is available, then I would take it. Moderna’s is quite similar but higher dose may lead to more side effects for same effectiveness.

    The Novavax vaccine is also quite good and appears safe, but not yet approved or tested in as many people yet.

    The AZ and J&J vaccines are quite similar and only about 70% effective, so not as good at preventing covid and may have more side effects, although one shot J & J is simpler (but one shot of either mRNA vaccine is likely as good or better effectiveness, just not approved for that.)

    All vaccines appear far safer than a chance at getting covid for people over 50. For children under 16-18, there is not enough data yet to warrant vaccination. For people between 18 and 50, the first available vaccine is likely the best, but there is a low enough risk from covid to not be in as much hurry to get it if you don’t have any pre-existing conditions that make you a bad covid risk, but you could wait until you can find the best vaccine for yourself.

    This is only my opinion, not a medical statement of fact. I got the AZ vaccine in a trial, and it was fine for me.

    1. Jonas says:

      Pfizer does appear to be the best overall on 2 doses -but don’t assume that one dose is good enough for mRNA vaccines -certainly not for Pfizer: The real world data from Scotland and England show a turn south for efficacy after about 30 days post 1st Pfizer dose -whereas still increasing for AZ. You are right that AZ and J&J are similar. To be honest, AZ could have been a single shot too.

      With Pfizer antibody response is boosted to 10 fold with booster -so it’s necessary.

      One thing to see longer term is which one last longer, particularly once antibodies have waned to a low level. Which one will have the best T cell and memory cell response?

      1. Marko says:

        “The real world data from Scotland and England show a turn south for efficacy after about 30 days post 1st Pfizer dose…”

        PHE is claiming a “plateau” post-35 days in the over-70 age group studied. The Siren study in HCWs shows no decline in effectiveness out to 56 days. Given wide error bars in each case, it’s too soon to say much about duration of protection with certainty :

        https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3790399

  36. Robb says:

    I’ve just read the article and all 160+ comments. This is a science blog? Then you know that for several decades labs have been trying to come up with a coronavirus vaccine and haven’t been able to do it. They failed the animal studies. The Covid vaccines didn’t do the animal studies in their rush to market. As one of you said: “ I work in IT where attempts to speed things up by doing them fast instead of properly are a common cause of project failures, so I’ve seen this lesson being learnt the hard way many times in my life.” Why risk a genetic material injection when Covid is so easily prevented with Ivermectin? Whoops-did I just mention a really cheap drug? Oh well. Early prevention saves lives. Ivermectin is being used in India, Africa, Egypt and other parts of the world. It is the answer to the media’s question why Covid death rates are dropping in Asia and Africa. It made sense to develop vaccines for smallpox and polio—we had no cures for them. But we have a cure for Covid. Ivermectin’s safety profile is strong. These vaccines? Harvard researchers just released a paper saying this new fangled mRNA actually can hang around a long time and actually can change your DNA. Where is your curiosity?

    1. donjoe says:

      Even according to the most favorable trial results Ivermectin is no more than half as good as vaccines at preventing severe disease and death due to COVID-19. Stop spreading misinformation, you can’t do with Ivermectin what you can do with vaccines.
      Where’s our curiosity? Where’s your elementary scientific literacy, that you would make such bold claims and not back them up with so much as a link to a single study?

      1. Robb says:

        Apparently you are unaware of the reports from physicians using ivermectin. You might start with FLCCC. You might check out the Senate hearing last November-December on the lack if early treatment in the US. You might also check with India, Africa and the other countries that have lowered their death rates with ivermectin.

  37. Marko says:

    The AZ kerfuffle turns out to be much ado about nothing:

    https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2021/azd1222-us-phase-iii-primary-analysis-confirms-safety-and-efficacy.html

    “76% vaccine efficacy against symptomatic COVID-19
    100% efficacy against severe or critical disease and hospitalisation
    85% efficacy against symptomatic COVID-19 in participants aged 65 years and over”

    NIAID should never have gone public with their complaint. This could have been handled more reasonably, and if had been Moderna or Pfizer rather than AZ, it would have been.

    1. Rob Sutherland says:

      Thanks Marco,
      Great find, as usual.
      Re your last sentence, I suspect you are correct!
      If anything, the point the monitoring board should have had an issue with would be the ‘100% efficacy against severe disease…’ as the numbers in that category were so small.
      No vaccine will be 100% effective at preventing the serious stuff.
      As per my earlier response, all this misplaced focus on the ‘efficacy numbers at preventing mild/moderate disease’ (from Phase III trial data), when real world data on effectiveness at preventing the serious stuff is the most important metric, still confuses me.

      1. Chris Phillips says:

        Yes – they really should put a confidence interval on that 100% figure, though I think all the vaccine developers have been saying this kind of thing in their press releases.

        I reckon that for severe disease (on a Bayesian calculation with a flat prior) the expected efficacy would be about 94%, with a confidence interval of 75-100%. As the STAT article says, Moderna had a larger number of 30 severe cases – still all in the placebo group – giving an expected value of 97% and a confidence interval of 88-100%. (But judging by the totals, these aren’t comparable definitions of severity anyway – Pfizer had only 10 in total, though the efficacy figures there are worse, with a wide interval, because 1 was in the vaccine arm. This looks like sheer bad luck, judging by the real-world estimates that have been coming out.)

        I think the additional data on severe cases make these results stronger on the whole than the ones released a few days ago.

        1. Marko says:

          Moderna did the very same thing as AZ. They touted their first interim results on Nov 17 (based on a data cutoff of Nov 7) when they could have waited just a few more days for the final data cutoff of Nov 21, by which time their total events had climbed from only 95 at the interim look to 196, and their “severe” cases climbed from 11 to 30.

          Nobody wondered why they didn’t just wait, because everyone was eager to see the data ASAP, just as they were for AZ.

          There’s a double-standard here, and nobody will convince me otherwise. This is standard, US mafia-style capitalism. I’ve seen it too many times, and it makes me sick.

          1. WST says:

            Just had a look at the Moderna 16/11 (94.5%) and 30/11 (94.1%) announcement and compared with similar AZ’s announcements.
            Moderna is explicit about “interim” analysis and the fact that there are still unresolved cases, 151-95=56
            ” First interim analysis included 95 participants with confirmed cases of COVID-19
            Phase 3 study met statistical criteria with a vaccine efficacy of 94.5% (p <0.0001)
            Moderna intends to submit for an Emergency Use Authorization (EUA) with U.S. FDA in the coming weeks and expects the EUA to be based on the final analysis of 151 cases and a median follow-up of more than 2 months "

            Nothing about unresolved cases in AZ 22/3 interim announcement but from 25/3 we can learn that there were 49 cases (of total 190).

            IMHO, these are not comparable cases.

          2. Not-an-epidemiologist says:

            The difference was that back last year, we needed the vaccines urgently and there was a desperate rush to get those interim analyses out (and arguably they should have been released earlier on fewer case numbers). Cases were also ramping up rapidly at that time (Pfizer and Moderna got swamped with their final case numbers in the space of about a week, as I recall).

            Right now, there’s no urgent rush to seek FDA approval. AZ can’t even meet its existing demand. The US has plenty of vaccine (apparently).

            It’s a completely different situation — unless I’m missing something here (and I really hope I am at this point).

          3. Marko says:

            AstraZeneca vaccine: Australia’s drug regulator dismisses questions raised in US about outdated data

            https://www.msn.com/en-au/news/australia/astrazeneca-vaccine-australia-s-drug-regulator-dismisses-questions-raised-in-us-about-outdated-data/ar-BB1eU1oP

            “…This minor issue would normally occur in private, and any sort of clarification would normally occur outside of the public arena.”

            The reason this wasn’t handled “normally” is because it was a calculated hit job. Australia didn’t take the bait. Other countries would be wise to follow their lead, as I suspect most will. They’ve seen these kinds of tactics from the US over and over again, from China 5G to Russian natural gas. At some point the scam stops working. Some, however, fall for it again and again, like Charlie Brown repeatedly hoping that this time, Lucy will play nice.

    2. Marko says:

      Pushing back against U.S. health officials, AstraZeneca says new analysis confirms efficacy of its Covid-19 vaccine

      https://www.statnews.com/2021/03/24/pushing-back-against-u-s-health-officials-astrazeneca-says-new-analysis-confirms-efficacy-of-its-covid-19-vaccine/

      “…Eric Topol, director of the Scripps Research Translational Institute, said that the results were “better than expected” given the clash between the DSMB and AstraZeneca. He added that he is “relieved since the world needs the vaccine badly.” ”

      Ha. After Topol and others have pissed all over the AZ vaccine, the world will have second thoughts about using it. Exactly as planned.

    3. Not-an-epidemiologist says:

      Hmmm … if this was so close, I’d love to know why AZ pushed out the interim analysis as a press release. It’s not like there was a massive rush to do this (unless I’m missing something?) — demand for the AZ vaccine is vastly outstripping supply at present without the US coming onboard, and the US isn’t running out of vaccines from other sources as far as I’m aware. If AZ were just a case or two away from reaching the 190 primary endpoint figure four days ago, surely they’d just wait? It’s not October 2020 any more.

      This is all really odd. There will be several very engrossing books on this in a few years’ time, I’d suggest …

    4. Jack says:

      AZ should not have published their interim data, but it was an even bigger failure for NIAID and Fauci to comment and leak the efficacy figures as low as 69%. In my mind, they caused real harm by this when the final efficacy exceeded the range given to the Washington Post.

      1. Chris Phillips says:

        I can see why they would feel they had to comment on the board’s strongly worded criticism rather than being seen as concealing it. But publishing that 69% figure does look very questionable. Based on the Washington Post information, it sounds as though that was a worst-case scenario if cases still to be checked all went the wrong way. Inevitably that is too subtle a point to have been communicated in most of the media coverage.

      2. johnnyboy says:

        If they had delayed the interim results, then you would have had a chorus of posts from the commentariat going “they are witholding their data, they are hiding something, there must be something wrong with the data, why can’t they being more transparent”. Damned if you do, damned if you don’t. When it’s been drilled by hundreds of articles that AZ are doing everything wrong, there’s no way they can win at anything, at least in the press/internet. But in the end I think most of the public doesn’t really give a shit about any of this, these are all tempests in armchair scientists teapots. People just want to go back to normal, and those who aren’t dumbfuck antivaxxers will take whichever vaccine they’re offered.

        1. Not-an-epidemiologist says:

          “If they’d delayed the interim analysis”… by what, three days? They’ve now released the final analysis, so any delays were clearly going to be minimal. It seems bizarre to release an interim analysis when you’ve already likely hit your primary end point. There was no pressing need to get this out a few days early.

          AZ was clearly advised to analyse the final potential cases prior to a press release, and they ignored that advice. I assume that’s because of incompetence from their PR department rather than anything more untoward, but to do this after everything else that’s happened seems very odd behaviour from a major pharma company.

          1. Marko says:

            “AZ was clearly advised to analyse the final potential cases prior to a press release, and they ignored that advice.”

            Since there remain unresolved pending “potential cases”, they’re still ignoring that advice, yet no more complaints after the most recent press release. There’s obviously some good reason for the delay in reporting those cases as part of the final analysis, and it would make sense to immediately release a complete interim analysis, and then a complete final analysis after a week or two, similar to the Moderna reporting progression. As it is, AZ will need to issue another release when they’ve resolved those remaining cases.

            This was a hit job. With many tens of billions in future vaccine sales at stake in the years to come, it’s not unexpected.

            If I was AstraZeneca, I’d publish the results and then tell the FDA to stick their EUA where the sun don’t shine.

          2. Not-an-epidemiologist says:

            It doesn’t sound as though the US needs the AZ vaccine (especially as J&J and Novavax come online — and both of those rank more favourably to AZ in just about every metric other than cost.) So, I doubt they’d honestly care. I don’t think this was a “hit job” (that sounds uncomfortably like a conspiracy theory) — it seems more like increasing frustration with a company that at the very least appears to be putting PR ahead of transparent science (remember the US trial halt last year).

            The thing I still don’t get is why AZ felt the need to rush the initial press release. As I’ve said, they’re already behind on fulfilling existing supply contracts (as the UK and EU know only too well, as they very publicly fight for the limited existing vaccine stock). They are making no money from this. They will be vaccinating most of the world with this vaccine, regardless of what the US wants or thinks, even without this trial data.

            Even if AZ felt that there was no rational basis for waiting and they needed to get this PR out for reasons only they are aware of — the risk vs. reward in deliberately ignoring your independent trial monitors instead of waiting a few days for the final analysis, seems way, way imbalanced in favour of risk. Why piss people off like this? Why almost wilfully invite criticism of your handling of the data, when there were already questions being asked about this from previous trials? It’s … nuts, and so pointlessly, stupidly, maddeningly counterproductive.

      3. Rob Sutherland says:

        Jack, I think the biggest reason AZ released the interim report was to show the safety of the vaccine, given all the scary stories about very rare blood clotting issues.
        They would be damned if they had not released this interim data and severely scolded if they did not. As Marco and others have pointed out here (what a great resource this blog is!!) Moderna played the same game, without a word of reprimand.
        I think the now widely held narrative that AZ has repeatedly shot themselves in the foot is bit harsh. OK, the Oxford arm of the ‘team’ messed up the QC on the Italian-made batch of vector, resulting in the well-known half dose:full dose issue. Once they’d more fully understood the implications of that mistake, it turned out the extra efficacy was indeed down to the delayed booster idea. I do not think anyone else has tried to perform timeline optimization studies during their trials, but without this work (whether serendipitous or deliberate) we would not have known about this significant benefit of delaying the booster dose.
        The debacle in the EU where they refused to take into account real world data on the immune status of old versus young cohorts from last December, where they refused to take account of data from hundreds of thousands of recipients, many in the over 65 age group (the ‘Scottish’ data from Feb 19), cannot surely be Oxford-AZ’s fault?
        Then all the flip-flopping in the EU before finally accepting the data.
        Then we had the rare blood clotting issues. Again, not AZ’s fault?
        And then we have a US-based regulator behaving in a manner that you can guarantee would not have happened to a US company. And for what? 3 points on the ‘efficacy’ scale re mild/moderate disease? As Chris pointed out, these numbers are essentially identical given the confidence intervals around the small numbers.
        As I said earlier, criticize them for the 100% claim re effectiveness re serious stuff, but for 3 points on the efficacy scale?
        Why-oh-why is almost everyone still fixated on the ‘efficacy sweepstakes’?

        1. WST says:

          IMHO the only thing that can be said is that FDA/AZ relation was not good, rest are guesses. There was an issue about AE reporting early on, and maybe other irritants… so this was a last straw.
          AZ did an irresponsible thing and certainly did not anticipate the reaction, took a risk and got burned.
          Publishing worse case 69% figure was really mean, but what if this was the correct value, worse cases do happen . This would have created even worse problems for AZ.
          To me, it’s a series of very human errors, in a backdrop of mutual mistrust.
          The results from a 30k trial could not elevate any safety doubts about AEs in 1:1,000,000 class.
          US government invested 1,2B$ in AZ vaccine, ordered 300 million doses, sequestered 30M produced doses in anticipation of US EUA.
          AZ vaccine is still an US project as well and still looks like a part of US vaccination strategy.

          https://www.nytimes.com/2021/03/11/us/politics/coronavirus-astrazeneca-united-states.html

    5. Med Chem says:

      And well said yet again thrice, Marko

    6. Med Chem says:

      And well said yet again thrice, Marko

  38. johnnyboy says:

    So here we go, final results published: 76% efficacy instead of 79%. Still 100% protection against severe disease. Was that 3% really worth a middle-of-the-night freakout by the DMSB ? Who is it that really undermined public confidence here ?

    1. Med Chem says:

      Well said yet again twice, johnnyboy

      1. Badbob says:

        Another stellar showing from the placebo arm. 100% protection against death. Get a grip all you vaccine zombies

        1. Chris Phillips says:

          100% protection against death in the unvaccinated?

          Anti-vaccine loons really are as stupid as we always thought, aren’t they?

          1. sgcox says:

            “There are no cure for stupid”
            https://www.youtube.com/watch?v=CTqwQPe1z7U

    2. Jack says:

      Agreed. Fauci et al made a big mistake going public. I wonder if Derek’s views have changed since writing the update.

  39. SJ says:

    “the company’s press release (as discussed below) is apparently more of an interim read than reflective of the final data.”
    The press release from AZ on the 22nd did state right at the beginning that it was based on interim results. Also the NIAID did a press release on the same day stating the exact same thing. Not sure why you didn’t mention that or the fact that all the other trials release interim results first because they have to and then follow with the full results.

  40. Bill says:

    “Why-oh-why is almost everyone still fixated on the ‘efficacy sweepstakes’?”
    >>>>>>>>>>>>>
    Because it’s a number the public thinks they understand (they don’t) and is used as a figure of merit (it isn’t) for choosing between available vaccines. Which few people can do anyway.

  41. Marko says:

    Mask and social distancing norms are steadily being eroded, variants be damned. Where we’re headed, ready or not :

    https://i.imgur.com/iHFpFcE.gifv

  42. drsnowboard says:

    When this thing started, and some folk got out of the gate early to develop a vaccine, I seem to remember any efficacy over 50% was going to be fantastic. Now we are quibbling over a 3% change in figures over 3 days of analysis with figures in the 70’s. For the current variants, the scientific challenge has lessened and the PR / govt oversight / procurement battle has just started. I don’t disagree with review of AE’s , it’s what the system is there for. But the review has said the thromboembolic events are not significant. The public health argument now should be : how do we convince the majority of our populace to get vaccinated?

  43. medchemist says:

    Does anybody know, whether the P1 mutant (currently causing a horrible spike in cases and deaths in Brasil) is significantly resistant to the immunity invoked by any of the approved vaccines?

    1. Alex Beribisky says:

      All the vaccines approved in the U.S. as well in the EU were shown to be effective against the P.1 variant, with only mild decrease in neutralizing antibody affinity (about two to three fold). If anything, the B.1351 (South African variant) is more of a concern.

      https://www.biorxiv.org/content/10.1101/2021.03.12.435194v1.full

      https://www.biorxiv.org/content/10.1101/2021.03.01.433466v1.full

      https://www.reuters.com/article/us-health-coronavirus-brazil-variant-exc-idUSKBN2AX1NS

    1. Chris Phillips says:

      Thanks for that. Just to highlight the key point in the abstract:
      “… new strains have emerged with multiple mutations: P.1 from Brazil, B.1.351 from South Africa and B.1.1.7 from the UK (12, 10 and 9 changes in the spike respectively). All have mutations in the ACE2 binding site with P.1 and B.1.351 having a virtually identical triplet: E484K, K417N/T and N501Y, which we show confer similar increased affinity for ACE2. We show that, surprisingly, P.1 is significantly less resistant to naturally acquired or vaccine induced antibody responses than B.1.351 suggesting that changes outside the RBD impact neutralisation.”

      One wonders whether this leaves the speculation about high reinfection rates in Manaus, Brazil. Probably people were right to be cautious about accepting the sky-high estimates of initial infection rates there.

  44. Marko says:

    More cases of concerning P.1 variant confirmed in Vancouver lab than entire U.S.

    https://bc.ctvnews.ca/more-cases-of-concerning-p-1-variant-confirmed-in-vancouver-lab-than-entire-u-s-1.5364043

    Canada is doing it all wrong. In the US, Trump taught us that if you don’t test, there are no cases, and thus no problem. The same applies to variants. We don’t look for them, we don’t find them, so no worries.

  45. Marko says:

    Sudden rise in COVID-19 case fatality among young and middle-aged adults in the south of Brazil after identification of the novel B.1.1.28.1 (P.1) SARS-CoV-2 strain: analysis of data from the state of Parana

    https://www.medrxiv.org/content/10.1101/2021.03.24.21254046v1

    1. Chris Phillips says:

      Thanks. From the abstract:
      “Patients aged 20-29 years experienced a tripling of their CFR, from 0.04% to 0.13%, while those aged 30-39, 40-49, 50-59 experienced approximate CFR doubling.”

      Those are grim figures.

      How utterly stupid people are when they try to discourage younger people from being vaccinated on the basis of a 1 or 2 in a million chance of a fatal side effect.

      1. Tony M says:

        Would be good to see more detailed data. Particularly on the age/sex/Pre-existing condition risk for both infection and case fatality rates. For example. early data from China indicated an increase in death rate with age, for males and for those with pre-existing conditions (Cardiovascular disease – 13.2% – 10.5%, Diabetes 9.2% – 7.3%, Chronic respiratory disease 8.0% – 6.3%, Hypertension 8.4% – 6.0% and Cancer 7.6% – 5.6%) Source: https://www.worldometers.info/coronavirus/coronavirus-age-sex-demographics/

        However, the instances of these pre-existing conditions also increase with age. Consequently, it is difficult to determine how much the increase in death rates is attributable to the preexisting condition an how much is attributable to age.

        For example, an analysis of 601 deaths in New York as at 12 May indicated that of 601 deaths in the 18 – 44 year age bracket, only 17 had no underlying condition with 108 unknown. Source: https://www1.nyc.gov/assets/doh/downloads/pdf/imm/covid-19-daily-data-summary-deaths-05132020-1.pdf

        If someone has a link to statistics on IFR, CFR and hospitalisation split down by age, sex and Pre-existing Condition vs No Pre-existing condition it would be welcome. Thankyou in anticipation.

      2. Bob says:

        You really are a Wally. Here’s two good reasons – 1- The vaccine doesn’t work all that well against this variant and -2 – vaccines are understudied as to potentially worsening disease with variant infections.
        Plus long term the vaccines have no hope of working (effectively preventing serious Covid -19 or death) or eradicating sarscov-2 not a snowballs chance in hell. I base this on long standing real world evidence with influenza and their vaccines.

        1. sgcox says:

          If vaccines make Covid another flu, I take it. Anytime.

        2. Chris Phillips says:

          That’s the lastest anti-vaccine hymn sheet, is it?

          (1) An unevidenced claim that what you call “the vaccine” doesn’t work “all that well” against the Brazilian variant. (In fact some of the recent findings seem to be pointing in pretty much the opposite direction.)

          (2) Not content with that unevidenced claim, a scare story that vaccines will actually make infections by the variants worse (!).

          (3) A scare story that vaccines won’t be capable of preventing severe disease – which is demonstrated by the trial data to be completely false.

          (4) Name-calling. Admittedly your least weak argument …

          1. Bob says:

            Stark raving mad looney, praying to the Flying Spaghetti Monster is as good a tactic to ward off the virus. Escape is an inevitability and vaccination is a very clunky prophylactic tool for this type of virus – as you will find out in time and you can analyse the data

          2. Chris Phillips says:

            Ah, sure – we’ll “find out in time” you’re right, because now you can’t come up with a single piece of evidence to back up your claims.

            Do you really think there’s any point posting this kind of stuff in a science-oriented forum?

        3. Derek Lowe says:

          You need to realize that coronaviruses and influenza viruses are fundamentally different things. Please read up before posting again – thanks!

          1. Bob says:

            Both are respiratory RNA viruses that are prone to antigenic shift and drift. I knew that without any need for reading up. That’s a close enough proxy for me to realise that long term vaccine protection is very unlikely. I’d be interested to see how do you think it could be any other way? Given that there are several companies scrambling to develop boosters against variants and none of these have crystal balls to predict random mutations I predict widespread vaccine failure. The preclinical data from the most closely related coronavirus vaccines is also scary and the experimental N has now exceeded half a billion souls.

          2. Chris Phillips says:

            Bob:
            “Both are respiratory RNA viruses that are prone to antigenic shift and drift. I knew that without any need for reading up. That’s a close enough proxy for me to realise that long term vaccine protection is very unlikely.”

            What is the evidence for antigenic shift (as opposed to antigenic drift) in the coronavirus?

            Certainly the UK Scientific Advisory Group for Emergencies said in September there was no evidence of it:
            https://www.gov.uk/government/publications/sage-55-minutes-coronavirus-covid-19-response-3-september-2020/sage-55-minutes-coronavirus-covid-19-response-3-september-2020

          3. bob says:

            Chris, in the evolving world of study of this novel corona virus initial opinion was that neither drift or shift would be likely to occur. Our WHO initially denied airborne transmission too – lack of evidence doesn’t mean that common sense should not apply. You better believe both are probable as zoonotic reservoirs for the virus are proven beyond any doubt and we most likely got the blasted virus as a result of such a shift. As you may or may not know vaccination will serve to accelerate antigenic drift (as proven by simple in vitro experiments passaging cells in the presence of virus and convalescent serum/antibodies). So, if you still can’t see the evidence I can understand that you will only see in time when that evidence presents itself. You and Derek might want to do some reading https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3237677/

          4. Chris Phillips says:

            Bob

            The link you give contains no reference to antigenic shift.

            So, to be clear, the one fact you thought was so well known that you didn’t need to read it up – antigenic shift in coronavirus – and which your anti-vaccine propaganda is apparently based on, is actually not a fact at all.

            There is believed to be no antigenic shift in coronavirus. You think differently, but you’re unable to produce any evidence. You just think people are wrong about it. And of course we shall “see in time when that evidence presents itself”.

            It’s pretty shameless stuff, when you’re trying to persuade people not to have life-saving vaccinations.

          5. bob says:

            “Coronaviruses have a strong history of host shifting as evidenced by phylogenetic incongruences in the family tree”
            Reference article;
            18. Rest J.S., Mindell D.P. SARS associated coronavirus has a recombinant polymerase and coronaviruses have a history of host-shifting. Infect Genet Evol. 2003;3:219–225. [PMC free article] [PubMed] [Google Scholar]

          6. sgcox says:

            In that paper, authors found a single recombinant in the whole genre. Happened thousands if not millions years ago. Hardly a “proof” that our current virus will suddenly become some super mutant monster. coronavirus are very stable organisms(machines ?) for RNA viruses. Any attempts to bring flu or HIV is complete nonsense,

          7. bob says:

            SGCox – Where do you think MERS came from? Hint it was since that paper was written in 2003. And the current SARS-CoV-2 where from?
            I don’t know where you learned reading comprehension either: This is directly from the abstract in the referenced paper:
            “However, current sampling suggests host-species shifts between mouse and rat, chicken and turkey, mammals and manx shearwater, and humans and other mammals. The sister relationship between avian coronaviruses and the 3′ RDRP fragment of SARS-CoV suggests an additional host-species shift. Demonstration of recombination in the SARS-CoV lineage indicates its potential for rapid unpredictable change, a potentially important challenge for public health management and for drug and vaccine development”.
            Now read your comment again! They say you can’t argue with stupid!

          8. Chris Phillips says:

            Bob

            You seem to be equating antigen shift with recombination rather than reassortment.

          9. Bob says:

            Chris, sgcox and your good self should get together to publish a paper about antigenic shift in corona viruses, you clearly know more than you were letting on earlier today🤣🤣🤣

          10. sgcox says:

            Publish a paper on antigenic shift ? I wish but probably a bit too late, there should be dozens already in print and MedArchive.
            Simple Google search – top hit:
            “Antigenic drift, random genetic mutation of an infectious agent resulting in minor changes in proteins called antigens, which stimulate the production of antibodies by the immune systems of humans and animals. These mutations typically produce antigens to which only part of a population may be immune.”
            Absolutely normal event for any infections organism. Precisely what we observe now with B1.351 and others. We (humans) will deal with it. No need to call the doom and call other people names just because they disagree with you.

          11. Chris Phillips says:

            “Chris, sgcox and your good self should get together to publish a paper about antigenic shift in corona viruses, you clearly know more than you were letting on earlier today 🤣🤣🤣”

            Surely more a question of you clearly knowing a lot less?

            When you wrote “antigenic shift” you actually meant recombination, not reassortment? (You understand that reassortment is primarily what causes the difficulties with flu vaccination?)

            Sorry to be a bore, but when someone is posting false information in order to dissuade people from taking a life-saving vaccine, I find it anything but a laughing matter.

          12. bob says:

            Chris both of those are mechanisms of antigenic shift (which you denied happened in coronaviruses and covid-19). Now read back on your comments and admit defeat and stop trying to get the last word in. I am not anti-vax but very clearly anti these vaccines as they have clear potential to cause a catastrophe. Properly tested vaccines with long term safety data are life saving medicines – there’s no doubt about this as the evidence confirms it. In relation to any of the EUA vaccines we do not know what the long term effects will be – as regards safety or efficacy. It’s now accepted fact (AZ’s official warning in product literature is proof of this) that short term effects have come out in the wash that were not found in clinical development & these were initially denied by the WHO and overarching regulatory authorities while many national bodies saw a worrying safety signal and suspended use. Using common sense and analysis of the evidence from ill-fated vaccine development attempts concerning the most closely related coronaviruses and from long standing use of other respiratory RNA viruses which undergo antigenic shift/drift I really do think we are wasting our time and are potentially heading for disaster with ADE. The latter would be very bad news for affected folk and their families and also damage future vaccine and therapeutic development. Can you show me any long term safety or efficacy data to reassure me?

          13. Chris Phillips says:

            “Chris both of those are mechanisms of antigenic shift”

            In that case, what you mean by antigenic shift is not what other people mean, which is reassortment.

    1. Med Chem says:

      Link noted.

      Except as parent of offspring who once upon a time first talked at the more usual 12-15 months, I’m distracted by the linked tweet of a baby who, “Just said her first word, 4 days shy of 7 months,” and for whom, “We are working on her application for Oxford as we speak.”

      Am assuming that’s Oxford the University. Good luck bringing up a child prodigy.

  46. Chris Phillips says:

    “Would be good to see more detailed data. Particularly on the age/sex/Pre-existing condition risk for both infection and case fatality rates.”

    That seems a strange first reaction to data showing – prima facie – typically a doubling of case fatality rates for the Brazilian variant.

    I really hope it’s not motivated by a desire to say “But healthy young people still don’t need to be vaccinated”.

    Whatever the breakdown of fatality, this finding – if confirmed – will mean that people refusing the vaccine are likely to kill about twice as many other people on average, if they spread this variant.

    1. Med Chem says:

      “This finding – if confirmed – will mean that people refusing the vaccine are likely to kill about twice as many other people on average, if they spread this variant.”

      …Link please to peer reviewed scientific paper, in support of this sweeping conjecture.

      And as posted previously, commenter may (or may not) have passed on a virus to ailing grandfather in late 1975. No recollection of widowed grandmother holding it against me for the next nineteen years.

      1. Chris Phillips says:

        ““This finding – if confirmed – will mean that people refusing the vaccine are likely to kill about twice as many other people on average, if they spread this variant.”

        …Link please to peer reviewed scientific paper, in support of this sweeping conjecture.”

        Let me break it down into easy steps for you.

        (1) If the findings are correct, the fatality rate is about twice as high for this variant.
        (2) So if you spread this variant you will kill about twice as many people.

        So far the evidence here seems to be indicating strongly that anti-vaccine campaigners really are every bit as stupid as we thought.

        1. Med Chem says:

          If this thread traced back right, it starts from a link provided by commenter Marko (27 March, 2021 at 12:56 am) to a medrxiv.org pre-print reporting an increase in deaths and case-fatality ratio in a province in Southern Brazil.

          Let’s break this down into steps:

          1. Seems to this physical scientist a single paper rarely settles anything in epidemiology
          2. Also seems epidemiology variables rarely (if ever) fully understood, rendering extrapolation from one region of the world to another scietifically moot
          3. The pre-print hasn’t been peer reviewed
          4. Scientific grandstanding by commenters implying fit and healthy people killing other people not the version of the science I grew up in awe of – as observed on the BBC by a revered sage of the era, “Students are not here to worship what is known, but to question it.”

          To reiterate, please provide link to peer reviewed scientific paper that makes points 1-3 redundant.

          Meanwhile, vaccinated observer berated as anti-vaccinator for baulking at grandstanding by zealous anti-anti-vaccinator. Conflict of ethos seems mired up in idea of asymptomatic spread, a respiratory virus concept which, on page 11 of the following link, a pathologist implies was unconsidered before 2020…

          https://www.hartgroup.org/wp-content/uploads/2021/03/HART-REVIEW.pdf

          Not a thesis (or website) that fits the pandemic macrodrama “narrative.” Intriguing how scientific peer review, questioning minds, media impartiality and respect for individual liberties all went out of fashion this time last year…

          …Cue usual fervent fingers clammering away d-e-n-i-a-l-i-s-t at usual man-not-ball keyboard. No denying 126,592 total deaths in the UK within 28 days of a positive test. Data in, but jury out a while deliberating yet.

        2. Chris Phillips says:

          “MedChem”

          Are you really incapable of understanding the simple English phrase “This finding – if confirmed“?

          God help us.

          1. Med Chem says:

            God help us indeed

  47. Franksnbeans says:

    Watching you ignore Novavax phase 3 data has been eye opening. I wonder, is it you, or is it your masters? Either way, it’s shameful. Even deleting tweets that mention it. You feel good about it?

  48. Chris Phillips says:

    A study in UK care homes indicated a 56% lower infection rate among residents from 4 weeks after a single dose of Pfizer or AstraZeneca, and 62% lower from 5 weeks. This is based on PCR testing, so it relates to infection rather than symptomatic disease.

    The effect was similar for both vaccines, and the UK variant was prevalent during the study. Other findings include a lower Ct value (implying lower viral load) among those who were infected at least 4 weeks after vaccination (the difference in the distribution of Ct values in Figure 1 looks dramatic to me).

    Those who were never vaccinated (despite vaccinations being done in their care home) had lower infection rates than the pre-vaccination residents. Possibly because they were “receiving end-of-life-care” and were less exposed, or possibly because they benefited from reduced transmission owing to the vaccination of others. When they were excluded from the analysis, efficacy against infection rose to 76% from 5 weeks.

    Also (requiring confirmation owing to small numbers) that vaccination made little difference to those who had previously been infected, suggesting they were already protected. The risk of infection among those unvaccinated but previously infected was reduced by 88%.

    They comment further that their efficacy estimates may have been reduced because they had probably underestimated the number of residents who had been infected previously.

    https://www.medrxiv.org/content/10.1101/2021.03.26.21254391v1.full.pdf

    The authors comment:
    “To the best of our knowledge, our findings constitute the first real-world evidence on vaccine effectiveness against infection for ChAdOx1, in any age group.”

    Bearing in mind that the vaccinations were 67% AstraZeneca and 33% Pfizer, on the whole this seems to suggest that protection against infection (including asymptomatic infection) may be quite a bit higher than the 50% implied by the AstraZeneca Phase III results – particularly as they are looking at single doses in a population with a median age of 86!

  49. sgcox says:

    Small mistake : Higher, Ct values after vaccinations, not lower.
    More cycles, ~31 is necessary to detect virus compared to 26.
    That means about 30 fold drop in the virus load in vaccinated people if they get infected !

    1. Chris Phillips says:

      Ah yes, sorry. First I was going to write just lower viral load, and then I changed it to Ct to make it more pedantically accurate (!).

  50. Marko says:

    CDC Director Walensky : “Right now, I’m scared…I so badly want to be done…so I’m asking you to just hold on a little longer. Now is one of those times when I have to share the truth and I have to hope and trust you will listen,” Walensky said, saying she’s going to pause and “reflect on the recurring feeling I have of impending doom.”

    https://twitter.com/kaitlancollins/status/1376553225155977219

    After a year of averaging about 1500 deaths/day, we’ve settled on accepting 1000 deaths/day as a a reasonable cost of doing business, when just another month or so of bearing down could have cut that figure in half, or more, as was achieved in the UK. The current rise in case counts was entirely predictable a month ago, when the rate of decline began to flatten out, given that we knew the B.117 variant would soon become dominant.

    This is as unacceptable now as it would have been under Trump. Public health continues to fail in the US, resulting in unnecessary deaths.

    1. Bill says:

      We might be lucky if we only stagnate at 1000/day. Michigan incidence is skyrocketing and some say school openings are leading the way.
      https://www.detroitnews.com/story/news/local/michigan/2021/03/26/michigan-has-a-new-leader-in-the-surge-of-covid-cases-kids/4750748001/

      But schools are opening all over. Tomorrow’s headlines?

    2. stewart says:

      The overall UK figures are still falling, but now only slowly, and not for all areas and populations.

      The rate and change of rate are now low enough that noise (clusters) obscures the trend for smaller areas, but there’s a noticeable upward trend in West and South Yorkshire, and to a less degree in Greater Manchester, east Lancashire, and Humberside. Some upticks elsewhere have reversed.

      Rates in children are reported to be up.

      I can but hope that vaccination counteracts the increase in transmission due to yesterday’s relaxation of some restrictions.

      1. Marko says:

        I agree that even the UK may be a bit premature in reopening, but I wish the US had suppressed cases and deaths to at least the same level before loosening restrictions. The UK is currently at a US equivalent of 300 deaths per day or less – more than the typical impact of the flu averaged over a year, but within the range of normal excess death rates, so I can better understand their rationale for beginning to lift restrictions. Still, it would be a shame if they have a new upturn in death rates at this point, after doing so well since the peak of the winter surge.

        If the US as a whole progresses anything like Michigan, things could get pretty ugly over the next few weeks. What really bothers me though, is that a death rate of “only” 1000 deaths per day over the next month would be considered “mission accomplished” to so many.

  51. bewd says:

    Conclusions. The AZD1222 vaccine is associated with development of a prothrombotic disorder that clinically resembles heparin-induced thrombocytopenia but which shows a different serological profile
    https://www.researchsquare.com/article/rs-362354/v1

  52. sgcox says:

    Ok Bob, you mean shift, not drift, sorry. Do not think we observed it yet in Sars-Cov2 or any of four established human coronaviruses.

  53. Chris Phillips says:

    Canada has suspended the use of AstraZeneca, citing a risk of fatality of 4 in a million based on European data on blood clots.

    “There is substantial uncertainty about the benefit of providing AstraZeneca Covid-19 vaccines to adults under 55 given the potential risks,” said Dr Shelley Deeks, vice-chair of the National Advisory Committee on Immunization.

    https://www.theguardian.com/world/2021/mar/30/canada-suspends-use-of-astrazeneca-covid-vaccine-for-those-under-55

    1. Chris Phillips says:

      Sorry – I should have specified that it has been suspended only for those under 55.

      It would be fascinating to see the assessment of the risk from COVID-19 that this decision is based on.

      1. JF says:

        We have 31 cases and 9 fatalities in Germany by now, according to our official news channel

        https://www.tagesschau.de/newsticker/liveblog-coronavirus-dienstag-193.html#31-Verdachtsfaelle-von-Sinusvenenthrombose-nachAstraZeneca-Impfung

        Of the 31 cases, 29 are women. I think that women outside the group running serious will not volunteer to take the AZ vaccine any more.

      2. Rob Sutherland says:

        Chris,
        Things just continue to get more and more ridiculous up here in Canada/Ontario.
        I posted some of this in an earlier thread on Mar 19, but now we have the NACI getting involved again. As a reminder:
        “Up here in Ontariario, vaccination is a mess!
        Only a week or so ago Health Canada finally OK’d the AZ vaccine for everyone over 18, but another Fed agency (NACI – National Advisory Council for Immunization) came out with recommendation to limit AZ to those under 65. This was based on lack of data showing ‘efficacy in over 65s’, despite the huge Scottish and English studies coming out some time before they made this announcement.
        I’d never heard of the NACI prior to this, so maybe they do indeed live under a rock!
        If that was not sufficiently confusing, the NACI also OK’d a booster delay of up to 4 months, for which there is no data AFAIK. A week later, they may have relented in the face of loads of evidence for AZ vaccine’s effectiveness in over 65s, but it is hard to keep up…..
        On top, you have the Provincial Governments doing their own thing as well. Only Quebec has followed the UK approach almost from the beginning, but now most (I think) are now following the 4 month delayed booster approach.”

        Last night I witnessed a highly unimpressive interview on CBC with the head of NACI.
        She tried to justify the earlier flip flop on the AZ vaccine noted above by claiming again that when their original decision was made NACI was following the early trial data in which insufficient data was available re efficacy in over 65s.
        Jesus H Christ! What does she think happens to the immune system after 64 years and 364 days?? It is old folks that bore the brunt of earlier waves of the Pandemic and those most requiring vaccination ASAP.
        She cited ‘new data’ as the reason for dropping the over 65’s restriction. New data (UK Scottish and English data presumably) that came out well before the original decision to deny the vaccine to the over 65s.
        She then had the chutzpah last night to essentially blame AZ for all the problems this vaccine has had!! She reckons Health Canada needs to do a risk-benefit analysis in the younger folks to ensure that we do not see any HIT-like issues on Canada, before they will no doubt do another about-face! She also (mistakenly) claimed that no other vaccine (let alone covid vaccine) has been associated with this HIT-like syndrome.
        Meanwhile the B.1.1.7 variant is beginning to cause all sorts of bad things up here with ICU-occupancy running very high, lock-downs on the upswing again and as we all know on this blog, the UK variant is now getting into younger groups and causing increased lethality therein.
        Holy crap!
        She totally failed to see the irony of her organization performing the modern day equivalent of the Hokey Pokey wrt the AZ vaccine and how such has had a terrible effect on folks desperately trying to get vaccinated up here.
        “You bring the vaccine in,
        You keep the vaccine out,
        In, out, in, out,
        You screw it all about…”
        Such effects will not just affect acceptance of the AZ vaccine when they perform their next flip-flop. It will instead cause a drop in acceptance of all covid vaccines.
        Due to these and other uncertainties generated by the blood clotting issues, most lay folks are desperately trying to avoid the AZ vaccine.
        I would take it in a heartbeat at 70y/o!!
        I tried to register to get access to the AZ vaccine for me and the wifey during the short period in which it was OK to get this in a pharmacy as an over-65 year old. We heard absolutely nothing back from the two pharmacies we registered with. Meanwhile Toronto has insufficient folks turning up to get the vaccine (we live outside the Greater Toronto area) and are pleading with folks to come on down and get it.
        So finally, I got registered in my local area to get what will likely turn out to be the Pfizer vaccine (based on the Q’s I was asked re allergies to PEG).
        AAAGGGHHHH!!!!

        1. Bob says:

          Careful what you wish for: Hungary – highest rate of vaccination in Europe and among the highest current death toll. ???? Solve that contradiction in terms, especially as priority was given to the most vulnerable for vaccination! Bad vaccines? Or evidence of their uselessness? Up for debate.
          What on earth could be going on?
          Hmmm… search for bobs commentary in this thread … possible answers emerge.
          Real world evidence of vaccine ‘efficacy’ in the UK is attributable to a massively prolonged lockdown rather than vaccination effects & antiquated clinical data convincing the likes of Chris Philips of it’s veracity rather than it’s fortunate timing. Also many susceptible individuals in the UK undoubtedly succumbed to the vaccines effects rather than those of the virus (see spike in deaths recorded officially but excuses are offered – underlying conditions, would have died anyway blah blah blah anything except the vaccine direct dialled the reaper).
          Wake up, the alarm is set and the resounding failure of this strategy is going to be an alarming wake up call. Why don’t flu vaccines reduce flu mortality? Why then would covid vaccines? WAKE UP. All wrong. Horrible mistake. Let’s perpetuate it and run booster vaccinations and variant vaccinations.

          1. Chris Phillips says:

            Bob

            You said above “I am not anti-vax”.

            Your latest post is pure, standard anti-vax propaganda, in its crudest, most nonsensical and scientifically illiterate form.

            Though on the whole you are probably wise not to try to dress it up in scientific terms, if you can’t be bothered to “read up” at all!

          2. Derek Lowe says:

            Bob, if this is all you’re going to bring, I would prefer that you take it somewhere else. Not interested in hearing leftover anti-vaccine propaganda, and you’re not going to get very far with it on this site anyway.

  54. bob says:

    Hi Chris,
    2/3 epidemiologists believe that the current vaccines will be ineffective by next year
    https://www1.racgp.org.au/newsgp/clinical/current-covid-vaccines-could-be-ineffective-by-nex
    You should tell them they are all wrong. So the strategy to “save the world” and “end the pandemic” will be to reformulate and revaccinate? This is a stupid strategy as viral mutations will not cease while this losing strategy is implemented. The cycle of doing the same thing and expecting a different outcome was nicely summed up by Einstein.
    Unbelievable that governments are now giving vaccine bonuses and passes to help circulate new variants!

    1. Mariner says:

      Interestingly, few of the scientists quoted on that linked article think that the current vaccines will prove completely ‘ineffective’. And, in fact, other than the headline there is little discussion of what is meant by the word ineffective. The survey quoted is actually from The People’s Vaccine, a charitable organisation calling for the vaccination of everyone on the planet through the suspension of parents! Not exactly what you seem to be aiming for, bob.

      1. Mariner says:

        Should have been ‘patents’, obviously. Flipping auto-correct…

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