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Moderna’s Vaccine Efficacy Readout

As expected, we have more vaccine news this morning. And the news is good. Moderna reports that their own mRNA candidate is >94% effective (point estimate), with 95 total cases in the trial to date, split 90/5 between the control group and the vaccinated group. 11 of those were severe infections: all 11 in the controls and zero in the vaccine patients. Of the 95 total cases, 15 were in participants 65 years and older, but there’s no word on the split between controls and the vaccine arm there. All of these points are at 14 days past the second dose of the vaccine, which is going to be a standard time point for all the trials (except the J&J one-dose candidate, of course).

The safety readout looks like what we were expecting as well: the Grade 3 events were fatigue in 9.7% of patients, myalgia (muscle pain) in 8.9%, arthralgia (joint pain) in 5.2%, headache in 4.5%, and just “pain” in 4.1%. I would assume that there is overlap in these categories. The company says that these were “generally short lived”. The FDA’s guidance on event reporting would class these as “significant, prevents daily activity”, but not requiring hospitalization. So my read now with the data we have is that up to 10% of people taking the shot will spend the next day or so in bed, feeling like they’ve been hit with a really bad flu. That’s not enjoyable, but I will definitely make that trade in exchange for coronavirus immunity (see below). More data are being collected, of course, so we’ll get better reads on both safety and efficacy as the trial goes on, as will be the case with the Pfizer candidate and the others as well. We have to make sure (as much as we can) that there aren’t worse effects poking up out of those Grade 3 events, but so far, so good. Update: the most reaction I’ve personally had to a vaccine is to GSK’s Shingrix, and I see that it also has about 10% Grade 3 events. So if we’re in that range as the trial goes on, that should work out.

The second press release from the company today is also significant: Moderna says that new stability testing shows that their vaccine remains stable for up to six months under standard freezer conditions, up to 30 days under standard refrigeration conditions, and up to 12 hours at room temperature. There’s no dilution or further handling at the point of administration. This is much more like what you want to see, as compared to the more demanding storage conditions that seem to be needed for the Pfizer candidate. This is how a lot of medicine (and food, for that matter) is already distributed and stored – our infrastructure is a lot more prepared for this.

So we’re already starting to see some differentiation between the candidates, with likely more to come. We’ll see if there’s any statistical daylight in efficacy between the Pfizer and Moderna candidates as more cases accrue (I have no idea if that’ll be the case or not). Likewise with safety. But we already have a difference in shipping and storage, and it’s in Moderna’s favor. As mentioned before here, there are several other categories that could differentiate all the vaccine candidates: point efficacy (as we have now, 14 days after the second), effect on severity of disease when it does occur, duration of efficacy (which we’ll need time for, and there’s no other way), overall safety (which also needs big numbers and will sharpen with longer time points), and whatever differences in all these categories may show up in different patient populations. Those will take time to emerge, too, most likely,

But make no mistake: right now the vaccine news is very good indeed. Effective ones are coming, and what I said when the Pfizer results came about applies even more now, because this good news is coming against a stark background. The coronavirus statistics here in the US now are very, very bad, with cases, hospitalizations, and deaths all rising. Many areas of the country are facing ICU capacity shortages as we head into these rising numbers, and in the coming weeks a lot of people are going to die. It’s never been more important for people to take action against the pandemic: isolation as much as possible, mask wearing, avoiding indoor groups, and all that stuff that we already know about but that apparently too few people are following through on. The curves from Europe have been accelerating at a similar alarming rate, but take a look: their case numbers starting to turn back down again, and there’s no reason we can’t do that here. And we’re not going to be doing all this forever; I really think that the vaccine results we’re seeing mean that the end of all this is finally in sight. We have to make it through to getting our population vaccinated. Hang on.

228 comments on “Moderna’s Vaccine Efficacy Readout”

  1. Luke says:

    Administration of these should start soon. Pandemic is raging. I understand KOL worked hard to prevent any EUA before the election for political reasons, but that’s behind us now.
    Time to authorize distribution and administration.

    1. steve says:

      Nonsense, there’s no evidence that results were withheld for political reasons. Who really believes that Moderna withheld their results and then let Pfizer come out with them first? Let’s get real and eschew silly conspiracy theories.

      1. Jody Gordon says:

        It would be completely irresponsible for a drug company to announce a vaccine candidate in the week before an election. For one thing, science should not be in the business of influencing elections. But also, this would have the appearance of a political play, and would cause widespread distrust of the vaccine’s safety. It would have undermined our public health effort to announce it before the election. So yes, they did the right thing.

        1. PDINV says:

          You are absolutely correct. Now people totally trust them. Pfizer announce efficacy of 90%, then 92% from Russia, then 94.5% from moderna, and then 95% from pfizer (I thought they were only allowed to peek once? I hope the trial is not unblinded now). The people TOTALLY trust this…

          1. PHILLIP S BUDZENSKI says:

            Love this response!

      2. Ryan Booth says:

        The FDA’s decision to have two months of safety data after half of the trial had gotten the 2nd dose was … completely arbitrary. I mean, there’s no easy way to argue for less (“You don’t care about safety!”) or more time (“People are dying and you’re waiting for no good reason to approve the vaccine!”).

        The FDA also convinced Pfizer to not do an initial readout at a lower number of cases.

        This conveniently meant that neither Pfizer or Moderna came out with any info until after the election. To be sure, I think that both Pfizer and Moderna are happier with the delay, because they didn’t want their vaccine to be labeled the “Trump vaccine” and have people refuse to take it on political grounds, and there would have been suspicion if this came out after the election

        1. Eric the Analyst says:

          I’m sorry, but this is not true, and I think it’s really important to be clear about the truth in this situation:

          *The FDA did not convince Pfizer to delay their analysis. *

          The company went to the FDA and sought protocol amendment to skip the first interim analysis. It wouldn’t matter anyway, as the safety data would not be available until mid-November. However, the statistical uncertainty of the first interim (on 32 events) could harm public perception of the vaccine (my interpretation). Back to facts: While that protocol amendment was pending (to shift interim to 62 events), the pandemic exploded and cases began accumulating at a rapid pace: In the few days in between when the protocol amendment was approved, and the analysis was completed, ca. 30 more cases accumulated. That’s how we got to 92 cases.

          Please correct me if you have a contradictory source?

        2. DrOcto says:

          The Trump administration gutted the FDA, why would they do him any favours?

        3. Bioduuude says:

          “To be sure, I think that both Pfizer and Moderna are happier with the delay, because they didn’t want their vaccine to be labeled the “Trump vaccine” and have people refuse to take it on political grounds, and there would have been suspicion if this came out after the election”

          I feel that those who are looking to win a Darwin Award should be allowed to do so.

          If you are so foolish that you would not take a vaccine because Trump’s name was associated with it, then enjoy your short life.

    2. Rifka says:

      Luke you’re definitely part of the problem on this planet. Seek spiritual counseling, or a daily enema.

    3. Shazbot says:

      Lead off by poisoning the well, eh? Real data takes time, that’s all there is to it. Might as well say it was accelerated by getting as many people sick as soon as possible so the number of cases endpoints were reached faster.

    4. David Garfield says:

      Do we know when similar data (effective or not) are coming from the AstraZeneca/Oxford or J&J efforts?

  2. Chris Phillips says:

    So, to my mind, the 64-thousand-dollar question is whether these efficacy rates in the 90s are going to be repeated with the other types of vaccines, or whether they will be unique to the mRNA ones.

    1. Michael says:

      The thing is, Novavax has *far* more impressive antibody titers than the mRNA vaccines in its earlier-phase trials. I am really excited to see how its efficacy reads out.

      That said, I do wonder whether Oxford/AZ will hit 90%.

      1. Emi says:

        The russian vaccine uses an adenovirus vector (actually two) and they have a 92% efficacy at 20 cases. I know 20 cases isn’t not statistically ideal but it probably gives us an idea that they’re gonna work. The amount of antibodies produced, how and who got the most antibodies in previous phases probably correlate with their actual efficacy.

        1. Tom says:

          Imagine believing the Russians lol

          1. Anon says:

            Imagine laughing at Joe McCarthy, at a time where the USSR was much more evil than Putin’s Russia today and we actually had communists in the US taking orders from the USSR, and turning around and believing every “OMG Russia” story that is sourced to anonymous intelligence officials, i.e. the same people who lied us into war with Iraq.

          2. Zambo says:

            @Anon why do you pop up on here every single post where Russia comes up. Can you say hi to vlad for me?

          3. Russiagate is BS says:

            @Zambo It’s telling whenever the Russiagate crowd gets called out on their nonsense, the only response is to call someone a secret Russia plant/bot. Remember when people who were doubting the evidence of chemical weapons programs in Iraq were accused of doing Saddam’s bidding? That’s always the respite of someone who is sowing or has swallowed war mongering propaganda unthinkingly. “The only reason that you don’t believe every story that the CIA stenographers at the NY Times or WAPO write is because you love Putin/Iraq/Insert “New Hilter”.

      2. Craig says:

        Novavax stimulates about 5x more antibodies, if I recall. Is there any “negative” side effects to having too many antibodies or is a more-the-merrier kind of thing?

        1. Barry says:

          IgG titer in the plasma has correlated very poorly with disease outcome for Covid19. Some who recovered from severe infection mounted no IgG response; some who mounted whopping IgG responses died. It’s the easiest thing to measure, but it’s a lousy surrogate read-out for vaccine efficacy against Covid 19.

        2. PHILLIP S BUDZENSKI says:

          Novavax IgG antibodies are directed at the spike protein. Of course a non-specific IgG antibody titer might not be associated with survival, but a SPECIFIC antibody titer…time will tell.

      3. PHILLIP S BUDZENSKI says:

        Agree.

  3. Proud girl says:

    Thank u presadent TRUMP 🇺🇸

    1. Nemo says:

      Sure, that guy who repeatedly claimed that Covid was ‘Fake News’ and “It’s going to disappear. One day, it’s like a miracle—it will disappear.”

      https://www.theatlantic.com/politics/archive/2020/11/trumps-lies-about-coronavirus/608647/

      An unfinished compendium of Trump’s overwhelming dishonesty during a national emergency

      CHRISTIAN PAZ
      NOVEMBER 2, 2020

      1. Prowd girl says:

        It is fake and President Trump delivered the cure with his outstanding leadership. Why can’t u libs just be happy for once #tds

        1. nemo says:

          Amazing, it’s fake and he delivered the cure.

          That’s pretty magical.

          Sorry guys, I know better than to feed the trolls. Especially when they’re members of neo-fascist hate groups.

          I’ll stop now.

          1. Marko says:

            ” Amazing, it’s fake and he delivered the cure. ”

            LOL.

            Thanks a lot. Now my keyboard is covered in coffee and spit.

          2. Charles H. says:

            Actually, I think “she”‘s being satirical, but Poe’s law.

        2. FoodScientist says:

          Are the Proud boys a gay pride kind of thing? I have been curious about this.

          1. Coronahoax says:

            Dragging the LGBT community isn’t the W you think it is leftist.

          2. nemo says:

            Proud Boys are a neo-fascist hate group that has recently ‘re-branded’ as an explicitly antisemitic,

            https://www.jpost.com/diaspora/antisemitism/proud-boys-leader-trying-to-rebrand-the-group-as-explicitly-antisemitic-648831

            https://www.splcenter.org/fighting-hate/extremist-files/group/proud-boys

            Gay men began hijacking their hashtag a while ago.

          3. Anonymous Trans* says:

            No, they are neo-Nazis and hate LGBT people.

        3. Carolin malott says:

          Seriously? You are working with “alternative “ facts. Hint: there is only one set of facts and they are not alternative. Pledge allegiance to your demagogue who also said Covid will just go away. You are choosing to ascribe vaccine development to the same idiot who repeatedly said “it will disappear”, “it’s like the flu” and suggested treating it with bleach. Oh right, and is now throwing roadblocks up in front of the president elect. Please tell us what you are smoking so we can all feel as happy as you. FYI – Pfizer – first to announce results, used its own money (not warp speed) to develop their vaccine at risk.

          1. James says:

            This seems obvious to me, but somehow the media and half the world just wants to take their easy wins from communication gaffs.

            “alternate facts” clearly meant alternate data and that they dispute the data that someone else put forward. The word facts is being misused, but sadly, people misuse english words all the time. Look at how people use “literally” these days.

            No, I’m not right winged or a Trump fan. I just think people get away with terrible actions while the world is focused on some dumb shit someone said.

    2. Eli Kagan says:

      More like thank you science. The election is over thank god. Can we please go back to sanity?

      1. Hopeful Layman says:

        Thank you, Eli.

        And yes, this is very encouraging news. And there could well be more forthcoming: J&J promises a one-shot vaccine (although if I recall correctly, theirs did not prevent upper respiratory infection in the early primate studies, so hopes for sterilizing immunity are probably not too high) — and, even more encouragingly, as Michael points out: Bring on Novavax!!!

    3. nemo says:

      BTW ‘Proud girl’, are you associating yourself PBG?

    4. nemo says:

      BTW ‘Proud girl’, are you associated with PBG?

  4. Adrian says:

    We do not know whether these vaccines provide sterilizing immunity or only turn symptomatic carriers into asymptomatic carriers.

    In the latter case the vaccines might make things worse if people stop social distancing before close to 100% of the population are vaccinated.

    And asymptomatic people working as nurses or in retirement homes are already a huge problem.

    1. Bryon says:

      In the monkey tests the vaccinated monkeys quickly eliminated (day or two) all of the virus from their upper airways despite getting a large direct dose. So there’s reason to be optimistic that vaccinated humans will not shed/transmit the virus to others

      1. David G Whiteis says:

        “In the monkey tests the vaccinated monkeys quickly eliminated (day or two) all of the virus from their upper airways . . .” Is this, then, sterilizing immunity? Sounds like it to me.

      2. Hopeful Layman says:

        “In the monkey tests the vaccinated monkeys quickly eliminated (day or two) all of the virus from their upper airways . . .” Is this, then, sterilizing immunity? Sounds like it to me.

        1. Marko says:

          There’s an echo in here….

          1. Sc says:

            I’m guessing Dark Day got his alts mixed up?

    2. Michael says:

      I agree with Bryon. It’s likely that, even if infected, the amount and duration of shedding would be limited.

      In addition to the animal trials (also replicated in mice), we know that all three previously seropositive people on the fishing boat were PCR-negative after their outbreak, and all 24 previously seropositive participants in the Wisconsin summer camp were PCR-negative after their outbreak. And the T-cell study posted by Derek a few days ago said that zero of the “strong T-cell response” group of frontline workers were infected.

      Finally, the secondary attack rate (per WHO) of asymptomatic carriers is 33% that of symptomatic carriers — presymptomatic carriers have an SAR of 63% of symptomatics.

      I have a hard time wrapping my head around the amount of pessimistic mental gymnastics required to think that rolling out >90% effective vaccines will “make things worse.”

      1. M says:

        There is a small percentage of people (not saying Adrian is one of them) who think the worst no matter what. But I think the “end of the world” doomsayers will be wrong (again). Eventually, they’ll be right, but nobody will be around to give them credit. Or care.

        1. Adrian says:

          There are real risks if the vaccine is used in the wrong way, or with misleading communication.

          No mental gymnastics is required for noticing that the “no promise of protection until 1 month after the first shot” part is often omitted in the media coverage. It would be a huge problem if a government would fail to emphasize this properly when rolling out a vaccine.

          And the theory people bring here that non-sterilizing immunity would still prevent spreading the disease to other people is not backed up by a human trial. It might be true or not, COVID-19 has already given us plenty of surprises so let’s not assume the best case before we have data on that.

          1. Michael says:

            I hear you on the promise of protection point, but I think that message can be delivered effectively.

            I was clearly informed when I got my flu shot last month that it would take 10-14 days for my antibodies to kick in.

        2. Zambo says:

          It’s the same people that insisted we’d never get an effective vaccine, and if we do, it wouldn’t for years. Now that it’s clear it will happen far before that they’ve moved onto anything from possible lack of sterilizing immunity to cost to logistical challenges (not that these aren’t issues but they’re blown way out proportion by these people for the most part).

          1. Tom says:

            Sadly most health officials and government people are in that camp. Expect to be locked down forever.

          2. confused says:

            How would that even work? Once COVID deaths drop after the vaccine, and it is no longer “new”, most people will stop being afraid of it so how could political will to maintain restrictions possibly be maintained?

            That political will doesn’t exist in many places *now*! Here in TX, we have a mask mandate but it’s imperfectly followed at best, and a court just shot down El Paso County’s local order (and that county has very high hospitalizations — more than the Greater Houston area, which has 10x the population).

          3. Roger Callaway says:

            It’s hard to predict the future.

          4. confused says:

            Sure, but human nature is not *that* changeable, and neither are long-established cultural trends easily changed within a year or two.

      2. Michael says:

        “I have a hard time wrapping my head around the amount of pessimistic mental gymnastics required to think that rolling out >90% effective vaccines will “make things worse.””

        I am hopeful for vaccines. But I do think there’s a potential window of peril as vaccination starts, where early vaccine recipients are not fully protected yet and change their behavior… and the strong social norms encouraging distancing and masks weaken. It’s going to take us a long time to get to a decent chunk of the population vaccinated. We need a strong message about the need to stay careful even as vaccination begins.

        1. Michael says:

          For the record, this is a different Michael. I am not grappling with my own quote.

          1. OtherMichael says:

            Ack. I’ve seen you around here before, and I always worried it’d be confusing. Here we’ve got the confusion!

  5. JS says:

    Let me rephrase my question from the other vaccine thread:

    Are they keeping track of cases in household members? If yes, might we get some idea of the reduction in the ability to pass on the virus?

    Are they collecting case data between the first dose and nominal starting point (here 14 days after second dose) ? In other words will we know (at too low significance?) if there is good protection after one dose?

    With such a good protection, might we guess that a smaller dose would be better from a public health point of view? For example half as much to twice as many people? Lower doses were tried in the earlier phases.

    1. gcc says:

      I’m also not totally clear what cases are counted in terms of their timing relative to the injections. In other words, what does efficacy “at” 14 days past the second dose of the vaccine mean? Do cases after the first injection but before the second get counted? If those are counted, I would think that would mean the vaccine might actually be *more* than 94% effective at preventing disease in people who have had two shots of the vaccine (since presumably one shot is less effective and it also presumably takes some time after administration before an increase in immunity). Or are cases only included in the efficacy calculations if they were after the second shot?

      1. JS says:

        Seems clear that they only count the cases 14 days+ after the second dose when coming up with the 95% number.

        Question is when the vaccine starts to work well. Could be that it is quite protective some time after the first dose. And you might be able to get a reasonable readout on that from the existing trial.

        1. Hopeful Layman says:

          Related question (I think?) —
          How might any of the following scenarios play out:
          (1) A person contracts COVID, “recovers”, then gets vaccinated. What’s the efficacy? Is this vaccination even necessary?
          (2) A person contracts COVID (or at least gets exposed), and gets vaccinated during the early stages of the disease.
          (3) A person gets the first shot, then contracts COVID (or at least is exposed), then gets the booster shot a month later, while still in the early stages. Will this effect efficacy?

          Given the ferocity with which COVID is currently roaring through the population, any/all of these scenarios seem likely.

    2. Patrick says:

      Maybe, but we haven’t actually tried it. There’s a minefield there and I don’t think it can be responsibly navigated outside of more trials, which means not super soon.

      1. JS says:

        Absolutely you need a separate trial before using a lower dose. But it might be doable given the time until lots of doses become available and so could be of use. But it will have a cost.

    3. Nga Takiwi says:

      Interesting idea, but logistically challenging. Instead of recruiting patients, you’d need to recruit ‘families.’ Do you study couples, married / unmarried, with / wo kids, older relatives cohabitating? How often do you test patients v family members? How can you tell if trial participant spread virus to kin or was protected from the infection their partner acquired elsewhere? Tough nuts to crack. Doable with time and resources, but those are finite.

      1. JS says:

        Indeed there are many complications and the results could be quite murky.

        But, hypothetically, you could ask the participants in the current trial of they live with someone and if any of those have tested positive in the relevant time interval. There may be regulatory/legal issues with that, I don’t know. And there is some risk of biases, both from people guessing which arm they are in and for the 95 positive cases.

        If samples from the participants and family members had been collected every few days, more could have been done, but that would have been a major logistical challenge.

        1. Marko says:

          They could get a good read on whether vaccinated patients ever became asymptomatic carriers by doing antibody tests on them. The vaccine itself would induce anti-spike antibodies , of course , but checking for anti-nucleoprotein antibodies should be able to detect most of those those who had been asymptomatically infected. I would hope that they would do these tests at some point in the follow-up.

          1. arcsix says:

            In an interview with Bloomberg today, the Moderna CEO said that they would be doing exactly that (looking for non-spike antibodies in trial participants):

            https://podcasts.apple.com/us/podcast/moderna-ceo-game-changer-vaccine-is-easier-to-ship/id326301337?i=1000498884828

          2. Marko says:

            Ah , that’s good to hear. Thanks.

  6. Steve Scott says:

    Suppose 100 people are in a crowded indoor event. They all have taken the Moderna vaccine. One of them is an asymptomatic carrier and spreads it to the others, without realizing it. Potentially, up to five of them could be infected, although not seriously enough to require hospitalization. Now maybe this wouldn’t reflect a real life situation, but it points out the highly important finding that the vaccine seems to reduce the severity of the infection. This sort of question is likely to be raised more and more, in the future.

    1. JDPatten says:

      Which, of course, is the reason to continue precautions. No vaccine is going to be 100%. A good vaccine will just be one (very?) helpful element in the whole lengthy effort. No one element will make the disease disappear promptly.
      Patience, patients!

      1. Muh Lockdowns, muh masks says:

        Yes, we must sacrifice many more years of our lives (and our children’s) to fully eradicate a virus that kills people on average who are older than our average life expectancy. Sounds like everyone in these comments has a cozy house and hasn’t missed a paycheck this year. I am about to have a child, and I don’t know if they will be able to see my or my wife’s faces, or anyone’s for that matter, until we are discharged. And when will they see anyone else’s face? Who knows what that’s going to do? What sort of developmental delays are we going to see for decades from our children’s lives being interrupted for at least a year? How many suicides? How many drug overdoses? How many missed preventable disease screenings?

        And before anyone tries to Orange Man Bad me, how did Fauci’s favorite country Italy do? They implemented the harshest possible lockdown, mandated masks, etc. and are still dealing with a massive second wave. And if you try to talk about their second lockdowns, in most cases their curve was already flattening prior to the lockdown orders being issued. I could post a random assortment of case/deaths/hospitalization charts and there is no way any of you could tell me which countries locked down, when, or issued mask mandates.

        1. Tom says:

          The restrictions are permanent. They were always meant to be. Rolling lockdowns and no large events is the future. Governments and the Faucis of the world are having too much fun.

          1. Michael says:

            Ah yes, the combined financial and political influence of the hotel industry, urban real estate industry, sports industry, restaurant industry, live entertainment industry, travel industry, airlines/cruises, convention halls, banquets/weddings, religious organizations, cinema, etc., etc., etc. all pale in comparison to that of the shadowy “Big Distancing” cartel that will no doubt keep all of the above shuttered forever.

          2. WestWallaby says:

            As a European, I would like to offer my deep condolences to the inhabitants of the United States of America who are still located on Planet Earth.

          3. confused says:

            It doesn’t work that way. Even if one assumes the existence of a certain percentage of “petty tyrants” in governments who enjoy exerting power (and to be clear, I do *not* believe Dr. Fauci is one) , economic pressures and the fact that COVID will no longer be “new” soon will prevent extending measures much beyond their necessity.

            In many parts of the US there are already practically no measures in place!

          4. Hopeful Layman says:

            “In many parts of the US there are already practically no measures in place!” Well — true, but that’s hardly a model to follow. A “false optimism” (or nihilistic apathy) like the one you’re describing here is as destructive to our overall health and mental health as is the apocalyptic doomsday vision expressed above. I’m with Derek, Fauci, and the other reputable sources — There’s a light at the end of the tunnel, it’s getting a little brighter, and if we hunker down and ride this out together, we can get there.

            p.s. I agree with MLmm about the stark loneliness and alienation that goes along with not be able to see people’s faces. Which is why I’m willing to live that way for a while longer, so we can sooner reach the point when we no longer have to.

          5. confused says:

            >>Well — true, but that’s hardly a model to follow.

            Sure, but my point is that we are erring in the *opposite* direction — less than would make sense, not pointless restrictions.

        2. Hopeful Layman says:

          No one’s talking about “many more years” of anything. If we have decent uptake and good public health practices for SEVERAL (okay, maybe “quite a few”) MONTHS after initial rollout, we can slowly inch our way back to “normal” over the course of 2021. Precise timelines are impossible to calculate, but I’m not aware of any predictions extending indefinitely.

          1. Tom says:

            They’ve been alluding to permanent restrictions the whole time because they don’t want to come out and just say it yet. But travel, large events, conventions, theme parks, parties etc are all gone. There’s no way back to that even if they want one and they don’t.

          2. Hopeful Layman says:

            “. . . use the combination of a vaccine and public health measures to turn this thing around.” (Fauci)

            “Turn this thing around”? That doesn’t sound like perpetual lockdown or masking to me.

          3. Ken says:

            I think, though, that “normal” in 2022 will be different than what we had in 2018 because demand has changed, and you can’t fight the markets. I for one would not consider going on a cruise, and it may be a few more years before I visit a movie theater.

          4. Michael says:

            Two weeks after my second dose, I will have zero hesitation about going to the movies. Absolutely zero hesitation.

          5. Dark Day says:

            “. . . demand has changed, and you can’t fight the markets. I for one would not consider going on a cruise, and it may be a few more years before I visit a movie theater.”

            Well, for what it’s worth, here was Fauci’s prediction in mid-September, as reported by the New York Times. He was assuming a vaccine with approximately 70-75% efficacy at the time. Of course, any prediction like this is an estimate — it will all depend on those “numbers” and how they look by then. Speaking for myself, both my work (as a writer/critic/author) and my passion — the love of my life — is music, primarily blues and jazz, performed in clubs, theaters, show lounges, at festivals, etc. I’ll go back to those as soon as they’re open. And yes, in my world we hug and shake hands as everyday forms of greeting, so although it will be a little tentative and uncomfortable for a while, I’m sure most of us will eventually go back to that, as well.

            “Dr. Anthony Fauci said a vaccine would need to exist for nearly a year before people might feel comfortable returning to theaters unmasked, which he said would likely be mid- to late 2021.”

          6. Hopeful Layman says:

            Michael, realistically speaking, I think it will be a little uncomfortable and nervous for some of us, for a while — not to get over-dramatic about it, but almost like someone recovering from PTSD, The anxiety will be there. I’m sure I’ll run into beloved friends I haven’t seen for a long time, and the first question will be, “Can I give you a hug?” Some folks will be cool with it, some won’t (yet) — we’ll all have to learn to negotiate that stuff. As for theaters, I’m guessing a lot them will probably be at partial capacity for quite some time, with empty seats (or rows) separating individuals and/or groups. And as much as I love snarfing popcorn at the movies, I’m guessing a lot of places will require masks for a while, also. (Hard to know what performance venues like bars, nightclubs, supper clubs, etc., where eating and drinking are part of the deal, will do about the masking situation — let alone sports stadiums and outdoor festivals, where concessions stands are also an integral part of the business.)

          7. Dark Day says:

            Ken, would you consider going on a cruise or entering a theater if there was a “Proof of Vaccination Required” to get in? Not a government mandate, but a business decision on the part of the cruise line or the theater itself — not unlike the “Immunity Passports” that some airlines have been considering.

          8. confused says:

            The only thing that I expect to change long-term from this is more telecommuting… but that’s because it made economic sense before COVID but company cultures hadn’t adapted yet, IMO.

            I think people will “snap back” in most places quicker than you’d think. But then, I feel like most people here in TX don’t care much *now*.

          9. Dark Day says:

            With all respect, Confused, how is that possible? Texas’ numbers are spiking horribly, and the toll taken on the Latino community is beyond tragic. How can people remain in such denial? And no, I’m not intentionally singling out Texas here — this is apparently the situation all over the country. People “stop caring” even as others get sick and die all around them? And for that matter, if they don’t “care” enough now to be careful, will they “care” enough to get vaccinated in a few months? Or will this “Nobody tells me what to do!” attitude extend even to that?

          10. confused says:

            >>With all respect, Confused, how is that possible?

            I think because people often find “personal stories” more convincing than statistics, and because people’s social circles are not random samples of the population – and neither are COVID hospitalizations/deaths.

            If you are young, and most of the people you know are young, it’s quite likely that the people you know who have had COVID experienced it as a relatively mild disease.

            And COVID can be very unevenly distributed even within a relatively local area (e.g. one metro area such as Houston).

            None of my family/close friends have had it, even in those living in areas with pretty high COVID rates… but that’s because we are mostly able to work from home or (for older family members) are retired, and take it seriously. The one person I know who had it was a mild case… also not unexpected, because most of my social circle are close to my age, therefore low-risk.

            But a person with those same social-circle experiences who was more skeptical of the “medical establishment” (and many people are, thus the extreme success of various quack medical things) could easily interpret that as “look, COVID is no big deal!”

        3. Athaic says:

          that kills people on average who are older than our average life expectancy.

          (sigh)
          I wish people would pay more attention in highschool. Or that the intricacies of the age pyramid are part of the curriculum, as a start.

          Average life expectancy is precisely that, an average. And it’s not a average of an evenly distributed population.
          Someone reaching 50 is more likely to reach one-hundred than someone in their teenager years
          As an extreme example, according to the wikipedia article on life expectancy, in ancient Rome, the life expectancy was 25 years at birth, but 53 years upon reaching age 25.

          tl;dr: “older than the average life expectancy” is a fallacious argument.

          1. confused says:

            This is surprisingly poorly understood! One of my high school biology teachers told us that people died of old age in their 30s during the Middle Ages…

            Also, I’m not sure that average age of COVID death > life expectancy is generally true. It does not seem to be the case in Texas, which has an unusually low median age for US states. Slightly less than half the COVID deaths are over age 75, but life expectancy is 78.5.

            I know early on that was said about Italy, and some places in the Northeast US, but this probably depends on age distribution of the population and who is infected.

            And some places in the US early on were seeing primarily long-term-care deaths, which obviously would skew very old.

            It probably *is* true that COVID has fewer “life years lost per death” than flu pandemics, which have a different age profile — but not nearly so much so as is sometimes claimed. There are lots of deaths in “middle-aged/early elderly” age groups who could easily have 20-40 years left.

          2. Ken says:

            One of the reasons for that discrepancy was the very large number of people who died in childhood from measles, rubella, pertussis, and other diseases for which we now vaccinate. That’s what “herd immunity” meant before vaccines – every new generation caught the disease, and the survivors were immune.

          3. confused says:

            Essentially, yes. ‘Herd immunity’ of a sort did happen, but didn’t last because of population turnover — new non-immune people were being born and old immune ones were dying.

            But I fear the term ‘herd immunity’ has almost lost its meaning this year — a lot of people seem to be using it to mean the transition from “pandemic” to “endemic” state of the disease, which I think is something quite different. The 1918 flu didn’t spike back to pandemic levels later due to population turnover (even though there weren’t flu vaccines until WW2), though the virus didn’t go extinct either.

          4. Charles H. says:

            It’s not entirely fallacious, though your arguments have weight. People also just “wear out”. How quickly this happens depends on the kind of life they have lead. Working at exhausting physical labor for years on end can make it happen more quickly. This is less common now than it used to be, but it still happens to a large number of people. And there are other chronic stressors. Various kinds of pollution poisoning count as common examples.

            That said, people never die of “old age”, they die of something else that is made more fragile by old age. Heart attacks, strokes, cancer…the list goes on and on. This year COVID has been added to that list, though some only want to consider the effects caused by COVID…which were already on the list. IIRC a lady in her 120’s was found to be down to a very few types of antibody precursors. Well, she eventually died of something else, and that definitely wasn’t listed as the reason. But her immune system had clearly become fragile.

          5. WST says:

            re: Confused (who isn’t? btw)

            “But I fear the term ‘herd immunity’ has almost lost its meaning this year — a lot of people seem to be using it to mean the transition from “pandemic” to “endemic” state of the disease, which I think is something quite different.”

            Well, that would be the Herd Immunity Threshold in a compartmental model. Have not seen it used much in this way…

            Typically the HE denotes a final stage of the compartmental model when the virus get extinct.
            So:
            “Essentially, yes. ‘Herd immunity’ of a sort did happen, but didn’t last because of population turnover — new non-immune people were being born and old immune ones were dying.”

            …this is incorrect, if HE did happen, then the virus would disappear.
            This has never happened in any epidemic, so the conclusion should be that this model with its never occurred artefacts fail to explain dynamic of an epidemic and should not be used. I sincerely hope that most of these models will be also covid fatalities and epidemiologist concentrate at observing and analysing the reality. IMHO there is not enough descriptive information to try to set up models. But numerology has apparently future…

            “But I fear the term ‘herd immunity’ has almost lost its meaning this year — ” absolutely, if it ever meant anything in this context. It’s a notion from the vaccination world, but even here the mathematical models prevent us from seeing the reality. Vaccinations must be massive, often targeted or “circular” to stop an epidemic outbreak.

            “The 1918 flu didn’t spike back to pandemic levels later due to population turnover (even though there weren’t flu vaccines until WW2), though the virus didn’t go extinct either.”
            There were 4 waves, second the worse and third roughly 1/4 of it and a smaller 4th wave.

          6. confused says:

            >>re: Confused (who isn’t? btw)

            I chose that name so as not to be seeming to project more certainty than I have.

            >>…this is incorrect, if HE did happen, then the virus would disappear.

            This is what I’m saying, people are using the term differently!

            I’ve seen it used to mean R falls below 1 due to immunity levels. I think this *did* happen in e.g. measles, ending outbreaks, but it did not remain below 1 long enough for the virus to die out (due to population turnover), so eventually another outbreak occurred.

            >>This has never happened in any epidemic,

            Do we actually know this? IIRC there are some diseases historically mentioned which no longer seem to exist, e.g. the “English sweat” from the 1600s.

            >>There were 4 waves, second the worse and third roughly 1/4 of it and a smaller 4th wave.

            But that’s all the 1918-1920 period. I’m talking about the time between 1920 and the introduction of flu vaccines… the virus didn’t become pandemic again.

          7. WST says:

            I just wonder how useful is use of concepts like R from a models that predict things that never happened, use assumptions about reality that are not met… There is definitely a need to have some sort of rough estimation of how infectious a pathogen is, so I see WHOs R0 estimation as a “figure of merit” that can help to position different pathogens and potential epidemics but would not read too much to it. What does R mean in an pandemic episode that is strongly based on super spreader event?
            Many countries publish “effective R” as a way to see a trend, but…its based on incidence data that is not randomised. Who knows (could be a nice paper…) what is the impact of that on Re ?

            Direct trending can be done by looking at 7 or 14 days increase rates.

        4. Nessuno says:

          How did Fauci’s favorite country Italy do? They implemented the harshest possible lockdown, mandated masks, etc. and are still dealing with a massive second wave.

          Yes, we did, until early May, but then we reopened a month too soon, when there was still significant community diffusion in the most affected regions.

          The original plan for ending the lockdown was to stagger the reopening by separating each phase by two weeks, to give the health authorities time to analyse the data and slow down things if needed, starting from early May and ending in late June. Unfortunately that wasn’t to be because as soon as some sectors reopened everybody else started to protest they weren’t allowed to reopen too and the government gave up, so by early June the only restrictions left were school closures and mandatory masks inside shops and on public transport.

          At the same time the opposition decided that people were visibly tired of COVID-19 and took their cue from Trump: the leader of the largest opposition party personally attended anti-masking demonstrations, publicly refused all summer long to wear a mask and sponsored denialist meetimgs in parliament where masking and social distancing rules were flouted, while the regional governors belonging to his party started signing local ordinances reversing social distancing regulations in public transportation and shops and a number of politically connected doctors and hospital managers, all of them appointed to their positions by the same governors, started claiming that SARS-CoV-2 had muted, was clinically dead, was going to disappear soon, there was no need for any kind of restriction anymore and so on.

          By August the epidemic flared up again in several tourist destinations, with multiple outbreaks connected to nightclubs and restaurants, so the government closed them again and started mandating testing for all travellers returning back to their cities from those areas and for travellers entering or reentering Italy from other countries. That was enough to regain control but the baseline number of cases didn’t go back to what it had been in July. You will not be surprised to learn that the opposition protested against the “useless damages to the economy” again, joined this time by some of the smaller parties who were nominally supporting the government but evidently had made the same calculation, and started to claim that there was no more need for emergency measures and the government was planning to institute an unconstitutional “health dictatorship,” whatever that means.

          In September there were local elections scheduled in most of the country so the government felt compelled to show that things were going back to normal by reopening all schools and universities and by inviting all employers to recall the people who were still working from home back into the offices because restaurant and bar owners were being affected by the reduction in the number of customers. Of course that, and buses and trains going back to full capacity, was seen by a lot of people as an indication that social distancing and masks weren’t needed anymore, and the number of daily cases started creeping up again.

          By mid October everybody who wasn’t actively trying not to see started to realise that the curve was trending in the wrong direction and doing it fast but the government had just barely managed to renew the decree giving it the powers needed to deal with the pandemic so there was no appetite at all for reinstating restrictions, and they decided to wait a few more weeks… you can look at the charts to see how well that went.

          Now it’s November and there are restrictions again in some regions, but masks aren’t mandatory inside offices, working from home is only recommended and where I live high schools are closed and bars and restaurants close at 6pm but everything else is still open. Meanwhile I had two coworkers who shared a room with me for 8 hours every day test positive to COVID-19 and I’m still going to the office contact tracers have a huge backlog of cases to process and basically gave up, the number of cases, hospitalizations, occupied ICU beds and dead is still growing and the feeling here is that it will be a lot worse than in March and April.

          All of this to say that the spring lockdown worked very well, but we haven’t been in lockdown for a long time, and it shows.

          1. Dark Day says:

            Isn’t that more or less the scenario for most of the European countries currently struggling with a new “wave”?

          2. Nessuno says:

            I left out the final paragraph.

            Probably lockdown worked both too well and not well enough. It wasn’t sufficient for complete eradication but at the same time it made possible to live an almost normal summer, so we had months in which it became too easy for a lot of people to convince themselves that COVID-19 was a solved problem, something there was no need to worry about anymore if not even something that had never been worth worrying about. Many became increasingly overconfident and careless but the virus was still around and that bit us hard in September, when all the behaviours that had been risky but didn’t have too many visible consequences when virus prevalence was low started generating more and more cases, and it took too long for many to adapt. Arguably many haven’t yet.

          3. confused says:

            Sounds plausible. Here in TX (and in many other states outside the Northeast/West Coast) I think part of the issue re: public acceptance of measures was that our stay-at-home order came before we were hit hard, so the “whole thing is overblown” argument started to look very plausible.

            I think many public-health people missed how *little* people in the central US identify with places like NYC, ie they expected the NYC experience in March/April to be meaningful to people in the central US, when it largely wasn’t.

          4. FrankN says:

            Nessuno: Thx. for the Italian perspective.

            Dark Days: “Isn’t that more or less the scenario for most of the European countries currently struggling with a new “wave”?”

            Its somewhat more complicated, at least here in Germany. Quarantining worked quite well, at least in the beginning, when the initial cases, directly imported from Wuhan, could be contained. Authorities then were surprised by the skiing holiday import, especially from Austria and South Tirol, and made a few crucial mistakes such as allowing Carnival celebrations.
            Once present, the Virus worked its way through the afffected communities – generally suburban middle class, rather South than North German (for less distance to the Alps), with intensive contact into nursery homes. Lockdown measures were harsh – not as harsh as in Italy, but still including curfews in a few counties, plus closing schools, restaurants, non-essential shops and businesses. Still, those harsh measures didn’t manage to contain the disease in various counties. E.g., mortality in Tirschenreuth, Bavarian Forest, has been higher than in New Jersey, which last time I checked was the most affected state in the USA.

            Miracously, it all ended sometime in May, for reasons yet unclear. More outdoor life, sunshine-induced presence of Vitamin D, maybe also the (rather late) stipulation to wear masks indoors, might all have helped – but the lockdown measures themselves were rather ineffective, partly even counter-productive. E.g., some states closed down hardware stores, others left them open, resulting in substantial shopping-related traffic across state borders, something you rather want to avoid when aiming at keeping outbreaks locally contained.

            During late spring and early summer, the situation was fine. We had our regular local outbreaks among Eastern European contract workers – not just slaughterhouses, also cucumber pickling, asparagus, berry & cabbage harvest, atl. But since those contract workers hardly mixed with the locals, these outbreaks could be easily contained.

            The situation changed with the holiday season, when people with migration background visited their (or their parents’) native country, and returned infected. This concerned especially Anatolia, Albania/ Kosovo, to a lesser extent also Russia and Ukraine. By mid-August, infection rates started to go up in places with substantial migrant population, e.g. Duisburg/ Herne, Offenbach, also Berlin. Large indoor weddings with up to 400 guests, as typical for some of these communities (and not allowed in Spring), provided for an effective spread. Notably, all these nuclei for the second wave had hardly been affected during the first wave, which primarily hit the suburban middle class of German descent.

            Another factor was incoming tourists. Berlin as self-declared “Party Capital of Europe” in September attracted lots of Swedes, Balts, Poles, Czechs, Brits, possibly also Spanyards and Italians – all untested, un-monitored, and of course using a different Corona-App (if at all) from the German one. The outcome was expectable (unfortunately not for our politicians).

            As for the outgoing side: Bavarian school holidays traditionally only start in mid-August, when the weather may already turn cooler on the North and Baltic Sea, so Bavarians rather flock towards the Adriatic. By mid-August, however, the South Balkans CovID-Cluster had already, yet unrecognised, expanded into Croatia (also NE Italy?), resulting in quite some holiday-makers returning infected. By that time, authorities were somewhat better prepared to check for post-holiday infections, but it was still quite a mess (and Bavarian authorities “losing” some 20.000 CoViD-tests certainly didn’t help).

            Holiday infections weren’t just a Bavarian phenomenon, but affected, e.g., Austria and the Czech Republic as well. The next stage, expectably, was cross-border spread into Germany. Quite early, already by late August, infection rates went up along the German border to Luxemburg and Belgium. The Austrian border followed suit, and at the moment it is counties along the German-Czech border that have the highest infection rate. Today, at least two weeks too late, the Saxony State government has decreed a ban on “shopping tourism” for cigarettes or petrol to Poland/ Czechia – however that shall ultimately be enforced and controlled…

            Finally, there is the Polish and Ukrainian diaspora. Typically female, working in hospitals or elderly care, w/o school-age children. After school holidays have ended, i.e. in September/ early October, they tend to spend a few weeks with their parents back home. You don’t have to be a prophet to imagine what happens afterwards – a look at Polish/ Ukrainian infection rates is sufficient. Expectably, the “second wave” is now hitting nursery homes again in full force, quickly filling up ICUs and driving up the death toll. Of course avoidable, had our government(s) finalised nursery home regulations and precautionary standards a couple of weeks earlier.

            Essentially, most of what happens at the moment in Germany was foreseeable, and avoidable with proactive attention to the problems potentially caused by tourism (both outgoing and incoming), cross-border shopping and commuting, in nursery homes (and, of course, poorly ventilated food-processing facilities).
            Well, these opportunities were missed. Here we are again with “lock-down light” (schools, barbers and book stores remain open this time), plus anti-constitutional activism. E.g., a State’s Supreme Court has ruled today that ordering mask wearing in all pedestrian zones is unconstitutional: It sufficed to order mask wearing in situations with a reasonable chance to encounter someone else within 1,50 m distance – a chance that is rather low in a small town at, say, Monday morning 9 am.

    2. Michael says:

      Rollout won’t instantly restore normalcy, but keep in mind that explosive epidemic spread like we see in the current pandemic won’t last forever in a vaccinated world (or even in a non-vaccinated world, eventually). Nor do I think that indoor events such as the one you describe would need to be cancelled in the future on account of a slim chance of contracting a cold-like illness.

      So yes, patience, but also near-term optimism.

  7. EJ says:

    I think many people that used to be vigilant in the US have tossed away the coronavirus as something thats out of their control. Just ignore it and move on…

    Anyway, aren’t the mRNA vaccines the ones that are relatively easy to mass produce? If so, this *is* really great news, even if other factors (like sterilizing immunity or some mild long term effects) don’t pan out.

    1. confused says:

      >>I think many people that used to be vigilant in the US have tossed away the coronavirus as something thats out of their control.

      Yes, this, plus politicization of the response.

      Also, I think there is likely to be a “personal stories mean more than statistics to people” factor as well. Most COVID cases are relatively mild, so if one knows people who have had it and it *wasn’t* serious, that may have more impact than the statistics.

      COVID deaths are fairly “concentrated”, and people’s social circles are not random samples of the population, as well.

      1. Hopeful Layman says:

        . . . all of which reinforces the argument that we need good, aggressive, culturally diverse vaccine education/promotion initiatives ASAP. They’ll have to wait until after January 20, when (we hope!) the 24 / 7 noise and bullschitt will subside enough for voices of reason to have at least a shot at being heard. I don’t know, but I’m guessing that Biden’s Task Force is already planning out strategies.

  8. Dare says:

    Immunity of 95% at 14 days (Moderna), 90% at 28 days (Pfizer) gives under the null hypothesis (they work the same) a 5% loss of effect every two weeks. Looks like waning antibody-based protection to me, and 0.95^13 is 50%. Lasting immunity looks problematic on first view.

    1. Michael says:

      No, that’s wrong. Pfizer calculated 28 days from the first shot (day 0 + day 21 + 7 days).

      Moderna calculated 14 days from the second shot, or 42 days from the first shot (day 0 + day 28 + 14 days).

      For what it’s worth, Florian Krammer thinks that immunity might continue to ramp up for 3-4 months:

      https://twitter.com/florian_krammer/status/1328329655594721280

      1. Michael says:

        Also, Pfizer’s readout was “greater than 90%” and they haven’t announced the exact split like Moderna did. Fauci called the Pfizer number “close to 95%” on the weekend.

    2. Oudeis says:

      Have you seen specific numbers for Pfizer’s efficacy? The reporting I saw said “at least” 90% effective, and didn’t say how many of the 94 coronavirus cases were in the treatment group.

    3. Bash says:

      This is an incorrect way to interpret the data – to put it mildly

    4. Patrick says:

      This is *completely* nonsensical. It assumes immunity starts at 100% (totally wrong) and then drops off to the reported ranges in the time frame given. That’s … just not how any of this works.

      I’m not really even sure how best to engage with this: it is COMPLETE nonsense with no relationship at *all* to how vaccine immune responses work over these timescales.

      You would need data following the same cohort comparing effectiveness over time to even start this sort of analysis. The data given here *is not that information*. This is basically point efficacy immediately after the vaccine has been given (at the soonest practical point for collecting enough case information).

      *this* would be the starting point for a decay analysis, and then you would need data from the same cohort *much* further along (and a lot of it) to perform an analysis like this usefully.

      1. joeyh says:

        They’re not alone in misunderstanding the “14 days” this way. The Phizer announcement led to stories that got the same thing wrong on the Guardian, MSNBC, and Democracy Now, at least. Two of the three were due to a pulitzer prize winning science journalist misunderstanding it.

    5. David says:

      Dare: “95% at 14 days (Moderna), 90% at 28 days (Pfizer) gives under the null hypothesis (they work the same) a 5% loss of effect every two weeks”

      There is no meaningful difference between 95% for Moderna (which means 6 cases among vaccinated and 89 cases in non-vaccinated) and 90% for Pfizer (which means approximately 8 cases in vaccinated and 86 in non-vaccinated). To confidently distinguish between these two rates would require well over 500 total cases between the two trials (many stats assumptions underlie that calculation – your mileage may vary, but I’d think not by much).

      Further, the trials are sufficiently different in patient population and design (not just the 2 week / 4 week difference) that comparisons are not valid.

  9. Andy II says:

    Not sure if you have already debated but which one would you recommend us to take? Not we have two mRNA-based vaccines from Pfizer and Moderna, that show >90% protection. Both would be available in late December and the supply would be limited until later next year. In addition, other vaccines will be coming with protection rate of >70%. Will we discard “less effective” vaccine and focus on one of the better one for everyone?

    1. Ken says:

      For most of us it won’t be a choice, it will be “what is available from your health-care provider” plus “what your insurance plan covers”. Hopefully the latter will not be a major issue.

      1. Jason P says:

        I thought the Gubmint already “bought” millions of doses of some of these vaccines? If so the cost should not be an issue as they will be distributed “free.” (prepaid)

  10. Mister B. says:

    These are very encouraging news on many aspects ! It also proves that Science requires time even if this pandemic and the huge efforts for the Pharmaceutical Industry managed to drastically reduced it.

    HOWEVER, remember these are preliminary results. PhIII are designed to be statistically robust with a huge number of patients enrolled. Please, don’t rush things right now, that would be dramatic after such important work during months to be rigourous (so safe for patients).

    This is my only fear now, that with this very good but limited informations, important decisions would be make.

  11. M says:

    This is indeed fantastic news. Moderna obviously is going to need help with manufacturing doses, as they don’t have “Pfizer-like” capacity, but they’ve lined up CMOs to work on this. Progress!

  12. Jim Hartley says:

    Would any chemists please comment on the synthesis of the ribonucleotides used in these vaccines? mRNAs from cells are purified, hydrolyzed to nucleotides, purified to A, G, C, and U, the uracils are modified to improve stability, then converted back to triphosphates with a kinase? At tens of kilogram scale?

    1. MrRogers says:

      I don’t think uracil can be readily converted to methylpseudouricil.

  13. Jon says:

    Is there any chance the 5% not immune will be investigated as to why they weren’t immune to make the vaccine better?

    1. metaphysician says:

      As I understand it, that isn’t really an accurate way to characterize the situation. “5% of people still caught it” does not necessarily mean that those 5% somehow were unaffected by the vaccine. It also includes people who did have immunity, but that immunity was overwhelmed ( perhaps by excessive exposure ), and people who just plain “were unlucky”. The immune system is complex enough that, at least sometimes, you might as well treat it as a dice roll.

      So, you can certainly investigate those who still caught the disease to see if they didn’t develop antibodies or such, but you can’t assume that every person who caught it will have a clear identifiable reason that could be fixed.

  14. confused says:

    So with these promising results, what’s the timeline for these vaccines to get an EUA, expanded access, or some other regulatory mechanism where they can start being given to the most-at-risk populations (I realize there isn’t nearly enough yet for the general population)?

    One of the articles about the Pfizer results said that they needed to wait a certain amount of time for safety data, and that would be “third week of November”. Which is this week. But how long does the FDA side of the process take?

    And does anyone know what Moderna’s safety-data timeline is?

    1. Whatever says:

      This is my question as well.
      With the results that are coming out so far there is no way Pfizer/Moderna aren’t hitting 50% effectiveness at the end. So what is the delay at this point adding that is worth the 800-1000 dead a day it is costing?

    2. Hopeful Layman says:

      It’s not just the EUA process. From everything I’ve read, it will be a difficult and probably time-consuming process to even begin initiating the first rollout, let alone coordinating it among states that appear woefully unprepared for the effort:
      https://www.nytimes.com/2020/11/14/health/covid-vaccine-distribution-plans.html

      1. confused says:

        I’m sure it will be complex/messy and time-consuming, but I would still like to know the timeline to *start* it.

        I know there was concern about the first approved vaccines messing up trials for other ones, but with this level of efficacy, does that still matter?

        1. Hopeful Layman says:

          Realistically, given the chaos surrounding the transition from the Trump administration to the Biden administration, I’m guessing Biden and his people will pretty much have to start from Square One. Slaoui, Gen. Perna, et al. will have to brief them and get them up to speed on what’s been done so far (which we actually know very little about), but in terms of actual on-the-ground coordination of efforts, to say nothing of freeing up enough money for the states, that’ll be up toe Biden’s people to initiate and oversee.

          1. confused says:

            Quite possible, but would that affect the FDA’s timelines for issuing an EUA/expanded access/whatever?

            Also, how much is manufacturing/distribution being built out by the companies now (before approval)? I would think that considerable progress could be made on that side even if the government isn’t helping, assuming willingness to take the financial risk?

  15. M says:

    One thing I am very interested in, from a pure chemistry perspective, is why the Moderna and Pfizer vaccines, which are both liposome formulations, require such different cold chains.

    Any literature out on this yet?

    1. John says:

      I was wondering this too – is this from a difference in the liposome delivery, or the mRNA itself? Any word on this, Derek?

      Shame it’s gotten so hard to push past the trolls that have shown up here…

    2. FrankN says:

      I have back in September discussed this question with a friend of mine, who is working on the nanolipid component of the BioNTech vaccine. According to him, they essentially decided to play it safe, as Pfizer had the required infrastructure for -80C storage and distribution already in place. The main issue is the stability of the emulsion between the nanolipids and saline solution that surrounds them. The nanolipids might drift towards the surface, resulting in inconsistent dosage, thereby potentially compromising Phase 3 results – a risk nobody wanted to take.

      My friend didn’t see any major difference between the nanolipids used by BioNTech and Moderna – after all they both go back to the same source and patents. His best guess was that Moderna settled for the -20C cold chain because they couldn’t do any better (cooler).

      In the meantime, research is under way to which extent BioNTech/ Pfizer refrigeration requirements may be lowered. Some results, e.g. one week stability at normal fridge temperature, have already been released. More should be expected to come soon.

      Essentially, this is a non-issue, pushed to the forefront by interested parties, including Moderna and other competitors. I personally find it a bit disappointing that our host here, Derek, continues to ride this dead horse.

      1. Kamil says:

        Is it really a non-issue? You do realize there is a world outside of the USA. We will need to distribute billions of doses, sometimes to places that are very, very poor. I doubt they have good -20 infrastructure all over India or Nigeria, much less the ability to distribute a vaccine that needs lots of -80 storage.

  16. Marjorie says:

    This is all very well indeed, but what about the potential long-term adverse effects of mRNA vaccines that have been identified (mutagenesis, autoimmune disease, concomitant retrovirus infection) but will not be tested before it is administered to the general population.
    Do we have this kind of data for animals?

    1. Phil says:

      The Pfizer Phase III trial was expanded to include participants infected with HIV, which addresses the retrovirus point.

      For the other points, there’s no other mechanism besides a retrovirus or similar for an mRNA to persist in the body.

      1. Marjorie says:

        Thank you, if I understood you correctly, the first risk is related to the mechanism of the retrovirus. Do we know how long it will take to verify this with HIV and whether it involves stopping the antiretrovirals during the trials?
        And still, is there potential autoimmune disease risks for these two particular mRNA vaccines?

  17. MTK says:

    We need to get a massive vaccine education program underway as soon as possible that spells out in a clear fashion the benefits and possible adverse effects, especially since these vaccines require two shots. If people have a unanticipated (to them) adverse effect from the first shot and don’t fully understand the need for both shots, they are probably going to be quite hesitant to get the second shot or worse tell others not to get the vaccine at all. All of this could potentially compromise overall vaccination efforts.

    People are quite circumspect about the vaccine already. A concerted and effective effort to assure and inform the public is a necessity.

    1. M says:

      I think the first order of business for the new administration (in the US) is a refocus on the pandemic (this is basically already happening), so that we develop and implement even more effective ways of combatting the spread that also reduce the economic impact, and provide monetary relief for people/businesses/etc affected by restrictions. Second order of business is the vaccine education program that you mention, which will be very important.

    2. MM says:

      I heartily agree with this.

    3. M says:

      I also think it needs to be clear that there is a distinction between “anti-vaxxers”, who are a small number of people hopefully diminishing in size, from the much larger group of people who have legitimate concerns with the safety and efficacy of a quickly delivered vaccine. Labeling this second group as “anti-vaxxers” won’t help. I think the messaging has to take this into account.

      1. Dark Day says:

        I agree that people with well-founded skepticism should not be confused with dogmatic “anti-vaxxers.” It’s actually a good sign that folks are thinking carefully about this; if they’re approached with honesty and respect, and a listening ear, many/most of them can be reached.

        I think I might have said this elsewhere, but one bit of very good news is that Biden’s Coronavirus Task Force will be co-chaired by Dr. Marcella Nunez-Smith. She has been a powerful advocate for communities of color throughout the pandemic, and she is also spot-on in terms of advocating and educating for vaccine uptake — along with equitable distribution and access (closely related, actually, to the uptake issue) — for the people of those communities. She has a true “boots-on-the-ground” approach to public health and public health advocacy, and it was a very prescient move to include her among the leaders of the task force. If anyone can design and coordinate a powerful, culturally aware information / education campaign directed at communities of color and other “hesitant” population groups, she’s the one.

        1. M says:

          You might need to change your handle to “Bright Day” 😉

        2. Michael says:

          Dark Day, in addition to Dr. Nunez-Smith’s involvement, it will also hopefully help in the education campaign that Dr. Kizzmekia Corbett was a key developer of the Moderna vaccine.

          1. Dark Day says:

            Let’s just hope that doesn’t rouse suspicions of conflict of interest, as Slaoui has been accused of quite often.

    4. Hopeful Layman says:

      Aren’t the most serious side effects usually associated with the second shot? Not that this won’t be a problem, but if most people “survive” the first shot with minimum discomfort, they’ll be likely to be more willing to take the booster.

  18. mftkoehler says:

    Can we change the captcha to require some knowledge of chemistry? Might cut down on the polemics in the comments.

    1. M says:

      Perhaps a something as simple as CH4 + O2 -> ________ ?

      1. metaphysician says:

        My half forgotten chemistry knowledge says “that chemical reaction is gibberish, you need *two* O2s to balance the reaction”.

        :p

        1. M says:

          Well played – I should have put underscores in front of both the reactants as part of the captcha logic. I was too implicit and not explicit.

      2. cynical1 says:

        Why is it that all I can think of is the two Spinal Tap drummers who met a particularly ill fate?

        1. M says:

          I laughed.

          And now all I can think of is Bon Scott. Although he choked on his own vomit. The other Spinal Tap drummer choked “on vomit.”

      3. Wilhelm Cody says:

        “Perhaps a something as simple as CH4 + 2 O2 -> _StarShip_______ ?

        1. HAJ says:

          I’m not a scientist (just an average Susie Homemaker who’s interested real, science-based vaccine updates, and a Pfizer trial participant as well) and therefore cannot complete the Captcha problem you propose, but I’d happily forego the ability to comment on here if it meant the idiotic, pointless trolls would be silenced.

  19. Nico says:

    PLEASE Can someone explain to me what is the difference between keeping an aqueous solution at -20°C versus at -80°C? Does anyone know what the issues are likely to be? I understand that flash freezing at -80°C can prevent formation of crystalline ice that might damage the lipid nanoparticles but once it’s frozen what’s the difference between storing it at -80°C or -20°C? Could it be the adjuvants that alter water’s freezing point that much? That’s the only thing I could think of.

    1. sort_of_knowledgeable says:

      My understanding is that the solution is more of a gel that would melt at -20C than a solid. I expect work is proceeding on other storage solutions that would allow higher storage temperatures.

    2. Mammalian scale-up person says:

      The phrase you want to Google is “glass transition.” Basically these are big floppy rubbery things that have a stage where they’re not exactly frozen and not exactly liquid, they can move around a bit and re-organize. The rate and temperature at which they do so is determined by the exact sequence and lipids they are compounded with. In proteins we are concerned with storage temperatures above the glass transition state (but still well below the freezing point of the solvent) because the proteins can still aggregate and misfold at those temperatures if the protein structure itself is not particularly stable.

      1. Christophe L Verlinde says:

        Please pay attention. It is a mRNA NOT a protein vaccine, so what protein are you talking about?

        1. Mammalian scale-up person says:

          Good morning to you too.

          All large organic molecules (as opposed to small molecules) are evaluated for glass transition when the stability temperatures are identified. They are quite flexible even when the solvent is frozen. This includes nucleic acid sequences, large lipids, polymers, and indeed proteins as well.

          Have a nice day.

          1. sgcox says:

            mRNA can not “misfold and aggregate”. It is not a protein and behaves completely different, as Chris Verlinde pointed. We do precipitate RNA/NA of course every day in thousands of labs but it goes back to solvent once in normal buffer. Not so proteins.

          2. Mammalian scale-up person says:

            Beg your pardon, they most certainly do aggregate via salt bridging and groove reorganization / twisting, knotting, etc! Quite literally, one of the issues in RNA formulation and dosing with LNPs / liposomes is particle size, as it’s thought to be critical to tissue distribution. doi: 10.1007/978-1-4939-7138-1_13

            The lipid component in liposomes (and LNPs) most certainly does break emulsion, undergo glass transitions and destabilizes into larger particles and even material resembling aggregate which is not filter-able and becomes a sticky slime that cannot, for example, be drawn into a needle for injection. Salt bridge reorganization and matching sequences are well known to be an issue in sequence architecture, so much so that there are many bioinformatics programs that predict it to varying degrees of accuracy (see the latest Singh et al Nature Comm 10 5407). Long sequences of RNA (as opposed to oligos) have tertiary and even quaternary architecture and different melting profiles (**glass transition**, if you recall that was the original question – thermal stability) if you stick them in a DSC, and can be shear sensitive if they are large and unstructured enough; shear sensitivity contributes to instability and strand breakage, especially in shipping conditions which is a thing we consider when we are talking about frozen stability of a large molecule.

            Have a nice day to you too.

        2. anon says:

          You guys would do well to remember that this blog is often also read and commented on by industry professionals. Mammalian scale up person never claimed that the vaccine contains a protein, he drew a comparison between this mRNA/LNP case and how it is performed for proteins.

          Yes, in a lab RNA and NA go back into solution after you crash them out. But also in exploratory research, it is meaningless if we lose half of it on the way due to aggregation or other factors. Whatever experiment you want to use it for still works. This is not acceptable for a vaccine, however.

  20. Blaine White M.D. says:

    A vaccine that is at or above 90% effectiveness will certainly breakup and largely stop community spread. That will make most of us and the epidemiologists happy, save many lives, and let us get back in school and on cruise ships.

    However, I do worry about the vaccinated folks who are still getting the bug and think a bit of reserve remains in order for vaccines directed primarily at generating antibody against the SARS-CoV-2 Spike protein. Within the past month we’ve had therapeutic trial failures for both Lilly’s anti-Spike monoclonal antibody bamlanivimab as ineffective (https://blogs.sciencemag.org/pipeline/archives/2020/10/27/more-antibody-data) and Regeneron’s REGN-COV2 (2 anti-Spike monoclonal antibodies given to Trump who perhaps was lucky), which the Safety Monitoring Board stopped for patients needing high-flow oxygen or ventilation “because of a negative safety signal and an unfavorable risk/benefit profile” (https://investor.regeneron.com/news-releases/news-release-details/regn-cov2-independent-data-monitoring-committee-recommends). Those are examples of patients with plenty of antibody (because it was given to them) and still SICK with Covid-19. Failure of clinical trial of convalescent plasma (Agarwal et al. PLACID Trial MedRxiv 2020; doi: https://doi.org/10.1101/2020.09.03.20187252) may fall into the same general category of worry.

    We need vaccinated subjects encountering the virus in the community for many more weeks to get an idea who still gets infected and how SICK they may yet get (Liu et al. Anti–spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection. JCI Insight 2019; 4: e123158. https://doi.org/10.1172/jci.insight.123158). What the anti-Spike vaccine trials tell us so far is that there are still going to be such patients.

  21. steve says:

    So the Pfizer vaccine gives both B and T cell immunity but needs -80oC cold chain transport and storage while the Moderna vaccine gives antibody but not T cell immunity and only needs conventional freezer storage. Which would you pick?

    1. Hopeful Layman says:

      Do we know that for sure? From what I’ve read, the T-Cell response (and, for that matter, memory B-Cells) has not been determined conclusively. Have I missed something?

      1. steve says:

        Hopeful Layman – It was determined in the Ph2 that Moderna only induced antibody while Pfizer induced Ab and T cell immunity

    2. Alia says:

      The first one that I am offered, most probably.

    1. M says:

      Thanks for the link.

      This discusses differences in general terms, but doesn’t explain why the formulation for Pfizer requires -70C vs. why the Modena formulation requires only -20C. Both are liposome formulations so I’m interested in the differences at the molecular level. I suspect we won’t know for a while as they are both proprietary formulations.

  22. Wilhelm Cody says:

    Moderna provided much more detailed data than Pfizer so perhaps someone can do some calculations on possible ranges: my previously limited capability to do statistics as declined over 20 uses of non-use. What is the 95% confidence limit for the effectiveness given 90 cases in the control and 5 cases in the treated?

    1. Another Kevin says:

      Back of the envelope:

      Assume a sample size of 15000 on each arm (the study was supposed to be 1:1 vaccine:placebo).

      Fill in vaccinated: 5 cases, 14995 no event; placebo 90 cases, 14910 no event.

      Odds ratio is 0.055 (translates to “94.5% efficacy”)

      Confidence interval is 0.022-0.136 (or “86.4%-97.8% efficacy”)

      Obviously, I don’t know the number of patients in either arm,

      1. Wilhelm Cody says:

        thank you. That is good enough for me and very helpful. Pfizer should provide similar data.

      2. Jon says:

        Can you explain how you calculated the confidence intervals? Thanks!

  23. Susan Davis says:

    Will these vaccines be effective for people with suppressed immune systems and patients with diseases like RA on immunosuppressant drugs like Enbrel?

  24. PDINV says:

    Please see below. Is data reported after a median follow-up of around 2 months after 2nd dose, really any relevant AT ALL? OK, there was a tiny, tiny chance (given previous research) that spike protein as an antigen might not work, now that tiny chance is gone. Apart from that, the rest of the efficacy data is uninformative.

    See here “Epidemiologist, Immunologist, Physician, Harvard Public Health/Medical School. Discuss vaccines, immunity, infectious diseases, public health”

    https://mobile.twitter.com/michaelmina_lab/status/1328353639098966020
    “But that these vaccines are designed specifically around antibody based responses suggest these early phase 3 endpoints – which are detected within a couple of months of getting the vaccine – may be enjoying a major but temporary boost from the early vaccine effects

    When you get an infection or a vaccine, the body makes a HUGE number of temporary antibody secreting cells called plasmablasts. These are evolutionarily “designed” to infuse a huge and robust antibody response capable of clearing an active infection

    But over the month or so after the infection or vaccine, the plasmablasts have to die off – it is their fate. Over the coming weeks and months so too do the antibodies they produced. What remains after is usually a much smaller antibody producing cellular subset

    So I am a bit hesitant to jump on board with the >90% efficacy results because the time scale of the phase 3 studies thus far match the time scale of the temporary plasmablast duration and the antibodies they produced…

    Michael Mina

    So, w these early efficacy results, we may be measuring the effects of an impressive front line army that spins up in response to the vaccine – but then we should be careful not to assume the same efficacy persists to hold that line after most of the troops disappear!”

    So it is pretty clear to me that the way the FDA allowed them to report interim (as if these were treatments and not vaccines, yeah placebo vs vaccine data matters, but they have to be measured at relevant timeframes as dictated by science and the logistics of vaccination) was not aiming to produce good science, but good news.

    Hopefully, they will not decide to move everyone on the placebo arm to the vaccine arm now that “we have vaccines that are >90% efficacious”, then we will never know

    I look forward to reading your comment.

    1. Marko says:

      I think Mina’s take is legit , which is why the trials should continue even if an EUA is granted for immediate use in the highest-risk populations. Only offer the option to receive the vaccine to the placebo arm participants who fall within the high-risk criteria , and allow the trials to accrue more data over time to see if the antibody response , and efficacy , wanes.

      There’s not a whole lot of downside to doing it this way as opposed to granting full approval based on incomplete data , since there won’t be enough doses to treat everyone anyway. The companies will gear up their production efforts if they’re confident enough in what they’re seeing from the data so far , and if they’re not confident , I don’t know why we – or the FDA – should be either.

      1. PDINV says:

        Thanks for the reply.

        I just hope they don’t try to muddy the waters further by dropping placebo. Given that they don’t have enough doses or time to vaccinate a sufficient amount of people to make a differnce for this winter season, I don’t understand why they did not wait to report data in February or March (which would allow a far more reliable prediction for longer term immunity) whle ramping production of their vaccines to relevant quantities as well. As I said, I sincerely hope they are not aiming to use the “ethics” argument to drop placebo. In addition, they would have more robust data on safety in February which, although it already looks good, it would help to convince those who are on the fence about vaccination.

        Also, given that it is almost certain that efficacy will drop later (hopefully not by a lot), it would avoid the potential issue of the public questioning their “>90% efficacy” that has been triumphantly reported.

        My 2c

        1. TabeaK says:

          Because pandemic fatigue is a thing – no news on the chance of an efficacious vaccine all through the winter leads to an exponential growth of people resigning themselves to the inevitable and a resulting lack of taking precautions. Think it is bad now? Just imagine how much worse it would get without light at the end of the tunnel.

          I am not terribly concerned about the the vaccine skeptics – I fully anticipate we’ll get to a society where “no vaccine = no admission”, so we’ll see how long they hold out when faced with not being able to attend an event, travel, play sports etc… Fatalistic? Maybe…

          I am still not fully convinced the vaccine will arrive in time to make a difference to the population at large. High risk groups maybe, if started by the end of the year. Joe Average guys who has another year to go? Chances of picking up the infection along the way for some “natural” immunity – with potentially unpleasant side effects – are increasing every day. We have easily 200k infections a day. That is 6 million a month. 20 million+ through the end of the winter. Probably 2-3 times more due to lack of testing – after this winter with numbers as is we’ll have built some significant baseline immunity which should slow the spread.

          Unfortunately all accompanied by the carnage of daily deaths exceeding 2000+ and seriously burnt out healthcare staff and a fraction of folks needing a long time to recover from viral infection, but that genie is sadly out of the bottle and the vaccine is too late to put it back…

          1. PDINV says:

            Sorry but that’s not science and I’m not sure I accept that people wont’t take precautions while waiting for vaccine, while they do take precautions when companies announce efficacy of 90% and start of vaccination in December. Not going to continue this conversation.

  25. Mitch says:

    If Oxford/AstraZeneca is approve, what is the general thought of the safety with that type of vaccine (attenuated vaccines — adenovirus vector) vs the new mRNA based vaccines?
    I’d imagine the AstraZeneca one would logically be considered safer since we’ve used attenuated vaccines in the past before, correct? Assuming the efficacy is similar (or even a little less), I’d assume it’d be a safer gamble for a younger person to take that than the unknown mRNA and what may happen years down the road.

    1. Thomas says:

      mRNA is a natural constituent of the human cell.
      Viral infections bring viral RNA into cells. Thus, having RNA in cells is nothing new.

      1. theg9 says:

        Yes, but injecting such large doses of mRNA into tissues is definitely not natural. Here’s one scenario: what if nerve cells take up the vaccine’s mRNA and start producing a lot of copies of the spike protein, which leads to protein aggregate/plaque formation and increases risk for developing neurodegenerative diseases down the road? There’s no way I would take any mRNA vaccine until we had a decade worth of safety data on it.

        1. Mitch says:

          so is the Oxford vaccine safer in the fact that we’ve used that method before in the past?

  26. Daniel Jones says:

    South Dakota has a truly horrific mortality rate and a large part of it is based on folks denying they have it, denying they are at risk of death, or denying that what they have is COVID-19. The bad information, false narratives, and heartless propaganda are the reason for this… Why do I say this?

    I say this because re-reading an article on Hydrochloroquinine (KEE-RIST, I spelled it right the first time!) I saw mouth-breathing denialism in the comments section so I wanted to get good information out first. Not to attack, not to defend, just to get it out there. Only good information can fight bad information. So, yeah.

  27. Vincent says:

    Newbie question. If a vaccin is 95% effective, and everyone in the US would take it, does that mean 5% of the population will still get COVID at some point? Because that would mean 16 million people. With the current mortality rate, you’re looking at 350.000 additional dead victims.

    1. Bernd Meyer says:

      The hope (and general vaccine mechanism) is that those 16 million people simply won’t have anybody to get Covid *from*.

      Basically, someone who gets infected can infect others for a relatively short time — let’s call it two weeks. And for some of that time, they are should be aware that they are sick, so can do the sensible thing and isolate themselves.

      Currently, in those two weeks, the “average” infected person has enough social contact to infect maybe 1.4 other persons, meaning the number of infected people keeps growing over time. If a 95% effective vaccine had just a 30% uptake, enough of the social contacts would be immune for each infected person to infect just less than 1 other person, and the virus would eventually (but quite slowly) die out. But of course, the goal is not to *slowly* improve things with *current* levels of social contact — so ideally, we’d want a MUCH larger uptake, meaning each generation of infected is considerably smaller than the previous, even with closer-to-normal social interactions, and the virus would run out of hosts fairly quickly.

      If you look at Victoria, Australia, their second wave had hit around 500 cases/day at the start of August. Then social interactions were massively reduced (and masks became both compulsory and widely used), and within two months, cases had reduced to about 10 per day, and another month later, to 0. So despite there being plenty of people vulnerable to infection, each 14 day generation of infection was about 60% smaller than the previous one. An widely deployed effective vaccine just makes it possible to achieve that kind of reduction *without* the pain Victoria had to go through.

    2. PDINV says:

      The reported efficacy is 100% certain that it will have NOTHING to do with what the eventual effectiveness in the population will be. It is real data, but also irrelevant for several reasons. But to answer your question, no, overall mortality rate is not that high.

    3. Chris Phillips says:

      It doesn’t mean that 5% of the population will get COVID-19.

      It means that if the vaccine had no effect whatsoever on the transmissibility of the vaccine, only 5% as many of the people vaccinated would get symptomatic cases of the disease, compared with what would happen if they weren’t vaccinated.

      Of course, the hope is that vaccination will also affect the transmissibility of the disease, and that therefore the benefit will be much greater than 95%. If the vaccine also reduced transmissibility by 95%, universal vaccination would eradicate the disease within a matter of months.

  28. Jason P says:

    OK, to this observer these trials appear to have a huge hole in them.

    >>>>> there are several other categories that could differentiate all the vaccine candidates: … effect on severity of disease when it does occur <<<<

    How can these trials give any definitive information on severity? You have people running around in an environment where the virus is spreading, so that is good. But hasn't the information to date shown that infection severity is correlated to the amount of exposure: number of viral particles taken in at exposure? So someone who exchanges respiratory bodily fluids with and infected person is more likely to get a higher viral load transmitted, higher than the person who gets a few particles, while wearing a mask in line at the convenience store when the person walking by sneezes.

    So the data from this study are going to be used to make a 'severity of disease' determination? How? Sure looks like this is boot strapping data and not the Gold Standard. How does this work? Seems like the Gold Standard way of making such a determination is vaccinate and then in a controlled way, expose those people to various, known levels/concentrations of the virus.

    1. Thomas says:

      Look at the number of severe cases in each group, that is what counts.
      A vaccine is little good if the control arm has 4 severe cases and 40 non-severe, while the vaccine arm has 4 severe cases and no non-severe cases at all.
      But if th evaccine arm has 4 non-severe cases and no severe cases, we may conclude that the vaccine prevents severe disease.
      What we don’t know is whether the vaccine “converted” servere cases into not being severe, or whether 4 non-severe cases “just slipped through”. That is of little consequence, though.

      1. Chris Phillips says:

        If you want data on severe cases, it’s in Derek’s post:
        “11 of those were severe infections: all 11 in the controls and zero in the vaccine patients.”

  29. failed scientist and incel says:

    During the early part of the AID epidemic I recall government and academic certain labs (Gallo and friends) claiming ELISA results that were overly optimistic and ended up being false. I would be skeptical about any company’s reporting its own results. My hope is that some government institution would do a well blinded study to make sure that these vaccines really work. I’m sorry, but I think we have to be very suspicious of any drug company data, especially when they are competing for a huge prize like this.

    I have an idea. Lets get elderly inactive faculty who wont retire to participate in some kind of blinded studies of these vaccines. Steppin’ up like this would be helpful, and would show patroitism, which many seem to have trouble showing.

    1. Chris Phillips says:

      All these Phase III studies are double-blind.

      Maybe you don’t believe it. Maybe you think there’s a conspiracy or something. But regardless, they’re all double-blind.

      1. failed scientist and incel says:

        Were the blinded trials done in China? Great….

        1. Chris Phillips says:

          I’m sure they are. The Chinese aren’t stupid. They won’t be doing large-scale trials in a way that renders the results meaningless.

          Perhaps what you mean is that you don’t trust them to be honest about the results. That’s different.

          1. failed scientist and incel says:

            The later is correct. Who can trust their science?

            https://forbetterscience.com/2020/01/24/the-full-service-paper-mill-and-its-chinese-customers/

            Im sure they want to please the boss to get ahead. The boss being Pfizer.

  30. An Old Chemist says:

    Pfizer-BioNTech and Moderna’s Vaccines Are Leading the COVID-19 Race. How Do They Compare? (BioSpace)

    The two groups have proprietary formulations, which is why there are different storage requirements. Because the formulations are being kept secret, it’s not well understood outside the companies why there is a difference.

    https://www.biospace.com/article/pfizer-biontech-and-moderna-lead-the-charge-on-covid-19-vaccine/

  31. bacillus says:

    Color me skeptical, but after 25 years of mRNA vaccines against just about every disease under the sun with none clinically approved, suddenly two of them come along at once with >90% efficacy. Additionally, clinical trials participants are going to be handled well more skillfully than in real life where your family Dr. will be thawing the vaccine by placing it under his armpit, and maybe not tracking quite so rigorously as to when the vial in the fridge was thawed, etc, and I’d expect to see real-life efficacy to drop into the 70+% range. Still not bad. However, unless they significantly stop viral shedding, then vaccinees are going to be just as infectious as all of the subclinical non-vaccinees. My understanding is that both Pfizer and Moderna per FDA guidance have been measuring primary efficacy by reduction in disease severity rather than by reduction in infectiousness.

    1. Zooming says:

      A massive effort, a company putting all their best people on one project, and the US government guarantee that the result will be purchased even if it is the second or third to market can enable new runners cross the finish line. There’s lots of credit to go around, including some for the USA as the guarantor and cheerleader.

    2. Johno the Teacher says:

      Astonishingly, if near-unlimited funds are available to vaccine makers, stuff gets done . . .

    3. Mammalian scale-up person says:

      Completely agree that vaccine technology which only works under Emergency Use Authorization criteria, in dire situations when anyone will accept any efficacy at all is…awfully convenient.

    4. John says:

      I also have concerns about the small number of cases, 90 plus cases is considered to be small sized data sample in my field.

  32. exGlaxoid says:

    Pfizer has already said that they picked the coldest temp to ensure it would work. They also said in their press release that they were studying other storage conditions and other formulations that would perhaps allow higher temps. Given their extremely short timeline, they just did not have time to test for stability at higher temps due to not wanting to wait for the data to start the trial. I suspect that they will find that the vaccine is stable at higher temps and for longer times that they assumed at the start.

    I have a simple solution to the issues given, start by vaccinating the highest priority people (medical workers, nursing hoe staff, etc) that want the vaccine, then once they are mostly done, allow the next priority people to get in line, etc until everyone who wants it can get it. Once that is done then make it available for the other (more skeptical) people as they see it work in real life. Eventually, many work places, schools, offices, etc will require vaccination to continue work or school, and most people will choose to be vaccinated. But why argue over how to convince people to get it when there is not enough yet available for the people that want it.

    Once people see vaccinated people getting back to life (after 28 days or so), the rest will either decide to try it or eventually get sick and get immunity that way. Worrying about how long immunity lasts or long term issues is pointless given that we will find all of that out in due time, long before it matters. I’ll take a shot even if it only is good for a year, as I am tired of staying home and not having a life. And they (both mRNA shots) appear quite safe based on the early data so I don’t see much risk to the shots so far.

  33. myst_05 says:

    Doesn’t this create an interesting bioethics dilemma? Moderna was only able to complete their Phase 3 so quickly because there were a lot of cases and there were a lot of cases because of the lax pandemic response. So shouldn’t we praise Donald Trump’s lax response for helping us develop the vaccines more quickly? If not, shouldn’t we condemn the government for banning vaccine challenge trials and thus requiring us to reach 11 million cases before the Phase 3 trial could be completed?

    IMO now would be a great time to admit that vaccine challenge trials were a fantastic idea. Or admit that Trump has done a good job. One or the other HAS to be correct, logically speaking.

    1. metaphysician says:

      Put bluntly: absolute poppycock. That a given event has a happy side effect does not change the entire moral calculus of the event… and that one event turned out to be bad does not make another completely unrelated event good.

    2. Zooming says:

      A US president has a big, visible platform, but has no authority to order local facilities to open or close. He cannot open or close a single school restaurant bar or gym. He could promulgate rules for federal facilities, but these are tiny dots in most states.

  34. exGlaxoid says:

    Pfizer is now saying that its vaccine is 95% effective, and has completed the safety data period for review. I hope that the FDA will move quickly to review the data and get this done fast. I know they want to appear fair and careful, but any unneeded delay will clearly result in much pain and death. Since there appear to be few side effects other than typical ones, I don’t see how they can do much other than approve it, unless there is some new data somewhere. I’d take the gamble on a vaccine tested in at least 20,000 people verses the uncertainly of catching a disease any day.

    1. Bill says:

      I think I also read that of the 8 vaccinated who got infected, one had serious disease. That’s disappointing. I was hoping that serious disease might be out of the picture for the vaccinated group.

      1. Michael says:

        True, and that one unlucky individual needs to be studied for immune response and analyzed for pre-existing co-morbidities and risk factors. Perhaps another vaccine platform will be even better at reducing risk for people like him/her. We have always believed that different vaccines might be indicated for different demographics.

        Big picture so far is that with the combined mRNA results to date, severe cases are 20 placebo, 1 vaccine.

  35. Dumb gradstudent says:

    Why does pfizer’s vaccine need much lower storage temp? Do we know what’s different in their formulation? They’re both mRNA based.

    1. Bill says:

      I’ve seen discussion that it may not be as different as is seems. The choice of storage temperature was said to be a preliminary, very conservative assessment that they are now in the process of reviewing for potential relaxation. TBD

  36. Abigail says:

    Any vaccine will “work” based on these calculations.

    Here is my back of the envelope analysis; please comment and correct me if there is a flaw in the logic.

    1. According to the WHO, 80% have mild illness or asymptomatic; 15% have moderate to severe illness and 5% require ICU. The vast majority of hospitalized patients are those in the high risk category. ( eg. age, and underlying health conditions) So, out of 10,000 people, around 500 people will end up in the hospital if vaccines are not around.

    2. If the vaccine is tested on 10,000 people and is 95% effective, 5% or 500 will develop COVID-19. So, either way, 500 people will end up in the hospital. So, how is it 95% effective? Additionally, Most people selected in a clinical trial are NOT people with underlying health conditions. They may have a few different age groups, but trials are never conducted without careful selection of volunteers. This virus affects people with Underlying health conditions more than others.

    3. In the numbers released by Pfizer, 9 people develop severe illness from placebo group and 1 from the vaccine group. So, it’s 90% effective to prevent severe disease? If the numbers hold, 100 out of 1000 will still get severe illness. So, how is it 95% effective ?

    Regarding adverse effects: They will spin it every which way they can. Pfizer and Moderna will get approval very soon, if there are adverse reactions, they will spin it as ” adverse reactions happen with all vaccines”. Note that long term studies on fate of mRNA, lipid formulations, etc. are not available.

    If people fall sick, they will spin it as, ” it’s decreasing spread ” which can never be proven because people also wear masks. There are some locales where people don’t wear masks, but there are other variables in play that they will discount.

    Lastly, they know that people want to go back to normalcy as soon as possible, so they have that aspect in their favor. When people are desperate for food, economic activity, they will believe in whatever they hear or read.

    1. Shehla says:

      If 20 % of 10000 people end up in hospital that is 2000 people not 500. So does this mean vaccine may prevent 1500 people from ending up in hospital ( 15%) ?

    2. Ken says:

      Abigail, here are the flaws in your logic in [brackets]:

      1. According to the WHO, 80% [of the population who contract COVID-19] have mild illness or asymptomatic; 15% have moderate to severe illness and 5% require ICU. The vast majority of hospitalized patients are those in the high risk category. ( eg. age, and underlying health conditions) So, out of 10,000 people [with COVID-19], around 500 people will end up in the [ICU only] hospital if vaccines are not around.
      [There is also a percentage of people with moderate to severe illness who go to hospital beds but do not use an ICU, but I won’t quibble about that now.]

      2. If the vaccine is tested on 10,000 people and is 95% effective, 5% or 500 will develop COVID-19. So, either way, 500 people will end up in the hospital. [WRONG: 500 people out of your 10,000 will develop COVID-19, so now apply your percentages from 1. above: 9,500 people will not contract COVID-19 that otherwise would have. 80% of 500 or 400 people will have mild illness or be asymptomatic; 15% or 75 people will have moderate to severe illness and 5% or 25 people would require ICU. i.e. ‘end up in the hospital’] So, how is it 95% effective? Additionally, Most people selected in a clinical trial are NOT people with underlying health conditions. They may have a few different age groups, but trials are never conducted without careful selection of volunteers. This virus affects people with Underlying health conditions more than others.

      3. In the numbers released by Pfizer, 9 people develop severe illness from placebo group and 1 from the vaccine group. So, it’s 90% effective to prevent severe disease? [no, they were looking at total infections. While severity was reported out from the study, effectiveness was only looking at total cases.] [Separately from the 95% effectiveness reported; with such a small sample size (10) you would expect that there is a wide uncertainty. If the next severe case turned up in the control group, your best estimate for “severe protection” would be 1/11 or 91% . If the next severe case turned up in the treatment arm, instead if would be 2/11 or 82%.] If the numbers hold, 100 out of 1000 will still get severe illness. So, how is it 95% effective ? [see above, total infections not just severe is the readout]

  37. Barry says:

    The claim of 95% effectiveness does *not* mean that 95% of those immunized did not get the disease. It means that of the cases diagnosed (symptomatic) 95% were in the control (placebo) arm of the study, rather than in the treatment arm.

    1. Abigail says:

      It still doesn’t answer my concerns. How will we ever know if the vaccine works based on the definition you provided? If 100 people get immunized, how many will it protect? 95 people?

      As a scientist, if you come across data that shows 95% efficacy using new technology that doesn’t have a product in the marketplace, would you not doubt it? They are claiming 95% in humans; they know that people are desperate, the virus causes severe disease only in a small section of society, and they are making money in the name of science. I would love to see data where they immunize people in nursing homes. I highly doubt this vaccine will protect the most vulnerable people in society who need the most protection. My 2 cents.

      1. Rick Deveraux says:

        As Barry tries to explain, Moderna isn’t saying what you think they’re saying. They’re not saying that their vaccine is 95% effective and that therefore only 500 out of 10 000 will eventually get the disease.

        What Moderna is saying is that if the vaccine didn’t work (the null hypothesis) then the people in the treatment group would get just as ill as those in the placebo group.

        At this point that means that you would expect 90 cases in the treatment group and 90 in the placebo group (a 50-50 split). Instead, Moderna observes 90 cases in the treatment group and 5 in the placebo group (a 94-6 split). This is a major deviation from the null hypothesis and so the conclusion is that the vaccine DOES work.

        1. Abigail says:

          Based on your analysis, if 44,000 people receive the vaccine, with 22,000 received placebo (P) and 22,000 the vaccine. (V). P group should have 19,800 cases (90% of 22,000) and the V group should have only 1,100 cases (5% of 22,000).

          Reported data from Pfizer: 170 got Covid; of which 162 Placebo got Covid, and 8 Vaccine got Covid. They haven’t provided data from all 44,000 volunteers. It’s an assumption that the numbers will hold when Covid strikes all 44,000 volunteers, based on this limited number of positive cases, which is 162/(162+8) x 100 = 95%. This is a flawed assumption.

          Another way to calculate: 162/22,000 = 0.74% placebo got Covid. And 8/22,000 = 0.036% vaccine got Covid. These are very small numbers to draw any meaningful conclusions, given that only a very small percentage of cases ( vaccine or no vaccine) are hospitalized.

          1. Chris Phillips says:

            What puzzles me about comments like these is not that people don’t understand statistics, but that they don’t realise that they don’t understand. Apparently, they think they understand statistics better than statisticians do!

          2. Rob says:

            It’s a bit different statistically, but not unlike flipping a coin 170 times and having it come up heads only 8 of them. The numbers aren’t that big, but you would certainly think something is unusual about your coin.

      2. Ken says:

        “It still doesn’t answer my concerns. How will we ever know if the vaccine works based on the definition you provided? If 100 people get immunized, how many will it protect? 95 people?”

        You are forgetting the actual herd immunity being provided by a vaccine. if it indeed protects 95% of the population, suddenly the rate of infections drops by a factor of 20. Not that you’d need to go to 20 bars instead of one to pick up COVID-19, but instead of one person infecting 10 people, suddenly that one person only infects (on average) 0.5 people (assuming similar habits of mask wearing, washing hands etc.). The “Ro” goes from above one to below one. And that means that within a few infective cycles, we can cut this down to localized outbreaks instead of a pandemic.

  38. Abigail says:

    Chris Phillips, wouldn’t it make more sense for you to point the flaw in the logic of my statements instead of making random statements?

    Rob, agreed. The coin is biased, but they have looked at only 170 cases out of 44,000. At midnight on Election Day, Trump was leading Pennsylvania by over 800,000 votes. Does it mean he won?

    1. Chris Phillips says:

      Abigail

      There is no logic there to find a flaw in. There is just an assertion that random sampling doesn’t allow conclusions to be drawn about the population. You are simply asserting that the whole field of statistics is nonsense.

  39. Abigail says:

    Chris, even if random sampling is used, the virus causes severe disease in people with underlying conditions at a significantly higher rate than the general population. Most healthy people are asymptomatic or have mild symptoms. The biggest impact is those people where it leads to severe disease. While all details of the trials have not been published, I doubt they have included such people and if they did, it may be a handful.

    If you randomly sample a healthy population, when the disease affects mainly people in high risk categories, how is it 95% effective? If, on the other hand, they found that the vaccine protects 90-95% of people in the high risk category, I would be among the first to congratulate the scientists.

    1. Chris Phillips says:

      Abigail

      Obviously, what I was referring to was the stuff in the comment I responded to, about not being able to conclude anything about what would happen to “all 44,000 volunteers” from what happened to those who were infected so far.

      Not the quite different point you’re now raising about whether the volunteers are representative of the population as a whole.

    2. Britt says:

      Abigail, all the trials emphasized recruiting people who are older and with underlying conditions, for the very reasons you mentioned. (For example, here are the demographics for Moderna’s trial participants: https://www.modernatx.com/sites/default/files/content_documents/2020-COVE-Study-Enrollment-Completion-10.22.20.pdf) And they do subgroup analyses to check that their conclusions hold within these subgroups.

      You are not the first person to think of these potential pitfalls– scientists and biostatisticians are very aware of what needs to be done to design a trial that will be able to prove what they’re trying to prove, and they design it accordingly.

  40. Shehla says:

    Efficacy and effectiveness are 2 different things. 95% efficacy in the trial does not mean 95% effectiveness in the real world. However , I would have been so disappointed if efficacy was 50%in the trial.With the 95% efficacy result now
    there is hope for better effectiveness of vaccine in the real world.

    1. RHB says:

      Stats never were my strong suit, so not compus mentis to comment on Pfizer and Moderna clinical data (but will be meeting a statsman this week for civilly disobedient English natter…). Maybe all commenters right and any contradictions merely semantic.

      May or may not be materially relevant, but just to add that from around year 2000 onwards, Pfizer’s focus shifted from exploiting in-house research (once upon a time quaintly coined “ethical pharmaceuticals”) to external acquisitions. Inventive, productive and respected research site at Sandwich, UK (where Amlodipine, Fluconazole and Viagra came to light), duly shut down. Draw your own conclusions about what’s happened since.

      As for Moderna, back in 2013 I had cause to look at the then patent estate of the then recently launched start up. As alluded to previously in comments on this blog, the then (and current) newly arrived Moderna CEO was a named inventor on most of the then patent estate.

      May or may not be materially relevant, but CEO inventorship record seemed a little curious at the time, given the CEO’s previous career pathway in investment and venture capital. Even curiouser, given a Forbes article earlier this year that referred to a CEO educated as an engineer who later acquired an MBA. Even looked like a couple of the patent filings might have pre-dated the CEO’s arrival at Moderna. More on the CEO here:

      https://web.archive.org/web/20201116154313/https://www.statnews.com/2016/09/13/moderna-therapeutics-biotech-mrna/

      Think I heard Moderna now capitalised at around $30 billion, yet still few (if any?) approved products. Must be a lot riding on the mRNA SARS 2 vaccine. Fans on the edge of their seats. Squeaky bum time, as the one and only Sir Alex used to say once upon a time over here in Limeyland (as the Man Utd of old closed in on yet another Premier League title – after 3 home PL defeats on the trot, closing in on a 1-0 home win over W Brom last night with a retaken penalty to the roar of an empty stadium about as good as it gets lately at the newly renamed Theatre of the Absurd Dreams).

      Maybe pertains to other thoughts posted lately on mRNA vaccines:

      https://blogs.sciencemag.org/pipeline/archives/2020/11/18/vaccine-possibilities (19 November 2020 at 6:49 am et seq):

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