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Preparing For the Vaccine Results

So let’s take a few minutes to think about what happens when the vaccine trials start to read out. I’m making the assumption that the data will be freely available in a timely manner (which means before any decisions are made), because the alternative to that is Not Real Good. Another not-real-good alternative would be to declare the first one to read out the instant winner, because (as noted by Anthony Fauci) that would certainly screw up the trials of the others. But if we avoid these mistakes (no guarantees are expressed or implied), there are still a number of fairly likely things that I don’t believe the general public is quite ready for.

One of those: what if the first vaccine results aren’t very impressive? This could happen. I’m really hoping it doesn’t, but anyone in the business will tell you that you don’t know what efficacy is really going to be like until you run an efficacy trial, and that goes for vaccines as much as for anything else. I will say that the available biomarkers (antibodies and T cells) are much stronger in vaccine work than they are in many other areas, but on the other hand, it’s immunology. Which is full of fun and interesting surprises. So if the first trial to really give a solid efficacy read comes in lower/weaker than we’d all like to see, my guess is that the press and the public won’t take it too well. There will be a rush to “OMG We Can’t Make A Vaccine To Corona” takes, I think, which will sow some despair and panic. I would expect the stock market not to take the news well, either.

But even if the first results aren’t great, it doesn’t mean that we’re (necessarily) hosed. That’s the good thing about having several different vaccines going, with different platform technologies. We are really going to have to wait and see what the various approaches are going to produce, even though “wait and see” is not exactly the zeitgeist right now. We have the different adenoviruses (and other vectors, which will come later), the inactivated-virus vaccines, the mRNA candidates, the recombinant proteins – there’s no reason to think that these are all going to come out the same, and that’s going to be important to keep in mind.

To that point, here’s another possibility that’s quite possible: the Patchwork Quilt of Efficacy. What if we get a mixture of results, with Vaccine A being pretty good, but not in older patients, while Vaccine B seems better in that cohort but is harder to roll out for distribution, while Vaccine C showed more even results over various patient cohorts but is beaten by some other candidate in any particular one, while Vaccine D was strong but definitely had more adverse events. . .you see what I mean. I can easily imagine something like this happening, and the thing is, it’s not just going to drop all at once. We’re going to get those various results one after the other and will have to fit them into an unavoidably messy picture, adjusting our plans as more data points become available. Overall, I think it could be a serious mistake to declare a winning vaccine too early (unless something comes in just kicking coronavirus ass all over the field, which would frankly be fine), but telling everyone to wait while we see what the next ones bring is probably not going to go over well. There will be tremendous pressure to just start dosing people with anything that looks reasonable, and you can’t blame anyone for it.

Regarding those adverse events, I’m no immunologist, but the one that I’m worried most about is probably Guillain-Barre syndrome. Pronounce that one something like gee-YAH bur-RAY for maximum effect, but I’ve heard plenty of other more Anglicized pronunciations in the wild. No matter how you say it, GBS is an autoimmune response that leads to an attack on the myelin sheaths of the nervous system – bad news, obviously, but the good part is that most cases resolve. Not all of them do, though, and even many of the resolved ones involve spending time in a hospital in pretty serious condition. GBS happens spontaneously after some respiratory infections, for immunological reasons that are still being worked out, and is most commonly seen in younger women. It can come on after vaccination, in the same way as it can come on after infection, and it’s widely recognized as one of the big problems with the 1976 swine flu vaccine rollout, and is certainly something that vaccine developers in general keep an eye out for. We do not want to have to wrestle with this problem, but it’s a rare enough event that only the large Phase II/Phase III trials will have a chance of giving us a read on it at all. For context, the 1976 vaccine is believed to have caused one extra case of GBS per 100,000 people vaccinated – it’s the sort of thing you might well not pick up on at all until you’re going out into the broader population. “Teenager Rushed to Hospital After Coronavirus Shot” is not a headline that will do anyone any good.

That wider population is always the worry, immunologically. We all have different immune systems – that’s the point, otherwise one plague or another would have wiped us off the planet by now. The number of rare immune-linked disorders is large and various because of this, and that means that the response to any new vaccine could show some oddities as you start heading out into millions of people Tens or hundreds of millions – yeah, you would have to expect some rare and bad events to poke up, and if one of them happens with major media coverage, things could get ugly.

Even if things go well, though – and I continue to think that for at least one of the vaccine candidates they will – there are some complications. All but one of the vaccines being tested now (J&J’s is the exception) will need a booster shot some weeks after the first one. And from the antibody titers we’ve seen in the Phase I trials, you wouldn’t necessarily expect that much protection with just one shot. People are going to have to realize this: the first shot will not mean that you’re in the clear, as ready to shed your mask and hit the streets as you might be. For that matter, it’s still going to take some time after the second shot to reach protective levels, so it seems, so it’s not like even the booster will mean that you can hit the karaoke bar that evening. We will need to be ready for “I Got the Vaccine And I Got Coronavirus Anyway” reports that will turn out to be due to one of these situations. The logistics of getting everyone through a two-shot immunization course will be nontrivial, in any event.

OK, I don’t want this post to be too depressing – we need to keep our eye on the likelihood that we’re going to see an effective vaccine in the coming months. That’s going to be great, but nothing says that launching it into the world has to happen smoothly. One last point: when we launch that vaccine (or those vaccines), we are not only going to have to be transparent about why the choice was made the way it was: we’re also going to have to be transparent about who gets it first and why. Frontline medical workers, surely, and others in similar positions. People who do economically vital jobs (supply chains, etc.) whose work unavoidably puts them at higher risk. You can come up with more categories easily, but one category that I hope we avoid is People Who Know Some People. If there’s a perception that the well-connected are cutting the line, that’s not going to go over well, either, and it shouldn’t. I would recommend being completely open about the order of vaccination and trying to stick to it, visibly. Ideally, this should be publicized before we even start getting vaccine readouts, but we’ll see. . .

228 comments on “Preparing For the Vaccine Results”

  1. David G Whiteis says:

    I hope this isn’t a scientifically illiterate query. Theoretically, the idea that a vaccine won’t be a “one-size-fits-all” proposition could be a good thing; if several vaccines made the cut, and each could be targeted to a specific population, then the volume of production for each could be reduced. However, this rasies a question: Leaving aside for a second the ethical implications of a relativly privileged individual in a relatively privileged country like the U.S. having the resources and access to do this, is it feasible, from a medical standpoint, for a person to get vaccinated, then later on discover than another vaccine has been found to be more effective for his or her personal situation, and “switch” to that one? Or is mixing vaccines the equivalent of mixing medications? Are we “stuck” forever (pardon the pun) with the first one we choose?

    That being said, I fear very much the effects of out-of-context scare headlines such as the ones postulated here (to say nothing of the “viral” effect of social media). A handful of outliers, reported sloppily, could annihilate the possibility of enough people trusting a vaccine in order to ensure its success in enhancing immunity. (In some ways, I think, we might have already seen this with the reporting on the Hong Kong “reinfection” incident.)

    I also fear the “logistics of getting everyone through a two-shot immunization course” — I’m afraid that “nontrivial” doesn’t begin to describe it. It will mean doubling the amount of vaccines made available (from about 320 million to about 640 million in the U.S. alone) and doubling the cost involved. Perhaps more importantly, it will create a significant barrier for efficacy — we need to remember that being able to plan a month ahead for something like this is a privilege that many people in the world — poor people, homeless people, people with mental health problems and/or chaotic persona lives — do not enjoy. People whose lives are a matter of week-to-week, day-to-day, or even hour-to-hour survival are not likely to be able to keep their appointments. This won’t be a trivial issue moving forward.

    1. Dan says:

      I’m not old enough to have personally witnessed the polio vaccine rollout, but my understanding is that quite a few people ended up getting both versions of that at one point or another. But you’d want to test the safety and efficacy of that separately – it’s unwise to assume that they’d be safe together just because they’re safe independently, and depending on the means (particularly stuff like the adenovirus vector vaccines, in my layman’s understanding – which has been greatly improved by Derek’s posts), it’s possible that the first shot could interfere with the second and make it less effective than it would otherwise be.

      1. Paul W says:

        I remember the polio vaccine rollout very well. I received both the Salk vaccine (an injection) and the Sabin Oral Series (SOS). A lot of the needle-shy baulked at the Salk vaccine; it was the SOS that delivered the knockout blow to polio in the US. The SOS required two (or more?) doses over a period of weeks. I remember the ampules being on a shelf in our refrigerator.

        1. Walter Sobchak says:

          The Salk vaccine was rolled out in 1955. I was 8 years old and I remember standing in line in front of my school waiting to be vaccinated. We all got vaccinated. There was no real alternative. The Sabin Vaccine rolled out in 1961. I was 14. I took that vaccine too.

          There were no anti-vax activists back then.

          We were very glad to have either vaccine. Polio was scary. I think a lot scarier than covid because polio targeted children and young adults.

          There was an excellent PBS special about the polio vaccines earlier this year. I highly recommend it:

          Watch The Polio Crusade | American Experience | Official Site | PBS

          1. Derek Freyberg says:

            As with Paul W and Walter Sobchak above, I had both the Salk and Sabin polio vaccines as a child. As an adult, I’ve also had both the current pneumonia vaccines (I understand those are targeted to slightly different strains, though I believe there’s overlap) and both the shingles vaccines, Zostavax and Shingrix (though Zostavax is no longer routine in the US as of a month or so back). Typically, there is not a problem receiving two different vaccines against the same illness. But there is apparently a consideration with adenovirus-based vaccines (the mRNA vaccines) that people might have antibodies against the adenovirus and the vaccine therefore not provide immunity against the new antigen – and this has been discussed before on this blog and elsewhere. So I suppose there may be situations where you can’t just take each currently favored vaccine in turn (even assuming availability).

        2. Stefan Stackhouse says:

          We all had both Polio vaccines as soon as possible after they came out. We and our parents were all terrified of the images of unfortunate kids just like us in iron lungs, and avoiding that was reason enough to get both vaccines just to be safe.

          The only case where some people were reluctant to get the vaccine was right after a bad batch was produced of the Salk. That was a temporary monkey wrench in the works, but action was taken, the public was reassured, and vaccinations were soon back on track.

      2. Charles H. says:

        FWIW, I had both the Salk and the Sabin vaccine, but they were well over a year apart. From what I gathered at the time the Sabin vaccine worked better for those who had previously had the Salk vaccine. There were fewer side effects. Etc.

        You can’t really generalize this though. Some viruses can be worse with multiple vaccines. (Dengue fever is the only one I’m really sure of here, but it’s an existence proof.)

        1. HFM says:

          Also FWIW, I’ve had both too. I vividly remember getting the live oral vaccine as a child – I’d very patiently put up with an armful of needle holes, and then the last one they simply fed to me as a dropper full of grape-tasting stuff. I was outraged. You mean I could’ve just eaten them all?! My parents tried to explain to me that polio was special, but I wasn’t having it. Those lazy, child hating doctors needed to get on it and make all vaccines in edible form.

          About 25 years later, I was working in a virology lab, and somebody wanted to work with polio on common equipment, so I got the booster – the inactivated stuff. Only side effect was a double-take from the guy screening blood donors, when I gave blood a month later.

      3. Marko says:

        “… it’s unwise to assume that they’d be safe together just because they’re safe independently”

        We test the safety of drugs independently and then we gobble down 2-5 ( or more ) combos of them every day without thinking about it.

        Safety of vaccine combos will be evaluated just like dug combos are evaluated , via post-marketing surveillance.

        Not that I believe we do such a bang-up job on such surveillance , but that’s the theory , anyway.

    2. RandomWok says:

      The situation Derek mentioned about no “one size fits all” vaccine is not a new one. There have always been differences in efficacy and demographics for current vaccines. There are differences between Zostavax and Shingrix, between the injected and nasal spray (FluMist) versions of the flu vaccine (efficacy/inefficacy between pediatric and geriatric populations). So if different flavors of the Covid-19 vaccine target different segments of the population, it won’t be the first time we encounter that – the caregiver would make the selection based on label criteria.

      1. David Winsemius says:

        There were relatively few “caregivers”, if by that you mean a personal physician who has a 1-1 relationship with the recipient, involved in the administration of the polio series … either the Salk or the Sabin versions. They were both administered in schools where entire classes were assembled in public areas and walked up one at a time to the chair or table where the shots or ampules were administered.

        1. RandomWok says:

          Current vaccinations are delivered either in a physician/nurse practitioner/pharmacist setting, hence I used the generic term “caregiver”. If it is rolled out on an industrial (mass-vaccination) scale, others (paramedics, etc etc) would also be involved. But the choice of the vaccine administered would be based on predetermined guidelines, i.e. Label. I’ve administered vaccines myself, and the choice of product is tailored to the patient. All these solutions are already in place.

    3. Philip says:

      People have gotten both versions of the shingles vaccine. From the CDC (a source you could trust):
      “You may have already got a different shingles vaccine called Zostavax. If you did, you still need 2 doses of Shingrix.”

      1. Alan Goldhammer says:

        Yes, both my wife and I got both. The Shingrix has a very good adjuvant and high level of antigen. the first shot for me was fine. The second one brought on every side effect on the product label and as it noted, all of them were gone the next day. Most of our friends also had reactions with the second shot. It beats getting shingles.

    4. Barry says:

      A few of the vaccine candidates do use a “vector” (commonly adenovirus) virus to carry the Covid antigen code. With these vaccines, you will mount immune responses to both the covid antigen (probably Spike or the RBD of Spike) AND to the viral vector. A second vaccination using the same viral vector might be defeated by your host-vs-vector immunity.

    5. A Concerned Conservative Scientist says:

      I’m also curious if and how insurance companies will weigh efficacy when deciding which vaccines to cover and tier.

      I can’t imagine the average patient trying to decide between vaccine options if their HCP gives them a choice. How would someone determine their own risk tolerance, especially given new modalities such as mRNA and DNA vaccines with little long-term safety data?

  2. bacillus says:

    I would argue that the ultimate aim of any COVID vaccine is to protect the most vulnerable, and the death statistics identify the elderly, and people with certain underlying medical conditions as the primary at risk groups. Based on the flu vaccine, the current approach is to vaccinate everyone in order to protect the vulnerable. However, with pediatric vaccines, we just target babies and young children, since most adults can shrug off the infectious diseases that dote on an immature immune system. Also, in the case of flu, it is secondary infection with Streptoccci that poses the greatest risk of dying, and we now have an anti-Strep vaccine specifically aimed at old people. Shingles vaccines have also been developed with the elderly in mind. In answer to the original poster, there is good evidence that one can effectively switch between the two shingles vaccines. This being the case, one could argue for a more nuanced flu vaccine program than universal vaccination which has appalling take up rates. Regardless, I think it is important to include sufficient numbers of “at risk” individuals in any Phase 3 trials for COVID, as I believe that we should expect far better compliance with these groups than the population as a whole. Moreover, this is where efficacy is most likely to show up, and hopefully this will encourage les autres as the vaccine becomes more readily available. Short of mandatory vaccination, I can’t imagine too many of the general population rolling up their sleeves for a vaccine that, even if effective, will be of little consequence to the recipient.

  3. Giannis says:

    It’s very unlikely that the first shot will not offer at least some protection. Especially the AZ vaccine only increases the antibody titres by 4x after the second shot.

    1. joeblo says:

      Since our fearless leader has proposed releasing AZ’s vaccine before the election (and end of Phase III), I’d wonder if AZ would go along with that. Would they risk their reputation? Can he really force them to produce it (Defense Production Act) and distribute it in such a short time without their cooperation?

      1. G Man says:

        Today we learned that China has, in fact, been administering the sinopharm vaccine since July, outside of the clinical trials.

        1. Charles H. says:

          Is that the one they’ve been using on the military for several weeks?

      2. Luke says:

        AstraZeneca is incorporated in England so ultimately lies outside Trump’s jurisdiction. That said, as they sell a lot in the US he could probably make things unpleasant for them if they didn’t toe his line.

      3. Roy Badami says:

        But Emergent BioSolutions has a contract to manufacture the Oxford vaccine in the US.

        If the US government were to order Emergent BioSolutions to hand over the vaccine, it might be hard for AstraZeneca to stop them.

  4. A Concerned American says:

    Why did this Radical Left-Wing Mob Bomb-Thrower Marxist Derek Rowe trash our esteemed President Trump regarding the convalescent plasma approval? What medical school did Rowe attend, what clinical experience, what medical training or education has this egocentric pseudoscience specialist Derek Rowe fool ever had? ZERO!

    Perhaps Derek Rowe would be better off in the streets doing some Rioting, Looting, and Burning with the Radical Liberal Democrat Mob that he loves so much. Rowe should not be trusted since he is clearly a Communist Agitator. He even stifled free speech and justified outrage at his disgraceful slander against President Trump. Rowe likes to hurl abuse at our Great President, then he shuts down the comments so no one can call him out on his warped political statements.

    Rowe should should keep his asinine political and medical opinions to his little junk-science Bolshevik mind.

    Should Rowe keep disseminating political falsehoods and socialist propaganda, his illegal dispensing of medical advice will have to be investigated.

    1. Anonymous says:

      You son again?

    2. G2 says:

      Maybe Rowe is that bad, nevertheless I love the informative blog of Derek Lowe…

      1. John Wayne says:

        This is a great opportunity to do some Dr. Jekyll and Mr. Hyde posting, but with more rhyming.

    3. chemist says:

      The only expertise Derek has is sitting in front of a fume hood making molecules that go on to fail in FDA trials

      1. A Concerned American says:

        Pitiful. Derek is nothing but an Apothecary Wanna Be.

        He should focus on medicinal herbs and homeopathy instead

    4. GamingBuck says:

      russian bot

      1. johnnyboy says:

        Was thinking the same. Russia’s ‘Internet Research Agency’ must be all maxed out on facebook and broadening its target sites.

        1. chemist says:

          “Comments that don’t conform to what I expect in my liberal safe-space echo chamber must be made by Russian bots.” Seriously, how stupid can you be?

          1. johnnyboy says:

            You might not be a russian employee, but you’re definitely a russian tool. Same difference, except in the latter case you’re stupid enough to spend your time trolling without getting paid for it.
            No need to reply, though I’m sure you will.

      2. chemist says:

        “Anyone I don’t like is a Russian bot” – you’re dangerously brainwashed. I bet you’ll have a full mental breakdown when Trump wins again.

        1. Joe Blo says:

          Please, triggered bot… keep posting the same thing over and over.
          You fail to realize, that makes it easier to filter out your pointless spam, and whether you are man or machine is of little difference to readers.

          The original post about Derek Rowe was actually at least (unintentionally) funny!

      3. A Concerned American says:

        Your 3 years of fake Russian collusion mythology and fabrication got you NO WHERE.

        Time to give up all of your Radical Left-Wing Kool-Aide talking points

        1. confused says:

          is this performance art? or lunacy?

          1. Bubba Zinetti says:

            Poe’s law?

    5. Oudeis says:

      I can’t tell whether this poster is serious, or a satirist making fun of people who seriously say things like this, or a troll who doesn’t believe this stuff but wants others to think he does so as to rile them up.

      I think our fifteen-year experiment in internet democracy has returned statistically significant results. Can we shut down the trial and apologize to the victims?

      1. anon says:

        I was thinking the same thing…must be satire, I hope…

        1. chemist says:

          You’ll realize it’s not satire when Trump is re-elected

          1. x says:

            2020 was the Democrats’ election to lose, and boy, are they ever trying to lose it, armies of Russian bogeymen nothwithstanding.

      2. Bryan Standley says:

        It has to be satire. It’s too perfect.

      3. eyesoars says:

        Definitely a ‘Poe’. You can’t tell whether it’s a parody or not because there are real-life whackos whose beliefs are so crazed they can’t actually be hyperbolized.

    6. Seebs says:

      You seem sorta unhinged. If this isn’t an intentional parody, you should probably think seriously about taking some deep breaths and slowing down a bit. Derek’s science reporting is excellent.

    7. zero says:

      This is clearly sarcasm as a performing art. No person who actually holds those opinions is capable of such polished delivery; their rage-froth and pulsating fury get in the way.

      Thank you stranger for helping point out how absurd certain people are being about all this.

    8. An Engineer says:

      You’re not concerned or American, Go Home FSB no-one like you here.

      1. Charles H. says:

        He could well be US citizen. I’ve met some that were as reasonable. I sincerely hope they’re a microscopic minority, but I’m not sure. As was noted, Poe’s law makes it impossible to be certain, but the follow up posts make it more likely that it wasn’t satire. So either trolling or fanaticism is most likely.

        1. An Engineer says:

          I’m just embarrassed by my typo should be *no-one likes you*

          I feel so dumb for not proof reading. /sigh

    9. Rory says:

      Poe’s law strikes again.

    10. Eric says:

      The easiest way to recognize a propagandized person is to find the guy on the comment thread who insists that everyone else is propagandized. An open-mind person is never completely sure about their views. A fool insists they are right. And everyone instinctively recognizes the fool.

    11. The Fool says:

      Mr Concerned Amelican:
      Delek Rowe is not Ladical Reftist.
      He is more of a lealist.
      Prease collect your post.

    12. loupgarous says:

      Derek is just as entitled to his views as you are to yours. Furthermore, he hasn’t slandered you as you have slandered him. Those of us who visit this blog do so because we enjoy how Derek writes. I suggest you take your rants over to a place more Biblically associated with global warming.

    13. Silverlake bodhisattva says:

      Well, THAT was interesting…..

    14. J R in WV says:

      Maybe ya’ll need your sarcasm detector readjusted? Just a suggestion, there. I think “A Concerned American” is adopting the speech style and absurd fabrications of certain political leaders in order to bring about distrust and disbelief i those political leaders, ie Mr Trump.

      In which case you are all wasting your time denouncing A Concerned American for his hysteria, as the hysteria is well focused on the falsehoods propagated by someone who badly needs to be re-elected in order to run out the statute of limitations on multiple felonies committed during and just aftere his first election campaign.

      Or, on the other hand, A Concerned American may actually believe all that spew, in which case, eww…yuck!

  5. chemist says:

    Derek is such a pu$$y. Turning off comments on any post that’s political because he prefers living in a Twitter echo chamber where all his followers give him ass-pats for his Trump Derangement Syndrome. Hey Derek, you’re a sanctimonious POS!

    1. A Concerned Conservative Scientist says:

      Do you have anything to contribute regarding the subject matter of this blog post? Perhaps your perspective as a fellow chemist regarding multiple commercial vaccines being available simultaneously? I like reading the blog and its comments section because of the variety of scientific and clinical perspectives offered. While I may sometimes disagree with the politics of a particular author, it doesn’t necessarily mean their opinion on technical matters is bunk.

      You must know that calling someone names is not an effective way to change someone’s mind, let alone their politics. If you don’t like this blog, don’t read it. Perhaps your time could be spent more productively elsewhere instead of playing the politics police.

    2. A Concerned American says:

      Derek is nothing more than a Radical Left-Wing Anti-American bomb-thrower.

      Shutting down comments to stifle dissent demonstrate what a totalitarian dictator he thinks he is.

    3. A Concerned American says:

      Agreed. Sanctimonious horse-crap from erk Rowe, a peddler of snake-oil pseudoscience should be halted at once.

      Derek Rowe is our nation’s worst nightmare, his Cancel-Culture mentality should be terminated, and his blog shut down for false propaganda.

      1. Pedwards says:

        If you’re going to sock puppet in order to give the idea of support, at least put in the effort to change the name on the comment

      2. David G Whiteis says:

        “. . . I’m a perfect imitation of myself . . .”

      3. An Engineer says:

        I take it all back “A Concerned American” and “chemist” Might not be FSB, could be MSS. Seems more their MO to make appeals to “our nation”. FSB is more subtle usually, and has a better grasp where our buttons are then this troll seems to.

        1. Wet Dog says:

          How about FOS? That checks all the boxes nicely

        2. chemist says:

          I was born and raised in the United States, I’ve lived on the East Coast and Midwest. All of you guys have some kind of weird delusion that any dissenters must be foreign agents. Do you think the government of Russia or China gives a single crap about Derek Lowe’s blog? FWIW, I’ve been reading this blog since 2009 when I was a wee undergraduate and even emailed Derek questions about graduate school. The Democrats and MSM really messed with your head huh?

          1. An Engineer says:


            I believe you completely, please keep regaling us with your majestic wisdom typed by your totally American hands on your American keyboard from your American desk. I sit in aw of your American opinion. I wait in wrapped attention for your American thoughts…

            FSB go home.

    4. An Engineer says:

      FSB GO HOME, leave us in peace.

      1. chemist says:

        You’re talking to a native born American citizen, but I guess feel free to indulge in whatever delusions help you feel better about yourself.

        1. drsnowboard says:

          Err, the first rule of the internet is don’t feed the troll but in your case , I’ll make an exception. You do seem to assume that everyone in this comments section is ‘american’ and so deplorably biased according to their political stance. I am not, however that doesn’t mean I don’t recognise your bile and bilge as (even sarcastically, which I doubt) characteristic of a re-election campaign that from afar is specialising in propaganda, misuse of federal funds, voter suppression, declaiming opposing viewpoints, tacitly supporting racism and conspiracy theories, and avoiding any kind of debate. Now , where might we have seen that before in the last 100 years? And I broke Godwins Law, if that helps.

  6. David Eugene Young says:

    Has anyone done the math and has hazarded to make a guess how many covid19 cases will appear within 3 months of the placebo group? Let me make a guess. I imagine that there will be about 60 cases in the first three months for the 15,000 who get the placebo. Now, how many in the vaccine arm? 10? 15? Even 20 (out of 15,000 in the first three months and the vaccine should meet FDA specifications (approval depending also on side effect profile, of course). Of course, if everyone who enters the trials tends to be “cautious” by nature, there may be few cases even in the placebo arm, and therefore less of a difference between vaccine and placebo. I don’t imagine that these studies are attracting many 28 year old pub-crawlers or Daytona beach partiers. What if only 15 people in the placebo group get Covid (and maybe 6 in the vaccine arm). Such small numbers are less impressive. This means that it might take 5 or 6 months to generate meaningful differences.

    1. Steve Scott says:

      From posted today, Aug. 25.

      “Each of the phase III clinical trials in the U.S. aims to enroll 30,000 individuals. This number is the lowest needed to rigorously show that 50 percent of people are protected from getting COVID-19 over six months—the Food and Drug Administration’s minimum bar for approval.

      Investigators will monitor the vaccinated and placebo, or control, groups until the number of symptomatic infections between them reaches 150. If the researchers can show, with 95 percent statistical confidence, that cases in the vaccinated group add up to half of those in the control group or fewer, the vaccine will have met its primary target. “Still, none of us will really be happy with 50 percent,” says Gilbert, who leads the statistical center for the federal government’s COVID-19 Prevention Trials Network, an organization that is trying to recruit volunteers for the phase III studies. “We all want 90 to 95 percent protection.” Should a vaccine prove far more protective than the FDA’s minimum bar, he adds, there may be no need to wait for 150 cases. “We might look at 50 cases, and if the vaccine reduces disease rates by 80 percent, we might declare it successful and [apply] for approval within three to four months,” Gilbert says.”

      1. daksya says:

        So how does the evaluation of a Phase III trial work?

        I assume all subjects are administered regular PCR tests – how often?

        Since it is double-blind, how does the following work: “We might look at 50 cases, ..” – do they unblind only these 50 cases, or all subjects at that site? How would they make the determination whether to unblind at 50?

        Why aren’t asymptomatic infections not considered?

        Finally, should 150+ qualifying infections be detected within, say, one month, can the trial be concluded then?

        1. David E. Young, MD says:

          There will be an independent review committee (independent of Moderna or which-ever vaccine maker) that will un-blind periodically. No one else including Moderna, knows the results. The independent review committee will inform Moderna if the trial needs to continue. They might recommend stopping the trial for one of two possible reasons. Number 1, the difference in infections is so great that it would be unethical to not unblind right now. In otherwords, the success of the vaccine is so great that at (2 months, 10 weeks.. what ever) there is ample and compelling reason for the FDA to approve right then and there. Number 2, the difference in infections is zero, zilch, nada at (3 months 15 weeks, 18 weeks… when ever) that it seems highly unlikely that a significant difference will ever occur. In this case, the review committee would give the recommendation to abandon the trial because of failure.) The chances of either of these happening early on is low. Most likely there will be there will be some reason to believe in success at 3 months and the manufacturer will unblind at at 3 months.

          True, I don’t know for sure that there is a independent review committee for these vaccines, but a lot of large studies have that in place. It is a way of giving the pharmaceutical sponsor a means of knowing if they are making progress or not. It is a way of getting a drug out sooner if it transpires that the drug greatly exceeds expectation. It is a way to give those on placebo the real medicine (ethically) if the drug turns out to be beat expectations. And it is a way to inform the company that they are wasting time and money if the treatment looks like it will be a failure.

          1. Barry says:

            Surely the most likely case to unblind would be adverse effects, rather than inefficacy or a home-run?

      2. Alan Goldhammer says:

        all the trials that I have seen for vaccines are world wide and not just US. Mask wearing and social distancing practices vary considerable in the various countries.

    2. David G Whiteis says:

      I share David Eugene Young’s concern about the “small numbers” problem. On the other hand, the numbers in at least some of these trials might not be quite as small as he fears. Sinopharm and AstraZeneca are doing Phase III trials in Peru, which is one of the world’s COVID hotspots; Moderna is conducting trials in poor and very at-risk Latino communities in South Texas.

      So even though we may not have a lot of “28 year old pub-crawlers or Daytona beach partiers,” signing up, at least some honest efforts are being made to conduct trials among high-risk populations with a good probablility of yieliding high infection rates.

    3. Simon Auclair the Great and Terrible says:

      The REAL small # problem everyone’s scared to address is that there are only 101 integers <100 and only 10 single digits but an infinity of integers above a bazillion!

      Isn't that stupid?

      We MUST ACT. I propose adding 1a, 1aa, 1aaa…100zzz to ease the burden on the smallest numbers.

    4. Charles H. says:

      I really don’t think you can estimate the number of expected cases ahead of time. Rate of COVID infections in an area seems to peak and fall quite quickly (in terms of planning a study…say within 4 weeks). So I think you need a retrospective study compared the the prevalence in the population even to predict what the control group will have experienced.

      1. Marko says:

        It’s simple. You look for countries or regions that have leadership the likes of Trump or Bolsonaro. You’ll have more than enough infections for your trial.

  7. Thoryke says:

    In the meantime, we’ve still got that “Where will we get all the glass for shipping out the doses?” problem to contend with. Any likely suppliers for those vials would have been a much wiser place for federal funding than that old camera company….

  8. Bill says:

    Lay questions.

    If you get an early vaccine and a much better one comes along. Can you double up?

    Any likely hood that if annual Covid shots may emerge the winner…could they be merged with annual Flu shots?

    1. Harvey 6'3.5" says:

      On the issue of doubling up, I think it depends on which vaccine and how well the first one worked.

      For example, if you already had one vaccine with an Adenovirus serotype 5 backbone, the immune response to the backbone may prevent the second vaccine from working.

      Also, if the first vaccine induced a very strong immune response, you’re probably a little more at risk of injection site pain and other side effects from the immunogen itself (the spike protein in most of the Covid vaccines), while if you didn’t get a good response, the second vaccine might improve your immune response.

      As a personal example, I was dosed with the smallpox vaccine as a child. When I began working on recombinant vaccinia virus many years later, my laboratory required testing for smallpox vaccine titers due to Asilomar-type concerns. My titer was low, so I received a new dose of smallpox vaccine as an adult. Other than annoyance of being pricked a bunch of times because they didn’t have the injection device for the vaccine anymore, no side effects.

      1. PV=nRT says:

        I had to get a tetanus shot each year I worked as a post doc in a mouse lab. The first 3 years weren’t so bad. The last 3 years made me not able to use that arm for a day.

        1. kismet says:

          Oh, god that seems so irrational. Many of us here work with mice and I have never heard such an inane requirement. Is it even legal to require such *unnecessary* medical procedures?

        2. David G Whiteis says:

          I thought the duration of immunity for the tetanus vaccine was about ten years. I’ve never heard of anyone having to get an annual tetanus booster shot.

      2. Alan Goldhammer says:

        LOL! When I was a fellow at NIH, I was working on some of the lethal factors of B. pertussis aka Whooping Cough. I had a 250 ml beaker of log phase growth shatter in my hands when I was removing it from the shaker table in the warm room. Panic quickly set in with a 5 month old baby at home who had not received her first vaccination. One of my colleagues helped me clean things up and ‘Wescodyne’ everything down.

        I went home and washed my clothes three times and stood in the shower for what seemed to be an eternity, lathering up. Everything turned out OK, no pertussis infection at all. We did get some nice publications from the research.

      3. Carr says:

        I’m another layman coming here (found the site via commenters on ars technica) for the knowledgeable comments on the process of understanding and combating this virus.

        I have a question about ADE. Assuming that none of the main vaccine candidates are shown to cause ADE, would the potential mixing of vaccines from one manufacturer with another, over the course of two years if as seems likely this becomes a yearly routine, potentially cause ADE?

        My thought is that since each candidate is designed and works differently, getting one type, and the another, could cause ADE when a person is exposed to the virus. As I’ve read the articles, one might potentially retain the T-cell response from the first vaccine, which could combine with the different T-cell response from the second, and the neutralizing antibody response from the second vaccine, leading to a different overall response when exposed to the virus, than was observed with either vaccine independently.

    2. Hap says:

      Is it possible that some of the carrier viruses may trigger an immune response to the carrier? That would make it unhelpful to administer another vaccine using the same carrier. It wouldn’t matter, though, for other vaccines using different carriers or modalities.

      1. Charles H. says:

        That is, indeed one of the worries. That’s one of the reasons one of the vaccines is based around a Chimpanzee adenovirus. And one of the worries about needing a second vaccination shot.

        Another problem is lots of people have already been exposed to many adenoviruses, so they need to base it around one that people haven’t been exposed to. This is tricky. It’s one of the things being tested in the phase 3 trials. (Well, they looked at it in the phase 2 trials, but that was with a much smaller population.) So far reports are that “they’ve handled the problem”, but we’ll see.

  9. cynical1 says:

    With regard to Guillain-Barre syndrome, I think the real question to ask was wether “natural” infection with the particular H1N1 subtype of the NJ 1976 Swine flu would also have been associated with Guillain-Barre syndrome. For instance, if that virus had become the pandemic it was supposed to be, then they also may have seen an uptick in GBS from the virus infecting people. GBS is associated with respiratory illness.

    Same goes for SARS-CoV-2. Are they seeing increased levels of GBS as a sequela of infection? If they are, then I would not necessarily be surprised to see it with a vaccine, particularly an attenuated virus. According to Wikipedia, about 10% of cases of GBS are attributed to CMV. CMV is pretty ubiquitous but if we were vaccinating 40 million people with a novel CMV vaccine right now all at once, I wouldn’t be surprised to see an uptick in GBS, especially if it was an attenuated virus vaccine. Whatever autoantigens trigger GBS are still there in the attenuated virus at some level.

  10. Anonymous says:

    “A handful of outliers, reported sloppily, could annihilate the possibility of enough people trusting a vaccine in order to ensure its success in enhancing immunity.” Yes! We already have too many even well-educated people who are vaccine-phobic. I think this may be the biggest hurdle (of many big ones) to success of a vaccine. Why aren’t we seeing greater public health efforts to prepare the public for the importance of getting vaccinated? We are all geared up in a historical effort to have production lined up before the trials are complete but without adequate public enthusiasm to whom are we going to give all those ready doses?

    1. Duncan says:

      In the age of social media, ‘sloppy reporting,’ doesn’t matter. It’s a culture war and social media is the modern equivalent of the megaphone. I’ve no idea what you do about it but this isn’t about reporting, or even necessarily facts about public health. This is the first truly modern mass vaccination and it won’t be anything like the old ones. To be honest with you I’d take the vaccine for no reason other than that I just want to go to watch and play rugby again.

    2. David G Whiteis says:

      We’ve been hearing that a massive public education/information “vaccine literacy” campaign is “in the works,” but so far nothing has been initiated publicly (as far as I know). Unfortunately, and as much as I loathe the idea of politicizing something like this, the toxic and factually muddled political atmosphere emanating from Washington and making itself felt all across the country is probably a main reason wny — it’s a fetid ideological swamp that few public health advocates want to dive into (e.g., the threats that have compelled Anthony Fauci to hire security guards to protect his family).

      I will say — at risk of drawing even further ire and fire from “Chemist” — that I know for a fact that for as long as Donald Trump is pesident, response to a vaccine in the Black community — and most likely the Hispanic community as well — will almost certainly be tepid at best. Any vaccine that gets approved under his watch will be “claimed”: by him as a victory (we’re already seeing the beginnings of this now) — an immediate, probably fatal blow to its acceptance in communities that have come to perceive him as virtually an existential enemy. It’s an unfortunate fact that to be truly effective among the populations that need it most, the only way a vaccine can be rolled out effectively and trusted enough to be used widely will be that it doesn’t successfully complete Phase III trials until after November 3 (assuming BIden / Harris win the election), if not until after January 20. This is almost certainly one reason why we haven’t heard voices of vaccine advocay among African-American political, intellectual, and cultural leaders.

      I’m guessing that under a Biden/Harris administration, a lot of voices like that will begin to make themselves heard — and remember, issues surrounding health and public health have traditionally been the bailiwick of a Vice President, and Harris would obviously be an ideal candidate to help make this happen.

      1. wendy says:

        I will wait patiently for a vaccine approved by the WHO. Anything produced rapidly in the US to boost Trump’s election hopes is suspect.

        1. Daniel Murdoch says:

          The WHO that aided and abetted the Chinese Communist Party’s coverup of this virus when it was a localized outbreak in Wuhan? The WHO that told us not to wear masks? The WHO that told us that stereotypes were a bigger problem than the actual virus? With the WHO’s opinion and a couple dollars, I’d get a bus ride. Same goes for the opinion of anyone who still gives the WHO even a shred of credibility.

          1. Fred Fnord says:

            Good. More well-tested and effective preventatives and treatments for the sane among us. If we’re very lucky you will be considerate and get tested frequently and quarantine yourself when you have it, although given your statements thus far I am not hopeful.

  11. Duncan says:

    With respect Derek, give the public a bit more credit! Perhaps spend some time away from the internet.

    I think that most people are prepared for the idea that there will be a priority list (probably a strongly enforced one) for being vaccinated first and most people, me included, think that’s a good thing.

    I think that most people are quite aware that vaccines are generally more than one dose and can manage that. When I took my little girl for her vaccinations I knew that they were multi-dose. Similarly I had a chicken pox vaccine recently and it was made clear to me that it was double dose.

    I think most people are prepared for the vaccine A, B, C and D scenario and if anything I think most people would see that as a positive thing. I am 40 and in good health, I have to understand that I’m not going to be the immediate priority for the gold standard product.
    Furthermore I’d imagine that the public HOPE that better products will come along in time than whatever emerges in 2021.

    And I also think that people are prepared for there being side effects and that a vaccine will not result in zero covid.

    On top of all this there is still the prospect of treatments before vaccines. With respect Derek I think that in the real world, rather than the online one, there is more of a ‘wait and see’ mindset than you think.

    Politicians and the media have not given the public nearly enough credit throughout this pandemic – there is no reason for scientists to do likewise.

    1. David G Whiteis says:

      ” . . . there is still the prospect of treatments before vaccines . . .”

      This is the one that I’m still hopeful about, and I’m a little unsure why most of the predictions we’ve seen concerning the relative efficacy of a vaccine haven’t at least considered the scneario where a vaccine is adequately effective, and for the people who still contract the virus, a good therapeutic could reduce its symptoms to the level of a mild flu or something similar. Wouldn’t that bring at least some level of additional hopefulness to the predictions?

      In other words, I see quotes like this one (from USA Today, admittedly not a medical or scientific journal, but the kind of thing from which most mainstream Americans get most of their news):

      “It’s not likely any vaccine will be 100% effective and it could be that people who are immunized might still get sick, but less severely. ‘I think we’d have the chance of having a vaccine that substantially blunts the frequency of severe disease and therefore reduces mortality,’ said [William] Schaffner [Vanderbilt School of Medicine]. That alone will be a huge win, but the need to keep wearing masks and socially distance might still be there. ‘I don’t think we’ve communicated that,’ he said.”

      Things like that can make readers feel, despairingly, as if we’re going to be staggering miserably (and masked) through “COVID Limbo” for the duration of what used to be called our “lives.” But the inclusion of a good treatment in the scenario could modify that pessimism significantly, I think. (But then maybe I’m just grasping at straws [or “spikes”]?)

      1. Jason M says:

        “the need to keep wearing masks and socially distance might still be there.”

        I think what most scientists, and frankly public officials in general, fail to understand is that people will simply not live like this for much longer. Masks and social distancing are (correctly) seen as minor inconveniences by public health officials, but they are still deeply inimical to what makes most of human life livable in the first place. If a vaccine isn’t available and at least beginning to be distributed by summer of 2021, people are simply going to go back to something approximating pre-COVID life anyway. Society, and the economy, simply cannot and will not endure more than a few more months of this.

        And I say this as a person who generally associates with other urban, educated, left-leaning individuals. The almost unanimous opinion among a wide age spectrum of friends and family is that if none of the first batch of vaccines are sufficiently efficacious, they will simply take the risk and live their life again.

        1. David G Whiteis says:

          Jason — Thank you very much for your comments – I agree 100% that masking and distancing, although absolutely necessary right now, are ” . . . deeply inimical to what makes most of human life livable in the first place.”

          That being said, though, increasing numbers of my closest friends (all of whom are involved, in one way or another, in the music industry [jazz and/or blues], so they’re hardly stereotypical “conformists”) seem to be accepting masking, at least, as the “new normal.” Granted, most of these folks are African-American and at least 45 or 50 years of age, so they (rightly)feel especially vulnerable. Nonetheless, these are folks for whom a soul handshake that dissolves into a hug (or, for women, a hug and a peck on the cheek) has been pretty much standard greeting between friends up until now. So people will “adapt,” even if it means giving up something essential.

          For my part, though, I’m with you. I still feel very deeply that masking one’s face, and living in a world of “faceless people,” is very alienating and depressing, and that people can stay “distanced” from each other, not be allowed to hug or touch each other if they want to, and not be able to see each other’s faces (i.e., “emotional distancing”) for just so long.

          In fact, I’d argue strongly that we’ve seen, we need to consider seriously whether a lot of the messaging from public health advocates and policy makers during this pandemic has been misguided, leaving people feeling “blamed” for what is, in fact, natural (and emotionally / psychologically necessary) behavior, especially in times of fear and uncertainty. It’s not just the “right” who have politicized this issue — I’ve seen reluctance to wear a mast equated with “toxic masculinity” and a host of other ideological crimes. For some reason, a lot of well-meaning scientists and medical people seem not to understand the cognitive dissonance that arises when, all of a sudden, things like “empathy,” “caring,” and “loving our neighbor” are redefined as avoiding our fellow human beings, quite literally like the plague (i.e., “shunning our neighbor”) — when behavior that under normal circumstances would be considered mentally unhealthy, if not downright sociopathic, is redefined as good, compassionate, and socially well-adjusted.

          How do we expect people to react when the very things that we need most in times of crisis, the things that reflect the “better angel of our nature” — gathering together, showing our empathy through facial expressions, hugging one another and being physically close — suddenly become cast as vectors of death and pestilence?

          Human beings are social animals; we are bred for “social gathering,” not “social distancing.” I think that too often, well-meaning public health mandates carry with them a strong whiff of “virtue signalling” that ingnores this facet of why so many people have a hard time doing what’s necessary to help contain the virus, at least until a viable medical solution comes along.

          1. Jeff says:

            This is one of the most insightful takes on mask-wearing that I’ve read to date. Thanks for sharing your thoughts.

          2. x says:

            Found the superspreader.

            As to the implied question “how can we resist our nature?” the answer is “consciousness”, and those who are unable to exercise conscious intellect will suffer accordingly. The universe doesn’t care how you feel.

        2. David G Whiteis says:

          . . . that being said, though, and with all respect, I do hope that if there’s no vaccine or treatmenet by mid-2021 (and assuming that the rate of new cases has not fallen significantly), you and your friends don’t just “simply take the risk and live their life again.” Remember — it’s not just YOUR risk, it’s the risk of all the folks you and your friends come in contact with, many of whom probably aren’t as young and healthy as you. I know I’m preaching to the choir here, but it is something that we all need to remember.

          1. confused says:

            Maybe “should” in some abstract sense – but the vast majority of people won’t.

            And I don’t think I agree about even the “should” in an abstract sense – if distancing was continued that long (after summer 2021), I tend to think the mental health harm, social harm, and opportunity costs (e.g. lost time with family and such) would lead to more total loss of “quality of life” than COVID itself could.

            This of course depends on how common/bad the aftereffects of mild infections are, but that should be known well before that time.

          2. David G Whiteis says:

            Well, so far, “functional immunity” seems to be following a pattern of “one step forward, two steps back” (e.g. Spain, and now Maine, where a single indoor wedding reception appears to have ignited a fresh outbreak [85 cases and counting] at a prison where one of the attendees works. One person has already died.) The virus’s abiliy to find new, unsheathed targets appears virtually limitless. Okay, a vaccine *could* chanage that. But given the most recent estimates for the levels of efficacy and uptake that would be necessary to even approach widespread immunity (, I’m afraid my “Cassandra” gene is a lot more active right now than my “optmist” gene.

        3. confused says:

          Yeah, I agree that this will happen.

          I can’t even really see willingness to keep up the precautions lasting to summer 2021… if deaths don’t rise again during the fall, I think a lot of people will give up by Christmas vaccine or not… but I live in a red state.

          1. Hap says:

            I don’t think any of this is forever sustainable – for now it’s useful because I don’t want the people around to get sick and because we’re playing for time to find a vaccine or some other cure equivalent. People are social animals, and eventually they will want to be social.

          2. David G Whiteis says:

            A lot of folks point to countries like China and Japan, where in fact wearing a mask has definitely become the “new normal,” even for children.

            I admit that it would break my heart to never again be able to see the smile of a child, but from the photos I’ve seen, that’s the way it is there. And it might be the way it’s going to be in the U.S. for the forseeable future:

            It will take its toll, and not just on the kids. I’ve already asked a couple of friends who are elementary school teachers how it feels to teach classes all day without ever being able to see a child’s face. They tell me it’s heartbreaking . I know at least one teacher who told me that she wakes up in tears several times a night, having been yanked out of a dream where she’s teaching unmasked kids who are smiling and laughing. She says it’s like a kick in the gut every time.

          3. Michael says:

            David, don’t stress the most clickbaity news articles about how long restrictive measures are likely to take — it’s inherently uncertain and we have to be careful not to project our current reality of cumbersome testing, minimal treatment options and explosive spread far into the future. Even as far as masks in schools, the article that made you worry about the “foreseeable future” quoted one expert saying they might not be needed by Q2 2021, another hoping for Q3 2021, and the author (but not experts) using the phrase “couple of years” around more pessimistic quotes from two experts.

          4. Charles H. says:

            I live in a blue state, and a number of people have already “given up” on precautions. I see people wearing masks around their neck. Distancing isn’t being well observed.

            Well, I live in a well monitored senior center, and there hasn’t been any transmission within this center. On person got COVID, but got it at a hospital, and didn’t bring it back. But people are unhappy. Plexiglass screens are hard to talk through. I suggested today that they would be improved by baby monitors on both sides of the plexiglass, and maybe that will be done…but I’m not sure it will be enough as many residents are hard of hearing.

          5. David G Whiteis says:

            Masks are mandated in Illinois in indoor public places (businesses, schools and child care facilities can actually face fines of up to $2,500 for allowing non-compliance, although I don’t think that has been enforced, at least not yet). Even outdoors, though, there’s still a lot of vigilance about masking — theChicago daily newspapers have run several articles featuring photos of people caught strolling along the sidewalk unmasked, a pretty obvious “shaming” campaign.

            Nonetheless, there are some people who walk, jog, or ride bikes barefaced. These, though, are almost all younger folks. I don’t remember seeing anyone who looked over 40 without a mask, except for a few street people or people obviously under the influence of something. And, as I mentioned earlier, all of my close friends who are over 40 wear masks all the time, and most of them say they’ve accepted it as the “new normal.” I don’t know whether that means they’ll remove them when/if they’re no longer mandated, but it won’t surprise me if at least a lot of them don’t.

          6. David G Whiteis says:

            More from the Illinois masking front:

            I don’t quite know where a lot of folks here are getting the idea that this is going to end anytime soon. I also don’t know how people think that a vaccine that will almost inevitably still allow “some” infection / reinfection (thus, continued spread) of COVID will change this.

            I’m afraid we’re facing a future of masked, isolated people shunning one another like the plague; empty stadiums, concert halls, auditoriums, and nightclbs; no more close fellowship in the few public gatherings still allowed (e.g., churches); no more arts taught in schools (you can’t put on a play, sing in a choir, or play in an orchestra or a band while wearing a mask and “distancing” yourself from others); for that matter, little if any actual socializing in schools at all, and very little arts or performance presented for actual audiences in public.

          7. Michael says:

            David, you have to get the idea of “forever” out of your mind. All the rumination about “forever” is achieving is adding to your own suffering in what is already a difficult time, and assaulting the mental health of those around you.

            Between now and “forever,” let me ask you these questions. Will treatment options become more, or less plentiful and effective? Will functional immunity in the population increase, or decrease? Will vaccines get better, or worse?

            And if this is really is some monster alien virus that will be a forever pandemic with no immunity under any circumstances, then we might as well get back to normal now and take our lumps, while focusing on treatments. But you know that’s not rational.
            Distancing/masking is, when you think about it, a fundamentally hopeful approach — that we want to avoid people with vulnerabilities and a naive immune system getting infected now, because it will be safer later when vaccines better prime our immune systems and treatments improve.

          8. David G Whiteis says:

            (Sorry about the double-post — I misplaced the last one by clicking the wrong “Reply” button.
            Is there a way to self-delete when this happens?)

            So far, “functional immunity” seems to be following a pattern of “one step forward, two steps back” (e.g. Spain, and now Maine, where a single indoor wedding reception appears to have ignited a fresh outbreak [85 cases and counting] at a prison where one of the attendees works. One person has already died.) The virus’s abiliy to find new, unsheathed targets appears virtually limitless. Okay, a vaccine *could* chanage that. But given the most recent estimates for the levels of efficacy and uptake that would be necessary to even approach widespread immunity (, I’m afraid my “Cassandra” gene is a lot more active right now than my “optmist” gene.

          9. Michael says:

            By “functional immunity,” I mean on an individual level — that recovered or vaccinated individuals will avoid serious symptoms upon subsequent exposure. Nobody is credibly suggesting that, in August 2020, Spain or Maine has reached herd immunity, or that contracting COVID in August 2020 isn’t potentially very dangerous to a naive immune system given the paucity of available treatments. But “forever” won’t have the same conditions in place as August 2020.

            Anyway, I get the message and won’t engage with you further on this.

          10. Anonymous says:

            @David G Whiteis: I agree with @Michael here. I am sorry to read that you are distressed by the pandemic, but help is available: please talk through your feelings with your spouse, family, friends, with someone online, a counsellor, a helpline, your dog – whatever you find helpful.
            I have been struggling with mental health myself due to both this pandemic and health issues in my family, and I have found talking to a counsellor has helped me a lot.

    2. Michael says:

      I agree with Duncan. I do share Derek’s concerns about risky behaviour immediately after the first dose (or even second dose) of a two-dose vaccine. I think the clinical trials can establish when the antibody titers are typically high enough to presume that most vaccine recipients are functionally immune, or at least not naive, to the virus — let’s say that we consider the immune systems of vaccinated individuals “primed,” depending on the data, at 14 days after the second dose.

      I think not only *can* governments responsibly ease restrictions on “primed” citizens, I think they *must* do so in order to encourage uptake, provided that the vulnerable “unprimed” remain distanced in the event of asymptomatic spread. I would envision three ways to incentivize getting the vaccine one general public rollout starts:

      Individual incentives — permitting “primed” individuals unrestricted socialization with other “primed” individuals. This should pose a very low public health risk if the Phase III trials demonstrate high efficacy, and adds to the self-interest in getting vaccinated.

      Peer encouragement incentives — considering allowing mass gatherings once a certain percentage of the public is “primed,” perhaps tied to falling hospitalizations or infection rates as well if they are still high at the time of vaccine rollout to the general public. Maintain a public list of “primed” percentage so the public can watch rising uptake numbers in real time.

      Community incentives — create local community vaccination clinics, for example at election polling places, for “first dose” and “second dose” sessions. People can still do it on their own if that schedule doesn’t work. But this creates local reinforcement of the vaccination drives and provides a handy reminder of the need for both doses.

      1. David G Whiteis says:

        Michael — Mind if I (re-)share a few ideas I think I’ve suggested elsewhere?

        RE: Incentives — in the absence of a governmental mandate (which apparently would be Constitutional, but would be politically infeasible in the U.S.), at least some private entities — restaurants, bars, performance/entertainment venues such as nightclubs, show lounges, auditoriums, gambling casinos, etc. — could have an impact by mandating that proof of vaccination would be required for entry (not unlike having show an ID to purchase alcohol). It might mean fewer patrons for a while, but it couldn’t be much fewer than the current “25% – 50% capacity” restrictions that a lot of places are being held to right now — and, in the long run, it would attract more patrons who otherwise might not feel safe going out. I’m sure there are plenty of other people like me, so hungry for normal human contact again that we would revel in the opportunity to gather safely together with other “vaxxers” in normal social settings.

        Such policies would also, one hopes, encourage vaccine “fence-sitters” to get vaccinated, just so they can join the fun. Let the vaxxers be the “in-group,” and the anti-vaxxers be the “other.” In other words, a “carrot” approach rather than a “stick” approach might be the most feasible,and the most likely to produce good results. (A significant piece of that “carrot,” I think would be the opportunity to spend time in the company of other “safe” people without fear, which is a feeling that I think many of us miss very deeply.) It’s possible, also, that this could lead to a kind of positive, proactive social “shaming” of people who refused vaccination (I could actually envision “Vax Parties” springing up around the country, making it “cool” to be vaccinated).

        RE: Community-based vaccination sites — It’s not only “vaccination hesitancy,” but very real and practical barriers to access and affordability, that can create significant obstacles for many people. We need to think in terms of bringing the vaccines to the community, not forcing people to find a way to get to the vaccines. For this reason, non-traditional venues such as neighborhood pharmacies, church facilities, schools, and other community-based locations should be repurposed as temporary vaccination centers whenever and wherever possible. (I seem to remember the gymnasium of my elementary school being used this way for either polio or measles vaccines when I was in second or third grade in the early 1960s, so this kind of thing is not entirely unprecedented.) This might also help reduce vaccine skepticism in communities where local institutions and venues are trusted much more than “official,” often geographically remote, points of service.

        Might I suggest that traveling mobile health clinics could also be a valuable part of the solution? They have been shown to be effective in other contexts, such as delivering health care to the homeless, and helping to provide medical and social services to at-risk mothers and children. In fact, if Bill Gates, Jack Dorsey, and other well-meaning billionaires are sincere in their protestations that they want to do all they can to assist in this crisis, they might do well to partner with the government in investing in, and equipping, a fleet of buses to serve as mobile health clinics to deliver vaccinations to poor rural communities in the U.S. They could also spur investments in clinics in underserved urban settings. The benefits could be immeasurable.

        1. David G Whiteis says:

          p.s. — In terms of your “peer encouragement incentives,” Gov. Pritzker in Illinois seems to have more or less the same thing in mind with his five-phase re-opening plan (we’re in Phase 4 right now, although with a few areas spiking pretty seriously, there could be at least a partial rollback coming). The final Phase 5, a fuill reopening, is defined as follows:

          “What’s allowed: Conventions, festivals and large events are permitted, and all businesses, schools, and places of recreation can open, with safety precautions continuing. The only way Phase 5 will begin is with a vaccine, or a widely available and highly effective treatment, or with the elimination of any new cases over a sustained period.”

          It’s a little unclear what he means by “safety precautions continuing” (I’m assuming that doesn’t mean social distancing and masking forever, since “all businesses and places of recreation” presumably include stadiums, bars and nightclubs, convention centers, etc.), and his “vaccine OR treatment OR no new cases” metric is rather vague. Nonetheless, it would appear that the incentive to get vaccinated under this plan is pretty strong.

    3. Derek Lowe says:

      I hope you’re right – but we’ll soon be finding out. . .

  12. Dang says:

    Derek, great comment about the likely “Patchwork Quilt of Efficacy”. The same patchwork quilt effect might apply to safety as well. Isn’t it possible that a vaccine might BOTH reduce the number of infected individuals who become symptomatic AND also increase the mortality rate (in selected subpopulations or the population at large)? Imagine if 50% of unvaccinated individuals become symptomatic after SARS-CoV-2 infection and 1% die, whereas only 25% of vaccinated individuals become symptomatic but 2% die. How can we know we aren’t walking into such a situation unless we wait long enough to obtain data on the rates of severe outcomes in both placebo and vaccinated groups. Rushing is dangerous

  13. Lane Simonian says:

    There are a slew of troubling considerations:

    Vaccines may not make a person immune but only asymptomatic. Some people thinking that they are immune will no longer practice safe behaviors and will contribute to the further spread of the virus.

    The novel coronavirus will develop into different strains and a new vaccine will have to be developed every year like for the flu.

    The focus on a vaccine has eclipsed efforts to develop therapeutic treatments.

    Vaccines will be forced out under the right to try doctrine before any are shown to be either safe or effective.

    The vaccine watch is somewhat reminiscent of an old saying (paraphrased): the optimist says we live in the best of all possible worlds and the pessimist is afraid that he or she is right.

  14. The Moar You Know says:

    Wow, Derek, sorry, you’ve got some shitposters.

    We’re I dictator of the world, a position, by the way, I have no interest in as it sounds far too much like a lot of extremely unpleasant work, first thing I’d do is ban all comment sections. That piece of yours yesterday was a beautiful piece of fresh air. No comments, no bullshit, just some Derek perspective and I got to sit for a few minutes and think about what you said. I got to spend some time contemplating. You should do that a lot more often. The comments detract, mostly.

    Second thing would be the end of any and all “social media”, while I’m daydreaming.

    Thanks for the blog, it is a public service.

    1. G2 says:

      In the “usual” scientific blogs the comments are verhy sound and helpful. If you don’t like it, don’t read it.

      So Derek, please keep the comment section.

  15. Bryan says:

    I am curious what readers think of this:

    For those behind the paywall or do not wish to click on the link, the summary is that there is no emphasis on vaccines that will prevent transmission of SARS-CoV-2, the virus that causes COVID-19. They (Dr. Adam Finn and Dr. Richard Malley) argue the current vaccines in trials act to prevent the disease but not transmission.

    Is this true? If so, do we share their concerns? Thanks.

    1. johnnyboy says:

      Haven’t read the article, but if your summary is correct, the good Drs are talking out or their asses. Truth is we don’t know what the various vaccines will or will not do, because the data’s not out yet. As much as one can appreciate the NYT, you should stay away from the layman media for anything that has to do with science.

    2. Retiredmedchem says:

      Summary of the NYT column isn’t quite right. The authors’ point is that the vaccine trials should also be looking at transmission of SARS-CoV-2 (the virus) as an endpoint in addition to protection against covid-19 (the disease). However the authors criticize current clinical trial design for not looking at virus transmission. I don’t know if there is any publicly available pre-clinical data regarding effect of any of the candidate vaccines on virus transmission. I’m not an immunologist, so would be interested in thoughts on this from folks better informed than myself.

    3. Marko says:

      All of the trials will be monitoring transmission to a degree , just not as actively or directly as that author would prefer. The author has been on this same bandwagon for years , not just for COVID.

      If you really wanted to monitor transmission effects to the max , you’d drag every trial participant in on a regular basis ( weekly? ) for a PCR test , and then when you detect a positive , you’d monitor all of their recent contacts as well. Somebody would have to pay for all that extra monitoring , however , so I don’t see it happening.

  16. Thomas says:

    I can also imagine people getting an antibodies test before getting the vaccine. Especially if vaccines are scarce.
    Though this is a lot of extra work. And I don’t know about manufacturing these tests.

  17. WOW. Gobsmacked.

    I think that DL is correct to feel gloomy about the prospective reporting on the results of the various vaccine trials. The media are already fired up to trash anything that happens under Orange Man’s watch. No matter what the outcome of vaccination trials, you can just hear the Biden campaign gabbling on and on about how badly it has been handled. So, there’s little objectivity in the media and certainly no willingness to help the general public set anything in context.

    Add to that the actions of Blue-State governors such as the one here in NJ who is apparently hell-bent on keeping the people in some kind of fear-imposed house arrest, and it’s clear that there will be all sorts of political shenanigans – likely on both sides – around the vaccine and the virus, leading into the election. I can see NJ teachers demanding the vaccine and then still refusing to let schools go back because they want to wait to see whether it has protected them.

    He’s also correct that a two-shot vaccine regimen will be inordinately difficult to deploy, particularly if the time between doses is critical. Are vaccinators going to be working door-to-door? The question of “who gets it first” is also not trivial – after front-line health workers will it simply be based on age? Old people are at most risk of succumbing to the virus, but they are also least likely to have well-functioning immune systems and so may see poorest benefit from vaccination. This may generate headlines of the “Nursing home residents are vaccine guinea-pigs” variety. Will there be priority for people who work for all of us simply by keeping supermarkets open? Make your own list.

    Response to the vaccine *will* vary. Some people will not develop significant protection. This must happen every year with the ‘flu vaccine, and noone blinks twice about it, but this virus? with all that surrounds it? It’ll be a miracle if people believe the reports, regardless of how good they may be.

    It’s up to every one of us to strip the politics out of how we describe and explain the vaccine trial results to our lay family, friends, and colleagues. We should encourage them to get vaccinated because as someone said previously, vaccines do generally offer some degree of protection.


    1. Ken says:

      At the moment I’m having trouble convincing some family members that oleander is poisonous, hydroxychloroquine has negligible effect on treatment outcomes and no preventative value, and convalescent plasma may be helpful in some cases but there hasn’t been enough research. We haven’t even gotten around to discussing vaccines, though (fortunately) none of them have bought into the QAnon nonsense about microchips and Bill Gates yet.

      1. Lane Simonian says:

        At least, you have one plus.

      2. chemist says:

        Good on your family for resisting your BS

  18. MTK says:

    I am becoming increasingly skeptical of vaccines coming to the rescue.

    Not for any scientific or technical reasons, although the multi-shot nature of most is a concern, but rather because of public acceptance. I have a reasonable degree of confidence that one or more safe and effective vaccines will be developed, but not a lot of confidence that the public in large numbers will want it.

    We’ll have those that are general vaccine skeptics, those that believe it’s some mind control scheme, then those that won’t take it believing that corners have been cut in getting it out as quickly as possible. We’d probably be better off getting one or two out on a limited basis rather than having them widely available quickly. In that way some sense of trust could be built. The worst outcome of course would be if one of these were rolled out and somehow ended up being either unsafe or ineffective. The lessons of the ’76 swine flu or LYMErix vaccines shouldn’t be forgotten.

  19. NM says:

    Derek, with every politically-tilted post, you lose a bit of credibility to the public. Sorry, it’s true, and I think on some level you know this.

    Has nothing to do with what you say, which is probably mostly true, but the fact that you’re saying it at all.

    The medical community can either be a) trusted or b) make political statements. Not both.

    1. An Engineer says:

      As “the public” doesn’t sign Derek’s pay check, were I in his shoes my desire for “credibility” would be /shrug.

      As to the binary categorization you assert, I don’t think it is that simple.

      I herd NPR (nice and left leaning) play a clip of Derek saying something that meant essentially “it’s complicated” when asked about the state of a potential treatment. The reporter then went on to imply after the clip that Derek had said that the treatment was terrible and didn’t work.

      So simply having a nuanced position even when voiced on an ostensibly friendly platform is a liability. If Derek is anything he is nuanced. There is no way he will come out of any spotlight in the American discourse without getting some of the ick on him, so he might as well get tarred for his actual opinions not those projected onto him.

      If Derek were a public official I would agree with you NM; he isn’t this is a personal blog.

      Keep speaking truth Derek it makes you more credible in my eyes. I hope you never listen to the peril clutchers.

      NM: this came out a little pointed (sorry), it’s not personal I just disagree.

      1. chemist says:

        The mainstream media has committed intentional and malicious psychological abuse against the American public with constant 24/7 negative coverage of the Trump administration (compare to how they covered for the Obama administration despite many horrific scandals which I won’t get into here). What you are seeing with Derek is he is simply succumbing to the programming. All of the scientists I know who use social media feel enormous pressure to conform to the left-wing narrative. One tweet of “wrong-think” and you are a pariah. I’ve opted out and I think for myself.

        1. An Engineer says:

          “I’ve opted out and I think for myself.”


          I am very proud of you for your achievements in “Right Think”. We all are. Please continue to be “opted out” from this discussion. Your absence will be a triumph. We will all congratulate and cheer you from afar. Your Opt-outedness will be as legend! Go forth brave young one and Opt-out as hard as you can!

          1. chemist says:

            Continue to live in your world of delusion for all I care. Eventually that cognitive dissonance is going to be a quite a whopper!

      2. Nathan Moss says:

        Thanks for the respectful reply. I think the interesting thing you assert is that “the public doesn’t sign Derek’s paycheck.”

        But with public health opinions, the public response _is_ the payout. So while you’re correct, the public does not sign his paycheck, he’s put quite a bit of effort in posting about vaccine candidates, effectiveness, and distribution strategies whose effectiveness will ONLY be shown via public acceptance.

        FWIW, I think the president is a buffoon and I’m not “one of them.” But I know enough about human nature to see that it is incredibly contradictory and self-defeating to making political-themed posts which bemoan a group of people and their leader, and then call them idiots for not listening to your medical advice; advice which requires massive, population-spanning compliance to be effective for _yourself_.

    2. loupgarous says:

      You’re wrong. Medical professionials are obliged to comment when Biden, Obama and Trump all go into full-on huckster mode promoting how they (a) had things under control withe the flu a few years ago or (b) are going to kick SARS2’s ass. The Wall Street Journal goes into great detail about how, if they’d been dealing with SARS 2, Obama and Biden would have had a couple of million deaths back then. .

      Meanwhile, President Trump’s also done a great job of slaying himself with the jawbone of an ass.
      I don’t like Trump’s opponents, but it’s impossible to defend what Trump says on medical issues. He’s reliably wrong when he slips a white coat on and holds forth on medicine – especially when he talks about complex medical issues on which there’s considerable room for those who have actually worked on those issues professionally. Even those of us who’d like to defend Trump on general principles can’t do it when he talks about medicine.

      1. chemist says:

        Trump’s a layman. Of course he isn’t going to sound educated when speaking about medicine. But the “experts” giving him advice haven’t helped much. And a vote for his opponents is literally a vote to destroy the country. Biden wants to give amnesty to all illegals his first day in office. Does that sound like a good plan to you? I’m willing to bet illegal immigrants played a major role in the spread of COVID in CA and TX particularly. They aren’t going to be obeying any quarantine or masking orders, that’s for sure

        1. loupgarous says:

          “Trump’s a layman. Of course he isn’t going to sound educated when speaking about medicine

          The issue isn’t the President not sounding educated. It’s his repeated bad calls on things such as opening schools on schedule (setting up superspreadeers of SARS2 to spread it to others and his bad advice regarding the usefulness of hydroxychloroquine (wasting considerable time and effort to disprove).

          I will say that Trump’s good calls on things such as rational allocation of scarce resources such as ventilators where and when they were needed (back when Gov. Cuomo of New York was demanding most of the national stockpile of such things to be sent to one state (New York) have been vindicated. I just wish the President had let his good judgment guide him more often and the press hadn’t misreported his record there.

          .But the “experts” giving him advice haven’t helped much.

          Which experts would those be? The unhinged-sounding woman invoking the wrath of God against those who disagreed with the President, who could have been disavowed with a simple White House press conference statement? Or Dr. Fauci, whose advice has been on the whole very good and whose patience with what seems at times to have been a public disavowal by the President on Twitter was very professional?.

          And a vote for his opponents is literally a vote to destroy the country. Biden wants to give amnesty to all illegals his first day in office

          Congress hasn’t repealed our immigration law since it was enacted. That President Trump has moved to dismantle illegal executive orders aimed at undoing the Congress’s clear intent not to change our immigration law is a point in Trump’s favor despite his bigoted remarks on the subject.

          If we want immigration law changed or any other law changed, we should change our representation in Congress, or just call our representatives and tell them so. We as citizens ought to tell the President when we wish he’d present himself better.

          But the other major party hasn’t given us anyone better to replace Trump with. I agree that a Biden presidency or a Harris vice-presidency (neither of whom have denounced rioting in the streets) would be disastrous for our nation.

    3. MAP says:

      Ridiculous. I went back and re-read the post based off of this comment to see if I was crazy. I’m not. What about Derek’s post is political? I’m guessing you’re a Trump supporter who is just primed to take everything as an attack against him. Derek outlines what might be expected to happen as vaccine phase III trials begin to roll out–what could go wrong and what could go right. His scenarios seem to apply to either party controlling the White House.

    4. Derek Lowe says:

      I’ll take that chance.

      1. An Engineer says:

        That’s a Hole-in-one I’d say.

        Derek does in four words what I failed to say in… more words. It’s just “Upscale Elegance”, through and through, Mmm mm mmmm Mmm mm good.

        Sorry for feeding the trolls Derek… I just get so mad some times, and/or Duty calls:
        I hopefully the great computer god that lives in the sky will forgive me someday /pray.

      2. Nathan Moss says:

        Funny. With responses like that, so will the public.

      3. Riah says:

        Thank you for another very good post. All credit to you for not shying away from important topics which might not be to everyone’s taste.

    5. hans says:

      I greatly appreciate this blog. I’ll venture that Derek has thought extensively about his positioning as a journalist. Scientists are fallible, and know it, therefore opinion is what they offer. Derek is acting as a scientist by providing his professional opinion, regardless of whether or not that opinion steps over the squiggly time-varying line that divides technical from political.

    6. Thomas says:

      Note how Derek points at content and not at politicians or a party. He’s definitely not lowering himself to the level of usual political chatter.

    7. Fred Fnord says:

      “Goodness me, sure one of the political parties in the US is actively hostile to science in every way, but if a scientist points this out, he is clearly the one in the wrong and will make…”

      I’m not clear on the result you are expecting. Like, the Republicans already refuse to accept any science that does not go along with their preconceptions. What worse result are you afraid of?

  20. confused says:

    Isn’t a ~1 in 100,000 chance of a usually-non-fatal-though-serious side effect (GBS) pretty much insignificant compared to COVID? I mean, the COVID death rate is much higher than 1 in 100,000 even in young healthy populations like the USS Theodore Roosevelt.

    I guess it could still be a PR disaster, though, reducing vaccine uptake.

    I do wonder if the specifically *political* aspect of a “rushed” vaccine will be mitigated if tons of other nations also roll it out on quick timelines (as I think they will if the data looks at all positive).

    1. Whatever says:

      The death rates for covid on the CDC people for 24 and under are currently less than 1 in 100,000 (330 out of >100 million in the US). Under 14 it is roughly 1 in 1,000,000 (66 out of >60 million). Granted the covid number is still rising but I wouldn’t use the word insignificant when considering vaccine risk versus covid risk for healthy people under the drinking age.

      1. David G Whiteis says:

        Even if they’re not at high risk of dying, they can still continue to spread it to others who may be.

      2. confused says:

        Well, 100% of the population isn’t infected yet. So comparing deaths to total population isn’t apples-to-apples.

        But you are probably right about the youngest age groups. I was thinking mostly about people my age (I’m 30) being “young and low-risk”, but yeah there’s a big difference there.

        Perhaps a lower age limit should be set on the vaccine in the initial rollout, until it’s clearer what the low-probability side-effects are.

    2. loupgarous says:

      Good point on how vaccine problems can be spun out of control and exaggerated by the media. It’s entirely possible we’ll have that issue this year or next.

  21. Liam R says:

    Not that anyone really cares, but a better pronunciation guide for Guillain-Barré syndrome would be: Gee-YAHN BAH-ray.

    The Mayo Clinic seems to be the source of the gee-YAH-buh-RAY suggestion, which is wrong.

    1. Klagenfurt says:

      I hear it’s unheard of in Wilkes-Barre, PA.

  22. 10 Fingers says:

    After reading some of the (as usual) helpful and thoughtful comments and the (as has happened recently) particularly high concentration of unhelpful comments I fell compelled to share two things:

    1) ““Anti-intellectualism has been a constant thread winding its way through our political and cultural life, nurtured by the false notion that democracy means that ‘my ignorance is just as good as your knowledge.’” – Isaac Asimov

    2) Thanks, Derek, for continuing to share your knowledge and to provide a forum for thoughtful discussion.

    1. Drive, drive says:

      Looks like we’re stuck with that.
      A while back, learnin’ books ‘n stuff was Communist. Now it’s Racist.
      Same ol’.

  23. loupgarous says:

    Thanks, Derek, again, for presenting complex issues in understandable ways!

  24. An Inhabitants of a Pale Blue Dot says:

    Reading this blog and its usually wonderful discussions around Science is a daily routine for me. Thank you Derek for reminding us not to celebrate our ignorance.

  25. Jonathan says:

    Could you address the feasibility and safety of taking multiple types of vaccines? I don’t know any better but am I foreclosing on taking a better vaccine in the future by taking a mediocre one at the start?

    1. Vaudaux says:

      There is lots of precedent for two or more distinct vaccines being used for the same disease. Many readers of this blog are old enough to have had two different vaccines for at least four diseases: polio, pertussis, pneumococci and shingles.

      1. Jonathan says:

        So would it make sense to inoculate people with several vaccines to increase effectiveness?

    2. Simon Auclair the Great and Terrible says:

      No you are not unless they are both delivered by a viral vector and the same one.

  26. Spingos Konstantinos says:

    Whatever results those trials might have they have not taken into account the primary mechanism of protection that vaccinations provide which is the indirect population protection meaning that the propagation rate of the infection is critically reduced with a less than optimal direct individual protection.
    In that line of thought the only meaningful way that those trials should have been ran was by taking a whole town, splitting its population at half, vaccinate active or sham, and follow up.

    1. Marko says:

      Yep. Something like this :

      Effect of influenza vaccination of children on infection rates in Hutterite communities: a randomized trial

  27. Ian Ringrose says:

    I expect that is one vacine totally stops people getting infected it’s trail will end a lot sooner then a vaccine that has less clear results, as there will be unblinded data people seeing when they pvalues become convincing.

  28. Philip says:

    Typo: “you can make hit the karaoke bar”
    I assume you want “you can hit the karaoke bar”

    Please delete this message.


  29. Petros says:

    Don’t the reports that several individuals have been reinfected with Covid enhance concerns that any immunity offered by vaccines may be shorter lived than hoped for?

    1. Marko says:

      It’s probably not just several , but rather hundreds or thousands. We’re in the same place with regard to reinfections that we were when Trump said we only had 15 cases and that “soon , very soon , that will be down to zero”. We had such a low number of cases only because we weren’t testing enough to detect the others that were present.

      What it takes right now for a “confirmed” reinfection is a COV2 genomic analysis on both the first and second case which shows a difference between the two infecting strains. You could probably fit the number of people who’ve had that sort of analysis done in your living room , while maintaining social distancing. All of the anecdotal reports of reinfections have been dismissed with a wave of the hand , but not with data.

      1. chemist says:

        Why bother making a vaccine if people can simply get reinfected with COVID?
        I caught COVID in May. Had a bad fever that went away with rest and fluids. Retested in August. Still negative. Have no concerns about catching it again.

        1. Marko says:

          “Why bother making a vaccine if people can simply get reinfected with COVID?”

          If a vaccine substantially reduces severe disease and death , it will be a success.

          So far I have seen no reports of deaths in cases of suspected reinfection.

        1. David G Whiteis says:

          “[Dr. Maria Van Kerkhove, head of the WHO’s emerging diseases and zoonosis unit] reiterated that no matter whether someone has been infected or not, they should continue following suggested social distancing guidelines, wearing face coverings and follow other recommended health precautions.” Substitute “no matter whether someone has been vaccinated or not” for “no matter whether someone has been infected or not,” and you’ll get a good glimpse of the future that lies ahead.

          1. Marko says:

            “….you’ll get a good glimpse of the future that lies ahead.”

            Is that you , Nostradamas ?

            There is a real , if not likely , possibility that a vaccine or first infection with COV2 will relegate subsequent infection to something similar to that of common cold coronaviruses. For all we know , when those coronaviruses were “novel” in humans , they caused very severe disease. Even today , some people die from “common colds”. There is even some pretty convincing circumstantial evidence that the deadly “Russian Flu” of the late 1800s was due to one of today’s common cold coronaviruses.

            Any future outcome of COV2 is completely unknowable at this point. Stop pretending otherwise with your fearmongering , Nostradamus.

          2. confused says:

            Vaccines can work better than natural immunity. At worst, it’ll end up in the annual flu shot.

            I just absolutely cannot see people continuing with social-distancing measures after the vaccine has been mass-distributed. (And public officials who try to push that will probably be laughed out of office.)

            Vaccines (and better treatments) will reduce the risk a lot, *and* time will make it no longer “new and scary”. *That* factor makes a huge difference, IMO.

  30. Troublemaker says:

    I’m curious why DL didn’t mention some other possibilities – that don’t seem to exclude any of those he did mention: By the time vaccine A is ‘approved’, early evidence will strongly suggest it is nearly ineffective with the current strains of sars-cov-2 or with the strains which are a small but rapidly growing fraction of the new infections. By the time vaccine B is successful in Phase III trials, no one cares because the strains it was effective with are no longer found. How about this one: Vaccine C is effective with strain 7 thru 13 but ineffective with strains 1-6. Vaccine D is effective with strains 1-6 but not with 7-13. And whichever is the first used interferes with the other. Or how about this – use of the Ad2 (or Ad6) vector precludes its use ( and the only effective vaccine) for the next, far, far worse viral Pandemic.

    1. Derek Lowe says:

      I’m not seeing much evidence (at all) for strains that can evade the neutralizing antibodies raised by the current vaccines. That’s why I didn’t go down that line of thought.

  31. David G Whiteis says:

    . . . although — unless I’m misunderstanding what the reputable researchers are saying about this — this doesn’t necessarily mean anything catastrophic in terms of vaccine-induced immunity, which might well be stronger than immunity arising from a natural infection.

    And, at least for now, we don’t know how severe (or mild) the symptoms “usually” are in people who have been reinfected, and we don’t know how contagious these people are. They might be as contagious as any other asymptomatic or mildly symptomatic carrier, but there are no date to show that eithern way.

  32. Dr. Seymour Tushi says:

    I wish I could get vaccinated against this comment section

  33. Erik Dienemann says:

    Derek – great article on plasma yesterday and what that meant for trust in the FDA. It was good to see Dr. Hahn walk back the 35% comments, but I think he could have been clearer and more thorough in explaining the situation.

  34. Shedding Continues? says:

    There is something else missing from the discussion. Sterilizing immunity. Pipe dream without mucosal route of administration? If so, will IM vaccinated continue to spread assymptomatically or with mild URIs? If vaccinated stop wearing masks and many others don’t get vaccinated, you could have more super spreader events after vaccines introduced and the outbreak worsens, hitting those who haven’t been vaccinated the hardest. Is anybody evaluating vaccines based on the outcome that matters from public health… reducing the probability of super spreader events?

  35. Richard W. says:

    If I understand Derek’s post, serious side effects may show up much later. So who cares who gets the vaccine first … they will be the people taking the most risk. If one is smart, they will get at the back of the line!

  36. Blaine White, M.D. says:

    Potential problems for both plasma treatment and vaccines arise from using evidence to construct a model for Covid-19 pathology that embraces both basic science and clinical experience. Covid-19 infection suppresses both innate immunity by obstructing interferon production (Blanco-Melo, 2020; DOI: 10.1016/j.cell.2020.04.026.) and also adaptive immunity by infecting lymphocytes (Pontelli, 2020;, inducing their apoptosis and lymphopenia (Chiappelli, Bioinformation 2020; 16:219), and so markedly limiting T-cell response. This results in an immune response involving predominantly MHC1 antigenic epitopes, NK cell activity, and macrophage activation. B-cells do eventually respond with IgG antibody, but for older patients and those with obesity and/or diabetes, anti-Spike Fc-glycosylated-IgG combines with the many viruses to produce IgG-Spike complexes that exacerbate the macrophage inflammatory response (Hoepel, 2020; into full blown macrophage activation syndrome (MAS). This results in excessive platelet activation and hypercoagulability with compromised microperfusion together with pulmonary endothelial fluid leakage and Severe Adult Respiratory Syndrome with progressive hypoxia leading to death. In addition to testing the cell counts and inflammatory markers of MAS (ferritin), determination of HbA1c reflecting the glycosylation state is an important prognostic indicator (Wang, 2020; doi: 10.1016/j.diabres.2020.108214).
    With that disease pattern, there are at least 3 major risks for limited effectiveness of vaccines targeting antibody production against Spike. (1) By random mutations during replication, the virus alters Spike amino acid sequences so that antibodies don’t recognize it, and the virus escapes immunity. (2) Induced IgG levels decay in a few months, and the vaccinated immunity is short-lived. (3) As in Liu’s primate experiments (2019;, upon post-vaccine Covid-19 challenge, the IgG-Spike immune complexes induce MAS that kills the patient. Studies of critically sick Covid-19 patients have generally found they have plenty of anti-Covid antibody. The problem appears to be that their antibody is strongly proinflamatory for macrophages and induces MAS. So how sure are we that adding plasma donation with unknown antibody quality to that situation will help?
    The point is that “Warp Speed” with regard to Phase 3 testing of either plasma treatment or vaccines is potentially very dangerous ignorant mental manure. We won’t know what happens to a vaccinated older diabetic patient who gets an actual viral challenge until there are lots of Phase 3 vaccinations, and that takes time. Without really knowing what works, we can make things worse and kill a lot more people. One of FDA’s central missions is to avoid that, and right now they must stick to their well-established standards for safety and effectiveness – all political pressure be damned.

    1. Lane Simonian says:

      For a non-scientist such as myself, this is the best explanation for the challenges presented by the coronavirus that I have seen. Are there ways to safely address t-cell dysfunction created by this coronavirus?

      1. Lane Simonian says:

        I may not have asked the question the right way. Are there ways to dampen negative immune responses while restoring some level of t-cell response?

        1. Blaine White, M.D. says:

          I want to respond to and encourage the very good questions from Lane Simonian.

          They are really 2 questions if we think separately about treatment (“Are there ways to dampen negative immune responses while restoring some level of t-cell response?”) versus vaccination (“Are there ways to safely address t-cell dysfunction created by this coronavirus?”). A short answer to both is, “Maybe.”

          With regard to treatment, the CoV suppression of production of Interferon-beta by infected cells is a big problem, since IFN-beta induces non-infected cells to make a library of proteins that confer strong resistance to viral infection. CoVs’ Nsp1 (Non-Structural-Protein-1) blocks synthesis of cellular but not viral proteins (Lokugamage, J Virol 2015; 89:10970), and CoV with Nsp-1 “knocked out” induces good IFN-beta production (Narayanan, J Virology 2008; 82: 4471). In fact, Nsp1 interaction with our protein cyclophilins is necessary for CoV replication, and the drug cyclosporine (FDA approved for transplant immunosuppression) binds our cyclophilins and markedly inhibits CoV replication (Pfefferle, PLoS Pathog 2011; doi:10.1371/journal.ppat.1002331 AND De Wilde, J Gen Virol 2011; 92:2542). All that suggests that inhibition of Nsp1 via competitive binding of cyclophilin by cyclosporine will allow production of IFN-beta and change the whole course of our immunologic response for the better. For example, T-cells pre-armed by IFN-beta signaling might not be an easy target for Covid-19. Cyclosporine also has an established role in management of MAS by hemotologists (Rose´e, Blood 2019; 133:2465). Nevertheless, because of the traditional role of cyclosporine in transplant immunosuppression, it took some kahones to use cyclosporine in Covid-19 patients (Heili-Frades, MedRxiv 2020; This report from Spain includes 2,739 hospitalized Covid-19 patients, and treatment of 1,053 with cyclosporine was associated with a 31% reduction of mortality. Furthermore, in the 976 hospitalized 51-70 y.o. patients, cyclosporine cut the odds of death in half. Unfortunately, IFN-beta levels were not reported. This Spanish group is now conducting a cyclosporine RCT, although a proposed U.S. RCT led by Dr. Carl June (a member of the National Academy of Medicine and the Richard W. Vague Professor in Immunotherapy at the University of Pennsylvania) has reportedly been rejected by FDA.

          With regard to vaccines, it may be possible to specifically target induction of sentinel T-cell immunity against multiple Covid-19 proteins. A group of French scientists (Gauttier, BioRxiv 2020; doi: are bringing to this effort their experience developing multi-epitope immunotherapy targeting lung cancer. They utilized an established vaccine platform for HLA-restricted peptides and 60 conserved (among circulating Covid-19 strains) small peptide sequences derived from 11 viral proteins. They used these complexes to test-immunize transgenic human-HLA-expressing mice with a single subcutaneous injection and generated immune-positive memory CD8 T-cells against antigenic epitopes. They went on to utilize these antigenic epitopes to challenge lymphocytes from recovered Covid-19 patients (in comparison to cells from uninfected controls) for production of IFN-gamma. This identified from recovered Covid-19 patients 25 CD8 T-cell immunodominant epitopes from 3 structural and 8 other Covid-19 proteins. From these they selected 12 CD8 T- cell antigenic epitopes that cover the 11 viral proteins and are predicted to bind efficiently to different human populations’ HLA-I alleles (A, B, C) with high genetic coverage in all geographical regions of the world. These 12 T-cell antigenic epitopes combined in a peptide vaccine could induce at least 4 to 5 memory CD8 T-cell responses in each geographical region of the world so as to achieve a long-lasting worldwide 60-70% ‘herd immunity’ with tissue sentinel T-cells. T-cell immunity is typically long-lasting, and that would largely bypass potential problems with both single-target (Spike) vaccines and focus on primarily an antibody response. We’ll see what happens.

          1. Lane Simonian says:

            Thank you for your detailed and insightful response. The general approaches in regards to treatments and vaccines make considerable sense, and hopefully the specific approaches will yield good results.

          2. HM says:

            Blaine, your comment and follow up responses to Lane’s two questions are wonderfully informative and very much appreciated. They, and the comments like them, are what make this comment section so valuable and make wading through everything else worthwhile. And, of course, Derek’s dedication to this blog and his readers is an absolute gift. While this pandemic is devastating and America’s political response to it is demoralizing, the scope, determination, and speed of the global scientific community is fascinating to observe in real-time. This blog really helps provide insight into, and understanding of, those efforts. Thank you both for taking the time to help strangers have a better understanding of both the darkness and the light.

          3. Marko says:

            Two US clinical trials are listed for cyclosporine , one by U. of Pennsylvania :



            I hope FDA doesn’t stop these , but it wouldn’t surprise me if they did.

            Here’s something on the company behind the multi-epitope vaccine :


  37. An Old Chemist says:

    Dr. Fauci just issued a crucial warning about coronavirus vaccines

  38. An Old Chemist says:

    Public confidence in effectiveness and delivery of COVID vaccines must be established for battle against the pandemic to succeed, says our panel.

    Elizabeth Weise, and Karen Weintraub, USA TODAY

  39. Pathcoin says:

    Well discussed issues about vaccines.
    There are many ways to skin the cat; but the most important question is whether to skin the cat.

    The first question is whether a vaccine is needed. This is not so easy to answer. Widespread testing shows that the most infections are asymptomatic or minimally/mildly symptomatic.

    If we decide we need a vaccine, the overarching question is “what constitutes an effective clinical vaccine?” Necessary but not sufficient conditions are safety, ability to induce a protective immunological response, and the side effects of the vaccines are less than or equal to the virus. And this is the kicker. Depending on the study, at least 25% and more 40% or more of infections are asymptomatic. Another significant cohort is minimally symptomatic. If the vaccines induces significant myalgias, arthalgias and low grade fever, significant enough to lose work and resistant to NSAIDs or tylenol, there will be significant patient push back.

    We have a good model. The seasonal flu vaccine. The vaccines has minimal side effects and most are well handled by NSAIDs or acetaminophen. Despite widespread availability, a significant portion of the population (and not just anti-vaxxers) do not get vaccinated. Anecdotally, people who didn’t get vaccinated and get the flu wish they were dead for the week or so of the disease and swear they will never skip another vaccination.

    Despite the widespread availability the seasonal flu remains with us. Some seasons are mild (due to the correct anticipation of the correct strain to vaccinate and some are not so good, due to an unexpected combination). Every once in a while a new strain emerges with devastating consequences, such as H3/N2 or the swine flu.

    Guillain-Barre is likely to be discovered only after widespread use of the vaccine. The background incidence is about 1.7/100,000 or 17/1,000,000. The swine flu increased this by 2 cases/million vaccinated or 1.9/100,000.

    Here’s the second kicker: older individuals, the one’s most needing the vaccine, are the most likely to develop GBS.

    1. cynical1 says:

      So my chances of getting GBS (regardless of mechanism) may increase by 2 in 1,000,000 or 0.0002% if I get a vaccine? Here, help me roll up my sleeve.

      1. Barry says:

        The damage a vaccine–even a good vaccine–can do to a rare individual is real. From society’s perspective the risk is wholly worthwhile. This is why the U.S. federal govt. stepped in to indemnify makers of (childhood) vaccines. A Covid vaccine would have to be written in

        1. David G Whiteis says:

          In today’s world, though, where out-of-context reporting on isolated incidents is rampant even in “mainstream” media and is absolutey viral (pardon the expression) on social media, even one or two such cases could create even more widespread anti-vax panic than we’ve already seen.

          For that matter, I fear that if one of the vaccines currently in Phase III trials proves ineffective and/or potentially unsafe (almost a statistical certainty, even if one or two of the others tests out okay), the public’s reaction will be, “See? Those things don’t work!” — and uptake of a subsequent, scientifically validated vaccine, will not be anything close enough to help us stem, let alone end, the pandemic.

          1. confused says:

            Why rule out all the vaccines that make it to Phase III working?

            I’m not sure “statistical certainty” is the right way to look at it. Sure many prior vaccine efforts have failed… but if COVID specifically is a good candidate for vaccine development (and most people’s immune systems *do* defeat it without help & produce antibodies — this isn’t HIV or something), that might not be terribly relevant.

            If it’s made it to Phase III, it’s shown some level of immunological response, right?

            And I’m not sure the uptake rate needs to be that high to end the pandemic, given that the R doesn’t seem that high (certainly not compared to, say, measles where you need like 95% or something) and much of the US and probably Latin America will have quite high immunity by the time a vaccine is distributed.

            Now, that won’t eradicate COVID. But I think it would reduce it to “normal respiratory illness” requiring no more precautions or interference with everyday life than the flu.

            The psychological impact of getting the shot shouldn’t be underestimated, either. A lot of what makes COVID really frightening is the lack of treatments… for someone of my age and health, the risk probably actually isn’t that high, compared to e.g. tropical diseases I never worried much about when traveling in the rainforest areas of Latin America. But the “nothing you can do” factor makes it a lot scarier.

          2. David G Whiteis says:

            “I’m not sure the uptake rate needs to be that high to end the pandemic, given that the R doesn’t seem that high (certainly not compared to, say, measles where you need like 95% or something) and much of the US and probably Latin America will have quite high immunity by the time a vaccine is distributed.”

            THAT, I think, mght actually be a light at the end of the tunnel that could surprise us. I do agree that even though we now know that some people can be reinfected (hopefully with much milder symptoms), it’s almost certain that many more people are carrying at least some protection, whether from antibodies stemming from undiagnosed asymptomatic COVID itself or, perhaps, memory T-Cells that “remember” earlier encouters with a coronavirus; this could well mean that the estimates concerning what it would take to reach herd immunity have been significantly inflated. Isn’t vaccine efficacy usually calculated assuming that we’re starting with “0” immunity to begin with? In this case, that certainly isn’t true. If it turned out that due to the variables I just mentioned, we have upwards of 30-40% of people carrying at least some protection against COVID, that could enhance the efficacy of a vaccine significantly.

            Of course, most/all of what any of us predicts here is speculation (he said, removing his Nostramus mask and Cassandra fright wig). The numbers will tell the story, and they won’t lie.

  40. PS says:

    Mark Meadows, White House chief of staff said to reporters today that he is optimistic, there will be a that there will be several vaccines candidates manufactured at scale i.e several 100 million doses of each and at least one or more of the eight with FDA EUA and ready to be deployed by this fall. Never underestimate this country!

  41. Ramkrishna Reddy Vakiti says:

    Vaccines targeting SARS-CoV-2 tested in humans

  42. EJ says:

    “I would expect the stock market not to take the news well, either.”

    Honestly, the US stock market needs a good paddling.

    I have quite a bit of my worth invested in the market, and I like seeing it go up, but not when its untethered from reality. It was already overvalued enough by end of 2019, but now its just silly.

    If bad vaccine headlines function as a cold bucket of water, good!

  43. Dr. Ew Pemakin says:


    Your point about patchwork of vaccines is right on target. Given the large size of these trials, an effective vaccine should reach statistical significance fairly quickly in an environment with reasonably high prevalence. But distinguishing between two effective vaccines will take a lot longer (maybe only a 5 to 10 percentage points between them). And, understanding subtle differences in subpopulations given smaller effective sample will not happen soon.

  44. TallDave says:

    efficacy may play a large part in demand

    mandatory vaccinations may get sticky, particularly if effective COVID treatments are available and vaccine efficacy is relatively low

  45. NorEastern says:

    In early February my daughter came down with gu-YAY ba-RAY syndrome. Seven days in the hospital and $50K in partly covered medical costs later she came home and lived with me for 4 months. It is a very dangerous condition.

  46. Roddy Jaques says:

    “Ideally, this should be publicized before we even start getting vaccine readouts”

    I believe the UK have already done this, I remember a few weeks (or months?) ago the Heatlh Secretary giving a press conference on the priority cohort should a vaccine become available.

  47. idiotraptor says:

    Prior to emergence of SARS, MERS, and COVID19, there were and (and so remain) four antigenically distinct human coronaviruses that cause comparably mild respiratory illness. Immunocompetent individuals can be repeat infected with these viruses since they do elicit robust and durable immunity. To be best of my knowledge, there are no compelling data to show the human immune response to SARS-Cov2 infection or prophylactic vaccines will be any different. Worldwide, clinical experience with COVID19 and post-infection immunity only numbers nine months. At present there is no human data that instructs what the durability and efficacy of natural infection (or vaccine) induced immunity might be. I am fully supportive of efforts to develop and deploy vaccine(s) to this virus. COVID19 complications and sequelae (thrombotic events, stroke, cardiac and neurologic problems) can significantly burden people who contract this disease; it is not the flu. It may be that, irrespective of any antigenic variants that evolve, period vaccination to SARS-Cov2 may be required to maintain durable (12-24 mos?) protective immunity.

  48. idiotraptor says:

    Prior to emergence of SARS, MERS, and COVID19, there were and (and so remain) four antigenically distinct human coronaviruses that cause comparably mild respiratory illness. Immunocompetent individuals can be repeat infected with these viruses since they do elicit robust and durable immunity. To be best of my knowledge, there are no compelling data to show the human immune response to SARS-Cov2 infection or prophylactic vaccines will be any different. Worldwide, clinical experience with COVID19 and post-infection immunity only numbers nine months. At present there is no human data that instructs what the durability and efficacy of natural infection (or vaccine) induced immunity might be. I am fully supportive of efforts to develop and deploy vaccine(s) to this virus. COVID19 complications and sequelae (thrombotic events, stroke, cardiac and neurologic problems) can significantly burden people who contract this disease; it is not the flu. It may be that, irrespective of any antigenic variants that evolve, period vaccination to SARS-Cov2 may be required to maintain durable (12-26 mos?) protective immunity.

  49. idiotraptor says:

    “periodic” vaccination

  50. jazzmanchgo says:

    If it turns out to be accurate that (1) Moderna’s vaccine is effective and safe for older patients, and (2) storage and transporation of the Moderna vaccine will be especially difficult due to the very low temperatures it requires — then would this be an example of a vaccine that could be “targeted” to a specific population, thus expediting uptake as much as possible by limiting the quantities that would have to be shipped and stored?

    1. Marko says:

      Moderna’s storage requirements aren’t so bad : shipping and storage at normal freezer temps , then 7-day storage at normal refrigerator temps during usage :

  51. wilber deck says:

    I would be curious to hear your take on the worry that a vaccine that increases the immune response to the coronavirus (this is usually how vaccines work) will end up making the disease worse. Since it is thought that serious cases of COVID-19 are the ones with an over-aggressive immune response, and treatments that moderate the immune response seem to be helpful, this seems like a real risk for any vaccine candidate that does not actually block the infection.

  52. Marko says:

    This is a preprint but it shows genomic evidence of a second infection of a 25 year-old American in which the second infection was more severe than the first. Now that the cat is out of the bag on secondary infections with the reporting of the Hong Kong case , and waning of antibody levels from primary infections increases with the passage of time , these reports will become more frequent :

  53. FrankN says:

    Derek – I hope you are still reading this! First of all let me express my appreciation of your blog (and also the commenting community that you have assembled, barring a few exceptions). Secondly, I don’t neccesarily expect an answer to my subsequent questions/issues right here – in fact, I feel that a separate posting on the issues raised might be more appropriate..

    On the issue(s): Your posting names the GB-syndrome as a possible vaccination side-effect. Earlier on, you have drawn readers’ attention to a fresh Swedish study:

    Rather in passing, that study (p.7) states:
    “Unphysiologically high expression frequencies of CD38, potentially driven by a highly inflammatory environment, were consistently observed among memory CD8+ T cells from patients with acute moderate or severe COVID-19 (Figure S3A, B). In line with these data, we found that CD8+ T cells specific for cytomegalovirus (CMV) or Epstein-Barr virus (EBV) more commonly expressed CD38, but not HLA-DR, Ki-67, or PD-1, in patients with acute moderate or severe COVID-19 compared with convalescent individuals and healthy blood donors, indicating limited bystander activation and proliferation during the early phase of infection with SARS-CoV-2 .”

    My interpretation, as a layman with English as second (non-native) language, is that there appears to be cross-reactivity between SARS-CoV2 and T-Cells geared against EBV and CMV. The latter two are among the viruses known to potentially trigger the GBS, alongside with Varizella Zoster (Chicken Pox), another virus from the Herpes family that wasn’t considered/ investigated in the a/m Swedish study. As such, I wonder whether your anticipation of GBS as a potential problem for CoVid-19-vaccination might be more than just theoretical..

    Now, the Swedish study didn’t delve into possible causes for the observed cross-reactivity (this would have exceeded the scope of what can reasonably be expected from such a certainly valuable and highly informative paper). So, the observed effect may have to do with some SARS-CoV-2 surface proteins, or the replication sequence, or whatever else may come to minds better informed than I am, but probably not with the spike itself – otherwise (given some 50-90% presence of EBV/ CMV/ VZV immunity among adults in developed countries) Phase 1/2 corona vaccine trials should in all likelyhood have resulted in more serious side effects than they did. Still, I feel there may still be some disaster looming ahead – the more, the more of Virus substance is involved (and especially many of those Chinese vaccines certainly use a lot of SARS-CoV-2 substance). Your’s, Derek, but certainly also readers’ comments on this issue is appreciated.

    Moving beyond: The problem of possible cross-reactivity isn’t just limited to SARS-CoV2, but extends to vector-based vaccines, i.e. Adenoviridae employed as vectors. Apparently, according to a recent study from Singapore (link 1 below), Adenoviridae may confer some cross-immunity towards Coronaviridae, which certainly would be helpful. OTOH, Adenoviridae have unexpectedly also been shown in vitro/ in mice to be cross-reactive with Hepathitis C (HCV, link 2) – studies about what this might mean for humans are still outstanding. Any respective comments on possible implications on SARS-CoV2 vaccine development and testing will be appreciated.…?id=10.1371/journal.pone.0146404

    Last but not least, there is the issue of antibody-dependent enhancement (ADE) already addressed by other commenters here. The issue is anything but trivial – ADE has been documented for feline (cat) corona, and has so far hampered any successful vaccine development against cat corona.

    I would appreciate your, Derek’s, comments on all issues raised.

  54. eub says:

    So. Now that Hahn has said the FDA would (wink wink) consider EUAs for vaccines that have not completed Phase 3, can we talk about
    1) what are historical examples of EUAs for vaccines that hadn’t completed Phase 3?
    2) how much partial Ph3 readout did that have, and what groups were targeted by the EUA?
    3) how did it play out?

    (I was not expecting, at his initial appointment, to be pining for Scott Gottlieb, but here we are now.)

    1. Dark Day says:

      Now watch for the percentage of people who’ll refuse to be vaccined to spike.

  55. An Old Chemist says:

    AstraZeneca’s COVID-19 vaccine candidate begins late-stage U.S. study

  56. Dark Day says:

    If anything keeps me up at night (aside from anxiety over the possbility that none of the currentl candidates will survive the Phase III trials), it’s this. Have these logistical-nightmare complications really been taken into consideration by those (incl. Anthony Fauci) who continue to predict that a vaccine should be “widely available” by mid-2021, and that some degree of “normalcy” might be seen before the end of the year?

  57. Erik Dienemann says:

    Derek – in case you’re still reading this entry’s comments, was wondering if you knew whether people would be “allowed” to receive a 2nd, much better vaccine if it came along 3 months after you got vaccinated with mediocre vaccine #1. My guess is this wouldn’t be allowed, since there were no trials done with multiple vaccines, meaning we have no data on vaccine-vaccine interactions (some of which could be bad, even a few months later) or even vaccine2-products of vaccine-1 interactions. For folks like me, who won’t be high priority, I might have the benefit of seeing a bunch more sets of phase III data, plus early reads on the first few approved vaccines to make a more informed decision of which one to get; plus we’ve been living in extreme quarantine since 3/2 (well before most), due to an immunologically very vulnerable family member, so we’re extremely unlikely to get infected and could afford to wait a few months for a “better” vaccine. Thanks.

  58. Blaine White, M.D. says:

    Convalescent plasma failed India trial. Dr. Lowe shut off the comments section on convalescent plasma because of its political nature, so I’ve put this here. Today on MedRxiv Agarwal et al present “Convalescent plasma in the management of moderate COVID-19 in India: An open-label parallel-arm phase II multicentre randomized controlled trial (PLACID Trial)” (doi: Covid-10 diagnosis was confirmed, and study entry criteria required patients have difficulty with oxygenation. There were 235 patients treated with convalescent plasma and 229 in a control arm with 28-day followup. There was no significant difference in mortality, which was 13.6% in the intervention group and 14.6% in the control group. Looks like another FDA “game changer” that is not.

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