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Early March Vaccine Thoughts

Some thoughts about the current vaccine trials and data, some of which are probably obvious, but which might be worth bringing together:

First, as many have been mentioning, it’s tempting but quite difficult to compare the vaccines (and vaccine candidates) head-to-head by looking at their phase III data. I would only feel safe doing this when large differences show up (like 60% efficacy versus >90% efficacy), and only then after a good hard look at the trial populations, the possible variant forms of the virus therein, and so on. We have to remember that this pandemic is not a set of trials versus relatively static targets like atherosclerosis or small-cell lung cancer. The SARS-Cov-2 virus has only recently jumped into the human population. Like most any virus, it is throwing off mutations all the time, but viruses that have been in the human population for much longer have often settled into some broad energy minima by now. The current coronavirus hasn’t had a chance to do that yet.

So the variants we’re seeing can indeed change the face of the pandemic (look at how the B.1.1.7 one took off in the UK, or B.1.351 did in South Africa). Not all of these are going to make a difference to the vaccines or to their trial data, but some of them (like B.1.351) certainly can. All this is to say that if we ran another Phase III with the Pfizer/BioNTech or Moderna vaccines in the same populations that (for example) J&J and Novavax have been seeing recently, that their numbers could be different than they were in their original trials and more similar to the latter ones. I’m still reserving judgement on the Oxford/AZ vaccine – those trials were run earlier, but the data on them is (famously) piecemeal and from some directions not very impressive.

That’s one point. A second one to remember is that all of these trials are designed to read out when they hit a certain number of cases, and their timing is thus dependent on how many people are getting infected. If the coronavirus is ripping through a given population, that’s very bad for them – but actually speeds up such a trial if that’s where it’s taking place.

Consider, then, the current cases of Novavax and J&J, both of whom still have ongoing US trials (the latter is for a two-dose schedule, as opposed to the one-dose trial that has completed). One of the very interesting things that’s been happening so far this year is a steep drop in coronavirus cases in almost every region of the US. I really don’t think anyone saw this coming (I didn’t), but it looks like there was a peak in the first week of January. Many other countries have seen something similar, and there’s been a lot of speculation about what’s going on. I won’t add any of my own, except to say that I’d bet that it’s not any one single factor, but several adding up simultaneously. (It’s also worth noting that in the last week or so this drop seems to have slowed, so now everyone gets to wonder if things are going to start going up again!)

At any rate, this has all surely slowed the pace of these clinical trials. I thought about this while reading some comments made by Novavax’s CEO Stanley Erck, as reported by Anjalee Khemlani. They have apparently been involved in talks with the FDA about getting their vaccine approved on the basis of their UK/South Africa data, without waiting for the US trial to conclude. And Erck has said that if the FDA doesn’t act on these data sets that it could delay approval in the US for months. The NIH-funded trial of the Novavax candidate just got underway in December, and with that start date and the variable case numbers, I can see what he means. I would think that the available data are enough for an EUA myself, and I’m very much in favor of getting another effective vaccine out there, particularly one whose production is likely to ramp up quickly.

I say this because I think we need to continue to get out in front of the variants. Despite a lot of scary headlines, I don’t think that we’ve seen any that really break through the immunity conferred by the current vaccines, but there is, as always, no guarantee that the next one won’t. Here’s a new preprint that looks at T-cell responses to the B.1.1.7, B.1.351, P.1, and CAL.20C variants, and it’s very reassuring: the T-cells raised by the current vaccines can handle these variants just like they can the earlier strains. So as long as that situation obtains, we have to get as many people vaccinated as possible, both to protect the recipients, and to slow down the generation of further variants themselves by cutting transmission.

I stand by the statements that I made at the end of this recent post. I think that we really are winning against the pandemic now, and we can do an even better and faster job of that. But we can also do an even worse and slower job, too, never forget, and it’s vital that we don’t let up now.

277 comments on “Early March Vaccine Thoughts”

  1. Brett says:

    That’s hard for Novavax. Not only is the number of potential patients who get Covid going done (making the trial slower and harder), but they’ll be dealing with defections from people who can get a different vaccine now that three of them are available (four if they ever approve Oxford in the US).

    1. Phil Ammar says:

      I am in the Novavax trial and have thought about leaping ship the second I’m eligible for a vaccine. I just got a phone call yesterday from the research center letting me know that my next appointment in April is cancelled, since they are going to be doing a blinded crossover study, and that as soon is the crossover is approved by the FDA, they will be scheduling the crossover vaccinations. I got the impression it would be happening soon, which will probably go a long way towards keeping people enrolled. Makes me wonder whether they are getting word from the FDA on whether they currently have enough data for the EUA, because if the do the crossover, I can imagine it extending the time for them to get statistically significant data about the efficacy.

      1. Geoff Morgan says:

        I am in the U.K. Novavax trial and being 73 years old received an invitation for the NHS jab. The Novavax study advised me of the crossover programme.
        However, they keep shifting the goalposts. Initially, the first jab was provisionally scheduled for around 15th March but now they are talking about mid April with still no certainty. I have now asked to be unblinded and am waiting for them to respond so l can get a NHS jab if l had placebo. Too much dither and delay.

        1. Des Fisher says:

          I know it is frustrating. In am on the trial too.

          I have now had my appointment for the crossover for 3rd April. I stayed with the trial, to try and help, but everyone must do what they feel comfortable with. Medical research is difficult and there are no defined roadmaps and timescales that we can hold the researchers to My choice was to continue, but I am a little younger and weighed up the risks accordingly
          I totally understand your wish to be unblinded to progress with the NHS offer
          I hope that your ‘unblinding’ and subsequent vaccine went well

          1. Alessandro says:

            I am also in the UK in the Novavax trial and I have booked my crossover appointments. The speed of the general vaccine rollout means that although I am in my 30s I should get offered a licenced vaccine within the next month or two and I am a concerned that if my partner, family and friends get vaccinated but I refuse (as I am in the trial) and then vaccine passports are introduced that I will not be eligible for one as it is not a licenced vaccine. I thought I was doing the ‘right thing’ by participating but now it has left me with a dilemma.

  2. Jonah says:

    I’ve been arguing for the EUA of Novavax since they first released their UK data. Based on the numbers and strains, it seems like the most effective vaccine yet, not nearly as reactogenic or difficult to produce as the mRNA or vector vaccines, and easier to modify/combine with influenza or new strains. Would have saved so many lives if they did a quick approval process in early February, but here we are.

    1. Eric says:

      An early approval would only help if there’s supply ready to go. In the UK, where the Novavax trial finished a month ago or so, we were told there wouldn’t be any to have until April at the earliest. I assume that’s why they haven’t rushed an approval out like they did with the Pfizer and Oxford ones.

  3. Luysii says:

    It is important to note that there is no correlation between neutralizing antibody and recovery from COVID19, but there is a correlation with SARS-CoV-2 specific CD4+ and CD8+ T cells. Two adults in Italy with agammaglobulinemia and NO circulating B lymphocytes developed COVID19 and recovered. B cell depletion for a variety of conditions is being used and some 31 such patients developed COVID19 which resolved without ICU care. This is from a very detailed paper by two experts Crotty and Sette [ Cell vol. 184 pp. 861 – 880 ’21 ]. Not a quick read, and something of a slog, but definitely worth the effort.

  4. Susan says:

    The US phase 3 of A/Z is ongoing and by all accounts should have numbers soon. ( I got my 2nd dose in that trial in late December.) Additionally, there are real world data from places where it is already approved. Hopefully that will make up for the “piecemeal” data from earlier trials. EUA in April?

    1. Roland says:

      Really interested to see results from this since they’re using a saline placebo rather than the meningitis vaccine used in most other Ox-Azn trials. I haven’t seen much discussion about it but there are reasons to expect significant unblinding with an inactive placebo and such a punchy vaccine, and that could push the symptomatic Covid infection results in either direction. (If I’m sure I had the vaccine and I get a mild cough it’s probably just the dry air or something so maybe I won’t bother with the hassle of mentioning it to study organisers? vs Maybe I’m taking more risks if I believe I’m vaccinated?). Notwithstanding the complicating factors Derek mentions, we’ll have a head-to-head between active and inactive placebo when comparing with the UK & Brazil trials.

      The est. completion date recently moved up from March 23rd to 16th on ClinicalTrials.gov so that’s very promising.

      1. Chris Phillips says:

        I thought I remembered saline having been used as a placebo in the AstraZeneca trials, but on checking I see that as far as UK/Brazil went it was only for the booster shot in Brazil (though that might still give a clue in principle).

        However, it was used as the placebo in South Africa, which makes the results there even more inconclusive. As you say, it could have an effect in either direction: if people are convinced they have received the vaccine, that may make them more self-confident and less cautious about contact with others.

        1. Eric says:

          My sister was involved in the AZ trial in the UK. She said even the meningitis vaccine was noticeably less reactogenic such that the blinding was not 100%.

        2. Roland says:

          Ah yes, the South Africa one was only ~2000 mainly young participants though and I don’t think we’ve seen detailed data from it, not much more than the ‘doesn’t work against B.1.351’ headline. It also involved intensive monitoring with monthly routine appointments (blinded care providers), so that might minimise the ‘had a cough and didn’t mention it’ cases and I presume that means there was routine PCR testing too so it’s not really comparable to any of the other trials.

          1. Rob Sutherland says:

            Here’s the link to the pre-print of the South African AZ study.
            It looks considerably better than I had anticipated, give the delays in getting the data published versus the many scary but uninformed headlines about this issue.
            https://www.biorxiv.org/content/10.1101/2021.02.27.433180v1

          2. Chris Phillips says:

            Rob Sutherland

            I think that is about T cells in relation to different variants, for everything but the AstraZeneca vaccine?

          3. Rob Sutherland says:

            This is to Chris Philipps @ 6 March, 2021 at 2:05 pm. Not sure whey there was no ‘Reply’ button.
            I am terribly sorry Chris, I included the incorrect link (cut-and-paste disease!).
            Here is the one I intended to link to:
            https://www.medrxiv.org/content/10.1101/2021.02.10.21251247v1.article-info

  5. Novacek says:

    “It’s also worth noting that in the last week or so this drop seems to have slowed, so now everyone gets to wonder if things are going to start going up again!”

    With luck, a lot of this may end up being storm related, in Texas (and other states to a lesser extent). Artificially lowering February 14-20 numbers (and potentially pushing the following week higher).

  6. JJ Walker says:

    I am in the Novavax trial. My 3 month appointment is in mid-April. I was told that they would start the crossover at that appointment (ex those who got placebo the first time would get vaccine the next time and vice versa). The MD/PI of my location indicated that the crossover was FDA approved and that they were working on new consent forms. The US is still averaging 70k cases per day. With 10,000 people enrolled in the placebo group that should generate 2+ cases per day assuming those enrolled are getting infected at a similar rate as the overall population.

  7. Rock says:

    This is pure speculation on my part, but I think that part of the reason cases are dropping in the US is that a significant percentage of the population are immune either through vaccination or contracting the disease. If we conservatively say that only a third of the cases are diagnosed, that means 100M infections. In addition, 77M doses of vaccine have been given. It is also reasonable to think that those not yet infected might be following CDC guidelines more closely.

    1. DataWatcher says:

      Also, I think the preponderance of vaccines have been administered to high-risk elderly patients, especially those residing in nursing homes and other care facilities. The original predictions was that if we did this, we’d see a drop-off in cases and deaths among that population first, and since they comprise a majority of serious cases, that would result in a noticeable decline overall. I’ll hazard a guess, as well, that among those most likely to be “spreaders” (relatively healthy and younger), a significant majority have contracted, or will contract, asymptomatic or mildly symptomatic cases and will not bother to be tested. All of which is to say that yes, I think it’s possible that the vaccinations are already showing results among the highest-risk (although not as dramatic as what we’ve seen in Israel), while at the same time increasing numbers of people who haven’t been vaccinated are continuing to join the “herd” the old-fashioned way.

      1. confused says:

        The US population as a whole doesn’t seem to have nearly high enough infection + vaccination rates to meet herd immunity thresholds; but perhaps the *population of people who haven’t been being careful* may be close or at it?

        1. Chris Phillips says:

          That is still the only plausible explanation I can think of for the fact that the decline in the infection rate has been so much higher in London than in the UK in general, both last Spring/Summer and over the past couple of months.

    2. Mary says:

      Not all mild infections develop immunity.

  8. DataWatcher says:

    I remain very hopeful about Novavax; efficacy against the “original” wild-type virus seemed to equal or surpass that of Pfizer/BioNTech and Moderna, and it seems to be at least as successful against B.1.351 as well. Also, if I recall, it was the only vaccine candidate to show indications of conferring sterilizing immunity in the early non-human primate trials (someone please correct me if I’m wrong about this). I would definitely vote in favor of rapid EUA approval based on the UK/South Africa data.

  9. phb says:

    FWIW: I received an email from Novavax a week or so ago saying they had completed enrollment and didn’t need me

  10. Marko says:

    Introduction of Two Prolines and Removal of the Polybasic Cleavage Site Lead to Higher Efficacy of a Recombinant Spike-Based SARS-CoV-2 Vaccine in the Mouse Model

    https://mbio.asm.org/content/12/2/e02648-20

    This is the design used by J&J and Novavax, per Krammer.

  11. Steve Scott says:

    Breaking news: (NY Times) Biden Says Vaccine Doses Could Be Available for All Adult Americans by End of May
    Merck will help manufacture the Johnson & Johnson vaccine.

    1. DataWatcher says:

      At risk of sounding like a broken tape loop, if they’ll just swallow their pride and consider an EUA for Novavax as well, that could put us in a very advantageous position by the beginning of summer.

      1. John Hasler says:

        Novavax is expecting an EUA by May.

    2. Wilhelm Cody says:

      It is likely the case that we could be done with adult vaccination by Mid spring.. The USA has more than enough doses to cover residents who may receive vaccination. Novavax will help with the rest of the world more than help with our program.

      Warp speed arranged for 300 million full courses of vaccine for delivery by July 31, 2020: 100 million from Pfizer, 100 million from Moderna and 100 million from Jansen (Johnson&Johnson). Pfizer and Moderna have picked up the pace of manufacture and the current administration has arranged for an additional 100 million full courses to be delivered by the end of July, for a total of 400 million full courses of treatment.

      The population of the USA is 331 million and 65 million are under the age of 16 (https://knoema.com/infographics/egyydzc/us-population-by-age-and-generation-in-2020) , so 265 million are allowed to get the currently authorized vaccines. Note that is also at the upper end of estimates of herd immunity, at 80% vaccinated.

      At the current rate of allocation of about 12.5 million courses per week (assuming Janssen delivers at a rate of 5 million per week going forward after this week), https://data.cdc.gov/Vaccinations/COVID-19-Vaccine-Distribution-Allocations-by-Juris/saz5-9hgg, https://data.cdc.gov/Vaccinations/COVID-19-Vaccine-Distribution-Allocations-by-Juris/b7pe-5nws) and the equivalent of 38 million courses delivered so far, we would reach 265 million total in 18.2 weeks or about the first week of June.

      However, all three companies are likely able to increase deliveries per week over that time. That would get us to the 265 million in May sometime, assuming we can find enough people to deliver the doses. That result would leave 135 million courses for the rest of the world.

      If Moderna, Pfizer, or Janssen can file in early summer for EUA on 12 to 18 year olds, we could vaccinate that population and still leave 70 million courses for the rest of the world. Novavax is extra. We have a commitment to buy 50 million courses if they get an EUA but can then ship those doses to the rest of the world.

      The only barrier to reaching 80% of the adult population vaccinated is the fraction of the adult population who might not be allowed get the vaccine for medical reasons or won’t for personal reasons. If that amounts to 10% of the adult population, then we would only reach 72% or so of the total population, which many still think would be sufficient for herd immunity.

      Right now is not the end of the pandemic. It may not even be quite the beginning of the end. It is definitely the end of the beginning.

  12. aviators99 says:

    Interesting preprint. I’ve been wondering about whether or not the difference in CD8+ response between Pfizer and Moderna in Phase 3 is in any way material w.r.t. long term immunity. I’ve asked here, but have not seen anyone’s opinion. I can understand why it would be potentially a taboo topic for public policy reasons, but would like to know what the science says.

    1. Marko says:

      The recent paper by Sette et al, linked in Derek’s post above, didn’t comment on any noticeable differences between the two vaccines re: overall CD8 response. See Fig 3 (diamonds=Pfizer, circles = Moderna). It does look to me like Pfizer sera might perform somewhat better at the lower spike Ag levels. Their main conclusion was that the vaccines’ response to the WT strain was largely maintained against the different variants.

      I haven’t heard much about this either, but given the similarity of the antigens and platforms used by Pfizer and Moderna, my guess would be that they perform similarly. The real-world results will tell us eventually, I suppose.

      1. aviators99 says:

        I agree. But it’s certainly curious that in the phase 3 trials there was a pretty significant difference between the CD8+ response.

  13. Jack Komisar says:

    As far as I know, neither AstraZeneca nor Novavax have applied for an EUA. News reports suggest that Novavax will filE an application in the second quarter of 2021. An EUA application requires tens of thousands of documents, so it is not a trivial task. The FDA has to review the documents and also to recalculate all the data from the individual records of each of the thousands of volunteers. It is a lot of work, and it takes some time.

  14. sgcox says:

    Any ideas why Novavax uses Sf9 and not mammalian systems ?
    https://www.nature.com/articles/s41467-020-20653-8.pdf
    I was not directly involved in Spike production for serological tests but as I understand everyone uses HEKs for proper glycosylation, consistency and assay performance.

    1. Local Haole says:

      It’s not a scientific reason, but choosing a cell line derived from an armyworm, rather than a healthy human fetus (as Human Embryonic Kidney 293 was), avoids some arguments available to the vaccine hesitant. I’ve already had to start pushing against that one in my own family… even before the Archdiocese of New Orleans got involved.

      As an immunologically naive chemist, I’m wondering, is it really a given that a fully glycosylated antigen must give a better immune response? Perhaps that is one issue that, as Derek has mentioned, we really haven’t had the opportunity to address prior this pandemic.

      1. TabeaK says:

        There a pro and con arguments for Sf9 vs Hek293 from a scientific point of view as well – they will be hard to nail down on the data side, however, without comparing a vaccine head to head made in both cell – which we’ll likely never see in the general population.

        Sf9, owing to its origin, will not be a silent harbor for all sorts of unknown human viruses – a common worry with human manufacturing systems and a subject of much testing. Sf9 are grown at lower temps typically and can produce far higher yields. You pay for this with slightly different glycosylation patterns – this could be beneficial or detrimental to mounting an immune response. Beneficial if the immune system recognizes the protein as slightly foreign and mounts a stronger response. Detrimental if the the particular glycostructure is relevant for a functional antibody. The latter doesn’t seem of too much concern based on Novavax data thus far I reckon, but I am sure there is a lot we don’t know about SARS-COV2 spike protein glycosylation.

        1. Local Haole says:

          Thanks, great points. I had recalled HIV (gp120?) using glycosylation as a cloaking device. Also been wondering if the original poster thought that “proper” glycoform would favor the native solution structure, conferring some benefit, along the same lines as the two-proline version. I find the 2P trick difficult to square with my cartoonish understanding of the immune system, jamming protein antigens through a wood chipper.

          1. Marko says:

            T-cells require the wood-chipped antigens, while the antibody-producing B-cells recognize native proteins, either in soluble form or bound to a cell membrane, so you don’t want your vaccine protein to be in a non-native configuration, thus stimulating a bunch of useless antibody production.

            The 2P modification is not likely to have a big impact, good or bad, on the T-cell epitope library generated by the wood-chipper, and may explain why the non-2P vaccines perform about as well on the severe disease/hospitalization/death metrics, where T-cell response may be more important.

  15. MTK says:

    I’ll be that guy.

    I’m not if favor of early EUA. Not because of any scientific or clinical reason, but purely due to public perception. The biggest threat, imo, is not that a vaccine not work, but rather that people won’t take it. The potential reward of early approval isn’t worth the risk of vaccine refusal. Or at least that’s how I see it. Regardless, it is a debatable issue.

  16. Mary says:

    I’d like to applaud J&J for their inclusion of thromboembolic events as possibly related to the vaccine and I believe based on VAERS data that this is what is being seen with the current vaccines. I am also quite concerned about the 0.1% risk of serious adverse events published in the FDA safety review. Why isn’t anyone else concerned about this?

    1. Chris Phoenix says:

      If I don’t take the vaccine, sooner or later I’ll get COVID. If I get COVID, I’ve probably got a >1% risk of death – I’m bald and it killed my healthy father.

      If I take the vaccine, I have a one-in-a-thousand chance of being laid up for a few days.

      If I could pay $100 to avoid a 0.1% chance of SAE, I probably would.
      If I can pay 0.1% chance of SAE to avoid a 1% chance of dying, I wouldn’t even be concerned.

      Also, if I get COVID, there’s a good chance I’ll spread it to someone else who will die. Could I live with myself knowing I was playing Russian roulette with strangers’ lives to avoid a tiny risk of a few days of fatigue? Maybe some people can, but I can’t.

      And then there’s the likelihood of “long COVID” or damage to my heart, brain, or genitals. No, I’m absolutely not concerned about vaccine results.

      1. Moran says:

        A thromboembolic event is not something someone should play with. Long term damage is too often the result (if you are lucky enough not to die). Young people are increasinly getting forced to get these vaccines, and for them such events are much more of a Russian roulette than Covid.

    2. Chris Phillips says:

      Reposting here, as these misleading comments about thromboembolic events have been made on more than one thread:

      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!

  17. sgcox says:

    Dolly is such a doll !

    1. Local Haole says:

      Yes! She got her shot from the father of Jad Abumrad, the Radiolab creator. I’d recommend a short series of Radiolab episodes about her, and how she met Dr Abumrad.

  18. Petros says:

    Look at Europe’s problems in getting people to take the vaccines, especially AZ. Their inherent vaccine reluctance has been exacerbated by fatuous comments from politicians. Germany has supplies of AZ but few willing to take it.

    Here in the UK, data announced this week is encouraging suggesting a significant drop in serious issues in the oldest age groups, who have now almost all been vaccinated with their first shot. These data appear consistent with those from Israel.

    In the UK over 20 million have had their first shot (ca 40% of the adult population) and approaching 1 million both jobs. The vaccine rollout is about the only COVID thing the UK Government has done a decent job on.

    1. Jonathan B says:

      Absolutely, the UK real world data is looking encouraging. As well as the early studies coming out, the daily Covid figures seem to be showing a positive effect. The decline in deaths from a late January peak has been accelerating as the vaccinations of those most vulnerable take effect, and the last few days have seen possible signs of case numbers declining faster as the more mobile elderly benefit from protection.

      And the majority is the AZ vaccine, Pfizer supplies have been limited across Europe due to a manufacturing hiatus at their Belgian factory.

      By the way, does anyone know if regulatory authorities consider real-world data when assessing authorisation, or is it only the properly controlled clinical trials? With set points for trials at risk of being delayed as cases fall, submitting lower numbers supported by other data might still allow timely assessment.

    2. No says:

      The main problem with the AstraZeneca vaccine in Germany is that it is only authorized for people younger than 65, and it is difficult to round up enough of them with high enough vaccination priority. Basically you need people with medical conditions that make them especially vulnerable (there’s no database of these people, they need some kind of doctors certificate) or medical personnel and care workers (you don’t want to vaccinate them all at once, because the side effects can lead to a few days of sick leave). There are a few people who don’t want the AstraZeneca vaccine, but I think that has been exaggerated.

      1. Chris Phillips says:

        Seriously, that’s the reason they have so much unused AstraZeneca vaccine?

        They haven’t authorised it for anyone under 65 except those with medical conditions, and they’re not going to vaccinate anyone else until all those top priority people are done? Even if it takes months to get enough of the other vaccines to do that?

        If so, that’s completely idiotic.

        1. A Nonny Mouse says:

          Reports say that certain centres only give the AZ vaccine and they are only handling about a tenth of the daily expected numbers as people don’t show for the AZ vaccine due to perceived “Aldi vaccine” label which it has been given by the politicians (and medical people in certain countries).

          I think that, in France, it’s no Sanofi vaccine so no UK vaccine allowed.

          1. bob says:

            The AvonCap findings showed that a single dose of the Pfizer-BioNTech shot, which began roll-out in Britain on Dec. 8, was 71.4% effective from 14 days at preventing hospitalisation among patients with a median age of 87 years, while a single dose of the AstraZeneca vaccine, which was rolled out from Jan. 4, was 80.4% effective by the same measures among patients with an average age of 88.

          2. Some idiot says:

            Again, a 2 cents worth (or 2 kronor worth…) from Denmark: last weekend my wife and I were looking at the statistics here in Denmark, and roughly speaking there has been 95-97% use of available vaccines in Denmark, in other words virtually all available vaccines have ended up in arms.

            Of that, the AZ vaccine is only a very small % of the whole, due to the much reduced delivery, due to their supply problems.

          3. WSR says:

            “I think that, in France, it’s no Sanofi vaccine so no UK vaccine allowed.”
            Not really, since 2/3 the HAS (French medical high authority) recommends use of AZ for 65+ , they have produced a nice write-up of the Scottish university study and are very positive about AZ.

          4. A Nonny Mouse says:

            @WSR

            I was eluding to Macron who didn’t want the EU to buy more Pfizer/Biontech vaccine and insisted that the same amount of Sanofi vaccine was ordered. This hasn’t helped the vaccine roll out at all.

            I am sure that both the French and German communities are much more convinced with the Scottish and England/Wales data release. It seems that German has now approved the AZ vaccine for over 65s.

        2. No says:

          The medical authority has authorized the AstraZeneca vaccine only for people under 65, due to lack of data for those above 65.

          Prioritization is a separate, orthogonal issue, that was decided before the 65 year age limit was known. Currently its those over 80 (these get priority for the other vaccines), those with medical conditions and medical personnel or care workers. So it’s not as idiotic as it seems, but IHMO it needs to change soon.

          1. A Nonny Mouse says:

            It depends on what you mean by lack of data; the AZ vaccine was shown (in a separate study) to elicit similar antibody response through all age groups, although only 8% of the trial volunteers were over 65.

            All the vaccines are being given to over 80s, but how many of these were in the volunteer studies?

          2. Chris Phillips says:

            It’s been more than a month since the recommendation was made not to use AZ for over-65s. How can that not have been enough time for them to work out a way of avoiding the vaccine sitting uselessly on the shelf?

          3. Jonathan B says:

            Some real-world data on vaccines in the over-80s here:
            https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3796835

            Both Pfizer and AstraZeneca around 80% effective against preventing disease severe enough to require hospitalisation. And that is early data from a single dose (UK approach) starting just 14 days from vaccination.

          4. Some idiot says:

            FWIW, in Denmark the AZ vaccine is now authorised for use in the 65+ age bracket, the real-world evidence from Scotland being used as rationale. Also, longer time allowed between doses.

  19. Bash says:

    I am no expert in the matter, but will offer my $0.02

    Variant hysteria is more to do with our modern technological capabilities to actually see them, rather than anything unique to SARS-COV-2

    My guess is the current crop of vaccines are all gonna do a marvelous job of emptying hospitals, and then our natural immune system + periodic boosters will relegate COVID-19 to medical conferences and symposiums

    1. Med Chem says:

      Here here re: “Variant hysteria…”

      …Being cynical, also to do with publishing papers (laudible aim, although can get tainted with bumping up your rating with the admins), justifying grant money and granting politicos yet another reason to boss plebeians around.

      Net effect some of us no longer take any notice, other than forwarding emails commenting on the latest broadcast inanity, today’s here in the UK being…

      https://www.bbc.co.uk/news/business-56260595

      …Welcome to this once sceptred isle, Dear Visitor, and bring a fat credit card with you for the quarantine hotel bill, the testing kits and the £2000 fine you’re threatened with.

      1. Chris Phillips says:

        Of course you have a perfect right to have what hunches you like about the seriousness of the threat from the variants, and about whether particular quarantine precautions are justified.

        No doubt we’ll get a better idea of that in the future. In the future we’ll probably find that some of the precautions we took didn’t have much benefit. But reaching that conclusion with the benefit of hindsight isn’t at all the same as concluding that people were right to argue against the precautions at the time. Unless they were able to back their arguments up with something stronger than a hunch.

        1. Med Chem says:

          Precautionary principle knows no bounds. Can be imposed by authority on whosoever they like. In the strange case of the quarantine hotels, seems just an applied hunch that causes a load of trouble. One man’s wisdom another man’s hunch and vice-versa.

          And oh yes, as matter of curiosity, who’s pocketing the extra 100 quid from the 75 quid a night mandatory quarantine hotels that charge 175 quid a night. And seriously, you cough up 210 quid for the testing kits? Another nice little earner.

          Meanwhile Way out West, the East Bay Mercury reports doubly vaccinated seniors in wheelchairs being entertained by a belly dancer (with picture to prove it). Youth sport resuming this week, limited indoor dining too. Go for it. Some parents getting stroppy after kids off school a year. About time too.

          And if I’m reading right, that’s in a County only just dropped down to a Red Zone. As for Texas, gone for broke. All restrictions lifted 10 March, re-application delegated to the 22 Communities if Covid hospital admissions exceed 15%.

          Back in the Land of Hope, Glory and Misery, youth and grassroots football pitches stand silent another 4 weeks. Killjoys rule okay.

          A returning schools foregoes 3 days teaching to administer lateral flow tests that any number of BMJ articles reckon have around 50% false negative rate. Kids we hear to be fit and well kerchinged again for another 10 days. False positive rules okay?

          Back of the envelope cost £22K for a senior school of a thousand up to Easter. Estimated between £44K and £132K more out of public funds for testing parents and grandparents.

          Another nice little diagnostic corporate earner. Thanks, but no thanks. Mister Moonshine’s moonshots. FFS, spend taxpayers’ and borrowed money on something less worthless, please.

          1. Some idiot says:

            I disagree with most of what you say, but that is just my opinion…! 🙂

            However, regarding outdoor sports, you appear to be totally correct. Calculations performed here in Denmark by the relevant body (SSI) show negligible/no predicted increases in cases due to people playing sports outdoors (in the absence of crowds). This seems to be backed up by what has (or has not, happily) happened in the weeks since that restriction was lifted.

            🙂

          2. Some idiot says:

            Hmmm… Looks like I accidentally put that comment in as a reply to the wrong one of your comments… However, I am pretty sure that you will know where it should have been…! 🙂

          3. Med Chem says:

            @Some Idiot

            One hundred percent behind your right to disagree. What used to be quaintly called civilised discourse.

            Yes, I’d seen that Danish study. Backs up hunch that 22 footballers, 6 subs, 2 coaches and 1 ref dotted in glorious synchronicity around one 68 x 52 metre astro in glorious fresh air somehow different from 100 revellers packed inside a 10 m x 10 m pub on New Year’s eve.

            Oh what a surprise that is. What once upon a time quaintly referred to by a Mister Basil Fawlty as Specialist Subject the Bleedin’ Obvious.

            Danish study come across as ref 12 in recent English Cricket Board scientific study, reaching similar conclusion about cricket ball as Natural Vector of Disease, hypothesis outlined in British House of Commons no less, last July by Old Etonian British Prime Minister Mister Borys Moonshine-Shot.

            Hunch along previous lines had somehow already come to mind – 2 batsmen, 1 bowler, 1 wicketkeeper, 9 fielders, 2 umpires nationally socially distanced round a 2 acre cricket field, nationally socially permabulated by other 9 opposing players and occasional father, mother, brother, sister, girlfriend and family dog.

            Right on again, Basil, you’ve got it. And oh yes, nearly forgot, two scorers sat at two metres apart at opposite ends of a three metre bench, of whom on occasion I was one.

            Thank you Mister Moonshine-Shot for permitting that some three months later than usual, a feat not ever managed at club level even by Kaiser, Fuhrer, Cosmic Catastrophe or Foot & Mouth disease.

            Over and out for this morning to…

            https://www.youtube.com/watch?v=iwU37osOkQA

            …Heard on car radio just now, while diverted as part of UK’s National Roadworks Month. Followed on by jazzed up derivation of Les Barricades Mysterieuses. Treble whammy. Oh what form Cosmic on this morning.

            Ps Ignore the bloke selling houses before the European Anthem that isn’t.

          4. Some idiot says:

            Perhaps if they inserted approximately 40-50 cloves in a fairly uniform pattern onto the surface of said cricket ball, then it could at least begin to _resemble_ a Natural Vector of Disease…! 😉

  20. Iain Flynn says:

    If according to the papers referenced in the blog and some of the comments, it’s T-cells not antibodies which dictate the course of serious illness, and the T-cells (from an earlier infection with the classic virus) are less prone to be misguided by the variants, how come the population of for example Manaus, Brazil, seem to have all caught the disease twice?

    1. Chris Phillips says:

      I think the key may be in the word “serious”. As far as I’ve seen, the question hasn’t yet been answered about what percentage of reinfections were serious.

      1. Iain Flynn says:

        But I think the death rate in the variant outbreak is just as bad as in the classic outbreak? Indicating that the T-cells from the classic infection conferred no benefits in the reinfection.

        1. Marko says:

          It’s certainly possible that reinfections are a major part of the second wave mortality figures in Manaus, but we still haven’t seen the data that shows that. The high mortality could be mainly due to increased virulence of the variant among naive hosts. This article suggests that younger people are having more severe outcomes in the second wave :

          https://www.parintinsamazonas.com.br/?q=279-conteudo-192899-aumenta-hospitalizacao-de-coronavirus-entre-pessoas-de-20-a-59-anos-no-amazonas

          It is worrisome, and it’s frustrating to me that we don’t have a clear answer to the reinfection question yet.

          1. Marko says:

            This chart by Topol on vaccine efficacy vs. variants is useful here:

            https://twitter.com/EricTopol/status/1367210904090148867

            To date, we still don’t have evidence that vaccines fail to provide significant protection against severe disease for any of the three major variants. I’d say the same applies re: protection conferred by prior infection. The unanswered questions we have about the variants are similar whether we’re talking about vaccines or reinfection.

        2. Chris Phillips says:

          There seems to be huge uncertainty about how many people were infected in the first wave. I am sceptical about the sky-high estimates. If the first-wave death rates were based on those, it probably doesn’t tell us much that the second-wave death rates were just as high, because that could translate to “rather low” in reality.

          1. confused says:

            Yes, I am pretty skeptical about Manaus being 75%+ infected in the first wave too.

  21. Spencer says:

    We are in a once a century pandemic and the Novavax efficacy data are on par with Moderna and Pfizer, and arguably better than JnJ and AZ and safety data better than all. We also know that Novavax vaccine is extremely effective against b117 and moderately effective against the SA variant, which we dont know fro Pfe and MRNA. its unfathomable that we wouldnt accept the UK/SA data for an EUA, when another vaccine would speed up the process of ending this pandemic.

    1. Novacek says:

      Except with today’s Merck/J&J news, we’ll have enough vaccines within a couple months. The limiting factor will very quickly become vaccine acceptance, not supply.

      Shortcutting the process for Novavax _even more_ than it already is hinders the former, to “solve” the later non-problem.

  22. Dan says:

    The reason cases are dropping like a rock is the CDC changed the cycles used to measure for the virus back in December?

    1. stewart says:

      Changing the diagnostic threshold, if it had a noticeable effect on case reporting, should show up as a sudden sharp drop followed by a return to the previous trend at a lower level. That is not what is shown by the data.

  23. John says:

    I do not know how to respond to the following question and wondered what thoughts the group may have. In previous trials with both the SARS and MERS Coronavirus vaccines (see below links), the subjects in the trials all developed pulmonary immunopathology when challenged with other common coronaviruses. Has anyone come across any studies that would indicate how researchers have overcome this hurdle with respect to the current COVID-19 vaccine?
    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0035421
    https://www.tandfonline.com/doi/full/10.1080/21645515.2016.1177688
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318931/

    1. Derek Lowe says:

      This also occurred with re-exposure to the SARS coronavirus itself, and this specific experiment was run in the preclinical animal trials (specifically because of the SARS vaccine experiment). The same reaction was not observered, fortunately.

      1. John says:

        Thanks, Derek. I assumed that was the case, but have not been able to point anyone to research that addresses that. Have you seen any studies to that effect?

  24. PJK says:

    Lack of a Novavax EUA borders on criminally insane (particular in a world where the agency is slinging approvals at Sarepta…). Congress should take the unusual step of legislatively mandating immediate emergency approval.

    1. confused says:

      I wonder what that would do to vaccine hesitancy, though.

      *If* those who say everyone who wants the vaccine will be able to get it in a couple months are correct, adding more EUAs now might not help that much – how quickly could Novavax “spool up”? Even a month or so delay might mean it wouldn’t have much effect.

  25. Marko says:

    Crotty and others have gone pessimistic:

    ‘ ‘When will it end?’: How a changing virus is reshaping scientists’ views on COVID-19″

    https://www.reuters.com/article/us-health-coronavirus-variants-insight/when-will-it-end-how-a-changing-virus-is-reshaping-scientists-views-on-covid-19-idUSKBN2AV1T1

    “….But, they say, data in recent weeks on new variants from South Africa and Brazil has undercut that optimism. They now believe that SARS-CoV-2 will not only remain with us as an endemic virus, continuing to circulate in communities, but will likely cause a significant burden of illness and death for years to come.”

    Where is that “data in recent weeks” that shows the burden of severe disease and death by variant infection is not going to be greatly decreased by the current vaccines, or, for that matter, by prior infection? Anyone have a link to that recent data?

    1. Chris Phillips says:

      I think long-term predictions (together with timetables for lifting restrictions announced months in advance) should be limited to those who haven’t made any inaccurate predictions previously. That probably means those who haven’t made any predictions at all.

      1. Med Chem says:

        Same logic could of course be considered re those restrictions based on inaccurate predictions put in place months ahead in the first place…

        1. Chris Phillips says:

          But obviously most restrictions have _not_ been put in place “months ahead” based on predictions.

          On the contrary, over and over again governments have rejected that kind of prudent caution, and delayed until circumstances have forced their hands. An example is the reckless termination of the mild pre-Christmas lockdown in the UK, which was followed by rocketing numbers of cases which forced a much more severe lockdown that is still in force two months later.

          Things could have been very different if the government had taken some action when it was advised to in the Autumn, and perhaps the UK variant wouldn’t be the potentially global problem it is now.

          But I think trying to engage fanatical denialists, who simply won’t look at the scientific evidence, is a fruitless activity.

          1. Micha Elyi says:

            “…over and over again governments have rejected that kind of prudent caution…”

            This is one of the downsides of living in a democratic republic during this post-Christian era. Elected governments respond to the people’s wishes; think that over, would you want it any other way?

          2. Chris Phillips says:

            I was just pointing out that that was what had happened in fact. I wasn’t trying to start a discussion about political philosophy.

          3. confused says:

            While you are right about responding to immediate circumstances vs thinking ahead, I am not totally sure I agree with the phrasing that circumstances “forced their hands” – some state governments in the US (South Dakota being a famous example, but there are much more populous ones, like Florida) did not much of anything during the fall surge. We will have to wait and see if they will pay a political price for that, but right now IMO it doesn’t look very likely that they will.

            The UK may be in a different situation though because of the NHS – the government is expected to ensure healthcare resources are available to everyone, whereas that expectation doesn’t exist in those US states?

          4. Marko says:

            “Elected governments respond to the people’s wishes; think that over, would you want it any other way?”

            Hahahaha. That’s the funniest comment I’ve seen here in a while.

            Maybe it’s just me. I live in the US.

          5. Med Chem says:

            @Chris Phillips, who thinks, “trying to engage fanatical denialists, who simply won’t look at the scientific evidence, is a fruitless activity.”

            What denialist? No denying this morning’s 124,025 and 140,062 numbers on the GOV.UK website. FYI, I’ve looked at the “scientific evidence” aplenty this last year. By physical sciences standards, not exactly rigorous. As Holmes once said to Watson…

            https://www.azquotes.com/quote/508687

            As for UK restrictions months ahead – 3 weeks declared 16/03/20 extended within days to 12 weeks, 4 weeks 05/11/20 predicated to the public on outdated numbers on the powerpoint, 12 weeks 04/01/2021 reviewed week later than committed to on 04/01, namely on 22/02/21.

            True to form, latest outcome announced in effect by decree. Apart from schools re-opening with facemaskery in class under pretence of lateral flow testing, restrictions left in place to 29/03/21.

            All with minimal debate in a House of Commons locked down to 10% in-person and 90% online attendance. The perfect sting, right down to the interesting democratic concept of retrospective voting.

            I know, perhaps I’ll try writing a satire. To convey “The Science”, constructing round a blog by chemist Diedrich Loewe might be an idea. Plenty of Replys to go at. Pass the insanityser, please.

            Meantime, no point evidence-based scientist trying to engage with flagrant anti-denialists, fervent anti-squared-anti-vaxers and fanatical anti-cubed-anti-lockdowners, all dressed up in voice of reason, sanity and science. Go join the Inquisition, Dr Torquemada.

          6. Chris Phillips says:

            Med Chem

            “FYI, I’ve looked at the “scientific evidence” aplenty this last year.”

            Strange that your comments here are so utterly devoid of scientific content, then.

          7. Chris Phillips says:

            “Take a look here, please…”

            It would be tragic that you think there is any scientific content in that post, if it wasn’t so funny.

          8. Med Chem says:

            He who laughs last…

    2. DataWatcher says:

      The way I read this, the “data in recent weeks” have to do with the increased transmissibility and immune escape potential of the new variants. Murray, for one, is “currently updating his model to account for variants’ ability to escape natural immunity and expects to provide new projections as early as this week.”

      This may well inhibit vaccine uptake — if people continue to read that they’re going to have to keep masking and isolating themselves, and that everyday life won’t really change much even after they get vaccinated (Fauci: “Even after vaccination, ‘I still would want to wear a mask if there was a variant out there, . . . All you need is one little flick of a variant (sparking) another surge, and there goes your prediction about when life gets back to normal”), more and more will probably conclude. “The jig is up — why bother?”

      1. DataWatcher says:

        “U.S. government predictions of a return to a more normal lifestyle are repeatedly pushed back, last from late summer to Christmas, then to March 2022.”

        1. confused says:

          This seems pretty unrealistic to me. Much of the US will be effectively back to normal much sooner than that, and all such claims will accomplish is widening already severe divides and increasing distrust of public health.

          I would think people who want a vaccine will have one by the summer, and after that, there is no point in retaining any restrictions.

  26. Moses says:

    @Micha Elyi.
    Governments are elected to govern on a broad platform, and are privy to information not available to the general public. In many circumstances they need to lead, not just respond to the electorate’s whims. This pandemic is one of those occasions.

    1. J Nehru III says:

      Indeed Moses. But where is the Land of Milk and Honey? What will it be like? Will we ever get there? Has the Good Lord spoken and has the Sea parted yet? Passing strange how the Lord foretold the Israeli vaccination programme all those millenia ago.

      And thought for the day from our very own contemporary Indian cricketer sage R Ashwin 1, who in tandem with A Patel 1 earlier this morning yet again rolled over England’s batting order to take India to a 3-1 Test series win…

      “If your back’s against the wall, lean on the wall.”

      1. Chris Phillips says:

        I wonder if the captcha could be upgraded to do a quick test of mental age.

        1. J Nehru III says:

          Buffet bowling, Phillips C. Is that the best you can do?

          Seriously though, always did want to be accused of thought crime, ever since reading that book set 36 years in the future, but first read 15 years earlier and now dated 37 years in the past. Wow, thought criminal. Mission accomplished at last.

          Funny thing time travel, otherwise called getting older by the day. As for captchas, no wish to get overly personal but I’d put yours somewhere the wrong side of 136.

  27. Amma says:

    How come most of the vaccines, barring a few, using different technologies, mRNA, adenovirus, etc.etc. From different countries, US, UK, Russia, India all work very well? Isn’t this strange and worth exploring?

    1. MrRogers says:

      Work on SARS taught us that targeting Spike was the key to making a vaccine that would work. Furthermore, not all vaccines have worked. For example, see Merck’s recent announcement.

  28. lizzy says:

    My thoughts:
    1) If you could choose to get any vaccine (including Novavax, J&J, AZ, or the 2 mRNA’s or others, which would you choose? Be honest.
    Yes you can choose in the US. The various vaccine locations in my state list what they are giving, all you have to do is choose the site of your vaccine of choice. Up until now, it really hasn’t mattered, but J & J is coming.
    2) There are differences, some meaningful, some not, it depends who you are. Months ago I looked up prior exposure to Ad26 in the US. It’s roughly 12%. Is that part of the decreased efficacy? Maybe. J&J will appeal to the young and the old and very frail since it’s only one shot. J&J won’t appeal to the Catholics whereas Novavax might. Those who want a “tested, used, and proved” technology may well avoid mRNA vaccines.
    3) Should the general public be given a choice, and right up front without having to scramble for a shot? Maybe. There’s so much anger out there about the various lock downs curbing our right to choose, it might enhance acceptance. Of course no one wants people to wait, but that’s not the true question here.
    4) On Novavax and its capacity to ramp up production. Many of these hurdles have already been solved. That’s what delayed the US Phase 3 trial from starting as scheduled late October 2020. 2 Billion doses by mid-year promised? (Angalie Kemlani)

    So, which one would you choose? Me, I’m already vaccinated. (12/16/20 & 1/8/21) And, I got my vaccine of choice …..Pfizer.
    3)

    1. debinski says:

      If elderly or with high risk comorbidities: Pfizer (slightly fewer AEs than Moderna)
      If young: J&J (one shot)
      BTW, how was the 2nd Pfizer shot? I had a fairly mild systemic reaction to the first but from what I’ve heard/read, the 2nd packs a bigger punch for most people.

  29. DataWatcher says:

    Osterholm: “The next fourteen weeks I think will be the worst of the pandemic.”

    (3:15) https://www.cbsnews.com/video/epidemiologist-on-new-cdc-school-guidelines-covid-19-variants-and-vaccine/?intcid=CNM-00-10abd1h

      1. confused says:

        I am fairly skeptical that COVID is genuinely rising in 29 states, as case numbers seem to be falling again; last week’s case “rise” seems to have been mostly winter storm effects suppressing week-before-last’s numbers.

        That doesn’t mean it *won’t* rise later this month (due to variants or behavior changes) but I don’t think it is yet.

        1. Marko says:

          Infection curves don’t turn on a dime. Exponential increase, or decline, first becomes non-exponential, then plateaus, then begins to move in the other direction. In declines , you go from R(t) well below 1, to R(t) near 1, to R(t) above 1. The US is in that transition state from the month-plus-long exponential decline phase to what comes next. Absent a policy shift away from our current reckless actions to something more prudent, what will follow is an increase in cases. The impact of the more transmissible variants will inevitably be notable, in just the next few weeks, if we do nothing to counteract it. The examples of this occurring elsewhere are already numerous.

          I doubt that 29 states have truly begun to increase already, but I’m sure a few have. I thought Florida was a good candidate among the major states to show a distinct upward move over the next couple of weeks, but right now NY and NJ look like prime candidates, perhaps because of the NY variant. Florida may yet take the cake, however, depending on the relative transmissibility increase of the variants that are more prevalent in the different states.

          1. confused says:

            Likely – but I am not sure how much can be predicted – especially since the winter storm-induced reporting issues (artificially low numbers 3rd week of February, then higher last week of February) mean that IMO it’s not that clear what is happening now.

            From this CDC graph
            https://covid.cdc.gov/covid-data-tracker/#trends_dailytrendscases
            the blip can be clearly seen, but the line after the blip is too short to clearly see what its slope looks like.

            “If we do nothing to counteract it” is a big ‘if’ given that vaccination is happening.

            Yeah, I thought Florida would flatten and turn upwards by now, too – we’re into March.

            Again, I’m not saying we *won’t* see a spring rise – but I don’t think we *are* seeing it (now), and due to the reporting issues I’m not sure we can even say how much the rate of decline has decreased. Next week we should know more.

    1. Marko says:

      I think he’s rightly expecting the impact from the variants, but I have a hard time believing a future surge will be the “worst of the pandemic”. Vaccinations, as well as the growing level of seropositives, will certainly limit the growth in hospitalizations and deaths compared to earlier surges. Case growth will increase , but even that should be somewhat muted, I’d think, in spite of the variants, but still, I wouldn’t be surprised by a strong surge.

      The exponential decline in cases we saw in the US from mid-Jan to late-Feb is clearly over, however. The same will occur with hospitalizations and deaths, with the appropriate lags. The same has been true in Canada and Europe, though Canada is still in a much better position than the US as regards the levels of daily infections.

      Relaxing restrictions at this time is lunacy, IMO. The UK is managing to keep a lid on things, whether thru restrictions or their rapid vaccine coverage, or both. Canada and Europe may also end up with a sensible response to the changing dynamics due to the variants, but I’m doubtful the US will.

      1. confused says:

        >>The exponential decline in cases we saw in the US from mid-Jan to late-Feb is clearly over,

        I don’t know; cases seem to be declining again after the reporting-hiccup-induced mess of the last two weeks, and I don’t think we have enough post-hiccup time to see whether the current decline is significantly slower. Tests are rising again, which further confuses things.

        Obviously they cannot continue to drop rapidly forever, and there is significant reason to think the end will be soon (B117 + relaxed rules), but I don’t think we can say we’ve observed it yet.

        1. DataWatcher says:

          “Tests are rising again, which further confuses things.” I agree. I really wish the reporting would focus on — or at least remember to mention — RATES, instead of just raw numbers.

          1. confused says:

            Yeah, that’s been a problem all along. I remember seeing, months ago, something like “NY, Florida, California, and Texas have the highest COVID hospitalizations”. Well, given that those are the 4 most populated states by a pretty huge margin…

      2. DataWatcher says:

        My intuitive sense is that we’ll probably continue to see a plateau and at least a moderate spike, and possibly more severe one in those parts of the country where restrictions are being thrown off carelessly. I do know, though, having just spoken with a friend whose mother lives in Jackson MS, that the mayor of Jackson is refusing to go along with the governor’s lifting of the mask mandate, and a LOT of the people in Jackson agree with him 100%. Wouldn’t surprise me to see similar things in Texas and elsewhere. So it may be that even in the states where restrictions have been loosened, there will be regional differences.

        Overall, though, it does seem as if most responsible predictions concerning that much-desired return to “normality” are being pushed back, many to sometime in the first quarter of 2022. Fauci’s latest suggestion is that the US shouldn’t loosen any restrictions until daily new cases fall “well below” 10,000. He’s talking about “cases,” not “severe” cases, for what that’s worth.

        1. confused says:

          I am in Texas, and for whatever anecdotal evidence is worth, no one I know is changing their behavior due to the removal of the mandate. Basically everyone either is concerned or doesn’t care, and people have been “fixed” in those categories for months now.

          It’s possible that the main effect will be less ineffective wearing of masks on ears/chins “to check a box” – those people simply won’t wear them at all.

        2. confused says:

          1st quarter of 2022 seems absurdly pessimistic to me given vaccination rates and the recent EUA for the one-shot J&J vaccine. I have to agree with Youyang Gu’s estimates that by June or so there will be no reason not to go back to normal.

          And conditioning “normal” on number of cases (as opposed to severe cases/hospitalizations or deaths) is really unwise.

    2. confused says:

      This seems… exceptionally unlikely.

      Late March-April rise due to B117 and/or behavior change? Extremely plausible, even likely.

      More severe in terms of deaths/hospitalizations than November-January? That seems extremely implausible, due to the amount of vaccinations in the elderly population – and that 30% or so of the total population is probably already infected (likely concentrated among those being less careful).

  30. Marko says:

    Canada wisely emulates the UK, and goes a step beyond, extending the second dose to four months:

    https://www.cbc.ca/news/health/covid-19-vaccine-spacing-1.5934299

    “…On Wednesday, the National Advisory Committee on Immunization (NACI) said it “recommends that in the context of limited COVID-19 vaccine supply, jurisdictions should maximize the number of individuals benefiting from the first dose of vaccine by extending the interval for the second dose of vaccine to four months.” “

  31. DataWatcher says:

    “New polling shows white Republicans among those most reluctant to get COVID vaccine”

    https://www.wowt.com/2021/03/02/new-polling-shows-white-republicans-among-those-most-reluctant-to-get-covid-vaccine/

  32. Marko says:

    “Five states are rolling back mask mandates. More could be on the way.”

    https://sports.yahoo.com/four-states-rolled-back-mask-032655499.html

    When repeal of the mask mandates becomes universal, we can then look forward to receiving our allotments of high-quality face masks via the US mail, courtesy of the federal government.

    You may be tempted to discard them, since the pandemic will be over by then, but I recommend hanging on to them for emergency use, like when you run out of coffee filters or toilet paper. Heck, in a pinch, a woman with some engineering skills could probably fashion them into a usable feminine hygiene product , I’d wager.

    The US always does the right thing, after they’ve tried everything else, and when it’s too late to do a damn bit of good.

    1. confused says:

      Historically, the US does tend to flail at the beginning of a crisis or dramatic change (Hoover and the Great Depression, utter failure of intelligence re: Japanese Navy early in WWII, early “space race” failures, etc.) but ends up coming out of the end of it stronger, for some reason.

      I think it’s the weakness/strength of a less centralized society.

      1. N G Heatley III says:

        Interesting comment about flailing and coming out stronger. Here in UK, Oxford-AZ vaccine collaboration arguably aspect of less centralised society. Parallels with wartime penicillin story, as told in JC Sheehan’s Enchanted Ring.

        Penicillin born in London, reared in Oxford, adopted in Illinois, taken to maturity in Britain by Beecham, Glaxo and Imperial Chemical Industries (ICI), and in America by Merck, Pfizer and Bristol. All cashed in on as post-war antibiotic companies, apart from ICI which missed out – long-dismantled former national economic bellweather nowadays rarely even gets a mention as grandparent of AstraZeneca.

        And strange how descendents of two generations in the past keep cropping up round here…

        https://blogs.sciencemag.org/pipeline/archives/2021/01/04/variants-and-vaccines#comment-339520

  33. Marko says:

    Danish study supports Nervtag’s finding of increased severity of disease with B.117. They found ~64% increased risk of hospitalization with B.117, along with ~55% increased transmissibility. Even with a lockdown, they figured the variant still had an effective R of ~1.25.:

    “Increased risk of hospitalisation associated with infection with SARS-CoV-2 lineage B.1.1.7 in Denmark”

    https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3792894

    I had my doubts about the Nervtag reports, but now I have to give them credit for sticking to their guns. It looks like they got it about right.

  34. Chris Phillips says:

    Reuters claims to have information on an Oxford/AstraZeneca study in Brazil:
    Preliminary data from a study conducted at the University of Oxford indicates that the COVID-19 vaccine developed by AstraZeneca PLC is effective against the P1, or Brazilian, variant, a source with knowledge of the study told Reuters on Friday.
    The data indicates that the vaccine will not need to be modified in order to protect against the variant, which is believed to have originated in the Amazonian city of Manaus, said the source, who requested anonymity as the results have not yet been made public.
    The source did not provide the exact efficacy of the vaccine against the variant. They said the full results of the study should be released soon, possibly in March.

    https://www.reuters.com/article/us-health-coronavirus-brazil-variant-exc/exclusive-oxford-study-indicates-astrazeneca-effective-against-brazil-variant-source-says-idUSKBN2AX1NS

  35. Marko says:

    Rasmussen, Balloux, Racianello et al. now have a boilerplate excuse for being wrong – “I was “disinterpreted” :

    https://twitter.com/angie_rasmussen/status/1367833291303219207

    1. Marko says:

      Balloux can claim he was disinterpreted about this recent tweet:

      “The drop in SARSCoV2 case fatality rates (deaths / confirmed cases) in the UK over the last month is remarkable.”

      https://twitter.com/BallouxFrancois/status/1367902600192987136

      The graph he uses to illustrate this shows nothing of the kind. It’s showing the rate of decline of Covid deaths, not CFR.

    2. Marko says:

      What’s remarkable about the UK data is that there has NOT been a remarkable decline in the crude CFR, at least according to OWID. In fact, there’s been a slight increase :

      https://ourworldindata.org/coronavirus-data-explorer?zoomToSelection=true&time=2020-12-18..latest&country=~GBR&region=World&cfrMetric=true&interval=weeklyChange&perCapita=true&smoothing=0&pickerMetric=new_cases_per_million&pickerSort=desc

      The increase could be due to the higher lethality of B.117, but I still would have bet that the vaccination campaign would shift the overall crude CFR dramatically lower. If CFRs don’t decline as populations are vaccinated, we have a problem.

      I’d like to see what a proper lagged CFR curve looks like, where you divide current deaths by cases from ~3 wks. earlier.

      1. confused says:

        What are reporting delays like in the UK?

        If cases are dropping sharply, and death reporting is sufficiently delayed, I think this can really skew CFR – as reported deaths continue to rise quickly while cases do not. Right now in TX reported deaths are still quite high while cases are drastically lower than a month or two ago.

        (Which would imply that the earlier CFR was artificially low, due to not accounting for “in the reporting pipeline” deaths).

      2. sgcox says:

        I have a different few on a likely vaccine effect on CFR. Once person get a severe case of COVID, it does not really matter how good was their immune system prepared for a fight against SARS-Cov2 reproduction in the patient. It clearly failed for one reason or other. The purpose of vaccine, as understand, is to stop progression from infection to actual disease and ideally transmission too. IFR is of course much more difficult to measure accurately but should be a much better measure of vaccination success than CFR.

        1. Marko says:

          I doubt the difference between IFR and CFR would explain something occurring over just a few months, absent a major change in testing regimes or access.

          The CFR, as currently measured, for over-60s vs under-60s must differ by a factor of 10 or more. As the former group falls out of the stats due to vaccination, there should be a dramatic shift in the overall CFR, as it more and more measures only the younger population. Maybe it will show up in time, but I find it curious at the moment.

        2. Chris Phillips says:

          Yes – based on the AstraZeneca trial data, shouldn’t we expect to see a smaller percentage of infections becoming symptomatic? So that even if deaths per positive test stayed constant, the IFR could be decreasing by quite a lot.

          Over the past few days in the UK, the rate of weekly decrease of positive tests has shot up (to 34.8% today), overtaking the rates of decrease of deaths and hospitalisations.

          1. Marko says:

            You might be right. I suppose we’ll have to rely on serology to give us a true idea of the number of infections, but most serosurveys have been a mess thus far, generally speaking.

            I just hope the current trends continue in the UK , and when they eventually lift all restrictions, nothing much happens with regards to hospitalizations and deaths. At this point, I’m looking even more to the UK data than that from Israel for such a hopeful sign.

          2. Marko says:

            After looking at the recent UK infection survey, I get the sense that the rising CFR over the last month or more is mostly due to the differential impact of the lockdown by age group, and probably offsets any effect on CFR we might have expected to see from the vaccine. If you play the timeline of infections by age (Fig 5) , it looks like the share of infections among the young is shrinking faster relative to the old since Jan 17 :

            https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/bulletins/coronaviruscovid19infectionsurveypilot/latest

            It’s only a community survey, so may not tell the whole story, but it does pick up asymptomatics as well as symptomatics.

            Changing demographic trends among those infected really makes a mess of interpreting CFR curves. It’s frustrating to me that this far into the pandemic, we still can’t seem to be able to generate a reliable IFR curve , broken down by age blocks, to follow over time.

          3. Mariner says:

            Wouldn’t surprise me if some of the infections are in spite of the vaccination program. Quoting an article on Sky News:

            “More than 40% of the over-80s have broken lockdown rules after getting vaccinated against coronavirus, new data suggests.

            The Office for National Statistics (ONS) asked more than 2,000 people over 80 in England about their attitudes toward COVID-19.

            Some 43% said they had met up with someone outside their household, support or care bubble indoors after getting their first jab.

            And 41% admitted they did so less than three weeks after getting their first dose, “appearing to break lockdown regulations”.

            So, older folk stuck indoors and isolated for months get a false sense of security because they had a dose of vaccine a couple of weeks earlier and therefore put themselves in riskier situations, at the time a more infectious variant is running rife around the country. I’m sure people are warned about the delay before any protection occurs when vaccinated but, well, people really don’t listen very well to the information they are given a lot of the time.

            Could certainly account for some of the CFR data given the timescales and numbers involved.

          4. Marko says:

            Yep, that could also be part of the story. After being cooped-up for a year, I can hardly blame them.

            Next Sky News headline: “Big spike in STD cases among over-80s”

      3. Doug H MD says:

        If CFRs don’t decline as populations are vaccinated, we have a problem.

        Really? Not sure if this is true. Lets face it, preventing infections in the well is very different from preventing death in the unwell.

    3. Doug H MD says:

      show m one prognosticator who nailed things as well as Balloux did last March?

      1. Marko says:

        Lipsitch, both better and earlier :

        https://www.cbsnews.com/news/coronavirus-infection-outbreak-worldwide-virus-expert-warning-today-2020-03-02/

        I never said Balloux at al. are ALWAYS wrong, but they often have been wrong, and they almost universally have looked for some way – like the “disinterpretation” excuse – to weasel out of admitting their mistakes.

        1. Doug H MD says:

          oh i would wager this is far more comprehensive and accurate:
          https://twitter.com/BallouxFrancois/status/1238837158007447558

          1. Marko says:

            Weighing in 12 days after Lipsitch did, and probably also numerous other experts, and then saying nothing of added consequence, is pretty weak tea as predictions go.

          2. Doug H MD says:

            . he actually forecast the likely wave forms and timing. find me a lipstitch quote where he did that.

          3. WST says:

            It’s important to keep in mind that these prediction from early 2020 assume a “naive” population, that is, not taking any protective actions. It’s a “zero hypothesis” for the epidemic’s consequences.
            Same can be said about the scary Imperial College simulation.

            These predictions did not materialize because lots of mitigations strategies were put in place.

            IMHO, with what we know today, a “naive” scenario would be even worse. Their predictions were based on mortality figures with unsaturated healthcare system.

  36. sgcox says:

    March vaccine update:
    All Pfizer vacinnee urgently asked to come to close proximity to G5 masts to receive a free security upgrade against new variants.
    Moderna and AZ are already updated via Elon Musk’ Starlink.

    1. Felis Catus says:

      Do I have to get a new phone as well, or do the nanochips take care of it themselves?

    1. Marko says:

      For some reason they left Michigan out of the states they graphed for B.117 prevalence. I’ve seen one estimate based on the Helix data that has Michigan at even higher prevalence than Florida, and it looks like an upturn in overall case counts may already be underway in Michigan. NYT may have dropped the ball on that one.

      1. Marko says:

        It looks like Michigan, rather than Florida, may be our canary in the B.117 coal mine. Big spike upwards today after many days of a more gradual rise in cases :

        https://www.theoaklandpress.com/news/a-day-after-the-one-year-anniversary-of-the-pandemic-coronavirus-cases-spike-higher-in/article_4ea318c0-81df-11eb-b6c9-ab9f4cbd39ca.html

        1. confused says:

          It seems like cases are falling slower in the northern US than the southern US (though I don’t know why), maybe whatever is responsible for that explains the Michigan/Florida discrepancy?

          I wonder if cases will not convert to hospitalizations and deaths as much as previously, due to vaccination of the more vulnerable older population?

          1. Marko says:

            I think this is beginning to look a lot like the very beginning of the pandemic – areas exposed to large importations of B.117 from the UK and Europe will be impacted first. The Northeast region is about flat now, i.e. R ~1.0, which will move up as the variant becomes more and more prevalent.

            Yes, of course deaths will be lower, relatively speaking, in any new surge. But there’s still a big chunk of over-65s who haven’t received their first dose, not to mention younger at-risk groups. The point is that lifting restrictions now makes no sense in the face of the inexorable – and widely-predicted – effect of the UK variant on US case growth dynamics. Waiting just another month or two to loosen up would save many lives, because virtually the entire at-risk population would be protected by then. But here, the economy always comes first. States are jockeying to take first advantage of the eventual reopening economic surge.

            You can expect to see different outcomes in different areas. of course. Some states and cities will recognize the threat and react appropriately. Other will plow ahead full-steam, unnecessary deaths be damned.

            Michigan is not in complete denial , at least :

            https://www.clickondetroit.com/health/good-health/2021/03/10/7-takeaways-from-whitmers-covid-update-metrics-starting-to-turn-variants-spreading/

          2. confused says:

            >>The point is that lifting restrictions now makes no sense

            I don’t disagree with that – I would have waited at least until it was clear what was happening with the variant (probably only a few more weeks).

            But I don’t think that’s the *only* point. Those numbers you linked earlier in these comments suggested that TX isn’t all that far behind MI in B117 prevalence, and TX case numbers are still dropping very rapidly. I think that suggests that something else is also happening (testing/reporting differences? seasonality working differently at low vs high latitudes?)

            Unless the B117 prevalence numbers are wrong.

            If B117 is 50% more contagious, then a 10% difference in prevalence should only be a 5% difference overall..

          3. Marko says:

            “…TX case numbers are still dropping very rapidly”

            I have a very hard time taking you seriously. Earlier you argued that it was too early to make statements about state-level R values, and that we needed to wait a week or two for the storm-related data disruptions to work themselves out. Now you’re confidently describing a trend you think you see in the Texas data, which was the state most massively impacted by the storm, and whose case data curves most clearly reveal that impact.

          4. confused says:

            I am describing what the numbers are, not necessarily saying that the trend is “real” – reporting issues would be a possible explanation for the discrepancy, sure!

            (However, to me it looks like the winter storm disruption was mostly over the week after the storm… I think this week and last week’s data are probably mostly OK.)

            But it’s not just TX, look at CA’s dramatic decrease, and other southern US states.

          5. confused says:

            And yes, a week ago I said it was too early to say whether the decline would resume after the winter-storm-related data disruptions. I still believe that was true, but it’s now a week later, and it has resumed (at least for TX).

            Now, reporting issues may also be in play, as hospitalizations are dropping slower this week, while case numbers are *very* low. But the trend is downward either way.

        2. Doug H MD says:

          doesnt Florida have a higher proportion of the variant?

          1. Marko says:

            Not according to the estimate for Michigan I posted just above. The thing is, we just don’t know with any precision about any states, because we can’t seem to figure out how to sequence from a swab. The only decent measure we have is the SGTF rates from PCR tests from one company, Helix, which does not cover every state and doesn’t cover any state completely.

    2. Marko says:

      Here’s where I saw the Michigan estimate :

      https://twitter.com/BayesOptimal/status/1367793078786998273

      The data are noisy for Michigan, which may be why the NYT left it out, but the curve fit looks reasonable to me. This projection has Michigan at over 50% B.117 prevalence as of yesterday.

      1. confused says:

        I’m rather surprised by the high estimate for Texas (39.6%) as, after the winter storm issues, cases and hospitalizations seem to have resumed falling at a pretty solid rate in Texas. (4921 COVID hospitalizations reported today vs. 5912 a week ago; 3.6k cases today vs 5.7k last Saturday, 4.3k yesterday vs 5.2k last Friday, 3.5k this Thursday vs 4.9k last Thursday).

        % positive is also falling.

        I don’t know if this is a pessimistic sign (since B117 will be very common very soon), an optimistic sign (because either B117 is not having as dramatic an effect here as expected from the UK experience or other factors pushing virus prevalence down are stronger than we would have thought), or if it’s more likely that the high estimate of prevalence is just wrong.

        1. Marko says:

          With a B.117 doubling time of only ~10 days, you’ll have your questions answered pretty clearly over the next few weeks.

          Even Israel, with their massive vaccination campaign, has seen their rapid decline in cases come to a screeching halt due to B.117. To think the US will be the “exceptional country” here is, of course, normal for the US, and particularly for the Covid denialists, who have an unblemished record of being wrong about this sort of thing. I suspect they’ll maintain that perfect record in this case, too.

          1. Doug H MD says:

            i agree it is likely due to this new variant but it is still just conjecture to say it is due to this

          2. confused says:

            I am definitely not a COVID denialist. I am extremely optimistic in the long term, or even medium term (this summer and on), but trouble this spring wouldn’t surprise me at all.

            Despite seeing that late February’s blip was winter-storm related, I rather expected B117 to reverse declines at least in Florida by the beginning of March, and I assumed (until seeing your post yesterday) that Texas’s still pretty sharp declines implied a low B117 prevalence here. And the CDC variant cases page shows fewer in TX than the other three really-high-population states (FL NY CA). Now maybe we are just sequencing less, but…

            But *if* TX really does have high B117 prevalence, something is weird, because TX numbers are still dropping sharply (today’s case number is really low even for a Sunday, hospitalizations down again, and % positive is dropping very quickly).

            I agree we will know in a week or two, so there is not much point in arguing a lot about this now.

            However, I don’t think the only explanation for the US following a different trajectory than Israel or (insert European country) is some “special US-only factor”. The US likely has a higher % infected than most places outside the Americas, other than e.g. Lombardy and such, just for one thing…

          3. Marko says:

            “…However, I don’t think the only explanation for the US following a different trajectory than Israel or (insert European country) is some “special US-only factor”. The US likely has a higher % infected than most places outside the Americas, other than e.g. Lombardy and such, just for one thing…”

            You picked a bad example to use :

            https://pbs.twimg.com/media/Ev7WONEXAAclXwG?format=jpg&name=small

          4. Bill says:

            I don’t understand the Israel situation. Seems they have 4X our US per capita vaccination totals but oddly have 2X our current per capita infection rate.

          5. Chris Phillips says:

            With regard to Israel, I suppose one factor is the prevalence of the more transmissible UK variant.

            But I would guess another factor may be that if people feel they are protected against serious disease, their behaviour will change, despite the fact that they may be less protected against getting and spreading the infection.

            Personally I wouldn’t be surprised if there were a third wave of infection in the UK in the next few months, though I hope that because of vaccination the fatality rate will be much lower than in the first two waves.

          6. Marko says:

            Yes, I’m afraid that might happen in the UK, as well. I had hopes they’d enforce a strong lockdown for about another month to really drive the numbers to near zero while their vaccine coverage expands, and then begin a gradual easing. I guess it’s next to impossible to do, however, given how sick people are of the lockdowns. The UK has done well over the last month and a half or so, though, for sure.

          7. Chris Phillips says:

            The Chief Medical Officer, Chris Whitty, as quoted by the BBC today, thinks the same:
            “What we are going to see is as things open up, what all the modelling suggests is that at some point we will get another surge of the virus and whether that happens, we hope it doesn’t happen soon, it might for example happen later in the summer as we open up or if there is a seasonal effect it might happen later in autumn or in the winter, there will be a further surge and that will find the people who have either not been vaccinated or where the vaccine has not worked and some of them will end up in hospital and some of them will sadly go on to die,” he says. “That is the reality of where we are.”

            Of course once the restrictions are lifted, it’s not really going to be feasible to continue the same kind of targetted action against potentially vaccine-resistant variants that has been done in the UK so far.

          8. Lily the Pink says:

            This scientist for one submits to the UK’s CMO that underlying epidemical science doesn’t proceed in isolation of external realities that go beyond steps to Stop the Spread.

            Also submitted – Science, public health and government exist to serve, educate and lead, not just to join forces to bring to bear well-intentioned but debatable measures, that bring into play all sorts of unforeseen and unintended consequences for the personal, social and economic wellbeing of a nation’s citizens.

            Further submitted – The preceding governmental purpose is a version of liberal democracy arrived at in the second half of the twentieth century, a version that arose out of the first half of the century’s history, and a version carried over into the current century.

            Lastly submitted – beneath politicking and public health sits an unspoken Hippocratic Oath of Government, saying that, in a liberal democracy, a fundamental aim of government is to balance the best interests of as many of the democracy’s men, women and children as humanly possible.

            So here’s a new work by R McGough III, grandson of Liverpool poet and nineteen sixties Scaffold writer and performer Roger McGough, a man who Wikipedia tells once upon a time also worked with the Beatles…

            https://www.youtube.com/watch?v=AAF1oLZLpxo

            …Specially commissioned to mark resumption of Liverpool’s schools on Eighth March 2021, eighty days after the Christmas 2020 term ended, an event marked in senior schools by mass lateral flow virus testing and mandatory face masks in class for all students.

            MARCH BALL

            By R McGough III

            The term lay before us
            What was left of it
            Three days of lateral flow
            Leaving after this
            Twelve school days to go

            Paper lay before us
            Near a thousand strips
            Nine nine zero negatives
            Leaving after this
            Three tested positives

            Sent straight home from us
            Nothing else for it
            Ten more days at home
            Leaving after this
            Five school days to go

            Anfield lies before us
            What’s left of it
            Six home defeats in row
            Leaving after this
            LFC nowhere but up to go

            Title lost before us
            No other reason for it
            Empty stadium to blame
            Leaving after this
            Football only in name

            Goodison over the park from us
            What’s left of it
            More home defeats than away
            Everton beat us out o’ sight
            Nothin’ atm’sphere on derby day

            Classroom lies before us
            What’s left of it
            Become a masquerade
            Their first (and
            Our last) masked ball

            Written the day after Premier League Champions Liverpool FC went down to a sixth home defeat in a row to lowly Fulham, the club’s worst ever sequence of home defeats…

            …That put into reverse a previous club record league run of sixty eight home games unbeaten at the recently re-consecrated Anfield Cathedral of the late Ian the Saint John, starting with a goalless draw at home to Southampton on Seventh May 2017.

            As educators, poetry lovers and young at heart Liverpool FC supporters of all ages contemplate a future where the recently late great Ian the Saint John scores another hundred last minute winners up in football heaven, any resemblance to Grandad McGough’s 1979 work “May Ball” is purely intentional, a work reflecting a grandfather’s long lost formative experience – “our first (and her last) University Ball.”

          9. Chris Phillips says:

            Is there a psychiatrist in the house?

          10. Dr Sigmund Freud says:

            As I’ve been saying since way back when… The sane man is one who knows he’s crazy.

            And of course I’m known for banging on about how… Being entirely honest with oneself is a good exercise.

            Yet even to this day, I can’t quite work out how come… Everywhere I go I find a poet has been there before me.

            And last but not least, let me tell you from hard won personal experience… From error to error, one discovers the entire truth.

            …If only people would listen to what I say.

          11. Chris Phillips says:

            Why not try posting as Donald Duck or Mickey Mouse next?

          12. Thomas Fairfax says:

            Let’s leave Mickey Mouse and Donald Chump out of this, shall we? The good Dr Lowe’s blog is far too serious for cartoon characters.

            Now I’ve noticed in recent posts Dr Lowe is back with the love of his life again – the one and only Medicina-Chemica. Maybe he’s gotten his senses back at last and broken off with that demanding Covida-Strada for good.

            I always did think Covida-Strada was trouble right from the start. Too theatrical by far. An attention seeker, a melodrama queen. Always in the limelight, wanting and getting centre stage. Behaves like royalty at times.

            I knew all along Covida-Strada wouldn’t last. Between you and me, I’m pretty convinced some of us were immune to Covida-Strada’s charms well before Covida-Strada ever showed up in the first place.

            Good riddance, I say. As the Greek philosopher Leuitinises wrote, when the goddesses Estra and Progestera over reach, the god Testoster must of necessity counter. Eternal verities always did last a long time.

            And talking of melodrama, the one and only Mr Borys Pflogiston up to tricks again in the other day’s Daily Telegraph. Always welcome at the Telegraph, Mr Pflogiston, ever since they gave him a columnist job after the Times had sacked him for making stuff up.

            The other day’s article written by Mr Pflogiston himself in person. By now, I expect he’ll have forgotten what he wrote. Grand plans for transport. Work always did come easy to those who don’t have to do it.

            Pflogiston photo-opped in Whitehole poring up at a massive roadmap of the British Isles alongside a civil engineer chappie, knight of the realm no less. Earnest forefingers pointing out from Westminster.

            Big transport plans afoot. Dealing with long term arteriosclerosis, strengthening sinews, developing musculoskeletal structure – sounds more like a job for Medicina-Chemica…

            https://www.telegraph.co.uk/news/2021/03/10/strengthening-sinews-transport-network-will-make-road-recovery/

            Tunnel to Northern Island even on the map table. Pity the nearest crossing goes to the Mull of Kintyre, but that’s economic geography for you. Meanwhile, the Parliamentary Accounts Committee same day concluded £37 billion test and trace budget had no clear impact on Stopping the Spread.

            Ever unperturbable, Pflogiston resolved to continue on the Covida-Strada roadmap… step by step, jab by jab… until we can get everything open… at the earliest by 21 June…

            …Because, you see, businesses would prefer us to take steps that are cautious but irreversible, would prefer us to trade risk for certainty, as the rate of infection is still high – much higher than last summer.

            Except it isn’t. In recent days the GOV.UK Covida website’s rapidly declining bar chart shows around six thousand daily cases out of one and a half million daily PCR and lateral flow tests combined, a rate of 0.4 percent.

            While early last July, at a shallow local inflectional minimum on the bar chart, the website regularly showed around six hundred daily cases out of one hundred thousand daily PCR tests, a rate of 0.6 percent. Fact duly checked.

            Between you and me, just wondering if Covida website starting to scrape the bottom of the false positive barrel, although let’s not hide from other facts – still 500 daily tested positive hospital admissions and 1200 patients currently reported on ventilators, whereas last July both numbers were two hundred respectively. Okay, give Covida-Strada till the end of March, if you must, Mr Pflogiston.

            You can find Mr Pflogiston wanting on any number of other facts. For a start, the state of major arterial road connections into and out of Merseyside, Manchester and the North Wales coastal strip…

            …Which roads this driver for one can tell you, during four and a half decades and tens of thousands of miles of being at the wheel in the region, have improved out of all recognition and should be low down the pecking order for spending GOV.UK fantasy funds.

            Now once you’ve finished fact checking Mr Pflogiston, just like the seventeenth century near namesake substance responsible for burning, later fact checked as figment and illusion by eighteenth century pioneers of modern chemistry…

            …You get that sinking gut feeling any real-life person even remotely associated with Mr Pflogiston could be suspect too. Cabinets, Ministers, Secretaries of State, Home Secretaries, Chancellors of the Exchequer and Duchy of Lancaster, MPs who vote like sheep, the opposition who vote like sheep too, press officers, advisers, experts, professors and professor sirs, political correspondents, earnest anchors, science correspondents who you can tell have never ever done a serious day’s science.

            In fact pretty much the whole admin advisory HR media PR stage-managed caboodle. All the chatterers, talking heads, twitterers and windbags. All cooped up together in their Covida-secure Home Counties, Metropolitan and Westminster bubble. Watch out folks, in case there’s a big prick about.

            …And then your mind starts to wander abroad. To Dr Deutschmarkel, who until recently you thought had managed to pull off a good war, but ‘cos of quarantine laws as loony as ours now sends Bayern and the Borussias off to Budapest to play Champs League home legs. And away legs too, ‘cos anywhere outwith Budapest and Prague just too unhygienic. Mein Gott!

            …And on to a good Dutch burgher who seemed so upstanding, until falling on ceremonial sword to confess irregularities, be upstanding again, extract sword, self-dust down and carry on as before. Pass the riot shield, will you?

            …And the lofty Vikings, all doing their own good things, although latest news is Danes and Norwegians pausing OXAZ jabs ‘cos of clotting risks, while Swedes, ever pragmatists, put risk into context of twenty million Brits still alive and kicking.

            Valhalla-on-Sea here we come. What’s it all about, Pipeline’s Some Idiot who lives in Denmark? Tell me if I’m nuts, please do, and by the way how are all the mink? Not heard much of Minky lately.

            And oh what a field day Holberg, Ibsen and Strindberg would have had with Covida-Strada. Oh how scandalised polite society would have been. Pity the modern day intelligentsia can’t go along to fawn at live performances ‘cos all the theatres shut.

            Just like Camus and Defoe had a field day with their plagues that took half a city’s populace in a year. No amount of wealth, beauty or twitter feeds could for sure save you, although Defoe’s seventeenth century public health stats do suggest wealth, as with many things in life, helped.

            If for no other reason than a better class of hole to bolt to. Control the rats and you control the plague. It’s the economies, the public’s and the republic’s health, stupid.

            So there we have it, fellow Covida-obsessives. Sooner or later any Covida-Strada dirty linen likely to come out in public. As the Nobel Physics Laureate once said to the Engineers – Nature cannot be fooled. Neither, in the long run, can Economics and Electorates.

            These, then, are some facts and opinions, as I, Thomas Fairfax, see them. I don’t expect anyone else to agree with me. How on earth could I expect that? Get the impression if look close enough, even identical twins rarely, if ever, one hundred percent completely identical.

  37. Marko says:

    The UK has estimated “R” values flowing from multiple sources:

    “The estimated COVID-19 reproduction “R” number in Britain is 0.7-0.9, compared to 0.6-0.9 last week, and the epidemic is shrinking roughly as quickly as it was before, the health ministry said on Friday.”

    https://www.msn.com/en-au/lifestyle/wellbeing/uk-covid-r-number-07-09-epidemic-still-shrinking/ar-BB1eh6uj

    Where are the news reports about the estimated “R” value in the US ? A month ago, when cases were plunging rapidly and the US “R” was in a similar range as the current UK value, people were happy to report about it. Now, sites like the Atlantic’s Covid-Tracking Project and Gu’s Covid-19 Projections are getting out of the business. I doubt this would be the case if Trump was still in office.

    1. Marko says:

      This site has about half of US states with an estimated effective R at or above 0.95 as of March 4 :

      https://epiforecasts.io/covid/posts/national/united-states/

    2. confused says:

      I don’t think we are far enough from the end-of-February data disruption to have a good estimate for many states or the US as a whole. In a week or two we should know better.

      I’m not ruling out political factors of course (the COVID Tracking Project is saying they now trust the federal data and so aren’t needed, which could be partly political, though I think the CDC data genuinely is better presented now too).

      1. Ron says:

        The US Death Rates are confusing–they have held quite a bit above the relative level of the Cases on the charts. And look at the CDC State Trend Comparison and remove CA. TX is still leading the rest of the states.

        1. confused says:

          The high death rates vs rapidly lowering case rates are because death reporting is really slow, I think. Lots of these deaths being reported occurred quite a while ago.

        2. Marko says:

          I wouldn’t be surprised if to see attempts at gaming of the case data by certain state gov’ts as the end of the pandemic nears. There’s a big economic incentive to make your state look like a safe place to visit as restrictions are lifted and travel resumes.

          Today the CDC site has the 7-day moving average of daily cases at ~68,000 , while both OWID and Worldometer have a figure about 10,000 lower. Not confidence-inspiring, to say the least.

          1. confused says:

            The higher CDC numbers might be due to older cases being reported all at once. That’s certainly caused other spikes in the CDC data.

          2. confused says:

            Yeah, that is it:
            https://covid.cdc.gov/covid-data-tracker/#trends_dailytrendscases
            In the notes at the bottom, ” On 08 March 2021, Texas reported 1,295 and Missouri reported 81,806 historical counts of probable cases.”

            83,000 historical cases on one day will raise the 7-day average by more than 10,000…

  38. Marko says:

    Good pic of the PET scan of a woman with inflammatory syndrome post-vaccination (Moderna) which shows activity at the injection site, axillary lymph nodes, and spleen :

    https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00464-5/fulltext

    This might be what most of us would show after vaccination, if to a lesser degree. I’m not sure how sensitive this procedure would be in following the immune response to routine vaccinations. I wish they’d done serology on her to see if she’d had a prior Covid infection, as her rapid and strong reaction to only the first dose of the vaccine might make more sense in that case.

    1. Marko says:

      This new paper by Shi, Krammer, et al. details the activity in blood and lymph nodes following vaccination:

      https://www.researchsquare.com/article/rs-310773/v1

      This was interesting, and might point to the mechanism for vaccine-induced mucosal immunity that enables prevention of infection (i.e. “sterilizing” immunity):

      “…Apart from the PB [plasmablast] response in blood, the S-specific PB pool that persists in the draining lymph nodes contained a substantial fraction of IgA+ cells. This observation is intriguing because it occurred after intramuscular rather than mucosal vaccination. Although none of the lymph node aspirates we collected came from subjects with a prior history of SARS-CoV-2 infection, it remains possible that the IgA+ PBs originated from pre-existing IgA+ memory B cells induced by previous upper respiratory infection with a seasonal human coronavirus…”

  39. Chris Phillips says:

    In vitro studies of serum samples from Pfizer vaccinees showed that by comparison with a wild type from January 2020, “neutralization of B.1.1.7-spike and P.1-spike viruses was roughly equivalent, and neutralization of B.1.351-spike virus was robust but lower” (for B.1.351, geometric mean titer of 194 compared with 532; P.1 was 437).
    https://www.nejm.org/doi/full/10.1056/NEJMc2102017

    1. Chris Phillips says:

      Obviously the signs are that the vaccines can get the pandemic under control, provided that the variants don’t exhibit too much immune escape, at least as far as severe illness is concerned. On the whole it seems that in that regard the South African variant is the one to worry about.

      Probably the earliest indications about that will come from Israel again, in view of reports that the SA variant is now “out of control” there. By which they mean that it has gone beyond the capability of contact tracing to control, rather than that it accounts for a large proportion of cases yet. Reportedly in late February it accounted for about 1% of positive tests:
      https://www.thejc.com/news/israel/warning-that-south-african-coronavirus-variant-is-out-of-control-in-israel-1.512502

  40. Doug H MD says:

    Reinfection risk is TRIVIAL per this study of HCWs in Israel 1 in 1000
    https://www.medrxiv.org/content/10.1101/2021.03.06.21253051v1

    1. Marko says:

      I agree it is likely trivial but it is still just conjecture to say it is based on this study without knowing what the comparable infection risk was for the not-previously-infected group.

  41. Marko says:

    Preprint on the California variant :

    https://www.medrxiv.org/content/10.1101/2021.03.07.21252647v1

    “… Our analyses revealed 2-fold increased B.1.427/B.1.429 viral shedding in vivo and increased L452R pseudovirus infection of cell cultures and lung organoids, albeit decreased relative to pseudoviruses carrying the N501Y mutation found in SARS-CoV-2 variants of concern (B.1.1.7, B.1.351, and P.1 lineages). Antibody neutralization assays showed 4.0 to 6.7-fold and 2.0-fold decreases in neutralizing titers from convalescent patients and vaccine recipients, respectively. The increased prevalence of a more transmissible variant in California associated with decreased antibody neutralization warrants further investigation.”

  42. Marko says:

    Krammer et al. preprint :

    “The plasmablast response to SARS-CoV-2 mRNA vaccination is dominated by non-neutralizing antibodies that target both the NTD and the RBD”

    https://www.medrxiv.org/content/10.1101/2021.03.07.21253098v1

  43. Marko says:

    Denialist guru tweets tend to age very poorly :

    https://twitter.com/AlexBerenson/status/1320112428869365767

  44. Marko says:

    Oh, no. Trump was right :

    Endotracheal application of ultraviolet A light in critically ill severe acute respiratory syndrome coronavirus-2 patients: A first-in-human study

    https://www.medrxiv.org/content/10.1101/2021.03.05.21252997v1

    Next we’ll find that guzzling Lysol is effective…..

    1. stewart says:

      I don’t find that preprint very clear. Am I correct in reading it as saying that “the treatment had no discernable effect”?

      1. Marko says:

        Per the preprint:

        “What is the bottom line? Under specific and monitored settings, endotracheal UVA light therapy may be an effective treatment for SARS-CoV-2 infection. Endotracheal UVA light therapy appears to be well tolerated in critically ill patients with SARS-CoV-2 infection.”

        I don’t think this will go anywhere , but you can bet the Qtards will run with it as they campaign to get the “stable genius” back in office.

        1. Bill says:

          Isn’t this another case of testing a treatment likely to be beneficial early…on late stage patients?

          I assume the goal was for the UVA to kill virus. And I thought at late stage the virus has done it’s deed and you’re now dealing with the consequences.

  45. Marko says:

    “Our Academic US research system is an Underperforming Big Idea”

    Bingo.

    https://twitter.com/raj_mehta/status/1369835818970406912

  46. Marko says:

    Another study showing that vaccination (mRNA) lowers risk of asymptomatic infection :

    https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab229/6167855?searchresult=1

    “…Compared to unvaccinated patients, the risk of asymptomatic SARS-CoV-2 infection was lower among those >10 days after 1st dose (RR=0.21; 95% CI: 0.12-0.37; p0 days after 2nd dose (RR=0.20; 95% CI: 0.09-0.44; p<.0001) in the adjusted analysis."

  47. Marko says:

    ” As transmission rate rises above 1, virus czar says 4th lockdown a possibility – Asked about Netanyahu’s assertion Thursday that the pandemic is largely over in Israel, Ash says: ‘I don’t know what the prime minister meant’ ”

    https://www.timesofisrael.com/as-transmission-rate-rises-above-1-virus-czar-says-4th-lockdown-a-possibility/

    1. Chris Phillips says:

      This seems to be another fairly strong indication that in general there may be further waves of infection following the lifting of restrictions post vaccination. Hopefully with a much lower fatality rate. But if I were anti-vaccination and hoping that herd immunity among the vaccinated would keep me safe, I would find that report from Israel very worrying.

      1. confused says:

        A post-lifting-restrictions wave doesn’t strike me as particularly surprising if a significant % is unvaccinated… but if people have had the *chance* to be vaccinated I don’t see the point of a lockdown or any formal measures; what are you waiting for as an endpoint if it’s not vaccination?

  48. Marko says:

    States where variants have been detected :

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

    Nothing in S.Dakota. Of course, the chances that your swab will get sequenced in S.Dakota is less than that it will be struck by lightning.

  49. Marko says:

    Mask mandates, Swedish-style :

    https://www.thelocal.se/20210311/stockholm-school-sends-pupil-home-for-wearing-face-mask/

    Meanwhile, Sweden’s Royal Family getting sick with Covid-19…..

    1. sgcox says:

      SARS-Cov2 is the Enemy of gods. If you die fighting it, Valhalla awaits you.
      At least they have been consistent.
      Norwegians got softie by sea oil.

  50. Marko says:

    Americans who will choose *not* to be vaccinated when one is available via new NPR/PBS/Marist poll:

    47% Trump voters
    41% Republicans
    38% White evangelicals
    37% Latino
    34% independents
    34% White non-college
    28% White
    25% Black
    18% White college
    11% Democrats
    10% Biden voters

    https://twitter.com/ryanstruyk/status/1370097266955055116

    So, hesitancy seems to be less correlated with skin color than with fundamental mental defects.

  51. Marko says:

    Novavax walking back their attempt to claim seropositives had no protection against S.Africa variant:

    “A previously reported initial analysis from the study through 60 days indicated that prior infection with the original COVID-19 strain might not completely protect against subsequent infection by the variant predominantly circulating in South Africa. However, the complete analysis of the South Africa trial indicates that there may be a late protective effect of prior exposure with the original COVID-19 strain. In placebo recipients, at 90 days the illness rate was 7.9% in baseline seronegative individuals, with a rate of 4.4% in baseline seropositive participants.”

    https://ir.novavax.com/news-releases/news-release-details/novavax-confirms-high-levels-efficacy-against-original-and

    1. Marko says:

      Combined with the serious questions about the immunoassays used to determine seropositivity, it looks more and more like the findings about seropositives in the vaccine trials were more about selling vaccine to seropositives, and less about doing good science :

      https://twitter.com/florian_krammer/status/1369668488500019209

  52. JS says:

    Infectivity does not drop very rapidly with Ct, even above 30:
    https://www.medrxiv.org/content/10.1101/2021.02.28.21252608v1
    Strong increase with age away from 20.

    I find the reliance on following guidance on isolation troubling:
    “In addition, we assumed that all identified secondary cases were infected by the primary case within the same household, because all other household members should isolate themselves from society once a primary case within a household is confirmed.”
    Similarly, there appears to be little consideration of the possibility that two people in a household were infected by the same outside person and testing positive days apart.

    Seems to me that both of these problems could result in a substantial overestimation of rates at high Ct and little is apparently done to control for this. But the age dependence remains interesting.

  53. Marko says:

    Twitter question:

    “So what happens if you get your first covid shot, but then a shark bites your arm off just above where the needle went in, like about 47 minutes after you got the shot? Does that dose still count? As a scientist I need to know these things.”

    Naturally, Akiko Awasaki has the answer :

    https://twitter.com/VirusesImmunity/status/1370400128016773124

    1. confused says:

      The first thing I think when I see “Actually, we did this experiment” is feeding graduate students to sharks – I am glad for the clarification it was with mice!

      Just in case, I will avoid sharks. (Got my first dose yesterday.)

      1. Chris Phillips says:

        I’m surprised they got ethical approval for that. Still, if it was just graduate students…

        But I doubt it’s safe to extrapolate from mice to sharks.

  54. Marko says:

    “Pandemics end when they “change from something that we as a society deem to be unacceptable, into things that can be fatal, but just in the background”, said Erica Charters, associate professor of the history of medicine at Oxford university.”

    https://www.ft.com/content/4eabdc7a-f8e1-48d5-9592-05441493f652?shareType=nongift

    I’ve thought that an acceptable “background” level of deaths per day in the US should be on the order of 1-200 deaths per day, putting Covid-19 in a similar range as a bad flu season, however, the way things are going, it appears to me that we’re going to be willing to tolerate much higher levels than that over the next few months as vaccinations reach full coverage. I don’t think anyone will bat an eye if deaths are running at 1000 per day, a rate that would have seemed horrific not too long ago. It looks like the UK may be willing to do the same, at an equivalent level of 200 per day or so. We’ve prematurely declared the pandemic over, in action if not so much in words, when in just a few months we could have done so legitimately, and saved tens of thousands of lives in the interim.

    1. Marko says:

      Today’s competing headlines :

      “Houston Methodist reports increase in cases of COVID variant first discovered in UK: Doctors said the variant spreading the fastest is the one first seen in the U.K.”

      and….

      “Of 10 Houston ZIP codes with the most COVID cases, only one has vaccinated more than 5 percent of residents”

      1. confused says:

        Why are those competing? I don’t see what uneven distribution of vaccines within the city of Houston has to do with B117?

    2. Chris Phillips says:

      A year ago in the UK the plan was to let the pandemic run its course and to immunise most of the population through infection. That was crazy, but I think the plan now will be to offer the adult population the vaccines and then, if herd immunity hasn’t been reached, let it run its course until it is. There is a certain logic to that, and in any case I think the political pressure to open up will be irresistible. (Though the South African variant is still a wild card.)

      I don’t have very much sympathy with people who refuse the vaccine (after all, they are putting others in danger as well as themselves), but it’s no use pretending there won’t also be a significant number of casualties among the vaccinated.

      1. Marko says:

        The UK plan for lifting lockdowns is more gradual than I’d realized :

        https://www.bbc.com/news/explainers-52530518

        If compliance is good, they may yet achieve a more flu-like level of pandemic impact by the time of full lifting of restrictions, by which time vaccination should be covering virtually all of the at-risk population. This would be about the best outcome one could hope for, IMO.

        The vaccine-averse will then account for most of the ongoing mortality, by their own choice.

        It does seem like boosters are coming soon. My hope is that they can incorporate variant coverage into the first round of booster shots. The data would have to be pretty compelling for me to line up for a 3rd shot of the exact same vaccine in 2021. Perhaps routine antibody titer screening will become a thing, if they can get the correlates of protection defined adequately.

      2. confused says:

        What do you define as “significant”? The vaccines do seem to be very protective against severe disease/hospitalization/death. Obviously, any number of deaths is “significant” to those who die and their family/friends… but I’m not sure deaths among the fully vaccinated would necessarily be expected to be “significant” at a public health/whole population level.

        1. Mariner says:

          The Chief Medical Officer (or perhaps the Chief Scientific Adviser – I always get Whitty and Vallance mixed up), mentioned a figure of 30,000 further deaths this year, even if things go as hoped/planned. That would be another 25% on top of where we are now.

          1. confused says:

            But surely the *vast* majority of those 30,000 would be unvaccinated?

            I was talking only about deaths among those fully vaccinated.

        2. Chris Phillips says:

          I think there are several aspects, as far as the UK is concerned.

          One is that the restrictions are already starting to be lifted, and according to the timetable they may be fully lifted in June – about 6 weeks before some of the adult population is due to receive even a first dose. Schools have already gone back. Over the last few days the rate of weekly decrease of positive tests has plunged to only about 5% (from around 30% a week ago). So it looks as though the number of cases will start increasing again in a week or two.

          Also in the UK a lot of the vaccinations are AstraZeneca. Given that the Phase III trial was mainly pre-variants and indicated only around 50% reduction in infections, and given the increased transmissibility of the UK variant which is now predominant, I think in terms of infections a third wave could be quite substantial.

          And then regarding protection against hospitalisation and death, suppose for the sake of argument that that given contact with someone infected, AZ provides a 50% reduction in infection and an 80% reduction in hospitalisation and death. The trouble is that translates to only a 60% reduction in the infection fatality rate. If there is a substantial third wave of infections in the UK, I wouldn’t be surprised by 5-10,000 more fatalities among the fully vaccinated.

          In addition, people are already straining at the leash to fly off all over the world for Summer holidays. If the South African variant does show significant immune escape (which it certainly seems to against AZ), I don’t see that it can be kept out of the country in that situation.

          1. stewart says:

            This is the second hiccup in the fall in the number of positive tests. This time it is associated with a large increase in the number of tests performed. (The nature of that increase is not made immediately clear at the UK government’s summary page, but I suspect that it’s an increase in lateral flow tests at least partly associated with the reopening of schools last Monday.) So there is an alternative hypothesis that the slowing of the rate of fall is because a greater proportion of infections are being detected. As evidence to the contrary, the previous hiccup didn’t line up with the previous peak in testing.

            We’ll have an answer in a week or so.

          2. stewart says:

            The official estimate of R has just been reduced by 0.1%, to 0.6%-0.8%. (It’s striking that this occurs just as the decrease in the number of positive tests stutters.)

            But the official estimates of R for the UK have had a poor record of lining up with the trajectory of reported positive tests – during the summer the daily count of positive tests crept up from 500 per day to 1000 per day while the estimate of R remained below 1. My tentative hypothesis is that the clumped nature of COVID outbreaks means that surveillance testing is less effective at capturing the progress of the epidemic, but I’m far from convinced that that is the explanation.

          3. Chris Phillips says:

            Yes, you may be right about the hiccup in the decline in positive tests being the result of an increase of lateral flow testing (with allegedly a high false-positive rate). Such a large change in one week would be remarkable.

            Not that my expectation of a third wave was based on that.

            As for the death rate, I wouldn’t be surprised by the 5-10,000 figure I suggested, but I wouldn’t be surprised either if the outcome among the vaccinated were better than that. (But I think either way the prognosis for the unvaccinated in the next few months is not good.)

          4. Marko says:

            With the case number/percent positivity confusion added by the increased usage of LFTs, plus the likely gaming of the numbers in certain US states in the hope for economic gains, I’m going to be watching the daily hospitalization data provided by the CDC as an alternate measure, although I’m not sure it’s any more reliable. At the end of the day, it may be that excess deaths will be the only reliable measure of the true impact of the pandemic, with its inherent long lag time.

            This is the CDC page. I’m sure the UK has something comparable :

            https://covid.cdc.gov/covid-data-tracker/#new-hospital-admissions

          5. Mariner says:

            Marko, this is the UK government’s Covid data site:

            https://coronavirus.data.gov.uk/

            There is a decent amount of finely-grained data available through the site, enough that I can enter my postcode and discover how many positive cases/deaths have been recorded in my local ward of a couple of thousand people over the past day.

            In reply to Stewart, earlier in the thread, I agree that surveillance testing probably under reports when cases are increasing. Our local area has increased numbers once again this week after another outbreak in one of the local fish processing factories and we’ve had a few ‘bumps’ such as this in recent weeks. Random testing of households will show the general indication of numbers, but will miss the events when 50 or more people in the same workplace all catch the virus at once and, of course, this is likely to push the r0 well over 1 in a local area once members of these workers’ households are subsequently infected.

          6. Marko says:

            Thanks, Mariner. Yes, the daily “Patients Admitted to Hospital” chart would be the UK equivalent to the CDC page I linked.

            It’s interesting the for both the US and UK, the 7-day average of daily hospitalizations and case numbers peaked at the same time during the winter wave, indicating that they might both be roughly similar real-time measures. I suppose that might make sense if test acquisition and reporting has more of a lag relative to the admissions data.

          7. Chris Phillips says:

            For the UK, the household infection survey published weekly by the Office for National Statistics probably ought to be the most accurate measure – albeit subject to a time lag – as it’s based on random sampling.

            But given that infection rates were lower among the volunteers in the vaccine trials than among the population at large, it seems likely that the same will be true of participants in surveys like this. It’s not as though they were randomly selected and then forced to take part. They are still public-spirited volunteers, and therefore not necessarily typical of the population in general.

          8. confused says:

            >>plus the likely gaming of the numbers in certain US states in the hope for economic gains

            I am *extremely* skeptical of this sort of thing, at least at the level of any actual falsification (as opposed to data-presentation choices where either choice would be basically defensible, like whether the top-line “cases today” number is confirmed+probable or just confirmed).

            It sounds like something that would be tempting at first glance, but far too many people would have to be involved.

  55. Nodez says:

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  56. Marko says:

    Ontario, just across the lakes from Michigan, where the B.117 upturn is already underway. And Minnesota may not be far behind. Counting your chickens before they hatch, in graphical form :

    https://twitter.com/WalkinRobinL/status/1370540890574499843

  57. Marko says:

    Frieden twitter poll on a 4th surge :

    https://twitter.com/DrTomFrieden/status/1369314127131406337

    I think we easily hit 100k per day and way before July 4. The UK has shown that you can stop a B.117 surge with a lockdown, but I don’t think we’ll impose them widely enough to stop a new surge.

    1. confused says:

      If a 4th surge happens, I’d expect it to peak way before July; by then surely most people should be protected? At the current vaccination rate, I’d think we’d be running out of people to vaccinate by then (there are maybe 270M eligible people, so assuming 75% uptake about 200M people; as we have 105M shots given + current rate is well over 2M/day, and J&J is just one shot so we don’t need 400M…)

      I can totally see a 4th surge happening due to variants + reduced caution (possibly already starting in Michigan… OTOH the summer surge in the US last year didn’t happen in all states, this one may not be nationwide either) but it might not be a particularly large one due to vaccination rates.

      Also, proportionately higher vaccination of the older population may “break the correlation” between cases and deaths.

    2. Bill says:

      I would think a likely outcome will be a fairly imminent surge based on thoughtless reopening, restarting schools, teens at play by the millions at spring break. Then taking it home to infect their households.

      But hospitalizations significantly less than before. I believe more than 50% of the likely hospitalization candidates are currently vax’d, and the number is growing daily. Unfortunately being stymied by current trend of making every worth group the new priority. With everyone eligible, no one is priority.

      Surge gestation in March…peaks in April. Back down again in May or June.

      1. confused says:

        I am skeptical of Spring Break having a noticeable impact: that sort of prediction has repeatedly been made and never quite worked out. A year ago now, Texas and Florida (which hadn’t yet taken measures at the state level, though some companies, school districts, etc. were starting to) were predicted to be “the next New York” 2-3 weeks after Spring Break. This didn’t happen, and these states weren’t hard hit until summer (and I think the failure of that prediction was part of why TX/FL were overconfident going into summer, after significant reopening).

        Similar predictions were made about Fourth of July, Thanksgiving (while the fall surge was certainly dramatic, Thanksgiving doesn’t seem to have made it worse; some areas in the Great Plains/Midwest were already peaking, in fact), the recent Super Bowl, etc.

        The pattern seems to be fairly large (months-scale) waves, fairly consistent across large regions of the US, with holidays having much more of an effect on reporting than on the actual trend.

        One likely exception is New Orleans being about the only place in the South hit hard last spring — this genuinely probably was due to Mardi Gras.

  58. Chris Phillips says:

    Here’s a pretty clear indication that booster shots in the Autumn are being planned in the UK, either for vulnerable groups or the whole population. Interestingly, this may start as early as August, which would probably be before all the under-50s have received their second doses:
    https://www.bmj.com/content/372/bmj.n664

  59. Marko says:

    Good thread about the new Nature paper on increased mortality of B117 variant :

    https://twitter.com/_nickdavies/status/1371441682089132032

  60. Marko says:

    Neutralization titer as the correlate of protection :

    https://twitter.com/florian_krammer/status/1371483579138576388

    1. Chris Phillips says:

      Thanks. I thought the suggested relationship between protection against infection and protection against severe disease was interesting:
      “The 50% protective neutralisation level was estimated to be approximately 20% of the average convalescent level (95% CI = 14-28%).The estimated neutralisation level required for 50% protection from severe infection was significantly lower (3% of the mean convalescent level (CI = 0.7-13%, p = 0.0004).”

      Encouraging if correct, though the statistical uncertainty is high.

      Their estimate of waning also suggests annual vaccinations would be necessary.

      1. stewart says:

        Positive reports from a monoclonal antibody study, via press release.

        https://www.gsk.com/en-gb/media/press-releases/vir-biotechnology-and-gsk-announce-vir-7831-reduces-hospitalisation-and-risk-of-death-in-early-treatment-of-adults-with-covid-19/

        Press reports elsewhere are that it’s ineffective in late treatment, but if cases can be caught early through contact tracing it looks good. Research is ongoing to see whether it is effective as an intramuscular injection (as opposed to intravenous administration).

        1. Chris Phillips says:

          There’s a commentary in Nature about these results and similarly positive ones for early administration of an Eli Lilly cocktail of two antibodies (87% reduction in hospitalisation and death):
          https://www.nature.com/articles/d41586-021-00650-7

          There is also a link to the preprint mentioned in the GSK press release, showing that their antibody maintains activity against the new variants. Interesting that it was originally isolated from a SARS patient in 2003:
          https://www.biorxiv.org/content/10.1101/2021.03.09.434607v1

        2. Chris Phillips says:

          [My comment was held for moderation, so I’ll try again with only one link rather than two]

          There’s a commentary in Nature about these results and similarly positive ones for early administration of an Eli Lilly cocktail of two antibodies (87% reduction in hospitalisation and death): https://www.nature.com/articles/d41586-021-00650-7

          There is also a link to the preprint mentioned in the GSK press release, showing that their antibody maintains activity against the new variants. Interesting that it was originally isolated from a SARS patient in 2003.

  61. hardnox fort says:

    The AZ-vaccine is getting halted across europe.
    At first it was reported to be related to clots in healthcare workers in Austria and the story was more or less closed after investigations did not seem to turn up anything linking them to the vaccine.

    But the later occurances in Denmark and Norway are related to a “very unusual combination of symptoms”: Clots, bleeds and low platelet counts.
    At least 3 people have died (60 year old female, 30-40 year old female, unknown) and several more are in serious condition.
    https://www.nrk.no/norge/seks-sporsmal-og-svar-om-astrazeneca-og-blodpropp-1.15417926

    1. Chris Phillips says:

      I think it should be noted that these suspensions have been decided at national level (or lower), against the advice of both the European Medicines Agency and the World Health Organisation, which have said that there is no evidence that these events are linked to the vaccine, and that it should continue to be used pending further investigation:
      https://www.bbc.co.uk/news/world-europe-56404542

      According to AstraZeneca the number of such events following vaccination is actually lower than would normally be expected to occur by chance. That seems plausible in view of CDC data, which put their incidence at around 4 per million people per day, with roughly a tenth proving fatal. Reportedly 17 million people in the EU and the UK have been vaccinated with AZ.

      1. Marko says:

        Belgium’s health minister is being reasonable about it :

        https://twitter.com/BNODesk/status/1371563480449486848

      2. confused says:

        Even if the effects *were* real, isn’t this number of occurrences far too small to be of any relevance compared to COVID risks?

        1. Chris Phillips says:

          Even if – despite the statistical evidence – these events had anything at all to do with vaccination, immunisation by the vaccine would still be four orders of magnitude safer than immunisation by the virus.

          Isn’t it obvious by now that most people are going to have to be immunised one way or the other?

  62. Marko says:

    White House races to blunt potential Covid-19 surge

    https://www.cnn.com/2021/03/15/politics/covid-19-white-house-vaccine-plan/index.html

    This is all sounds nice, but while they’re at it, whether there’s a surge or not, why don’t they “race” to achieve a daily death rate more like that of the UK, or, for that matter, Canada ?

    At 4 deaths/day/million, we’re at double the UK’s rate, and more than quadruple Canada’s. So, every day we have ~660 “excess deaths” relative to what we’d have if we just matched the UK’s recent performance.

    We won’t race to eliminate that excess death gap, we’ll take a leisurely stroll instead, because those excess deaths are considered an acceptable sacrifice to make as we pursue a rapid reopening of the economy.

    1. confused says:

      While your general point that the US has done poorly relative to most other nations is correct, I think the long lag from infection -> death and from death -> reporting of death means that the rate of deaths being reported now has little correlation with the current virus situation infection-wise.

      (Especially as vaccination being more common in the elderly population means IFR is likely changing.)

  63. Marko says:

    After weeks of declining cases, echoes of hot spots emerge in Upper Midwest, New York City area

    https://www.washingtonpost.com/health/2021/03/16/covid-cases-rising-michigan-new-york-city/

    “..Michigan has seen a rise in hospitalizations and positive test results. Minnesota’s numbers are creeping up, as are Maryland’s and New Jersey’s. Many places, including New York City and surrounding counties, are no longer seeing steady declines in cases, despite intensive vaccination efforts….”

    New Jersey (and Italy) should be viewed as warnings that relatively high seropositivity doesn’t preclude the threat of increased caseloads.There’s still plenty of susceptible hosts around. Lifting restrictions just as the VOCs are about to become dominant is lunacy, especially at a time when ~30% of over-70s in the US have yet to receive their first vaccine dose.

    1. Marko says:

      If Michigan had a VOC Tracker like Ontario’s it would probably look very similar right now:

      https://pbs.twimg.com/media/EwnIfw8WQAUqV5N?format=jpg&name=small

    2. confused says:

      I am generally fairly optimistic, but yeah, it would have been far more sensible to wait a month or so for basically the entire vulnerable population to be vaccinated.

      OTOH, what do we expect vaccine uptake to be among the over-70 population? Probably better than the population overall, but surely not 100% either.

  64. Marko says:

    Three-week lockdown needed to stop explosive COVID-19 variant growth, Ontario science table says

    https://toronto.ctvnews.ca/three-week-lockdown-needed-to-stop-explosive-covid-19-variant-growth-ontario-science-table-says-1.5351152

    This is what the CDC should be recommending to localities in places like Michigan and NJ that are already in the early stages of an upturn. Give the vaccines more time to reach at-risk groups and allow the variant more time to become fully dominant so that when you begin to lift restrictions again you can see what you’re dealing with.

  65. Marko says:

    For Topol, Florida is still the “bellwether” :

    https://twitter.com/EricTopol/status/1372269468815036417

    At times, he’s really clueless.

    1. confused says:

      I agree this is wrong – maybe it is because the other states that have high B117 levels have mask mandates? But it seems the Northern US is largely seeing plateau or slight rise, while the Southern US is largely seeing slight decline or plateau (more than slight in some states, but nothing like the February decline).

      Not that there is all that much correlation between mandates and outcomes state-by-state. Since masks do work, I think the real reason is likely that mandates don’t correspond terribly well with actual on-the-ground behavior.

      TX – where I live – just rescinded its mask mandate, but most businesses, as well as local-government facilities (libraries, city offices) at least in urban areas, seem to have kept requiring masks. I doubt people were actually wearing them in private gatherings, and outdoor it’s probably not terribly important, so it might not change relevant behavior much.

    2. confused says:

      Another odd thing with Florida – https://floridahealthcovid19.gov/ shows that % positive and cases may be starting to rise again, but “COVID-like illness” ED visits are still down (the Monday spikes are very dramatic and regular, but comparing the same day of week, there is a clear if not terribly strong downward trend).

      That’s sort of weird because I’d expect lab reporting delays to mean ED visits were more “leading indicator” – maybe there’s more delay in the ED reporting than I expect?

  66. Marko says:

    CDC seems to be trying to get its VOC act together. They now have month-old variant prevalence estimates for 19 states :

    https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/variant-proportions.html

    1. confused says:

      New Jersey above Florida is surprising! No Michigan in the table, though.

      February 13 is 33 days ago.
      If the old “% of B117 doubles every 10 days” is still true, well… 3.3 doublings (2^3.3) is 9.84, which would put New Jersey and Florida over 80% B117. I wonder if that’s really true?

      (It could have slowed down some – not truly exponential at higher levels – or if the 10 days was just an approximation… 12 days would mean 2^2.75 = a factor of 6.72 or only a bit over 60% for NJ.)

      1. Marko says:

        The 10-day doubling only holds early-to-midway thru the logistic curve. Most countries show about a 3-wk gap between 30-35% prevalence and 70-75% prevalence per the B.117 Wikipedia table:

        https://en.wikipedia.org/wiki/Lineage_B.1.1.7

        The CDC numbers may be minimum estimates for the date cited (Feb 13) since they represent samples collected over the previous 4 wks, unless they’ve been corrected.

        For Michigan all we have at the moment is the Helix data based on SGTF PCR assays.

        1. confused says:

          I figured the 10-day would slow down over time. But yeah, these are probably an underestimate for Feb 13 – wonder if those effects cancel out? You posted a link March 6 with estimates ~40% for TX and ~50% for FL and MI; if those were correct then, those states must be majority-B117 by now, 12 days later.

          (Although this CDC page suggests low B117 in TX.)

          Also, do we know how easily the B.1.427/B.1.429 ones spread? If it’s more than “baseline” that could also slow down B117 taking over… Those have extremely high percentages given in the Southwest (over 40% in Nevada and over 50% in California!) That’s especially surprising since between Feb 13 and now California’s cases have plummeted … which might suggest those variants aren’t that significant? Hard to tell though because the southern US seems to be doing better than the northern, maybe because of seasonality?

  67. Marko says:

    Covid Tracking Project making an encore to report on Michigan :

    https://twitter.com/COVID19Tracking/status/1372713658254467076

    They messed up the numbers on the “Hospital Admissions Today” chart, probably because they’ve already fired their proofreaders.

  68. Marko says:

    This shows Alberta experiencing a similar B.117 trajectory as Ontario, with a great cartoon illustration that shows how most policy makers and the public (mis)understand exponential growth:

    https://twitter.com/GosiaGasperoPhD/status/1372665347283640322

    1. Curious says:

      Marko, Have you gotten vaccinated? If not, why? Also, which would you choose of the 3 currently available in the US? I really respect all of your comments and insight on these threads. That’s why I’m asking.

      1. Marko says:

        Yes, I got vaccinated. I’m old enough that there was never much doubt that I’d do so. When I looked for vaccine availability at the major pharmacy chains, I could have selected either Pfizer or Moderna just by choosing the store that only had one or the other in stock. J&J wasn’t in the mix at that time. I chose Moderna, but only because the pharmacy closest to me had that in stock.

        I might well have chosen J&J if it had been available, just because of the one-shot simplicity, and then get a booster after 6 months or so if that’s the recommendation. I’d have a hard time picking what I think is the superior of the three, and I’d have been happy to get any of them.

        I would have preferred to delay my second dose by some number of weeks but the website had no easy mechanism to cancel and reschedule, unless you claimed that you were symptomatic , so I got my second dose just yesterday. Overall the registration process was a clunky mess and I just wanted to be done with it.

        1. Curious says:

          Thank you very much for your reply! Would you have a preference regarding which of the 3 you’d choose as a healthy 35 year-old? Or would you potentially hold off for a while?

          1. Marko says:

            If I was in that position, I’d go for the J&J vaccine, just to reduce the hassle, then see how the efficacy and side effect landscape plays out in coming months to decide which, if any, booster you might need. Your risk of a severe Covid outcome is already very low. If you get only one dose of any vaccine, that risk probably declines another ten-fold or more. Scavenging for additional risk reduction via choice of vaccine is probably not as good a use of your time as would be checking the air pressure of your car’s tires.

            If you’re confident in your ability to avoid infection, waiting a while is a good option too, as more info and more vaccine options will become available with time. Given that there are still many over-65s who are struggling to get vaccine appointments, by waiting you’d help de-clog the system for them , and maybe the pharmacies would make the process easier (allow walk-ins!) in order to attract enough customers for their vaccine allotments.

  69. Curious says:

    Appreciate your insight. I have an appointment to get J&J on June 5th. Hope you are feeling well after your second dose.

    1. Marko says:

      Thanks. Just a sore arm and some brain fog so far, but I can’t really blame the brain fog on the vaccine.

      1. Curious says:

        There were a bunch of cancellations at the vaccination site near my house this past Saturday, so I jumped on one and got the J&J. Fever, chills and body aches for about 12 hours and then good as new. I’m also pregnant (3rd trimester), so it was a nerve-wracking decision to make. But, as everyone in my “inner circle” seems to be loosening up their restrictions during a time where I need to be tightening my own, I felt the need to protect myself and baby for the remainder of the pregnancy since covid carries heightened risks for pregnant women. I also live in NJ where cases are rising. Hoping it was the right decision! Again, appreciate all your insight and commentary on these articles.

  70. Marko says:

    A graphic on the AZ vaccine risk/benefit calculus by age :

    https://twitter.com/EricTopol/status/1379832662685229058

    No idea if this is accurate, but the Covid-19 risk is based on UK incidence rates in Feb., which are now considerably lower. The risk/benefit now would thus be a little dicey for the under-30s, but increasingly less so above that age range.

  71. stewart says:

    Science published something (paywalled) on the Russian EpiVacCorona (protein-based) vaccine. The abstract seems to say that it is ineffective.

    https://science.sciencemag.org/content/372/6538/116

    1. Alex Beribisky says:

      If interested in having a read:

      https://www.iimmun.ru/iimm/article/view/1699/1188

      1. stewart says:

        Ah, I see that the abstract in Science is ambiguous. It is consistent with either no induction of antibodies, or with the normal decay of antibody titres over time. And not being clear as to where it was in the vaccine development process (phase I and II studies reported) also allows scope for misinterpretation.

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