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Adenovirus-Vector Vaccine Roundup, Feb 5: Sputnik and More

We’ve had yet more news in this area in the ten days or so since my last vaccine news roundup post, so here’s a look at the current situation. Most all the news has been in the viral vector area, so I’ll stick to that this time around.

The big news here is the publication of the Gamaleya Institute’s “Sputnik-V” vaccine data. In the end, we have data on about 15,000 patients who were vaccinated, and on about 5,000 in the placebo control group. Volunteers got a dose of an adenovirus-26 vector vaccine, followed 21 days later by a dose of the identical construct in an adenovirus-5 vector. This is to try to avoid the immune response to the vector itself, which has always been a concern with any of the viral-vector vaccines (against the coronavirus and against anything else!) Another concern is the possibility that once you’ve had such an adenovirus-vector treatment, that you might be in trouble for further vaccinations that use the same vector (and this remains an open question).

Counting from the day of the second dose, there were 16 cases of disease in the vaccinated cohort, and 62 cases in the controls. That comes out to a two-dose vaccine efficacy of 91.6%, with a 95% confidence interval of 85.6% to 95.2%. In no subgroup (age, gender, etc.) was it lower than 87%. As with most of the other trials, this is largely based on symptomatic disease – the participants were checked by PCR at the beginning and on the day of the second dose, but at no other times. Importantly, and in line with the other vaccine trial data we’ve seen so far, there were no cases at all of moderate or severe disease in the vaccinated group after the date of the second dose. Figure 2 of the paper shows that the effect of the first shot kicks in around day 16-18 – a bit longer than what’s been seen with the mRNA vaccines, but the curve afterwards shows the same strong protection. Safety looks good, with few adverse events and nothing serious connected with the vaccine itself.

So these data look strong, strong enough that a single-dose trial is underway as well (and that will make an interesting comparison with J&J’s Ad26-vector vaccine, for which we have single-dose data with a two-dose trial underway). We’ll be getting more real-world data on this one, as it’s being deployed in several countries, and it will certainly be worth seeing how it handles the variant strains that we’re seeing now. My expectation is that it will deal with the B.1.1.7 one at nearly the same efficacy and drop down to the 50-60% efficacy range against the B.1.351 strain, as has been seen with the other vaccines where we have such data. Based on the numbers we have, I see no reason why this vaccine can’t make a solid contribution to fighting the pandemic, and I’m very glad to have another efficacious one out there for use. Update: a skeptical take on the publication here!

For updates on the Oxford/AstraZeneca vaccine, I’ll refer everyone to this post, and likewise for updates on the J&J vaccine, this recent post. Update: since this was written on Friday, reports have come in from South Africa that the AZ/Oxford vaccine does not appear to be very effective in preventing illness against the B.1.351 variant, and the SA government has announced that they’ve stopped dosing with the vaccine. This is not good news for anyone.

As for the CanSino Ad5 vaccine, there are reports in Chinese media of positive safety and efficacy data, which means that it’s officially moving into Phase III. That sounds a bit odd, considering that it’s apparently being offered in Pakistan, Malaysia, and other countries already, but these are odd times. There is also word of a combination trial with this one and the Sputnik vaccine as well, which would replace the second (Ad5) dose of the former with the CanSino one. And the AstraZeneca/Gamaleya combination trial was reported just today as ready to start in Azerbaijan and a whole list of other countries.

Of the other viral vectors I reported on in the most recent post, the big news has been on the Vaxart oral candidate. Unfortunately, the company reported that they were unable to detect serum neutralizing antibodies in most trial subjects, which has to be considered an unwelcome development. Their press release sounds a lot more positive than that (as is so often the case), but it’s rather light on actual data. It may be (although it seems less likely) that the real-world efficacy of this candidate will depend on its mucosal immunogenicity and that the lack of neutralizing antibodies in serum is a red herring, but the only way to convince people of that will be with lots of strong efficacy data in human trials.

The Reithera vaccine has had a news report about being available in Italy in September, but on closer inspection it’s “if the Phase II and Phase III trials, which haven’t started yet, go well”, so that’s not too useful. And the Washington Univ./Bharat Biotech intranasal adenovirus vector candidate is set to go into Phase I trials on 75 people in India.

195 comments on “Adenovirus-Vector Vaccine Roundup, Feb 5: Sputnik and More”

  1. A Nonny Mouse says:

    Is there a specific reason why these are having to be given to immunocompromised people rather than the mRNA ones, or is it just the case here in the UK?

    1. Jack says:

      I want to know the answer to this too.

    2. Roland says:

      Both Pfizer and AstraZeneca vaccines are being given to the immunocompromised in the UK. You can check official guidance here: https://www.gov.uk/government/publications/national-protocol-for-covid-19-mrna-vaccine-bnt162b2-pfizerbiontech

      If there’s a preference at GP level possibly it’s because there’s more data on the longevity of protection between dose 1 and 2 for the AstraZeneca one? Immunocompromised people are obviously going to start with lower protection in the first place so it’s especially important it doesn’t fall toward too much before 2nd dose. (I can’t see anyone seriously expecting the Pfizer one would drop off more, if anything the opposite, but that’s where we’re at with this 12-week experiment).

    3. Harvey 6'3.5" says:

      Derek,
      If you could explain why Novavax isn’t submitting their British and South African test results for FDA approval, I would really appreciate it. These results just appeared and disappeared, without any explanation as to why the company (which is located about 4 miles from where I live in a biotech cluster), isn’t pursuing FDA approval until after a phase III trial.

  2. Juan says:

    “Another concern is the possibility that once you’ve had such an adenovirus-vector treatment, that you might be in trouble for further vaccinations that use the same vector (and this remains an open question)”

    In today’s pre-print on Oxford/AZ focusing on the efficacy against B117, there was a reference to individuals who had previously been vaccinated with the Chimp Adenovirus used in the Covid vaccine showing same anti Spike protein antibodies as the majority who were naive to the vector.
    Also of note that the average viral load in asymptomatic PCR positive participants was lower in the vaccinated cohort. So another indication of reduced transmission on top of the indications seen before.

    1. Chris Phillips says:

      “Also of note that the average viral load in asymptomatic PCR positive participants was lower in the vaccinated cohort. So another indication of reduced transmission on top of the indications seen before.”

      And in the symptomatic cases the duration of positive testing was shorter in the vaccinees. This effect looks quite dramatic.

  3. curious says:

    What’s the difference between first dose of Sputnik and the JJ vaccine?

  4. Fiodor says:

    There are some important details missing in Sputnik trial:

    twitter.com/hildabast/status/1356584374175629313

    The Sputnik vaccine that was tested will be different from the one to be distributed:
    “Initially, we developed a vaccine in two forms: liquid (which is stored at –18°C) and freeze dried (which is stored at 2–8°C). In this study, we studied the liquid form of the vaccine that requires storage at –18°C. Storage at 2–8°C, a favourable temperature profile for global distribution, has been approved by the Ministry
    of Health of the Russian Federation”.

    Also 16,501 subjects were enrolled in the vaccine group but only 14,962 were evaluated after second does, 1539 or 10% left the trial. Is such level of attrition normal in a trial ?

    1. AlexB says:

      Point 1 – If you go the added value section in the manuscript’s beginning, the paragraph you mention is there as well but with one-word difference – “Storage at 2–8°C, a favourable temperature profile for global distribution, has also been approved by the Ministry
      of Health of the Russian Federation”. From what I understand, it is the liquid form of the vaccine that is being used in Russia and for export purposes for the time being.
      Point 2 – If you take a look at the FDA briefing document for the Pfizer vaccine, you will find that about 6% were excluded from the trial around at the second dose stage. So nothing too unusual in my eyes.

      1. Fiodor says:

        re: AlexB
        You are right both version of the vaccine ” liquid (which is stored at –18°C) and freeze dried (which is stored at 2–8°C). ” are approved for global distribution by Russian Federation executive.
        And current deliveries are of this liquid (called “frozen” in the Phase I study) vaccine. But if you look at the Sputnik web side and all announcements, the freeze dried version is promoted and the low storage temperature requirement is apparently an important selling point.
        It can be expected to ship later on, while it’s a different product from the one tested in Phase III.
        Phase I tested both versions and there were differences in the immune response, these are different products.

        “At day 42, receptor binding domain-specific IgG titres were 14 703
        with the frozen formulation and 11 143 with the lyophilised formulation, and neutralising antibodies were 49·25 with
        the frozen formulation and 45·95 with the lyophilised formulation, with a seroconversion rate of 100%. Cell-mediated
        responses were detected in all participants at day 28, with median cell proliferation of 2·5% CD4+ and 1·3% CD8+
        with the frozen formulation, and a median cell proliferation of 1·3% CD4+ and 1·1% CD8+ with the lyophilised
        formulation.”

        1.6% of Pfizer participants dropped out after the first dose against 9.6% for Sputnik. This needs an explanation.

        1. AlexB says:

          @Fiodor Thanks for replying. 🙂

          You are right that there are pending questions regarding the freeze-dried form of Sputnik V. The question here is, does it make sense to run a separate phase III trial on it… Not really an expert in the field, so that is more of a question to the national regulators in terms of what they want to do. Based on the data from the Phase I/II paper that you quoted (a potential decrease in immune response), a small sub-trial with the lyophilized version may not be a bad idea.

          As to the Pfizer exclusion data, check out: https://www.fda.gov/media/144245/download, search: “Participants excluded from Dose 2 all-available efficacy population”. The numbers are for the vaccine and placebo group respectively (percentages are in brackets): 1257 (5.8) 1292 (5.9).

          Overall, though (again, to my untrained eye) I cannot say that I have more questions to the developers of this vaccine compared to their Western counterparts. There is a general issue when it comes to details of trial protocols – developers around the world do not release these very readily. So more details and transparency are definitely welcome!

  5. MTK says:

    Good. We need as many effective vaccines as possible that are available to as much of the global population as possible.

    The problem here is the stupid and entirely useless “approval” given by the Russian government based on little to no clinical data. All that does is fuel mistrust in it. That should be a lesson for the FDA.

    1. Joey says:

      Could make the case for the opposite; the Russian government approved a vaccine early that ended up being extraordinarily effective – an example of the kind of calculated gamble that saves lives during a pandemic. The FDA is guilty of the opposite kind of decision-making, willing to accept almost zero uncertainty to make decisions, which ultimately costs lives. An example was their initial hesitancy to guide that delaying second dose likely doesn’t impact efficacy significantly. Another example is their continued failure to guide AstraZeneca and Novavax to submit EUA requests.

      1. Not-an-epidemiologist says:

        A still further example was the FDA shifting the interim analysis goal posts for Phase III trials from 32 cases to 62 cases, and requiring longer-term safety data, than what they’d initially requested. Emergency approval could have — and should have — been given sooner. To deliberately push back the goal posts for the first interim analysis when the country was in the midst of a raging pandemic was not a sensible move.

        (I realise, of course, that the timing of the US election may have played a large role in that decision. An intervention based on political necessity is the only semi-acceptable explanation in my mind for the FDA’s behaviour on this point, but even then it’s a pretty unpalatable justification given that so many lives were at stake (and suggests a level of utilitarianism that hasn’t been matched in any other decision regarding this pandemic). I greatly look forward to reading the historical analysis of that decision once enough time has passed …)

        1. confused says:

          Yes. Their dealing with COVID really has not decreased my view that the FDA is far too overcautious.

          I agree that there could be vaccine-hesitancy-related valid reasons not to give an EUA *before the election* (an approval October 31st might mean fewer people would take the vaccine), but that could not justify delaying it to mid-December.

          Waiting for a full 2 months of safety data makes sense before approving it *for the general population*, but not *for the highest-risk groups* — the death rates in these groups are so high that side effects are scarcely relevant.

          And the argument that an early approval wouldn’t have done any good due to production limitations doesn’t hold in this case either – there are only ~1.3 million nursing home residents in the US, about another 800k in assisted living facilities (as of 2015 data, anyway), and likely nearly 10% of these have already died of COVID…

          1. DataWatcher says:

            ” Their dealing with COVID really has not decreased my view that the FDA is far too overcautious.. . .”

            Especially given that predictions continue to look grim — over 630,00 deaths by June, with upwards of 700,000 possible if the new variants become more dominant. A lot of people poo-pooh’d the predictions of upwards of 400,000 by January, but those turned out to be spot-on, so . . .

            https://www.usnews.com/news/health-news/articles/2021-02-05/coronavirus-model-predicts-us-death-toll-to-top-630-000-by-june

          2. confused says:

            630K by June – yeah, unfortunately doesn’t sound that surprising.

            We’re currently over 460K reported, and given lag from infection -> death and death -> reporting of death, it’s almost certain we’d hit 500K even if no one got infected after today.

            Yes the predictions of ~400K by end of January turned out to be close to right, but the IHME model kept getting changed to predict wildly different things. If it had predicted that outcome in April, I’d be a lot more impressed.

      2. MTK says:

        I would argue that vaccine refusal/hesitancy will result in more suffering than approval delays especially considering that early on all the vaccines, including Sputnik were in short supply.

        In fact, polls say Russians are one of the most hesitant of populations in terms of taking the vaccine with 59% saying they will flat out not take the vaccine.

        1. DataWatcher says:

          In the long run, I think you’re right. The hesitancy problem is bad enough in the U.S., where high percentages of health care workers, first responders, and other essential workers are refusing to get vaccinated (and by doing so, also setting a bad example and increasing doubt and hesitancy among others). In other countries, it’s even worse. Although Russia isn’t a particularly religious society (they’ve had enough bad experiences with secular totalitarian regimes to make them understandably fearful), cultures dominated by fundamentalist religion seem to be especially prone to vaccine resistance. Even Israel, despite their extremely encouraging results vaccinating the high-risk elderly, is running up against roadblocks with their Orthodox communities.

          1. kamil says:

            On the other hand, do we know that vaccine hesitancy and emergency approval are even related? The vaccine could be given to volunteers, there would be plenty of people who actively want to take that risk. What is more vaccine denialism is usually (but not exclusively) built on pseudoscience which is independent of the actual data. It does not matter if we wait 1, 2 or 6 months to gather safety data for most deniers, because they also fear vaccines with multi-decade safety track records!

          2. confused says:

            @kamil Yes, I agree that hesitancy in the long run will probably not have that much effect.

            “Reasonable” hesitancy based on the speed of approval would presumably go away once millions of people have been vaccinated for a while and actual safety is clear.

            Non-rational hesitancy based on pseudoscience and conspiracy theories wouldn’t be affected much either way.

            There could be a marginal effect, but I can’t see it being relevant compared to the advantage of vaccinating the highly-vulnerable population faster (COVID deaths are really quite “concentrated”).

          3. DataWatcher says:

            Remember, Confused, there’s also “reasonable” hesitancy among communities of color, who have very valid reasons not to trust the U.S. govt. or the U.S. medical system. There may, indeed, be some conspiracy theories intermingled with the legitimate distrust, but the overall results are the same. This needs to be addressed, honestly and forthrightly, if we want the vaccination initiative to have its desired effect. It’s not just that Black and Latino folks are dying at disproportionate rates; for any kind of population-wide immunity to even begin to take place, all communities, not just the most privileged, need to be protected as fully as possible.

          4. confused says:

            But don’t you think that as the vaccine becomes less “new” that hesitancy will abate too?

            There is definitely a point here regarding equality/justice in who is protected first though.

            I do not really think this pandemic will end by full-on “herd immunity” though. Flu pandemics don’t, in the sense that transmission goes down to zero and the virus dies out; it just becomes a circulating seasonal virus.

            Is there any reason to think the same won’t happen for this?

        2. confused says:

          I am not sure, but I think this depends on what you think about “second order” effects.

          Most of the deaths are in a fairly small proportion of the population, so vaccine hesitancy in *the population overall* may not be the best measure; you’d want to look at hesitancy in say those over 65 or 60 or whatever.

          But then there is a question if the death rates fall dramatically, and hospitalization falls a lot, but infection remains common at least among younger people, will people be willing to “go back to normal”? I think so, especially once it stops being psychologically ‘new’, but it’s an unresolved question.

          1. DataWatcher says:

            If infection remains that common among younger people, there will still be enough “rare” cases of serious infection and/or death to keep the overall population, as well as scientists and public health experts, very wary, and for policymakers to keep restrictions in place.

          2. confused says:

            I kind of doubt that – scientists and public health experts, sure, that’s plausible, but the overall population? (And sooner or later political pressure would IMO drive policymakers to follow the latter rather than the former…)

            This CDC page suggests ~80% of deaths are over 65. And vaccination won’t be zero among younger groups, and natural immunity from infection is increasing too… That could probably reduce the effect by at least a factor of 10, and COVID is very roughly 10x worse than flu*.

            That would be enough of a dramatic drop-off IMO for the public to see it as “basically solved”.

            *~400k deaths in 2020, vs. ~12-60k annually for flu

          3. DataWatcher says:

            Israel will be instructive in this regard — they’re doing an excellent job vaccinating the elderly, with extremely impressive results. Not so good, though, with the younger population, the Palestinian population, and the significant number of “resistant” people in the Orthodox community. So far, I don’t think their rate of new cases has begun to “flatten” at all, nor have their overall hospitalization rates.

          4. confused says:

            I don’t know what the best source is, but from Worldometers at least, Israel cases do seem to be declining somewhat in the last 2-3 weeks after peaking in the 2nd half of January…

            Of course, cases are declining tons of places with much less vaccination so…

          5. WST says:

            re: Confused
            Israeli official stats , open in Chrome and ask for translation
            Interesting stuff is “sever cases” and “new sever cases” etc.

            https://datadashboard.health.gov.il/COVID-19/general

    2. Marjorie says:

      “The problem here is the stupid and entirely useless “approval” given by the Russian government based on little to no clinical data”

      The Gamaleya Institute explains it (again) in the Lancet publication:
      “the vaccine candidate was provisionally approved in Russia according to national legislation. Such registration allows the vaccine to be used in high-risk groups, with enhanced pharmacovigilance”.

      As I understand it, that temporary approval opened the possibility to vaccinate people at high-risk, because of commorbidities or/and a high exposition to the virus through their occupation.
      But more importantly, that approval was necessary to include vulnerable people in phase 3 trials (without them the phase 3 would have been somewhat unuseful).

      Furthermore, Russia already declared at that time that mass vaccination would take place in October for doctors and teachers, and early 2021 for the rest of the population.

      All this seems quite consistent, so I believe there was a misunderstanding with this approval.

      1. Marjorie says:

        “high exposure”, not “high exposition”, sorry for my french accent.

    3. Stanslav Radl says:

      There are nearly no data of the Astra Zeneca vaccine use in older population. And it was approved by FDA for this group of patients without any limitations. For example, Swiss authority rejected approval for this reason and in some EU states, the use is limited only for people under 55 or 65 years of age.

      1. WST says:

        AstraZeneka is not approved by FDA, not even an EUA submitted.

  6. # says:

    Just a clarification: CanSino’s vaccine hasn’t been approved for use in Pakistan yet because they just recently concluded their phase iii trial enrollment. It is in fact Sinopharm’s vaccine that has been approved for use – and that too for adults under 60.

  7. debinski says:

    I’m not sure I trust the Sputnik data. They still haven’t made their protocol available and don’t even define what a moderate or severe COVID case is in the body of the Lancet article. I had to dig into the “supplementary” material to find it. It looks like they changed the criterion for body temperature that qualified as either mild or moderate COVID because the font is different. That seems suspicious since they claim to have zero moderate cases in the vaccine group (and no severe either). They changed it to 38.5 C is moderate. So what do they do with a temp = 38.5 C? It is also unclear how they defined mild. It says “Body temperature below 38.5 C, cough, weakness, sore throat; No symptoms of moderate and severe course”. Only 4 possible symptoms? Do they need to have all these symptoms or just 1? If it’s just one, then an asymptomatic patient (with +PCR) could be included because temperature below 38.5 includes normal temperature. Their protocol is very sloppy at the least.
    Supplementary material: https://www.thelancet.com/cms/10.1016/S0140-6736(21)00234-8/attachment/17995120-059e-4a34-bd67-f247f6a656b5/mmc1.pdf

  8. debinski says:

    “They changed it to 38.5 C is moderate.” This should read that they changed it to below 38.5 C is mild and above 38.5 C is moderate.

  9. debinski says:

    Maybe I should be wearing a tinfoil hat today but I am finding other oddities with the Sputnik study. “The primary outcome was the proportion of participants with COVID-19 confirmed by PCR from day 21 after receiving the first dose.” However this is a 2 dose study with subjects receiving the 2nd dose on Day 21. So their primary endpoint is measured before the 2nd dose could have had any effect. Weird. And here is how they defined their safety analysis group: “The safety analysis (including rare adverse events) included all participants who had received two doses…” Since when do you ignore AEs that happened after the first dose in subjects who dropped out before the second? How convEnient. I don’t think you have to be a complete paranoid to think there might be some manipulation of the endpoints going on here.

    1. debinski says:

      Their rule for inclusion of serious AEs for analysis is seriously flawed: “The analysis of serious adverse events included all participants who had received at least one dose at the time of database lock AND FOLLOWED PROTOCOL WITHOUT VIOLATIONS.”

    1. Doug H MD says:

      reinfection an anomaly? Depends what you mean by anomaly. Ultimately it is likely it will be the norm I suspect.

  10. DataWatcher says:

    Meanwhile, Gottlieb seems to be cautiously optimistic . . .
    https://www.cnbc.com/video/2021/02/05/dr-scott-gottlieb-we-donat-have-herd-immunity-but-thereas-a-reduction-in-the-transfer-of-infection.html

    Quite a few folks here have suggested that population-wide immunity will depend on a combination of vaccine uptake and people who’ve been exposed and recovered (meaning that the usual “official” estimates of a necessary 70-85% vaccine uptake could be too high); according to Gottlieb, we might be seeing the first, preliminary stages of this now.

    Of course, if re-infections or new infections from mutant variants with greater immune escape capacity continue to appear, that optimism could easily dissipate in a hurry — ditto if more previously infected people are discovered to have experienced drastic reductions in antibody protection.

    1. Marko says:

      “Quite a few folks here have suggested that population-wide immunity will depend on a combination of vaccine uptake and people who’ve been exposed and recovered….”

      Seropositives + vaccinated = progress towards HIT, right?

      Wrong. The problem is , it’s not strictly additive, since you’re vaccinating seropositives. If you go from zero to 50% vaccinated in a background of 30% seropositives, you won’t have 50 + 30 = 80% immunity, you’ll have 65% , because 50 x .3 = 15 of that 50 you vaccinated are seropositive.

      Of course, it will be even worse than that, because by the time you get to 50% vaccinated, your background seropositivity has risen above that initial 30% by some significant amount.

      Vaccinating seropositives indiscriminately at this time is lunacy. It’s a policy designed only to ensure that nobody escapes the profit-sucking vacuum of Big Pharma.

      1. Doug H MD says:

        the best case for doing it is to avoid the need to figure out if people were in fact previously infected. But that is a weak case as you could simply say those with a known PCR positive test.
        Is this really just about profit?

        1. Marko says:

          We have LFT tests that are cheap and fast (15 min) , requiring only a finger-stick, that would pick up the seropositives of interest, i.e. those with sufficient antibody to register as positive would be the ones least likely to need the vaccine at the moment.

          At the very least we’d restrict seropositives to only one dose of vaccine. We already have data showing that for them, the first shot functions like the second in those who are naive.

          1. Oudeis says:

            I see your point, and you may be right, but there are other issues here. Can those fast seropositivity tests be produced and distributed quickly enough that they won’t be a serious bottleneck in vaccine distribution and lead to a ton of wasted doses? Are they accurate enough that they won’t leave a bunch of people thinking they have immunity and then ending up in the hospital?

            I admit the people making these decisions haven’t earned a ton of deference, but I have to think they’ve considered these issues and have some reasons for rejecting your position, even if those reasons turn out in the end to be flawed.

  11. DataWatcher says:

    I wasn’t suggesting vaccinating seropositives; I was suggesting a combination of seropositives PLUS vaccinated people (not necessarily implying an overlap). If I wasn’t misunderstanding him, think that’s what Gottlieb was saying, too.

    1. Marko says:

      If that’s what Gottlieb was implying, why isn’t he beating the drums to STOP vaccinating seropositives indiscriminately. There is no screening for seropositives of any kind going on in the vaccine campaign currently. In fact, the widespread recommendation coming from all the blue-check “experts” is that previously-infected patients should rush to get a vaccination, just like everyone else.

      1. DataWatcher says:

        You’re right, of course — at least for now, with all else being equal, seropositives should not be prioritized for vaccines. I don ‘t see how that would even impact pharma profits in the long run, because I think it’s safe to assume that eventually the entire population would be targeted; and if, as is likely, annual or semi-annual boosters become necessary, it will be more or less a moot point.

        1. Marko says:

          “I think it’s safe to assume that eventually the entire population would be targeted”

          I think it’s safe to assume that’s Big Pharma’s plan. Whether it’s necessary is another matter. What if it turns out that natural infection converts CoV2 into just another common cold coronavirus ,for the vast majority and for life? That is Big Pharma’s worst nightmare, and they will do whatever is necessary to make sure that nightmare doesn’t occur. If you vaccinate everyone, nobody can ever find out that natural infection was so adequately protective, and then you convince those vaccinated that the vaccine only protects for a year, and that they’ll need annual boosters for life. Profit-boosters, they should call it.

          1. DataWatcher says:

            Again, I agree with you in theory. My question isn’t meant as a flame or an attack, but an honest question: Is there a scientifically valid way to research whether “natural infection converts CoV2 into just another common cold coronavirus ,for the vast majority and for life,” without risking the health and lives of your test subjects if this proves NOT to be the case? I wonder how many people who’ve been infected would volunteer NOT to be vaccinated if the stakes were that high? And again I’m not attacking or trying to be difficult — it’s an honest question that I think is crucial to this entire discussion.

          2. Marko says:

            ” Is there a scientifically valid way to research whether “natural infection converts CoV2 into just another common cold coronavirus ,for the vast majority and for life,” without risking the health and lives of your test subjects if this proves NOT to be the case? ”

            You go with what you know at the time. Right now we know that the typical seropositive is vastly more protected than the typical naive person. So, right now, it’s simply unethical to vaccinate them while naive persons are left wanting. When the time comes to vaccinate the seropositives, we can see if the data available at that time tells us whether it’s necessary or not.

            The data may never be available, which could also be part of the plan. There’s a curious lack of reinfection data this far into the game. You hear about the occasional reinfection if it qualifies as scary, but nothing about the likely many thousands that are occurring that are asymptomatic or mild. Very strange.

          3. DataWatcher says:

            Meanwhile, what do you think about Osterholm’s “Category 5 Hurricane” warning? Does this really portend a rewind of 2020, only worse?

            https://www.webmd.com/lung/news/20210201/category-5-covid-hurricane-approaches-expert-says

          4. Marko says:

            If it’s a Cat 5 hurricane, it will probably hit Florida first, which would give Hemingway a familiar topic for a new book if he was still around.

            Florida is at ~7% UK variant prevalence. That should be over 50% in 3 wks or so, which would be enough for us to notice if a storm is indeed arriving.

          5. Marko says:

            BTW, I would warn Osterholm that he’s well on his way to becoming the Thomas Friedman of Covid metaphors, something nobody in his right mind should aspire to.

            First it was “We are dawning on the age of the variants”, missing only the accompaniment of The 5th Dimension, now it’s “Cat 5 Hurricane”, and on tomorrow’s talk shows it will be “Time to call an audible”. At this rate, he’s on the slippery slope to lasting ridicule, right alongside Friedman.

          6. DataWatcher says:

            He’ll still have to work a little harder to match Friedman’s latest: “Vladimir Putin Has Become America’s Ex-Boyfriend From Hell”

          7. Marko says:

            I don’t think anyone could ever top Friedman. He’s the undisputed GOAT of enhanced interrogation of metaphors.

      2. babybird says:

        Already seropositive people are likely highly connected (that’s why they are already seropositive) therefore they block future transmission more effectively than vaccinated individuals who are essentially selected at random connectivity wise.

        simplistic herd immunity calculations lead to simplistic (wrong) answers

        There really is no point vaccinating recovered individuals it is a clear waste of vaccine.

        1. Chris Phillips says:

          I’m sure that’s right. When people are immunised by infection, the immunisation is distributed in a way that is very efficient at reducing future transmission. More so than vaccination, but at least for now I’m sure vaccination should be targeted at reducing severe illness and death.

  12. DataWatcher says:

    Well, if I were a little more conspiracy-minded, I might also suggest that this also relatea to the fact that as we progress further along with the vaccine rollout, almost everything we’re hearing about potential benefits and good news continues to focus on case numbers and positivity rates, rather than severity (unless I’m mistaken, this applies also to the South African “immune escape” data, with the exception of the J&J success in preventing serious illness, hospitalizations, and death, although similar results from Moderna and Pfizer/BioNTech have not been emphasized, even though they’re at least equally impressive).

    We’re also still waiting for the Moderna and Pfizer/BioNTech transmissibility data. If I recall correctly, J&J did not show signs of bringing about sterilizing immunity in their early non-human primate trials, although Novavax did.

  13. Marko says:

    The Supreme Court is now a major participant in “Operation WTF” :

    “Kagan Warns the Supreme Court’s New COVID Decision May Kill People”

    https://slate.com/news-and-politics/2021/02/covid-elena-kagan-supreme-court-kill.html

  14. Doug H MD says:

    “The data may never be available, which could also be part of the plan. There’s a curious lack of reinfection data this far into the game. ”
    That is slowly changing:https://www.webmd.com/lung/news/20210204/study-young-covid-survivors-can-get-reinfected#1 but i agree with you.
    There is a real concerted effort to make sure all those who had natural infections get immunized.
    I fond that odd given how little data we still have. It may be that in this case immunization is better than natural infection in terms of immunity . But that surely is NOT always the case

    1. Marko says:

      There’s a fair number of studies that consistently show that seropositivity confers a high degree of protection against reinfection for a minimum of six months or so. What we haven’t seen is data that would tell us what the IFR for reinfection (Re-IFR?) might be, and I can’t believe that the clinical data isn’t available that would begin to tell us that. People that have been admitted during the recent wave that have a history of PCR positivity from >3-4 months ago could be compared to those with no such history to give us a first-pass estimate on this. Similarly, those who’ve participated in any serosurveys could be followed up on to determine their outcomes from subsequent infection.

      The data from Manaus and S.Africa in this regard is critical, but the last I heard they had only a handful of “confirmed” reinfections in S.Africa, presumably because they’re holding to the “two sets of genomic data” criterion, which is unnecessarily restrictive for a first go at finding out what’s happening there.

      1. Doug H MD says:

        It does seem inexcusable. we are still largely not asking the RIGHT set of questions.
        And we are failing to proceed on the obvious ones like better masks and better rapid tests.
        by the way, thank those who maintain this website for the captcha quiz: my math skills are getting better!

        1. Marko says:

          “…thank those who maintain this website for the captcha quiz: my math skills are getting better!”

          I view it as an Alzheimer’s tracker, and find my progression troubling.

          1. sgcox says:

            Wait till they add logarithms.

  15. Doug H MD says:

    Cat 5 hurricane?
    maybe
    check out the epidemic curve from SA. it is interesting.

    1. confused says:

      I don’t know what the best source for South Africa is, but Worldometers seems to show that things are improving rather quickly, with a peak in cases around Jan 7 and a peak in deaths about Jan 19, and a very rapid dropoff since.

      But I don’t know how effective their measures are (compliance levels “on the ground” etc.)

  16. Bash says:

    Why do I get the feeling the obsession with variants has less to do with COV-2 and more to do with our relatively recent technological abilities in this field?
    I mean, its not like every other virus in existence doesn’t mutate too, including ones from times past which we have defeated with traditional vaccine technology.
    Is this a bit of info overload?

    1. Doug H MD says:

      interesting speculation
      have a gander at the epidemic curve of SA by the way

      1. Bash says:

        OK I just had a look at SA and it was not what I was expecting. You’d expect to see that kind of curve after a 6 month vaccination program.

        So what’s going on?

      2. Marko says:

        I don’t quite get it. Could not the S.Africa curve simply represent the result of a successful lockdown?

        1. Bash says:

          As someone who has been to SA many times, I have a very high level of skepticism of lockdown compliance

          1. Doug H MD says:

            that is what i hear on the ground too

        2. Doug H MD says:

          well it could be.
          Shall i find examples like this not under lockdown?
          are you implying that epidemic curves only come down after lockdown or complete herd immunity?

          1. Marko says:

            No, of course not. Epidemic curves can go down for a variety of reasons – lockdowns, seasonal behavioral changes, rising levels of immunity, etc. I just don’t get why the S.Africa curve is so surprising. It looks similar to that of the UK, and many others that were then followed by new surges.

            I’d be pleased if it turns out that the S.Africa curve represents a near-attainment of herd immunity, but I have no reason to expect that as the explanation.

          2. DataWatcher says:

            “I’d be pleased if it turns out that the S.Africa curve represents a near-attainment of herd immunity, but I have no reason to expect that as the explanation. . .”

            Especially after what now appears to be the false optimism about Manaus. It seems likely that with the ongoing proliferation of variants, “herd immunity” may be an impossible pipe dream:

            “People will need to continue taking precautions even once they are vaccinated, because of the potential for more contagious variants to spread. . . It’s critical to vaccinate as many people as possible and to prepare for long-term behavior change. It’s likely that wearing masks and taking other measures to prevent transmission, especially in the winter months, will become an ongoing part of our lives.” (Christopher Murray, Institute for Health Metrics and Evaluation [IHME], U. of Washington)

          3. Moran Feldman says:

            DataWatcher, you have demonsied the virus. Some level of herd immunity exists even against influenza, which mutates much more easily.

          4. DataWatcher says:

            Well, to be fair, Murray “demonized” the virus, not me — I was merely reacting to his interpretation of the data. As a layman with some working knowledge of epidemiologic principles but no actual clinical training (which is why I’m “DataWatcher,” not “DataAnalyst”), I think I’m one of many trying to ferret out the truth among the drastically different, often contradictory “expert” opinions out there, most of which are using the same basic data and research findings to arrive at markedly different conclusions.

          5. confused says:

            I think it is utterly irresponsible for people like IHME to be talking about taking precautions forever, because:

            – this is likely to discourage vaccination (for those who aren’t personally afraid of COVID, one of the major motivators is “going back to normal”)

            – it doesn’t make a lot of sense given human nature. Once COVID is no longer “new and scary” fear will wane quickly and therefore political will to maintain measures

            I am pretty skeptical that variants long-term will matter more than seasonal flu evolution, and quite likely less (IMO the most likely outcome is SARS-COV-2 ending up as the fifth common cold coronavirus pretty quickly…)

          6. confused says:

            I mean, it seems entirely plausible that we won’t reach “herd immunity”, in the sense that transmission goes down to zero and the disease dies out.

            But other pandemics haven’t ended that way either.

            If immunity isn’t good enough long-term to prevent reinfection, but is good enough to prevent severe disease long-term, then we don’t get “herd immunity” as such… but this just turns into one of many circulating seasonal respiratory viruses, which is plenty good enough to go back to normal. We don’t take dramatic precautions against the four “common cold” coronaviruses, parainfluenza, RSV, etc. etc.

            And – why don’t we worry about variants developing from the four “common cold” coronaviruses? Wouldn’t the same apply for this post-pandemic?

          7. DataWatcher says:

            It’s not directly analogous to COVID, but from what I understand, the CDC estimates that influenza has resulted in between 9 million – 45 million illnesses, between 140,000 – 810,000 hospitalizations, and between 12,000 – 61,000 deaths annually since 2010. That would indicate that there is, in fact, significant variance — not enough to threaten to become a public health crisis like COVID, but certainly not a minor “glitch,” either. Even if it did diminish in virulence, COVID would be starting from a much higher “threshold” than 61,000 deaths per year, so I’m wondering (1) how far down the rates could realistically be expected to go, and (2) what the risk would be that future mutant variants could spike it back up again.

          8. DataWatcher says:

            . . . although both Crotty and Lipsitch seem to concur with you, and that’s a pretty authoritative pair.

            I think it hinges on the speculative, but thus far entirely unsubstantiated, suggestion that the virus will mutate into less virulent forms. Again, I wonder about that because it already does not kill the vast majority of its hosts, so there is no evolutionary reason for it to become less deadly, at least not for a long time. It can continue to become a lot MORE deadly, in fact, before it begins to threaten its own survival by killing off too many of its hosts. And as another poster pointed out, smallpox is at least one example of a virus that never did make that transition, so any hope that this one will do so it just that — hope — until we see definitive data.

          9. DataWatcher says:

            Here’s a NYT article on the Crotty/Lipsitch predictions. Crotty is a bit more optimistic — he sees COVID as becoming no more serious than the common cold, while Lipsitch thinks it could become like the flu, ” mild some years and more lethal in others,” and he’s also concerned about immune response among current and future variants — but overall they’re on similar pages:

            https://www.nytimes.com/2021/01/12/health/coronavirus-immunity-future.html

          10. confused says:

            >>I think it hinges on the speculative, but thus far entirely unsubstantiated, suggestion that the virus will mutate into less virulent forms.

            No – I think it’s about *us* being no-longer-immunologically-naive, not a change in *the virus*.

            The virus doesn’t have to mutate to become less deadly, it just has to stop hitting a population that’s nearly or entirely immunologically naive (which will be true most places in a year or so, one way or another).

          11. DataWatcher says:

            “The virus doesn’t have to mutate to become less deadly . . .”

            But what if, as seems to be the case, it increasingly mutates to develop greater immune escape capabilities? How long before we’ll all be “naive” all over again these new mutations? That’s what concerns me most right now, and I think it’s what’s concerning a lot of researchers, as well.

          12. confused says:

            Well, sure, it depends on what “immune escape” really means.

            But if the vaccines are this good at preventing severe disease and death(whatever the “top line” ‘efficacy’ numbers are), I think it would take a lot of worsening to make it even influenza-level bad for vaccinated people.

            The more interesting question is how good natural immunity will turn out to be – if it’s nearly as good as vaccination, I think the problem will go away really fast, because pretty quickly after people stop taking measures anyone who didn’t want the vaccine will be infected.

            And we don’t worry about mutation/variants for the four common-cold coronaviruses, do we?

          13. Dark Day says:

            “I think the problem will go away really fast, because pretty quickly after people stop taking measures anyone who didn’t want the vaccine will be infected.”

            Hope that doesn’t happen too early in the process; we could end up going through some pretty dark times before the problem “goes away” — Atlas’s mad “herd immunity” scheme come back to haunt us. And yes, in the meantime, it would also give more, and more problematic, mutant strains the opportunity to develop, as well.

          14. DataWatcher says:

            Yes, that’s more or less what I was wondering about, too. It seems clear, to me at least, that more natural infections = greater potential for mutation = greater potential for more dangerous variants. At any rate that seems to be the general consensus among the purveyors of “expert opinion” (Fauci et al.).

          15. confused says:

            @Dark Day: sure, but I don’t think it’ll be that long until most of the most vulnerable population is vaccinated.

            @DataWatcher: re mutation/variants: that sounds plausible, sure, but my question is – why does this never seem to happen (at a level that causes problems) with the four common-cold coronaviruses, parainfluenza, RSV, etc etc.?

  17. Doug H MD says:

    Still and yet: this is supposed to be the most readily transmitted variant, right?
    And still, dropping like a rock

    1. Doug H MD says:

      UK cases fell off the cliff too

      IMO this is simply epidemic dynamics.

      Not herd immunity overall. herd immunity in those places hardest hit is my guess

    2. Bash says:

      Its fascinating, truly.
      I don’t think comparisons with the UK are apt, as England has different lockdown compliance levels. And has been vaccinating for 2 months
      Could it be that the SA variant – while more infectious – is less virulent?

      1. Marko says:

        “Could it be that the SA variant – while more infectious – is less virulent?”

        I think it’s possible, but I haven’t seen any commentary to that effect. It would be great news, if true.

        1. Mariner says:

          Well, it’s summer in South Africa at the moment. Could this have an impact? More vitamin D and so forth (assuming vit D levels do have a significant impact on the severity of illness). Other than that small Spanish study from months back, I don’t think I’ve seen mention of any detailed studies about vitamin D and Covid-19.

          I realise it is summer in Manaus as well but they have a lot less sunshine there during this time of the year.

          Or, it could be that the SA variant is less virulent.

          1. Chris Phillips says:

            I think what happened last summer in the northern hemisphere, and what happened at the end of the summer, suggest pretty strong seasonal variability of transmission. Particularly in Europe, when most of the legal restrictions were relaxed but numbers didn’t increase much for a couple of months, but started to rise in most places in the autumn.

            Manaus is only just south of the equator, so a lack of seasonal variation there wouldn’t be surprising.

          2. DataWatcher says:

            Almost buried in one popular press report (Washington Post, 2/7/2021) on the immune escape potential of 351: “There was no evidence these follow-on infections were severe or deadly, but authorities view the South Africa variant — as well as another that emerged first in Brazil — as posing a particularly high risk for reinfections.” We really need some definitive data on severity in these “immune escape” cases before we conclude that the sky is, in fact, falling.

          3. Antibody says:

            Case numbers in the UK were hard to measure for a few weeks after restrictions were lifted because infection levels were so low. They started rising at almost exactly the same time as the government started paying people to eat out and re-opened the schools. There’s no need to look too hard for another explanation.

            As for vitamin D:

            Vitamin D and COVID‑19 infection and mortality in UK Biobank
            Conclusions: Our findings do not support a potential link between 25(OH)D concentrations and risk of severe COVID-19 infection and mortality
            DOI 10.1007/00394-020-02372-4

  18. DataWatcher says:

    In the past, we have certainly seen increased transmissibility correlated with decrease in virulence (e.g., “Spanish” flu). I’d like to believe this was possibly the case here. But it seems to me speaking in purely evolutionary terms, that COVD does not have a self-interest in becoming less virulent, even if it becomes drastically more contagious. Although the denialists and anti-vaxxers have hijacked these data, the fact does remain that the vast majority of infected individuals do not die; somewhere between 40-50% of them experience no symptoms at all. So the virus has a huge “cushion” to continue to increase its virulence before it becomes at risk of killing off too many of its hosts. (Haven’t we found, in fact, that 117 s probably both significantly more contagious — perhaps as high as 80% more — AND more virulent as well?) I’m not sure what the tipping point is, but COVID has a long way to go before it reaches it. And again, I fervently hope I’m wrong.

    Meanwhile, Oxford/AZ seems to be following the same patterns as the others in terms of it efficacy against 351 — reduced efficacy against mild/moderate symptoms, but possibly robust protection against serious symptoms that would result in hospitalization and/or death. And I concur 100% with Marko that this is the direction in which research — and, eventually, public policy – should be heading.

    1. JS says:

      Well, there is another selective pressure possibly at work. The less symptoms your host shows the more likely you host is to mix with others and thus to spread. If less early symptoms correlate with less severe disease, then you have selective pressure for less severe disease.

      1. DataWatcher says:

        Interesting, and potentially optimistic (if a bit counterintuitive — “Mildly symptomatic carriers should try to become superspreaders!”). Any epidemiological evidence that this could be the case?

        1. JS says:

          I would probably not word it quite like that. A somewhat anthropomorphized wording might be that it is a great strategy for a virus to turn all carriers into asymptomatic (super) spreaders.

          I am not claiming that there is epidemiological evidence for or against this. Far from my field of research.

          1. DataWatcher says:

            In fact, this does appear to be the history of the common cold virus, and many believe it’s at least partially responsible for the diminution of the 1918 influenza (“Spanish Flu”) epidemic. Again, incredibly good news if that’s what’s beginning to happen here, but so far I don’t think there are any data to suggest that possibility (and again, am I correct in remembering that the evidence shows 117 to be both vastly more contagious AND more virulent? Or am I mis-remembering some details?) . . .

          2. George Dorbell says:

            @JS: “…might be that it is a great strategy for a virus to turn all carriers into asymptomatic (super) spreaders.”
            @Datawatcher: “In fact, this does appear to be the history of the common cold virus…”

            …Interesting ideas, although not my field either. As for the counter-intuitive, to a physical scientist, grown up and educated in the second half of the 20th century, structure of matter, as nowadays understood, is pretty counter-intuitive. All that quantum mechanical mush that underlies all things great and small. Likewise the space-time-event continuum. Mind and space bending stuff. Envisioning consciousness and All That.

            Understanding of quantum mechanics and relativity began to fall into place this time last century. Followed in turn by molecular biology from mid-century onwards. Humbly submit scientific impact far from played out yet. Wonder how the scientists of 2121 will look back on the science of a century earlier?

            There’s another relativity, exemplified by the relativity of two BMJ papers published last year that prompted forty responses between them, mostly from medical doctors, with a few contributions from other disciplines, including a couple of software engineers and a journalist. The BMJ papers, published in consecutive issues, are:

            BMJ 2020; 369: m1808 “Interpreting a covid-19 test result”
            BMJ 2020; 370: m3563 “Covid-19: Do many people have pre-existing immunity?”

            Responses read as if written from personal experience and in good faith. Quite a few contradictions apparent. Job of honest science arguably to reconcile as many contradictions as possible, not to prioritise one set of views while dismissing another. Titles listed above perhaps give feel of what I’m referring to?

            If history of physics read right, contradiction still exists between relativity and quantum mechanics. Grand Unifying Theory of Everything still sought. Won’t be resolved by ditching one or other protagonist, otherwise why bother building the Hadron Collider?

            *****

            Reassuring that if common cold hypothesis holds, SARS-CoV-2 ultimately heading in less malevolent direction, as per destination the four common cold coronaviruses ultimately ended up at. All this mutant immune escapism stuff dead end side roads from main highway of travel. Knowledge a two edged sword – what you don’t know of, you can’t worry about.

            If so minded, over to open-minded and questioning immunologists, virologists and epidemiologists to consider the hypothesis JS floated. Maybe hypothesis conceivably fits some titbits of observed data, or new experimental designs could be formulated to test hypothesis?

            If verifiable, then could be radical implications for public health policies. Shock horror – some aspects of the last year’s restrictions might even turn out misguided. Those early 22nd century scientists may look back aghast. The Experts really believed THAT in 2020…

            Better watch out, lest again accused of peddling witless, malicious nonsense during a public health emergency. Careless Talk Costs Lives and All That. And thank you, Chris Phillips two comments down, for perspective on re-infection in 0.03 percent of people tested positive in Minnesota, as mentioned in passing by NBC.

            Fact is pessimism sells newspapers, websites and advertising slots better than optimism. As peddled by science correspondents who’ve never lived, breathed and slept with the devil in the detail of new ideas, data and theses. Hold the faith in new science.

            Humbly also submit not only an ongoing public health emergency, but a public truth emergency too. Happened that way throughout history. Big truth emergency in the era when quantum mechanics, relativity and idea of the space-time continuum came to the fore.

            Took a deal of resolving, which in turn led to yet more truth emergencies in the second half of the last century, fallout of which continues to this day. Don’t come back Senator McC, all not forgiven. Ditto Uncle J, The Chairman and El Generalissimo.

            Lest we forget, history of country where this written from is full of past truth emergencies. The history of the English speaking peoples no doubt gets told rather differently in other languages. But best not erase history and pretend it never happened, an illusory comfort blanket in the here and now, or re-write the language so a spade gets called all sorts of fancy names, none of which bear much resemblance to a spade.

            Era of a century ago, when quantum and relativity came to fore, also era after Freud and era of Wittgenstein, and things which can be known of but not put into words. Hold the faith in science as a force for good.

            ******

            Dr Y’s Twitter feed taken down last Friday evening. Open to all Twitter viewers. Very useful source of links and views, some of which I ascribed to, some not. I’d looked into Dr Y’s background – experienced research biologist, with 20 peer reviewed papers listed on ResearchGate on inflammatory and respiratory biology, published between 2008 and 2013.

            As far as I can make out from tweets on other feeds that had in the past retweeted Dr Y’s feeds, Dr Y’s Twitter account may have been hacked and unsavoury comments posted, purporting to have been made by Dr Y himself. Twitter’s algorithm intervened and suspended Dr Y’s account. In a screenshot posted on another feed, Dr Y commented that after this experience he was done with the Twitter platform.

            Am aware of a commenter on this blog who’s posted at least two links personally derogatory of Dr Y. Likewise an ad hominem comment from the private Twitter feed of the science correspondent of a national newspaper. A Dr C, an immunologist, as retweeted by another Twitter user, commented within minutes of Dr Y’s feed being taken down, “Dr Y is gone.” Dr C clearly not a fan of Dr Y.

            Friend of mine always does say Twitter is for the birds. Out of curiosity, I checked the critical Dr C’s Twitter feed – “These tweets are protected. Only open to approved followers.” Says it all. Case rested, M’Luds & Ladies.

          3. JS says:

            I was probably a bit careless in my original posting. All I really wanted to say was that there can be selection for milder disease, even if the original variant does not kill a significant number of hosts. Killing the host is not the only way a pathogen can prevent the host from transmitting, so can making the host stay at home or be shunned by others.

            Is this at work now? I doubt that it is the main driver at the moment. But it is a mechanism to consider.

            Not sure what evidence there is for this mechanism in the case of the Spanish Flu or the OC43 coronavirus epidemic around 1889, but I would be interested.

            For OC43 and the other old endemic corona types I think that this simple theory (proposed by others) is the more likely:
            1. Small children don’t get very sick, even if immunologically naive.
            2. As herd immunity develops, new variants will appear to escape the existing immunity.
            3. We thus keep getting exposed to slightly new variants throughout our lives.
            4. Once you have been infected once or perhaps a couple of times your immune response will be good enough to only get a mild disease from these new variants.

            Unfortunately there is apparently enough freedom to keep mutating and avoiding the existing immunity.

            Does this theory hold up to the data? There was recently a paper comparing the neutralization capability of old plasma for new variants of the endemic strains and vice versa which seemed to agree. The big question is if we have examples of the endemic strains being introduced into immunologically naive populations? May not exist. But if that did not cause something like what was seen around 1889 or today, then we will need to consider that the existing strains have evolved to cause less severe disease.

            At the moment what we see seems to be a combination of two effects:

            1. We have a virus that has just jumped from another species. As such it is not optimized for humans. Therefore it will find mutations that are more optimal, thereby increasing R (R0, Re, Rt). Indeed, we have seen a steady replacement of variants, even in countries without significant herd immunity. D614G and N501Y are prominent examples of this.
            2. As significant immunity is starting to appear in some populations, variants appear that avoid this immunity. E484K is likely an example of this. It is not that E484K only has recently appeared. It has been around for a while at a low level, as seen in the databases and as expected from the known mutation rate of the virus. Had it caused a significant increase in R (at least in isolation), we would have seen an increase long ago. We did not, so likely R is not significantly higher for E484K. K417N might well be in the same category.

            With luck the theory for the endemic strains above also applies to the current one and hopefully the vaccine works well. If so it will soon become the 5th endemic strain causing a cold every few winters. Or I may be too optimistic.

          4. Chris Phoenix says:

            Some viruses seem to mutate to become less lethal over time.

            Smallpox did not.

            Given the high fatality rates for SARS-1 and MERS, I think it’s way too early to say “This will turn into another common cold.” We can hope for it – but we can’t plan for it.

          5. George Dorbell says:

            @JS, @Chris Pheonix

            Looked up smallpox on CDC website. A variola virus. Same genus as monkey pox and cow pox – seem to recall history tells that Jenner injected a boy with cow pox, after noting milkmaids rarely caught smallpox?

            Not quite same for coronaviruses, if common cold hypothesis holds? Four out of six eventually turned benign, SARS and MERS didn’t – contained and stopped, so thankfully nature of menace never seen on pandemic scale.

            So maybe cause in ratio 2:1 for optimism over pessimism? As for planning for the worst, in a previous existence used to be referred to as risk management, before that as contingency planning, which get impression before that a less-existent concept. Talking pre-1980 here.

            All that risk management and contingency planning could get very consuming, and on occasion seemed to become an end in itself. As of course the SARS-CoV-2 epidemic has arguably become all consuming, especially for younger people caught up in a threat the vast majority of younger people aren’t at much risk from. The so-called new normal.

            Not entirely sure what I’m trying to say here, other than that idea of a fallback position arguably more realistic to live with. In case of a research project, building in a position to fall back on to keep project going in event of foreclosing data.

            By definition, fallback doesn’t become an activity in its own right, but actually implicit to plan of attack. Example would be project aiming for selective modulator of target A, a member of target class A-D, struggling to find orally bioavailable chemical matter, and, as fallback, doing key experiments that tested to destruction best compound with better PK from that small opportunistic area of chemical space that inhibited both A and B. Where a project I once worked on eventually fell back to.

            No idea if there’s an epidemiological parallel. Maybe, if must, starting with that three week lockdo’n, then keeping an open mind on where next based on critical look at data three weeks later, rather than slavishly extending to three months up front.

            *****

            As for… “For OC43 and the other old endemic corona types I think that this simple theory (proposed by others) is the more likely:
            1. Small children don’t get very sick, even if immunologically naive…”

            …Not sure how this fits with small offspring bringing home to mum and dad every common cold, rhinovirus and staph this, that and the other on offer at nursery and pre-school, which mum, dad and all the other mums and dads promptly take into workplaces. Yet children seem pretty much unaffected by the latest coronavirus on the block? Accounts of 1889 epidemic seem to imply children then very much at risk?

            Back to drug R&D. In that previous existence we had the CDTP – Candidate Drug Target Profile. For those outwith the business, CDTP was the property and biological activity profile you’d shoot for in order for a candidate drug to stand a chance of going on to clinical trials (and ultimately regulatory authority approval).

            CDTP not set in stone. Evolved as project evolved. And generally more than one way to tame your tiger. For example, highly potent but modest PK and physical properties, or vice versa. To get to the CDTP, you’d try to find a chemical start point that met the Screening Hit Target Profile (HTP) and then strive to optimise your chemical series in direction of the Chemical Lead Target Profile (LTP).

            Implicit in these earlier profiles would generally be potency vs drug target (IC50), physical and pharmacokinetic properties. Measured or calculated LogD value (lipophilicity) often a crude indicator of scope to optimise properties.

            Plotting Log[IC50] (pIC50) vs LogD an informative indicator of where chemical series sat. Generally the higher the pIC50: LogD ratio, the better. Increase in ratio as new compounds made often taken as broad indicator project progressing toward CDTP. Bonus – easy to explain to project biologists, managers and resource allocators…

            So what about defining an epidemiological CDTP to help understand and put into perspective the nature of the threat – a Contagious Disease Threat Profile?

            Key parameters host transmissivity (R number, encompassing host infectivity, guest interactivity, physical environment, etc), guest sensitivity (similar considerations, plus guest immune susceptibility), incubation time and infection-fatality ratio (IFR)? Maybe R x IFR % a possible composite parameter, or would that bring in double counting?

            Examples? Ball park numbers taken from UK influenza pandemic preparedness documents put together in the last couple of decades by Public Health England and the NHS…

            1665 London Plague: R = 4? IFR = 25-75%, R x IFR = 100-300%?
            (numbers interpolated from Daniel Defoe’s “Journal of the Plague Year”, a reconstruction sixty years later based on documents and records of the time; higher IFR reflects mass exodus from London that included five year old Daniel Foe)

            1919 Spanish Flu: R = 3? IFR = 2-3%, R x IFR = 6-9%

            2003 SARS 1: R = 1.8, IFR = 10%, R x IFR = 18%

            2011 Contagion the Movie: R = 4? IFR = 25%? R x IFR = 100%?
            (numbers made up…)

            2020 SARS 2: R = 3, IFR = 0.5%? R x IFR = 1.5%

            …Fair to add that this time last year IFR of 5% being cited for SARS 2, which gives 10x higher R x IFR than actually turned out.

            Shock horror – maybe looked at like this, SARS 2 better captioned MARS (Marked Acute Respiratory Syndrome)?

            Final thought. Drug R&D uses comprehensive compound and assay database to home in on Candidate Drug. No such thing for disease epidemiology, although maybe heading that way in some parts of the world. Door to Orwellian future duly opened, all in worthy cause of Staying Safe and Saving Lives.

            Maybe only yesterday’s person, statistically just entering last lap of life’s 400 metre race, who has any such qualms. On way to fait accompli for today’s persons sprinting round the earlier laps..? Be careful what you wish for.

  19. DataWatcher says:

    Meanwhile — “COVID Reinfections May Be Much More Common Than Realized” (No indication here that reinfections are less serious, either — “Evidence suggests there may not be a clear-cut return to normal.”)

    https://www.msn.com/en-us/health/medical/covid-reinfections-may-be-much-more-common-than-realized/ar-BB1dt3Uy?ocid=msedgdhp

    1. Chris Phillips says:

      It’s funny, because the numbers they actually mention – such as “more than 150” suspected reinfections in Minnesota (which has had nearly half a million positive test results) sound less common than I would imagine.

      1. confused says:

        Yes, 150-200 (I imagine that they would say “more than 200” if it was over that) *suspected* reinfections for a mid-sized-population state like MN actually sounds extremely positive!

      2. Marko says:

        There were about 75,000 PCR+ in the first wave ( say, thru end Aug ) , or ~1% of the Minnesota population. In the second wave ( Sept forward ) ~ 7% of the population tested PCR +. If the positives from the first wave were equally likely to become positive during the second wave, you’d expect to see .07 x 75,000 = 5250 testing positive in both waves, i.e. reinfections. If only 200 occurred, that would imply >95% efficacy of the “vaccine” of natural infection.

        1. DataWatcher says:

          And, to be fair, nothing (as far as I know) on whether any of those reinfections were mild, moderate, or serious, or whether any of them led to hospitalizations or death.

        2. Marko says:

          This is admittedly a very crude estimate. You’d want to separate the first from the second wave by 3-4 months ( say, July-Sept ) to ensure you weren’t picking up persistent PCR positives rather than reinfections, but I don’t think the basic conclusion would change much.

          It’s hard to say anything without a look at the data. These anecdotes from the media really don’t shine much light on the matter.

  20. Chris Phillips says:

    Sky News reports:
    The UK has been “vindicated” over its “brave” decision to offer vaccines doses up to three months apart, the World Health Organisation’s special envoy on COVID-19 has said.
    Dr David Nabarro told Sky News’ Sophy Ridge On Sunday the move had provided the rest of the world with a “great lesson”.
    The UK went against the advice of the World Health Organisation (WHO) by choosing to offer a second jab between three and 12 weeks after the first dose.

    https://news.sky.com/story/covid-19-uk-vindicated-over-brave-decision-to-delay-second-vaccine-dose-who-official-says-12211550

    1. Antibody says:

      “The UK has been “vindicated” over its “brave” decision to offer vaccines doses up to three months apart”

      Ah, a brave decision. Good, I wouldn’t have liked to think it was a panicky one in response to a huge spike of hospitalisation, caused by a total failure of the UK authorities to apply sensible public health measures over the festive season.
      I don’t suppose the WHO could say that exactly though.

  21. lizzy says:

    Datawatcher:
    Here’s the British paper showing that there is a “realistic possibility” that the B117 variant is more deadly. It sounds more like “who knows for sure”. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/955239/NERVTAG_paper_on_variant_of_concern__VOC__B.1.1.7.pdf

    As an anecdote, a client of mine who processes Workmans’ Comp claims for the Sheriff’s Department said the following. She works exclusively on sick leave for Covid 19. Because we live in a large metropolitan area, there are thousands of such claims, she is responsible for half of those whose last names end in “A”. They do require a positive PCR as well as documentation of symptoms. The claimants are followed. Their company records document a 20 to 25% reinfection rate with Covid 19. I asked if the statistics were a public record. They are being compiled, but no, they are not public.

    I found this information interesting but I can’t help but doubt its veracity. Certainly jailers have a high infection rate. Certainly working as a sheriff in the jail or on the front line is very stressful, especially now. It would be nice to get paid for taking time off. 25% reinfection rate? Serial payments for Covid 19 positivity? Hmmm.

    1. DataWatcher says:

      Unless I’m mistaken, 117 is the dominant strain in Israel. Nonetheless, Pfizer is kicking COVID a$$ all over the place among those who have gotten vaccinated (primarily the elderly). Israel’s overall infection rates continue to be high, but that may have a lot to do with vaccine resistance (esp. among the Orthodox community) and lax compliance with lockdown restrictions (esp. among younger people, who are also the cohort yet to be vaccinated).

      As for your anecdote, it’s interesting, but in fact prisons and jails are among our most serious hot spots, so although I don’t doubt a few people are gaming the system, I’d probably trust those reports for the most part. Now if those COVID sick leave requests continue to pour in after a significant number of the jail and prison staff have been vaccinated, we’ll definitely have reason to suspect something.

    2. Marko says:

      Did your friend tell you what the infection rate was for the jailers who had not been previously infected? If the attack rate among them over the same time period was very high, i.e. very much higher than 25%, then the reinfection rate might be plausible. Otherwise, I’d agree it sounds more like a bunch of slackers who’ve figured out how to game the system.

    1. debinski says:

      The more I look at the data and methods for data analysis in the Sputnik vaccine publication, the more I wonder how Lancet thought this was OK to publish – especially without a protocol being available.

  22. Marko says:

    “Immune escape” is probably the wrong term to describe what we’ve seen so far. What we’ve actually seen is “antibody escape”, which may not tell the full story about the remaining immune protection against severe disease. Shane Crotty reminds us not to forget about T-cells :

    https://twitter.com/profshanecrotty/status/1358502872049094657

  23. Quin says:

    New data from Israel: a hospital reports that of 440 hospitalizations since the beginning of January, 2% were people who were deemed “fully protected” by the Pfizer vaccine.

    Among the seriously and critically ill, the percentage was 1.5%.

    It is difficult to deduce effectiveness from this data, but at the end of this period, approximately 30% of the general population was vaccinated.

    https://twitter.com/tasmc1/status/1358785091355500547

  24. lizzy says:

    Here’s my main problem with just looking at moderate/severe disease, hospitalizations and deaths. You’re saying that that would be good enough. I agree but….
    All of these trials used for EUA are either under powered or weren’t continued long enough to give us meaningful results. You can’t just wait for a week or two after the second dose and say hospitalization was prevented 100%. The numbers are too low to be meaningful. It’s been almost 9 weeks since Pfizer’s EUA. Where’s the follow up data? Have I missed it? All this data is supposed to be transparent, right?

    At some point you need to look at what people do, not just what they say. Pfizer and Moderna say that they neutralize variants in their petri dishes pretty well. But they immediately went to work on retooling their vaccines to the South African variant.

    1. Marko says:

      I agree that the trial data on hosp./deaths was too sparse to tell us much. The on-the-ground data coming out of Israel, and hopefully the UK soon, should give us a better idea.

      I don’t expect the data from the US will tell us anything, ever. We seem to have perfected the art of patient data privacy to a ridiculous degree, such that if a patient doesn’t remember and then personally report his medical history to someone doing a study, it disappears into the ether, never to be seen again. The NSA and Jeff Bezos have it all , of course, but you’d have to pay them gobs of money to get a look at it, which Big Pharma and Big Insurance are more than happy to do, I’m sure.

    2. Doug H MD says:

      yes, where are the updates to the data by the way? Anyone know when we might expect them?

      1. guneapig says:

        The next trial participant visit/blood-draw in the US Pfizer trial is at 6 months post 2nd-shot. So, probably starting February-March-ish. Who knows how long after that for publication.

        1. Doug H MD says:

          thank you!

  25. lizzy says:

    One of the many things I’ve learned here is about how our immune systems mature over time, and more correctly hone to their target. If this is indeed the case, then protection from 2 doses of an MRNA vaccine should improve in the weeks to months after the second dose. I just want some follow up, but there’s none to be had. Yes, it would be complicated by the fact that both Pfizer and Moderna are actively vaccinating eligible volunteers in their placebo groups. That with variant emergence, seasonal fluctuations, rising numbers of vaccinated individuals certainly makes for squishy hard to interpret data.
    The VAERD database is public. Why not the follow up data.
    Yes, I see why you focus on the Israelis, the Brits, and now those South Africans. It’s real world. I certainly am the probie here, as I am certainly not versed in your field.

    As to HIPPA violations, my experience is that it’s more aimed at the individual doctors than subjects in research trials. You agree to have depersonalized data used by Big Pharma for “research purposes” as well as to hold them harmless when you sign up. Vaccine recipients also do so before they get their vaccines.

  26. Dentdelion says:

    Thank you Derek Lowe for all you do, for all of the readable, important information you provide. I have really enjoyed this blog and all the fascinating comments.

    I have a question for Derek and this group that I haven’t seen addressed anywhere: What are the physiological advantages AND disadvantages (excluding the psychological and public health, which are obvious) to 3 jabs (getting vaccinated now plus a booster) vs. 2 jabs (waiting for the booster and staying very isolated).

    I would love to hear all of your opinions! Thank you!

  27. Marko says:

    Pfizer vaccinee sera shows robust neutralization against the mutations of concern in the variants of concern. In Nature :

    https://www.nature.com/articles/s41591-021-01270-4

    The TLDR bottom line, for me :

    “The authors declare competing interests. X.X., V.D.M. and P.-Y.S. have filed a patent on the reverse genetic system. K.A.S., M.C., D.C. and P.R.D. are employees of Pfizer and might hold stock options. X.X., J.Z., C.R.F.G., H.X. and P.-Y.S. received compensation from Pfizer to perform the neutralization assay.”

    1. George Dorbell says:

      Just to clarify the “Too Long, Didn’t Read” bottom line dig – Pfizer exploiting the American government/people?

      Vaccinations here in the UK run by the National Health Service and offered free of charge (my turn tomorrow). Just occurs to wonder how paid for in the US – government, insurance companies, individuals?

  28. Marko says:

    New paper shows that a single dose of an mRNA vaccine gives ~1000 fold boost in neutralizing titers in seropositives, against Wuhan virus AND against the SA variant :

    https://twitter.com/profshanecrotty/status/1358907013044989952

    This makes the Oxford/AZ trial results in SA even harder to understand.

    1. Marko says:

      “This is now the third paper to find a very very good immune response after one shot of mRNA vaccine in people who had a previous SARS-CoV-2 infection. Time to discuss policy changes..”

      https://twitter.com/florian_krammer/status/1358939148313362433

      Long past time, IMO. We knew even before any of the three papers, just on basic principles, that seropositives were at less risk than the never-infected, and thus the vast bulk of them should be at the back of the line.

    2. Chris Phillips says:

      Thinking also about the results of the Johnson and Johnson vector vaccine, which didn’t seem to differ very much for the South African variant, perhaps this is more an issue with the AZ vaccine specifically than with the variant?

      Given that the interval between doses was 21-35 days, and for that interval the efficacy we already knew about was just 53.4% with a huge confidence interval from -2.5% to 78.8%, I wonder whether the new finding of -78.8% to 54.8% is really adding much to our knowledge.

      In fact, if it hadn’t been for the longer interval in the accidental half-dose group, can we be sure the result of the UK/Brazil Phase III trial wouldn’t also have been “no significant evidence of efficacy”?

      It seems they may now go ahead with something between a Phase III trial and mass vaccination in size – 100,000 people – to try to get a better idea about the effect on severe disease:
      https://www.sciencemag.org/news/2021/02/south-africa-suspends-use-astrazenecas-covid-19-vaccine-after-it-fails-clearly-stop

      1. confused says:

        >>Given that the interval between doses was 21-35 days, and for that interval the efficacy we already knew about was just 53.4% with a huge confidence interval from -2.5% to 78.8%, I wonder whether the new finding of -78.8% to 54.8% is really adding much to our knowledge.

        Well, all else being equal, and based just on those numbers and no special expertise, I don’t see how it *could* add much of anything given the massive overlap in the confidence intervals.

        It could *suggest* lower efficacy since the maximum and minimum are lower, but not really demonstrate anything at all.

        1. Chris Phillips says:

          Really that’s the point of quoting the confidence intervals, because the fact that they’re so wide makes it clear that while the difference in the point estimates may be suggestive, it’s nowhere near conclusive.

          It’s a bit surprising that it says on the Oxford University website that “viral neutralisation by sera induced by the ChAdOx1 nCoV-19 coronavirus vaccine against the B.1.351 coronavirus variant were [sic] substantially reduced when compared with the original strain of the coronavirus”. I don’t think they’ve shown that in statistically meaningful terms.

          1. confused says:

            Yeah, I think those numbers could at most support “may be reduced, possibly substantially” not “were substantially reduced”.

  29. Marko says:

    Adam Kucharski with a nice illustration showing why selection pressure for immune escape vs. transmissibilty increases as population immunity increases. V1 is a high-transmissibility variant and V2 is an immune escape variant :

    https://pbs.twimg.com/media/EtzSVBbXYAgrHmL?format=jpg&name=small

    In a country with good surveillance of incidence, seropositivity and genomics, you could easily determine the relative contribution of transmissibility vs. immune escape in any new variant by monitoring the case dynamics in high vs low seroprevalence areas. Of course, on this planet, such countries are few in number, if there are any at all.

    1. Marko says:

      In terms of the UK, you might think of V1 as the current UK variant, and V2 as the immune escape version with the 484k mutation, assuming that’s the one responsible for antibody evasion. As vaccination and population immunity continues, we should see more of V2 and less of V1.

      1. Mariner says:

        We know that B.1.1.7 and B1.351 share some of the mutations. I suppose it’s too much to hope that people with prior infection by B.1.1.7 might be more resistant to reinfection by B1.351? If nothing else, it would reduce the speed of spread of B1.351 in countries with lots of B.1.1.7 infections. Could give a bit more time for the ‘booster’ vaccines or treatments to be developed.

    2. DataWatcher says:

      Earlier on in one of these threads, someone suggested that vaccines that don’t confer sterilizing immunity could actually make things *worse* for this very reason — more resistant, possibly more virulent, mutant strains developing. At the time, that was criticized as being an overly pessimistic prediction. Do these findings indicate that maybe it was prescient after all?

      1. Marko says:

        What’s the alternative? Waiting until we’ve developed the perfect, 100% sterilizing, lifetime-protecting vaccine, by which time everyone in the US will have been infected, with another million or more dead?

        Immune escape and virulence mutations don’t bother us with the endemic coronaviruses. I’m not worried about them in CoV2 until we see evidence that they’re going to be a problem long-term.

        1. confused says:

          Yeah, I think this is going to pretty quickly go endemic… and after that, well, why don’t we worry about mutations/variants about any of the endemic respiratory viruses (not just the four “common cold” coronaviruses, but parainfluenza, RSV, etc. etc. as well)?

          I think pandemics and big outbreaks are generally either animal->human jumps or contact between previously totally disconnected human populations (smallpox in the Americas, measles in Polynesia). The latter isn’t really possible anymore since the world is so connected.

          Is there any case of a *previously circulating endemic virus* in humans suddenly mutating into a significantly greater threat?

          If not, why are we assuming endemic COVID won’t be as insignificant as the other endemic respiratory viruses?

          I really don’t get it. It seems the historical evidence is that respiratory pandemics end really fast — only stuff with other routes of transmission (bubonic plague, cholera) remain pandemic for more than two years or so.

  30. Marko says:

    “Seasonal human coronavirus antibodies are boosted upon SARS-CoV-2 infection but not associated with protection”

    https://www.cell.com/cell/fulltext/S0092-8674(21)00160-4?rss=yes

    It will be interesting to see what kind of workaround the denialist gurus come up with to explain this. “We weren’t talking about herd immunity against infection, we were talking about herd immunity against ( fill in blank ).”

  31. Marko says:

    People who are vaccinated (or previously infected) who nonetheless become infected (again) will probably contribute less to onward transmission that those who were never vaccinated or infected, but don’t expect this effect to be large. See :

    https://twitter.com/MonicaGandhi9/status/1359183934060285955

    From The Lancet study : “Secondary attack rate 17% (125 of 753), with variation from 12% when index case had a viral load lower than 1 × 10^6 copies/mL to 24% when index case had a viral load >=1 × 10^10 copies/ml.”

    So the secondary attack rate was cut in half if the viral load was 4 logs lower. Keep in mind that the recent data from vaccinees in Israel, as well as the study on reinfections among Marines, only showed about 1 log lower viral loads in those infected.

    1. Marko says:

      Just to be clear, I think vaccination (or previous infection) WILL reduce transmission rates significantly, but the main effect will come from reducing infections, i.e. reducing the viral load to effectively zero, or PCR negative, among those who would have otherwise become PCR positive infections, with the attendant high viral load.

      1. Doug H MD says:

        I hope you are right but we dont know that since the trials did not look at that.

    2. Marko says:

      A lot of people in the twitterverse are confused about this, e.g. :

      https://twitter.com/DiseaseEcology/status/1359213735424872450

      “…Transmission efficacy:
      IE*0.93^2 (.93 per log, 2 logs) = 89.9%…”

      Complete bullocks. The Israel data this is based on shows a two “Ct” reduction in viral load, which is a factor of 4, while two “logs” would be a factor of 100. It takes ~3.3 Ct reduction per log reduction in viral load, and, as outlined above, one log reduction in viral load won’t buy you much “efficacy” in reducing transmission.

      1. Marko says:

        BTW, for my UK friends, in America, bullshit + bollocks = bullocks.

        Also, when criticizing Balloux (always a worthwhile endeavor), “ballocks” is the proper term.

      2. Chris Phillips says:

        I’m not sure that factor for the effect of viral load is greatly inconsistent with the Lancet data you cited, but anyway it’s only having a small effect in that Twitter calculation – changing an infection efficacy of 88.3% to a transmission efficacy of 89.9%. (The second equation is a nonsensical way of expressing the calculation that’s been done – because obviously multiplying something by 0.93^2 should make it smaller, not bigger – and in the first 0.385 should be 0.615, though the result seems correct.)

        But my worry about the calculation would be whether those swabs the tweeter is relying on could have been presymptomatic rather than asymptomatic.

        1. Marko says:

          If the claim is only an additional 1.6% increment added to the percentage reduced transmission gained from fewer infections, then I agree that that’s plausible. I can’t reconcile the apparent confusion about equating Cts to logs, however.

          The Moderna data from the swabs on the day of the second jab were all in patients with no symptoms, so to me that data qualifies as a more-or-less random survey for asymptomatics in the trial population. Combined with the Oxford/AZ UK swab data, I think it’s safe to say that overall ( symptomatic plus asymptomatic) infections are reduced. By what percentage is still somewhat up in the air, I think. I’d guess it’s probably 50% or better.

          1. Chris Phillips says:

            I am just thinking that some of the “asymptomatics” might have been recently infected and might have gone on to develop symptoms soon after they were swabbed. Given that the calculation assumes four times more symptomatics than asymptomatics, perhaps that could bias the result. But probably that is a relatively small effect too.

            I don’t think the calculation would come out so well for AZ, where there wasn’t much of a net reduction in asymptomatics, but unfortunately that seems to be the worst performer on several measures.

  32. Marko says:

    Preprint of the Eran Segal at al. work on the vaccine rollout in Israel :

    https://www.medrxiv.org/content/10.1101/2021.02.08.21251325v1

    “By February 6th 2021, 45.3% and 29.7% of the entire Israeli population (89.9% and 80% of individuals older than 60 years old) received the first dose or both doses of the vaccine, respectively, or recovered from COVID-19.”

    If the vaccine has high efficacy in preventing deaths, it should start showing up in sharply lower overall daily death levels pretty soon, even if cases fail to decline dramatically, since they’ve already vaccinated virtually the entire population that’s at elevated risk of death from Covid-19.

    1. A Nonny Mouse says:

      Supposed to be some information coming out this week from the UK on the effectiveness of the Pfizer and AZ after one dose. It says the Pfizer is 65% effective after 2 weeks and the AZ is similar after 3.
      Just anecdotal at the moment, so let’s see.

      1. Chris Phillips says:

        Unfortunately it was the Sun newspaper wot broke the story, but if anyone fancies reading it, here’s a link:
        https://www.thesun.co.uk/news/14000732/covid-vaccine-protection-just-one-jab/

        1. Chris Phillips says:

          There is a bit more information in this report from Sky:
          https://news.sky.com/story/covid-19-vaccines-cut-infection-rates-after-the-first-jab-by-up-to-two-thirds-study-12214514

          Reduction of symptomatic infection after one dose – 65% in younger adults, 64% in over-80s. Reduction after two shots – 79-84%, depending on age. Protection began after two weeks. They are going to hold off publishing until there are more data.

          It would be interesting to see those first figures broken down into separate results for Pfizer and AstraZeneca. I presume most of the two-dose results will be for Pfizer.

    2. confused says:

      I don’t know what the best source for Israel’s COVID data is, but deaths look to be declining currently (so do cases, though not all that quickly).

      Not that that’s necessarily a sign of vaccine effect, deaths are declining in other places with a tiny % vaccinated.

      It may take a while to pick apart the effect … if it’s ever possible.

      IIRC in the 2009 H1N1 pandemic vaccination became widely available after the second wave was already dwindling – is there any way to know if there would have been a third wave otherwise?

      1. DataWatcher says:

        Hasn’t that actually been the case for most of the other “successful” vaccines in history? Has there even been a mass vaccination campaign launched in the middle of a pandemic while it was still basically out of control? I’m wondering what the historical precedents are for this. . .

        1. confused says:

          Well, IIRC they *started* the program several months earlier, it was more supply/distribution issues that kept it from being widely available until the 2nd wave was already declining – I think doctors etc. had already been vaccinated at the peak of the 2nd wave.

          Not sure what vaccination timelines were like in the 1957/1968 flu pandemics…

          COVID may be a bit different though since the age disparity of mortality is so large, I don’t think flu pandemics generally do that?

          1. DataWatcher says:

            I’m pretty sure the polio spread had subsided significantly due to public health measures when the Salk / Sabin vaccines were introduced. It might have been the same for smallpox, as well, at least in developed countries. Not so sure about measles, but from what I’ve read, an average of 6,000 measles-related deaths annually were documented during the first decade of reporting (roughly 1910-1920), but by the early 1960s, when the vaccine became available, annual deaths were somewhere between 400-500.

      2. Doug H MD says:

        to my mind it is a bit odd that Israel is now LAGGING not leading in terms of improvements.
        that better change quickly: a week more at most.
        And it better than STAY that way while other nations who lag vaccination continue to see new spikes.

        1. DataWatcher says:

          Isn’t a lot of that lag due to difficulties in getting younger people vaccinated, along with resistance among significant numbers of the population (e.g., the Orthodox community)? There might also be a problem with the virus being spread from (mostly asymptomatic) children to adults, but that could be just anecdotal.

          1. Marko says:

            For many of the elderly, going to get their first vaccine jab was probably the riskiest activity they’d engaged in over recent months. This effect could be temporarily dampening the impact of the positive results we’ve all been expecting.

      3. Marko says:

        Our World In Data has a good summary page up for the Israel vaccine data :

        https://ourworldindata.org/vaccination-israel-impact

        What’s missing is daily deaths by age group, but the hospitalization and severe disease graphs are reasonable proxies.

        1. Marko says:

          I can see why OWID may not have included the daily deaths by age group graph from looking at Segal’s data. It’s very noisy for the <60 group :

          https://pbs.twimg.com/media/Et4eOxKWgAACJSj?format=jpg&name=360×360

    3. Marko says:

      From Dvir Aran :

      “Third update of my estimations of vaccination effectiveness. Not as optimistic as my previous posts. Data is based on cases of vaccinated individuals up to February 9th. Findings:
      1. No protection up to day 21. We only see protection from day 0 of the 2nd dose.
      2. Protection after 2nd dose from being positive (not to be confused by transmission): 60-74% for ages 60+, 75-78% for ages 60-.
      3. Protection after 2nd dose from hospitalization: 71-82%. From severe case 69-77%…..”

      https://twitter.com/dvir_a/status/1359603522581454856

      Not the 95% efficacy promised in the commercials, but not too bad, really. It’s not unusual for real-world effectiveness to be less than trial-determined efficacy, and the numbers above may improve a bit over time.

      We have to remember that the UK variant presence in Israel may be playing a role here. I’ve always suspected that there may be a small immune escape component to that variant’s increased transmissibility.

      1. confused says:

        Are the numbers even comparable?

        Does “day 0 from the second dose” imply they are counting hospitalizations/infections immediately after the second dose? If so then it would *not* be comparable because it’s supposed to be 2 weeks after for the “95% efficacy” to kick in, isn’t it?

        1. Marko says:

          I think results will improve with time, but I’d be surprised if they hit the 95% level. There’s very little difference between the 0-6 and 7-13 days post-2nd dose values. I wouldn’t expect the magic to happen dramatically at day 14. If it rises to ~85% or so, I think most people will be quite happy.

          1. confused says:

            Oh I didn’t necessarily mean that it would become 95%, just think it’s important to compare apples-to-apples.

          2. Marko says:

            I think the efficacy results from Israel are very promising, overall. In the Moderna trial, efficacy was ~10 percentage points lower for the over-65 compared to the under-65 age groups, so there’s room for some improvement in the Israel data as younger groups are vaccinated.

            What I’m anxious to see is that death rates steadily decline to very low levels. I don’t care so much about infections if severe disease and deaths are eliminated.

          3. DataWatcher says:

            So far, aren’t all the vaccines showing very encouraging results in preventing serious cases and hospitalizations? I’m still not sure how “serious” a case has to be to qualify (I believe it was J&J that was 85% protective against “serious” illness and nearly 100% effective in preventing hospitalizations and deaths, so it was unclear to me exactly what those 15% of “serious” cases that didn’t result in hospitalization really were) — but I agree that this will be the true measure of success, along with documented evidence that transmissibility will be significantly reduced.

  33. Marko says:

    Inhaled budesonide in the treatment of early COVID-19 illness: a randomised controlled trial

    https://www.medrxiv.org/content/10.1101/2021.02.04.21251134v1

    ” The number needed to treat with inhaled budesonide to reduce COVID-19 deterioration was 8.”

    That’s an impressive figure, if it holds up in real-world use. It seems to me that with the early focus on the use of steroids like dexamethazone, trials like this on inhaled steroids should have received more attention and should generally have been much larger (although with an NNT of 8, it turned out that this particular trial didn’t need to be so big to show significance).

    1. Doug H MD says:

      Saw that too. One MAJOR problem: open label and look at 02 sats; not all that different

      i mean common, how hard to use a placebo and do double blinding?

      1. Marko says:

        Yes, it is frustrating. Almost every CoV2 trial that’s reported has a fatal flaw or two, it seems.

    2. Some idiot says:

      Interesting… I speculated as to whether or not budesonide would help around 10 months ago…

      I am not a completely neutral observer here. I am an asthmatic, and I have used budesonide (or variations on the theme) for some decades now. Since the drug calms down the inflammatory response in the lungs (thereby making a significant difference for asthmatics), it also has the effect of reducing the immune response in the lungs, which means that during the usual winter season it has the effect of having a sign over your head (written in a language viruses understand) saying “kick me!”. So I had expected to be one of the early one infected with COVID-19. However, once it became clear that the cytokine storm was the cause of serious illness, the thought crossed my mind that although (a) it may mean that I am more easily infected, it would probably also (b) reduce the chance of serious illness…

      Will be interesting to see how this one turns out, but it smells right (even though, as you say, there are problems with study).

  34. Marko says:

    “Can’t Find an N95 Mask? This Company Has 30 Million That It Can’t Sell.

    Health workers are still being forced to ration protective masks, but small U.S. manufacturers can’t find buyers, and some are in a danger of going under.”

    https://www.nytimes.com/2021/02/10/health/covid-masks-china-united-states.html?referringSource=articleShare

    This country is a bad freakin’ joke…..

  35. Marko says:

    The obese elderly are more likely to be superspreaders :

    https://twitter.com/EricTopol/status/1359634750521020416

  36. Marko says:

    Severe reinfection with South African SARS-CoV-2 variant 501Y.V2: A case report.

    https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab129/6132402

    Anecdotal cases like this get all the press. The likely many thousands of reinfections with variants that might’ve been expected to occur, but didn’t, and the ones that did occur but were mild or asymptomatic, are not reported on. And it’s not because this data is not accessible. One merely has to do the studies and then report them, which just isn’t happening, near as I can tell.

  37. Chris Phillips says:

    Here is the background paper on the Oxford vaccine prepared by the Strategic Advisory Group of Experts of the World Health organisation (known as SAGE), recommending its use on persons aged 18 years and above, with an interval of 8-12 weeks between the doses (unscrupulous EU politicians willing to say anything to save their careers at whatever cost to human life please note):
    https://apps.who.int/iris/rest/bitstreams/1331784/retrieve

    This SAGE is not to be confused with the UK’s Scientific Advisory Group for Emergencies (also known as SAGE).

    1. A Nonny Mouse says:

      There should also be the “real world” information coming from the UK shortly; the EU probably won’t take any notice now that we are a “3rd country”.

      They don’t seem to be taking any notice of the free trade deal so why this? (just had a chemical delivery sitting in France since last Monday- need POA for Fedex to take taxes, then decided to charge duty as declaring as being manufactured in the UK is not good enough…. Given up shipping to a contractor in Czech Rep as it was being paid for by the Danish client. In contrast, a shipment to the US was delivered within 30h of pick up!).

  38. Marko says:

    This is an incredible reference site for info on CoV2 variants and mutations :

    https://outbreak.info/situation-reports

  39. Marko says:

    The E484K immune escape mutation has already hitched a ride on the UK variant, which is bad enough, but now another mutation common to the SA and Brazil variants, L18F, is spreading rapidly in the UK :

    https://www.news-medical.net/news/20210210/Substrain-of-SARS-CoV-2-variant-in-UK-may-resist-antibody-neutralization.aspx

    1. DataWatcher says:

      “. . . propagation of mutations in escape residues (L18, E484, F490S, or S494) on the VOC strain suggests an increasing selection pressure resulting from the growth of the seroprevalent fraction of the population of England,” says Lipniacki and colleagues. . . This trend can be enhanced by the ongoing English vaccination program, in which *the relatively large time span between the first and second dose can be a contributing factor*.”

      1. Marko says:

        That’s purely speculation. “Can be enhanced” should be “might possibly be enhanced”. There’s no data to suggest anything at this point. That purely political statement detracts from the rest of the paper, which may explain why it has received relatively little attention.

        The first appearance of this mutation in the UK should not be a surprise – they’re one of only a few countries doing enough genomic surveillance to detect it. The success or failure of the UK vaccine rollout strategy relative to that of other countries, like the US, will be revealed by the incoming data soon enough.

  40. DataWatcher says:

    Meanwhile , it’s understandable why a lot of people are confused about the Oxford/AZ vaccine; between AstraZeneca’s continually botched (or at least muddled) reporting and the contradictory policies we’re seeing from various governing bodies and health authorities, “clear as mud” doesn’t begin to describe what’s going on. . . .

    https://www.ox.ac.uk/news/2021-02-10-world-health-organization-experts-provide-guidance-use-oxford-vaccine#:~:text=World%20Health%20Organization%20experts%20provide%20guidance%20on%20use%20of%20the%20Oxford%20vaccine,-COVID%2D19%20vaccine&text=WHO%20SAGE%20says%20Oxford's%20coronavirus,vaccine%20work%20is%20progressing%20quickly.

  41. Marko says:

    In Denmark B.1.1.7 is now at 27% in week 5

    https://twitter.com/MadsAlbertsen85/status/1359788645293715463

    “In week 4 we have sequenced 85.4% of all positive qPCR samples in DK (3082/3610) and 65.9% have a genome (2380/3610).”

    It must be nice to live in a country that knows how to control a pandemic, and then do comprehensive public health surveillance.

    1. Doug H MD says:

      daily new cases in UK, SA and Denmark make me wonder why i should be worried about that?

        1. Doug H MD says:

          well there is that

  42. Chris Phillips says:

    “That’s purely speculation. “Can be enhanced” should be “might possibly be enhanced”. There’s no data to suggest anything at this point. That purely political statement detracts from the rest of the paper, which may explain why it has received relatively little attention.”

    Yes. If we’re talking about the effect of vaccination, surely it’s a question of balance. Firstly, is it better to protect more people earlier with one dose rather than fewer people with two doses? And secondly, (at least as far as the AstraZeneca vaccine is concerned) is it better to have a longer interval between doses and produce a higher final level of protection, at the cost of a longer period of partial protection between the doses? Those questions can be answered properly only by quantitative analysis (for which we probably won’t have the data anyway until things have moved on), not by vague speculative waffle.

    But if people are speculating, I think they should bear in mind that for the UK the period in which the early vaccinees are between doses is one of a fairly strict lockdown in which infections, hospitalisations and deaths are declining rapidly. (Week on week deaths in the UK are now declining more rapidly than hospitalisations. This may be an early hint that vaccination is working, because so far deaths have been more heavily concentrated than hospitalisations among the priority groups for vaccination.)

  43. Fyodor says:

    Russian Society for Evidence-Based Medicine
    February 05, 2021

    Commentary on the publication of preliminary results of the Sputnik-V vaccine phase 3 trial

    http://osdm.org/english/2021/02/06/a-commentary-on-the-publication-of-preliminary-results-of-the-sputnik-v-vaccine-phase-3-trial/

  44. Fyodor says:

    …another review:
    Prof. Enrico Bucci – Temple University (USA)
    Prof. Raffaele Calogero – Turin University (Italy)
    Dr. Piero Carninci – RIKEN Center for Integrative Medical Sciences (Japan)
    Prof. Pellegrino Conte – Palermo University (Italy)
    Dr. Andrea Grignolio – CNR (Italy)
    Prof. Luigi Marchionni – Weill Cornell Medicine (USA)
    Dr. Angelo Parini – INSERM (France)
    Prof. Gianluca Sbardella – Salerno University (Italy)

    “More concerns on the “Sputnik” vaccine”

    https://cattiviscienziati.com/2021/02/09/more-concerns-on-the-sputnik-vaccine/

  45. sgcox says:

    It reads like some Corleone movie poster :0

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