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J&J and Novavax Data

Suddenly we have a lot more vaccine efficacy data to discuss! Yesterday came an announcement from Novavax about trials they’ve been conducting in the UK and in South Africa with their recombinant protein vaccine, and today comes equally anticipated data from J&J (Janssen) on their adenovirus vector candidate. We’ll have a look at the numbers in that order.

The full Novavax package should be coming out in a few days. But what we know now is that in the UK trial (roughly 15,000 people), the vaccine showed 89% efficacy. And the company says that around half of these participants were infected with the B.1.1.7 variant, so these are excellent results against that one and against “coronavirus classic”. The South African trial was smaller (around 4,000 patients), and the data have correspondingly more scatter in them. But the readout is clear: the vaccine is less effective against the B.1.351 variant, perhaps around 50%. Almost all the cases in this trial were from that one. Novavax says that they have already begun working on another protein vaccine to be used as a booster for those who’ve received another one, and that’s good news. Not least because Novavax also noted that they were seeing people infected with B.1.351 who had already been infected with the earlier strains. There appear to have been no significant safety signals during the trials (an initial report of volunteers being hospitalized appears to have been mistaken). Keep in mind that there’s another trial of the Novavax candidate still underway here in the US as well – the question is now how many countries will authorize the vaccine based on the data we have in hand and when this vaccine can be rolled ou

Now to J&J – then we’ll discuss some implications. Their data for the one-shot dosing protocol show 72% efficacy in the North American volunteers, 66% in Latin America, and 57% in South Africa. That last one has to be another B.1.351 effect. There were also no safety signals – adverse events were actually more frequent in the placebo group. There were also no real differences across different age groups, which is very good to see.

Now, these numbers from J&J are definitely lower than the Moderna and Pfizer/BioNTech vaccines. I wish that they were higher. But this is the landscape we have, and given the development timelines, I think we’d better get used to this it, because now the biggest and most advanced players have reported in. Broadly speaking, it looks like the mRNA vaccines have definitively higher efficacy, but we have to remember that their trials were run before the new variants got much of a foothold. We have in vitro data about how they might respond to B.1.1.7 and B.1.351, but so far we have no real-world efficacy reads. For all we know, the Moderna and Pfizer/BioNTech vaccines also come down to 50-60% efficacy against B.1.351.

But at any rate, with a 95% value (or the 96% seen with Novavax against “coronavirus classic”), you can have a good deal of confidence that you’re going to have solid real-world effects. When we see numbers like J&J’s, or (especially) AstraZeneca’s (the EMA says this morning that overall efficacy for that one is 60%), or probably everyone’s against B.1.351, we have to look more closely at the clinical outcomes. You may not be able to prevent so many people from going PCR-positive, but can you keep them out of the hospital? Out of the morgue?

J&J is saying that overall, their vaccine was overall at 66% efficacy at preventing all “moderate to severe”coronavirus infection (updated this), but 85% effective at preventing “severe disease” requiring hospitalization. They had a conference call this morning, and my impression is that this statement wasn’t clarified very much (we’ll hear more next week, I believe). But they also say that there were no coronavirus deaths at all in the vaccinated group. So the real-world effects are nothing to turn up one’s nose at – if this had been the first vaccine to report, we’d have been setting off fireworks. Similarly, it looks like the AstraZeneca/Oxford vaccine, for all the problems in figuring out its dosing and its efficacy numbers, also does a good job of preventing severe disease. We don’t have data on severity of disease from the Novavax team yet; I hope that we see it very soon.

Given the advent of the new variants – and the threat of seeing more of the same – all of these vaccines are going to have a part in beating back the pandemic. The AZ/Oxford, J&J, and Novavax vaccines do not have the ultra-cold-chain distribution problems that the mRNA vaccines have, and thus can have greater penetration into areas with less infrastructure. We also have to remember that these vaccines all have different manufacturing processes at many of their stages, which means that ramping them up doesn’t turn into a zero-sum cage match.

There are two more factors to consider. I keep coming back to the idea of antibody maturation via clonal selection of B cells, and I note that J&J says that the protection afforded by their vaccine did increase over time. That’s working in our favor with all the vaccines, but we have no idea (yet) if one of these might do a better job with this process than others. As far as I know, the only way to know is to keep collecting data to see if such differences emerge. The other thing to keep in mind is (as mentioned above) the possibility of retooling these agents to better deal with the new variants. My impression is that this would be easiest for the mRNA and recombinant protein vaccines (that is, for Moderna, Pfizer/BioNTech, and Pfizer) and harder for the viral-vector ones (J&J and AZ/Oxford). But we’ll need to clear up the regulatory framework on this – you’d think it should be much more like the clearance of (say) the yearly flu vaccine and not like coming in with a completely new vaccine.

It looks like we’re going to need these updates. The B.1.351 variant is clearly pushing the efficacy numbers down for the first crop of vaccines, and there is no reason whatsoever to think that the process will end there. We’ve got to stay ahead of the damn viruses however we can.

272 comments on “J&J and Novavax Data”

  1. Rajesh Krishnan says:

    I think you meant: “Moderna, Pfizer/BioNTech, and Novavax” not “Moderna, Pfizer/BioNTech, and Pfizer”.

    At some point, I hope you address questions on vaccines that are not targeting spike proteins, such as this one from Entos: .

    (I have no connection to Entos or the industry)

  2. Matt says:

    Great summary Derek. How do these results mesh with B cell and antibody evolution that you discussed in your 19-Jan post?

    Would we expect (certainly hope!) to see these efficacy numbers against B.1.351 improve 6 months after vaccination after some B cell and antibody evolution?

    1. Marko says:

      Affinity maturation alone would be expected to work in favor of this. Epitope spreading could add additional benefit. Working against that is antibody waning, particularly in the nasal mucosa where the infection takes hold, if “infection” or “symptomatic infection” is the topic of concern. For my money, if symptomatic infection doesn’t lead to severe disease, we’re home free, new variants or no. Time will tell, I suppose.

  3. Bryan says:

    “My impression is that this would be easiest for the mRNA and recombinant protein vaccines (that is, for Moderna, Pfizer/BioNTech, and Pfizer)”

    Did you mean Moderna, Pfizer/BioNTech, and _Novavax_?

  4. Drew says:

    Didn’t Novavax report 96% efficacy vs “coronavirus classic”, not 90%?

    1. JohnFvr says:

      Yes it did.

      1. Drew says:

        Looks like this is now corrected in the article.

  5. Rob says:

    With the new strains and the inevitable drift, it would be nice to have some effective therapies. Anyone know how the Merck drug is doing in trials? Plus it’s kind of amazing they aren’t using the monoclonals more.

    1. An Old Chemist says:

      @Rob: The progress of the Merck’s oral antiviral MK-7110, which is being developed in collaboration with Ridgeback Biotherapeutics, is described here:

      1. Rob says:

        Thanks, I saw that. I was hoping someone had heard rumors. I think they are supposed to unblind in a couple months (?).

    2. Joshua Scholnick says:

      Who is “they” and why are you amazed about monoclonal antibody use rates?

      1. Rob says:

        Doctors treating covid patients, who until recently were only using 20% of available monoclonal supplies. The drugs need to be used early, meaning outpatient, and you end up treating a lot of people who wouldn’t have needed them, but it’s not like there are lots of good alternatives. Among vulnerable populations, they reduce hospitalizations by up to 70-80%.

  6. JerryC says:

    When a vaccine doesn’t perform well in South Africa, is it known whether that’s due to the B.1.351 variant, to high HIV prevalence in SA, or to both? Has that been sorted out?

    1. Dan Ramirez says:

      They stated that 90% in South Africa had the variant

    2. Thomas Lumley says:

      They reported the efficacy in HIV negative people and it was still lower

      1. confused says:

        Do you mean HIV positive was lower? It doesn’t really make sense that having HIV would make a vaccine work better…

        1. Daniel says:

          Yes, there was no efficacy in HIV positive people (there were actually more cases in the vaccine group).

          1. Martin says:

            They said 49% efficiency for South Africa HIV positive group didn’t they? And 60% effective for HIV negative group when separated out.

  7. hardnox fort says:

    Also, the B.1.351 variant is reported as having been able to escape convalescent patients immunity in these studies. Or in other words: Even if the vaccines are less effective against the variants than the original, the effect still seems much more advantageous than trying to gain immunity by way of Corona-parties, which could end up as a semi-annual date, with potential for a severe hangover!

    Since partial escapes are such a tricky thing to proove – much less stratify in severity of illness – particularly the J&J results from 28 days to 49 days is very encouraging since it also covers B.1.351. Trying to extinct a potentially asymptomatic spreader with known zoonotic reservoirs is a championship in futility (At least mink have proven a 2-way contagion. Trying to gain confirmation of more 2-way contagiousness is getting into ethical concerns, but at least cats and hamsters are very susceptible!). Best case is that the inevitable escapes are causing less severity symptoms and that at least seems to be the case for the vaccines.

    1. Marko says:

      “Trying to gain confirmation of more 2-way contagiousness is getting into ethical concerns, but at least cats and hamsters are very susceptible!)”

      I’m waiting for the next deer season to give us a hint about animal reservoirs. It’s now known that CoV2 infects white-tailed deer, and deer hunters, upon success, get “up-close-and-personal” with their prey when they gut them.

      1. John says:

        True but at that time the reservoir is generally not breathing any more

  8. Carlos says:

    50%+ efficacy for a vaccine against a viral infection is still pretty good. I think we need to completely flood the planet with the vaccines; all of them. Let’s get as many people vaccinated as possible with something that works to some degree, even if it’s “only” 66%. We need to do this before the next viral cycle that will start in the Fall (at least in Northern Temperate climates). We can sort these product selection issues out later as we see more data, especially against variants.

  9. Jung Choi says:

    Doesn’t affinity maturation require persistence of antigen, albeit at declining levels? Once antigen is truly gone, no further affinity maturation can take place, per my understanding.

    1. Marko says:

      Immune cells can carry antigen around for quite a while, sort of like a lucky rabbit’s foot. Some have proposed that low-level viral replication may occur in the gut for 6 months or more, but I don’t think it’s been conclusively proven.

      1. Andres says:

        Is that in general for all viral infections or in this case for Coronavirus?

        If the former, it might be nature’s way of saying “it is not a bug, it is a feature”

        1. Marko says:

          I don’t think enough is known in most cases. Detecting hidden depots of very low levels of either antigen or competent virus in vivo is a tricky proposition, though the methods are constantly improving.

          Hep B is one obvious example. If you’re infected as an adult and “clear” the virus, you’re generally immune for life, but we know that you still carry the virus at low levels. One way we know is that if you’re ever put on strong immunosuppressants, there’s a good chance for reactivation.

          I tend to believe, as you suggest, that in many cases it is a feature rather than a bug.

  10. Franksnbeans says:

    “Broadly speaking, it looks like the mRNA vaccines have definitively higher efficacy,” Recombinant protein vaccine from Nvax had 96% efficacy against covid classic, beating both Pfe and Moderna against that strain. And they generated this value using a significantly older patient population than either of them.

    Now consider the need for a multivalent vaccine and how that changes the landscape going forward. Nvax positioned beautifully with their technology…moderna/pfe not so much.

    1. Doug H MD says:

      apples please meet oranges

      1. Franksnbeans says:

        Yes, Derek was comparing apples to oranges.

  11. Bash says:

    Since B.1.351 and B.1.1.7 has already been identified in many countries, is it not safe to assume that, just like classic SARS-COV-2 emerged, in a year all COVID-19 will be due to B.1.351 and B.1.1.7?

    Israel is reporting that B.1.1.7 has taken over there – that essentially took just a few months. Isn’t it an inevitability that B.1.351 will dominate in many places as well?

    Needing to boost the whole world over and over again every 6-12 months seems daunting… like borderline impossible

    1. Marko says:

      “Needing to boost the whole world over and over again every 6-12 months seems daunting… like borderline impossible”

      The profit motive routinely works to convert the impossible into the possible, often unnecessarily so.

      1. Doug H MD says:

        no mention of original antigenic sin?

        1. Marko says:

          “In the world of profits, ‘sin’ does not exist.” (Introductory Economics, U. of Chicago Press, 1972)

          1. Doug H MD says:

            But seriously, is anyone talking about this issue ?

          2. Marko says:

            What issue? OAS ?

            The only thing I can say for sure is that nobody was talking about OAS when you raised it in the middle of an unrelated thread, and that I simply used that lemon to make some lemonade.

    2. confused says:

      Well flu vaccines are annual…

      And anyway, immunity isn’t 100% or 0%. Partial immunity might be enough for most people, maybe boosters would only be recommended for people over a certain age or something.

      And historically respiratory pandemics don’t last all that long, anyway…

      1. Barry says:

        “respiratory pandemics don’t last that long”???
        Tuberculosis goes on killing a million or more every year, as it has for decades.

        1. confused says:

          Surely it is endemic, not pandemic?

          Malaria is incredibly deadly too, and has been for millennia, but that does not make it a pandemic.

          I was talking about how respiratory pandemics like the 1890 “Russian flu” (possibly not a flu – now suggested to have been a coronavirus), 1918 flu, 1957 flu, 1968 flu, 2009 flu tend to last 1-2 years, whereas plague and cholera pandemics have lasted far longer.

    3. kamil says:

      Why should it be impossible? First of all it is unlikely to be 6 months because once the virus is under control there will be less pressure for new variants to develop, simply due to fewer infections. Secondly, we already vaccinate every child with more than a dozen different shots, provide high speed internet and modern health care to every single citizen (in the developed world at least), I do not see how this is much more challenging.

    4. Michael says:

      It just all depends. If it still shows efficacy against variants, widespread vaccination is still an awful big brake on the circulation of the variant and resulting emergence of new variants (presuming that there is efficacy against transmission). Protection against severe disease likely will be even more efficacious, so the hospital situation gets a lot less scary with a lot of the vulnerable population vaccinated.

  12. Vlad says:

    What about the inactivated vaccines? Would they, in theory, be less affected by S-protein mutations or are the non-S antibodies not that important?

  13. BeanCounter says:

    I hope I’m not wandering too far from this thread, but I would appreciate any answers that the more knowledgeable posters may have:

    Does anyone know how many doses of the Novavax product could be ready for distribution in Q1 ?

    The news for J&J is very encouraging, but it’s unclear how much they can really supply once they get approval from the US FDA.

    If AstraZeneca got approval soon, would its supply to the US be hampered by production shortfalls in Europe ?

    And finally, any chance that the FDA could approve Novavax based on the data it released yesterday ?

    It looks like there are three vaccines now that are at least good enough to keep people from getting severely ill from this disease and it makes no sense to delay one more day on getting them released to the public. It just seems like common sense, and we shouldn’t let the concern over vaccine hesitancy in some people block the rest of us from getting some protection from this virus.

    1. Britt says:

      I don’t think we’re expecting Novavax approval in the U.S. in Q1. The assumption had been (similar to AstraZeneca) that the FDA was going to wait for the U.S. trial results, which for Novavax I believe won’t be ready until April or so. Unless you’ve heard something different?

      (I also doubt they have a ton of supply yet– I believe the U.S. Novavax trial kept getting pushed back because they were having trouble getting enough supply ready just for the trial.)

      1. BeanCounter says:

        No, I haven’t heard anything different – just wishful thinking. Hopefully they’ll all get approved and we’ll have significant quantities being produced in April. It does seem like arrogance when we have good data from a UK study and insist on waiting months to complete a US study while this pandemic rages. Perhaps, due to quantities available, it won’t matter.

  14. debinski says:

    The other issue to keep in mind when comparing efficacy rates across vaccines (other than just the B.1.351 and B.1.1.7 variants) is the fact that the primary efficacy endpoints were defined differently across trials. For instance, Pfizer was essentially including all symptomatic COVID cases (+PCR and one symptom required) where J&J was including only moderate/severe COVID cases (moderate = +PCR and either 2 “ordinary” COVID symptoms [fever, chills, etc] or at least 1 respiratory symptom [respiratory rate ≥20 BPM, SpO2 >93% but abnormal, pneumonia, DVT, or SOB]). It seems likely that if J&J included all symptomatic COVID cases, their %s might be even lower, but I guess it could go the other way also. I hope their FDA briefing doc will include data on mild cases.

    1. Marko says:

      “It seems likely that if J&J included all symptomatic COVID cases, their %s might be even lower, but I guess it could go the other way also.”

      Agreed, but I’d be surprised if the relationship could go in the other direction. It only makes sense to me that , for example, 90% protection against all infection, including asymptomatic, is better than 90% protection against symptomatic, and so on, for 90% vs severe disease or death.

      It makes comparisons between vaccines difficult, for sure.

      1. Marko says:

        On second thought, I suppose it might be possible if protection against symptomatic infection depends more on antibody while protection against severe disease and death hinges more on cellular immunity. In that case, different vaccines could present with progressions in their efficacy numbers trending in opposite directions.

      2. Martin says:

        I think J&J is spinning it’s results a little to make it seem better. Novavax’s results are good and used stricter end points.

      3. Mandark says:

        This is something that should be immediately obvious, but I see direct comparison of these efficacy values everywhere – in the media, but also (what is more surprising) in experts’ comments. I find the J&J results very disappointing given that they only include moderate to severe disease.

        1. debinski says:

          I am basically arguing against my own argument (from above) but it may turn out there is little difference between J&J’s primary endpoint and Pfizer’s. What it really comes down to is how many cases had only 1 symptom of COVID (and does it effect the efficacy calculation to include them or not?). But the fact still stands that we can’t really compare across vaccines because of the differences in endpoint definitions. That could be addressed in the future with a meta-analysis.

  15. Gary Cornell says:

    It would be easy to construct a model which shows that epidemiological the J&J, single-dose vaccine should be used (and reserved) for “younger” people who might engage in higher risk activities. Doing this could have a disproportionate effect on R0. Also, I would suspect that, on average, younger people are less compliant at getting two doses of a vaccine anyway, though that is a gut feeling only…

  16. Bob Lacatena says:

    Looking at the J&J Phase 1-2a data, their two dose regimen (18-55 only, for now) seemed to suggest that J&J might get into the range of Moderna and Pfizer if they weren’t trying for just one dose, for the sake of managing the pandemic. They also started a 2-dose Phase 3 trial in the UK last year:

    I would not be at all surprised if they didn’t eventually modify things to say “1 dose for now, but when things settle down and there’s more supply, we can do two…”

  17. wco81 says:

    If you have to “settle” for getting the J&J or the AZ vaccine with lower efficacy, can you still get a booster vaccine shot later from the Pfizer, Moderna or Novavax?

    Or maybe a booster specifically targeting the newer variants?

    And still get the maximal efficacy possible?

    1. sPh says:

      That’s a very good question – I hope Mr. Lowe is able to address it at some point later in the year.

  18. Scott Frey says:

    Keep in mind that the efficacy reported for J&J’s vaccine is from *one dose*. J&J is also running a two-dose trial. It’s conceivable that two doses of the J&J vaccine will be as or more effective than two doses of the Pfizer/BioNTech or Moderna vaccine. An article in Stat today indicates that results from the two-dose trial are expected in summer or fall. That seems like an eternity now; but ultimately it might be worth the wait, especially for places that still can’t obtain enough of the other leading vaccines.

  19. Chris Phillips says:

    “J&J is saying that overall, their vaccine was overall at 66% efficacy at preventing all coronavirus infection, but 85% effective at preventing “severe disease” requiring hospitalization. … But they also say that there were no coronavirus deaths at all in the vaccinated group”

    The J and J press release says 85% against “severe disease” but 100% against hospitalisation and death (after 28 days). Not that I can see that their definition of severe disease leaves much scope for not being hospitalised:

    1. OC says:

      Sorry but I disagree. It leaves plenty of room to not be hospitalised:

      To quote from pg 15 of the protocol:

      “All cases meeting the moderate case definition and that include ≥3 signs and/or symptoms from the list of signs and symptoms will be evaluated by the Clinical Severity Adjudication Committee to determine if the case is severe/critical in their judgement.”

      Some of those signs / symptoms are:

      – Fever (≥38.0°C or ≥100.4°F);
      – Heart rate ≥90 beats/minute;
      – Shaking chills or rigors;
      – Sore throat;
      – Cough;
      – Malaise as evidenced by 1 or more of the following, Loss of appetite, Generally unwell, Fatigue, Physical weakness;
      – Headache
      – Muscle pain (myalgia)
      – Gastrointestinal symptoms (diarrhea, vomiting, nausea, abdominal pain);
      – New or changing olfactory or taste disorders;
      – Red or bruised looking feet or toes;
      – Respiratory rate ≥20 breaths/minute;
      – Abnormal saturation of oxygen (SpO2) but still >93% on room air at sea level*
      – Clinical or radiologic evidence of pneumonia
      – Radiologic evidence of deep vein thrombosis (DVT)
      – Shortness of breath or difficulty breathing.

      Plenty of scope to have multiple symptoms described above but not be unwell enough to need immediate hospitalisation.

      1. Chris Phillips says:

        Certainly, but I was looking at this part of the press release:
        “In the study, the definition of severe COVID-19 disease included laboratory-confirmed SARS-CoV-2 and one or more of the following: signs consistent with severe systemic illness, admission to an intensive care unit, respiratory failure, shock, organ failure or death, among other factors. Moderate COVID-19 disease was defined as laboratory-confirmed SARS-CoV-2 and one or more of the following: evidence of pneumonia, deep vein thrombosis, shortness of breath or abnormal blood oxygen saturation above 93%, abnormal respiratory rate (≥20); or two or more systemic symptoms suggestive of COVID-19.”

        Even “moderate” sounds nasty enough to me!

        1. Chris Phillips says:

          That definition in more detail is on page 14 of the protocol:

          1. OC says:

            With all due respect I’ve read the FULL definition. You appear to have missed the part where it extends to page 15 and specifically says:

            ““All cases meeting the MODERATE case definition and that include ≥3 signs and/or symptoms from the list of signs and symptoms will be evaluated by the Clinical Severity Adjudication Committee to determine if the case is SEVERE/CRITICAL in their judgement.”

            I.e. IF you have > 3 symptoms/outcomes that would satisfy the criteria for MODERATE disease then you can still be classed SEVERE with NONE of the symptoms / clinical outcomes mentioned specifically in the SEVERE list.

            That is why you had vaccinated candidates be classed as SEVERE and NOT hospitalised.

          2. Chris Phillips says:


            No, I didn’t miss that, because you had already posted something similar. Logically, it doesn’t extend the definition.

            But I think you are right, because the preceding sentence does imply that the committee can decide a case is not severe even though it satisfies the definition.

            In other words, the protocol gives a definition of what is severe, but then says the committee can decide a case is severe even though it doesn’t satisfy the definition, or that it isn’t severe even though it does.

            It seems like a funny way of going on, which leaves us not knowing what criteria were actually used. But it could explain how more cases could be “severe” than “hospitalised”. At least “hospitalised” is reasonably clear.

          3. OC says:


            I agree that the method they apparently used to determine the severity looks too subjective for my taste. I would have preferred them to rely on symptoms / clinical deterioration that can’t be skewed by individuals personal attributes. E.g. oxygen saturation, partial pressure, % of lung with ground glass opacity etc.

  20. Pere Camps says:


    Any mentions anywhere about getting “long covid” after being vaccinated? And after being vaccinated and catching the virus?

    Haven’t seen any mentions…


    1. expr says:

      I was going to ask this as well. Please put on you (astronomically long) list of future topics

  21. lizzy says:

    My thoughts on Novavax, specifically the South African arm of their study.
    4,400 participants only (so, how many dropped out?) Excluded both the 5% HIV positive and the roughly 1/3 of subjects who were seropositive to begin with. Now we have 1,400 in the placebo arm and 1,400 in the active vaccine arm. Primary endpoint symptomatic infection at only one week after 2nd dose. Efficacy was 60%, but just look at the confidence interval!
    (95% CI: 19.9 – 80.1) If you include the ~ 250 HIV positive individuals, the CI gets even worse: CI: 6.1 – 72.8)
    We seriously need better data

    1. Doug H MD says:

      well at least the CI did not include ZERO!

    2. Not-an-epidemiologist says:

      Yes. It might even be that the efficacy difference here is a trick of the low numbers (although this would be pretty unlikely). But these data do fit a general trend supporting a less-efficient immune response induced by the “covid-classic” spike against B.1.351.

      I’m still not convinced that this is enough to matter in the real world, in terms of severe disease trajectory outcomes. If I get vaccinated against covid-classic, am mildly symptomatic (and less transmissive) with B.1.351, and then resistant to both thereafter, I’m good. And, more importantly, that response is great on a population level — if vaccination massively reduces case fatality and decreases Re, that’s all that really matters.

      We don’t quarantine or lock down for seasonal influenza, so presumably if we meet that population-level end-point (i.e. containable levels of seansonal infection with an IFR around 0.01%) we’re happy. (I think we all accept that global eradication is not possible, at least in the short-to-medium term, right?) There is going to be a lot of interest in data coming out of Israel once they reach herd-immunity levels of vaccination.

      1. DataWatcher says:

        I think you’re right. It’s a little difficult to discern right now whether the apparent (implied) emphasis on “All infections are bad” among many public health spokespeople and policymakers will continue to prevail if, as you and many others have suggested, at some point the vast majority of infections result in mild or no symptoms. Is it simply that public health awareness has finally reached the level where it should always have been, or are we still in a kind of crisis-borne “phobic” mindset where we panic (for good reason right now) at the very word “COVID,” hence we”re not yet able to distinguish between the truly serious and the merely realistic? It’s not uncommon for people who have experienced trauma to react that way (e.g., people of my parents’ generation who survived the Great Depression and spent the rest of their lives literally saving pennies in jars for some dreaded emergency “in the future”); at what point will our public health policies look less like rational disease prevention and more like an outward manifestation of collective PTSD?

        1. Ancient Briton says:

          Re: “Are we still in a kind of crisis-borne “phobic” mindset where we panic at the very word ‘COVID’?”

          For the record, phobic mindsets not entertained under this family’s UK rooves. Late 60- and 50somethings would like 20plus and 20minus offspring to enjoy life’s opportunities, just like 60- and 50something once upon a time did at that age, not to see offspring part of younger generation lockdo’n for months becoming a year on end.

          90Something and 80something, known quite well by family of four, feel just the same, as reportedly do number of elderly neighbours, all part of older generation lockdo’n at home for months becoming a year on end.

          Shock horror – fact is nobody asked last March if we wanted to be kept safe and saved. At whatever cost. No thanks, even back then. We’ll take necessary precaution, take our chances and protect ourselves. The NHS can do its own protecting.

          Get it, Pipeline commenters? Quote 21 September 2020 from a UK Professor of Public Health, presumed not invited to join the UK Scientific Advisory Group for Emergencies (SAGE), in response to a BMJ article (2020, 370) entitled, “Covid-19: Do many people have pre-existing immunity?”

          “A long series of trials inoculating individuals with a range of viruses, including coronaviruses, and investigating who developed symptoms and became ill, consistently showed increased risk for those who were stressed.[1]

          These trials also showed that social connectedness protected against infection.[2] The findings have been corroborated in other studies.[3,4] The greater level of risk from covid-19 among populations at high risk for stress is entirely in keeping with the possibility that stress and social isolation play a role in diminishing immunity to this virus.

          The solutions of lockdown, social distancing and quarantine have created very great stress for a significant proportion of the population and an unprecedented level of social isolation for those most at risk, so it is perhaps not surprising that appetite is low for considering the possibility that preventive measures may have contributed to the pandemic.”

          FYI, Dear Pipeline Reader, ref [1] in the good professor’s response is an article by a distinguished American Professor of Psychology, reporting a talk entitled:

          “The Pittsburgh Common Cold Studies: Psychosocial Predictors of Susceptibility to Respiratory Infectious Illness,”

          …Given at an international conference of behavioural medicine held in Mainz, Germany, 25-28 August 2004 (International Journal of Behavioral Medicine, 2005, 12, 123–131).

          Meanwhile in the underworld at The Parish Church of Saint Martin Bladon, just across the river from Blenheim Palace, the graveyard’s most distinguished interree may plausibly be listening out aghast, as the nation goes forward unforearmed against unperceived threats for months becoming a year on end. What goes round goes round.

        2. confused says:

          What I’m concerned about here is the issue making the already deep sociopolitical divides in the US even worse.

          A lot of people at least here in TX are *already* not taking it seriously, and a lot of states have less restrictions than us (it’s not just tiny-population rural ones like South Dakota either – Florida is no-mask-mandate, though apparently some cities have ones they’re not allowed to enforce, and it’s the 3rd largest state in the US, larger than NY).

          So I don’t really expect a broad refusal to “return to normal”.

          What I am more concerned about in the “medium term” is resentment and division if some places retain mandates for a while after hospitalizations/deaths fall dramatically.

          (In the long term, it will just become part of the background anyway.)

          1. DataWatcher says:

            Personally, I’m less concerned about “deep sociological divides” and “resentment and division,” most of which were there already (just ask Gretchen Whitmer). My worry is that individuals “not taking it seriously,” along with states like Florida with their lenient enforcement of restrictions, will continue to be COVID “incubators,” so to speak, even if other people, and other regions of the country, succeed in lowering their numbers drastically — thus impairing our overall ability to begin to get the pandemic under control. Without a coordinated nationwide effort, in which we’re all more or less on the same page, any kind of widespread immunity (or even lowering of risk) will be extremely difficult to achieve.

          2. confused says:

            Well, if a vaccine provides really good protection against severe disease (I don’t care so much about very mild, common cold-like effects) then once everyone who wants it has gotten it, I’m not sure how much spread elsewhere matters, since vaccinated people will still be safe even if exposed.

            57% efficacy or whatever doesn’t sound great, but IMO it’s efficacy against severe disease/hospitalization/death that matters in the long run (AFAIK no one’s investing heavily in vaccines against the four common-cold coronaviruses).

            >>most of which were there already (just ask Gretchen Whitmer).

            Well, the divides themselves were of course pre-existing, but I really do think the political chaos of 2020 in the US was greatly exacerbated by COVID. The attempted kidnapping of Gov. Whitmer was post-COVID, so I’m not sure we can say that would have happened otherwise. In fact, former President Trump’s criticism of her and other governors over COVID measures has been blamed for inciting/exacerbating those events.

          3. DataWatcher says:

            Yes — although the reports continue to be somewhat confusing, from what I understand it sounds as if even the J&J vaccine, which apparently showed 85% efficacy against “serious” symptoms, showed virtually no hospitalizations (or deaths) at all. (I apologize if I’ve gotten something wrong here.) So at the very least, even if the new variants gain ground in the U.S. over the next few months, the pressure on hospitals and medical care resources should drop dramatically as more people get vaccinated.

            Of course, the wild card is still the likelihood of more (and more threatening) mutations developing if more of us become asymptomatic or mildly symptomatic carriers (and spreaders) after getting vaccinated. For me, anyway, that’s the most pressing concern: As people begin to feel less fearful, hence less likely to adhere to strict public health behaviors, the virus could easily continue to spread “sub rosa,” so to speak, until erupting all over again in a new, more deadly form. That’s one reason why I suspect that the much anticipated “return to normal” may not be what a lot of us would like it to be — we’ll have to keep masking and distancing, even if none of us are getting sick, just to reduce as much as we can the possibility of that kind of thing happening.

          4. confused says:

            >> So at the very least, even if the new variants gain ground in the U.S. over the next few months, the pressure on hospitals and medical care resources should drop dramatically as more people get vaccinated.

            Yes. And a huge proportion of the deaths (and significant fraction of the hospitalizations, though the age-bias is much less extreme than for deaths AIUI) come from a very small % of the population. Even if we need 80% for herd immunity (or really probably more like 60% since

            >>Of course, the wild card is still the likelihood of more (and more threatening) mutations developing if more of us become asymptomatic or mildly symptomatic carriers (and spreaders) after getting vaccinated. For me, anyway, that’s the most pressing concern

            Maybe, but I guess my question is, why don’t we really worry about this for the dozens of everyday respiratory viruses circulating? Is COVID “inherently” more dangerous, or is it just because we’re immunologically-naive to it?

            I mean didn’t stuff like measles kill most of whole generations when it hit totally-naive populations in the Pacific Islands? I am not sure the deadliness of a disease in a totally-naive population is any guide for what it will be like in a pre-exposed population.

            >> That’s one reason why I suspect that the much anticipated “return to normal” may not be what a lot of us would like it to be — we’ll have to keep masking and distancing, even if none of us are getting sick

            I really don’t see people in general doing that. If hospitalizations/deaths fall really low, 6 months after that keeping measures in place won’t be politically viable. Social (and economic) pressures will just be too great.

          5. DataWatcher says:

            ” . . . I am not sure the deadliness of a disease in a totally-naive population is any guide for what it will be like in a pre-exposed population.”

            That’s why we need to keep such a close eye on Manaus. The situation there still has to be fully sorted out, but it certainly looks as if any previous assumptions about “pre-exposed” vs. “naive” populations might have to be re-considered. Let’s hope that for some (as yet unknown) reason the situation there is anomalous, but alongside the reports of immune escape in B.1.351, it does not look encouraging.

          6. confused says:

            Well, what do we mean by immune escape? Are we just talking increased rates of reinfection, or severity comparable to no previous infection? IMO there’s a *huge* difference there.
            (Also, didn’t the discussion in the comments on the previous post basically suggest Manaus wasn’t that close to herd immunity to start with, unlike Iquitos, so there may be no anomaly at all?)

          7. DataWatcher says:

            ” . . . If hospitalizations/deaths fall really low, 6 months after that keeping measures in place won’t be politically viable. Social (and economic) pressures will just be too great.”

            Sorry to be a killjoy, but . .

            ““Governments and the public need to plan for the real prospect that COVID-19 must be managed on an ongoing basis. It’s critical to vaccinate as many people as possible and to prepare for long-term behavior change. It’s likely that wearing masks and taking other measures to prevent transmission, especially in the winter months, will become an ongoing part of our lives.” ( Christopher Murray, Institute for Health Metrics and Evaluation [IHME], U. of Washington)


        3. wubbles says:

          The West didn’t even try. Where are the massive factories going up with goverment money? The N95 production plants run by Uncle Sam? There is a complete lack of seriousness.

          See also the FDA not using Baysian methods to accelerate trials. They just don’t care.

      2. Steve Bragg says:

        Based on CDC numbers, around 80 percent of the deaths and hospitalizations are people over the age of 60. It you get that population mostly vaccinated, those bad numbers will plummet. There are 75 million in the USA aged 60 and over.

        1. Some idiot says:

          Similar numbers/pattern here in Denmark. Hopefully we will have all 60+ (plus at-risk) vaccinated by end April/mid-May. Will be very interesting to see what happens to %hospitalisations after that (my guess is that it will fall significantly).

    3. Daniel says:

      I don’t think many dropped out, it was a Phase II trial that they adapted to test efficacy, so it wasn’t intended to be big enough to properly test for efficacy.

  22. wojtsen says:

    Hi Derek,

    In their press release, J&J says that the vaccine has 66% efficacy at preventing moderate to severe COVID, not „all coronavirus infection”. Did they state something else during the press conference?

    1. Not-an-epidemiologist says:

      Except that they don’t state that at all:

      “In the South Africa Phase 2b clinical trial, 60% efficacy (95% CI: 19.9 – 80.1) for the prevention of mild, moderate and severe COVID-19 disease was observed in the 94% of the study population that was HIV-negative.”

      It seems clear (to me at least) that the proviso is there to exclude asymptomatic cases, which they presumably didn’t screen for.

      1. Marko says:

        Except that they do state that, exactly :

        “Among all participants from different geographies and including those infected with an emerging viral variant, Janssen’s COVID-19 vaccine candidate was 66% effective overall in preventing moderate to severe COVID-19, 28 days after vaccination.”

        You’re talking about S.Africa only. That was not the subject of the comment you responded to, who was correcting Derek’s inaccurate statement.

      2. Martin says:

        That’s Novavax’s SA data, he was talking J&J.

  23. lizzy says:

    Here’s my problems with the differing efficacy data and its relationship to real world data of these trials.

    First, efficacy usually means relative risk. ( 1 minus vaccinated/unvaccinated) You all know this. It’s highly dependent on the prevalence of the disease which changes according to location ,presence or absence of variants, and % seropositivity.

    Second, efficacy changes over time. To the extent that antibody maturation through b cell clonal selection happens, I would assume that efficacy would improve, but there the details get fuzzy in my mind. I think the data derived from this process reflects native infection where continued viral presence and mutations can drive clonal selection. But vaccine induced spike proteins? What evidence do we have that they mutate? Maybe I don’t understand. I’ll reread (again) Derek’s post. Obviously, efficacy does NOT always go up over time, witness the 52% efficacy of only one dose of Pfizer’s vaccine. (Again, another maybe, since if you exclude the first week after vaccination, efficacy goes up to 90%)
    Third, each vaccine picks different endpoints on which to base their efficacy, 50 days for J & J. But then, it’s only one dose. Does this roughly compare to one week after Moderna’s second dose? ( I doubt it) Novavax press release is one week after second dose, both MRNA’s started with 2 weeks after second dose and then updated things.

    Lastly, there will probably be differences in translations into real world data. It will be messy due to timing, percent of the various populations with immunity, variants and more.Then there’s the real world data, which will again be messy at best, UK’s experiment with one dose of RNA vaccines will be interesting as well as expected better real world experience with J&J’s single dose vaccine. No failed second appointments, many fewer mistakes in administration. Visions of a burly fireman “swirling not shaking” Moderna’s vaccine prior to injecting it, is laughable.
    Lastly, there’s the difference in primary endpoints. We’ve got 3 “symptomatic infections” with follow up versus one moderate to severe infections.

  24. lizzy says:

    Question: I thought original antigenic sin and antibody dependent enhancement were dependent upon strong recruitment of macrophages which is not the case in these T1>T2 vaccine candidates?
    Am I mistaken?

  25. DataWatcher says:

    I know this sounds like pessimism again, but it’s an honest question. It’s good news that very likely the vaccines can be modified to buoy up efficacy against B.1.351. However, does this portend a future in which we’re constantly trying to “play catch-up,” attempting to develop, distribute, and administer new versions of the vaccine to head off mutations and variants? I realize we do that, more less, on an annual basis for flu, but flu is not remotely as virulent as COVID (and not nearly as many people receive the flu vaccine), and if the coronavirus mutations continue at their current rate, in theory we could be looking at multiple “new” vaccines having to be developed and administered every year. It’s been difficult enough to roll out “one” version of the vaccines, let alone several per year (and worldwide, to boot). Is this too pessimistic a reading of what we’re beginning to see now?

    1. Rich Ward says:

      I guess I’m not quite so pessimistic overall. I think we may be in an era where at first we do need regular boosters but we are early in this disease’s ‘life’. Over time it may become less deadly, we may get some residual protection from our earlier covid vaccinations, we may get vaccines that target several viral proteins rather than just spike which should be harder for the vaccine to mutate around. Lots of reasons to think we can get on top of this disease; and if part if that is the requirement for annual vaccination then I’m in!

    2. Charles H. says:

      Caution: I’m a programmer, not a medic or biochemist.

      I would expect that the number of modifications to the “spike protein” that would work at all is rather limited. We may well not have seen the worst yet, but there isn’t an unlimited pool of possibilities. So my guesstimate is that we’ve seen half of the viable ones….though that isn’t based on anything in particular.

      So it’s my expectation that this particular area of modification has passed it’s peak rate of change, and will be declining. That doesn’t mean that other areas won’t change in ways that protect the spike, though. There will be a strong push for that kind of evolution. Say, e.g., changes that inhibit antibodies from binding to the spike, but which aren’t changes in the spike. These will probably generally be disadvantageous to the virus in the absence of antibodies, say things that inhibit access to the spike, but which move out of the way at the proper time.

      1. Calvin says:

        I think we were lulled into this false sense of security last year. While there is a limit on the total number of variants for Spike, the number is rather larger than you may think. The number looks more manageable when we look at single point mutations (20 amino acids per mutation). However, what the new variants show is that we’re getting multiple mutations. So the total number of options gets really big.

        And then add to that, the other proteins within SARS are not silents partner either. So mutations in other parts can also have an effect. These are incredibly hard to model because the effects are very much non-linear. I once had a project where we have solid highly measurable differences in potency caused by remote changes, even though the binding site (by X-ray) was the same. Those compensatory mutations are real but hard to model.

        So sadly, this virus will keep pumping out variants, and we just have to hope that none of them are worse.

        SARS CoV1 had higher mortality but did not have quite the infectiousness of SARS CoV2, so I would not want to predict that it’s all going to be fine. We have to vaccinate and reduce the spread.

  26. Not-an-epidemiologist says:

    Derek, a link to the best source on Novavax we have at present (their press release) would probably be better than a Stat news article. Note that the efficacy in HIV-negative individuals (which is the valid comparison stat) was 60% efficacy (95% CI: 19.9 – 80.1). That figure of 50% efficacy was for HIV-positive trial members only — and these represented only 6% of the trial subjects, so I don’t think that’s the number we should be headlining. Please — a lot of people read this blog, so it’s important to get these numbers right.

    Another point, re. B.1.351 re-infections — the press release states that (my emphasis) “Importantly in this trial, approximately 1/3 of the patients enrolled (but not included in the primary analyses described above) were seropositive, demonstrating prior COVID-19 infection at baseline. Based on temporal epidemiology data in the region, the pre-trial infections are thought to have been caused by the original COVID-19 strain (i.e., non-variant), while the subsequent infections during the study were largely variant virus. These data suggest that prior infection with COVID-19 may not completely protect against subsequent infection by the South Africa escape variant, however, vaccination with NVX-CoV2373 provided significant protection.” Of course there will be some reinfections (we know from the UK studies that you’ve got about a 5% chance of re-infection, although you’ll often be asymptomatic) — the real question is how many reinfection events did they see? “May not completely protect” does not imply many, especially in the context of the press-release-spin of the subsequent phrase.

    Finally: “the B.1.351 variant is clearly pushing the efficacy numbers down for the first crop of vaccines, and there is no reason whatsoever to think that the process will end there.” Well, there is at least one reason — at some point, escape mutations will negatively impact on S-protein function, and will begin to reduce infectiousness. The question is, how far can the protein change to retain function whilst avoiding a polyclonal antibody response?

    (On that last point — it should be possible to computationally find almost all mutational variants that can efficiently bind ACE2. It would be useful to know what range of variation the spike can tolerate, and what variants enhance binding. Hopefully someone’s doing this …)

    Funny how six months ago an efficacy of 60% would have been celebrated; now (even against a variant that doesn’t fully match the antigen) it’s seen almost as a failure …

    1. DataWatcher says:

      I’m sure it’s not statistically possible to discern this, but I can’t help wondering — What will the overall effect be when multiple vaccines of varying efficacy get effectively distributed and administered, most likely to attempt to immunize against at least two or three different variants of the virus, each with a somewhat different level of resistance to each of the various vaccines? It will be a complex matrix of efficacies, contagiousness, virulences, and relative immune escape potentials. Can such a thing even be calculated? If not, (to be brutally honest), what good will all of these predictions and projections do? I ask that question with all respect, because I think it’s an important one.

    2. Daniel says:

      In terms of the reinfections in the Novavax trial, they say that 2% of both seropositive and seronegative participants in the placebo group tested positive (see slide below). My rough calculations are 13/600 infections in the seropositive placebo group and 31/1540 in the seronegative placebo group.

      However, the trial wasn’t designed to assess the protection that being seropositive gives, so they won’t have matched the seropositive and seronegative groups demographically. It’s worth noting that in the Pfizer trial, 1.3% of both seropositive and seronegative participants were reinfected, despite there being no new variants at that time. So I wouldn’t freak out too much.

      1. Marko says:

        I don’t believe those numbers for a minute, from either trial. They don’t comport at all with reinfection studies that have been done, few as they are, like the recent SIREN study as well as this larger study :

        “Reinfection is rare. Natural infection appears to elicit strong protection against reinfection with an efficacy >90% for at least seven months.”

        1. Doug H MD says:

          My own experience in the clinic is that 1% number will likely be right. After 6-8 months. But based on too few observations so wide CI

          1. Marko says:

            Explain what you mean by that. Are you implying that primary infection does not confer a very high level of protection against reinfection, as does the “trial data” supposedly quoted above , which suggests it provides no protection whatsoever ?

        2. Marko says:

          Shane Crotty agrees. The vaccine reinfection data stinks to high heaven. They’re simply trying to sell vaccine to people who certainly shouldn’t be getting it now, in a time of vaccine scarcity:

          1. Doug H MD says:

            “Bottom line is still that the current COVID vaccines should have important efficacy against all SARS2 variants known, and getting as many people vaccinated as possible as quickly as possible is very important to blunt the spread.” Crotty

    3. Franksnbeans says:

      Well informed comment from Not-an epidemiologist

  27. lizzy says:

    J & J data certainly are disappointingly vague. I’ll wait for the FDA briefing document.

  28. Marko says:

    “One Dose Now for Everyone Most Likely to Die: Forget boosters and more trials. America’s overly prudent vaccination strategy is killing people.”

    The Brits out-thunk us on this. Maybe we’re finally about to wise up.

    1. Bash says:

      I suppose there needs to be a paradigm shift, where the risks of short cuts and “best guesses” outweigh the costs of potential negative effects

      Multiple phase, placebo controlled clinical trials are the Gold standard. However, I’m becoming of the opinion that this approach will become less and less relevant as we go forward, as the virus will continuously be several steps ahead

      Alternatively, some kind of mRNA booster / vaccine which can cover multiple S variants (both real and imagined, like, a 3 in 1, or a 6 in 1?) would be like winning the lottery

      I am increasingly convinced that 2021 is another write-off…

      1. Marko says:

        “I am increasingly convinced that 2021 is another write-off…”

        In the US, perhaps. Not for Israel, though. They’re going to smash Bourda’s dreams of perpetual Warp Speed profits.

        1. Bash says:

          Israel is doing an incredible job and showing the way for everyone. Also its great to see that the vaccine works in the real world

          However, their borders cannot stay closed forever, and they will need to have vaccine updates like everyone else – just potentially without the carnage

      2. confused says:

        Depends on what reinfection with a slightly different variant does, surely?

        If decreased immunity doesn’t protect against reinfection, but *does* prevent against severe disease, IE it’s just another cold or mild flu, does it really matter?

        I mean, isn’t COVID pandemic because the world was 100% immunologically naive in December 2019? That’s not going to last, one way or another (but the vaccines will get us there with far less deaths).

      3. Michael says:

        It would be costly, but it probably wouldn’t be too hard to enroll 25k people who have had the first dose of the vaccine, of whom you’ll give half a second dose and half placebo, and do a comparison between the groups.

        This is effectively a shortcut, lopping a month off the trial time, because people have already received the first dose.

        And you might accept fairly weak statistical evidence that points in the right way — provisionally.

    2. Barry says:

      The clinical trials in hand for Pfizer and for Moderna were a two-dose protocol. To deploy them single-shot would be off-label. That’s not forbidden, but it is treading into the broad deployment of an untested protocol. We don’t now its safety, we don’t know its efficacy. We don’t know that a delayed second dose would provide the same or equivalent boost as seen in the Phase III.

  29. Bash says:

    Pfizer CEO says he expects all current vaccines to become eventually ineffective

    We are going to transition to a world where ~15bn doses of vaccine need to be produced, distributed, and administered, and where “updates” to shots need to be able to turn around in under 100 days (per Bourla) – and that includes regulatory approval

    This is going to take years…

    1. confused says:

      I really doubt it.

      If a new variant just has reduced protection (not zero protection), I wouldn’t think everyone needs to be re-vaccinated, just the higher-risk groups (and that assumes we’re talking “reduced protection against severe illness” – if people get infected but the symptoms are ‘common cold’ it hardly matters).

    2. Philipp says:

      If data from other coronaviruses are anything to go by (which, according to Bloom Lab, they are), boosters will be needed every two to five years.
      A money-printing machine for Pfizer and Moderna, but nothing that will have any effect on how people live their lives.

      1. Chris Phillips says:

        It’s news to me that people are being vaccinated for other coronaviruses every few years.

        1. sPh says:

          Coronavirus vaccines used in animals, particularly cattle, are mostly annual and/or event driven (pre-pregnancy in the case of cows). I’m not aware of any coronavirus vaccines for primates (which doesn’t mean there aren’t any) so it may work differently for humans, but I would wager on the annual “flu vaccine” appointment becoming a 2-shot affair from 2022 on.

          1. confused says:

            If so, I wonder how many years it will take before people in the US start being as casual about the COVID vaccine as they are (or were pre-COVID anyway) about the flu vaccine?

    3. DataWatcher says:

      That’s a really pessimistic take on Bourla’s comments. Yes, he said that requiring an annual booster shot re-tooled to address the challenges of new variants is a possibility, but he said it in this context: “it looks like we have the tools to make Covid like the flu. That means it will not disturb our lives or the economy. We just need to be very vigilant about [tracking new] strains. And we need to be very vigilant about vaccinating people.”

      Also, unless I’m mistaken, boosters of this nature wouldn’t have to go through the entire, laborious testing and approval process all over again, every time. We don’t do that with the flu vaccine, do we?

  30. Gradient says:

    I hope there is a way to fix this without turning it into a perpetual bonanza for pharma. Some smart experimentalists already have libraries of pseudoviruses capable of expressing the spike with any set of mutations they care to dial in (e.g., doi: They could use (probably are using) this system to explore future mutations. It should be possible to map the most important spike mutation sites that preserve ACE2 binding but confound antibody binding, and make a multivalent vaccine aimed at addressing that population. Best of luck to them.

  31. WTF says:

    Can’t believe people actually listen to this character, he got the boot from Vertex and landed at the absolute worst company in Boston, the place is a laughing stock.

    1. sgcox says:

      “You have enemies? Why, it is the story of every man who has done a great deed or created a new idea. It is the cloud which thunders around everything that shines. Fame must have enemies, as light must have gnats. Do not bother yourself about it; disdain. Keep your mind serene as you keep your life clear.”
      Victor Hugo

      1. Ancient Briton says:

        Well quoted, sgcox.

  32. Matt says:

    There are some experts (won’t name) who used terms like: “Truly striking” “Tremendous” “Extraordinary” “Miraculous” “A great day for science and humanity” for Moderna and Pfizer vaccines when those were announced. Though we know that both of these stand no chance to make a vaccine for multiple variants, though they may make one for each variant. This is huge!

    We know that new variants are circulating. We are mass vaccinating with Moderna and Pfizer without testing their efficacy against the new variants. Is that not a problem? In a Brazilian region they have found that new variant is killing folks who have had Wuhan version of Covid19.

    Perhaps Novavax and J&J vaccines are far superior than the Moderna and Pfizer vaccines and they have been tested for.

    Novavax, because of the platform they use can easily make vaccine for multiple variants and may prove to be the best!

    The HIV positive may need to be treated with Vyrologix aka Leronlimab (from CytoDyn).

    1. Marko says:

      “In a Brazilian region they have found that new variant is killing folks who have had Wuhan version of Covid19.”

      Any sourced data on that ? I’ve been looking and haven’t found any. I don’t get it. It ain’t brain surgery, if someone had a positive PCR in the first wave and again in the current wave, they can be considered reinfections, full stop. No need for two sets of genomic data. There’s no evidence that flare-ups of lingering infections are occurring to any meaningful degree after that long of an interval. In a place like the US , I could understand the lack of data. Our medical records technology is a joke. But in a backwards place like Manaus, I can imagine they’d have a much better system.

      1. Matt says:

        Please try and follow work done by Nuno Faria, a virologist at London’s Imperial College

        1. Chris Phillips says:

          If you’re talking about the paper published a fortnight ago in Science, this work has already been discussed at some length here. It is an estimate of how many people had been infected by October 2020. It is a very indirect estimate, heavily dependent on extrapolation and modelling, and it is about a factor of five larger than the result that was obtained from random sampling.

          I don’t think it even mentions the new variant, let alone saying anything about deaths from reinfection by the new variant.

          1. Matt says:

            The mutation that could allow Covid-19 to escape antibody protection has now been found in samples of a rapidly spreading strain in the UK, according to a report published by Public Health England – its being termed as E484K.

      2. Matt says:

        Considering what has been observed by Nuno Faria it is imperative to depute Dr Fauci and his team to do fact finding about the variant virus. If the new variant does not respond to antibodies of Wuhan Covid19, that may be the “COVID2021”.

    2. A Knowing Mess says:

      It’s a lot easier (and faster) to make mRNA vaccines for new variants than it is for recombinant protein vaccines – you literally just change the nucleotide sequence in your vector.

    1. confused says:

      Why is “no new side effects” an “uh oh”?

      1. DataWatcher says:

        Sorry. Somehow I posted the wrong link. This was my original “Uh oh” link . . . Congressman Stephen Lynch has tested positive for COVID after receiving BOTH Pfizer shots. In light of what we’re hearing from South Africa and Brazil, this is not an encouraging development. Granted, he’s asymptomatic (so far), which is a good thing (and commensurate with what the efficacy endpoint data would suggest), but it won’t help allay public skepticism, and it also casts further doubt on whether the vaccines, as they stand, can confer any degree of sterilizing immunity.

        1. DataWatcher says:

          Here’s the link to the story about Lynch . . .

        2. Chris Phillips says:

          Should we be surprised by that, considering some people not only tested positive in the trials, but had symptoms (one even severe, if I remember correctly)?

          There have been some press reports in the UK suggesting this shows there is something wrong, even when it happens after a single dose. I think we have to expect this will happen to quite large numbers of people, even for the vaccines with 90%+ efficacy.

          1. DataWatcher says:

            And also, of course, we don’t know when Lynch got his second dose. If it was just a few days before he tested positive, he could have contracted COVID in the interim between his shots, or even just after the second one, since it takes some time for the vaccine to become fully effective after it’s administered. I just hope the reporting makes this clear; the last thing we need is more “vax” sensationalism. (And yes, I realize — that horse has already left the barn. . .)

          2. confused says:


            And even if it was 14 days after second shot, 95% efficacy isn’t 100%. No one claimed the vaccine would prevent all infections, ever.

            And while I share your concern about public perception/media, in terms of actual effectiveness of the vaccine, what I really care about is preventing severe disease – if the vaccine turns COVID into the common cold if you do get it, that’s IMO good enough (especially once all the really vulnerable people have been vaccinated, so asymptomatic spread is much less of a fear).

          3. DataWatcher says:

            Yup — Although, at risk of sounding like a depressing tape loop, I still worry about the possibility of more (and more dangerous) mutations arising from that situation. As long as it can spread, it can mutate, whether people are getting symptoms or not. If I’m wrong about this possibility, I’ll be very glad, but so far I’m not aware that it hasn’t been ruled out as a definite potential problem.

          4. confused says:

            I’m sure it’s possible.

            But if post-widespread-vaccination COVID isn’t more deadly than any of the dozens of other respiratory viruses circulating, why should we worry *more* about mutations in SARS-COV-2 than any of those (RSV, parainfluenza, the four common-cold coronaviruses etc.)?

            No one is really working on developing vaccines to drive the four common-cold coronavirus circulation to zero to avoid potential future dangerous mutations, as far as I know.

          5. Michael says:

            Keep in mind also that the Congressman is asymptomatic, which puts him in the “protected” category of efficacy and not the “unprotected,” seeing as 95% measured symptomatic cases.

            I think it’s more cool than scary that it rendered him asymptomatic despite close contact with an ill staffer, and I suspect (and Fauci openly suspects) that we will get data showing minimal onward spread from vaccinated asymptomatics.

          6. DataWatcher says:

            May I ask a stupid-sounding layman’s question? An asymptomatic carrier is, obviously, still “carrying” the virus — ostensibly in the nasal pharynx, which is why the dangerous respiratory symptoms aren’t presenting. Would his or her viral load still be sufficiently small to avoid serious risk of contagion? This doesn’t seem to have been the case with non-vaccinated asymptomatic carriers. I’m just wondering about the mechanism of this, and I apologize if this question sounds as uninformed and clueless as I’m afraid it does.

            (For that matter, from what I remember about the early J&J non-human primate trials, the vaccine did not eliminate the presence of the virus in the animals’ nasal regions. Any more recent data on this?)

    1. Marko says:

      Thanks. Yes, I’d seen that article, but it’s still all just speculation, no hard – or even soft – data.

  33. Jab Jab says:

    27% of those tested by Novavax were aged 65 – 84, which makes their results even more impressive. I believe Pfizer capped the age at 70, and only had a small percentage age 65-70. And didn’t JnJ only go up to age 55?

    1. Dan.In.Chicago says:

      Jab Jab

      No, J&J did not only go up to age 55. I am in the study, and I am 68.

      1. Chris Phillips says:

        Yes – the information “Jab Jab” posted is completely false.

        The Johnson and Johnson trial included 13,610 participants over 60. I posted a comment correcting that yesterday, but it was “held in moderation” and hasn’t appeared. Presumably because I backed up my statements with links to source. Unfortunately automatically deleting comments containing links has the effect of preferentially filtering out reliable information.

        1. Marko says:

          I’ve found that if you keep to one link per comment it works OK. Then you can add additional links with sequential comments in reply to your first one. It is a pain, though.

  34. Bohemian says:

    Thanks for your article comparing vaccines of MRNA/PFE and Novavax and JNJ.

    What’s clearly missing here is although the mRNA platform can be most efficient at creating a new variant spike protein in the fastest time, MRNA and PFE cannot increase their respective antigen dosages from 100 and 30 micrograms for multivariants without harming the patient or significantly reducing the antigen load and subsequent effectivity for each variant. Only NVAX has this multivariant capability at just 5 micrograms per dose. Surprised this article didn’t mention that huge advantage that NVAX has for actual implementation of multivariant vaccines similar to its quadrivalent flu vaccine NanoFlu.

  35. Quin says:

    Assuming the vaccines are “sufficiently” effective at preventing hospitalizations and deaths, how are countries planning on “returning to normal”?

    Not getting the sense that there is much thought or planning being given to this.

    The ranbalicer twitter feed has some bullet-level discussion in the Israeli context, but it does not create a sense of optimism.

    1. Marko says:

      “Not getting the sense that there is much thought or planning being given to this.”

      Surprise, surprise, huh?

      My advice to countries like the US and UK is to not do it the way countries like the US and UK would do it, but to swallow their pride and look to for solutions from the countries that have managed the pandemic successfully so far, and will likely have similar success subsequent to vaccine deployment.

      1. confused says:

        I don’t know that success in controlling the pandemic will have all that much correlation with success in re-transitioning back to normal. The really successful nations tend to have *both* policies *and* natural advantages (generally islands eg Iceland, Taiwan, Australia, New Zealand or near-islands eg South Korea) and the latter won’t help much with transitioning back.

        In fact it might cause issues when they do reopen their borders, and since COVID won’t actually be extinct they will have to convince people that post-vaccine exposure to COVID is no longer a big deal.

  36. lizzy says:

    For Jab Jab:
    From the Pfizer VRBPAC document: (didn’t format well.)
    Table 4. Demographic Characteristics, Participants
    Nb (%)
    Nb (%)
    Nb (%)
    Sex: Female 9794 (48.9) 10107 (49.9) 19901 (49.4)
    Sex: Male 10239 (51.1) 10137 (50.1) 20376 (50.6)
    Age at Vaccination: Mean years (SD) 50.3 (15.73) 50.1 (15.78) 50.2 (15.76)
    Age at Vaccination: Median (years) 51.0 51.0 51.0
    Age at Vaccination: Min, max (years) (12, 89) (12, 91) (12, 91)
    Age Group: 16 to 55 years 8396 (41.9) 8454 (41.8) 16850 (41.8)
    Age Group: ≥65 years 4294 (21.4) 4319 (21.3) 8613 (21.38)
    Age Group: ≥75 years 860 (4.3) 852 (4.2) 1712 (4.3)

  37. DataWatcher says:

    Some states and cities in the U.S. have “phased” or “tiered” reopening plans linked closely to projected case-positivity rates, death rates, and/or hospitalization rates over specified periods of time (e.g., a case-positivity rate at or below a certain target, maintained over several weeks, will allow for a loosening of some, but all, restrictions, with more loosening as the rates continue to fall). In Illinois, at any rate, this seems to be encouragingly successful at improving things post-holiday-spike, even before the vaccine has had a chance to take wide effect. Of course, maybe we’ve just dodged the bullet so far in terms of the new variants — I’m not aware than any of them have been documented here yet.

    Of course, there’s no national version of this plan, and given our Federalist system of governance, there probably couldn’t be one even if it were politically feasible (which it wouldn’t be).

    1. Ken says:

      Around June of last year, I saw an analogy for the US response: “It’s like you have a swimming pool with fifty people in it, and twenty of them have promised not to pee in the pool.”

      1. DataWatcher says:

        Good one!

  38. lizzy says:

    From a 1/27/21 letter to NEJM:

    Perhaps this woman is worth watching. She is looking into clonal B cell maturation to Moderna’s vaccine. Hopefully there will be more to come from her.

    Although the memory cellular response to mRNA-1273 is not yet defined, this vaccine elicited primary CD4 type 1 helper T responses 43 days after the first vaccination,2 and studies of vaccine-induced B cells are ongoing. Longitudinal vaccine responses are critically important, and a follow-up analysis to assess safety and immunogenicity in the participants for a period of 13 months is ongoing. Our findings provide support for the use of a 100-μg dose of mRNA-1273 in an ongoing phase 3 trial, which has recently shown a 94.5% efficacy rate in an interim analysis.

    Alicia T. Widge, M.D.
    National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD

  39. Marko says:

    Brazil researchers find people infected with two different coronavirus strains

    A perfect recipe for trouble. Recombination can create troublesome new strains quickly. I’m kinda surprised this is the first time this has been seen.

  40. Marko says:

    Kristian Andersen on why the increased “transmissibility ” of the Brazil and S.Africa variants may be largely, if not entirely, due to immune escape :

    We can sort this out by comparing their rate of spread in areas with high seroprevalence vs low, but actually getting that data is another matter.

    1. Chris Phillips says:

      Yes, I think we need more data. Those tweets are too speculative for my liking. The main argument for the hypothesis – that the apparent increased transmissibility of the Brazilian and South African variants is due to immune escape rather than an inherent increase in transmissibility – is that they arose in places where there had been large numbers first time around (together with that problematic estimate for Manaus). But all kinds of variants are more likely to originate in places with higher numbers of infections.

      And I don’t think it makes sense to argue, as he does, that the Brazilian and South African variants aren’t like to rise rapidly in prevalence the USA if they aren’t inherently more transmissible. If the reason is instead greater immune escape, that will also make them more transmissible in practice, given the large numbers who have already been infected in the USA.

      In the absence of better data it seems likelier to me that the UK, Brazilian and South African variants all share features that make them inherently more transmissible (say 30-40%), and that that is accounting for at least a significant part of the apparent increase in transmissibility of the Brazilian and South African types.

  41. Marko says:

    Early estimates from Geneva, Switzerland come up with 33% increased transmissibility of the UK variant there, consistent with similar work in Denmark and the UK :

    1. Marko says:

      Oops, that should be a 33-47% increased transmissibility, based on a generation time of 5 or 7 days, respectively.

      1. Chris Phillips says:

        It’s nice that the estimates do seem to be converging, but I wish they would express them in terms of daily growth rate, and take out of the equation uncertainty about the serial interval (and also associated averaging fallacies).

        I reckon the daily growth rate is the quantity of paramount practical importance in terms of controlling infection. The R number may be telling us something about herd immunity requirements, but I think the usual estimate of 1-1/R is based on far too simplistic a model to be quantitatively accurate.

        1. WST says:

          Correct, the growth rate is the metric that does not depend on any (irrelevant) model, another one is cases doubling time.

          If you assume that the model is right, R can be only estimated from incidence statistics taken from random samples, which is practically never done. The non randomised incidence statistics are biased towards symptomatic cases, especially if positive % is high.

          But, we know that the SIR type models two major predictions, herd immunity and random distribution of Resistant never occur in practice and seropositivity in tests is age and geo stratified, nor randomly distributed.

          So, we have now R estimates based on irrelevant model and calculated with wrong method…
          Rather amazing….

  42. Marko says:

    I hope this doesn’t come about :

    “This paper makes a clear and scary prediction of a specific variant – Q498R, that will arise on the background of the existing variants + will be up to 4-fold more infectious”

    That would put us in measles territory of transmissibility. Don’t even want to think about it….

    1. Chris Phillips says:

      While the tweet by Igor Ulitsky does say “up to 4-fold more infectious”, the preprint referred to says binding affinity is improved 4-fold by Q498R plus N501Y. Regarding infectiousness, it says only that Q498R “will probably have even higher infectivity” than N501Y alone. Ulitsky is only a Twitterer, not an author of the preprint, so I think he is being inaccurate.

      1. confused says:

        Meaning that binding affinity doesn’t 1-to-1 correlate to in-practice transmissibility?

        Also how can future mutations be predicted like that?

        Anyway, I don’t think there’s time for a new variant starting from zero to become strain-on-hospitals common before the vulnerable population is vaccinated at least in the “first world”.

        The UK variant apparently appeared in September, right? That’s 4 months ago. 4 months from now most everyone with a high risk of death in the developed world should be vaccinated (unless they refuse vaccination, of course).

        1. David L says:

          Shane Crotty retweeted the Hensley Lab which has done work supportive of virus selecting for binding in seropositive populations and against it in naive populations.

      2. Marko says:

        So, not so “clear and scary”. Thanks. I didn’t look at the paper (too tired), but I should have suspected as much. This is like people extrapolating a 6-fold reduction in neutralizing titers into a 6-fold reduction in vaccine efficacy.

        Sorry for contributing to the already-rampant “fear porn”.

  43. Marko says:

    Thetys vagina engulfs carbon, helps fight climate change :

  44. Steve Green says:

    The top line J and J study results cannot be directly compared with the Moderna and Pfizer results since the main outcome endpoints are completely different. Setting aside the differences in the definitions of a Covid Event the Time periods over which an event is counted is completely different between the studies. The primary endpoint for the J and J study counts events up to 28 days after the single dose received while the Moderna/Pfizer trials look at events after 7 days following the second dose. I‘ve looked at the cumulative incidence curves of the treatment groups of the Pfizer study and it seems that the estimated event rate at 28 days after the first dose is ~20% in the active control group vs. ~45% in the placebo group. This efficacy is a lot less than the 95% efficacy claimed for the primary endpoint including only events after approx 28 days after 1st dose (or 7 days after 2nd dose). It is possibly comparable to the J and J efficacy up to 28 days (although the different event definitions need to be accounted for). In their press release J and J suggested much stronger efficacy over time which suggests the effect beyond 28 days might also be very strong and perhaps more comparable with the MRNA vaccines. We will have to wait for full data fro J And J to be able to judge this more fairly. Note that the follow-up study by J and J may give even better efficacy and give a boost to immunity that might even prove more effective against the South African variant which seems to be a problem at the moment.

    1. Steve Green says:

      Sorry, of course at 28 days after first dose is 0.2% vs 0.45%. Sorry for the typos

      1. billnyc says:

        Minor point but Moderna started counting 14 days after 2nd dose, Pfizer was 7.

        I do think it’s possible we may see that JnJ is not so far off from the mRNAs, but it remains the be seen.
        It’s too hard to get any meaning from either of the mRNA in vitro studies against the variants, but Pfizer deserves extra shame for getting so much of it wrong… using Wuhan as a control, only including a few of the mutations…. I don’t know why they bothered.

        We really need some standardization in assays across the different vaccines, otherwise what’s the point? It shouldn’t be so hard to figure that out.

        1. Marko says:

          “We really need some standardization in assays across the different vaccines, otherwise what’s the point? It shouldn’t be so hard to figure that out.”

          We need a ‘Consumer Reports’ for vaccines.

  45. Marko says:

    When you can see the cluster of flashing ambulance lights from the Space Station, it’s not “just the flu” :

  46. lizzy says:

    Ok Marko,

    I’ll inform Consumer Reports for you. I’m sure they’ll hop right on it.
    I hope you get some good sleep tonight and dream of vaginas and not variants or ambulance rides.
    All kidding aside. I have really enjoyed hanging out here over this weekend. So much to learn. So much to explore.

    1. Marko says:

      “I hope you get some good sleep tonight and dream of vaginas…”

      LOL !!

      I’ll make a point of it…

  47. FrankN says:

    Derek – on the mediocre J&J results in South Africa, you postulate: “That last one has to be another B.1.351 effect.”

    Not neccessarily. Check out

    “Ad26 seroprevalence was 43.1–53.2%, 66.2%, 67.8%, and 54.6% in adults in South Africa, Kenya, Uganda, and Thailand, respectively.”

    So J&J may, with their Ad26-based vaccine, have run into the same sort of problems as CanSino encountered in China with their Ad5-vaccine: Substantial pre-immunisation against the vector limiting the vaccine’s efficacy.
    In fact, I saw something like that coming. J&Js Ad26-based Ebola vaccine also fared rather poorly in their Central African tests, at just 50% efficacy.
    The vaccine might still be o.k. for N. America and Europe, but will probably not be of much help in Sub-Saharan Africa and South East Asia. In addition, applying an Ad26-based CoViD vaccine in Africa implies “back to the drawing board” when it comes to Ebola.

    1. Chris Phillips says:

      That sounds like a very good point.

      But on the other hand (1) with J and J it seems to be more a question of lower efficacy everywhere, and the difference in efficacy between Sout Africa and elsewhere was smaller than for Novavax, and perhaps smaller than might have been expected for an only moderately efficacious vaccine on the basis of the in vitro studies and (2) there is still the finding of no hospitalisations, even in South Africa. Though it would be nice to see the numbers of hospitalisations/deaths in the South African placebo group for comparison. If they are small, the confidence interval may be less impressive than the “100%” figure in the press release.

      1. Michael says:

        Eric Topol said he reviewed the data with J&J and said there were “40-60” hospitalization events, all in placebo, including the events in South Africa. He didn’t break it down further than that.

        1. Chris Phillips says:


          I wonder why Topol should have been given privileged access to the data.

          I suppose there are two different questions here: (1) Is the rate of serious cases smaller in the vaccine arm? (2) Is the percentage of infections that produce serious cases smaller in the vaccine arm?

          I presume the second question is easier to answer for the vaccines with a lower “headline” efficacy (meaning the answer to the first question).

    2. Doug H MD says:

      No deaths mean no help in your book?

  48. Marko says:

    Single Dose Vaccination in Healthcare Workers Previously Infected with SARS-CoV-2

    ” ….In times of vaccine shortage, and until correlates of protection are identified, our findings preliminarily suggest the following strategy as more evidence-based: a) a single dose of vaccine for patients already having had laboratory-confirmed COVID-19; and b) patients who have had laboratory-confirmed COVID-19 can be placed lower on the vaccination priority list.”

    It doesn’t matter what the findings are, we’ll continue to rush to jam two doses into the arms of healthy seropositives while at-risk seronegatives wait for weeks to months for any dose of a vaccine, because capitalism.

    1. Marko says:

      In case any of the authors of the above paper are reading here, your “Methods” section has a mistake :

      “…. stratification into three groups:
      Group 1: IgG positive with history of symptomatic COVID-19
      Group 2: IgG positive and with asymptomatic COVID-19 and
      Group 3: IgG antibody negative. ”

      The rest of the paper makes it clear that groups 2&3 are the seropositive groups, not 1&2 as stated in Methods.

    2. Marko says:

      Similar results and recommendations from the Florian Krammer group, similarly likely to be ignored:

      “Robust spike antibody responses and increased reactogenicity in seropositive individuals after a single dose of SARS-CoV-2 mRNA vaccine”

      The constipated public health blue-cheks will say ” This data strongly suggests we need a large RCT to verify this effect, because those results would enable important new vaccine-sparing policies, which , in the next pandemic, we’ll perhaps be smart enough to consider implementing BEFORE so many people die unneccessarily. “

      1. Marko says:

        One of the most often wrong blue-cheks does it again. I suggest more fiber in her diet :

        “Biggest caveat here is that looking just at antibody titers doesn’t tell us much about functional protection. This is interesting but needs further investigation.”

        We know that seropositivity confers near-universal protection against INFECTION for many months, which is more than we can say about vaccines. Is that not “functional protection” ?

        1. DataWatcher says:

          “We know that seropositivity confers near-universal protection against INFECTION for many months, which is more than we can say about vaccines. . .

          Not any more, apparently:

          “Even if you’ve had coronavirus, there’s a ‘very high rate’ of being reinfected with the new variants if they become dominant, Dr. Anthony Fauci says. ‘If it becomes dominant, the experience of our colleagues in South Africa indicate that even if you’ve been infected with the original virus that there is a very high rate of reinfection to the point where previous infection does not seem to protect you against reinfection, at least with the South African variant that’s the one that we know the most about when it comes to reinfection,’ Fauci, director of the National Institute of Allergy and Infectious diseases, told CNN’s Wolf Blitzer on Monday.”

          1. Doug H MD says:

            data to back that up please?

          2. Marko says:

            That’s still not a good reason to waste scarce vaccine doses on the seropositive in the US right now, when the immune escape variants are rarely being detected.

            We’re fast approaching the point of fully a third of the US being seropositive, and those people are at considerably less risk of infection and severe outcomes than those who haven’t been infected yet, and this will probably hold true for the immune escape variants as well, should they eventually become dominant. It’s simply unethical to vaccinate the former before the latter.

            The danger that lurks is that data may reveal that previous infection obviates the need for vaccination altogether, by near-universal protection against severe disease, thus lopping off a third of Big Pharma vaccine profits. Thus the PR push to ignore science and vaccinate seropositives ASAP, and the publication of clearly bogus vaccine trial data that suggests that prior infection is not in the least bit protective against reinfection.

            Fauci is gaslighting for the benefit of the vaccine companies. Crotty had the audacity to suggest that the vaccine data on reinfections smelled fishy, then when he was called out on it by Lipshitz, he cowered like a puppy caught peeing on the carpet.

            We’re not being told the truth, because people are afraid to tell the truth.

          3. DataWatcher says:

            For the sake of our future (and our current mental health!), Marko, I hope you’re right, although I’m not convinced that Fauci is really a “gaslighter.” But does this mean that the data in that other link I posted were also fudged? We’ve already seen at least one Israeli reinfected with 351 after recovering from (presumably, though I don’t know) 117. Shouldn’t that be a warning sign, at any rate?

          4. DataWatcher says:

            . . . meanwhile, though, another reason I fervently hope you’re right is because it would mean that significant mass immunity might be achieved with far less vaccine uptake than the usual 70-85% that’s been predicted; if upwards of 25% of the population is already protected via seropositivity, then that potential HIT might be around 60% uptake or even lower. Might that help explain why the Israeli numbers are already going down so encouragingly after roughly 30% of the population have been vaccinated?

          5. Marko says:

            One reinfection in Israel? Is he dead? In the ICU? Anecdotes are not convincing data, about anything.

            Forget about HIT. We need to reach a 100% threshold of protection against severe disease/death, or as close to that as possible. The quickest way to do that is to get one dose into all seronegatives ASAP. Then get a second dose into that same group, and possibly a first dose also into seropositives, depending on what we’ve learned by then about their evolving protection.

            Seropositives, or those who know they’ve been infected by virtue of a past PCR+, would do well to take matters into their own hands. First, do the dignified thing and stand aside until others more at risk have received a vaccine dose. Second, if you were recently infected and you have no dignity to worry about, wait at least several months to get the vaccine, because the booster effect will probably be stronger and more durable if you do.

            For the very old and those at elevated risk for other reasons, wanting to get as much protection as fast as possible is completely understandable. I wouldn’t stand in the way of them getting both doses as soon as they can, regardless of serostatus, though they would still likely benefit from waiting a while if they’d had a recent infection.

      2. DataWatcher says:

        It’s certainly the case that the ongoing plethora of conflicting interpretations of data, along with the wide disparity in terms of predictions, all from recognized “experts” in immunology, virology, and/or epidemiology, can be distressingly conflicting. (And no, I’m not talking about tinfoil-hat crazies, I’m talking about respected authorities in their fields. For instance, both Crotty and Lipsitch have agreed, more or less, that COVID will eventually become an endemic, relatively benign, disease akin to something ranging from a common cold (Crotty) to a flu that would only be serious for immunocompromised or otherwise at-risk people (Lipsitch) — not unlike the flu as we know it today (although, admittedly, they did make those predictions before the most recent mutant variants had made themselves known).

        But then there are folks like Christopher Murray (Institute for Health Metrics and Evaluation, U. of Washington), making predictions decked out n full Cassandra drag . . .

  49. Daren Austin says:

    Not even a P value to reverse engineer the efficacy for J&J. Novovax looks like an eventual effective pathway forward for spike protein vaccines.

    1. DataWatcher says:

      What’s the projected timeline for Novavax? We’ve hearing that they probably won’t be ready for rollout until early this summer at the earliest. Expectations for their vaccine have been high for quite a while, and it’s beginning to look as if those expectations might have been realistic (I admit they’re the one I’ve been highest on, almost since the beginning, especially after their early primate trials suggested a strong possibility of sterilizing immunity). Any idea whether their approval might come earlier than expected?

  50. lizzy says:

    I too have always liked Novavax and wanted to get a peak under the hood at their proprietary nanoparticle matrix made with “smoke bark”. I wondered what would happened if you scientists could “shrink wrap” the Novavax matrix around some stabilized mRNA, just so cells could display the spike on their cell surfaces.

    It’s very ambitious of them to buy land close to their headquarters in Pennsylvania and create manufacturing sites on the spot. I just hope they’ve got the kinks out.

  51. Marko says:

    The beginning of the end is becoming apparent in Israeli data. As long as they keep the foot on the gas with vaccinations, and don’t prematurely hit the bars all at once to celebrate, hospitalizations and deaths look to be headed steadily down, and eventually, out.

    1. DataWatcher says:

      Even more encouraging, since they’ve been facing off against B.1.1.7 for quite some time. But I’m also guessing that adherence to public health practices in Israel is probably a lot better than it is in the U.S. (and most Western countries) — so the vaccine doesn’t have to “go it alone,” so to speak. Now, even if/when B.1.351 makes its appearance, they’ll be in a much better position to deal with it. Of course, they’re a much smaller country, so population-wide policies are a lot easier to facilitate. Even so, though, wouldn’t it be nice if the rest of the world could take a page or two from the Israeli playbook . . .

      1. Michael says:

        Funny that you say that, DataWatcher. I have been following the Israeli vaccine news very closely and their number-crunchers lament Israeli compliance with lockdown measures, given that UK, Ireland and Denmark have falling cases despite B117 prevalence and less of a per capita vaccine rollout. There was a recent tweet that cases are high because it’s “British variant with Israeli lockdown compliance.”

        But with respect to the cohort who have been fully vaccinated, the data is super encouraging.

        1. DataWatcher says:

          Okay, that was just a guess, based on what’s probably a stereotype of Israel as an overall more socially conservative society with more social cohesion (among its Jewish population, of course) than many Western countries. Either way, though, their numbers are encouraging, maybe especially so since only about 30% of their population have been vaccinated and they’re already showing significant declines in infections, deaths, hospitalizations, etc.

          Meanwhile, though, are there any theories as to why the UK, Ireland, and Denmark are now seeing ” falling cases despite B117 prevalence and less of a per capita vaccine rollout”?” Glad to see it, but it seems counterintuitive to me. Nonetheless, I hope it portends what could happen in the U.S. over the next few months!

          1. Doug H MD says:

            why is falling cases counter intuitive. It is what happens with every exponential curve. Boom and bust. Knowing precisely how big the boom is a tricky business to be sure.

          2. Chris Phillips says:

            I have read that there are serious problems with compliance among some ultra-conservative religious groups in Israel. As in other countries.

    2. Quin says:

      The Israeli data is encouraging, but …


      1. Chris Phillips says:

        I suppose there is a good chance that – just as the overall infection rates in vaccine trial volunteers seem to have been significantly lower than for the population as a whole – the efficacy of vaccines in the trials may not reflect their performance in the real world.

        For example, if vaccine volunteers tend to be more careful, they may typically have been exposed to a lower dose of the virus than others. Perhaps the efficacy of the vaccine will vary according to the dose.

  52. DataWatcher says:

    If this is the wrong thread, I apologize — but the good news is that an effective over-the-counter self-testing kit will now be available. Could be a game-changer, but it looks as if it’s not going to really come into play until we’re well into extra innings: According to this article, about 8.5 million will be available by the end of this year, which isn’t anywhere near as many as we’ll need. Also, the kits will cost $30 each (and, being over-the-counter products, most health insurance probably wont’ cover them — can’t speak for Medicare / Medicaid). In addition, using them apparently requires the use of a smartphone, which not all people (especially not all high-risk elderly) own.

  53. Marko says:

    E484K hates to be left out :

    “Detection of E484K mutation in B.1.1.7 VOC 202012/01

    The COG-UK dataset (total sequences 214,159) was analysed on 26/01/2021. The spike
    protein mutation E484K (found in VOC 202012/02 B1.351 and VOC 202101/02 P1) has
    been detected in 11 B1.1.7 sequences. Preliminary information suggests more than one
    acquisition event. ”

    1. Marko says:

      Gupta Lab already has the neutralization data on the UK plus 484 variant. They must have expected ( justifiably ) that this was coming to have done this so quickly :

  54. Doug H MD says:

    Why is it that young people seem to have more severe side effects from the mRNA vaccines than do the elderly but much higher incidence of asymptomatic infection?

  55. Doug H MD says:

    “The South African Novavax trial appears to confirm these early findings. Two percent of the South African participants that received a placebo got Covid-19 during the trial. That proportion was the same for people who had previously been found to have antibodies and those who didn’t.

    “These data suggest that prior infection with Covid-19 may not completely protect against subsequent infection by the South Africa escape variant,” Novavax wrote in its news release on the trial results.”
    Color me unimpressed. Show me some real data . How many exactly? How sick? any deaths?

    1. DataWatcher says:

      I will say that the different reports — or the different interpretations of the reports — from South Africa have been confusing in their wording. Novavax reported that prior infection “may not completely protect” against reinfection, which says nothing of severity or even likelihood (we already know that reinfections have occurred, albeit rarely, so it’s established that prior infection “may not completely” protect against reinfection.) That, in and of itself, was notable but not necessarily alarming Since then, though, the wording has become more ominous. The quote from Fauci, that there’s a “very high rate” of reinfection, is only one example.

      Meanwhile, though, there continue to be serious unanswered questions from Manaus, and now we have the reports of the multiple-strain infections in Brazil, which brings an entirely new, and even more dire, scenario into the mix. We also don’t know how vaccine-resistant p.1 might be, although it does seem clear that vaccines are less effective against B.3.5.1.

  56. Doug H MD says:

    Marko: you wrote:”Crotty had the audacity to suggest that the vaccine data on reinfections smelled fishy, then when he was called out on it by Lipshitz, he cowered like a puppy caught peeing on the carpet.”
    Lnk please?

    1. Marko says:

      It’s in Crotty’s twitter thread that you’ve already been to once before. Lipshitz’ lame reasoning was that seropositives have already demonstrated that they’re more prone to infection than others, so that might explain their equivalent infection rate in the trials compared to seronegatives. The trouble is that multiple other studies show very high “efficacy” of protection for sero+ vs sero-, nevertheless Crotty “fully agreed” that this was a sufficient explanation for the bogus trial data.

      1. Chris Phillips says:

        Do you mean it was lame reasoning in the sense that he should have gone further and said there was something wrong with the data? Otherwise it sounds like a valid reason why the comparison could have been misleading.

        Wouldn’t the absolute numbers of reinfections of any kind be very small in the Novavax trial? Given that the trials are statistically powered to look at infections, not reinfections, and only part of the trial was in South Africa, I think they would need to give confidence intervals, not just percentages, to show that the comparison meant anything at all.

        1. Marko says:

          The same argument should apply to the reinfection studies that have shown very high (>90%) protection for seropositves vs seronegatives.

          What I find suspicious is that both the S.Africa and the Pfizer vaccine data showed equivalent infection rates among each group. In S. Africa, if the immune escape is 100% with the variant, I could buy it, maybe. But to see the same thing with the Pfizer data raises a big red flag. Crotty saw it that way , too. Then, after an intervention by someone higher on the food chain, he seemed to sense that it was not an appropriate topic of discussion among polite company and dropped it like a hot potato.

          1. Chris Phillips says:

            It seems hard to make much sense of the figures that are coming out of most of these trials, either by way of publication or leak.

            From the Novavax press release, I read it that of the 4400 participants, about a third were seropositive on enrolment. The overall efficacy is billed as 49.4% (for symptomatic cases), but with a huge confidence interval of 6.1% – 72.8%. It sounds as though that excludes those who had already been infected (“approximately 1/3 of the patients enrolled (but not included in the primary analyses described above) were seropositive”).

            Plugging the estimates posted by Daniel above into my little script to calculate efficacy, I get a confidence interval for the efficacy of seropositive status in preventing subsequent infection of 0-43%. Again, a huge interval.

            Only 6% in South Africa were HIV positive, so I have difficulty believing that – statistically speaking – any valid conclusions whatsoever can be reached for that subgroup.

            I don’t understand why the raw figures from these trials can’t be published in some form other than press releases. Maybe I’ve missed something or am forgetting something, but have detailed data from the Phase 3 trials been published yet for vaccines other than AstraZeneca?

          2. Marko says:

            “Plugging the estimates posted by Daniel above into my little script to calculate efficacy, I get a confidence interval for the efficacy of seropositive status in preventing subsequent infection of 0-43%. Again, a huge interval.”

            You make a good point. It could be that once the complete data is teased apart, if that’s ever possible, nothing much of significance is said about the relative protection provided by previous infection vs by the vaccine. This only heightens my suspicion that this is a marketing ploy. Float the idea that previous infection provides absolutely zero protection by press release, then if there are widespread cries of disbelief, release a more full dataset that moderates those claims somewhat so as to tamp down the suspicion. Or, if you think you can get away with it, never release the full data and just leave the doubters hanging. Either way you’ve seeded the idea, and given folks like Derek some ammunition to keep saying that vaccination is more effective than natural infection at preventing subsequent infection and disease.

  57. Marko says:

    The denialist gurus are masters of the “own goal” :

  58. Marko says:

    The graphic in this Topol tweet shows why one vaccine shot is plenty for seropositives, and why it may not be necessary at all :

    The strong anamnestic response to the vaccine dose is mostly complete by day 5-8. You’d expect a similar quick response to reinfection, likely resulting in asymptomatic or mild disease, if any.

    1. A Nonny Mouse says:

      Yes, my antibody positive son had quite a significant response to his dose of the Pfizer vaccine. He said it was like the day when he probably had the virus itself (similar to others at the hospital who had had a mild reaction) plus a very sore arm for 2 days.

  59. Doug H MD says:

    “The strong anamnestic response to the vaccine dose is mostly complete by day 5-8. You’d expect a similar quick response to reinfection, likely resulting in asymptomatic or mild disease, if any.”

    is there any good data on why we need one shot in seropostivies? Are they really at risk of dying with any frequency if reinfected?

    1. Marko says:

      No, but I’m with you on that. In this case, I think the absence of evidence is pretty damn good evidence of absence.

  60. Marko says:

    The data on the UK variant is coming in similarly from all over. Here’s Canada (Ontario) weighing in:

    ~8% per day relative prevalence increase vs other lineages. Will be at ~50% prevalence by the end of the month. Where’s the US data? Anyone? Bueller?

    Racaniello’s new CYA excuse is that it’s not more transmissible, it’s more “fit”. I’ve lost all respect for him as a scientist. He’s incapable of admitting his mistake.

    1. Marko says:

      One caveat for the Canada data : It’s completely based on the PCR S-gene dropout proxy (SGTF) rather than genomic characterization, but it’s a good bet that it’s the UK variant or one that’s close enough for gov’t work.

  61. Marko says:

    We’ve seen how contagious insanity is over recent times , but this may be one instance when sanity is becoming contagious :

    Experts tout delaying 2nd COVID vaccine dose as US deaths mount

  62. Marko says:

    I was skeptical, but the evidence is mounting for low level infection persisting in a significant subset ( ~5% ) of patients for several months :

    SARS-CoV-2 persistence is associated with antigen-specific CD8 T-cell responses

  63. Chris Phillips says:

    Sorry if it’s a bit off-topic, but I wondered whether anyone had any thoughts about the UK’s testing “blitz” for the South African variant, prompted by the discovery, in testing of samples, of 11 cases that haven’t been linked to international travel.

    So now they are trying to do universal testing of all adults in the areas where it has been found.

    I wonder what the thinking behind this is, and whether it is likely to be effective. It seems unlikely to me that it can be kept out of the UK without much stricter quarantine enforcement, and with the overall rate of positive tests falling quite rapidly (evidently including the UK variant) I don’t see why community cases of the South African variant should increase significantly in number so long as the lockdown continues.

    Presumably they are trying to reduce the numbers to a minimum until we know more about the variant, but what then, if the vaccines aren’t effective enough against it? Perhaps the idea is to delay its spread and to keep significant restrictions until a retuned second wave of vaccination in the Autumn?

    1. Ancient Briton says:

      GOV.UK, PHE and SAGE in high visibility jackets.

      Yesterday’s official spokesperson same one and only who didn’t understand PCR testing the other week…

      “Surge testing” – honestly, we might as well be ducking witches.

  64. Chris Phillips says:

    New from Public Health England:
    Detection of E484K mutation in B.1.1.7 VOC 202012/01 The COG-UK dataset (total sequences 214,159) was analysed on 26/01/2021. The spike protein mutation E484K (found in VOC 202012/02 B1.351 and VOC 202101/02 P1) has been detected in 11 B1.1.7 sequences. Preliminary information suggests more than one acquisition event.

  65. Chris Phillips says:

    New from Public Health England:
    “Detection of E484K mutation in B.1.1.7 VOC 202012/01 The COG-UK dataset (total sequences 214,159) was analysed on 26/01/2021. The spike protein mutation E484K (found in VOC 202012/02 B1.351 and VOC 202101/02 P1) has been detected in 11 B1.1.7 sequences. Preliminary information suggests more than one acquisition event.”

  66. Mariner says:

    I’ve just had a thought. We know that the South African variant B1.351 appears to be able to evade antibodies in convalescent sera from some people who have previously had ‘older’ variants of the illness, leading to some reinfections. What about the antibodies of those who have had the UK variant B.1.1.7? Has this been tested anywhere at all (I may have missed it).

    It occurred to me that the similarities between these two variants might just lead to greater immunity between them from previous infections? Just guesswork.

    I suppose the B.1.1.7 variant hasn’t been around all that long so you wouldn’t expect much waning in immunity from those infections which might make a difference.

    Either way, it could end up being the case that B1.135 isn’t perhaps able to spread as easily in populations which had faced a lot of B.1.1.7 infections. I suppose we’ll have to see if many more of the South African variant infections are discovered from these attempts as large scale testing?

  67. Bash says:

    So, I am starting to wonder why the ‘experts’ in this field aren’t parsing the data appropriately. Reinfection has been mentioned many, many times, but what are the circumstances? Was the 2nd infection more, or less severe? Was it trivial?

    And regarding efficacy; if overall efficacy against different strains is 50%, 70%, 80%, but across the board efficacy against severe disease is constant, then what am I missing?

    If we look beyond the next weeks or months, and instead look at 10 years from now – COVID-19 is with us forever, but ideally as a managed illness where everyone is vaccinated and only gets mild/moderate bouts at worst. I don’t know any infectious disease expert who has said anything otherwise

    What am I missing? Why are we still talking about sterilizing immunity?

    1. DataWatcher says:

      Meanwhile, I think one reason for the growing worry has to do with the proliferation of mutant variants, and the concern that it could evolve further and completely evade immunity, undermining vaccination efforts entirely, becoming ever-more contagious along the way. The nightmare scenario is a virus as contagious as measles that also consistently mutates into newly resistant strains.

    2. DataWatcher says:

      You’re right, though, Bash — we continue to hear “expert” testimony, from Fauci on down, saying that we’ll know we’re getting somewhere closer to “normal” when CASES (or INFECTIONS) drop precipitously and remain at that low level (exactly how low is never specified). It’s acknowledged that J&J and the others will protect against serious infection and hospitalization, but the link between that and potentially “normalizing” our lives and the economy seems not to be discussed.

      So I ask the same question you do — Am I missing something? Would there still be too many problematic, *potentially* serious COVID cases that wouldn’t necessarily result in hospitalization but which we’d need to monitor carefully? Or is it, indeed, that a population full of asymptomatic/mildly symptomatic carriers would be a population full of “mutation incubators,” eventually resulting in a massive re-outbreak of more contagious, resistant strains? Or is it the fear that if people hear this they will become too lax, get too careless, and start acting as “superspreaders” again, before overall population immunity is ready to handle it?

  68. DataWatcher says:

    I’m not sure the extent to which this report from Israel can be generalized — it’s a preliminary report from one particular situation, it’s not from an academic journal, and it’s anecdotal. It doesn’t address 351 or P1, both of which seem equipped with significant immune escape potential, and it doesn’t address the issue of severity in cases of reinfection. Nonetheless, it seems encouraging . . .

    “[Maccabi Healthcare Services vaccine statistics analyst]  Ekka Zohar said she was encouraged by the light symptoms of vaccinated people who caught the coronavirus, as well as by the low infection rates. ‘None have been hospitalized and they have very very light symptoms,’ she stated. ‘We are talking about headache and a mild feeling of sickness, and they are almost completely without fever. It’s really a very light illness.'”

    Here’s the source:

    1. DataWatcher says:

      On the other hand, it’s now looking as if a new 117 variant has appeared, which is better than the original at evading immune protection.

  69. Chris Phillips says:

    Published results of the Phase 3 trials of the Sputnik vaccine in the Lancet:

    Assuming this is right, is the greater efficacy than for AZ attributable to the two doses using different vectors?

    1. Marko says:

      If I read this sample data right, it looks like seropositives could have made up ~15% of the overall trial group :

      “17 (15%) of 114 participants in the placebo group had RBD-specific antibodies on day 42, probably associated with asymptomatic COVID-19; however, none of these participants were SARS-CoV-2 PCR positive, nor did they report the onset of respiratory symptoms in the electronic diary or when interviewed as part of the telemedicine follow-up.”

      1. Chris Phillips says:

        Thanks. I suppose that shouldn’t really tend to bias the efficacy figure, provided the randomisation was OK.

        One detail I found reassuring was that the headline efficacy figure was above 90% for all age groups, though numbers in the 60+ group were relatively small.

  70. Marko says:

    New study on the UK variant :

    “We examined the effect of SARS-CoV-2 variant B.1.1.7 on the symptoms, disease course, rates of reinfection, and transmissibility in the UK. We found no change in symptoms and no increase in overall disease severity. We found a low rate of reinfection (0.7%) and no evidence of increased rates associated with B.1.1.7. We found an increase in R(t) of ~ 1.38 (95% CI
    1.06-1.71), but evidence that lockdown measures are effective even in regions with very high
    (>80%) proportions of B.1.1.7.”

    This involves the variant before acquisition of the 484 mutation, of course. It will be interesting to see if there are forthcoming attempts to explain away the Nervtag report claims of increased mortality, or whether their caveat of “not so confident in these results, really” is considered sufficient.

    Not that this study is the last word. There may be yet more to come on this, but I have a feeling that there’s not much going on with mortality differences, and certainly not a 30% increase.

    1. Marko says:

      This is a sensible, and important , recognition of the realities of trying to study reinfections:

      ” We make the assumption that testing positive for SARS CoV2 after an interval of 90 days with at least seven days of freedom from symptoms in the interval is consistent with
      reinfection. Repeated positive testing has been reported shortly after hospital discharge and
      showed that PCR positivity could be detected up to 28 days post symptom resolution. While the chosen cut-off of 90 days between two positive tests is unlikely to be due to prolonged PCR positivity, this cannot be ruled out, but would only affect a small number of cases.”

      Requiring genomic identification of both the primary and second infection means never having enough data to say anything at all. Particularly now in S.Africa and Manaus, where we need to know what’s happening with regards to immune escape variants and reinfection and the associated morbidity and mortality, they need to relax the strict standards. Look at first wave vs second wave PCR+ infections/reinfections, which is separated by several months, and accept that a tiny fraction of your reinfections may actually be reactivations. Just get some data out there.

    2. Chris Phillips says:

      I think the NERVTAG caveat was good enough. I think they put the likelihood of increased fatality at 40-50%, and certainly the published discussion was hedged with caution at every step.

      Of course, the handling of it by politicians was quite different – as with the early 70% estimate for increased transmissibility and Hancock’s claim that vaccines would be only 50% as efficient against the South African variant (based on in vitro studies).

  71. Marko says:

    Extremely high SARS-CoV-2 seroprevalence in a strictly-Orthodox Jewish community in the UK

    “A total of 343 households, consisting of 1,759 individuals, were recruited. Serum was
    available for 1,242 participants. The overall seroprevalence for SARS-CoV-2 was 64.3%
    (95% CI 61.6-67.0%). The lowest seroprevalence was 27.6% in children under 5 years and
    rose to 73.8% in secondary school children and 74% in adults. Antibody titres were higher in
    symptomatic individuals and declined over time since reported COVID-19 symptoms, with
    the decline more marked for nucleocapsid titres.”

    Seems like a likely hotspot for immune escape mutation selection pressure.

    1. Chris Phillips says:

      That is interesting. Unless I’ve missed it, they carefully avoid mentioning where the study was done. But I remember noticing during the first wave that there were high positive test rates in an area associated with such a community. That area seems on the whole to have rather lower rates now than neighbouring ones.

      I don’t know much about immunology, but I wonder whether it can be bad to have high levels of previous infection. Isn’t this how pandemics subside in the natural order – they burn themselves out? If it’s true that “Russian flu” in 1889 was really coronavirus OC43, isn’t that what happened to it?

      As for the argument that we should stop vaccinating because it will encourage immune escape, that seems crazy, because the data suggest that even moderately effective vaccines will cut the numbers and reduce the likelihood of mutations.

      1. Marko says:

        Yes, for the seropositive people in that community the worst is over for them if subsequent infection is essentially just like a common cold, so for them immune escape mutants might just mean they’d get that cold sooner than they otherwise would if it was simply a matter of their antibody levels waning over time.

        However, for those uninfected in that community or those surrounding, immune escape mutants mean that viral spread is going on around them at a higher level than it otherwise would be. The seropositives have effectively converted to seronegatives, and the virus has a higher density of susceptible people to spread among.

        Think of a community with 99% seropositivity. Even measles would fail in that environment, much less coronavirus. But with an immune escape mutation that is complete in its effect, it would be like Day 1 of the pandemic, except that now people would get infected without getting very ill , assuming the cold analogy holds up. They’d still spread the disease to the vulnerable nearby, however.

        Once everyone is either infected or vaccinated, I think variants are no longer a concern if the common cold model holds. We just get more colds when a new one pops up, perhaps. But lots of people can still die before we get to that point, and immune escape and transmissibility variants will make it that much harder to protect the vulnerable until we get them vaccinated.

        I agree that the fear of immune escape shouldn’t hinder our vaccination efforts. We can potentially vaccinate all of those at risk of serious disease in the matter of a few months if we get our shit together. Vaccinating seropositives and healthy young hospital desk-jockeys in a time of vaccine scarcity is not consistent with having our shit together.

        1. Chris Phillips says:

          But do you actually think it would be better if there were no acquired immunity, only immunity conferred by vaccines?

          Why should acquired immunity lead to more immune escape than immunity conferred by vaccines?

          1. Marko says:

            “But do you actually think it would be better if there were no acquired immunity, only immunity conferred by vaccines?”

            No, absolutely not. For all we know, natural immunity may be superior to vaccine-acquired, both in quality and durability. The reinfection studies provide good reason to make that bet already. I’d prefer if young children never need vaccinating at all, instead acquiring their immunity naturally as for the other human CoVs. For older adults and other at-risk groups, however, It’s clear that it will be safer for them to get their first “exposure” via vaccine. The question about natural immunity that remains unanswered regards the variants. Does natural immunity fail to protect you against severe disease outcomes with some variants? That doesn’t appear to the case with the other human CoVs, but we don’t know yet with CoV2. That’s why I’m so impatient about getting the relevant reinfection data from places like Manaus and S.Africa regarding this question. To put it simply, I think we need to see a durable 5-10x reduction in the rates of severe disease and death, from any and all strains, among those who’ve been infected before or those who’ve been vaccinated, before we can put the idea of perpetual vaccine updates and boosters to bed. I’m still hopeful we will see such a reduction.

            ”Why should acquired immunity lead to more immune escape than immunity conferred by vaccines?”

            I don’t see any reason to think it would, other things equal. Waning Ab titers might provide fertile ground for immune escape mutations, and right now there’s probably more of that among the naturally-immune. Immune escape in either group is bad only to the extent it frustrates our efforts to save lives by getting all of the at-risk vaccinated, by expanding the pool of infection-susceptibles and thus continually re-fueling outbreaks. Manaus and S.Africa are probably good examples of this, though vaccines aren’t likely to save them any time soon. However, they may be the first places to demonstrate our hoped-for “CoV common cold #5” final outcome, once everyone has been infected once, but they will have paid a dear price to get there first.

  72. Marko says:

    Bats don’t deserve the bad rep. Blame the virus. :

  73. Marko says:

    Higher viral load means greater transmission :

    “In our study, the viral load of index cases was a leading driver of SARS-CoV-2 transmission. The risk of symptomatic COVID-19 was strongly associated with the viral load of contacts at baseline and shortened the incubation time of COVID-19 in a dose-dependent manner.”

    It’s nice when you find out that things you think make sense actually do make sense.

  74. Marko says:

    This will ruin Rasmussen’s day :

    Mechanistic transmission modeling of COVID-19 on the Diamond Princess cruise ship demonstrates the importance of aerosol transmission

    I only wish they’d called it “miasma” instead of aerosol.

  75. Marko says:

    B117 frequency in US states :

    ~5% in Florida and ~1.6% in California ( about 5% in San Diego County per a different report)

    I think this qualifies as “liftoff” in the US. In ~3-4 wks, should be over 50% prevalence in Fl. if the pattern holds.

  76. Marko says:

    Protection against infection (including asymptomatic) afforded by seropositivity in 18-20 yr old Marines :

    “…To make it similar to the vaccine trial endpoints: 3 symptomatic cases in the 189 initially seropositive individuals, and 347 symptomatic cases in 2,247 seronegative individuals. If this were a vaccine clinical trial, the point estimate for vaccine efficacy would be 89.7%”

    And this was in a high attack rate environment.

    1. Marko says:

      Against all infection, including asymptomatic :

      “This study of primarily young, male Marine recruits found that the presence of antibodies to
      SARS-CoV-2 conferred an 82% reduced incidence rate of SARS-CoV-2 infection. ”

  77. Marko says:

    UK Biobank seroprevalence study :

    “…One of the most significant findings of the study is that 99% of participants who had tested positive for previous infection retained antibodies to SARS-CoV-2 for 3 months after being infected, and 88% did for the full 6 months of the study. This discovery provides an early indication that the antibodies produced following natural infection may protect most people against subsequent infection for at least 6 months.”

    1. Chris Phillips says:

      I can’t really work out from that what they’ve done. Whether all the participants were tested every months for six months, or whether they were recruited continuously for monthly testing. The phrase “provided at least one sample” suggests the latter.

      In which case they can’t really say anything about the rate of persistence of antibodies until three months after infection, only about persistence after the first test. Given that the study started a month and a half after the peak of the first wave in the UK, it may well be that people were typically recruited several months after infection.

      Given that previous studies have indicated quite a rapid waning of antibodies in the first few months, does this indicate that the waning becomes more gradual after that, which would be good news? I suppose one would have to dig more deeply into the details of the various studies to work that out.

      1. Marko says:

        “Given that previous studies have indicated quite a rapid waning of antibodies in the first few months, does this indicate that the waning becomes more gradual after that, which would be good news?”

        Crotty has said he thinks there’s a bi-phasic decay curve, with a long tail of persistent antibody, but I don’t think there have been studies taking sequential samples over a long enough period to really pin it down yet. My guess is that there are some long-lived plasma cells cranking out some background antibody level for a period measured in years that will be measured with sensitive assays as the field matures. Regardless, the B-cell memory response will be there to kick into gear upon reinfection.

        The main takeaway for me was the finding that 99% of PCR positives developed an antibody response, showing that very few people are incapable of doing so, which is comforting.

        I know that some asymptomatics generate weak Ab responses, but presumably they’d still have the memory reserve. The lack of much circulating Ab would mean that they’d be more likely to be reinfected than the stronger seropositives, I assume, but the fact that they were asymptomatic on the first infection may indicate that they’d also handle the next one well.

  78. DataWatcher says:

    “J&J applies for emergency authorization; FDA expected to greenlight in coming weeks”:

    Time is of the essence — hope this doesn’t take too many of those “weeks” to happen.

    1. debinski says:

      VRBPAC meeting is set for Feb 26 according to the article. That’s 3 full weeks already – seems unnecessarily slow.

  79. Marko says:

    Handy graph of B117 progression in five countries :

  80. Marko says:

    Want to know what the daily deaths figure is in Sweden for today? Check back in two weeks :

  81. Marko says:

    No jump in suicides in 2020 , per suicidologist:

  82. Marko says:

    “We’ve updated our preprint on the transmissibility of SARS-CoV-2 VOC 202012/01, aka B.1.1.7, with new statistical and modelling methods. Headline: we estimate VOC is 43–82% more transmissible than preexisting variants. ”

    Includes a graph showing a possible signal of increased severity/mortality, though the error bars are wide. It at least hints in the same direction as shown in the Nervtag report.

    1. Chris Phillips says:

      On transmissibility, that isn’t a confidence interval, but the range covered by six separate estimates, each with its own confidence interval. The confidence intervals range from 38-48% to 75-91%. Clearly (at least) one of those estimates is way out. I had thought the estimates were converging to mid-30s, but we seem to be still in the realm of “guesstimates”.

      1. Marko says:

        Yes, it’s frustrating the way the transmission estimates have been ping-ponging back and forth. This study in the US pongs back to the lower range :

        “….with a doubling rate of a little over a week and an increased transmission rate of 35-45%. “

  83. Marko says:

    “Police cracking down on COVID-19 lockdown breaches in Lancashire found an illegal drinking den, complete with full bar, snooker table, a large TV and, er, two sheep.”

    The sheep were issued citations as they were not wearing face masks.

    1. Chris Phillips says:

      When, oh when, will people learn about the dangers of zoonotic disease?

    2. DataWatcher says:

      Uh . . . according to the denialists and the anti-vaxxers, it’s the “sheep” who DO wear face masks. Rampant speciesism??

      1. Chris Phillips says:

        Meanwhile, in the UK, goats have been paid £50,000 to attend Zoom meetings. Strange times.

        1. Marko says:

          Strange quote from the story :

          “She added that it was “more fun” than selling manure to make ends meet.”

          That’s not really saying much, is it ?

  84. Mike says:

    Derek (or other smart people) – if someone was going to take the J&J, or other adenovirus vaccine, would supplements with perceived antiviral characteristics lower the vaccine effectiveness in anyway? Something like quercetin, or a regimen of quercetin/zinc/VitC. Could these supplements, their antiviral/zinc ionophore potential, have negative effects and maybe people should supplementing prior to vaccination?


    1. Derek Lowe says:

      I’m pretty cynical about those, to be honest. I don’t think that they have much noticeable antiviral effect to start with, but no, even if they do something, the mechanisms by which they might slow down a virus wouldn’t be expected to interfere with the vaccine mechanism, either. Should be fine!

  85. egil says:

    Does anybody have a link where effectiveness of the J&J vaccine is reported with confidence limits? Given that they break up their estimates by countries, I suspect they are quite wide.

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