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The J&J Vaccine at the FDA

The briefing documents are out at the FDA site for Friday’s hearing on the J&J vaccine. Here’s a summary at STAT from Matthew Herper and Helen Branswell, and I agree with their take: overall, the numbers look good. Update: here’s a good Twitter thread from Hilda Bastian, and here’s one from Eric Topol.

Like every other vaccine that we’ve seen the clinical data on, this one also seems to completely prevent deaths from the coronavirus. I might be mistaken, but so far I don’t think we’ve seen a single SARS-Cov-2 fatality in the treatment group of any of the Phase III trials. As for severe disease, this one had a strong effect as well, but it might take a bit to kick in completely. 14 days after the single dose, there were 29 people hospitalized with coronavirus in the placebo group and only 2 in the treatment group, but if you look at the 28-day mark there were zero hospitalizations at all.

This makes one think that the full protective effect might be coming on a bit more slowly than the Pfizer/BioNTech and Moderna vaccines, but making cross-trial comparisons like that is risky. The coronavirus landscape has changed since the earlier vaccines, and you can see some of that in the way that the J&J data break out their South African trial. Overall vaccine efficacy was 72% in the US versus 58% in South Africa, where there’s been a lot more B.1.351 variant circulating. But they also have data from Brazil, where the P.2 variant there doesn’t seem to have made much of a difference, and the B.1.1.7 variant first noted in the UK doesn’t seem to be a problem, either.

What about protection against asymptomatic infection? Of the roughly 10,000 people in the treatment arm of the trial, 2892 of them were tested with or without symptoms for signs of coronavirus infection. The FDA’s take on the data (see numbered page 35 of this document) is that there is weak-to-no evidence of such protection out to day 29, and around 60 to 70% efficacy in the post day-29 data. Like the other trials, it seems very likely that all of this will also reduce transmission of the virus, although the study isn’t designed to track that specifically. We’re getting reports from Israel and the UK, though, that would seem to confirm this. I would be very surprised if the levels of efficacy we’ve been seeing didn’t have a strong effect on transmission, but you have to get the numbers to be sure, and I’m glad that those are starting to show up.

There’s a lengthy discussion of subgroups in the treatment groups (starting on numbered page 27 of this document), but what I get out of that is that there aren’t any huge differences. I’ve seen a couple of mentions this morning of lower efficacy against severe disease in >60 year old patients (see that document’s Table 16 on page 32), but the FDA document points out that this may be an artifact of only including cases that were confirmed at the trial’s central location by the time of the data cutoff. Looking at the overall numbers, the older patients look much more similar to the other cohorts, at around 75% VE against severe disease.

Now, about overall efficacy. It’s easy to look at the figures and say “Hey, that’s fine, but it’s not up to what Moderna and Pfizer/BioNTech showed”. That still might be true, but we don’t know what those latter two would have shown if they’d been run at the same time as the J&J trial. It’s also tempting to look at the J&J adenovirus vaccine and the Oxford/AZ adenovirus vaccine and decide that adenovirus vectors are a step behind the mRNA technology, but for the same reasons, we can’t be sure that’s right. Note that the Gamaleya Institute vaccine in Russia posted better numbers, for one thing. And the differences between the three adenovirus vector vaccines themselves are pretty significant: J&J’s data are for one shot of an Ad26 vector (a two-shot trial is still running), and their sequence has the stabilizing protein mutations in the Spike. Oxford/AZ is a different adenovirus (from the chimpanzee population), and their sequence is wild-type Spike without the stabilization. And then Gamaleya is a two-shot regimen, one with Ad5 and the other with Ad26, with the Spike mutations. Update: it’s not clear, actually, if that one does, so for the time being we’ll assume that it’s just wild-type Spike. (Both mRNA vaccines have the stabilizing mutations as well, for the record).

So while we can’t avoid trying to compare all these, we also have to realize that between the fundamental differences and the differences in the timing and locations of the trials, that our comparisons have a substantial chance of being off to some degree. What have we done in the past when we have had such comparisons to make? Good question! But we’ve never had a situation like this, where a whole list of different vaccines, many from completely different platforms, have been rolled out so quickly against the same evolving pathogen. So it’s not like there’s a standard playbook for all this. If we never see this sort of thing again, by the way, that’ll be just fine with me, considering what conditions cause it to happen.

So this vaccine looks certain to get Emergency Use Authorization in the US, and by the time we get on into April it should start making a difference in the vaccinated-population numbers. Production has been slower than J&J were estimating at first, although it now looks a bit better than their more pessimistic estimates. As detailed here, adenovirus vector production is yet another art form, and anything with a big cell culture step in the middle of it has the potential to act up (and for reasons that can be quite difficult to figure out).

But the big message is the same: right now, variants and all, we’re winning. The vaccines work, there is a whole list of them, and their production is increasing while we watch. The countries that have gotten off to faster starts vaccinating their populations are already seeing the effects, and no bad safety signals are yet complicating things. Nor are we seeing evidence so far of antibody-dependent enhancement (worse infections recurring in people who have already been vaccinated). If we can keep this pressure up and keep ramping up vaccine supplies and their rollout around the world, we are going to beat this virus. Good riddance to it.

211 comments on “The J&J Vaccine at the FDA”

  1. David Eugene Young says:

    Good, up-beat blog post, Derek

    1. sticks says:

      To paraphrase Ringo Starr, “He’s got blisters on his fingers!”. I imagine that it was typed/written quickly and with great enthusiasm. I read it that way. 😉

  2. Marko says:

    A good summary thread with some of the important tables :

    https://twitter.com/hildabast/status/1364561482185199625

  3. John says:

    How does this compare to a single dose of the other vaccines? It seems to be similar, or even slightly worse?

    1. Michael says:

      Good point. The difference seems mainly to be that Jansen set out to test for effectiveness of the single-dose and applied for FDA approval on that basis. I suspect that there isn’t any fundamental difference, and that their decision to run a two-dose trial almost concurrently suggests that they weren’t too confident themselves. Jansen was just cannier.

      The data doesn’t show how long the single-dose protection lasts, which is the main benefit from booster shots. The efficacy also seemed a little worrying for a fairly common subgroup – over 60s with hypertension. It should be interesting to see the results of their two-dose trial when it’s ready.

      On the plus side: it seems to be equally effective after two weeks as after four, and we now have data for efficacy against the variants.

      1. Wilhelm Cody says:

        The J&J presentation at the Vaccine Advisory Committee meeting has a very nice graph at about 3 hours and 15 minutes into the meeting showing efficacy versus time after dosing. Efficacy basically increases mootonically out to at least 56 days, to around 88%. Data after that is too uncertain but hints at continuing increase. https://www.youtube.com/watch?v=Qd7mlCD-rEA

        1. DataWatcher says:

          That efficacy increase is extremely encouraging. My earlier concerns that the J&J might end up being a “second-tier” vaccine for poor and underserved communities are beginning to be alleviated.

          1. Mariner says:

            I think I’m correct in remembering that the Oxford/AZ vaccine was originally mooted as potentially being able to be used as a single dose? We know that one apparently has increasing efficacy over time to some degree so perhaps it’s a function of adenovirus vector vaccines? Would be good news if so.

  4. JB says:

    If you look closer at the numbers, the numbers are virtually identical between South Africa and the USA after 28 days. This suggest the SA mutation may not be as big of a worry for reducing efficacy.

    One glaring concern for me is that there was only 21 cases in the last 63 days of the study compared to over 600 cases in the first 63 days (in both the placebo and vaccine groups). This seems rather incredible given the spike in cases in all countries from Nov-Jan. Frankly, it gives me some distrust in this study.

    1. debinski says:

      The fewer number of COVID cases after Day 63 was due to the fact that only a minority of subjects had been in the study for >63 days. If you look at Figure 1, you can see that fewer than 8000 subjects made it to Day 63 and fewer than 4000 made it to Day 70. It drops off precipitously as you go further out.

      1. Jack says:

        But doesn’t the low duration of the study then undercut the strength of its data? Basically you are only looking at a 35 day window between 28 and 63 days with a significant amount of people in the study.

        1. Ian Malone says:

          Worth bearing in mind the situation is quite similar for the mRNA vaccines, if you look at Fig 2 of the FDA briefing document for Moderna https://www.fda.gov/media/144434/download you’ll see similar numbers out to 90-100 days to those in J&J. Interesting also to see that the cumulative incidence curve in placebo is quite different between the groups, reflects the ongoing prevalence, but that later acceleration in infections during the Moderna study might partly explain the higher efficacy those vaccines reported.

  5. CB says:

    Impressive findings for effectiveness after first (!) dosing of COVID-19 vaccines against hospital admissions in Scotland: The first dose of the BNT/Pfizer mRNA vaccine was associated with a vaccine effect of 85% for COVID-19 related hospitalisation at 28-34 days post-vaccination. Vaccine effect at the same time interval for the Oxford/Astrazeneca adeno-vector vaccine was 94%: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3789264

    1. Doug H MD says:

      and if you can explain how they arrived at those results in a flow sheet i will give you the nobel prize

      1. Not-an-epidemiologist says:

        1. Compare rates of covid hospitalisation of vaccinated vs naive individuals (weighting for age, sex, socioeconomic background, number of PCR tests prior to vaccination (hmmm), and co-morbidities)
        2. Group these data into 6 day bins (of time of infection after dosing)
        3. Arbitrarily choose the most flattering efficacy numbers from those bins (even if the data from that bin is sparse)
        4. Report only that figure, along with the Pfizer figure for the exact same bin
        5. Ignore the fact that earlier and later bins do not perform nearly as well, and that the real figure is likely around the 60-70% mark.
        5. ???
        6. Profit (or at least, gain vast amounts of uncritical press coverage that have locked these figures into the general consciousness).

        I wish I was joking.

        (And, you know, at least it should encourage people to get vaccinated, and that’s a good thing. But as a scientific study, it’s appalling. Hopefully peer review will remove some of the cherry-picking hyperbole.)

  6. Metacelsus says:

    My question is, why did it take the FDA so long to evaluate the data? J&J delivered the data to them on Feb. 4. (I actually asked the White House COVID team in an AMA on reddit but they gave a vague non-answer.)

    1. confused says:

      Yeah, I would like to know this too. I read somewhere there is a minimum time required so that public input can be taken into account (but still, couldn’t that be waived for a crisis like this? Is there no mechanism at all for that?)

      1. In Vivo Veritas says:

        Assembling the ad board (all busy experts in their own fields), giving them time to process the data, public commentary….this is actually remarkably fast! If you think <3 weeks is long…. try submitting a small molecule for…. anything other than COVID. 🙁

        1. ezra abrams says:

          “busy experts in their fields”

          really ?

          who, aside from an ER doc or a surgeon or oncologist has any excuse not to be 100% on covid ?

          if they are that important, actually MDs literally saving lives, the FDA can find someone else

          1. In Vivo Veritas says:

            Look here Ezra:
            https://www.fda.gov/media/144232/download
            More important than most of us…..
            It took 3 weeks from submission to EUA approval. You must not be in the business if this gives you cause to complain…..

  7. JJ Walker says:

    The ethical question is who gets the J&J vaccine and who gets the mRNA vaccines.

    1. confused says:

      Potentially- but if they are as-far-as-we-can-tell equally effective in preventing deaths, it may not be as critical as all that.

      Still, I do think it would be best to give the potentially-more-effective mRNA vaccines to older people…

      OTOH, the best plan might be to give the one-dose vaccine to those less able to/likely to show up for the follow-up, if that could be predicted.

    2. Philip says:

      Location could be a determining factor on which vaccine is available. I would send the Pfizer vaccine to places that had the -70 C cold storage facilities to handle it. The Moderna vaccine would go where they have access to normal freezers near by. The J&J vaccine would be put on VaxMobiles and sent to places where getting the other vaccines would prove difficult and where getting people to vaccination sites would be difficult or dangerous.

      1. Doug H MD says:

        Pfizer says they dont need such ultra cold storage now

        1. Charles H says:

          Well, for two weeks. If you want to keep the vaccine longer than two weeks you still need the ultra-cold temperature. And, IIRC, they say refrigeration is enough for overnight. (Sorry, didn’t save a link.)

          1. Not-an-epidemiologist says:

            I think the only source is still the Pfizer press release from a week ago (https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-submit-covid-19-vaccine-stability-data)

            They’re now saying up to 5 days at 2-8°C (and up to two weeks at -25°C to -15°C).

            Which is fantastic news. But the thing that’s doing my head in is, why is this only coming to light now? Did they only just bother to check? We’ve known that Moderna was claiming similar levels of stability with their lipid nanoparticles since mid-last year. We’ve had endless discussions on the difficulties of cold-train transport and storage that Pfizer’s vaccine was creating. So I’d always assumed that Pfizer must (must!) have tested stability at different temperatures at the start of production and found that it couldn’t be stored at warmer temperatures than -70°C.

            I really hope there’s another explanation, and not that this was just a careless, belated afterthought. When you think about all the trouble and expense this knowledge would have saved if they’d found this out several months earlier …!

          2. Doug H MD says:

            anyplace that needs to keep a vial open longer than that shouldnt be using this vaccine

          3. Watson Ladd says:

            If you are not getting shots into recipients in two weeks after shipping you should be banned from getting more vaccine. Shots in arms save lives.

          4. Ben S says:

            From the outset Pfizer has always been storable for 120 hours at standard refrigerator temps, once it’s out of cold storage – the tough bit has been before that point.

      2. DataWatcher says:

        “Location could be a determining factor on which vaccine is available. I would send the Pfizer vaccine to places that had the -70 C cold storage facilities to handle it. The Moderna vaccine would go where they have access to normal freezers near by. The J&J vaccine would be put on VaxMobiles and sent to places where getting the other vaccines would prove difficult and where getting people to vaccination sites would be difficult or dangerous.”

        Given the urgency we face, I think you’re right, especially since the J&J vaccine seems to be very effective against serious illness and death. A part of me, though, is still uncomfortable with the idea that we could be moving toward yet another “two-tiered” situation, where poorer and more at-risk communities (often communities of color) end up with the not-quite-so-efficacious vaccine, even though it’s in these communities where the majority of deaths are taking place. I also wonder whether this could actually increase hesitancy in these communities, where distrust of the medical establishment is already high for good and legitimate reasons.

        1. confused says:

          I do see your point – but an one-dose vaccine might actually be *better* for poorer communities, since car availability might be shaky…

        2. Philip says:

          This is a tough nut to crack. Getting vaccine into as many arms as possible (the world, not just the US) hopefully will slow the development of dangerous variants, not forgetting the people getting the vaccine are very well protected from serious disease by all three vaccines. But how do you tell people that they have no choice in which the vaccine they get because of where they live or work.

          We should have been better prepared. Better prepared to test, including rapid tests. Better prepared for PPE. Better prepared for the economic melt down. Better prepared for therapy trials. I hope we learn from the total mess.

          1. Chris Phillips says:

            Just out of interest, are people being allowed to choose which vaccine they get?

            I was puzzled by a report which seemed to suggest there was low uptake of the AstraZeneca vaccine by the public in Germany. I didn’t see how that was possible, unless the public were being given a choice, or at least being told in advance which they would get. As far as I know, neither of those is true in the UK.

          2. Some idiot says:

            FWIW, here in Denmark you are offered a vaccine (and told what it will be). To the best of my knowledge, if you say “no thanks” then you don’t get a second chance. Or at least not until all those who want one have been vaccinated.

            My vaccination starts tomorrow after work…! 🙂 Pfizer/BioNTech.

          3. TabeaK says:

            In Germany, people are not being given a choice. If you are eligible, and that is only the super high risk categories, you get scheduled for what is available. A significant number of folks have declined to be vaccinated when finding out they were allocated AZ – part of that due to some very strong hyperbole in the press early on (and unfortunately some German experts jumped on the bandwagon) that the AZ shot does nothing against mutants. Which is of course wrong, but the damage is done.
            Now, Germany has no good system for calling a potential standby – say someone eligible declines and the vaccine goes to the next in line – they also refuse to widen the eligibility criteria at this point – e.g. all leftover AZ shots can go to teachers or cancer patients or something like that. The vaccine appointment system is bureaucratic monster – all in the interest of maximum fairness of course – but it is sluggish and inefficient. There are hundreds of thousands of people who’d happily take a leftover AZ shot, but they are not eligible and won’t be for months.

    3. Mammalian scale-up person says:

      The JnJ vaccine can be produced and scaled much quicker than the RNA vaccines. It uses standard equipment. The JnJ vaccine can solve the whole problem of “not enough vaccine to go around, so we must carefully ration it and put together complicated eligibility criteria that we must police and fuss over” and changes the problem to “how do we get people to accept vaccination” instead.

      Depends on how effective your local logistics and roll-out is, I suppose. In the US we have been so slow that emerging variants causing yet another wave are a real concern – I would argue, give whatever you have, as fast as you have it, brand be damned. Adding another layer of complexity when the US has demonstrated we’re already terrible at figuring out logistics doesn’t seem like a great idea. Let’s keep it simple and worry about getting vaccines in arms, period. At this point I wouldn’t even care too much about coordinating timing of boosters, just give people shots and tell them when to come back. If they come back at the right time frame, great. If not, well they have some protection and it’s better than a kick in the teeth. If they come back after the time frame is passed, start over. If they come back too late but you have the JnJ available, give them that and tell them they are all set. Don’t make it complicated. Don’t ask health care providers to take 30 minutes out of a 90-hour workweek to make an appointment when they are busy sticking ventilators in people – set up a line in the hospital parking garage at 6am, everyone with an employee badge gets a shot, a sticker and a lollypop. Imposters stole their friend’s badge? Who cares, we don’t have time or resources to be the Shot Police, tell them their punishment is to write a glowing review on social media about how great it is to be safe from Covid.

      This is like complaining that you got a Toyota Camry and other people got an Avalon, when all you had before was your feet.

      1. M says:

        The US is 4th in the world (behind Israel, UAE and the UK) in terms of percentage of population dosed. The EU is 3x lower. Israel, UAE and the UK are also much smaller land masses than the US. I think the US can continue to improve, and I agree that things can be made simpler, etc. but I don’t think the US has been “terrible” at the logistics.

        1. Mammalian scale-up person says:

          I would also agree with the sentiment that “nearly everyone sucks at the logistics of vaccine rollout,” but I am thinking of it more in absolutes than relative awfulness. We had loads of advance notice to figure things out, it’s not like it was a surprise. The US coordinates much more complex logistics every day for Amazon deliveries, and somehow saving people’s lives and getting back to normal was deemed LESS effort-worthy than delivering people their Fire Sticks and yoga pants?

          West Virginia seems to be doing pretty decent; my Northeastern state, with a much larger tax base and ostensibly more health care expertise has been standing around with their thumbs up their behinds in comparison. So disappointing.

          1. confused says:

            I think the difference is that Amazon is one company, plus whoever they’re paying to deliver.

            Whereas for the vaccine roll-out you have the actual manufacturers, federal government (FDA and CDC), state government, possibly county public health agencies, and the actual shot providers – at least four and possibly five levels of organization involved.

            Certainly we can and should do better. OTOH I think we are actually doing fairly well *given all these previously established structures*.

            But I think it is important to learn from this where things can be streamlined for potential future issues.

          2. M says:

            I agree with confused. Also, I don’t know that it’s fair to say we had a lot of lead time on this. Who in March of 2020 thought we’d have 2 approved vaccines by December 2020? Most of the experts were saying 12-18 months at a minimum. So the arrival of vaccines came a hell of a lot faster than I think anybody thought they would back in March, and even over the summer. Few are saying we can’t do better. We can. And we are. I just take issue with the idea that we suck at this when the data suggest that we’re doing a decent job, actually.

          3. Marko says:

            The KISS rule should been the primary criterion for any rollout plan, and a ten-second glance at this chart would have provided the basis for that :

            https://twitter.com/VirusesImmunity/status/1364327660244066306

          4. DataWatcher says:

            Also, without getting mired in a political debate, we need to admit that until mid-January, not a lot of real, detail-focused planning and preparation had been done. Under the current administration, what should have already been in place and ready to go months ago is just now beginning to take shape. It’s now looking as if the 3-million-million-shots-per-day goal will be attainable within a relatively short time.

            We still, however, have a lot to do in order to ensure access for poor and underserved communities, both urban and rural, and to launch an intensive, culturally aware advocacy campaign to address the ongoing problem of vaccine hesitancy.

          5. Bill says:

            The fact that rollout was disorganized, often chaotic, state to state isn’t as significant as it might have been. Progress has been metered by vaccine production rate, not the efficiency of arm jabbing. Had we been much more, or much less organized, our gross vaccinated numbers would be the same today.

            That said…I think the Brits have it right. By the time you prioritize everyone of merit, you’ve prioritized no one. Everyone is first. Should have been hard core age based with the objective of keeping the max possible numbers out of the hospital…and the morgue. We underperformed badly at that. And it was heavily paid for in avoidable loss of life.

          6. confused says:

            >> Should have been hard core age based

            Frankly, I think it should have been LTCFs first, even before Phase 3 trials were done – something like 5% or more of the US LTCF population has died of COVID (not IFR, *total* population).

            Compared to risk on that scale, any side effect that didn’t show up in Phase 1/2 would be totally irrelevant.

            And there are so few people in LTCFs that there wouldn’t have been that much supply needed. (1.3 million in nursing homes as of 2015, not sure how many in assisted living facilities…)

          7. johnnyboy says:

            Am not a logistics expert, but logically, the more centralised a structure you have for vaccine administration, the more efficient you will be. In the UK vaccination has been handled by the NHS (thank god for once the tory government didn’t give it out to some made-up company set up two weeks before by some spouse of a lord, like they did for all the rest) which is a highly centralised healthcare system, where all patients are registered in a database. Easy to figure out how many vaccines to send out where, easy(ish) to get the nursing and admin staff for doing the actual job, easy to get volunteers to help as they already have volunteer registered in a database, etc… Other european countries with a centralised system are behind, but that’s mainly because they’ve been more conservative in approval of the vaccines, and there’s also much more anti-vax sentiment there, as well as politics (bad press against AZ stoked by politicians, etc…). In the US, without any centralised system, and with the work left to each state to deal with, I imagine you’ll have a massive disparity in efficiency, with poorly organised states with a laissez-faire mentality likely falling behind. To me it’s a wonder you’ve done so well, comparatively.

          8. Some idiot says:

            Here in Denmark everything is centrally-controlled as well. The roll-out has been slower than the UK, but that has been due to (a) later approval in the EU and (b) availability. Basically, every time Denmark gets confirmation of a coming shipment, invitations are sent out to the “next on the list”, with big, centralised vaccination centres. Although there have been some complaints about the booking system, I feel that (a) they have been overblown a bit, and (b) on the whole, it works pretty well.

            You have a good point concerning vaccine scepticism. Here in Denmark, you can feel it simmering under the surface, but since the government has made great pains to stress that it will be voluntary, then it doesn’t seem to be much of an issue. Certainly, and thank goodness, the restraining factor has been vaccine supply, not supplies of arms (or missing logistics).

            Incidentally, here in Denmark at least, the AZ vaccine has been received very well. The only “negative” side was that in one hospital they were sufficiently incautious that they vaccinated a very significant percentage of the staff in one go (>>50%, if I remember correctly), and a decent percentage of these ended up sick the next day due to the usual side effects. But the general response was along the lines of “well, at least we know it works well, and we will remember to give it to other staff in staggered waves.” So all good here…! 🙂

          9. JS says:

            As for vaccine skepticism in Denmark the latest survey I could find says this, loosely translated:
            “How much do you agree or disagree with the following statement: I would follow the advice of the health authorities if they recommend people like me to get an approved corona virus vaccine”. 71.6% totally agree, 15.3% partly agree, total 86.9%. I would say that this represents an extremely high level of support in the population.

            As for how the rollout has been going, one thing that has received a bit of criticism is that elderly people confined to their own homes have not been vaccinated. Little support for transporting them to vaccination centers and no traveling vaccination teams. Norway and Sweden have apparently been able to take care of this.

        2. EK says:

          That aged well. 3/9/2021

      2. TabeaK says:

        If you think the US is slow look all over Europe with the exception of the UK. I do agree with you that overly complicated eligibility criteria bog things down too much. Any person vaccinated reduces risk in the long term. While vaccines are ultra scarce it does of course make sense to prioritize at risk populations first, but in the US at least we seem to be coming to stage where we won’t have to worry about supply but rather about inefficient local distribution.

        If you make it too hard for people to get a vaccine appointment, a big chunk will give up and not re-engage…

        1. Some idiot says:

          I’m happy to say that in Denmark, the roll-out to nursing homes was both swift and effective. The residents (and employees) were asked whether or not they wanted to be vaccinated (about a week before the event) then a van rolled up with personnel, and everyone who had said “yes thanks” (basically everyone) got their vaccinations…

    4. metaphysician says:

      My own quick take: unless there is a clear and obvious ethical difference (ie, one is super effective while the other is only marginally effective)? The ethical response is “there is no important difference, use whichever as is convenient”. Trying to achieve a greater level of ethical certitude than the evidence and fallable human judgment can actually provide would be the bigger sin.

  8. M says:

    Derek, any thoughts on the California strain that’s started to show up on news feeds?

    https://www.sciencemag.org/news/2021/02/coronavirus-strain-first-identified-california-may-be-more-infectious-and-cause-more

    Form the above link, appears to be a bit too soon to say we’ve got a problem here, but it also doesn’t say that can’t change.

    1. Derek Lowe says:

      So far I think some of the headlines are getting out in front of the evidence, but yeah, it definitely bears watching. There’s unfortunately nothing impossible about the idea of a variant that does a much better job escaping existing antibody/T-cell profiles (!)

      1. M says:

        Agreed. Certainly something to watch as this unfolds. Giving the virus less chances to mutate is yet another reason why vaccinations are so critically important. Let’s not even give any possible variants a fighting chance.

      2. confused says:

        Is it at least promising that California’s COVID numbers seem to be rapidly dropping? Or is that likely more due to measures?

    2. DataWatcher says:

      . . . and now, yet another troubling new variant in New York —

      https://www.nytimes.com/2021/02/24/health/coronavirus-variant-nyc.html

      1. confused says:

        Article seems to be paywalled… how good is the data?

        1. DataWatcher says:

          I don’t know what happened — it’s a New York Times article. Here it is, and I apologize for the lengthy post:

          “A New Coronavirus Variant Is Spreading in New York, Researchers Report”

          By Apoorva Mandavilli
          Feb. 24, 2021, 6:23 p.m. ET

          A new form of the coronavirus is spreading rapidly in New York City, and it carries a worrisome mutation that may weaken the effectiveness of vaccines, two teams of researchers have found.
          The new variant, called B.1.526, first appeared in samples collected in the city in November. By the middle of this month, it accounted for about one in four viral sequences appearing in a database shared by scientists.
          One study of the new variant, led by a group at Caltech, was posted online on Tuesday. The other, by researchers at Columbia University, has been submitted to a preprint server but is not yet public.
          Neither study has been vetted by peer review nor published in a scientific journal. But the consistent results suggest that the variant’s spread is real, experts said.
          “It’s not particularly happy news,” said Michel Nussenzweig, an immunologist at Rockefeller University who was not involved in the new research. “But just knowing about it is good because then we can perhaps do something about it.”
          Dr. Nussenzweig said he was more worried about the variant in New York than the one quickly spreading in California. Yet another contagious new variant, discovered in Britain, now accounts for about 2,000 cases in 45 states. It is expected to become the most prevalent form of the coronavirus in the United States by the end of March.
          Researchers have been scrutinizing the genetic material of the virus to see how it might be changing. They examine genetic sequences of virus taken from a small proportion of infected people to chart the emergence of new versions.
          The Caltech researchers discovered the rise in B.1.526 by scanning for mutations in hundreds of thousands of viral genetic sequences in a database called GISAID. “There was a pattern that was recurring, and a group of isolates concentrated in the New York region that I hadn’t seen,” said Anthony West, a computational biologist at Caltech.
          He and his colleagues found two versions of the coronavirus increasing in frequency: one with the E484K mutation seen in South Africa and Brazil, which is thought to help the virus partially dodge the vaccines; and another with a mutation called S477N, which may affect how tightly the virus binds to human cells.
          By mid-February, the two together accounted for about 27 percent of New York City viral sequences deposited into the database, Dr. West said. (For the moment, both are grouped together as B.1.526.)
          The Columbia University researchers took a different approach. They sequenced 1,142 samples from patients at their medical center. They found that 12 percent of people with the coronavirus had been infected with the variant that contains the mutation E484K.
          Patients with the virus carrying that mutation were about six years older on average and more likely to have been hospitalized. While the majority of patients were found in neighborhoods close to the hospital — particularly Washington Heights and Inwood — there were several other cases scattered throughout the metropolitan area, said Dr. David Ho, director of the Aaron Diamond AIDS Research Center.
          “We see cases in Westchester, in the Bronx and Queens, the lower part of Manhattan and in Brooklyn,” Dr. Ho said. “So it seems to be widespread. It’s not a single outbreak.”
          The team also identified six cases of the variant that pummeled Britain, two infections with a variant identified in Brazil, and one case of the variant that took over in South Africa. The latter two had not been reported in New York City before, Dr. Ho said.
          The university investigators have alerted the authorities in New York State and in the city, as well as the Centers for Disease Control and Prevention, Dr. Ho said. He and his colleagues plan to sequence about 100 viral genetic samples a day to monitor the variants’ rise.

          1. DataWatcher says:

            Sorry, here’s the rest:

            The E484K mutation has independently cropped up in many different parts of the world, an indication that it offers the virus a significant advantage.

            “Variants that have an advantage are going to rise pretty fast in frequency, especially when numbers are coming down over all,” said Andrew Read, an evolutionary microbiologist at Penn State University.

            Dr. Ho’s team reported in January that the monoclonal antibodies made by Eli Lilly, and one of the monoclonal antibodies in a cocktail made by Regeneron, are powerless against the variant identified in South Africa.

            And several studies have now shown that variants containing the E484K mutation are less susceptible to the vaccines than was the original form of the virus. The mutation interferes with the activity of a class of antibodies that nearly everyone makes, Dr. Nussenzweig said.

            “People who have recovered from the coronavirus or who have been vaccinated are very likely to be able to fight this variant off, there’s no doubt about that,” he said. But “they may get a little bit sick from it.”

            They may also infect others and keep the virus circulating, which might delay herd immunity, he added.

          2. confused says:

            It seems to me that *all* these variants can’t win out. I mean, if B117 (or any other) becomes the dominant strain, doesn’t that mean it pushes all the others out?

            So we should really only be worrying about one (at least one at a time – if conditions change, which variant has a selective advantage might change), right?

          3. Marko says:

            “I mean, if B117 (or any other) becomes the dominant strain, doesn’t that mean it pushes all the others out?”

            No, two variants can “win out” at the same time, because there are two populations of hosts with distinct susceptibilities – seronegatives and seropositives. The B117 variant, which spreads faster, doesn’t have much, if any, immune escape potential, but it might win out among seronegatives. The S.Africa or Brazil variants might not spread as fast, but could win out among seropositives.

            With the US at potentially 25-35% seropositives by now, there’s plenty of opportunity for even a relatively slowly-spreading immune escape variant to make an appearance.

          4. Daniel says:

            Looks closer to P.2 in Brazil, which has E484K but no N501Y, than the SA variant and P.1. P.2 made up most of the cases in the J&J Brazil arm, where there was no effect on efficacy. It also doesn’t really seem to have changed the course of the Brazilian epidemic in the same way that the other variants have in their respective countries.

            I’d guess that this variant is more transmissible or immune evading, since it’s rising in prevalence, but at the moment I’m not convinced it’s more worrying than SA or indeed the Kent variant.

          5. Marko says:

            “…but at the moment I’m not convinced it’s more worrying than SA or indeed the Kent variant.”

            Agreed. We should probably be more concerned about recent detections of the Kent variant containing 484K, which has now been seen both in the UK and NY. The combination of more rapid spread PLUS antibody escape could be bad news, potentially more so than either P1 or B.351.

          6. confused says:

            @Marko: two could win out *briefly*, but isn’t that only true when there are a significant number of seronegatives? I’d expect that it won’t be that long before most people are either vaccinated or infected.

          7. DataWatcher says:

            @Confused [and/or anyone else] — That again raises a question I’ve asked several times: at what point does the continued proliferation of mutant strains begin to eliminate the variable of immunological “naivete”? In other words, at what point is a mutant strain so different that it’s effectively a new virus, against which a seropositive or vaccinated person has few, if any, defenses?

          8. confused says:

            Well, this doesn’t happen with other respiratory viruses, does it?

            I’ve read that exposure to other flu strains decades before is possibly why flu pandemic mortality doesn’t tend to skew as strongly toward the elderly as one would “expect” – if that is true, it would suggest that even “novel” flu strains aren’t 100%-starting-from-zero.

            I am skeptical of new COVID variants mattering after a year from now, not based on any expertise, but just on the fact that I can’t think of a single historical case where a mutation in a disease *already in the population* caused a major new outbreak.

            Every one I can think of was either from animals or contact with a previously-separated human population (measles in the Pacific Islands, smallpox in the Americas, etc.)

            Is there a case where that’s happened? If not, doesn’t that suggest that it probably won’t happen here either?

            Is there one?

  9. M says:

    And yes, we *are* winning!

  10. sgcox says:

    Interesting note in Nature about vaccine comparison.
    https://www.nature.com/articles/d41586-021-00409-0
    Basically, all approved are working nicely but comparisons between say 70% and 90% are not valid till we get more real world data outside of controlled and differently measured trials.
    At least how I read it.

    1. Doug H MD says:

      give me a head to head trial. in 70-90 year olds

      1. Jonathan B says:

        The Scottish data provides that – in a way. Clearly it has shortcomings, no one is going to pause all vaccination while we monitor the first to get it for several months, so it is emerging data. And it depends on the date of UK licensing for which AZ was several weeks later than Pfizer.

        But so far it looks as if those two were roughly equally effective, certainly within statistical confidence, in an older population. Scotland vaccinated their care home residents first then moved to over-80s.

        And no comparable data for Moderna, Novavax or J&J – not yet approved/available in Scotland.

    2. Not-an-epidemiologist says:

      Although it doesn’t help with in comparing the J&J vaccine, this recently-accepted study in Cell (https://www.sciencedirect.com/science/article/pii/S0092867421002269) has one of the first apples-to-apples comparison of sera from Pfizer and AZ vaccinated individuals that I’ve seen (and certainly one of the better ones).

      It’s not the main point of the paper, but it’s very interesting to see how much better Pfizer performs in a neutralising assay against both covid-classic (an early Wuhan strain they’re calling Victoria) and B.1.351. As the authors note (my emphasis):

      “Neutralization titres for the Oxford-AstraZeneca and Pfizer vaccines were similarly reduced with B.1.351 by 9 and 7.6-fold respectively. For the Oxford–AstraZeneca vaccine when compared to the Pfizer vaccine, more sera failed to reach FRNT50 at 1:20 dilution and since the reduction in FRNT50 titres between the two vaccines were quite
      similar this effect was due to the 3.6-fold lower starting titres for the Oxford-AstraZenca vaccine versus the Pfizer-BioNTech vaccine.”

      So we’re starting to be able to compare these directly, and all the data is pointing in the same direction (sadly, but not surprisingly).

      (Interesting aside — this paper must come close to holding the land-speed record for peer-review: Received 8 February 2021, Revised 16 February 2021, Accepted 17 February 2021, Available online 23 February 2021.)

      1. Marko says:

        That is a good paper. I also found this part interesting , for two reasons:

        “The ability to generate ultra-high affinity RBD variants for ACE2 in the sub-picomolar range by in vitro evolution (Zahradník et al., 2021); a higher affinity than almost all monoclonal antibodies described to date, is a cause for concern. Whether such viruses with extreme ACE2/RBD affinity are viable is clearly unknown and extreme caution should be exercised as to whether this scenario should ever be tested using live viruses. ”

        The first interesting thing is that it highlights how increased ACE2 binding affinity and antibody escape are to a large degree the same thing, something too rarely mentioned in discussions of transmissibility vs. immune escape, and the second is the way it illustrates how capable we might be at engineering more dangerous viruses, should we choose to do so.

  11. JJ Walker says:

    Placebo group cases by baseline seropositivity

    Seronegative: 509 cases in 19544 subjects (2.6%)
    Seropositive: 4 cases in 2030 subjects (0.19%)

    I think we can confidently say that prior infection provides immunity (obviously vaccination is a better way to obtain herd immunity)

    1. Marko says:

      This is at least believable. The Pfizer trial data reportedly showed equivalent infection rates in seropositives as in seronegatives, which makes no sense. With the large confidence interval that would be involved here, the J&J numbers are consistent with other studies (like SIREN) that have shown high (~90%) protection provided by prior infection for many months, at least.

      The high reinfection rates in the S.Africa trial data are more plausible given the high prevalence of the immune-escape variant there.

      1. Chris Phillips says:

        Yes, thankfully the data on reinfection rates seem to be much more consistent than those on vaccine efficacy. I reckon those figures amount to an expected efficacy of 90.6% and a confidence interval of 80.6% to 96.9%.

    2. Marko says:

      Published yesterday :

      “Association of SARS-CoV-2 Seropositive Antibody Test With Risk of Future Infection”

      https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2776810

      ” In this cohort study of more than 3.2 million US patients with a SARS-CoV-2 antibody test, 0.3% of those indexed with positive test results had evidence of a positive nucleic acid amplification test beyond 90 days after index, compared with 3.0% indexed with negative antibody test results.”

      With all the caveats about sampling biases and yada, yada, yada, the numbers from everywhere all seem to come up with ~10-fold reduction in infection rates for seropositives.

      1. DataWatcher says:

        At risk of asking a horribly obtuse layman’s question, does this mean that a lot of what we’ve heard about the dangerousness of asymptomatic carriers might have been overblown? And of course this doesn’t address the issue of transmissibility post-vaccination at all. (Although to be fair, I don’t think it addresses the transmissibility of the mutant variants, either.)

        1. Marko says:

          I think the idea of transmission by any carriers, symptomatic or not, will be overblown once everyone is either vaccinated of has been infected. Same for the variants, until the data proves otherwise.

          The SIREN and other studies show that seropositivity confers major protection against reinfection, asymptomatic or otherwise. Whether it’s 90% or some other number is not important, it contributes significantly to reduced transmission. Vaccines will also contribute in that regard, if perhaps less so. Even this reduction in transmission is only important now, while we’re still trying to get everyone vaccinated. After that happens, we’re probably going to view CoV2 as just another cold or flu, getting our yearly boosters or not, just as we do for flu.

          It sounds like some info is forthcoming on the S.Africa variant, which could change my outlook, but I suspect it won’t. My guess is that they’ll show that reinfections are still relatively rare, even with the variant being dominant, and when they do occur, result in less severe disease than primary infection, on average.

  12. Marko says:

    Covid-19 vaccines made by China’s Sinopharm, CanSino release efficacy data

    Wuhan unit of state-owned Sinopharm, whose first vaccine was approved for general use in December, says second product has an efficacy rate of 72.5 per cent.

    CanSino puts efficacy rate of its vaccine at 65 per cent, but says it is 90 per cent effective at preventing severe symptoms.

    https://www.scmp.com/news/china/science/article/3122980/covid-19-vaccines-made-chinas-sinopharm-cansino-release-efficacy

  13. lierborgu says:

    Derek, could you point me to a source for Gam-COVID-Vac using S-2P as the antigen? I was assuming they were using wild-type spike, but my search just now didn’t bring up any information on which version of spike they are actually using … thanks! 🙂

    1. Derek Lowe says:

      You know, I’m going to have to modify the post, because I can’t track down the reference that my brain thought it had! And I see that the Lancet paper just says it contains the Spike sequence, no mention of modifications. Bert Hubert tried to track down this point as well, and wasn’t able to come up with anything: https://twitter.com/PowerDNS_Bert/status/1349013133059387394?s=20

      1. sgcox says:

        There is a recent Gamaleya patent with a beautifully corrupted PDF.
        https://patents.google.com/patent/WO2021002776A1/en?oq=WO2021002776A1
        It says like “optimised Spike DNA sequence” but no more detail.
        I think optimised covers a lot and really nothing at the same in patent language but I am not an expert.

        1. Not-an-epidemiologist says:

          If no other context is given, I would think “optimised” is more likely to refer to codon-optimised rather than actual sequence changes.

          A December 2020 review (https://www.nature.com/articles/s41577-020-00480-0) suggests the Gamaleya vaccine uses the wild-type S with no stabilisation mods. And the Gamaleya Lancet pub (https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31866-3/fulltext) states:

          “The vaccine comprises two vector components, recombinant adenovirus type 26 (rAd26) and recombinant adenovirus type 5 (rAd5), both of which carry the gene for SARS-CoV-2 full-length glycoprotein S (rAd26-S and rAd5-S).”

          Which I think is pretty clear.

  14. Marko says:

    The Isreali Clalit Health study is now out in peer-reviewed form, in NEJM :

    https://www.nejm.org/doi/full/10.1056/NEJMoa2101765

    1. Marko says:

      Israeli, Isreali, IsReally – take your pick….

  15. Marko says:

    That was quick : “Moderna to test booster shot targeting South African variant”

    https://thehill.com/policy/healthcare/540409-moderna-to-test-booster-shot-targeting-south-african

    1. confused says:

      Likely true… but if it’s not severe, then it doesn’t matter any more than reinfection with (insert any regular circulating respiratory virus) does.

      That’s why I really think the focus should be “these vaccines overwhelmingly prevent hospitalization/death” vs. talking about 66% efficacy vs. 85% vs 90% or whatever… because preventing severe illness is what matters, not preventing cold-like symptoms.

    2. M says:

      This article actually is far more positive about the situation than the headline would lead me to believe. But that isn’t surprising.

      I think yearly boosters of vaccine to combat variants will probably become the norm (as it is with the flu) for the foreseeable future. Obviously what we need to improve is worldwide access to and education about vaccines so we can get as many people as possible vaccinated, and as quickly as possible. New variants come from existing variants, and the fewer people that existing variants can infect, the fewer new variants will arise.

  16. Luysii says:

    The science is lovely and the entire readership here wants to get vaccinated, but there is a large public health disaster looming which has nothing to do with vaccine efficacy. Minorities aren’t signing up for the vaccine, and they are our most vulnerable population.

    Granted the following are 3 small and nonrandomized samples, but the minorities who need it the most aren’t getting the vaccine (and not because it is being withheld from them).

    Sample #1 Yrs Trly and wife second shot yesterday —

    My wife and I received the booster dose of the Pfizer vaccine today. We live in a town that is 45% Latino (mostly Puerto Rican). Both times we were there, the vaccinees were almost all Caucasian, a disaster in the making. The nurse I spoke with said that what we’d seen about Latinos not getting vaccinated was typical in her experience. She also noted misinformation going around among them, such that vaccination would make you sterile.

    Sample #2 a friend who was vaccinated elsewhere (but in the same metro area)- “That was my experience at the State Curative site at XXXXXXX. Large African-American population in that area; however, only caucasians getting the vaccines on both occasions. Puzzling.”

    Sample #3 a college classmate and friend –”Welcome to the club. I received my vaccine through Hopkins as a practicing clinician. My wife received hers as a DC resident through the DC Government in a Black neighborhood; all of the vaccinees there were whites from Foggy Bottom and Georgetown. the DC Government then got smart and has been allocating vaccine by specific neighborhood.”

    Why are minorities not showing up for the vaccine?

    Well here’s our Vice President during her debate with Pence. Harris was asked if Americans should take the vaccine and if she would. Harris says that if doctors “tells us that we should take it, I’ll be the first in line to take it, absolutely. But if Donald Trump tells us that we should take it, I’m not taking it.”

    Well Trump did tell us exactly that.

    Is it her fault that minorities aren’t taking the vaccine?

    1. DataWatcher says:

      No, it’s not her fault at all. She merely echoed what a lot of people were already thinking. There are very real and valid historical reasons for “minorities” to distrust the U.S. medical care system and scientific research in general (Tuskegee was far from the only example of Black folks being used as unwitting guinea pigs for medical experimentation and research; even today the data clearly show wide disparities in quality of care received by white and “minority” patients). One thing that has not occurred under the Biden administration has been a coordinated, culturally aware, community-focused advocacy initiative to address these concerns. Fauci has done what he can, and now we’re beginning to see a more concerted effort on the part of some major Black church leaders; but it will be a yeoman’s task to undo decades upon decades of well-earned distrust. The chickens are coming home to roost, and unfortunately we are all paying the price.

      1. luysii says:

        She certainly wasn’t helpful, and as a leader we should expect better of her. Trump was (correctly) excoriated for what he said about masks. Are you giving her a pass?

        Why not try this?

        A non-coercive way to get people to accept vaccination for the pandemic virus

        Many people are afraid of being vaccinated (for anything, not just the pandemic flu). Yelling at them won’t help. Calling them stupid won’t help. You can’t pass a law to coerce them, but here’s a law that would likely convince them that it is a good idea.

        Can you think of it?

        I’m not sure if congress could do it, or whether it would have to be done state by state.

        Just require all death certificates for people dying with COVID-19 to state whether they’d been vaccinated or not. Certainly now all of the deaths will be in unvaccinated people, but as time passes (say 3 – 6 months) and 95% of them remain in the unvaccinated (as studies of the vaccine have shown) and 1/3 to half of the population is vaccinated, people will take notice.

        I don’t know any legislators, but maybe you do, and you should suggest it to them.

        1. steve says:

          Considering the constant unending torrent of lies that spewed from Trump she was absolutely right. She should no more have listened to him about vaccines than about masks, hydroxychloroquine or injecting bleach. All she was saying is that we should listen to medical professionals, not people like Trump.

          1. Bill says:

            I think the point is not to side with Trump or Harris, but rather what was the end result of her pontification?

            The suggestion is she wound up enhancing vaccine hesitancy among disadvantaged groups to score political points. And now we are where we are.

          2. steve says:

            I doubt that what she said did anything like you’re claiming since she said she listen to medical experts. The groups you refer to didn’t listen to Trump anyway and were better off for it.

          3. DataWatcher says:

            I would be the first to criticize her if I thought she’d done harm, but this time I don’t think she did. She said, “Listen to the scientists,” and the scientists (aside from Atlas, who didn’t deserve to be called one) have all endorsed the vaccines with unreserved enthusiasm. My own personal take on it was that I was very glad none of the vaccines got any kind of approval before the election, because Trump would have immediately taken the credit, and that would have further hurt their legitimacy in the eyes of a lot of the very people who most need it and are already among the most hesitant — poor people and people of color.

            That being said, I do wish Harris would embark on a more enthusiastic and proactive vaccination advocacy campaign.

      2. Todd says:

        Brilliantly said. There’s a lot of mistrust of medicine and STEM in general due to major efforts to mistreat Black and run Black people out of any position of status. Let’s see, there’s J. Marion Sims, the AMA shutting down HBCU med schools in the 20s due to specious reasons, unethical experiments on contraceptives in PR and Guatemala, and so on. The medical community has long looked at Black and Latin people as either guinea pigs or manual labor. Even as a Black STEM professional, I’m often looked at as a self-hater just for my job.

        There’s a lot of pain there, and it’s going to take a lot of effort to fix it.

        1. Marko says:

          Exactly. And when the system has consistently put up roadblocks that prevent a population from being able to access (or afford) quality medical care, one shouldn’t be surprised when they become suspicious as that same system urges them to seek that care (as a vaccine), for free!

          “No, the Tuskegee Study Is Not the Top Reason Some Black Americans Question the COVID-19 Vaccine”

          https://www.kqed.org/news/11861810/no-the-tuskegee-study-is-not-the-top-reason-some-black-americans-question-the-covid-19-vaccine

          1. DataWatcher says:

            Excellent article, Marko. I’ll be sharing it with as many health professionals and other “relevant” folks as I possibly can. I’m a little surprised that Marcella Nunez-Smith, who is one of the leading authorities on health/healthcare inequities and strategies to address them, hasn’t been more specifically forceful about this. Every time I’ve heard her speak as one of the co-chairs of Biden’s COVID task force, she’s basically delivered an academic presentation, full of a lot technical language and abstractions — very little that either well-meaning people who need to be informed, or actual people in the community who have doubts and hesitations, will probably be able to relate to. We need an active “boots-on-the-ground” perspective and strategy, and that’s what I thought she could provide.

  17. Marko says:

    The Search for One Vaccine to Rule Them All : Scientists are working on a ‘universal’ vaccine that could protect against a broad range of coronaviruses

    https://futurehuman.medium.com/the-search-for-one-vaccine-to-rule-them-all-d44bae3d634a

    One of the labs working on this is Bjorkman’s at CalTech, the same group that identified the new variant(s) in New York.

  18. joh says:

    Can anybody comment on this please?
    Appears cell fusion can proceed even in presence of neutralizing antibodies?

    ‘data indicates that syncytia formation as pathological consequence during Covid-19 can proceed at low levels of Spike protein and may not be effectively prevented by antibodies’
    https://www.cell.com/iscience/fulltext/S2589-0042(21)00138-3

    So effectively may mean that spike protein , even in presence of antibodies , may cause cell fusion ( what is the timeline of tissue damage/cell death then)

    Then one commment re possibility that vaccination can possibly cause fusion on same basis .Suppose it could be , but then only at local level/injection site?
    So all in all: any implications for different vaccines and also low level/waning antibodies post vaccination?

  19. Chris Phillips says:

    Preprint from Imperial College REACT-2 survey including data on antibody positivity among those vaccinated with Pfixer-BioNTech:
    https://www.imperial.ac.uk/media/imperial-college/institute-of-global-health-innovation/REACT-2-round-5-preprint.pdf

    Unfortunately showing much lower prevalence after one dose than after two in older age groups (less than half for those over 80), though of course nothing to show whether the ultimate effect of the second dose will be diminished by being delayed.

    1. Daniel says:

      This was what the phase 2 Pfizer trial showed, very low titers after 1 dose in the elderly. It’s interesting, therefore, that 1 dose seems to work fairly well in over 80s from the UK data.

  20. Marko says:

    Nice graphic from The Economist showing CoV2 lineages and VOCs :

    https://pbs.twimg.com/media/EvFgH7KVIAYJSe3?format=jpg&name=large

  21. Aaron says:

    I’m curious, what do ya’ll think if someone gets one of the non-mRNA vaccines, and then 6 or 8 months later we finally have decent supply, should we get a booster? Should we get the full 2-dose? Or is all that still up in the air and just get whatever we can get in our arms, and worry about the experts telling us how to manage boosters/whatever whenever they start coming out with them?

  22. Marko says:

    “Taking into account the counterbalancing rises in both vaccinations and variants, along with the high likelihood that people will stop taking precautions, a fourth wave is highly likely this spring, the majority of experts told The Times.

    Kristian Andersen, a virologist at the Scripps Research Institute in San Diego, said he was confident that the number of cases will continue to decline, then plateau in about a month. After mid-March, the curve in new cases will swing upward again.

    In early to mid-April, “we’re going to start seeing hospitalizations go up,” he said. “It’s just a question of how much.”

    https://www.nytimes.com/2021/02/25/health/coronavirus-united-states.html

    I think this is about right. You can see the slowing of the decline in cases already. Watch Florida for an early preview of coming attractions. We’re the US, so you can rely on us to count our chickens before they hatch, behaviorally speaking.

    The good news is that most of the over-65s will be protected by the vaccine by the time any new surge gets underway, limiting the corresponding rise in hospitalizations and deaths. The bad news is that the B.117 variant, if is indeed more lethal, could offset that favorable effect via it’s impact on the unvaccinated and seronegatives.

    1. confused says:

      This may very well be true, but I think the “slowing of the decline in cases” visible *right now* is at least mostly not this effect, but a bump in the 7-day averages as the result of last week’s numbers being *artificially low* due to a combination of holiday effect from President’s Day and low reporting due to winter storm (Texas is ~9% of the US population, and wasn’t the only state affected).

      Some states may also be ‘bottoming out’ for non-variant-related reasons (is there a lot of B117 in e.g. South Dakota)?

      Now, a spring surge is still quite possible, maybe even likely (especially for cases) but I don’t think what we’re seeing now is it.

      1. confused says:

        (That is, we might see a larger drop next week than this week, but then it slows down after that… or something like that.)

        I think your quote from the article is quite likely correct — but overconfident.

        It’s one thing to say at least some rise in March-April is more likely than not/’the smart way to bet’, but I doubt the parameters — how much behavior is changing, what % of people have immunity from prior infection, exactly how prevalent variants are in many parts of the US, exactly how much more transmissible B117 is, etc. — are well enough known for certainty.

      2. Marko says:

        When exponential increase or decline begins or ends, it’s easier to see on a log scale :

        https://ourworldindata.org/coronavirus-data-explorer?yScale=log&zoomToSelection=true&time=2020-10-31..latest&country=USA~GBR~CAN~DEU&region=World&casesMetric=true&interval=smoothed&perCapita=true&smoothing=7&pickerMetric=new_cases_per_million&pickerSort=desc

        If you think the previous decline is going to resume in the US, I have a piece of oceanfront property in Kansas I’d like to sell to you.

        1. Marko says:

          Link got split, but if you copy/paste it, it works.

        2. confused says:

          For next week, at least, I think it’s pretty likely… I really do think low reporting last week has ‘broken’ the curve (look at TX’s numbers from last week).

          Florida is flat to slightly declining depending on what metric you look at; if variants are driving this, wouldn’t you expect a time lag between FL and the overall US numbers.

          1. Marko says:

            In most states, I think the impact of the variant(s) won’t be as important over the next couple of weeks as will be the easing of restrictions and behavioral change. As the uptick begins, the influence of the variant will continue to increase, accelerating the process.

            Any of a number of states could be first to show evidence of a new surge beginning. I just happen to think Florida is a likely candidate. The variant is probably more established there than most other states, and they’ve been itching to let the economy rip, so I don’t think they’ll reimpose restrictions soon enough to stop a new wave once it begins. Florida has done a pretty good job of targeting the elderly with their vaccine rollout, so a new surge in cases may not cause a similar surge in hospitalizations and deaths, and there won’t be that pressure to tighten things back up. Their current death rate is nothing to brag about , however.

          2. confused says:

            How much easing of restrictions is actually happening though? Isn’t Florida pretty much open already?

          3. confused says:

            A week later, it does look as if the late February ‘blip’ was holiday + as cases seem to be going down again relative to last week (even with Alabama adding 2,000+ from a backlog going back to May).

            Of course, that doesn’t rule out a later-in-March rise either due to variants or behavior change (Mississippi removed their restrictions, and Texas will on March 10). But I don’t think we are seeing it now (even Florida 7-day-averages and COVID-like-illness ED admissions still seem to be falling, though pretty slowly).

          4. confused says:

            Sorry, “was holiday + winter storm effect” (probably mostly the latter)

  23. debinski says:

    FDA meeting on J&J EUA has just started. I’m not sure I recommend watching. I can feel the plaque forming in my coronary arteries as once again, they spend too much time on pleasantries and forgetting to unmute. But here’s the link:
    https://fda.yorkcast.com/webcast/Play/3098af8852e64bc79930bdaa1001d3af1d

    1. debinski says:

      And technical difficulties. Now the audio went out completely. 🙁

  24. Marko says:

    Expect a major hissy fit from “Earth’s Virology Professor” about this one:

    “Collectively, our data show that while the S-614G [i.e.(S)pike-614G] substitution results in subtle increases in binding and replication in vitro, it provides a real competitive advantage in vivo, particularly during the transmission bottle neck, providing an explanation for the global predominance of S-614G variant among the SARS-CoV-2 viruses currently circulating.”

    https://www.nature.com/articles/s41586-021-03361-1

    Of course, B.117 is even more transmissible than D614G, but Raccianello is so dug in to his early position that he can’t allow himself to admit to either of these two realities. It’s becoming downright entertaining to witness.

  25. Marko says:

    If you got one of the lipid nanopatticle vaccines, watch out for this newly-reported major side effect :

    https://twitter.com/GYamey/status/1365258715318878208

    1. confused says:

      Uh, that’s got to be a joke, right? Time traveling nanoparticles is too crazy even for a conspiracy theory…

      1. Marko says:

        It better be reaI. I get my Moderna shot next week and I’m planning to go back in time to re-work my stock trades. Every one of them.

  26. Marko says:

    ” ‘We’re not there yet’: Biden officials issue somber warning about uptick in Covid-19 cases ”

    https://www.statnews.com/2021/02/26/biden-officials-issue-somber-warning-about-uptick-in-covid-19-cases/

    1. M says:

      Counterpoint:

      https://covidtracking.com/analysis-updates/good-news-despite-data-wobbles-weekly-covid-19-data-feb-25

      This suggests the President’s Day holiday and the weather events nationwide led to an underreporting the last couple of weeks (artificial drop), and now a backlog is coming in (artificial rise).

      I think it’s too early to draw any conclusions about what a 3-day uptick really means. I don’t fault the CDC for being ultra cautious, we should remain vigilant and keep an eye on this. But I’m not convinced we need to push any panic buttons.

      1. confused says:

        Yes, that is probably what happened this week.

        That doesn’t mean that cases won’t rise in March due to variants and/or people thinking it’s over – it seems very plausible, even likely – but I don’t think *this week’s* data is that effect.

        1. M says:

          Variants are the biggest worry in my mind. Otherwise, I think we’ve reached a point through natural infection and vaccination that the number of seropositive individuals (in the US) is nearing or possibly even over 50%. This is based on CDC disease burden estimates and vaccination numbers. Of course, there are caveats with burden estimates that have to be considered, and we don’t really have a good way of knowing how many vaccinated people were also seropositive to begin with (already infected). It’s not 100%, but it’s also not 0%

          1. confused says:

            And the more important number might actually be what % of people *above a certain age threshold* are seropositive. Not for herd immunity as such – but if severe cases/hospitalizations/deaths drop really low then transmission/cases don’t matter all that much.

            50% seems a bit high, but not unreasonable – CDC’s 83 million infected through end of December is 25% of the population, maybe we’re up to 30% now, and CDC says 47 million (~14%) with at least one vaccine dose. Counting in overlap between those groups, and people who *just* got their first dose, it might be more like 40%.

            But overlap between immunity-from-infection and vaccination may be relatively limited, since one would expect that people who think COVID is ‘just a cold/flu’ are more likely to be infected *and* less likely to seek vaccination early in the rollout.

  27. DataWatcher says:

    Positivity rates in Illinois continue to drop. Right now they’re at the lowest they’ve been since the beginning of the pandemic; Chicago’s is 2.9%, which I believe is the lowest it’s been since before last August.

    1. Bill says:

      Is there really much significance to positivity rates? In my town they were giving free, drive-thru community tests with rates under 1%. The the test shortage hit and now they only test people they think have the disease. Rates over 9%.

      Seems without quantifying the sampling characteristics, rate is meaningless.

      1. confused says:

        I would think so too, but in the fall and IIRC in the summer too, they did rise before other metrics like hospitalizations/deaths, and cases alone can be misleading (by cases, the summer surge looks worse than the fall one; by deaths, it’s clearly not).

        … But n=2 may not be enough to show they are meaningful (I don’t know that you can count different states as ‘independent’ experiments).

        And depending on what the age distribution of vaccinations is, the link between positives/cases and hospitalizations/deaths may be broken. COVID tracking project says that the % of US deaths in long-term-care-facilities is about half of what it was a few months ago (16% vs. 35%+).

        1. confused says:

          *by cases, the summer surge looks worse than the SPRING one. Not fall

  28. Marko says:

    97% of over-70s in UK have received at least one jab, and vaccine hesitancy doesn’t seem to be that big of a deal across age groups :

    https://pbs.twimg.com/media/EvJIfj7XEAA4or5?format=png&name=small

    1. confused says:

      Wow, 97% is *really* good uptake.

    2. Marko says:

      Slavitt brgging : “Nearly half of the U.S. population ages 65 and older and nearly one in five Americans have received a first Covid-19 shot, a White House adviser said ”

      https://twitter.com/aslavitt46/status/1365363536461987851

      So, ~20% of Americans compared to ~35% of Brits. Hooray, USA!

      1. Marko says:

        Actually, it’s ~29% of all Brits, ~35% of adults :

        https://ourworldindata.org/coronavirus-data-explorer?zoomToSelection=true&time=2020-11-07..latest&country=USA~GBR&region=World&vaccinationsMetric=true&interval=total&perCapita=true&smoothing=0&pickerMetric=new_cases_per_million&pickerSort=desc

        1. Marko says:

          Actually, my first comparison above is more accurate. Slavitt’s brag was a lie, it’s not “nearly one in five” Americans who’ve received one dose or more, it’s nearly one in five over age 18, i.e.,adults (CDC link below). The proper comparison to the UK is thus : UK, ~35% of adults vs. US, ~19% of adults.

          This is a consequence of the UK’s sensible one-dose-accelerated rollout, which will result in the UK achieving a very low rate of daily deaths well before the US does, even though they started the vaccination campaign at ~50% higher daily death rate than in the US.

          https://covid.cdc.gov/covid-data-tracker/#vaccinations

          1. Marko says:

            Explainer: What J&J’s authorized COVID-19 shot means for the U.S. vaccination campaign

            https://www.reuters.com/article/us-health-coronavirus-vaccines-johnson-j-idUSKCN2AR0Q3

            “Between J&J, Pfizer/BioNTech and Moderna, the United States is on track to receive 240 million doses by the end of March, enough to fully inoculate 130 million Americans.”

            Using the UK strategy, that’s enough to vaccinate 240 million Americans – the entire adult population, and then some. After approving the J&J one-dose jab, it’s criminally schizo not to adopt the UK strategy at this point. More US citizens will die than need to as a result.

      2. Marko says:

        “NHS statistics going up to February 21 show 90.3 per cent of all over-65s in England have had their first dose”

        https://www.dailymail.co.uk/news/article-9299781/Coronavirus-UK-60-people-Isle-Wight-jab.html

        1. A Nonny Mouse says:

          Also seems that the one dose AZ is giving 90% protection from hospitalisation and working better than the Pfizer jab.

          Seems that full data will be available this week.

          1. Marko says:

            Yep. And I’m sure the US-centric “experts” are getting prepared to tear that data apart once it’s released. Here’s the Daily Mail piece about it :

            https://www.dailymail.co.uk/news/article-9308401/AstraZeneca-vaccine-reduces-risk-Covid-infection-90-effective-Pfizer-jab.html

            “A single shot of either jab cuts the chance of needing hospital treatment by more than 90 per cent, ‘real world’ results from Britain’s NHS vaccination program show. But the Oxford-AstraZeneca vaccine, shunned by millions across Europe because of concerns over trial data, is proving slightly more effective at stopping severe Covid-19 illness than the Pfizer jab.”

            It was also reported that the O/A jab was more durable than Pfizer in prevention of symptomatic infection.

            I find it entertaining to witness the Europeans suddenly making flattering statements about the O/A vaccine, after their initial disparaging remarks.

    3. Chris Phillips says:

      That is encouraging, but I don’t think it can be taken at face value, as it comes from an opinion survey with a 68% response rate:
      https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/healthandwellbeing/bulletins/coronavirusandthesocialimpactsongreatbritain/26february2021

      I would guess that people who don’t respond to opinion surveys may also tend not to respond to invitations to be vaccinated.

      I thought the percentage of people who said they were complying with the rules about staying at home was interesting: only 54%, compared with 65% in mid-January and 81% in May 2020. In a sense it’s encouraging that a relatively lax lockdown is still effective in reducing the numbers.

      1. Marko says:

        True. Surveys like this are more like opinions about opinions, but it does seem the UK hesitancy numbers are lower than those seen in similar US surveys. If we can get an uptake of 90% or more among over-65s in the US , as they’ve already accomplished in the UK, I’d be a little surprised.

        It could be that when push comes to shove, virtually everyone will choose to get the vaccine. I hope that’s the case, anyway.

        1. Chris Phillips says:

          I hope uptake will be high, but I am hearing anecdotally of a lot of resistance, and if it does need an annual booster I’m not optimistic that it will be anything like universal.

          I must confess that as someone in my 50s I’ve never felt the need for a flu vaccination, and I’m not sure how likely I’d be to take it up if it were universally available. This year it is available to over 50s in the UK and I haven’t taken it up, though that is mainly owing to the desire to avoid unnecessary contact because of COVID-19.

          1. A Nonny Mouse says:

            I decided not to get a flu jab as it have been virtually wiped out this year due to the lockdown.

            Had it once in my late 20s and it totally knocked me out for a week and I lost a huge amount of weight from sweating and not eating. Only time that I have been ill in my life and don’t recommend “real” flu to anyone.

          2. sgcox says:

            This is a more efficient and reliable way than what G. Partlow and others promote as weight loss regimes.
            Fewer side effects too.

          3. Scribbler the third says:

            Arise Sir Phillips, a seeker of the holy grail has found thee. Bagsy I be the light knight, which makes thou the dark knight. Bad luck, old chap…

            https://www.youtube.com/watch?v=ZmInkxbvlCs

            …Suspecting, Sir Phillips, you might not get the preceding generation’s humour. Just as, despite much huffing, puffing and scribbling, this scribbler will never really get those scribblers who went before him, digging trenches, landing on beaches and designing tools that made parts that went into aircraft engines. With drawings and hieroglyphics left behind to prove it.

            Now if memory serves right, it was Parsifal not Galahad who brought back the Grail and hurled Excalibur mid-lake, which gleaming sword legend says a ladylike arm reached out to clasp.

            And in interest of chivalry the dark knight must have a squire too. For what keeps a legend alive and kicking is that in time the two squires will in turn become knights and ride off to seek a grail of their own choosing. And in the end one squire may become Parsifal, which of course means the other may become Galahad, Lancelot or Whosoever.

            As for Sir Graham and Sir John, both never, this scribbler suspects, wanted to be knights, preferring to be jesters, a noble calling indeed, for even kings, lords and knights of the realm need to be reminded how courts, squires and servants see them.

            Sir Derek’s blog gives insight into many and varied scientific minds of all shapes and sizes. Open, questioning minds and diversity of thought always did make for an upstanding and creative court. In the right hands, can even aspire to become a form of higher scientific Camelot. In the wrong hands, don’t get a scribbler started.

            Once upon a time the scribbler recalls a wooded escarpment where legend says a wizard lived and knights in shining armour still lie deep in slumber behind iron gates, ready to arise and ride forth in hour of a nation’s greatest need.

            Last reported sighting four score years ago aloft above the south eastern skies of a small island nation, on steeds with hearts manufactured from parts made by tools designed by scribblers, who left behind drawings and hieroglyphics to prove they’d done their bit, even though rest of their lives lived out in everlasting belief that, compared with other blokes their age, they’d given of not much at all.

            Sobering thought indeed for a mere latter day Sunday afternoon scribbler.

          4. Chris Phillips says:

            At least it gives the carers a bit of a break.

          5. Scribbler the third says:

            Permission to speak, Sir. Carer Sir, not cared for. Joint age the other side of 160. Even more than your 136 captcha, Sir. Fortnightly visits, usually on a Wednesday.

            No miming through double glazing, no leaving Aldi crate in porch, no national social distancism in garage with door open wide in accord with national social ventilationism regulations. Open wide and say aah, I always say Sir. Usually does the trick, eh doc?

            Business as usual, as mutually agreed a year ago. Didn’t take us long to decide. Ninetysomething’s decision as much as mine. Always been an independent thinker. All good as can be expected in circumstance of National Covid Year.

            Plenty of resilience for ninetysomething to fall back on, all the way back to those two months in solitary in the Isolation Hospital in the 1930s.

            Got off lightly of course. The latter day ninetysomething before that had caught diphtheria twenty years earlier in another local hospital, where isolated for scarlet fever. Double jeopardy survived.

            But no family’s immunity’s immortal – five year old taken with meningitis in 1914 and fortysomething done for by TB ten years later. All ancient history now, thanks to miraculous double indemnity of economic prosperity and vaccination.

            Economic prosperity. Remember that quaint old concept, Dear Covservative government, Prime Ministers, Chancellors, Cabinet Ministers, Junior Ministers, Senior Advisers, Press Officers, Whitehall insiders… grave Knights and earnest Lords of the Realm… National Covid Service…

            …Headmasterly CSA, schoolmasterly CMO… virally replicating, mutating and multiply negatively tested and traced SAGE scientists, profs, experts, Imperialist academics and State Registered Nannies… all secured and employment packaged up in state sponsored stipends.

            We cannot believe it, Sir. All done in our elderly, vulnerable and indomitable names, without even bothering to ask in the first place if we wanted our children, grandchildren, and great grandchildren god-willing to be, sacrificed at the alter of covservative single issue social, economic and public health policies.

            PM Pflogiston thinking is as PM Pflogiston thinking does. In other words, the any one thing uppermost in mind at any one moment is most likely to turn out a figment of the imagination, just like the original phlogiston did.

            Seventeenth century stuff, thought responsible for burning, shown not to exist a century later by Lavoisier, Priestley, and those olden days experiments in bell jars with candles, that refused to comply with Phlogiston Theory by having the sheer blind cheek to stop burning before all the damn phlogiston burnt away.

            Never mind, Mum, right from the first public library books subjected to 72 hour covid-secure quarantine… covid-secure poop sacks of ironies, inanities and insanities…

            …Have kept your daily newspaper, the two of us sat inside, and the birds at the nut feeder outside the window… in fortnightly laugh and cry out louds… the whole arse about face year long… the latest being arrest and ten grand fining of a sixty five year old NHS Key Worker protester. Get that Granny, Plod!

            https://www.bbc.co.uk/news/uk-england-manchester-56312817

            …Massive turn out of forty protesters outnumbered by fifty police officers. With respect, Sir, ball’s back in your court Sir. Perhaps your first and second serving is better than your buffet bowling, Sire. Any respectable sport played against a duffer all day long soon gets boring.

          6. Chris Phillips says:

            Amazing stuff. Most trolls at least pretend not to be.

          7. Henrik I says:

            To live is to war with trolls in heart and woul. To write is to sit in judgement on oneself.

        2. Marko says:

          Here’s a new US-based survey :

          https://www.kff.org/coronavirus-covid-19/poll-finding/kff-covid-19-vaccine-monitor-february-2021/

          It looks like the most hesitant group in the US is not blacks or Hispanics, it’s Republicans.

  29. Marko says:

    A good review of the past year’s counterproductive public health messaging :

    https://www.theatlantic.com/ideas/archive/2021/02/how-public-health-messaging-backfired/618147/

  30. Marko says:

    Good thread by Kristian Andersen on the VOCs and VOIs, with no “scariant” fearmongering :

    https://twitter.com/K_G_Andersen/status/1365461953775235073

    1. DataWatcher says:

      The article by Grubauch et al. was published in February of 2020. Do you think its reassuring tone still holds true today, given what we’ve seen with B.1.351 et al.?

      1. Marko says:

        I think it holds until we have data that suggests otherwise. If it’s shown that vaccination or prior infection provides little or no protection against hospitalization or death once infected with a given variant, then we’ll have something to worry about.

        B.117 spreads faster and may be more deadly than the strain the vaccines were based on, yet it appears the UK is well on its way to turning B.117 into the common cold.

        1. DataWatcher says:

          Isn’t B.117 the dominant strain in Israel, also? Among the vaccinated population there, Pfizer is kicking COVID a$$ left and right.

        2. DataWatcher says:

          Meanwhile, from what I understand, In the UK, it has already been hinted strongly that social distancing and mask wearing will continue into next winter.

          1. Chris Phillips says:

            The government is saying it hopes all restrictions can be lifted by June. Apparently that includes social distancing. I’m not sure about face coverings.

            Then again, is that much different from what the government hoped to do last Summer? We know how that went.

            Admittedly with vaccination it’s not self-evidently impossible, as it was then. But it still seems extremely optimistic to me. By that date, the plan is for everyone over (say) 55 or so to have had two doses of vaccine, but a lot of younger people won’t even have had one. Maybe it can be done, but I wouldn’t put money on it.

          2. DataWatcher says:

            Chris, I agree that predictions — whether Pollyannaish or Cassandra-ish! — are a fool’s game. That being said, though, I will predict that that things will get a lot more “normal” for vaccinated folks than they will for the unvaccinated, and it’ll happen pretty rapidly. Even Dr. Fauci, who tends to be pretty conservative about such things, is very close to saying that groups of people who’ve been vaccinated can congregate socially with very little risk. I’m guessing that “vax parties” will become quite popular pretty soon, and before too long it will begin to look like good business for restaurants, bars, nightclubs etc. to have special “proof of vaccination required for admittance” nights where people will be able to congregate and move about more freely than the “general’ crowd can usually do.

            Illinois still has its “Emergency Travel Order” prohibiting travel to certain states (and/or requiring a mandatory two-week quarantine upon returning), but last week they lifted those restrictions for fully vaccinated people. I think that’s a harbinger for things to come.

            The wild card, of course, is the ongoing evolution of mutant strains with increased immune escape potential (e.g., New York).

  31. Mary says:

    Kudos to J&J for being upfront about the risks of thromboembolic events, but am I the only one who has issues with the risk profiles. The serious adverse events risks (0.1%) is very high and much worse than Moderna and Pfizer .

  32. Chris Phillips says:

    Here is an anguished commentary on the prospect of vaccine passports from the Guardian:
    https://www.theguardian.com/commentisfree/2021/feb/27/vaccine-passports-alternatives-mills-harm-principle-discrimination

    First it invokes John Stuart Mill in favour of the principle. But then it points out, fairly enough, that not everyone may have the option of vaccination. But then it goes further and points out that some people won’t want to be vaccinated and asserts – without any further discussion – that if the result of this in effect was racial discrimination, then this would be “morally unacceptable”.

    I think the author needs to acquaint herself with the difference in (UK) law between direct and indirect discrimination, and with the circumstances in which the latter is legal, and to reflect on that.

  33. Marko says:

    Evidence of antibody affinity maturation and/or epitope spreading beyond 28 days with the J&J vaccine:

    https://pbs.twimg.com/media/EvP-clbVIAMJRr2?format=jpg&name=small

    This is what’s seen with natural infection, and suggests that spike antigen bits stick around for quite a while, even with the vaccines.

  34. Marko says:

    Good summary table here of the nine EUA or near-EUA vaccines :

    https://jamanetwork.com/journals/jama/fullarticle/2777059

  35. Marko says:

    OT, but this is truly mind-blowing – deep-sea bacteria that can grow photosyntheticly using the thermal radiation emitted from black-smoker vents :

    https://www.pnas.org/content/102/26/9306

    1. Marko says:

      It’s old news, but new to me.

  36. ralph says:

    It’s a bit perplexing and disappointing that FDA isn’t considering Novovax for approval anytime soon, apparently because they haven’t completed a Phase 3 trial in the US (not to be completed until April!) even though they have completed one in the UK and demonstrated apparently superior efficacy to even the Pfizer and Moderna products. Do we have to be this provincial and mindlessly bureaucratic?

    1. DataWatcher says:

      Also, if my memory serves me correctly, their vaccine was the only one that demonstrated clear evidence of sterilizing immunity in the early non-human primate trials.

  37. Marko says:

    It sound like the NY variant with 484k may soon graduate from Variant of Interest (VOI) to Variant of Concern (VOC) :

    https://twitter.com/FaceTheNation/status/1366070802735579137

  38. Marko says:

    Slide from J&J vaccine seroconversion study which shows 74% reduction in asymptomatic infection from day 29-71 :

    https://twitter.com/PaulSaxMD/status/1366105306804203520

    1. Moran says:

      The interesting question is how this figure changes over time within the period of 29-71. Is it going up or down? This is quite a long period.

  39. Marko says:

    Lipsitch et al : Interpreting vaccine efficacy trial results for infection and transmission

    https://www.medrxiv.org/content/10.1101/2021.02.25.21252415v1

    “….Applying this approach to published data from the RCT of the Moderna vaccine, we estimate that one dose of vaccine reduces the potential for transmission by at least 61%, possibly considerably more. “

  40. lizzy says:

    So Marko:
    Staying up all night again? You’re getting the Moderna jab this week. Your resilience will be down and the above efficacy will be less unless you SLEEP.

    Another Monday and off to work.

    1. Marko says:

      My understanding is that you have to stay for a period of time after your vaccination so you can be observed for any severe reactions. I’m planning to use that time for a power nap.

      1. Chris Phillips says:

        Talking of recommended behaviour around vaccination time, does anyone have an informed opinion on whether to abstain from alcohol – before, during or after? Advice online seems to come from diametrically opposed schools of thought.

        1. Marko says:

          If alcohol interferes with vaccine efficacy, then I’ve had a lifetime of wasted vaccines.

        2. DataWatcher says:

          Actually, to be honest, a greater concern for me is stress. I’m sure I’m not the only one who’s been living under a pretty constant level of elevated stress for the last year or so; not sure about the extent to which this can inhibit vaccine efficacy, but we do know that it can weaken the immune system overall.

        3. A Nonny Mouse says:

          I listened to a Q&A session on Saturday morning (Radio 4 news) and they vaccine expert said all this about alcohol was rubbish.

          1. Bill says:

            Now more than ever, you can find an “expert” who will say anything. Time to get skeptical.

            PS — I can’t believe that vaccine hesitancy is now a Republican thing. Seriously? Not this Republican — I’m two and done.

      2. Anxious Mom says:

        Remember JW Ulm’s concerns regarding the mRNA vaccine nanolipids crossing the BBB and stimulating glial cells? I’m not a scientist, just a 37 year-old pregnant mom who wants to get vaccinated but scared off by those concerns. Curious as to whether you would choose the J&J vaccine over an mRNA vaccine with those concerns in mind? Or would you wait til after baby is born in May?

  41. Chris Phillips says:

    Here is the preprint of the real-world study of vaccine efficacy in the UK which has been in the press over the last couple of days:
    https://khub.net/documents/135939561/430986542/Early+effectiveness+of+COVID+vaccines.pdf/ffd7161c-b255-8e88-c2dc-88979fc2cc1b?t=1614617945615

    1. Mariner says:

      Encouraging data and I didn’t spot any glaring flaws from a quick skim through the paper. If these results hold true, the numbers of hospitalisations and deaths in those vaccinated should drop greatly during the next couple of months. Let’s just hope the protection is long-lasting as well! If the paper can be peer-reviewed quickly and the data holds up, then the various doubting European countries must change their minds about allowing the use of the AZ vaccine in older people. It’s a crying shame that so many countries have plenty of doses of vaccine which they aren’t really attempting to use at present.

      It remains to be seen just how much the UK government will spin and overstate the data. Hancock already praising our regulator as ‘the best in the world’ and insinuating that the AZ vaccine is more effective than the Pfizer. For some reason, the politicians don’t bother to consider confidence intervals when making their bold statements.

      1. Chris Phillips says:

        My concern is that the 80% protection against hospitalisation (and the similar protection against death for Pfizer) is made up of about 60% protection against symptomatic disease and a further 50% on top of that.

        Obviously it would be more useful to know how it broke down into protection against all infection and further protection on top of that . Based on other data, one might guess something like 40% against infection and 70% on top. But if so it probably wouldn’t take us to herd immunity – that would happen when restrictions were relaxed, and the protection against death might still leave (at a guess) something like 1 in 500 of those infected dying, which would be quite a lot more deaths.

        But I suppose we can hope for higher efficacy against asymptomatic disease in the younger part of the population, and higher efficacy overall for everyone after two doses.

        1. Mariner says:

          I have to admit, it was quite a quick skim through the paper. However, what is the general risk of hospitalisation or death for the over-70s once infection is confirmed?

          Here’s a quick quote from the stated results:

          “On top ofthe protection against symptomatic disease, cases who had been vaccinated with one dose of BNT162b2 had an additional 43% (95%CI 33-52%) lower risk of emergency hospitalisation and an additional 51% (95%CI 37-62%) lower risk of death. Cases who had been vaccinated with one dose of ChAdOx1 had an additional 37% (95% CI 3-59%) lower risk of emergency hospitalisation.”

          I’d assume that the additional lower risk of emergency hospitalisation is comparison to the in the general unvaccinated population. The fact that it says there was an ‘additional’ 51% lower risk of death made me think it was all cumulative. So, 43 or 37% less (depending on vaccine) reduction in the usual level of hospitalisation in that age group with a further 51% lower risk of death in comparison to the proportion who usually die once hospitalised. At least, that’s how I understood it. This would relate to a relatively small fraction of those unvaccinated people over-70 who died once infected.

          Or perhaps I’m just being overly-optimistic? I didn’t attempt to look at the numbers themselves too closely.

          I woulc

          1. Chris Phillips says:

            Yes, that’s how I understood it. My concern is that although an 80% reduction in the death rate sounds very good (and indeed is very good), if the prevalence of the infection rises because restrictions are relaxed then it’s not really an 80% reduction. If the infection rate rose by a factor of 5 it would give us the same death rate we have now (even if everyone were vaccinated).

            But maybe I am being too pessimistic.

          2. Marko says:

            I think your interpretation is correct, Chris, but it still could be the case that these protection levels improve with time, what with all we’ve heard about antibody maturation occurring over an extended period and such (see Johnson & Johnson “Johnson” graph, below). Also , the results for the very elderly will be worse than for the overall vaccinated population. I can see the rationale for moving up the second dose for those over 75 or 80.

            https://pbs.twimg.com/media/Evc1FenXEAI6u-N?format=jpg&name=small

  42. Anonymous says:

    I’ve been hearing a lot from people that being vaccinated does not guarantee that you still can’t be a “carrier” and give it to someone else. Do we know anything about how that works and if there any studies ongoing to confirm?

  43. Marko says:

    I guess British Columbia really is British – they’re adopting the UK vaccine strategy :

    https://www.cbc.ca/news/canada/british-columbia/b-c-immunization-plan-covid-1.5931543

    “…Also on Monday, the province announced it is extending the time between first and second doses of COVID-19 vaccine to four months.”

    Smart move. I wonder if the rest of Canada follows suit….

    1. Marko says:

      This preprint might be a sign that Australia is leaning in the same direction:

      “Reanalysis of the Pfizer mRNA BNT162b2 SARS-CoV-2 vaccine data fails to find any increased efficacy following the boost: Implications for vaccination policy and our understanding of the mode of action”

      https://www.medrxiv.org/content/10.1101/2021.02.23.21252315v1

      1. Not-an-epidemiologist says:

        That’s a bit of a stretch. A few random Australian immunology researchers != Australian public health policy.

        Also, it’s a bit of a foolish preprint, IMO. The “modelling”, such as it is, is just facile linear regression (with some truly astonishing assumptions thrown in about constant infection rates in the placebo group) — it’s rookie stuff from people who really should know better. Even if the conclusion matched the neutralising titre data from the trials (it doesn’t), and even if it wasn’t extrapolating from extremely scarce data points (it is), there is much better data coming out of Israel suggesting that in a real-world context 2 shots are significantly more effective than one (e.g. https://www.nejm.org/doi/10.1056/NEJMoa2101765).

        1. Marko says:

          “That’s a bit of a stretch. A few random Australian immunology researchers != Australian public health policy.”

          Not random. Not a stretch :

          “NS and MH provide guidance to the Victorian Government COVID-19 response and receive funding from the Victorian Government for the Optimise Study and COVID-19 modelling work. NS received funding from Johnson & Johnson in Jun-Sep 2020 to provide incidence projections for potential vaccine trial sites. BC serves on the Australian National COVID-19 Health Research Advisory Committee that provides guidance to the Australian Federal Government COVID-19 response.”

          The issue is not whether two doses are better than one. It could be that twelve doses, given every week for 3 months, is optimum, but that would be pretty useless knowledge when vaccine is scarce as it is now. The is whether to delay the second dose until vaccine supply catches up with the demand.

          One dose for everyone at risk followed by a delayed second dose, as the UK is doing it, will save lives compared to the US “strategy”, based on what we know about one-dose vaccine efficacy so far, and supported by the “real-world context” of plunging death rates in the UK relative to the US.

          1. Not-an-epidemiologist says:

            Point taken about the author list — I was being a bit harsh — although bear in mind that almost everyone in the epi and immuno fields has been seconded to health department work down here over the last year in some capacity. (I believe dosing schedules have to be in accordance with TGA approval, not decided by the government, although I can’t be bothered checking. Regardless, given the current federal government’s lack of interest in vaccination, dosing schedules are unlikely to change in the foreseeable future.)

            Btw, I fully support (as I have in my comments here all along) the UK policy of delaying the second dose. It’s sensible and obvious, and it’s very clearly working. However, I wouldn’t (currently) support stopping at a single dose, at least for Pfizer. (You could probably convince me for AZ; indeed, it might even be beneficial if we assume a booster shot will be forthcoming, as I am not sure how well a second homologous boost will work given the problems with the first one.)

            One thing’s for sure, though — I would never advocate any decision re. dosing on the basis of that risible preprint. I won’t say it’s the worst manuscript I’ve seen over the last year, but it’s got to be in the top ten.

          2. Marko says:

            I don’t support stopping at a single dose, either. I can just see from the data to date that more lives would be saved using a one-dose strategy, until supplies increase enough to make it a moot point. People with a history of Covid-19 should be put at the back of the line , as well.
            For countries with limited access to vaccines, these policies should be no-brainers. I have no problem with making exceptions for the very elderly, or others, if the incoming data suggests it’s necessary.

            The Pfizer and Moderna dosing schedules were determined more by a desire to rapidly advance their trials than by the immunology, and it has fixed in everyone’s mind that we have to “go by the book”. How these people avoid suffering cognitive dissonance after we just approved a single-dose vaccine is beyond me.

    2. A Nonny Mouse says:

      We are 3 months….. You have to book a second dose at the same time as the first; mine was on the 16th and the next is 4th May.

      1. Mark says:

        Where is that the policy ?

        1. Chris Phillips says:

          That’s the UK. I think strictly speaking the policy is a 12 week interval.

          So significant numbers of second doses will be starting about a month from now. But still the target is to give a first dose to all over-50s by mid-April, and to all adults by the end of July.

          1. Marko says:

            OK, thanks. I knew about the UK, of course, but didn’t know that’s what the comment referred to.

  44. Dan says:

    Is the J&J vaccine less desirable because it is not amenable to booster shots that cover future variants?

  45. Chris Phillips says:

    Here is a preprint on the Brazilian variant:
    https://github.com/CADDE-CENTRE/Novel-SARS-CoV-2-P1-Lineage-in-Brazil/blob/main/manuscript/FINAL_P1_MANUSCRIPT_25-02-2021_combined.pdf

    “Using a two-category dynamical model that integrates genomic and mortality data, we e stimate that P.1 may be 1.4–2.2 times more transmissible and able to evade 25-61% of protective immunity elicited by previous infection with non-P.1 lineages.”

    The modelling can’t separate out the effects of increased transmissibility and immune escape. Instead they present a joint probability distribution for the two (Figure 4A). So it’s not going to be a question of x2.2 transmissibility AND 61% escape. One could be at the top of the range and the other at the bottom, or both could be in the middle.

    1. Marko says:

      NYT piece by Carl Zimmer on P.1 :

      https://www.nytimes.com/2021/03/01/health/covid-19-coronavirus-brazil-variant.html

      Still nothing on the relative mortality rates in reinfection vs. primary infection, but any way you look at it, P.1 was a bad actor in Manaus.

  46. Marko says:

    Some good news on variants (not-as-scariants?) for a change, from Sette et al :

    Negligible impact of SARS-CoV-2 variants on CD4+ and CD8+ T cell reactivity in COVID-19 exposed donors and vaccinees.

    https://www.biorxiv.org/content/10.1101/2021.02.27.433180v1

    “Here we performed a comprehensive analysis of SARS-CoV-2-specific CD4+ and CD8+ T cell responses from COVID-19 convalescent subjects recognizing the ancestral strain, compared to variant lineages B.1.1.7, B.1.351, P.1, and CAL.20C as well as recipients of the Moderna (mRNA-1273) or Pfizer/BioNTech (BNT162b2) COVID-19 vaccines. Similarly, we demonstrate that the sequences of the vast majority of SARS-CoV-2 T cell epitopes are not affected by the mutations found in the variants analyzed. Overall, the results demonstrate that CD4+ and CD8+ T cell responses in convalescent COVID-19 subjects or COVID-19 mRNA vaccinees are not substantially affected by mutations found in the SARS-CoV-2 variants.”

  47. Marko says:

    Texas Gov. Abbott – Visit Texas and help us superspread B.117 :

    https://twitter.com/PatrickSvitek/status/1366837879352291347

  48. Mary says:

    Anyone else whose read the safety data concerned about the thromboembolic events possibly associated with the J&J vaccines and the 0.1% risk of serious adverse events?

    1. Chris Phillips says:

      To be clear, this is what the FDA says about thromboembolic events:
      “There were no meaningful imbalances in unsolicited adverse events in 28 days following vaccination between vaccine and placebo recipients in the safety subset. … Numerical imbalances were reported between vaccine and placebo recipients for thromboembolic events (15 versus 10) and tinnitus (6 versus 0). Based on currently available information, a contributory effect of the vaccine could not be excluded, although the imbalance was small (representing a difference of 0.06% of vaccine recipients vs. 0.05% of placebo recipients), and many of the participants had predisposing conditions. FDA will recommend surveillance for further evaluation of thromboembolic events with deployment of the vaccine into larger populations.”
      https://www.fda.gov/media/146217/download

      The difference in the rate of these events between the two groups is tiny, and certainly not statistically significant. Considering the number of possible comparisons for different events, if this is the best that anti-vaccine propagandists can come up with, it’s a testament to the safety of the J and J vaccine!

  49. exGlaxoid says:

    As a note, I was recently un-blinded in the AZ clinical trial, and got real vaccine. I was a bit surprised in that I had absolutely no side effects from the shot, not even a sore spot on the arm with the first or second shot. So not everyone has bad effects fro the shot, and based on what I have heard, the sore arm is common, but fewer people have any systemic effects. My wife got the Moderna shots recently, and also had only the slightest of soreness at the injection site and arm on the second shot only.

    So for those who have heard how bad the vaccine can be, they are not so bad, and the worst side effects tend to be in people who had already have covid (even if asymptomatic) and younger people, who have more vigorous immune systems.

    1. A Nonny Mouse says:

      What is the period between doses in the US trials?

      (I, too, never had any effects with the jab. Next is 4th May as it is the UK).

  50. Oscar says:

    Derek:

    You mentioned that the J&J vaccine has an efficacy of 75% against severe, although I keep hearing an 85% figure touted in the news and from health officias.

    “Looking at the overall numbers, the older patients look much more similar to the other cohorts, at around 75% VE against severe disease.”

    When I read the FDA briefing, it indicates that the efficacy against severe disease is in the 75% range after 14 days, and 80% after 28 days for people in that 60+ age range (but the number of cases is only 15 in both the placebo and immunized group), with an 83% efficacy for all age groups overall after 28 days.

    Are you using the 75% figure because the total number of cases is so low after 28 days? (Also, am I trying to draw conclusions that cannot be drawn because of the small number of severe cases overall, with the confidence intervals being so high?)

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