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Variants and Vaccines

Well, here I am with the first “In the Pipeline” post of 2021, and damn itall, I’m right back to the stuff I was writing about last time. I still expect this year to be the time when we beat back the coronavirus pandemic, and (as a minor side effect for me) to be the year when I can spend more time blogging about other things than viruses and vaccines. But that time is not yet.

No, definitely not. There are a lot of things happening right on top of each other at the moment, and it’s impossible to say yet how they’re going to balance out. On the plus side, we have two vaccines approved in the US, and other countries are starting to use the Oxford/AstraZeneca vaccine or one of the Chinese vaccines. And we have more promising candidates that will be reporting very soon (J&J and Novavax). The minus side is that we’re going to need those very much, because manufacturing and distribution constraints are very real problems. We can argue (a lot) about those, their extents, who’s at fault or not, and all the rest, but I think that we can stipulate with no problem that they are indeed constraints. We have to get a large number of people vaccinated in a short period of time, the largest in the shortest, and as it stands right now neither of those numbers are anywhere near what we need.

I have every expectation that the pace of vaccination will pick up. But the other factor at work is the new coronavirus variant. Since I wrote that post, it’s become even more clear that yes, B.1.1.7 is indeed more infectious. The data from the UK are no longer consistent with its numbers being due to any sort of statistical accident, and it’s now been reported in numerous countries and several US states. At this point, it seems likely that it may follow the same pattern in those areas – and in the US – that it did in the United Kingdom, spreading more rapidly until it becomes the dominant strain in these populations.

That’s not good. Reports so far don’t show B.1.1.7 leading to more severe infections, but spreading the same disease we have now more quickly is still one of the last things we need. The latest data would seem to point to increased viral load in the upper respiratory tract as a big part of the problem – people are presumably shedding more infectious particles more quickly, which would certainly do it. There are many people talking about the cellular entry part of the infection process and whether B.1.1.7 is better at that, but I’m still reading up on the details. That could well be what leads to the increased viral load, but there are other possibilities, too. We’re going to know more about the details, and soon – a huge amount of work is going on in real time – but the increased R for this variant seems hard to refute.

So it’s the UK that’s in the worst shape with this variant right now, from what we can see, and what are they doing about it? This Helen Branswell piece at Stat will get you up to speed. As many will have heard, there are proposals from the British government to delay the second dose of the existing vaccines in order to get first doses into as many people as possible. It appears that our existing vaccines do indeed protect against B.1.1.7 infection, although more data on that would be welcome, but they sure don’t protect the people that aren’t dosed with them; on that we can all agree.

The delayed-dose idea had been floated before, and I wasn’t exactly an early adopter, but the more contagious version of the virus has made me reconsider. But as I was going on about on Twitter the other day, we have to be clear that this is, in fact, an experiment on the population. It seems likely that delaying these doses will likely work out OK. But we don’t have much evidence either way. I’m in favor of doing it, but I’m not happy about ending up in that position. I don’t trust immunology to always work the way that I think it should work, but it seems that we have little choice.

And by “we”, I mean all of us. As mentioned, B.1.1.7 is showing up around the world, including areas whose medical capacities are already being strained. The U.S. is very much included – look, for example, at the situation in Southern California. If things go badly, we could be seeing a big wave of this variant across many parts of the country in the next weeks, and it could be spreading much faster than our vaccination program can knock things back down. We have to get ready for that possibility, and there are already proposals here to adopt the delayed-second-dose protocol. Just in the last day or so, in fact, there’s been another proposal to use 50µg doses of the Moderna vaccine instead of the 100µg doses authorized in the EUA. Moncef Slaoui pointed out that the data submitted by Moderna show that the two doses produce similar immune responses in the 18-55 age group.

That’s another one that you can say will probably work, but there are things to worry about, both in the Moderna dosage idea and the general delay-the second-dose plan. I’ve been watching some very competent people argue these points both ways: here’s Florian Krammer with the possibility that these ideas could end up generating more resistant variants of the coronavirus. The Stat article linked above has similar worries from Paul Bieniasz at Rockefeller and Isabella Eckerle in Geneva, along with other experts who still think it’s the right way to go. But the worries are not just scaremongering from randos online or anonymous bureaucrats who don’t want to fill out more forms; it’s a real possibility, and its chances have to be weighed against the effects of the greater spread of the existing variant with slower vaccination schedules. Both of these could lead to very bad outcomes. Not dosing more people could exacerbate the problem of regions getting overwhelmed with the more contagious variant, with needless deaths due to the loss of hospital capacity. But if we spread out such vaccinations too much and manage to generate another variant that partially or even completely escapes the existing vaccine response, we will be in even worse shape.

I do not know how to make this decision. I really don’t. We have degrees of harm, probabilities of harm, logistics, timing, public health capabilities, politics and more to consider, and not a lot of time in which to consider them. Anyone who uses the phrase “no-brainer” to describe this call should be dropped from your list of people to take advice from. This is the opposite: it’s a decision that all our brainpower may still not be sufficient to make clear. But we’re going to have to make it anyway.

259 comments on “Variants and Vaccines”

  1. Masher says:

    I posted the following on the “Vaccine Roundup Late December” thread, just a few minutes before this new thread was created:-

    A new article in the Daily Telegraph (UK) reiterates the thinking of Prof. John Bell (Oxford vaccine group) on this:-

    The article is behind a paywall, but key points are … his “gut feeling” is that the vaccines already on stream will be effective against the new UK strain, but there is a big question mark against the South Africa one, as its mutations are substantial changes in the structure of the protein. He goes on to say that it’s unlikely that these mutations will entirely evade the vaccines, which will still have a “residual effect”. He also said it should only take a month or 6 weeks to make new vaccines in response, and that we are likely to have to respond to further variants as time goes on.

    1. sgcox says:

      I think Sir John Bell is concerned about E484K mutation in SA variant
      It has been shown to be selected (among many others !) in in vitro studies using artificial recombinant virus.
      He might be overcautious here.

      1. Chris Phillips says:

        Further indications of possible immune escape as a result of mutations seen in the South African variant:
        Despite this inter- and intra-person heterogeneity, the mutations that most reduce antibody binding usually occur at just a few sites in the RBD’s receptor binding motif. The most important site is E484, where neutralization by some sera is reduced >10-fold by several mutations, including one in emerging viral lineages in South Africa and Brazil.

    2. Alethea says:

      There is some evidence that Blood Type A is more susceptible to COVID19, SARS-cov2,- – and IF infected, the Type A course is worse. Is there any data about Type A response to the Pfizer vaccine? Moderna vaccine? etc

  2. Tom Maguire says:

    Probably worth emphasizing, in terms of public health capabilities and politics, that we are operating in a low-trust environment. There is likely to be a gap between “What Makes The Most Sense” and “What The Public Will Believe”.

    Eg, I like the idea of a half-dose for Moderna for the 18-55 cohort but rather than just use “off-label” authority it would be better to sound out the FDA and try for a formal EUA. But make sure we know the answer before formally asking!

    1. kevin smith says:

      Speaking as a dermatologist, intradermal administration of vaccine will cause the vaccine to be taken up and processed by the Langerhans cells in the dermis, which then present the antigen to the immune system. This is perhaps 10x as effective as an intramuscular injection; and was considered way back when there was a shortage of Hep B vaccine, shortly after it was introduced.

      Intradermal injections are a bit more technique-dependent than intramuscular injections, but not that tough. Dermatologists give intradermal injections of things like corticosterioids and botulinum toxin [BOTOX™ et al] all the time.

      It might be worth looking into intradermal vaccination if that would allow us to elicit a full response with a smaller amount of vaccine.

      1. Mike G says:

        Can somebody look into this plausible-sounding possibility?

        1. Charles H. says:

          The problem with all these ideas isn’t that they aren’t reasonable, it’s that it would take time to research the answers. Generalized answers are only (at best) “probably correct”, with a huge uncertainty about the value of probably.

          1. Donald Chabot says:

            I don’t think there is time to look at intradermal for the near future. The vaccines are working very well, so not sure why anyone would suggest that as a major undertaking at this point.

          2. SVF says:

            A reliable french medic commented that the Pfizer vaccine was given intradermally on some of the “photo opps” he’d seen, and not intra-muscularly as recommended. Am

      2. Wetdog says:

        One issue with the mRNA vaccines is that you might NOT want them to be ‘more efficient’. They are running on the ragged edge of acceptability in terms of local reactions. If this wasn’t a pandemic situation, you would be seeing Pfizer and Moderna back at clinical trials trying to find a better balance between immunogenicity and anaphylaxis.

        As has been pointed out, it’s doable, not even a bad idea. But not something else that hasn’t been thoroughly tested on top of all the *other* things that haven’t been thoroughly tested.

        1. Marko says:

          “They are running on the ragged edge of acceptability in terms of local reactions.”

          One anaphylaxis case per 100k doses is “ragged edge of acceptability” ? The risk to benefit calculus puts the Covid vaccine exactly in line with the flu vaccine in this regard. I’m OK with the anti-vaxxers refusing to get their shots, however. It frees up doses for the rest of us :

  3. Carl says:

    What’s the history of single dose and/or low dose vaccinations leading to vaccine resistant virus mutations?

    1. Steven Kaye says:

      Signal boosting this. I’m very interested if anyone knows of studies on this.

    2. Giannis says:

      It has never happened. If moderna had chosen the 25μg route and showed a 85% efficiency nobody would care. The graphs in the NEJM are almost identical between the 25 and the 100μg groups. Objecting to lowering the dose for fear of increasing vaccine escape is ridiculous, especially hearing that from established immunologists.

      1. Patrick says:

        I would call the groups attention to Derek’s words on no brainer decisions. No other thoughts.

    3. Not-an-epidemiologist says:

      Not relating to low-dose (what defines low-dosage?) or single-dose vaccines in particular, but this review in PNAS from 2018 covers the (very few instances of) vaccine resistance in general:

      The authors argue that it’s much rarer than drug-resistance and also that the consequences on host and pathogen are less clear than with drug resistance. Which is reassuring.

      1. Carl says:

        Thank you for the study. Vaccine escape sounds quite rare. Regarding what I meant by “low dosage”, I simply meant instances where vaccine escape occurred and it was later determined or theorized that the cause was too little of the vaccine had been used in some population.

    4. Barry says:

      There is zero evidence for under-dosing provoking viral (or bacterial) resistance to vaccines, and excellent reason to be against it ever happening.
      Vaccines train the host’s immune response; they don’t exert any pressure on the pathogen directly

      1. A says:

        There aren’t any data on it, but we haven’t actually vaccinated against that many diseases so it’s not all that surprising.

        While there’s no direct pressure, there is indirect pressure in that the immune response is acting on a fixed version of the viral genome.

        The biggest difference here is that many of the vaccines are mRNA-based, not live-attenuated, so the antibody response is more specific to spike. It’s a lot of different pieces of spike to which the body is trained to react, but less than live attenuated, so it would make sense that those are more susceptible to evasion. That being said, making updated versions based on mutations is also much easier, so I would guess we’d be able to keep up, given the current rate of novel strain emergence (i.e. maybe 2 over the course of over a year, neither of which will likely have done enough to fully evade).

  4. Gerard van Westen says:

    Very much agree… Rock and a hard place..

  5. Ian Malone says:

    I’ve been contemplating for a while that the “the vaccines were rushed” objections failed to understand what the actual implications of that are. The vaccines that have made it through phase 3 have really good safety and efficacy data, about as good as we ever get, what we haven’t had the chance to do is exactly what Derek discusses here: scope out the best dosing strategies. We’ve proved the hardest shot we can take works, but can we get away with less? Yes, there’s some phase 1 & 2 work, but it can only signpost things to look for in the actual trial. Now we’re falling back on it for “should works”, but there’s only so many of those you can stack on top of each other before one of them proves not to.

    (Link needs correction, the 50ug p201 data is not in the FDA’s briefing document, it’s in Moderna’s section 5.3, “Vaccines and Related Biological Products Advisory Committee December 17, 2020 Meeting Briefing Document- Sponsor” from not being an immunologist I don’t know how to interpret those numbers other than to say yes, they’re similar. Important to note though that these are not efficacies.)

  6. sPh says:

    While planning and coordination in the US could have been better the startup of such a huge effort was bound to have problems including stops/starts and some wastage. The percent vaccinated and percent of material delivered numbers three weeks from today will be a lot more representative of how the spring will go than partial (and possibly misreported) numbers from a first rollout over two holiday weeks. Let’s wait for those numbers before risking the entire program with rushed off-label use.

  7. Marko says:

    I’m not so worried about an adjustment to the vaccine schedule or dosing setting us up for a flood of immune escape mutations , simply because we’ve seen little evidence of it with natural infection, where a variety of immune responses occur in individuals, from meager to robust in both intensity and duration.

    Of course, the study of reinfections has been pretty limited since the outset, so there could be something we’re missing, but if we’re suddenly so concerned about immune escape now, I wonder why we haven’t been paying more attention to reinfections to give us a heads-up on this problem.

    1. Roland says:

      I think we’ve learnt chronic infections in people with poor immune response are one of the big concerns for mutations. Among others there’s a particularly well reported case described here by Ravi Gupta involving variant coronavirus populations responding to convalescent plasma:

      However I haven’t come across anyone urging against convalescent plasma use because of mutation risk. (Possibly it’s a harder thing to say when an identifiable individual is infected and it may save their life, rather than abstract future vaccinations which are expected to save unidentifiable lives.)

      If ‘poorly vaccinated’ individuals were a risk for immune escape shouldn’t we have seen issues around those who appeared to have cross-reacting antibodies from previous, different coronavirus infections? Or am I misunderstanding the proposed mechanism here?

      Ultimately a big part of the mutation risk is a numbers game. More infected individuals – some of them with funky immune responses – give the virus more opportunities to get lucky with a nasty set of mutations. Vaccinating as widely as possible will bring that dimension of the risk down fastest and in a predictably proportionate way. Other components of the risk are harder to assess. Which isn’t to say we shouldn’t care about them at all, but it would be a very brave decision to give up a confirmed advantage now in return for a hoped-for theoretical advantage later.

  8. Sc says:

    I agree desperate times call for desperate measures. I just wonder if these on-the-fly vaccination modifications are being considered less because they’re the most sensible option and more because politicians think they can dodge blame if something goes bad vs the flak they’d get doing other things like actual lockdown measures. I guess part of any response is dealing with political realities but it’s just frustrating that we’re doing this dance of talking about half doses and longer waits while we’re also letting people eat and drink inside restaurants and packing kids back into schools.

    1. paperclip says:

      This. For the interim at least, we should view vaccines as just one weapon at our disposal. We have masks (and enforcing them!), social distancing, and (maybe even) contact tracing. Think of the countries that did well even before vaccines came over the horizon.

      1. Adrian says:

        It is always disturbing when masks are listed as first weapon against COVID-19, especially the cloth masks that are unfortunately widespread in many countries but are in the “perhaps better than nothing” territory with little robust data on actual benefits.

        Social distancing is the one weapon that matters.
        And this is the one where enforcing is most important.
        Enforcing social distancing means closing restaurants and schools and airports.

        The mask murder of keeping schools open while enforcing masks there is where masks are killing people – masks are being used as excuse for not enforcing social distancing.

        Thailand is among these countries that did well all the time, but right now they are facing their first wave of infections.
        One of the first actions of the government was to close all schools and daycares for the whole month of January.

        I live in Finland, a country where during the first wave in spring everyone followed the government recommendations of doing social distancing and NOT wearing a mask.
        Restaurants and schools were closed.
        Per capita we had one of the lowest infection rates in Europe.

        Countries like the UK or France where masks were enforcement widely but that failed on social distancing are now in the next lockdown.

        1. Mariner says:

          Here in the UK, masks weren’t actually required until some time after the first wave had peaked. I seem to recall, the rulings (which a lot of people ignore – many don’t bother and others think they should be worn as chin straps) weren’t brought in until after the summer.

          The one point about masks – even cloth ones – is that there have been some studies indicating that use of them may lead to milder illness if somebody did become infected. Worth the inconvenience if you can keep people out of hospital – providing the public messaging makes people aware that they aren’t ‘protected’ by wearing one. Not sure it does in this country.

          1. Mariner says:

            To correct myself, I meant to say masks were mandated during the summer. Around early August or thereabouts, I seem to think. Many months after the early peak in infections.

          2. Adrian says:

            “indicating that masks may lead to milder illness” – that’s a pretty weak statement on a pretty weak data basis, it is similar to “taking vitamin D may lead to milder illness”.

            You are wearing a mask and I am taking vitamin D (which is in any case recommended here up North).
            Based on the available data it is not really decidable which one is more effective to protect oneself.

          3. Adrian says:

            Just to make my case clear:

            I did spend Christmas alone because visiting family would not have been responsible.

            I have no respect for people who want to force everyone to wear masks, and then use wearing masks as excuse for doing unbelievably irresponsible things like visiting other people for Christmas. The situation would be a lot better without all these idiots who are wearing masks instead of focusing on social distancing.

          4. Mariner says:

            An experiment with an animal model indicated masking may reduce infection rates and also, perhaps, lessen severity of infections:


            I seem to recall I read this on one of Dereks posts last year, although I may be mistaken.

            I am wearing masks where suitable and also taking Vitamin D through cod liver oil tablets – just a general health supplement, not super high levels as some apparently are. Spacing goes without saying.

          5. Tom H says:

            @Adrian, masks and social distancing do not need to be mutually exclusive. The way our public health organization puts it, masks reduce risk (to others!) when distancing is not possible — such as in supermarkets or on public transit.

            We have no silver bullet (at least not until the vaccines are more widespread) so it’s all about risk mitigation: staying at home, avoiding crowds, distancing, masks, cleaning etc. Each one reduces risk, and combining all of them reduces risk even more.

          6. Adam says:

            Buy your groceries online. There isn’t much excuse to wear a mask instead of social distancing. Although I know many people have come up with excuses.

          7. Adrian says:

            It is a deadly mistake when people list masks as first action.

            Social distancing is the most important action.
            Everything else cannot be more than mitigation when social distancing is not possible.

            Enforcing mask usage without enforcing social distancing is mask murder.
            Enforcing mask usage without enforcing that schools and restaurants are closed is mask murder.

            And when you are using a mask, please use proper single-use surgical masks.
            If you want to mitigate risks, cloth masks are a bad choice.

          8. Tom H says:

            No one here is listing masks as the first or only action. But wearing one does reduce the risk of infecting someone else — it’s not always possible to be 2m away, whether in a supermarket (not everyone has realistic online options), a train or a bus, or an apartment building hallway or staircase. Yes, distance first. But when you don’t have enough distance …

          9. Adam says:

            When you don’t have enough distance you make distance. You move away from others and let them know you are uncomfortable. Or you only leave your house at off hours.

            As far as online shopping goes there is always Amazon. Rice and beans can always be ordered. Weight loss in a pandemic isn’t such a bad thing either.

            The amount of excuses people will come up with because they don’t want to do change their routine is astounding.

          10. T says:

            Everyone simply buying groceries online is not a solution. Online groceries do not magically drop out of the sky; they require a whole system of staff and equipment that is not set up to cover every citizen (or even a large percentage). During the first UK lockdown, many more people than usual tried to buy groceries online and it overwhelmed the system. There were huge delays and backlogs and many supermarkets stopping taking new orders, which meant that vulnerable people who were meant to be shielding (i.e. those for whom it was really dangerous to go to a supermarket) couldn’t get the groceries they needed.

          11. T says:

            @adam please don’t give medical advice when you’re clearly unqualified to do so. Weight loss in a pandemic is absolutely a bad thing if your weight is already low. Being malnourished and/or underweight increases your vulnerability to infection. Expecting people to change their social/work routine is one thing (I haven’t been in any building other than my flat and the supermarket since last March), but suggesting the entire population gives up eating fresh foods through a long-running crisis that has already gone on for almost a year is absurd. Besides, you say you can “always” order rice and beans: do you really think that would still be true if every person in the US starting ordering them in bulk?

          12. Adam says:

            I wasn’t aware that most of the people being admitted to the hospital with Covid are underweight. Maybe you know more than the CDC?

            “Approximately 90% of hospitalized patients identified through COVID-NET had one or more underlying conditions, the most common being obesity, hypertension, chronic lung disease, diabetes mellitus, and cardiovascular disease.”

            Haha. I did mention people love to make excuses about why they can’t shop on Amazon. It’s amazing how much people fight logic. I’m going to start calling them Amazon deniers!

            I order lentils and they arrive next day. Try harder and stop being such a jerk.

          13. Chris Phillips says:

            About masks I would put them in the “necessary but not sufficient” category if people are having face-to-face interactions (which they shouldn’t be if they can possibly be avoided).

            I’m sure they can help by stopping larger droplets that travel mainly by inertia. They will not (unless they are airtight with a filter) stop smaller droplets that essentially move with the air.

            I do sometimes hear people talking as though masks give protection in situations where they won’t, and it makes me think there is a danger they will produce over-confidence. But I still think the main reason their use was officially discouraged early on was simply that they were in such short supply.

          14. T says:

            @adam Ok but personal insults aren’t a substitute for a logical rebuttal. I’m sad to say I’m not an Amazon denier at all; I use Amazon far too much. Yes if you order lentils they will arrive tomorrow. Do you know why? It’s the same reason that in normal times it is very easy to order toilet paper; there is relatively low demand and an adequate supply. However, if demand spikes, as it would to if every person in the US stopped going to the supermarket and shopped online, this would no longer be the case. The last lockdown in the UK already showed that online food shopping infrastructure is quickly overwhelmed, and likewise the shortage of flour/pasta in many countries during that time showed that many people trying to bulk buy nonperishable foods at once soon overwhelms the supply. Your suggested solution only works if hardly anyone uses it, i.e. it may help you feel smug and superior but it is not a workable solution in a global pandemic.

          15. T says:

            Incidentally, the European nation-wide strict lockdowns in response to the first wave were very effective, and none of them involved banning grocery shopping. In fact they banned pretty much everything except grocery shopping.

          16. Michael says:

            All the talk about next-day lentils here has ignored the fact that the highest prevalence of spread, in city after city, is in neighbourhoods with high percentages of essential workers. To say nothing of workplace outbreaks in packing/processing plants. No matter how hard you lock down the Zoom class, essential workers can’t work from home and aren’t being supported in their ability to isolate if sick.

            It’s an easy morality story to yell at the guy down the street for going to the store for lentils, but it ignores what is actually epidemiologically relevant. It’s also convenient for governments to yell at the work-from-home public for going out for lentils when it keeps the pressure off them actually devoting resources and attention to essential workers bearing the brunt of the pandemic.

        2. Adam says:

          T, you insulted me first. I thought if you could dish it you could take it? Apparently not. In any case I don’t think it’s so bad to call out someone who is lazy and putting others lives at risk. Lazy is a charitable word for your actions I think?

          No one can order lentils because Amazon might become overwhelmed? It hasn’t happened yet but I’m glad you are taking precautions not to overwhelm Amazon. Bezos thanks you for such concern.

          The solution works perfectly well but you’re stubborn and want to continue life as normal. Essential workers are at grocery stores and one study showed it’s a likely superspreading event. But continue shopping at the store and being irresponsible.

          1. Michael says:

            But essential workers also work for Amazon and deliver the Amazon order. Do they not count?

          2. Adam says:

            Delivering a package with no contact is lower risk than being in a store. It’s incredible how much people will fight to go grocery shopping even though it’s actually a high risk activity. Probably the same people denying Covid exists.

          3. Tom H says:


            You do realize that Amazon also has warehouses where the distancing is far more difficult?

            And while Amazon grocery delivery may work great for you, it is absolutely not available everywhere.

  9. luysii says:

    The readership here all want to take the vaccine, the only question is how to get it to them quickly. This ignores another huge problem — people who don’t want to take the vaccine. Draconian laws to force it on them will lead to legal resistance which will slowly wend its way through the judicial process. Just think of how effectively ‘the resistance’ used it.

    How to convince them to want to take the vaccine? Yelling and screaming will not help. Calling them stupid may make you feel better, but it won’t help.

    I think that just requiring death certificates on people dying of COVID19 to state whether or not the individual has been vaccinated will help. Not right away, because most people haven’t been vaccinated, but down the road when 1/4 to 1/2 the population has been. With 95% vaccine efficacy, most of the deaths then will still be in the unvaccinated. Statistics do move people, and the over 80 cohort has already self-isolated (if they can) due to the statistics out there.

    For more please see –

    1. Adrian says:

      You are not running out of people who would be queuing for a shot as if it was a new Apple product anytime soon – during the first half of 2021 vaccine shortage is the problem.

      After that what matters is that the vaccines have proven safe and effective in practice.
      If you look at how COVID-19 vaccines have been approved in the UK and India, the approval itself cannot be trusted and current discussions about delaying the second shot are not helpful.

      There is also the unresolved question whether the current vaccines actually reduce infections and transmissions, or whether they only help with the symptoms.
      We do not have data on that.
      As of today, we cannot even rule out that these vaccines are a selfish self-protection for people who might then become superspreaders.

      1. Bob Marlee says:

        See username link: More than half of *HEALTHCARE WORKERS IN CALIFORNIA* have turned down the vaccine. It’s unthinkable, and unconscionable. I personally think they oughtn’t be working if they turn down the vaccine. This is a group whose seen the ravages of what this disease can do first hand, and yet there’s still all kinds of magical thinking about them being okay so far so there luck will see them through.

        I suppose at some point, once everyone has had the opportunity to take it or not, we can just go back to normal and let all those who rejected reason get sick, but that’s a huge cost on society, never mind the possibility of potentially infecting those who were infected if it turns out the vaccine is not sufficiently long-lasting.

        1. Bob Marlee says:

          Correction: Possibility of infecting those who were vaccinated.

        2. luysii says:

          If this is true, it just shows what a problem we have, and why it’s time to start working on it now. There is a lot of fake stuff out there unfortunately. I do find this hard to believe.

          1. Bob Marlee says:

            Username points to a similar story from the LA Times.

        3. Stroodle says:

          It’s more complicated than that though. If you’re 25, would you honestly rather take an experimental treatment that hasn’t been in humans for more than half a year, or risk a disease with a >99.999% survival rate for your age? What if you have an underlying immune condition (i.e. psoriasis) and don’t want to risk worsening it?

          If all the vulnerable population receive vaccinations of >95% efficacy, why do we need herd immunity? Going off covid’s apparent 5-25x death rate than the flu, is it a sin as a young person not to get the flu vaccine for 20 years straight? Unfortunately medical professionals don’t really get a choice on the matter.

          1. A Nonny Mouse says:

            My 23 year old son received the Pfizer vaccine this morning (even though he has antibodies and may have had it) but he is, as you say, a medical student who is having to do clinics to relieve pressure on the staff. He has no problem with it.

            In contrast, my neighbour who is a GP (MD, USA) is extremely reluctant to take it as it is so new. As most of her work is now via the internet, she can probably escape it for a while.

          2. luysii says:

            “If you’re 25, would you honestly rather take an experimental treatment that hasn’t been in humans for more than half a year, or risk a disease with a >99.999% survival rate for your age?”

            Change this to

            If you’re 25, would you self-isolate, not party, not go to bars, not meet people with the possibility of sex because of a disease with a >99.999% survival rate for your age?

            This is exactly why the pandemic has spread so in the USA. Many people in this cohort have made this calculation.

    2. MagickChicken says:

      Sadly, I don’t think vaccination status on death certificates will help. Recall that these are the people who say that car crash victims are being used to inflate the stats.

  10. aviators99 says:

    I don’t understand how you can say something is “an experiment on the population” and are “in favor of it” in the same article. I mean, COVID-19 was already a severe crisis before we started Phase 3 trials. If we weren’t going to insist on good data before administering it to a population, why didn’t we start in July? Now it’s *really* bad? This just doesn’t follow my personal scientific mindset.

    1. Daniel Barkalow says:

      It’s important to get good data on safety, especially with something in a new class of vaccine. It’s important to get good data as to whether the vaccine mechanism works at all. Once you’ve got some idea of the properties of this treatment in humans, it makes more sense to extrapolate what would happen with a variation on the plan. There’s some data suggesting that after a 3-month wait for the second dose, the first dose Pfizer vaccine was still about as effective as it was after 2 weeks, and the sample size of people who hadn’t gotten the second dose ran out rather than any signs of loss of effectiveness at that time. Moderna didn’t see signs of being close to the minimum effective dose.

      Of course, there’s no reason not to have the FDA decide whether to approve alternative plans with an actual proposal and analysis of the data. If nothing else, Moderna would need to write up instructions on how to give smaller doses correctly, rather than health care providers just doing it differently.

    2. Texas says:

      And what about people who already received one dose?
      They didn’t sign up for this experiment of either delaying the second dose or getting a half dose later.
      One thing people might be overlooking is public’s (dis)trust. A lot of people were already hesitant to get these vaccines, and I can only imagine the response if people in charge start going by “gut feelings” with not-well-tried- approaches.

  11. Jonathan says:

    Somebody put the challenge in personal terms like this:

    What if you have two elderly grandparents, both highly and equally vulnerable, and infections are rife. And you have two doses of Pfizer vaccine. Do you vaccinate one of them twice, or both of them once knowing that most of the benefit would still be available and you are likely to get further doses within three months?

    1. DrSAR says:

      That’s a good way to put it. Here is an extension: Or, do you split one dose and administer it to both. And then wait and administer the booster again with half the dose.

      If this feels like we are proposing experiments then it’s because we are.

    2. Giannis says:

      Use half a dose scheme. Second half dose in 4 weeks. 2 half doses always beat one full dose.

      1. Jonathan says:

        It is interesting to ponder the balance of risk. Departing from authorisation by extending the interval between doses of the Pfizer vaccine, departing from authorisation by halving each dose, or leaving as many people unprotected as vaccinated when we are talking about elderly vulnerable individuals when there is a surge in cases.

        To some extent reading between the lines of the JCVI summary paper the UK used to justify their temporary policy (linked from the previous thread) I surmise they based their decision on the decades of knowledge of vaccine immunology, which suggests that in almost all cases the immune response from a single dose lasts three months but does decline slowly without a booster. One key question was whether the novel mRNA technology used by Pfizer would mean a different behaviour from previous vaccines, which I imagine is why they referenced the evidence on duration of the Moderna vaccine response which also uses mRNA. (I would think there ought to be some clues for the Pfizer product in existence though those aren’t referred to; I would have assumed the Phase 1 trials would have included monitoring responses over time, and BioNTech must have data on their previous experimental cancer vaccines).

        I seem to recall (though immunology has of course advanced since I had any involvement) that differences in dosing tend to have less predictable effects on the level of immune response.

      2. Adrian says:

        “2 half doses always beat one full dose.”

        This is not true.

        As an example, for the Oxford vaccine there is an obvious reason why everything after the first shot might have fewer benefits.

  12. CasualSeer545 says:

    Studies on Moderna’s vaccine suggests a massive reduction in the asymptomatic spread of COVID after just the first dose, a 63% reduction was seen.

    Given that asymptomatic transmission of COVID is thought to be responsible for 40% of transmissions, wouldn’t we see a significant reduction in cases by maximizing the amount of people that get that first dose, and delaying the follow up shot?

    What I can’t find documentation on and would be interesting to study would be how many people get sick with COVID and go on to need hospitalization after just one dose. If we could establish that one dose can prevent serious illness, that could be something to think about as well.

    1. Patrick says:

      Sure, This data is an excellent argument for that approach, but it has nothing to say about two things:

      durability of immune response with one dose and potential immune escape due to reduced immune response.

      And now we are stuck balancing unknowns. It’s … not fun.

    2. OC says:

      No doubt may have some issues around statistical significance but the Astra Zeneca interim results published in the lancet pretty strong suggest it has SOME protective effect after one dose:

      1. Chris Phillips says:

        Bear in mind that the UK policy is not one dose but two doses separated by up to 12 weeks. As far as AstraZeneca goes, such evidence as there is suggests that the longer interval may actually be more effective, though the statistical power of the data is weak. For Pfizer the data are lacking because the protocol was more uniform.

        Some press reports suggest exasperation on the part of AZ that the Oxford academics have frustrated their requirements for a clear-cut Phase 3 trial. Clearly there has been a lot of bungling on some people’s parts. On the other hand, partly by design (and partly not) a range of conditions have been used, and perhaps some useful information has emerged from that.

  13. Mariner says:

    Just to note, we’ve had a new hard lockdown announced in the UK which effectively begins tomorrow. Schools to close until at least mid-February (but for children of key workers) but early years childcare (under-5s) can apparently remain open with the children of key workers taking priority. My 5 year old will be out of school I’ll take my 2 year old out of nursery as well, regardless of the childcare juggling which ensues.

    Ultimately, this lockdown is what was clearly going to be required and should have been brought in before the mixing of households on Christmas Day was given the green light. Once the worrying data about the new variant was clear, why allow that? Once again, a doubling (or two) of infections too late. And, of course, many children returned to school today for the first time since before Christmas – ridiculous that they didn’t close them today. More dithering.

    I hope that the spacing of the second dose of the vaccine will save many lives and the ambition to have so many of the vulnerable receive their first dose by mid-February is good, though this government don’t exactly have a record getting anywhere close to their targets.

    1. Retired but still interested says:

      One problem with delaying the second dose of the Pfizer vaccine without any efficacy data is the social effect on the subjects of this experiment. Although alleged ‘partial immunisation’ may help reduce strain on the NHS – clearly a good thing – the ultimate outcome given lack of any evidence is that (to highjack a current government slogan) recipients should essentially ‘ act as if you’ve never received it’. My 83 year old mother will never leave her house with any confidence again.

      1. Some idiot says:

        Agreed… Whatever, physical distancing will be here for some time now… My mother-in-law (nursing home) received her first vaccine dose 31-12-2020, and will receive the second before the end of January. But we reckon it will be months before we can see her again (under very strict controls; I will probably have to just stand outside and wave and smile…!) and it will probably be (earliest) second half of this year before things start loosening up a bit…

        1. Retired but interested says:

          For those only getting one dose within the protocol the uncertainty will be permanent without knowing the level (or lack of) immunity. As it’s only this group that can provide the data, it’ll be a unknown for quite some time. That obviously means there is potential danger from anyone they come into contact with. Even given that no vaccine gives complete protection, for some the doubt will end any/most social contact for good.
          Definitely a much better scenario for those that receive the Pfizer vaccine within the protocol guidelines, or the AZ vaccine where there is at least some data.

          1. Chris Phillips says:

            I don’t quite follow that argument. I would follow the argument that the most vulnerable people might benefit from greater protection from two doses, and therefore reduced risk of death or serious illness.

            But the argument that they should be given two doses so that they will feel freer to mix with others is far more questionable. Vaccinated people mixing with others is going to remain risky for all concerned while infection levels remain high. Risky for those who have been vaccinated, because the vaccines aren’t 100% effective, and also risky for those who haven’t, because vaccinated people will still be capable of spreading the virus if they have asymptomatic infections (certainly for the AZ vaccine, and probably for all of them).

            We’re going to need everyone, including those vaccinated, to carry on showing restraint for some months, until infection levels fall (or until a vaccine proves to be 100% effectve in suppressing transmission).

          2. Some idiot says:

            Chris, I’m in no way shape or form an expert in these matters (I’m just a process chemist…). But throughout the pandemic I have been very impressed with the chief medical officer here in Denmark. He is extremely open, extremely professional, and tends to hit the nail on the head… So for what it’s worth, here is his take on the question (I am paraphrasing, but this is close to word-for-word what he has said at press conferences):
            Number one priority is to reduce serious illness and death. Therefore, all those most at risk of serious illness and death should be given full vaccination ASAP as per the protocol from the clinical trials (I am talking Pfizer mainly here, plus a bit of Moderna; AZ isn’t approved here yet; ai am really looking forward to hearing his evaluation of that one once it is approved). That way, (a) the majority of serious illness and death will be prevented, plus those looking after them will have a significantly lower workload.
            When asked about delaying shots, he basically said that he wouldn’t do anything that was not backed up by the clinical data…

          3. Some idiot says:

            P.S. He also said (about a month ago) that he expects “some level of” physical distancing for at least the next 9-12 months, so yes, even when, say, 50% of people have been vaccinated, we are still going to have to be careful for a while…
            Just hoping that the 2021-2022 New Years Eve party will be an occasion for a _really_ good party!

  14. Manny Schneck says:

    “Anyone who uses the phrase “no-brainer” to describe this call should be dropped from your list of people to take advice from. This is the opposite: it’s a decision that all our brainpower may still not be sufficient to make clear. But we’re going to have to make it anyway.”

    Isn’t that exactly what makes it a “no-brainer”? If you’re just gonna have to pick one, worrying about it or fruitlessly thinking _harder_ doesn’t help the matter.

    1. sort_of_knowledgeable says:

      English idiom, or at least American English usage is to use “no-brainer” when the choice is clear. When there are two alternatives but no basis to which is correct then some variant of “it’s a coin flip” is used.

      Also when the stakes are this high, it is worth a lot of effort to see which alternative is more likely to produce a better outcome even if it just a 51% to 49% chance.

  15. Dylan says:

    I know this may well not be the place to ask this question, but is there any evidence showing a difference between time to onset of symptoms and/or transmissibility between the old and b.1.1.7? I.e. would we expect to be getting I’ll quicker?

    1. Mariner says:

      I have also wondered if the higher viral loads from infections of the new variant apparently measured in some studies would also lead to fewer asymptomatic cases? Seems logical to me, but then I am not a virologist/immunologist!

      1. Adrian says:

        The theory that viral load at infection might influence the severity of COVID-19 was never more than a plausible but unproven theory.

        If higher viral loads are what causes the increased transmissibility, the stable percentage of serious cases would hint that virus load at infection is irrelevant for later severity.

        Even the increased virus shedding does not seem to be associated with worse severity for the person shedding the virus.

        This data also disproves certain “masks may lead to milder illness” theories that were based on this theory.

        1. Calvin says:

          Adrian, I think you maybe need to speak to some virologists…… Higher viral load is ALWAYS the major factor in driving disease state. You can see that in RSV, Influenza, Dengue etc. Remember the virus isn’t the disease. It’s not just semantics that means that we say that HIV causes AIDS. But the virus does cause the disease and we know that if we stop replication that we stop disease or reduce severity. Partly that’s because the process of viral replication is entirely destructive to cells. They literally explode. Every disease caused by a virus is improved when we stop replication. Historically, it’s been hard to study viral load in people systematically but it’s been clear for a long time that it drives disease. And we know that if we reduce it by a log we can see significant beneficial results (this is well know if you happen to work around the human challenge models for RSV/flu for example).

          There are a number of other factors, mainly host factors but also which cells get infected, but viral load is always the key driver. And we also know that viral load is partly driven by the initial inoculum. This is why mask do indeed have a positive effect. They reduce that initial infection, which makes it harder for the virus to get to the LRT. They don’t prevent infection but they do have a positive effect. What we didn’t realize is that if sufficient people wear them the effect is non-linear, it gets positively magnified. If I am outside and I can fully socially-distance, then I’m cool not wearing one. But if I am anywhere near people, particularly for any amount of time, or inside it goes back on. I hate he damn things, but they work. They reduce viral inoculum which is always a good thing

          1. Adrian says:

            “Higher viral load is ALWAYS the major factor in driving disease state.”
            “This is why mask do indeed have a positive effect.”

            Calvin, you should learn to make less bold claims and question your assumptions – especially when the data indicates that they might be wrong.

            COVID-19 is not yet well understood, and it is for example plausible that while higher viral load might be associated with more cell destruction in the upper respiratory tract this might be unrelated to the probability of progression to severe COVID-19 which happens in other parts of the body.

          2. Calvin says:


            If you are going to throw out those types of comments on a scientific forum, then let me quote some literature at you. You can do your own searching. Viral load is directly correlated with disease severity. There are other factors too, but viral load is a biggie.

   and numerous references therein

            This is known stuff. Increased viral load is bad. Reduced inoculum is good.

            And yes, I do challenged my assumption. I was certain that masks were pointless back in March/April because, unless they were N95 and above and used properly, the data showed that you could still be infected. What I didn’t appreciate is that slowing transmission, even imperfectly, could have a dramatic effect and masks are part of that because they reduce transmission and reduce inoculum. And if enough people wore them the effects are greater.

            And I’m cool with that. New data became available and so I changed by view.

          3. Adrian says:

            Masks designed and certified to filter viruses do reduce transmissions. That’s why surgical masks have been used in hospitals for decades.

            The benefits of cloth masks are less clear, they strongly depend on the material and whether the masks are properly cleaned after each use.
            It doesn’t make sense that after one year there are still people using these instead of surgical masks.

            The theory that wearing a cloth mask results in less severe COVID-19 if infected has been often repeated but never clearly proven.
            The study you are linking as “proof” only says “the use of masks has been shown in a laboratory setting to reduce both disease transmission and severity of SARS-CoV-2 infection in hamsters”, and the decreasing CFR in the UK from 6% (sic) to 1.5% would be better explained with fewer undetected cases.

            If higher viral load of the new virus variant does not correlate with disease severity in the UK, that’s better data than experiments on hamsters.

          4. Charles H. says:

            Since this is a respiratory transmission disease, it’s not just the viral load, but where it appears in the body that affects transmissiblity. Higher load in the lungs and nasal cavity would be correlated as you suggest, but higher load, say, in the spleen and kidneys would probably not be. (OTOH, it probably would be associated with higher fatality rates.)

  16. Jack Komisar says:

    The efficacy of the Moderna vaccine after one dose was 80.2%, with a median follow-up time of 28 days (range 1 to 108 days). The efficacy was 92.1% after 14 days, with a 95% confidence interval of 68.8% to 99.1%. So the results look very good, with the caveat that the follow-up time was limited. I think we should give serious consideration to the one-dose regimen. Remember that we spent most of last year anxiously awaiting a vaccine that might give slightly more than 50% protection after two doses. That vaccine would probably have gotten an EUA and we would now be eagerly using it and marveling at how fast it was developed.

    1. OC says:

      There is strong evidence to support at least delaying the second dose to get as many people vaccinated with a single dose in as short a period of time as possible.

      We need to remember the knock on effects on other people’s care from having hospitals overflowing with patients.

      Perhaps there will be more midly symptomatic infections amongst those vaccinated only once than there otherwise would have been but the likelihood that this sees a material reduction in overall hospitalisations and deaths has to be very high based on what we know so far.

    2. HFM says:

      Agreed. If I was Queen of the FDA, I’d do the elderly and immunocompromised by the book, then prioritize getting the first dose into every healthy adult who wants one. There’s nothing sacred about a one-month delay.

  17. Daniel says:

    My hope is that most people will not actually have to wait the full 12 weeks between doses in the UK. We’re aiming to give about 12.5m people one dose by the middle of February; hopefully, J&J should be approved by then and we should have less of an issue with vaccine shortages.

    I do find the Americans criticising this decision unfair. Unlike the US, the UK doesn’t have millions of vaccines just sitting in fridges that haven’t been delivered. We just don’t have enough to give the vulnerable two doses with just AZ and Pfizer in the next few months. It doesn’t look like we can control B.1.1.7, even with lockdowns. If we don’t try this, we’re guaranteeing a huge number of deaths and hospitals being overrun. My guess is that if this variant spreads, you’ll see many more countries making the same decision as the UK, including the US.

    1. Bob Marlee says:

      I don’t think anyone’s criticizing this aspect, but rather acknowledging how gloriously unfortunate this complication is.

      The decision I’m personally dubious of is the U.K’s announcement to allow mixing and matching of vaccines for the second dose.

      1. A Nonny Mouse says:

        They DON’T! That was a NYT report which they have asked to be retracted. It is not true.

      2. Mariner says:

        The mixing of different vaccines is only recommended in some more extreme circumstances and shouldn’t really be at all commonplace. I agree, though, this is even more of a gamble than the spacing of doses.

        It remains to be seen if the spread of the new variant can be controlled with this new lockdown, but I wouldn’t rule it out completely. With schools closed, that removes one major vector for transmission which was still available during our November lockdown. Added to that, there was distinct distancing fatigue on show from many and a relaxation (however illogical) because people knew vaccines were coming. I’d imagine that this hard lockdown will sharpen a few minds about what is required and the rising death toll in coming weeks will hopefully prove sobering to those who weren’t careful enough during November and December.

    2. Chris Phillips says:

      “It doesn’t look like we can control B.1.1.7, even with lockdowns.”

      I think that is too pessimistic, but I suspect it does need a proper lockdown including school closures.

      It is worth noting that infection rates are now decreasing in Kent as a whole and in a number of local authority areas in London and Essex where they were previously highest. However, they are rising quite rapidly in other parts of London.

  18. exGlaxoid says:

    Remember that vaccine peoduction is still ramping up signifacntly, so if you can get more people vacccinated with the first shot, within a month or two, the number of doses available should go up quite a bit, so there should be more vaccine then, and if you prioritize second shots then, we could still treat more people with minimal delays past 3 or 4 weeks.

    There are at least two more vaccine production sites coming on board shortly, so that will help a lot. I am in favor of doing small tests of lower doses (Moderna), single shots (Pfizer and Moderna), and longer delays betweek the shots. If this was done as mini-trials, with no placebo, we could know how well it works within a few weeks to months. Just go offer shots to everyone (with informed consent) who shows up in a few citys of each variation and with in a month you should be able to see some results. The NIH, FDA, CDC, or any other acronym could run a trial, and the benefit is that some or all cities would see major cuts in disease. This is not a time to be slow and careful, as people are dying in droves.

    If you were in a plane that was crashing, would you wait for the FAA to tell you to try to prevent a crash or just start trying everything you can think of within reason. I look at this like the 4th 9/11 hijackked plane, they knew they were is dire trouble and tried to prevent the trajedy, and while they did not save themselves, they saves many other lives, and might have saved themselves, so not much risk, given they knew the outcome. For that I consider them heros. And now that people know what might happen on a hijacked plane, I don’t think passangers will sit and wait for someone to save them, they will save themselves. We need to start thinking like that and do anything to protect our fellow citizens.

  19. jbosch says:

    Since the race is picking up on speed (Vaccine versus new B1.1.7), our tracker (linked in the handle, or google Covid19Predict) that shows the course of the pandemic with slightly different metrics could be of interest to you.
    As of now, we only show the US (national, state & county level) but we are in the process of expanding worldwide. Where possible, we will go to what corresponds to the county level in other countries as well.
    We’ve looked specifically at London, UK data to see the impact of the new variant and it does not look good if we project this to the US. Now the UK is at least on lockdown, we know that the earliest a lockdown will be issued in the US is after the inauguration – and even then I doubt it will happen. So the outlook for the US is grim, to put it mildly. January, February, and March will likely outpace how many deaths occurred in December (75K)

    1. Marko says:

      Lockdowns in different states will happen before the inauguration. Trump is out of the picture already in that regard. Starting tomorrow , the 7-day average of deaths/day will start its inexorable rise to >3000/day, due to the catch-up on the holiday reporting and recording delays. This rise will force action in the most-affected states. The UK , adjusted for population, is already near that level, and their deaths/day will rise for another several weeks in spite of the new lockdown. Boris Johnson is at least providing some modicum of leadership, unlike Trump, who spends all his time either trying to overturn the election , playing golf , or looking for some excuse to start a war with Iran before he leaves office.

    1. OC says:

      Yeah thank god the do little FDA is brave enough to do absolutely nothing innovative in the face of a pandemic that is infecting 200,000 plus people a day and killing close to 3,000!

      This is the same organisation that delayed the vaccines for weeks so a committee could meet even though it isn’t supposed to be required for an EUA.

      Said committee then ended up adding ZERO useful to the understanding of the vaccine and NOT voting unanimously due to an esoteric concern about 16 year olds getting the vaccine – newsflash 16 year olds won’t be getting it for MONTHS at minimum given there is nowhere near enough doses to vaccinate the elderly and those working in health care!

      1. debinski says:

        Yeah I don’t think the higher ups at the FDA would be capable of running if their own house was on fire. It was painful to listen in on the Pfizer VRBPAC/FDA advisory meeting back in December. I kept wondering how many people died while they were congratulating each other, exchanging pleasantries and trying to figure out how to unmute themselves.

  20. Marko says:

    Denialist gurus’ wrongness preserved for posterity , on a timeline :

    1. Humorous Blacksmith says:

      To Tesco to “Harmonious Blacksmith” on car radio. Essential Shopping in accord with UK Tier 4, Alert Level 5: NATIONAL LOCKDO*N. In accord with customer, legal and national obligation, snout mask on. Targetted shop – in, round, check out, unmask, home. Marked Acute Respiratory Syndrome faced down again. Guard up, hubris down.

      Open Daily Pipeline. Him. Again. Man, not ball. Again. Preceding commenter, again. Usual cheap debating tricks, again. Quotes taken out of context, again. Labels clinician, scientists and commentators with different perspective “denialist gurus.” Enough for a football team duly taken out.

      If pro-lockdowner viewpoint so compelling, what need to bully counter view? One thing for sure, here in UK and wheresoever else both poles putting forward reasoned arguments deeply held – maybe reality somewhere in the middle, rather than all to side of CMO, CSA, PHE, NERVTAGERs, SAGEs, SPIBs & SPIMs?

      Heard Prof S talk at meeting near 20 years ago. Aim high. Twenty year survival for all cancer patients. Cancer as chronic not acute disease. Twenty years later, not there yet, but progress made. Inspirational and informational stuff for oncology relative newcomer to partake of.

      Adopted and adapted as opening theme for overview chapter to oncology medchem volume. Last nine months big setback for Prof S’s twenty year goal. Now retired, Prof S has taken up baton on behalf of UK cancer patients with treatment compromised by healthcare focus on Marked Acute Respiratory Syndrome. Has beseeched anyone with cancer symptoms to seek diagnosis asap. Hero of our time.

      As for Him Again’s unjust criticism’s other recipients, two are Oxford Profs. Known a few Oxford Profs in my time. Invariably knew their stuff. Papers disclosed on website Prof H runs include disclaimer if paper not peer reviewed. Unlike some websites and recent epidemiologically impactful papers that could be named.

      Dr Y from Pharma background. Retired respiratory biologist. Can relate to what Dr Y writes and says. Impression has looked deeply at the “The Science” and the “scientific evidence” and drawn different conclusions from CMO, CSA, PHE, NERVTAGERs, SAGEs, SPIBs & SPIMs that advise the UK Government on handling of Marked Acute Respiratory Syndrome epidemic.

      Nowt wrong wi’ that. Dissent happens all the time in science and sometimes science history falls dissenters way. Think Gallileo, for a start. Rest of Him Again’s hate list are journalists or other commentators, I think. Thank you Him Again for bringing some new names to the party. Will check out.

      Over to the Blacksmith to play comment out…

  21. DrOcto says:

    Even the most optimistic estimates still require most of the rest of the year to get just the 1st world countries fully vaccinated. I shudder to think what an uncontrolled virus spread will look like by then.
    Get vaccinated, ask for the validated protocol, at least until clinical evidence shows a more socially responsible option. Keep your head down, stay home, wear a mask, until it’s your turn to get it.

    1. achemist says:

      I would expect it to get a lot better once at risk groups are vaccinated.

      The majority of deaths and hospitalizations are elderly – if we knock that down the health care system can probably cope reasonably well and deaths wont be as high anymore.

      1. Adrian says:

        The risk groups are larger than you might think.

        The main risk groups are elderly and obese people, especially men.
        When the British Prime Minister was in an ICU with COVID-19 last year, there were plenty of comments from healthcare workers that fat men in their 50s with COVID-19 were a common sight in British ICUs.

        There is also an interesting question ahead whether people should be rewarded for an unhealthy lifestyle by getting vaccinated early.

        1. A Nonny Mouse says:

          And don’t forget that, in Sweden, anyone with a BMI of over 40 was not allowed to be hospitalised (similarly anyone over 80). These didn’t count in their statistics…..

          1. Stroodle says:

            This sounds shocking. Do you have a reference?

  22. David Kammeyer says:

    If we’re worried about vaccine escape mutations, and for that reason, we don’t want to delay a second shot, or give a half dose of Moderna, should we be giving the Oxford/AZ vaccine at all?

    If it only provides 70% protection, presumably this will give the virus room to adapt. The single dose Pfizer appears to provide quite a bit more protection than that, starting after two weeks. Is it really likely that the protection would fall all the way to 70% by two months or so? Is it really likely that the half dose Moderna vaccine would provide less than 70% protection?

    1. Mariner says:

      Don’t forget that the original target for success in Operation Warp Speed was for vaccines of greater than 50% efficacy or the ability to reduce symptoms greatly. That’s what we now have.

      If you’re worried about vaccine escape mutations with vaccines around 70% efficacy, what about if the original OWS target of just 50% efficacy had been met?

      In some ways, I think we’ve been spoiled by the surprising efficacy of the vaccines to be developed thus far. If just one or two had worked it would have been good news but the fact that most of them seem to be effective means that we might potentially be able to get out of this terrible situation years sooner and with many lives saved.

      Obviously, a lot still to be discovered about how long immunity/protection lasts and whether or not vaccinated people can still spread the virus. That’s going to be a work of years, I’d imagine.

  23. QuantStats says:

    Hello Mr. Derek,

    Have you read the latest take from Tyler Cowen on this? If you somehow have the time I’d be curious to know what’s your opinion on it.

    Here’s the post:

    In any case, thanks for your excellent work!

  24. Bill says:

    Want faster distribution? Trash the freezers. A hospital in northern California had a freezer failure and dispensed 600 jabs in the 2 hrs remaining shelf life. That’s probably 60X their unmotivated jab rate.

    This is going to take way longer than forecast. My paper towel scratchings say we won’t reach 80% vaccinated until mid 2022. True, my model is suspect, but it’s based on what I’ve seen and a reasonable assessment of likely future improvement.

    Note that even if Biden can accomplish 1M jabs for 100 days, that’s only 50M people — 15% of the population. How does a late summer target look now? And who believes Biden or any politician can do what he promises in a campaign? 15% may be a pipe-dream.

    1. COVIDiot19 says:

      But do we need to vaccinate 80%? Genuine question, not being sarcastic.

      Once we have vaccinated the most vulnerable (say the 15% you mention) – will we see ICU admission come down and deaths reduce?

      1. Adrian says:

        Depends on what the goal is – reducing the number of deaths or living as if it was 2019?

        Giving priority to the most vulnerable (obese and old people) should help bringing the ICU admissions and deaths down by a lot.

        Luke Letlow was 41 years old, not obese, no other preexisting conditions, when he died of COVID-19.
        If you let the virus run freely through the other 85% of the population, the US would still see double the current death count since even a much lower case fatality rate of 0.1% like flu would still be sufficient for that many deaths.

      2. Bill says:

        Might depend on where you live. I understand Florida and Texas, no doubt others have rejected the federal priorities and are vaccinating by age…much like the UK.

        But I’m in California and over-65’ers are fourth group. Behind essential workers like taxi drivers and grocery store box boys.

        Assuming the over 65’ers are the driving factor in hospitalizations, I doubt we’ll see any early progress. The hospitals are probably not overrun with box boys currently.

        1. Adrian says:

          An obese box boy might have a higher risk of hospitalization than a healthy pensioner who is able to stay at home.

          In the US over 65’ers are (slightly) more than 15% of the population, and (slightly) less than 50% of the COVID-19 hospitalizations.

          Over 40% of the population in the US is obese, this is the other driving factor in hospitalizations.

          1. Bill says:

            No expert here, but I believe obesity statistics are based on BMI>30 and high-risk obesity is considered morbidly obese BMI>35. If correct, the 40% you refer to are not designated high-risk.

            And we’re not talking about a specific high risk box boy in line ahead of a specific pensioner. We’re talking about all box boys being ahead of all pensioners. In my county at least, the list of essential workers is huge. Possibly contains well more than 50% of the workforce. Hence the elderly are towards the bottom of priority whereas they are the subset most prone to severe disease and death. It sounds like something Trump would come up with to get HIS economy going again. And I’m not even an anti-Trumper…just sayin’…

          2. Adrian says:

            Morbid obesity is BMI > 40.

            There is no fixed definition of “high-risk” for COVID-19, the question is where you place the cutoff.
            Age 80 has a much higher risk of dying than age 65.
            BMI 40 has a much higher risk of dying than BMI 30.
            Men have a higher risk of dying than women.

            Women in the age group 60-69 do not have a fatality rate that is much above the average, and if you define age 65+ as high-risk then BMI > 30 is also high-risk.
            If you define only BMI > 40 as high-risk, age limits might be more appropriately 75+ for men and 80+ for women.

            The majority of COVID-19 hospitalizations in the US are under the age of 65.

          3. Adrian says:

            “Hence the elderly are towards the bottom of priority whereas they are the subset most prone to severe disease and death.”

            This sentence misses an “if infected” at the end.

            risk of severe disease = risk of getting infected * risk of severe disease if infected

            A 70yo pensioner has a much higher risk of severe disease if infected than a 50yo worker,
            but the 50yo worker has a much higher risk of getting infected.

            You are over-estimating the share of over-65’ers among COVID-19 hospitalizations because you miss that pensioners have the option to practice social distancing, but essential workers like taxi drivers do not have the option to lower the risk of getting infected through social distancing.

        2. OC says:

          California’s approach is madness given the community is absolutely riddled with community spread. The vaccine should be being rolled out by order of risk of hospitalisation / death if our concern is to reduce said hospitalisation and death.

          In a country like Australia, Singapore, Taiwan, Vietnam, China etc where local transmission is zero or near zero it may make sense to vaccinate the people who may spread the vaccine as part of their work first (albeit 99% of this concern can be dealt with by effective PPE while vaccines are likely to be only partly effective at reducing onwards transmission.)

          In the U.S. or U.K. that approach makes no sense whatsoever as the virus is already widely disseminated in almost all social circles. Unless you want to live like a hermit for the next 9 months there is little way for an elderly or vulnerable person to avoid the virus by practicing social distancing.

          1. Ancient Briton says:

            Off out again. Essential Shopping. Fending for ourselves, as ever. Guard up, hubris down. Just like lab work past. HMPA, magic methyl, even methyl iodide on scale. After first few months, risks understood. Survival down to precaution. And, like to think, modicum of skill.

            Back in ample time for UK Parliament’s retrospective vote on latest National Lockdown. BBC reporting, “Conservative PM Mr Johnson will update MPs, most of whom will not physically be in the chamber, on the new rules before the vote, which is due in the evening.”


            Constituency MP emailed, suggesting formation of Conservative Party 1933 Committee, to meet in parallel with existing Party 1922 Committee, which in extremis can in theory vet Prime Minister for any politically unbecomimg conduct. Rarely happens, unless party poltical disaster seen as looming (in effect what happened to predecessor PM Mrs May)

            Proposed date of first meeting 30 January 2021. How very apt that date would be to any student of 20th century history.

  25. bacillus says:

    @Kevin Smith (dermatologist). There is at least one flu vaccine that is given ID using pre-filled syringes fitted with needles that only reach as low as the dermis. However, my understanding is that mRNA vaccines are given IM as relatively large doses are needed to ensure sufficient uptake by myocytes. There might not be sufficient antigen presenting cells available in the skin for this type of vaccine.

  26. Daren Austin says:

    Whilst the Moderna data on a single dose looks robust, if you look at the timing of cases for the Pfizer trial, you will see much extrapolation rests on the timing of just four infections in the active group between days 12 and 21. That’s a lot of weight for just a few cases. Figure 3 of the nejm paper. I can see why the fda have responded how they have

  27. Marko says:

    BREAKING: San Diego County reports 28 new cases with coronavirus mutation first found in the UK, raising county’s total to 32

    All of the new UK variant cases in San Diego are from specimens collected last week and come from 19 different households

    San Diego County’s health officer on new cases with UK variant: “The fact that these cases have been identified in multiple parts of the region shows that this strain of the virus could be rapidly spreading”

    Hard to evaluate the level of sampling bias here, but it seems likely that the variant is all over the US by now. The cat is out of the bag, as expected.

    1. Some idiot says:

      FWIW, the Danish authorities expect the UK variant to be the dominant one here by mid-Feb. And have now imposed stricter measures in order to prepare for that.
      Thankfully, it appears likely that all residents (and employees) in nursing homes here will have received both of their Pfizer shots by the end of January.

  28. Marko says:

    “We mapped how all mutations to SARSCoV2 receptor-binding domain (RBD) affect recognition by convalescent polyclonal human sera. Among implications: E484K (South African lineage) worrying for immune escape; RBD mutations in UK lineage less so. ”

    I don’t think you can say much with confidence about mutation clusters like those seen in the UK and SA variants by only studying individual mutations in isolation. The “2P” spike protein post-fusion to pre-fusion structural transformation ( critical to vaccine development ) was a product of several mutations, and should be the model we consider when we evaluate mutation clusters.

  29. medchemist says:

    I honestly don’t think we should dose once only or deviate from the clinical protocols whatsoever. The clinical trials were done with two doses, so it would be an experiment and against the vaccine producers to not apply their proven protocol. It would also undermine the trust of the public into the vaccination programs. And that is the last thing we need.

    We need to make sure all available doses are distributed quickly to the most vulnerable. At the same time, we need a strict lockdown to massively reduce infections, and after that, an effective and enforced testing-tracking-quarantine program. Asian countries can control this pandemic since a while – let’s copy their strategy until enough people have been vaccinated!

    1. Bill says:

      Additional deaths are the cost-side of traditional policy. You want to make sure the cost is worth the benefit. I think the UK has it right.

      From Covid data presentations everywhere, US Covid policy is arguably the worst in the world. You can argue the point, but you can’t argue the numbers.

      21M positive tests
      Est 55M infected
      365M dead

      No one else is close.

  30. Bill says:

    Change that last M to a T. Or else no one could read this.:(

  31. BeanCounter says:

    Instead of modifying dosages for the Pfizer and Moderna vaccines in the US, why not go ahead and approve the AstraZeneca vaccine immediately ? I know there was a subset of patients that were mistakenly given a half/full dose with different outcomes, but the standard dosing regimen still kept people out of the hospital. I don’t think the FDA is structured to make the decisions that need to made in a situation that is affecting our economy and collective mental health. The UK is taking a reasonable risk to deal with their situation. And, no, I’m not saying it’s a “no brainer”, but we don’t have time for the studies and analysis that we would like.

    1. Marko says:

      “…why not go ahead and approve the AstraZeneca vaccine immediately ?”

      Vaccine nationalism. Plus, the Oxford/AZ vaccine provides a scary example of the benefits of non-profit socialized medicine, and we must delegitimize such examples wherever they might arise.

  32. Mark Andrew says:

    Possibly stupid question, but has Oxford/AZ even applied for emergency use in the U.S?? You don’t hear anything about a pending analysis or decision.

    1. Derek Lowe says:

      They have a US trial that has not concluded yet; we won’t see anything like that until then.

  33. Marko says:

    New study puts the percentage of US population who had been infected in the US at 14.3% on Nov. 15. Extending the analysis would put us at close to 25% now, which agrees with some other estimates I’ve seen :

    This means that one of every four people receiving a vaccine today needs the vaccine much less than someone else who is not receiving the vaccine. A POC antibody test should be a required pre-screen for vaccine eligibility.

      1. Adrian says:

        Some problems with your Twitter math:

        1. Everyone can make up some formulas and numbers and write a paper based on that, don’t put too much weight into some random study only because you like the results.

        2. There have been only 350k deaths in the US so far, and antibody data from New York City last summer confirms that a CFR of 1% is realistic in the US. A 25% infections guess would imply twice as many deaths.

        3. Don’t assume immunity for people who were infected more than 3 months ago.

        4. Don’t assume less severe COVID-19 on second or third infection. There are people in the US who had worse COVID-19 during their second infection.

        1. Marko says:

          “Some problems with your Twitter math:….1. Everyone can make up some formulas and numbers and write a paper based on that, don’t put too much weight into some random study only because you like the results.”

          Yeah, right. I’m going to take my advice from someone whose take on the cumulative incidence in London wouldn’t even qualify as “Twitter math”. Or any other kind of math.

          I don’t “like” any particular results. I’m open to new evidence and to whichever direction it may lead.The paper referenced in the tweet I linked was from JAMA Network Open, a respected, peer-reviewed open-access journal. But that’s not the only source that comes to a similar conclusion, so does the CDC, in this paper : “Estimated incidence of COVID-19 illness and hospitalization – United States, February-September, 2020” The JAMA authors based their incidence calculation on an estimated 47 million total infections in mid-Nov , when only ~11 million had been officially reported. The CDC estimated total infections at ~53 million at the end of September, when only ~7.5 million had been reported. Carry either of those estimates forward to today, when we have almost 22 million reported infections, and an incidence of 25% today is hardly out of line. Show me even one published reference, of any kind, that supports a current cumulative incidence of only half that , or 12.5%, as you suggest. You can’t, unless you consider comic books a “published reference”.

          “3. Don’t assume immunity for people who were infected more than 3 months ago.”

          I don’t assume anything. I gather evidence. You should try it. This large study in the UK compared HCWs who became infected or not in the first wave to see whether seropositivity protected them in the second wave, over six months later. Since there were no symptomatic infections in the seropositive group( 0/1038 ), while the seronegative group had a 2.9% infection rate ( 290/10,137 ), we can conclude that natural immunity seems to have substantial “efficacy” of preventing symptomatic disease , perhaps as high as 100%, out to 6 months and beyond. Of course, we already knew that, from the meager reports to date on confirmed reinfections globally, including those from the UK, where they’re doing the genomic surveillance that would detect them if they were there.

          1. RHB says:

            I’d like to throw “prior immunity” from the 4 other coronaviruses back into the mix, as per previous interchanges on Manaus vs Sao Paolo epidemic profiles, and interpretation of numbers reported for the original Wuhan epidimic:



            Prior immunity could significantly change your (Marko’s) overview of calculations (twitter, back of envelope, rigorous, whatever), what do you think?

            Thank you Marko for the paper linked. Does seem to show immunity lasting well beyond three months. Chased up Ref 1 (out of Haifa/Palo Alto/Wilmington). Looked at ~127K PCR positive tests out of ~870K overall set. Effect looks small, but if I’m reading right, some indication that the half of the 127K tested positives with diagnoses of colds, etc, in the previous year had less serious symptoms than the half without such diagnoses.


            Bit woolly, but there it is. Caveat is that set biased toward those with symptoms. Doesn’t shed any light on prior immunity of all the tested negatives.

          2. Some idiot says:

            Thanks… I was looking for a useful reference/estimate for how much of an idea we have as to how long immunity can last…!

        2. Chris Phillips says:


          I think we all need to accept that the data don’t give us as much conclusive information as we should like. So we have to make the best evaluation we can, and on the basis of inconclusive data we should be neither dogmatic about our own conclusions nor dismissive about those of others.

          Previously you argued that the antibody testing data for London was providing a significant _overestimate_ of infections so far, despite the facts that (1) it was based on data from several weeks earlier, and the current rate of infection was very high and (2) the percentage of positive antibody results had been demonstrated to decline significantly on a scale of months, and the previous peak of infections in London had occurred 8-9 months previously.

          You don’t seem to make any distinction between infection fatality rate and case fatality rate, but from the context I assume you are talking about infection fatality rate. First you said it was between 0.5% and 1%, which I think is reasonable. But now you seem to be insisting on 1%. That is not reasonable, considering that you are arguing on the basis of a factor of two between theory and observation.

          Please, let’s all show a bit more humility and a bit less asperity.

          1. Adrian says:

            The study gives a range of between 0.5% and 0.8% fatality, which is at the lower end of what the data supports.
            Whoever came up with the 25% number assumes 0.4% fatality, which is even outside the range of the study estimates.

            Assuming ridiculously high infection numbers is newspeak for “COVID-19 is not worse than the flu”.
            Data from New York City indicated 1%, and current fatality data from the UK is also hinting more towards 1% than 0.5%.

            There is also a notable inconsistency when Marko claims 100% protection from reinfection 6 months after infection, while Chris claims antibodies might no longer be detectable after 8 months.

          2. Chris Phillips says:


            Saying that some COVID denialists have overestimated infection rates is no justification at all for underestimating them. We need data and arguments, not assertions.

          3. Marko says:

            The study gives a range of between 0.5% and 0.8% fatality, which is at the lower end of what the data supports.
            Whoever came up with the 25% number assumes 0.4% fatality, which is even outside the range of the study estimates.”

            The JAMA study central estimate of 47 million total cases on Nov. 15 yields an IFR of ~.6% based on reported deaths 3 wks later. Similarly, the CDC yields an IFR of ~.4% using their end of September estimate. My extension to today that posits a 25% cumulative incidence arrives at ~83 million total infections, which yields an IFR of ~.5% assuming 3000 deaths per day for then next 3 wks.

            Again, Adrian, show me the publication that argues that we’re only at a cumulative incidence of 12.5% today , as you’re suggesting. I’ll be waiting.

          4. Bill says:

            Am I reading this right that a month ago (11 Dec) CDC estimates total US infections as 91M?


            Seems like we must be well over 100M now. I asked before, and got shot down…but won’t increasing infection “immunize” the population long before our paltry vaccination progress does?

            What’s a defendable estimate for effective completion date of the vaccination program? I know they said spring…then summer…now fall. But does anyone have rough math to support that?

          5. Bill says:

            Oh, a closer reading of that CDC page says the 91M figure was applicable to the period Feb thru Sept. I can’t even guess what that translates to today.

          6. Marko says:


            Haha, yes , that update from the CDC, which I hadn’t seen, makes my estimate of today’s cumulative incidence of 25% seem conservative. They had it at ~27 % at the end of Sept. !

            Adrian needs to head over to the CDC and set those folks straight….

          7. Marko says:

            Similar analysis from The Economist :

            Thru Dec 10 – “…By combining new research with official death tallies, The Economist estimates that 60m-82m people have been infected in America so far, around 3.2m of them in the past week. ”


            60-82 million translates into a cumulative incidence of ~18-26% on Dec.10. Add at least 10 million to the totals since then, and you’re at an estimated incidence of ~21-28%.

          8. Bill says:

            Given the exponential nature of the Holiday Wave, wouldn’t surprise me if growth from September now has us over 50% of the population infected. Don’t know how precise their estimate is, but CDC is the top authority, right? Who would know better than them?

          9. Marko says:

            “..wouldn’t surprise me if growth from September now has us over 50% of the population infected.”

            No , you couldn’t get that high even using the CDC estimate. There’s only been ~6 mill. additional reported cases since Dec. 10. Using any reasonable multiplier to correct for undetected cases ( I’d say 3x-4x , the CDC might say a bit higher ) you’d only get to an incidence of ~35% or so today.

          10. Bill says:

            Did you predicate that estimate on post-Sept or as you said post-Dec 10?

            The 91M number was from Sept…three months ago. Account for growth from that point.

          11. Bill says:

            Total US infections per CDC:

            Sept 30 7.2M confirmed, 91M estimated (that’s what it says)

            Jan 6 21.2M confirmed, ??? estimated

          12. Marko says:

            No , 53 million is the Sept estimate, as shown in the CDC paper I referenced above. The Dec. update is done using the same methods outlined in that paper. It’s noted on the CDC webpage you provided. However, it appears that the Dec. update of 91 million actually applies to the end of Nov. data, not up to Dec. 10. You can see the data in “Table 1: Preliminary Estimated COVID-19 Cumulative Incidence, by age group — United States, February-November 2020”.

            So, that could raise the estimate for today using their numbers from ~35% to around 40%. Again , it depends somewhat on the multiplier used.

          13. Bill says:

            So the CDC data was mislabeled for term? That would make sense.

          14. Marko says:

            If you look at the CDC webpage you can see what probably happened. The page is updated with new data, apparently each month, and the brain-dead intern who does the updates probably plugs in the new data without ever updating the descriptive text.

            If they’re doing monthly updates, we should see Dec. data in the next week or so, I’d guess , so we can see what happens then.

            I have my doubts about the CDC numbers. I need to check on what kind of multipliers they’re using in the updates. If they’re using a constant multiplier throughout, their numbers are garbage.

    1. A Nonny Mouse says:

      My son had the Pfizer vaccine a few days ago even though he has antibodies (we both felt a bit “off” for a day in June, which the real medics says was probably the virus, which seems to have been proved).

      I don’t know about others who receive the vaccine and already have antibodies, but he has really suffered with pain at the site and feeling exactly as he did when he probably had it!

  34. Hólmsteinn Jónasson says:

    Lack of effective sterilizing immunity means that asymptomatic infections will allow the continued spread of the virus, despite being vaccinated ?

    1. Marko says:

      We don’t really know yet to what degree vaccination protects against asymptomatic infection. Data is being collected on that as we speak and we should have a better idea about it before too long, hopefully. Asymptomatics don’t spread the disease as efficiently as symptomatics, so there will be some benefit regardless. It will just require an education campaign to inform those who are vaccinated that they still might get infected and spread disease. In many countries, this will probably work out OK. In the US, it won’t work at all.

      1. Adrian says:

        Since March last year asymptomatic and presymptomatic spread is the main problem.

        It simply does not happen anymore that people sit a full day at the office efficiently spreading COVID-19 by coughing all day long, the silent asymptomatic and presymptomatic spreading is what makes this pandemic so hard to control.

        1. Marko says:

          Don’t hedge your statement by including symptomatics before symptoms develop. The discussion is about asymptomatics, and we have good data now that true asymptomatics spread disease less efficiently throughout their course of infection than do symptomatics.

          Yes, it would still be a problem, but much less of one, if all infections were asymptomatic. We’d be talking about common cold coronavirus #5. Frankly, that doesn’t concern me too much.

  35. Mad Jack says:

    And now for something completely different… An old amigo long gone, now returned from a spell roamin’ the land, name of Meddediah, Med for short, once well known in these parts as Med Chem.

    Much changed round here, thinks Med, droppin’ in on th’ local bar, El Corante. None of th’ old roisters in sight. Load ‘a noise goin’ on, load a roisterin’ and werritin’, bit o’ bickerin’ too. Worse night than last night, Med picks up. Bickerin’s getting worse and worse all th’ time, Barman tells Med on th’ side.

    Who’s doin’ Med asks. Load of Docs and ‘ologists, Barman says, turned up nine months ago and taken th’ place over ever since. Load o’ ‘omicians showed up the other week too.

    What about th’ Endemic? Med asks. Shouldn’t you be locked down to stop th’ spread of th’ Endemic? Med says. Nah, says Barman, got exemption, ‘cos Docs, ‘ologists and ‘omicians, all doin’ war work that’ll stop th’ spread once an’ for all. Control th’ Endemic, Stop th’ Endemic, Beat th’ Endemic. Clever fellas these docs, ‘ologists and ‘omicians, says Barman.

    Got it says, Med. Not my crowd, not at all. Seem hard work. Too much bickerin’ for a start. Yeah, says Barman, sure is. Sick o’ hearin’ all this ‘ology, ‘omics and docology all day, all night, I am. Owt else thee can tell me about for ‘arf hour to pass time, ‘cos Know Alls too busy boisterin’ an’ bickerin’ to order ‘nother round ‘o drinks.

    Okay says Med, I’ll tell thee what we used to get up to in these parts hereabouts, ‘afore all these Know Alls came along and started makin’ havoc. Out and out Med Chem it’ll be, with a bit o’ the old biol thrown in to keep things sane. I’ll need to slip into the old medicinal chemistry vernacular to tell the tale…


    Once upon a time in a fairy tale laboratory, by a fairy tale mere, which is what a lake been called back then in these parts… Beneath a fairy tale wooded escarpment, where legend said a wizard once lived, and beneath which myth still says behind a set of iron gates sleep slumbering knights in shining armour, ready to come forth at the land’s hour of greatest need…

    …There was a project team made up at project outset of two biologists with four decades experience between them, one medicinal chemist with two and a half decades’ experience, one computational chemist with a decade’s experience who knew a thing or two about structural biology, and two synthesis chemists with six decades’ experience between them, who could synthesise pretty much any chemical matter that could conceivably be reduced to the practice of chemical synthesis.

    The two biologists had won project laurels already and been knighted and ladyed. Arise Sir G***** and Lady R*****. The two med chemists were grisly, disreputable and regarded as borderline insane. No hopers from a managerial leadership perspective. Certainly no knighthood material there.

    Get out from under that table at once, Mad A* and Mad R**, stop bickering like dogs will you, the Project Manager had to order before every project team meeting. As for the synthesis chemists, both old timers, at home in lab doing what they loved best – Making Compounds. Synchem D*** and Synchem G**** just needed a little nurturing. Knew their stuff. Worked best left to own devices.

    Project name Target A Modulator, three letter acronym TAM. Project goal an orally efficacious modulator of Target A. No such modulator existed and, truth to tell, no-one knew for sure if such modulator could ever be found, and if found would manifest in human male to Stop the Growth.

    Complementary to Target A was Target E, for which an FDA approved injectable Target E Modulator (TEM) already existed, discovered decades ago at tail end of the Biochemical Serendipity Project and derived from Target E’s wondrous endogenous ligand. Known unequivocally in human female to Stop the Growth.

    Ah, the Serendipity Project. Before 1960 every project in every drug discovery lab was a serendipity project – penicillin from the mould, the Pill (and arguably dexamethasone in spirit too) from the Mexican yam root, librium from the flask put to one side two years earlier and resurrected after the lab clear up.

    From the early 1960s onwards, Serendipity Projects slowly went out of fashion, at least in the fairy tale laboratory beside the mere. The logicians and rational thinkers began to hold sway, joined from the 1990s onwards by the empiricists and the technologists. I screen therefore I am, as a Prof D********s always used to once upon a time say.


    So comp chemist Mad A* set to and came up with a directed screening set, which Sir G***** and Lady R***** tested in a high throughput surrogate TAM assay they’d devised. Comp chemist Mad A* distilled the data, and handed over the distillate to Mad R** to take a med chemist’s look.

    On standing and swirling the distillate for a few months, then scratching the further distilled data furiously, Mad R** crystallised out an orally bioavailable, weakly potent chemical lead that pretty much satisfied the TAM project’s Lead-Target Profile across the board. Project become a Lead Optimisation Project. First time in three decades trying I’ve ever worked with a truly novel lead, Mad R** reflected. No wonder been times medchem’s driven me near insane…

    Lead series modest, yet selective, potency in TAM receptor binding panel, surrogate TAM, cellular TAM and in vivo TAM assays; modest aqueous solubility, lowish single digit percent free across species; encouraging rodent pharmacokinetics, nowt much else showing up in wider target selectivity panel; no P450 inhibition or attenuation.

    No idea how that happened, Mad R** said to Mad A* next day, for weeks I’ve just felt a bit madder than usual, and lo and behold a confirmed lead popped out. Whereas in loads of past projects, I’d never felt saner and nothing whatsoever popped out. Funny old world, agreed Mad A*, always was, always is and always will be.


    Get out from under that table at once, Mad A* and Mad R**, the Portfolio Manager said, we’re giving you more resources, much more resources, to drive the TAM project forward, fast as you can, even faster. Faster! Faster, No Slacking!

    More resources, the Project Manager said, just what I’ve been pushing for. Great! We’re bound to meet the Project Thymeline now. But we don’t need more resources, the MAD Brothers in unison said, we’ve got Synchems D*** and G**** beaverin’ away, making just the right compounds to answer just the right questions and get us just to where we want to be.

    Another 50 compounds might just get us a Candidate Drug, Mad R** went on, all about locating where to put that pendant solubilising basic side chain, that Mad A* says his TAM structural model predicts will either occupy an adjacent pocket or jut out and interact with the hydrophobic phase. Correct, Mad A* played back. Then, said Mad R**, we might just need to fine tune side chain pKa to get the PK profile right and tinker about with predicted dose to man and all that stuff. You’re the med chemist, Mad R**, that’s your problem, comp chemist Mad A* said.

    Mmmm, the two PMs hummed in unison. You’ll never get a CD in just 50 compounds. The Project Thymeline Candidate Drug Derivation Analysis Cross-Project Report, sponsored by the Research Portfolio Thymeline Evaluation Committee, concluded that metrics say at least 500 compounds invariably needed to get from lead to CD.

    So the MAD Brothers got their extra resources, no questions asked Meetings! Meetings! The MADs barked and bawled all the way back to the lab, for Eff’s Sake save us from Meetings! Meetings!

    The MAD Brothers set forth. Synchems D*** and G**** pressed on with the 50 compounds goin’ to be made all along. Extra Chemistry Resource made up the project metrics. Sir G**** and Lady R***** upped assay throughputs to test ‘em all, as per The Lean Screening Initiative.

    Ask Mad R** where those 50 compounds came from and he’d say half were obvious to those skilled in the art, but don’t tell the Intellectual Property Attorney that. As for the other half, just a matter of searching, searching and re-searching the I**S database; sorting, sorting and re-sorting the Excel spreadsheets; plotting, plotting and re-plotting the Spotfire plots; finding, finding and re-finding the SciFinder searches; reading, reading and re-reading the literature; unfurling, refurling and re-flying the old kites; cycling and re-cycling the recycled old ideas; mining, defining and refining all Mad A*’s zany, zanier and re-zanyed ideas. With a bit of serendipity thrown in here and there for good measure – the samples mixed up, the right compound tested in the wrong asaay, and vice versa.

    All Mad R** could say for sure was that’s what worked for him, what’d evolved over a scientific lifetime. How other med chemists went about the job was their business, for them to work out, beyond the mundane of what database to access and which keys on the keyboard to press. Not for a Mad to tell a Sane what to, and vice versa. And anyway, diversity of thinking just the thing for bringing different ideas to the party

    Somewhere in here a month or more went AWOL. Tried and tested competency-based work review system, wrestled into place by scientists a decade before, replaced by all new singin’ and dancin’ People Performance Reward And Development Management Scheme, initiated by HR at bequest of The Main Board (known respectively as, “Humane Relics” and “Oh Them”). Months digitology wasted at keyboards set beneath wooded escarpment, where once upon a time the Wizard lived.


    As Synchem D*** used to say to Synchem G****, who at times could be a little hard of hearing, “PROGRESS MEANS CHANGE, BUT CHANGE DOES NOT ALWAYS MEAN PROGRESS.” And as G**** used to say back, “D***, in SCIENCE as in LIFE, the DEVIL is more often than not in the DETAIL.”

    The Project Team got a CD. Passed all usual hurdles and on to First TIme In Man for sighter of human PK. Compound not that potent, so PK needed to be good, which animal PK predicted it should. Good, but not quite good enough. Upper end of predicted human dose range heading for horse pill territory.

    Back to the drawing board. The obvious again. More potent compound needed. Chemistry team re-assembled. MAD Brothers ride again. The Synchems gone to pastures new. Corporately restructured into voluntary retirement. Spirit of the Age.

    Brave New Team. Stick a methyl group on the hydrophilic side chain, Mad A* says. Looks like there’s a hydrophobic pocket to pick up. Could get us an order of magnitude potency. As, conceivably, could tinkering about with that piperazine ring, thinks Mad R**. And that methyl group’s goin’ to bring chirality into play, so need to factor that into accessibility and synthesis. Chiral pool and All That.

    Scope for improvin’ that trifluoromethyl at the other end, says Mad A*. Hydrophobicity could be good – polar entities thereabouts, the model shows. Tetramethoxymethane, Mad R** thinks. Like that second generation A2 competitor compound Synchem M*** made all those years ago for profiling alongside our own pre-CD that in the end never went anywhere. Tetraethoxymethane ring closure from an ortho phenylene diamine.

    Not actually been done before from a 3-hydrazino pyridazine, SciFinder says. Bit of a surprise that, but can be that relatively simple chemistry never reported. Can mean, of course, doesn’t work. Simple failure rarely written up.

    Does the trick from the 3-hydrazino pyridazine. Intermediate tricky to isolate, take forward to next step pretty much straight away. Well done, Scott L (or was that someone else?). We’re in business. Take through to prototypic compound. Whoosh, ten-fold more potent. We’re on our way.

    Combine with that chiral methyl group on the tetrahydro-piperazinone side chain. Well done, Barry H. Whoosh, another ten-fold, we might even be there. Whoosh, 500 micromolar solubility, red hot rodent PK. I think we are there. Don’t tell anyone yet, give it a week or two, to dot a few i’s and cross a few t’s…


    Except we weren’t there at all. All went spectacularly ar*e about face, just as Stevie G had sorted the physical form issue on the second 100 gram batch. Polymorphism and all that stuff sort of issue that sometimes crops up and usually goes away, thanks to diligent chemists and wonders of chemistry. Whereas bad biology news usually sticks around to haunt and harry.

    Pre-CD cellular profiling panel that did for us. Quite a few hits. TEM cellular assay the worst. Yes, TEM – the complementary female receptor, the Target E receptor now modulated by… a Target A pre-CD. What the hell… How can that be? Repeat! Repeat! N = 2, asap.

    Duly replicated, N = 2, twice = N = 3. Pre-CD already sent for receptor A binding, that assay you’d ideally have… yet such a thrutch to purify the A receptor, so nobody does, apart from the contract houses. So you pay through the nose, but much cheaper than doing in-house.

    The data came back. Receptor A binding IC50 greater than 100 micromolar. Dead. Receptor A optimised out and Mystery Target Mr X optimised in. Observed cellular readout all thanks to mystery guest Mr X. Kerching! Next project!

    Fooled! Thought we knew what we were doin’ and didn’t. Mad R** moved on. At heart a finisher, not much interested in combing the ‘ologies and the ‘omics to hunt down that mysterious Mr X, even though an oven-ready CD waiting, all ready to cook up and serve out piping hot to The Managerial Leadership Team. Anyway, next project is back to the Oral TEM project, where there’s this novel highly Ligand Efficient hit that MAD A*’s been working up on the side.

    So the MAD brothers went their separate ways, riding off into separate sunsets, only to meet again the following dawn to sus out the Oral TEM project, roister together under tables just like before, and ride around on stallions in the atrium setting off six shooters all over the place…

    But that’s another story. Next up Mad R**’s turn to go out to grass. Voluntary redundancy notice to work out, opportunity to delve on the side into histories of mysterious flasks, moulds and Mexican yam roots.

    Later all fell back into place. Mad A* didn’t let go. Docked the Not the TAM pre-CD with all sorts of modelled targets and found a promising fit. Then stuff started coming out in the lit. Patent filings too. Better file ours asap. Target B. Oven ready CD on its way. All’s well that ends well.


    So, said Med Chem to th’ Barman, yer ged all that? Yeah, said the Barman, who’d heard over the years a few long tales from below the low wooded escarpment where a Wizard once upon a time lived, I geddit – the project thought it knew what it was doin’ but it didn’t, ‘cos without knowin’ it all the project began doin’ somethin’ else.

    Correct, said Med. You goddit. What yer think th’ Know Alls ‘d make o’ it? Med asked the Barman. Won’t geddit, said the Barman, ain’t th’ way they think. Yer goin’ ter tell ‘em the story? asked Med. Nah, said the Barman, eventually a few o’ th’ more questionin’, open minded and broad thinkin’ docs, ‘ologists and ‘omicians ‘ll geddit for ‘emselves and then ‘ey’ll tell th’ rest.

    Very wise, said Med Chem, if they can’t work it out for ‘emselves we can’t tell ‘em. Got to find it out for ‘emselves. That’s the life scientific for you. Bein’ told just won’t do. Always lookin’ out for new questions, answerin’ which might render some old longstandin’ questions superfluous.

    And for th’ uninitiated, that’s the sort of song and dance routine medchems, synchems, biols and all the rest of the project team do all the time. Once in a while ends up on Broadway or at th’ West End, but most of the time just does a run or two at a provincial theatre, and that’s it. Next show, please.

    Except of course not much gets to play Broadway or West End for nine months now, nor even come to think of it does much else get to play at all, all the way down to kids football on astros on Sunday mornings up and down the land, normally watched on by mums and dads, bros and sisses and grannies and grandads. The Pandemic only show in town. Almost become Greatest Show on Earth and Greatets Show Ever Told all rolled up in one.

    Whoops, on me soapbox ag’in. Is that the time? Better be goin’. Just goin’ outside for a little while, might not be back for some time…


    FYI, a real life Mad Jack’s orders of magnitude more serious story, from an orders of magnitude more serious era, can be found here. At around 50 minutes and 44 seconds in, Mad Jack gets a bollocking from his Colonel:

    Reference to a letter Mad Jack sent to the Times can be found below. At the time, said to have raised national indignation and outrage in the heart and soul of the British Empire:

    This is a poem Mad Jack wrote at Denmark Hill Hospital, London, in April 1917:


    “Good-morning, good-morning!” the General said
    When we met him last week on our way to the line.
    Now the soldiers he smiled at are most of ’em dead,
    And we’re cursing his staff for incompetent swine.
    “He’s a cheery old card,” grunted Harry to Jack
    As they slogged up to Arras with rifle and pack.
    But he did for them both by his plan of attack.

    …Off out again yesterday morning. Essential Shopping again, forgotten or omitted from the day before, or thought up afresh. Straight out the drive and on the car radio the Trumpet Voluntary comes on. Cosmic Scriptwriter on good form today. Cue to play out this comment, to work of baroque man of baroque way of thinking, from way back before modern era’s industrial thinking came entered the stage:


    In memoriam Synchem G****, taken off before his time around a decade ago; in salute Synchem D***, still going strong, but taking necessary precautions; and in salute Mad A*, Sir G***** and Lady R*****, wherever you all three are; along with all past, present and future from the labs beside the mere, below the wooded escarpment, where once upon a time the Wizard lived and the knights in shining armour still slumber, wherever you all now are.

  36. li zhi says:

    tl;dr but two things.
    DL claims vaccination doesn’t protect the unvaccinated and we all (do? should?) agree with that. But it is nonsense. If everyone but me were vaccinated, I’d be well protected – far better, statistically, than if I were vaccinated. Sure, it’s indirect protection, but so what? I’d be protected, I wouldn’t be directly protected but which would you say matters more? The other thing is just a carp. DL says more promising vaccines are on the way. I admit that I over punctuate and that I’m especially prone to adding unnecessary commas. But did he mean “more promising” or “more, promising”?

  37. Marko says:

    West Virginia has made a great technical discovery. They’ve figured out how to get a vaccine into a patient’s arm. In time , perhaps they can coach-up the other states :

  38. Chris Phillips says:

    I was a bit concerned to read a BBC report about a nurse condemning the UK vaccination policy because – having been told that it would take 10 days for the vaccine to offer protection – after three weeks she developed symptoms. She describes them as “quite severe”, including a “really bad” cough and breathlessness.

    It’s a bit disturbing that a nurse would not have understood that the Pfizer vaccine is only (say) 95% effective, so (say) 50,000 of the first million vaccinated will still be liable to symptomatic infection. (Obviously the figures will be larger for the AstraZeneca vaccine.)

    I don’t really think there is any story here for the BBC to report, but if they are going to report it they should provide some accurate information about vaccine efficacy, which they don’t. Apart from anything else, it’s not in the public interest for vaccinated people to be running around thinking they are 100% immune.

  39. Uncle Steve says:

    Aside from PCR tests, where is the evidence that the UK has a public health emergency? 111/999 calls close to normal for time of year. Critical care bed occupancy and hospital admissions: nothing out of the ordinary for Dec/Jan.

    And most tellingly, excess deaths now at baseline levels (p61 of 7 Jan 2021 government report below)…


    1. Chris Phillips says:

      Sorry, but I live in London and I _really_ have no patience left with this kind of crap. Probably I shouldn’t even bother to respond, if you’re just a troll. Albeit I can’t begin to believe why people should behave in such a way.

      But on the assumption you are really just plain stupid rather than malicious – read this. It’s just one of a hundred examples you can find in ten seconds using Google:

      1. Uncle Rob says:

        Hmm… Seen similar comments to Uncle Steve’s (and data) on various Twitter feeds.

        Can only respond to Chris Phillips with evidence seen and heard up here 200 miles away from London. Anecdotal, I know, but at rock bottom all I have to go on.

        Unlike last March and April, when out and about for essential shopping I see and hear no more ambulances and paramedic vehicles than usual…

        When I drive directly past the A&E entrance at a local (provincial) hospital, seems no busier than usual (if anything less busy…)

        Get a similar picture from an NHS worker at a different (provincial) hospital…

        Who also reports surgeries and medical centres “quiet as the grave.”

        Ditto my local surgery with car park almost empty at 8.30 this morning. Thankfully does look like surgery open again and barriers outside all removed at last…

        And I do remember very well on 9 December 2019 at around midday picking up an elderly relative after an overnight stay at a Midlands urban hospital and seeing several elderly patients (complete with drips in some cases) lying on trolleys in corridors…

        Which makes me wonder if the winter of 2020-21 is really any different from 2019-20 in that Midlands urban hospital…

        So where is the evidence? Maybe it is on the BBC…

        University College Hospital London. Maybe the evidence is London-centric, maybe the Westminster bubble become the London and Home Counties bubble? Just thinking out loud…

        And just occurs that on one of those bar charts on one of those Twitter feeds, hospital admissions up in London and South East but very little elsewhere?

        Hmm indeed. Maybe the new variant hasn’t reached the boondocks yet, who knows?
        And by the way, Chris Phillips, while you’re here – in a preceding comment, you ask…

        “Please, let’s all show a bit more humility and a bit less asperity.”

        Then next day Chris Phillips gives Uncle Steve the usual hectoring lecture for having the temerity to cite relevant data from a specified page of a government report.

        Hmm indeed…………

        1. Chris Phillips says:

          My apologies for feeding the trolls.

    2. stewart says:

      * Your own citation shows excess deaths two standard deviations above baseline, except for a final dip which might be incomplete recording.
      * Your citation is a week old; diagnoses are up by a third since then.
      * non-COVID deaths are running well below baseline, presumably due to suppression of other cases of death as side-effects of the pandemic responses.
      * we’ve just had the second highest recorded daily death toll (I suspect that a greater proportion of cases are been recorded, making the true figure about 25% under the spring peak, but numbers are rising).

      1. Uncle Rob says:

        Welcome to the party, stewart, don’t recall seeing your name here much before.

        Perhaps a dimwitted old medicinal chemistry troll, who clearly isn’t scientifically fitted to grace a medicinal chemistry blog the medchem troll’s been contaminating for the last decade, that’s fast turning into a Covid-Believer blog hijacked by Chris Phillips et al…

        …Could please make three observational comments:

        “Your own citation shows excess deaths two standard deviations above baseline, except for a final dip which might be incomplete recording.”

        …Could you please consider indicating which page and figure in the citation you’re referring to, as Table 7 on page 62 doesn’t seem consistent with the above statement

        “Your citation is a week old; diagnoses are up by a third since then.”

        …Could you please consider providing a link with unambiguous supporting data for the point you’re making.

        “non-COVID deaths are running well below baseline, presumably due to suppression of other cases of death as side-effects of the pandemic responses.”

        …Could you please consider clarifying this statement. Not my area of expertise at all, but to me reads as the pandemic response suppressing non-Covid deaths. Whereas another way of looking at this could be that delays in treatment of other conditions (e.g. diabetes) could now be leading to hospital admissions, some of whom may be Covid-symptomatic (to some or all degree) and PCR-tested positive.

        Thank you in advance of considering.

    3. Uncle Steve says:

      The fact that excess deaths are close to baseline is particularly striking given the lack of regular healthcare in 2020, e.g. missed oncology appointments etc.

    1. Marko says:

      I know how I’d place my bet: The Covid-19 situation is going to hell in a handbasket in the US, and the White House Covid Task Force is looking for some excuse that will help wipe the egg off their faces:

      No sequencing data. No evidence at all of a “new US variant”. Just a surge in cases and some cover-my-ass speculation designed to deflect blame.

      1. Marko says:

        Anyone know where I can go to cash in on my bet ?

        “Reports of a highly contagious new variant in the United States, published on Friday by multiple news outlets, are based on speculative statements made by Dr. Deborah Birx and are inaccurate, according to several government officials.

        The erroneous report originated at a recent meeting where Birx, a member of the White House coronavirus task force, presented graphs of the escalating cases in the country. She suggested to other members of the task force that a new, more transmissible variant originating in the U.S. might explain the surge, as another variant did in Britain.

        Her hypothesis made it into a weekly report sent to state governors……..Dismayed, officials at the CDC tried to have the speculative statements removed, but were unsuccessful, according to three people familiar with the events….”

        If Birx had a trace of credibility left, she just squashed it like a bug.

    1. confused says:

      As linked to in Marko’s comment above, this appears to be baseless speculation from an unfortunately-credible-sounding source; IE there is no such thing.

    1. Chris Phillips says:

      Thanks. It’s interesting that the latest ONS survey, released yesterday, presents estimates of the percentage who would test positive in different English regions. According to those, the curve has just passed a peak in London and looks flat in the South East and East (Figure 5; further on they estimate that around 80% of infections are now compatible with the new variant in London and the East, and two thirds in the South East):

      It seems the new variant is capable of being contained by a lockdown. From anecdotal evidence, this lockdown isn’t being observed as well as the first one, and according to a survey 44% of the adult population mixed with people from another household at Christmas.

      1. Marko says:

        Yes, it’s good to see that they may have turned the corner in London, but in the next couple of weeks London hospitals are going to be an absolute mess regardless.

        I get a little frustrated reading the UK reports when I see something like ” We estimate that 2% or 1 in 50 ) of the population in the UK currently has the coronavirus” , because it’s not clear to me what they mean by that. 2% were infected in the last week? The last 10 days? 2% are infectious right now?

        Only about 1 person out of 1000 in the UK gets a positive PCR each day, but I assume they’re correcting for undiagnosed cases and adding up several days worth of data to come up with the 2% figure, but I haven’t seen it explained in anywhere clearly.

        I think it’s a useful way to express things, and I see it done in a lot of media reports, but nobody ever explains exactly what it means. Not that the US media is any better, of course.

        To be fair, I haven’t really dug into all the UK gov’t reports that closely. I’m sure it must be in there somewhere.

        1. Chris Phillips says:

          I think it’s meant to be an estimate of the precentage that would test positive in an antigen test if they took one. Though I don’t understand for the life of me why they don’t describe it clearly in that way rather than saying something like “the percentage of people testing positive for the coronavirus”, which it clearly isn’t.

          Unfortunately things tend to be “dumbed down” to the extent that they are positively misleading.

        2. Bill says:

          Marko said
          I get a little frustrated reading the UK reports when I see something like ” We estimate that 2% or 1 in 50 ) of the population in the UK currently has the coronavirus” , because it’s not clear to me what they mean by that. 2% were infected in the last week? The last 10 days? 2% are infectious right now?
          UK has a well supported symptom tracking app: Currently estimated 834k with active infection.

          I assume they extrapolate from those currently reporting symptoms or within the last 10 or maybe 14 days. Don’t know if they kick it up for asymptomatics.

        3. Back of the envelope says:

          Agree UK numbers could be expressed better. Back of envelope UK guestimates derived from latest Office for National Statistics records as follows:

          Total number of tests ~ 60M (1 May 2020 onward)
          Total number of tested positives ~ 3M (ditto)
          Total number of deaths ~ 80K

          By way of examplars,

          Assuming IFR 0.4% implies 80K x 100/0.4 = 20M cases


          Assuming 3 undetected cases per 1 tested positive case
          Implies 3M + 9M = 12M cases (1 May 2020 onward)
          Assume in main Mar/Apr 2020 peak 10% UK contaged (7M)
          Gives total 12M + 7M = 19M cases out of UK population of 67M

          Further examplar,

          Assume 20M UK cases to date
          Assume 1000 x 23 deaths per day to end Jan = 23K
          Implies 23K x 100/0.4 = 6M cases
          Assume 7M vaccinations (1st shot) by end Jan
          Gives total 20M + 6M + 7M = 33M immune (50% UK pop)

          If for R(0) = 3, UK collective immunity 67% equates to 45M

          33M immune + 8M vaccinations in Feb + 4M new cases in Feb would fulfil


          * London (highest number of cases per head?) might be special case
          * Any underlying “prior immunity” brings UK end Feb date forward
          * 40% Prior immunity implies 27M UK prior immune
          * Would then be at UK collective immunity now
          * On face of it, doesn’t fit current skyrocketing cases
          * So prior immunity debunked?

          …Previously raised at:

          …Time might come where unthinkable starts to get thought..?

      2. Dan Defough says:

        Case of lockdo*n fatigue. The very term comes loaded with unsavoury overtones of civil disorder and martial law. Frankly, term arguably bit of an abomination for generation following generation living in a free and easy society that’s prevailed here in the UK from the early 1960s onwards, an era am just about wrinkly enough to have picked up vibes of what might have gone on before that. Conscripted military National Service and All That, ended on 31 December 1960, just over 60 years ago to the dot.

        Lockdo*n mentality hasn’t done our police forces any favours, either. Fining folk for going on country walks in the fresh air. Nonsene. So after 9 months, lockdo*n unsurprisingly unsustainable. Seems to work elsewhere in certain circumstances, but elsewhere’s not here. Constant chopping and changing of GOV.UK policy doesn’t help.

        Neither did “do as I say, not as I do” next to the very top last April from governement special advisor, and around same time from a government scientific advisor (now reinstated, it seems), and on and off from a sprinkling of junior politicos. Government by numbers and slogans on podia doesn’t help, either. Credibility duly lost.

        More to the point, where’s the hard evidence that non-pharmaceutical interventions actually make much difference to lives saved or lost, or indeed is there counter evidence that some aspects of non-pharmaceutical interventions could actually make things worse?

        Non-pharmaceutical interventions – ah, there’s a mouthful. Eleven syllables of euphemism to go alongside ten syllables of national social distancism, which really boil down to six syllables of self isolation, three syllables of two metres and two syllables of lockdo*n, which might even conceivably mean three syllables called fallacy. Clever stuff.

        And where’s the balance sheet House of Commons dissenters asked for in those two previous lockdo*n debates, that weighs up lives saved on one side against lives lost elsewhere, and all the other collateral social, economic and educational damage?

        Doubt the question even got asked in Wednesday’s retrospective parliamentary debate – Right Honourable Memebers of Parliament too busy voting retrospectively for prospective actions that might not even make the barest jot of difference. Except for a term’s 575 million boy and girl schooldays now being definitively flushed away, which for certain makes a difference to the 9 million British kids implicated and their 12 million British parents.

        So 44% adults mixing with another household feels a plausible number. For the record, on Christmas Day I was one of them – mixing with an elderly lady known quite well on and off for near seven decades, who gets out of the house a lot less than she did before last March, and who was visibly thrilled to be doing a bit of household mixing at long last.

        Some two weeks later the elderly lady has thankfully experienced no adverse effects from her little outing. Same goes for the rest of the elderly lady’s immediate family. Yah boo sucks Boris!

  40. Marko says:

    “All people living in care homes in Denmark have now been vaccinated. Vaccination started on 27 December.”

    If the proportion of Covid-19 deaths from care home residents is as high in Denmark as it is in the US, this means that in a month or so the daily death rate in Denmark should begin to show a major downward shift, other things being equal.

    1. RHB says:

      Let’s hope the fatality numbers in Denmark (and elsewhere) do start coming down in a month or so, or better still tomorrow, next week, or the week after that:

      1. Wider epidemiology could also be explained by prior immunity and real time viral infections from 1Q 2020 onwards?

      2. But if numbers don’t come down…

      3. Vaccination poorly effective in the elderly and frail, who by definition make up most care home residents, and who tend to have a weaker inherent immune response awaiting beefing up by vaccination? Or conceivably…

      4. Other etiology doing worst behind the SARS 2 facade? Or ditto…

      5. Any number of other things that could be thought out then brought into play..?

      6. Commenter has couple of way out hypotheses, but way premature to commit to the screen in the here and now.

      Let’s see how the coming weeks play out in the grandscale experiment called Life. Fingers crossed, minds open, hearts in the right place.

    2. Some idiot says:

      Another forecast from the authorities I heard yesterday: it is expected that all in Denmark who want the vaccine will probably have received the vaccine by the end of June (2021). At the moment, as you mention, all nursing home residents and employees have received their first. Total vaccination in Denmark is now just over 1% of the population.

  41. Marko says:

    “We need to fully determine the response of these new strains to neutralizing antibodies, and not just by a point mutation (e.g. N501Y) but all the mutations and their interactions. That also becomes important for better vaccine designs in the many months (?years) ahead.”

    Hooray! Even the blue-check “experts” are finally seeing the light.

  42. FollowtheData says:

    @Marko wrote: “I have my doubts about the CDC numbers. I need to check on what kind of multipliers they’re using in the updates. If they’re using a constant multiplier throughout, their numbers are garbage.”

    I’ve been tracking that particular CDC page in recent months. They had previously used a multiplier of 7.7 for the period of Feb through September 30. When they extended the period to February to November 30, they reduced the multiplier for the entire period to 7.2 (the one currently listed).

    And yes, there is a typo in the introductory paragraph. It should read “February through November ” to be consistent with Table 1.

    I too am interested to see an update that adds December to the estimate.

    1. Marko says:

      Thanks. I should have followed up on my comment. I figured out the multiplier for only the Sept. to Nov. period to be ~5.9 , so clearly they’re not simply relying on using the same multiplier for the updates. Still , I’m not sure I buy their analysis. I think the correct multiplier for the Sept.-Nov. period is unlikely to be any more than half of that of the earlier Feb-Sept. period, based on the much more severe under-reporting earlier vs later.

      The JAMA paper I referred to above has a progression of multipliers over different periods that seems to me, intuitively, to be closer to the likely reality.

    2. Bill says:

      CDC Estimate update is out. 91M as of 11 December.

      I still see the horserace to immunize the country being a run-away for infection over vaccine.

      Currently 27% of population for infection vs 7% for vaccine…or 0% if you only count for 2 doses.

      Haven’t done all the math but if 300k x 7 = 2.1M infections/day, who knows when or if vaccine will ever even match the pace, let along catch up?

  43. Jesse says:

    @Marko wrote: “I have my doubts about the CDC numbers. I need to check on what kind of multipliers they’re using in the updates. If they’re using a constant multiplier throughout, their numbers are garbage.”

    I’ve been tracking that particular CDC page in recent months. They had previously used a multiplier of 7.7 for the period of Feb through September 30. When they extended the period to February to November 30, they reduced the multiplier for the entire period to 7.2 (the one currently listed).

    And yes, there is a typo in the introductory paragraph. It should read “February through November ” to be consistent with Table 1.

    I too am interested to see an update that adds December to the estimate.

  44. Uncle Steve says:

    Unreliable PCR tests were responsible for this:
    “Faith in Quick Test Leads to Epidemic That Wasn’t”

    1. Uncle Rob says:

      Thank you, Uncle Steve, for the reminder about the 2006 Lebanon NH Whooping Cough Epidemic That Never Was. Which is not to say getting on for one hundred and fifty people didn’t genuinely feel unwell. Now re-etched on brain – filing under Proven Past Precedent.

      This scientifically inclined cricket fan was intrigued by the PCR testing item reported upon arrival at Colombo airport of the England team for the upcoming two test match series in Sri Lanka, headlined – “Moeen Ali Tests Positive for Covid-19”:

      And followed up two days later by – “Touring party all clear after being retested for Covid-19”:

      Which prompts a few questions, some of which the preceding articles answer already:

      Q: Did Moeen Ali take a test before departing the UK
      A: Yes, test negative (article doesn’t specify which test, by implication PCR)

      Q: Which test did Moeen Ali take in Sri Lanka?
      A: Lateral flow (negative), then PCR (positive)

      Q: Did any other England players test positive?
      A: Not on arrival, nor on repeat two days later

      Q: Was the Sri Lankan PCR test n = 1, or n = 2 (sample and/or test)?
      A: Not reported

      Q: Was Moeen Ali showing symptoms and/or feeling unwell?
      A: Not reported

      Q: Did any of the England team’s charter flight crew test positive on arrival or on later repeat?
      A: Not reported, and level of detail that never will be reported

      Bad luck Moeen, you’re banged up in your hotel room for 10 days. Released day before the First Test starts, but too late for selection as team usually pretty much decided by then based on performance in practice.

      Also from the first article:

      “England’s last overseas tour, in South Africa, was cut short in December after positive cases in the Cape Town hotel where England were staying. England returned two positive tests – that were LATER VERIFIED as FALSE POSITIVES.”


    2. WST says:

      Uncle Troll,
      In the current reality, PCR is extensively tested all the time against sequencing. D-vitamin, this is the latest in troll toolbox…

    3. WST says:

      Uncle Troll,
      In the current reality, PCR is extensively tested all the time against sequencing. D-vitamin, this is the latest in the trolls toolbox…

  45. Ex Pharma R&D says:

    Just to be clear, WST. Article you link is referring to sequencing of specific mutated variants, whereas Uncle Steve is referring to the standard PCR test used for mass screening. Here in UK up to 600K tests per day being done, as part of “Test and Trace.”

    Majority of these referred to as “Pillar 2 Community Testing”, run (as I understand) by Lighthouse Laboratories, which was set up in Spring 2020 following the initial UK epidemic.

    Being formerly involved in drug R&D, past experience of mass testing (albeit of chemical compounds rather than biological samples, including on occasion same test run across different sites within same organisation) tells that various issues may (or may not) crop up…

    …Including performance of standards in assay, reagent sourcing and QC, sample handling and tracking, sample cross contamination risks, false positive and false negative rates, number of replicate determinations (n = 1 routinely here in UK for coronavirus mass testing, so false positives not routinely ruled out by repeat testing), data recording, entry and retrieval, etc.

    Would like to add that setting up PCR assay logistics under time (and political) pressure to now run up to 600K tests per day sounds no mean feat. Lot of pitfalls encountered when mass screening assays first set up around 20 years ago in the neck of the Pharma woods I know best, although I’d like to think that sort of learning should now be part of common practice in any form of mass testing programme.

    1. WST says:

      “Just to be clear, WST. Article you link is referring to sequencing of specific mutated variants”
      This must be a misunderstanding, the table talks about % of all positive cases that are sequenced. First you sequence a lot and only then may detect mutants. Few countries developed PCR primers to easily detect the “GB” mutations but mass sequencing must precede detection of new mutations.

      1. Ex Pharma R&D says:

        Feels like we’re talking at cross purposes here. I’d like to see the performance of UK Pillar 2 Community Testing made public. Response to a UK Freedom of information request re operating characteristics of 600K daily PCR testing (e.g. operational false positive rate) pasted word for word below.

        Can be summarised as,

        “Trust us, we’re the Government and we trust the internationally recognised experts.” After the last 9 months, am not inclined to take anything at face value any more…

        “The PCR test is reliable and effective. Like any diagnostic test however, there is always the small possibility of a false negative or a false positive result.

        The PCR test is reliable and effective. Lighthouse laboratories that will undertake the processing of the majority of the tests have been reviewed by experts as part of their set up and each has a clinical virology lead. Like any diagnostic test however, there is always the small possibility of a false negative or a false positive result.

        We do not have a method for collecting data for false positive or false negative results arising from testing within the national testing programme, however ONS data on the current tests show they are very specific and the risk of false positives is extremely low.

        Published academic evidence from the UK and internationally demonstrates that self-administered test kits can be just as effective as clinician-administered tests in securing a good sample.

        Guidance has been produced and published:

        that allows laboratories to provide assurance of positive SARS-CoV-2 RNA results during periods of low prevalence and is being implemented.

        Positive test results should be treated as accurate and the patient should isolate until at least 10 days after their symptoms commenced and their fever has resolved according to the national guidance.

        Information from ONS on test specificity and false positives following a Covid-19 infection survey is available here –

        A summary for round 1 of the Quality Control for Molecular Diagnostics EQA for the PCR test can be found here:”

      2. Uncle Steve says:

        I sense someone playing the man not the ball

        Michael Mina, Assistant Professor at Harvard’s Center for Communicable Disease Dynamics, Department of Epidemiology, has interesting things to say on PCR testing

        Try @michaelmina_lab on Twitter

        1. Uncle Steve says:

          PS worth looking at “Tweets and Replies” for 10 January

          1. Uncle Rob says:

            Interesting. Advocates antigen testing (which can pretty much be done in real time) for “self-detection.” Linked article is here …


            Quote for the day: “To make any program work today, it must be on the people’s terms.”

        2. WST says:

          there is no ball….

          Michael Mina
          This is NOT to say that we should not do PCR. But if it takes more than a few hours to return a result, it should be reserved for clinical medical diagnostics. NOT for screening and finding infectious people. unless it is being performed 2x/week – which it almost never is.

      3. Some idiot says:

        FWIW (and just for information), Denmark is sequencing around 10% of positive PCR tests. Also are in the process of developing a PCR primer for one of the mutations in the UK variant…

        1. WST says:

          Thanks. SSI does impressive work.

          1. Uncle Steve says:

            Bottom line in the UK:

            Covid PCR test results tell us that we have an exceptional public health emergency

            Real-world data, such as the total number of people actually dying, tells us that the situation is not so very different from an average winter

            So are we miscounting bodies, or is something up with the tests?

          2. Chris Phillips says:

            I just wish I could understand your motivation. Whether you really believe people are just inventing all this stuff. Or whether you get some twisted psychological/psychiatric satisfaction from taunting people with it.

            Today I read that the UK’s first emergency mortuary has opened, about four miles away from me.

            Are you just trying to present us with a scientific distraction, by suggesting that there are people who are so psychologically abnormal that they can actually derive some kind of pleasure from this situation?

            If so, I think it’s a bit pointless, because mental illness is off-topic for this forum.

          3. Chris Phillips says:

            Perhaps worth noting the very next web page I looked at:
            “A hospital’s oxygen supply has “reached a critical situation” due to rising numbers of Covid-19 infections.
            A document shared with the BBC showed Southend Hospital has had to reduce the amount it uses to treat patients.
            It said the target range for oxygen levels that should be in patients’ blood had been cut from 92% to a baseline of 88-92%.
            Hospital managing director, Yvonne Blucher, said it was “working to manage” the situation.
            “We are experiencing high demand for oxygen because of rising numbers of inpatients with Covid-19 and we are working to manage this,” she said.
            “The public can play their part by staying home and, where they cannot, following the ‘hands, face, space’ advice to cut the spread of the virus.””


            Perhaps some idiot is about to say it is all perfectly normal, that COVID-19 is “fake” and that there’s no cause for concern. Human idiocy really does transcend all bounds sometimes.

          4. Moran Feldman says:

            Let me be that idiot. Please compare the cost (economic cost, health cost, emotional cost, moral cost, etc.) of even a single lockdown to the cost of rash building even 100 new factories for oxygen tanks.

          5. A Nonny Mouse says:

            Who knows where this will end up…

            The oxygen problem in hospitals is not with the actual oxygen supply, it’s with the internal pipework which was never designed to be using so much oxygen at once.

          6. Chris Phillips says:

            Moran Feldman

            Thank you for volunteering to be that idiot.

            But you’re not really being a satisfactory idiot.

            We are in a lockdown and even so we don’t have enough oxygen. For some reason you are asking me to estimate how much the extra oxygen requirements would cost if we didn’t have a lockdown. And weigh that against the cost of a lockdown. That doesn’t make any sense in the context of the situtation in Essex, does it?

            If you’re advocating abandoning the lockdown, you need to estimate the consequences of doing that, given that we are barely able to cope even with a lockdown – not just oxygen, but everything that would happen if we did that, including the likely collapse of health care for all other conditions, and perhaps the breakdown of all kinds of infrastructure (in the UK we’re already being warned there may be food shortages because so many people are now off sick or self-isolating) – and then convince us that would be worthwhile.

            To be honest I know you can’t do it, but I am interested in the psychological/psychiatric aspects of people who hold your point of view – or perhaps of people who don’t hold that point of view, but have some kind of personality disorder that means they enjoy pretending they do.

            Go on. Try to enlighten me.

          7. Richard of Loxley says:

            @Uncle Steve, Chris Phillips, Moran Feldman

            No sense of imminent social disorder round here when last out and about two days ago for essential shopping. Will check again when out shopping again tomorrow morning.

            Not denying that patients are dying in UK hospitals that are very busy (predominantly in London and the South East?). Up for debate, however, is the etiology of at least some of these patients, the UK Government’s policies being based on detected and extrapolated case numbers derived from interpretation of PCR mass testing data.

            Posted on Twitter is a report entitled, “The University of Cambridge Asymptomatic Screening Programme: Week 9 (30th November – 6th December 2020)”:


            In summary, the report describes how, in the week 30th November – 6th December 2020, nasal swab samples from ~9000 asymptomatic university students were combined in groups of 4 to 5 samples, to give ~1900 pooled samples, which were then subject to PCR analysis to look for the requisite amplified viral DNA fragment.

            10 of the 1900 pooled samples ostensibly showed presence of viral fragment. Fresh nasal swabs were taken from the corresponding students and these were retested individually by PCR. No positive tests were detected, implying that the pooled samples had all given “false positive” test results.

            So that seems a pretty clear proof that the PCR test can give a significant false positive rate. A further issue is the number of cycle times used, an aspect discussed in the New York Times by journalist Apoorva Mandavilli and Harvard Associate Professor Dr Michael Mina as long ago as 29 August 2020:

            Your Coronavirus Test Is Positive. Maybe It Shouldn’t Be.

            …And since discussed again in some depth by journalist Peter Andrews, along with discussion of a ten-point challenge to the seminal Covid-19 PCR testing publication made by a respected group of scientists:

            27 Nov 2020: Landmark legal ruling finds that Covid tests are not fit for purpose. So what do the Mainstream Media do? They ignore it

            1 Dec 2020: A global team of experts has found 10 FATAL FLAWS in the main test for Covid and is demanding it’s urgently axed. As they should

            9 Dec 2020: Flawed paper behind Covid-19 testing faces being retracted, after scientists expose its ten fatal problems

            FYI, the journal Eurosurveillance is due to respond to the retraction request by 31 January 2021 (some 3 months longer than the two days the journal took to receive, accept and publish the paper in January 2020). Meanwhile, as Peter Andrews concluded in his 27 November article:

            “Testing, especially PCR testing, is the basis for the entire house of cards of Covid restrictions that are wreaking havoc worldwide. From testing comes case numbers. From case numbers come the ‘R number,’ the rate at which a carrier infects others. From the ‘dreaded’ R number comes the lockdowns and the restrictions, such as England’s new and baffling tiered restrictions that come into force next week.

            The daily barrage of statistics is familiar to us all by this point, but as time goes on the evidence that something may be deeply amiss with the whole foundation of our reaction to this pandemic – the testing regime – continues to mount.”

            Enough said. Time here in the UK for a call on Government and scientific advisers to urgently take on board the need to review interpretation of PCR mass testing data.

            And to reiterate that I’m not denying that patients are dying in UK hospitals.

          8. Chris Phillips says:

            “Richard of Loxley”

            The report referred to in the tweet you link to says:
            “The false positive rate for all pooled screening tests to date has been 1 in 373(0.3%).”

          9. WST says:

            Uncle Troll,
            “Real-world data, such as the total number of people actually dying, tells us that the situation is not so very different from an average winter”

            “Estimating the burden of COVID-19 pandemic on mortality, life expectancy and lifespan inequality in England and Wales: A population-level analysis”

            …and conclusion up to week 47:
            ” Life expectancy at birth dropped 0.9 and 1.2 years for females and males relative to the 2019 levels, respectively. Lifespan inequality also fell over the same period by five months for both sexes.”

            It takes a lot of premature deaths to move such a large scale demographic metric. This settles the argument.

          10. Richard of Loxley says:

            @Chris Phillips

            Yes, I’d seen that false positive rate cited at 0.3%. And for week 30 Nov – 6 Dec rate is in effect 10/1937 = 0.5% (assuming one “positive” per pooled set), so in line with previous data.

            Am assuming the 0.3% figure refers to the University of Cambridge PCR testing lab. Thought I’d read elsewhere that the University had set up a dedicated facility within a university lab, or maybe University of Cambridge PCR testing is now part of the UK government’s Pillar 2 Community Testing? Either way, would seem reasonable to assume testing carried out to high standard, hence lowish false positive rate.

            Should also add that through pooling tactic, University of Cambridge in effect doing n = 2, whereas am pretty sure Pillar 2 does n = 1, so false positives not ruled out. And, of course, true or false, recipient advise to go and self isolate (or, in plain English, be self-banged up).

            Now I may be wrong on this, but intuitively does seem that the PCR false positive rate could vary from lab to lab, which is maybe why the UK government has been unable to supply an overall false positive rate. In case not seen already, please refer to recently posted comment on this thread which reproduces government response to that very query, put via Freedom of Information portal…


            Coming back to inter-lab (and other) variability, that’s something come across quite frequently in med chem when on receiving end of decade upon decade of biological data, latterly involving all the latest state of the art assay kit.

            But whatever the kit, there’s still the potential phenomenon of inter-operator variability to be aware of. Years ago now, but don’t get me started. Some previous comments on this thread on assay variables are here:


            While you’re here, Chris, P, any thoughts on PCR cycle number (Ct)? Struggling to get my head round this for UK PCR testing, even after scrolling through Public Health England’s…

            “Understanding cycle threshold (Ct) in SARS-CoV-2 RT-PCR: A guide for health protection teams”

            …As far as I can tell, no mention what recommended Ct is, other than cryptic summary:

            “Ct values are not directly comparable between assays and may not be reported by some RT-PCR platforms in use. Interpreting single positive Ct values for staging infectious course, prognosis, infectivity or as an indicator of recovery must be done with context about the clinical history.

            Low Ct values (high viral load) more likely indicate acute disease and high infectivity.

            High Ct values (low viral load) can be attributed to several clinical scenarios whereby therisk of infectivity may be reduced but interpretation requires clinical context.”

            …Have to say sounds frankly not a lot of help when you’ve got 600K nose job samples to process in a day. So decided to head across the Channel and down to Marseilles (ah, foreign travel to broaden the old mind, those were the days…), where Rita Jafaar et al hang out, taking a short detour via Thai Binh, Vietnam, where Van Thuan Hoang beavers away:


            ….Whoops, sorry about textuage. Worth every symbol, cos Rita Jaafar et al spell out in two short pages that at Ct = 25 up to 70% of patient samples can grow real-live virus in culture, whereas at Ct = 35, that drops to just 3%. Now, by way of aside, maybe that’s how come French kids are still at school while ours are at the XBox doing online learning?

            Dynamite that, if I could only find again that GOV.UK derived mention of Ct = …..35. Better firm up on the French having got it, so on way back from Marseilles call in on Oxford, where turns out three redoubtable chaps and a lady have been reviewing pretty much the same thing…


            Getting late, that’ll do. Couple of other related comments now posted after being with moderator a couple of days…

            Moeen Ali and the Strange Case of the Abandoned England Cricket Tour of South Africa:

            Back of the envelope calculations on UK case numbers. Might of course be way off. Delusional commenter no wish to blow own trumpet, but can’t help wondering if scrappy envelope as (or maybe, even more) informative than 42 non-peer reviewed papers put up on a College’s own website:

            Ball back in your court, Chris P, although, as you told commenter Moran Feldman in no uncertain terms, you don’t like playing against, “…the psychological/psychiatric aspects of people who hold… point of view – or perhaps of people who don’t hold that point of view, but have some kind of personality disorder that means they enjoy pretending they do.”

            Not usual to go for man not ball on the tennis court, but do please feel free to go ahead and give it a try.

            Oh yes, final thought – better calling PCR “false positive” from now on, “false diagnosis”?

          11. Chris Phillips says:

            “Richard of Loxley”

            Evidently you’re not the only one to have been “spreading the word” about this, though you do seem to be about a month behind the others. The Full Fact website published an article entitled “Cambridge Covid-19 test results don’t mean PCR tests are inaccurate” on 11 December:

          12. Richard of Loxley says:

            @Chris Phillips

            Thank you for the link. Perfectly reasonable “Full Fact” assessment, as far as it goes. Can’t help but pull out these paragraphs…

            “That’s not to say that false positives are not an issue at all, and it is important to note that some people may have suffered detriment (by the requirement to self-isolate following a positive test) after having received a false positive.

            It is also important to note that while PCR tests indicate presence of the virus in someone’s body, they are not a medical diagnosis for the Covid-19 illness.”

            First quoted pragaraph likewise perfectly reasonable re false positives (which, I submit, could conceivably turn into false diagnoses). Although have to say, “People may have suffered detriment,” a phrase that might flow readily off the keyboard, but, were I the recipient, would flow less readily into psyche, especially if unconvinced over the reliability of the PCR test result.

            Which brings back to three other points not to be let go of. Firstly, for testing performed in the rarified Cam backyard (which, once upon at time, I myself for three years knew well), Quality Control of University of Cambridge PCR testing no doubt top notch. Indeed, alluded to obliquely by a University College President in annual Christmas message, at 3 minutes in, and again at 3 minutes 40 seconds in…


            So to cut to the chase, questions remain – what does the Quality Control look like for the up to 600K PCR tests now being run daily in the UK, approximately 500K of which I believe fall under remit of “Pillar 2 Community Testing,” under auspice of Lighthouse Laboratories?

            Which leads in to a second question: What is the cycle number cut off for a result to be deemed positive in UK PCR mass testing?

            And so on to a third question: What is the false positive rate for each lab carrying out testing, especially for Pillar 2 Community Testing?

            Please do respond, Chris P, if you have any insights or can share links that shed light on answers to these questions. As mentioned previously, UK government response to these queries failed to satisfy the requester’s innate curiosity:


            Off out now for essential shopping. Maybe later, a walk in a nearby wood and then on to adjacent badlands to see what the sheep are up to.

            Sometimes nothing like a breath of fresh air to clear the head – and the other day read that outdoor exercise recommended for a viral infection, as will dissipate viral load in fresh air rather than sufferer festering inside and re-absorbing own viral load from own maladroit air.

            Does accord somewhat with personal experience on long ago walking expeditions at home and abroad, when feeling a bit off colour but not wanting to miss the great outdoors on a glorious day. Go for it and either keel over after an hour or two and give up, or suddenly start feeling much better and have a whale of a time for rest of day.

            Maybe even makes sense of long ago somewhat off colour school boys and girls, training for commercial, empire and society building on long ago school playing fields, being told by matrons, house masters and house mistresses – “Stop snivelling, get outside and play some sport – you’ll feel much better for it!”

            Although sad thing is little if any school sport played these last nine months, half a UK junior and senior club cricket season wiped out (estimated 25,000 matches up and down the UK), and currently all youth and grassroots sport suspended until, at very earliest, next GOV.UK restrictions review on 15 Feb.

            By way of aside, back of envelope risk assessments for two outdoor sports as follows…

            “Recreational” Cricket: 13 Players and 2 umpires dotted around two acre cricket field (with opposition’s 9 remaining players typically dotted perambulating around perimeter) = minimal risk

            “Grassroots” and Youth Football: Up to 30 in number (players, subs, coaches, ref), with 22 players and ref in perpetual motion on a football pitch, typically 68 x 52 metres = minimal risk

            Yes, I know helpers and supporters are there too, but changing rooms and pavilions off limits, so everyone is outside in minimal risk fresh air.

            Talking of which, encouraged to hear yesterday of psychologist Professor Yardley (co-opted on to SAGE?) advocating focus should be on viral transmission risk indoors, not outdoors where risk much lower. And even Man Himself, Prof Whitty, reported as saying pretty much same thing on BBC Radio Q&A.

            Bit sad, though, that outdoor activity seemed generally accepted as low risk at outset last March, yet, as veiled hysteria ramped up thereafter, even fresh air morphed into a potential dice with death. And of course with supreme Catch22ery, any protest against coronavirus regulations by a close knit group of people can merit police arrest for…. breaching coronavirus regulations.

            So what, as a matter of interest, Chris Phillips, do you make of Richard of Loxley’s latest online soapboxery?

  46. Marko says:

    “Australia, New Zealand, Taiwan and Japan are among those that won’t start vaccinating for months, in part to see how other populations react to the jab”

    How ironic. The US and the UK are acting as the world’s guinea pigs for a novel vaccine because they’re in such desperate straits after allowing the virus to rage in an uncontrolled manner. It’s beautiful , in a twisted way.

  47. Tom H says:

    Japanese approval requires local phase 3 trials. Only BioNTech-Pfizer has done those; their vaccine is in regulatory review at the moment. AstraZeneca is in phase 3 trials now, and Moderna is just getting started. So, they are not waiting for feedback from other countries, but the completion of their own approval process. Taiwan is also working through its own approval process.

    I will hazard a guess that Japan will approve the BioNTech vaccine in February and that’s when the vaccinations will start.

  48. Marko says:

    If there’s not a law against this sort of thing, there should be. Somebody need to go to jail :

    1. Bill says:

      It’s a 2-edged sword. If you insist that distribution adhere strictly to guidelines, some hospitals afraid of legal consequences have actually thrown expired vaccine away. Better to give it to anyone than to waste it. But when you allow that, the policy gets abused. And pretty soon you’re overrun with line cutters.

      1. Marko says:

        What are you on about? The distribution plan in this case was to vaccinate the privileged elites first, with no consideration of relative risks or prevention of transmission. It’s a reflection of the inequities that have shown their ugly faces throughout the pandemic, both in the US and globally.

        1. Bill says:

          Totally agree with your priorities. I think UK has it right and US has it wrong. Get the people vaccinated who are profiled for hospitalization. We’re vaccinating an awful lot of young people.

          But if at the end of the day you have a dozen doses left over and no “qualifying” people standing by to receive them…have the flexibility to inject them into whoever is available. Regardless of priorities.

          1. A Nonny Mouse says:

            This has already happened in the UK when police were given the Pfizer vaccine as the elderly recipients had either failed to turn up or refused the “foreign” vaccine (wanting the AZ one instead!).

  49. Marko says:

    Saliva viral load more predictive of disease severity than NP viral load, which makes sense :

  50. Marko says:

    Spike E484K mutation in a case of reinfection in Brazil :

    This is one of the mutations of the cluster in the fast-spreading South Africa variant.

    1. Marko says:

      New variant in Japan also has the E484K mutation, as well as the N501Y in common with both the UK and SA variants :

  51. Luis Filipe says:

    I agree that this will be the year where we will be turning the corner but will take time and patience with all the bumps etc along the way i think that we will only see some kind of “normal life” by the beggining of 2021 Winter

  52. Marko says:

    Moderna expects that RCTs will not be required for vaccine updates (i.e. for variants) :

  53. Chris Phillips says:

    I suppose I’m not the only one who has been wondering when Johnson and Johnson will report their Phase 3 results.

    Here’s a report about the expectations of “Wall Street Analysts”. I don’t know whether it’s based on anything other than the same information we all have access to, but it says the results are expected before the end of January and analysts are “cautiously optimistic” about them:

    1. Marko says:

      Here’s another one :

      “…Moncef Slaoui, the chief scientific adviser to the US Operation Warp Speed program, has said the emergency clearance could be granted by US regulators by early February.”

      I’d be inclined to opt for the one-dose J&J jab, if approved, even at marginally lower efficacy.

  54. Marko says:

    Collins English translation of ’azar’ :

    1. (= suerte) chance , fate
    2. (= desgracia) accident , piece of bad luck

    Slang : shit-show

  55. Marko says:

    This data, if accurate, suggests to me that the Pfizer vaccine provides near-complete sterilizing immunity, at least for a time :

    In the first week after vaccination, you’d expect the vaccine to have little impact on infection rates. Most of the protective effect would have been seen after 10 days or so.

    1. Marko says:

      On second thought, I have to temper my enthusiasm about this data. It’s possible that temporarily heightened innate immunity is responsible for some of the protection so early after vaccination. I think we need to see the data from two weeks post-vaccination and beyond to have confidence that a vaccine-induced adaptive response is responsible for the protection against infection.

  56. Marko says:

    On the transmissibility/immune escape of the SA variant :

    “…Using globally available data, we calibrated an SARS-CoV-2 modelling framework the South African pandemic and evaluated the novel variant for potentially increased transmissibility or immune escape. Assuming complete cross-protection, we estimate 501Y.V2 is 1.50 (95% CrI: 1.20-2.13) times as transmissible as previously circulating variants. Assuming instead that 501Y.V2 is identically transmissible, the new variant evades 21% (95% CrI: 11-36%) of previously acquired immunity. Reality may lie between these extremes, with an intermediate increase in transmissibility and mildly imperfect cross-protection from past exposure. Though our analysis does not identify where on this spectrum 501Y.V2 lies, the entire range has serious public health consequences…”

    1. Chris Phillips says:

      Thanks, that’s interesting. Obviously more data are needed, but it’s interesting that the estimate for increased transmissibility (on the assumption of no immune escape) is so similar to that for the UK variant.

      I hadn’t seen a quantitative estimate of the increased transmissibility before. In a sense I am relieved it is similar to the UK figure, as any seasonal variation would be expected to be working against the South African variant at the moment.

      1. Marko says:

        What scares me is that they estimate a cumulative attack rate for the 20-49 age group at ~75% in mid-Oct, before the new variant had made much headway. If immune escape is a mechanism in play, you can imagine the herd immunity threshold creeping up from that already high level. This is similar to what is happening in Manaus, Brazil , where they have a new outbreak after thinking they were at or near the HIT at an estimated seroprevalence of 70% or more , and are also now dealing with a variant with immune escape potential.

        If this potential escalation in the HIT comes with a similar IFR among new cases, i.e. if reinfections are suffering severe disease and dying at the same rate as the never-infected, that would be very bad news. It would suggest that CoV2 may never become the new common cold coronavirus, as has been my hope , but rather will be one that we’ll have to battle with new vaccines like we do for flu, indefinitely.

  57. Chris Phillips says:

    Here is a Reuters report on the latest results for the Sinovac trial in Brazil, from a press conference in Sao Paulo given by state officials and representatives of the Butantan research institute:

    And here is a roundup of the various claims about the efficacy of the vaccine:

    It seems the efficacy varies wildly depending on the severity of the disease – “they split the cases in six categories: asymptomatic, very mild, mild, two levels of moderate, and severe — the first two not requiring medical assistance.”

    They said that for mild, moderate and severe cases the efficacy was 78% (a figure already announced) but when very mild cases were included it dropped to 50.38%. There were no severe cases among the vaccinated, but the number was small and not statistically significant.

  58. Marko says:

    Israel is world-beating on targeting the at-risk for vaccination :

    “….73% of Israelis who are over the age of 60 or who have other high-risk factors have already been vaccinated with at least one shot…”

    Meanwhile, the US is probably the world leader in vaccinating 20- and 30-something desk-jockey administrative staff at elite medical institutions. So we can be proud of that.

  59. Marko says:

    Possibility of a new fast-spreading US variant in Columbus, Ohio. No sequence data released yet, though :

  60. Chris Phillips says:

    There’s apparently a study of reinfection in the UK, discussed in a Nature article entitled “COVID reinfections are unusual — but could still help the virus to spread”. (I am not including a link as comments containing links tend to be “held for moderation” and then to disappear.)

    The report is supposed to have been published today on medRxiv, but I can’t see a link to it in the news reports and it doesn’t seem to be showing up on the site’s own search engine.

    It’s difficult to understand the Nature report, as it talks of 44 “possible reinfections” but says that only 2 of them have been confirmed by “more stringent tests” (unspecified). I can’t make sense of the figures in the article, but in different places it talks of either of 83% or 99%+ protection – perhaps reflecting numbers for asymptomatic versus symptomatic reinfection, though it’s not clear. It speaks of the protection lasting “for at least five months”, but as that’s also spoken of as the length of the study, presumably the average period to reinfection was less.

    1. Mariner says:

      Depends to some degree on what is classed as a suspected infection in the first wave, I suppose.

      At lot of the data is based on untested cases back then so, if they class any spell of fever or coughs/colds as likely caused by Covid-19, it might make many of the suspected reinfections, just first infections.

      1. Chris Phillips says:

        The Nature article says “Participants underwent blood tests for SARS-CoV-2 antibodies and PCR tests for the virus itself every two to four weeks.” So I would hope a prior positive test of some kind was a criterion for reinfection.

        But I still can’t see the preprint, where presumably the definitions are explained. I don’t know why news services has such an aversion to linking to their sources (unless they are frightened it will make it too easy to check the accuracy of their reports – which I can certainly believe in the case of the BBC!).

  61. Chris Phillips says:

    When the news about the new UK variant was released before Christmas, it was suggested that it was no more deadly than other types but “up to 70%” more transmissible. It was rightly pointed out that this was likely to result in far more deaths than a more deadly but no more transmissible variant.

    Strangely, it has been announced today that it may in fact be up to 50% more deadly. But also today an estimate has been published that over a two week period the number of coronavirus samples from England consistent with the new variant had actually decreased slightly as a percentage of the whole, from 61% to 60%. (This seems to result from a combination of decreasing prevalence in the areas where it has been most concentrated – London and the East of England – combined with continued growth elsewhere.)

    1. Marko says:

      Here’s the Nervtag report :

      “Based on these analyses, there is a realistic possibility that infection with VOC
      B.1.1.7 is associated with an increased risk of death compared to infection with
      non-VOC viruses.”

      Their “realistic possibility” phrasing falls between “unlikely” and “likely or probable” on their confidence scale. Still, things are moving in the wrong direction for my tastes. I’ve been hoping for some evidence that the fast-growing variants are LESS deadly relative to WT.

      No mention of reinfections in the Nervtag report.

      1. Chris Phillips says:

        I hope they’ll be devoting some time in the next bulletin to how “substantially increased transmissibility” can translate into a decreasing percentage of cases that are consistent with the new variant in London and the East of England. And they are quite large decreases – from 81% to 70% in London and 78% to 59% in the East of England.

        1. Marko says:

          Yes, that is odd. I’m now more inclined to trust the transmissibility data coming from the other countries with the UK variant than the UK data itself. The increased mortality figures look to be another jumble in the making. Any time BJ announces something, watch out!

        2. Marko says:

          Do you know of a good site that publishes an ongoing crude CFR graph for countries like the UK and Ireland that have high prevalence of the variant? It’s an imperfect measure, to be sure, but if the variant is that much more deadly it should be showing up there.

          I have to assume they’re carefully taking into account the effect of overloaded and understaffed hospitals on death rates and subtracting that effect from any due to the variant. The crude CFR would be expected to trend upwards during very high infection rate peaks.

        3. Marko says:

          This thread by Theo Sanderson proposes an explanation for the conflicting transmissibility data. Not definitive, but might be part of the story :

          1. Chris Phillips says:

            Thanks. To a non-expert that has the ring of truth, though it would be nice to see the hypothesis worked out more quantitatively to see if it really accounts for the data. And to see how that dropout phenomenon would affect previous estimates of the difference in transmissibility.

            The part about the dropout rate increasing when infection rates are falling might also explain the other finding discussed recently, that the difference in transmissibility seemed to have fallen in the most recent period. So that apparent fall may not be real.

            I suppose NERVTAG is right to be cautious about the increase in fatality rate. However, looking at the daily UK hospitalisation figures, they don’t seem to have been falling in line with the decreasing number of positive tests recently, which would be consistent with larger hospitalisation and fatality rates for the new variant (but no rise in the rate of deaths per hospitalisation).

          2. JS says:

            Latest numbers from SSI in Denmark can be found here:
            Note that these numbers are based on sequencing, so not directly subject to the effect mentioned in the thread above.

          3. Marko says:

            Thanks, JS. It looks like the variant share in Denmark is still increasing at ~9% per day, so consistent with a transmissibility increase of 50% or so, depending on what interval multiplier you choose. It’s hard to argue now that a significant transmissibility increase is not real, but, amazingly, “Earth’s Virology Professor” , Vincent Racaniello, continues to do so and likely will until they pry the microphone from his cold, dead hands. His last words : “Founder effect”.

        4. Marko says:

          “Danish officials, crunching similar data slightly differently, estimate that it is about 20 to 50 percent more contagious than the original in their country, although they say their numbers are still so small that estimates may be inexact.”

          That’s a good, conservative statement. They’re probably being more circumspect because of the reactions to the inconsistent reporting of the UK numbers.

          1. JS says:

            If you search the website you can find various documents describing their analysis. Latest is this
            That one links to:
            Various reports here:

            They do comment on the lower estimate of the increase in transmission. Part of the difference is due to an assumed generation time of 4.7 days in the SSI study versus 6.5 days in the Imperial College study.

  62. Chris Phillips says:

    “[Moderna] today announced results from in vitro neutralization studies of sera from individuals vaccinated with Moderna COVID-19 Vaccine showing activity against emerging strains of SARS-CoV-2. Vaccination with the Moderna COVID-19 Vaccine produced neutralizing titers against all key emerging variants tested, including B.1.1.7 and B.1.351, first identified in the UK and Republic of South Africa, respectively. The study showed no significant impact on neutralizing titers against the B.1.1.7 variant relative to prior variants. A six-fold reduction in neutralizing titers was observed with the B.1.351 variant relative to prior variants. Despite this reduction, neutralizing titer levels with B.1.351 remain above levels that are expected to be protective.

    The two-dose regimen of the Moderna COVID-19 Vaccine at the 100 µg dose is expected to be protective against emerging strains detected to date. Nonetheless, Moderna today announced its clinical strategy to proactively address the pandemic as the virus continues to evolve. First, the Company will test an additional booster dose of its COVID-19 Vaccine (mRNA-1273) to study the ability to further increase neutralizing titers against emerging strains beyond the existing primary vaccination series. Second, the Company is advancing an emerging variant booster candidate (mRNA-1273.351) against the B.1.351 variant first identified in the Republic of South Africa.”

  63. Edward R Murrow says:


    Transcript of a webcast recorded on 5 January 2021 by Edward R Murrow III, grandson of legendary WW2 London CBS correspondent ED MURROW (1908-1965):

    This is London. I am standing on a rooftop overlooking London and at the moment everything is quiet. For reasons of national and personal security, I am unable to tell you the exact location from which I am speaking, for, under British Government Lockdo’n Restrictions, broadcasting at normal speaking volume without a face mask from an elevation above street level is illegal, in order to STOP the SPREAD into, onto and unto the street below by an unforeseen downdraft of wind.

    Over to my left is the great Dome of St Paul’s Cathedral. To keep the ENEMY at bay, worshippers are patiently queueing at a statutary distance of two metres apart, all wearing statutary face masks, in a historically unique display of National, Secular and Public Health England solidarity.

    Once the devout worshippers are inside St Paul’s, the daily service nowadays invariably begins with the newly normal traditional chant of HANDS, FACE, SPACE, uttered in unison by the entire congregation, continues with the newly re-worded Lord’s Prayer that begins, “Our Father who art in heaven, lead us this day out of our daily spread…” and ends with a rendition of Bunyan’s timeless hymn, “Onward Christian Self Isolators.”

    The great shopping thoroughfares of Oxford and Regent Streets, closed until further notice under Lockdo’n restrictions, stretch out below me, silently empty but for that unforeseen draft of wind, now gusting horizontally along the streets, silently dispersing the ENEMY into every nook and cranny and unto every door handle, letterbox and brass door knocker of every business, finance house, entertainment venue, retail outlet and domestic household throughout the Great City of London.

    For since Prime Minister Borys Pflogiston’s sombre announcement yesterday evening of LOCKDO’N 3 Tier 4, the Great Nation of Britain stands secured indeterminably against an ENEMY now told by British Science to be fifty percent more mobile than before, such is the ever present danger of the ENEMY the British Government declared war against on behalf of the Entire NATION, ten long months of blood, sweat, phlegm and tedium ago.

    Thanks to the Brexit Treaty that came into force one hour before midnight on New Year’s Eve, plucky Britain now stands alone against the ENEMY, a sceptred British Isle now no longer a piece of the main. Europe, ask not for whom the bell tolls, it tolls for thee.

    British Science can now move forward at speed, as in the formative years of long ago Great British Science of Great British Scientists like Newton, Boyle and Faraday, a BRITISH Science now unencumbered by continental laissez faire, cri du couer or je ne sais quoi, a BRITISH Science now boldly and imperturbably dispensing with the universal perfidy of external review by judgemental foreigner peers from nations with a less longstanding tradition of scientific excellence than the Great Nation of Albion Britain.

    So that at breakneck speed the latest ALBION BRITISH SCIENCE, hypothesised, researched and internally reviewed by ALBION BRITISH SCIENTISTS, is rapidly deployed nationwide, in the nationwide move to the restrictive but necessary rigour of ALBION BRITISH Government LOCKDO’N 3 Tier 4: STAY AT HOME, in order for The NATION to STAY SAFE, SAVE LIVES and STOP the SPREAD of the invisible mutant ENEMY mobilising inexorably north, west, south and east into, onto and unto every far nook, cranny, door handle, letter box and brass door knocker of the GREAT ALBION NATION.


    Down below me and over to the right I can clearly see Trafalgar Square, where stands the mighty monument to Lord Nelson, heroic victor over the navy of the French Emperor Napoleon Bonaparte, in the year eighteen hundred and five, a pinnacle of three centuries in which Britannia truly did Rule the Waves

    And down in the great square built to celebrate the great victory at Trafalgar, I can see a small group of dissenters, placards aloft, clearly violating government laws which, I understand, make illegal gatherings in the open air, at which dissenters infringe the governmental guideline about wearing face protection and maintaining an interpersonal distance of two metres in order to STOP the SPREAD.

    At this distance, I cannot make out the slogans on the dissenters’ placards. The dissenters will no doubt be protesting against government restrictions on Britons’ liberties, such as those I have just mentioned, restrictions deemed necessary to maintain the conduct of the War against the invisible ENEMY that is silently seeping into every nook, cranny and crevice of the NATION.

    Now, on personal order of the Home Secretary, a black maria arrives to accost the dissenters, who are duly escorted inside the back double doors of the law enforcement vehicle and taken away to the nearest state penitentiary, to be charged with the crime of protesting against restrictions on the right to protest. All due to that silent invisible enemy that, even in a society’s free, open and democratic fresh air, now has deadly capacity to spread into every nook, cranny, crevice and receptacle of the NATION.

    Yes, fellow Americans, here in the crucible of democracy, font and fount of Magna Carta, Habeas Corpus and the Englishman’s Castle, I am broadcasting of a law enforcement service administered by a Home Secretary known variously throughout Westminster and Whitehole as Nanny of the Nation, Queen of the Non-Sequitur and the Glueless Pritistick, who, I am reliably informed by a confidential source inside the Home Office, will later this evening once again gravely issue the latest non-sequitur…

    “We’ve seen our police officers yet again do incredible work to ensure that they help to stop the spread of the ENEMY… We ask everybody to be conscientious – we all know the regulations and the guidance, we have brought these measures in to save lives and to prevent preventable deaths.”

    And I am reliably informed in confidence by that same Home Office source that tomorrow the Nanny of the Nation will join forces with the Minister of Health, Mister Han’cock, to attend to further reinforcing the walls of Fortress Britain, not only to keep the ENEMY out but to keep Britons patriotically IN.

    For measures are being contemplated to fight the ENEMY’s latest mutant threats at airports, at seaports and, in cases of illegal re-migrants, on the beaches. Suppression of ENEMY mutant variant activity demands closet viral fifth columnists, deserters, and even those key worker heroes essentially leaving the FORTRESS on Essential War Work, must fill in an online Exit Permit form in triplicate, requesting sanction to depart the shores of the sceptred isle and giving justifiable reason for fleeing the Beloved Mother Country.

    Upon return, Essential Workers, returning fifth columnists, deserters, and any other miscellaneous gone AWOL public health emergency shirkers, must fill out an online Entrant Permit form in quintuplicate for inspection by the newly formed State De-toxifying service, an offshoot of the State Armamentarium founded last year to tackle History’s Worst Ever Emerging, Developing and Rapidly Escalating Public Health Crisis.

    Any deviant form filling will be met with on the spot arrest, conviction and sentencing to up to ten years in a state penitentiary, and, in due course, transfer to one of the proposed new Labour and Re-Education Camps, where instruction will be given in the old fashioned virtues of hard work for little reward on an unlimited hours contract, directed to the gain of those upstanding and more worthy contributors to society, who make regular donations to the needy and the less advantaged, and also pay regular and significant contributions to funding of deserving ruling governmental party causes.

    Meanwhile, I am reliably informed by my Home Office source, upon satisfactory completion in quintuplicate of the requisite online Entrant Permit application, returning Essential Travellers, shirkers and deserters will be escorted forthwith from airports, seaports and beach landing craft to pre-booked Quarantine Hotels for ten days detention.

    Upon arrival, a source from the Ministry of Health confidentially informs me, Essential Travellers interned at Quarantine Hotels will be segregated from returning deserters and shirkers in the hotels’ Penthouse Facilities, whereas deserters and shirkers will be accommodated on the hotels’ more modest lower and, in some cases subterranean, floors.

    A grateful Nation will be reassured to know detained internees will be subject to regular hygiene inspections to ensure the ENEMY is not being harboured within their suites, rooms or subterranean interrogational Viral Profiling Units, the cost of which a Grateful NATION will cover for Essential Travellers, whereas shirkers and deserters will of course need to foot the seventeen hundred and fifty pound bill from their own resources. A small price to pay for the privilege of returning to the safety and security of Greater Germ Free FORTRESS BRITAIN.


    Now let us move on, from a Home Secretary with powers of reasoning forged on two lesser courses at two lesser universities. Below me to the right sits Whitehole, deserted home of the Great Ministries of the British Government, where, zooming in and out relentlessly, civil servants and public health officials have been contingency planning from home ceaselessly from dusk to dawn to secure fallback positions in event of an even more catastrophic attack by the invisible ENEMY, that remains such a dire, deadly and deleterious threat to the safety of the ENTIRE NATION.

    Should LOCKDO’N 3 Tier 4, STAY AT HOME not do the trick, sources close to government have revealed that Prime Minister Borys Pflogiston will order immediate escalation to LOCKDO’N 4 Tier 5: STAY IN YOUR ROOM. Contingency plans are already in place involving airlifting in food to households, supply by drones and the ministrations of an Amazon Prime Minister subscription, available via an interest-free government loan under the Subscribe to Eat In scheme.

    My fellow Americans, the situation on the British side of the Atlantic Ocean remains grave. If the ENEMY occupying every nook, cranny, alleyway and blind alley of the great British NATION prevails, a dark age will truly be upon the NATION, an age upon which the British Government, under the self-professed libertarian leadership of Mister Borys Pflogiston, will have no option but against all instincts to declare the option of last resort – LOCKDO’N 5 Tier 6: STAY IN BED.


    And so as ordered, the Great British nation will all fall into a great synchronised sleep, as if medically sedated, remotely clinically monitored and fed by drip. Only stirring some indeterminate time later… To the sound of distant car doors slamming, tyres screeching… aeroplane and helicopter engines powered at full throttle… helicopter blades whirring and the vapour trails of single-engined jets disappearing into the deep blue yonder.

    And stretching sleep away from within quilted pyjamas, an awakened people will look around their households… And see that everything is gone… Furniture, appliances, devices, curtains, soft furnishings, crockery, cutlery, utensils, bicycles, scooters, cars, lawnmowers, tools… The lot. Even the family silverware, for families fortunate enough to have had any family silverware left to preserve. Electricity turned off remotely at the Smart meter, no running water.

    And all outside desolate too – rolled over wheelie bins, street lights uprooted, traffic lights all dead… Shops all boarded up… Everything all overgrown… The odd hungry dog and a feral cat chasing a scurrying rodent the only living things to be seen.

    And as the sound of helicopter blades and private jets recedes to the merest hum, the children will come out of their bedrooms too, and say… “Mummy, Daddy, there’s nothing left, everything’s GONE! WHERE’S it all GONE TO?”

    And Mummy and Daddy will look each other sheepishly in the eye and say, “Oh Dear, we must have nodded off… And left the Man in the Moon to nip down and take it all away while we were all asleep…”

    By now it will be cold and dark, apart from the light of the new moon and a few twinkling twinkling little stars. And in return, the children will look up at the night sky and say, “Yes, we can see, we can see very clearly for miles and miles – everything must be up there, up in the sky… where you always did tell us things sometimes ended up…”

    “…In our bedtime stories before we started to grow up… and started to work things out for ourselves… where the fairy tales, the moonshine and the things that go bump in the night all come from and… eventually all go back to. But it’s all right, we’ll all live happily ever after anyway, won’t we? Just like you always told us… Do as we’re told and nothing will ever go seriously wrong, will it?”


    Now, as darkness falls and the street lights below flick on, here in the great city of London on January five, twenty twenty one, it’s time for your presenter, Edward R Murrow III, to wind this webcast up. Overhead I can hear the sound of what, bizarrely, seems very like the anti-aircraft fire my grandfather used to hear night after night from this very rooftop all those wartime years ago. The rest, as they say, is history.

    Talking of history, the online encyclopedia, Wikipedia, tells of Louis Pasteur, the French chemist and microbiologist, who in the nineteenth century first observed the simple, yet profound, phenomenon of optical activity, nowadays known to chemists around the world as chirality, who propounded germ theory, and who gave the world vaccines for anthrax and rabies, saying, in translation from French to English, “In the fields of observation, chance favours only the prepared mind.”

    Wikipedia also tells of the Latin phrase “Virtutis Fortuna Comes” being the motto of an RAF base at East Fortune, East Lothian, Scotland, operational in the First World War and between the years nineteen forty and nineteen forty seven.

    And of a similar Latin phrase as motto of the ancient Northern family of Turing, whose written history goes all the way back to the year thirteen sixteen AD.

    Good night America, and good luck Old Fortress. They say fortune does tend to favour the bold who work things out for themselves, draw their own conclusions and act accordingly.

    In other words, fellow Americans, descendents of our forebears who boarded sailing ships and headed for the New World, either by choice or sad compulsion. Known generally as Fellow Americans. Who Carpe Diem, as ever.

    As for the stay-at-home stick in the muds left behind here in Merrie England, as the old sayings go, gather ye rosebuds in May, ne’re cast a clout before May is out, and Carpe Diem too for all you’re worth.

    Seize the Day – for the day sure won’t be coming our way again. Same old same old doesn’t do twice. Deep down, we’re all born knowing what adds up and what doesn’t.

  64. Chloe Dawson says:

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