CoronaVirus Disease (COVID-19) Thread : Fuck em, should’ve gotten vaccinated

Discussion in 'The Mainboard' started by shaolin5, Jan 20, 2020.

  1. Shawn Hunter

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    Think it’s a stretch to say that he implied they deserved to die. It’s pretty well known obese people are far more likely to die than fit people. Looks like to me he is trying to downplay its deadliness in kids by saying it’s largely the obese ones dying because they are obese.
     
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  2. Pile Driving Miss Daisy

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    I thought kids were allowed as long as they have a recent negative test and are masked. Anyone 12 and up has to be vaccinated even if they get the shot right before.
     
  3. PeterGriffin

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    Idgaf, if he thinks that (CDC stats ‘16-‘17) 13.9% of toddlers aged 2-5, 18.4% of children 6-11, and 20.6% of adolescents 12-19 don’t need protection and their deaths should be written off, I think there’s a problem. Lee County representing again, what a fucking shithole.
     
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  4. Pile Driving Miss Daisy

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    Also the whole fucking point that a lot more kids are getting hospitalized, even if they aren't dying, and that is creating situations where kids with other illnesses CAN'T BE READILY ADMITTED. It's absolutely fucking amazing how much they skirt around the hospitalizations issue causing other people to die of treatable illnesses.
     
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  5. bro

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  6. Pile Driving Miss Daisy

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    This is pissing me off still, if they want to hedge their bets then say so but it seems like no one is on the same goddamn page when it comes when 5-11 year olds will likely be able to get their shots.
     
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  7. Tobias

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    makes it even more great and totally not infuriating that a large reason for this wishy-washy bullshit is because they are scared of pissing off antivax shitheads
     
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  8. beerleagueman

    beerleagueman Well-Known Member

    Walensky has been a disaster …Better off not doing tv interviews
     
  9. Pharm

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    Pharmacist I’m friends with on Facebook

    370EF849-1DC0-4070-B440-70EC2BC22D83.jpeg
     
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  10. Henry Blake

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  11. MA

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  12. pperc

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    it's entirely possible memory b-cell recall responses will boost antibody levels to non-spike targets quickly if re-exposed to antigen. I would be very curious if they are doing ELISPOT assays for B or T-cell recall responses as part of this study.
     
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  13. Lyrtch

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    i hate the booster discussion so much, its really a replay of the offisification of bureacratic systems we saw throughout the pandemic
     
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  14. a.tramp

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    Exactly what I was telling a guy earlier!
     
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  15. pperc

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    yeah, right on. at least look at FACS based surface markers for memory cell phenotypes, right?
     
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  16. slogan119

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  17. a.tramp

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  18. slogan119

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    So you’re saying capitalism goes against your values, huh? Now imagine poor people’s dignity.
     
  19. Pharm

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    Asking
     
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  20. afb

    afb Spoiler Alert: Pawnee, IN may not be on a map.
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  21. IV

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  22. a.tramp

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    Would be a real shame if a dirty lib was stationed at the door to administer surprisingly painful nasal swabs every day.
     
  23. Henry Blake

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    https://www.medscape.com/viewarticle/958292#vp_1

    Eric J. Topol, MD: Hello. This is Eric Topol for Medscape, with our Medicine and the Machine podcast that I have the privilege of cohosting with Abraham Verghese. Today we have a terrific guest, Florian Krammer, who is at Mount Sinai. He did his training in Austria and came to Mount Sinai as a postdoc, and continues on there as an endowed chair and professor in vaccinology. He is one of the leading virus experts in the world and has become an important source of trusted data and perspective during the pandemic. So, welcome, Florian.

    Florian Krammer, PhD: Hi, Eric. Thanks for having me.

    Where We're Headed With Delta

    Topol: We have many things to discuss today, but obviously what's on the mind of many is the Delta variant. Can you give us a sense of what this has meant as compared to the prior variants and the original strain? How did we get here and where are we headed in the pandemic because of Delta?

    Krammer: That's a very interesting question. Delta seems to be different compared to other variants. Most of the variants that we started to see since late 2020 had an advantage in terms of spread, so they were probably more infectious — specifically, the Alpha variant that was clearly visible, but also the other variants that were picked up during surveillance because they expanded. The Delta variant is very good at that. The Alpha variant already had high infectivity, but Delta is much more infectious than Alpha. That's one of the issues that we're facing.

    If you look at immune escape, which was always a question with these variants, Delta doesn't stand out that much. It's not comparable to something like the B.1.351 variant, which really had a huge increase in neutralizing antibody titers. Delta has an impact on that, but it's not as big. So just from looking at neutralizing activity, you wouldn't think that the virus causes issues in vaccinated individuals. But it seems that it's more infectious and it replicates better in the upper respiratory tract. That causes an issue specifically with unvaccinated people.



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    We also see more breakthrough infections and even transmission in vaccinated individuals. That's a problem. But it's hard to see where we're heading with that specifically because it's so variable. If you look at different countries and regions worldwide and what it looks like right now in the United States, we might be at the peak of the Delta wave and cases might come down. In the UK, cases started to come down and then went back up. But in other countries, the Delta wave wasn't actually that big and it was very short. I'm hoping that the case numbers will go down — and we are seeing the first signs of that — and hopefully they will stay down. But it's really hard to predict what will happen after that.

    Immune Response: Vaccines vs Natural Infection
    Abraham Verghese, MD: You've done a lot of work on antibodies, and for most of us who are not in this world of antibodies, it's a very confusing issue. What are we measuring? What does it tell us about immunity? Can you share some pearls with us about the nature of antibodies from vaccine and from natural infection?

    Krammer: In general, there are still discussions about the role of different arms in the immune response and the protective effect that we see with vaccination and with natural infection. Of course, antibodies are easy to measure and neutralizing antibodies are interesting because, of course, they neutralize the virus and are a correlate of protection for many other viruses. In the past few weeks and months, we have actually seen a lot of data that suggest that neutralizing antibodies are an important correlate of protection for SARS-CoV-2. More data are coming out.

    But there are other arms of the immune response that often co-correlate with antibody responses. For example, typically, if you have a good antibody response, you also have a good T-cell response. We actually know they can't have a good antibody response without a good CD4 T-cell response, so it's more complicated than antibodies alone. Different arms of the immune system do different things. My suspicion is that the neutralizing antibody response is really important for protecting you from infection and mild disease. But once you have a breakthrough infection, a T-cell response, more or less, prevents you from progressing to moderate to severe disease. There are different phases where these different arms of the immune system are important.

    There are also, as you said, differences between immunity that is induced by natural infection and what is induced by vaccination. I wouldn't say one is better than the other, but they are certainly different. If you get a natural infection, you also develop antibodies and those antibodies are very often also neutralizing, but the response is relatively variable. Some people have very high antibody responses and some people have low ones. In addition to that, you get these T-cell responses not just to the spike protein, but to the whole range of open reading frames that the virus has — there are a lot of proteins that are encoded by SARS-CoV-2 — and you get mucosal immunity because the virus replicates on mucosal surfaces and that stimulates things like secretory IgA production or tissue-resident memory T cells.



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    This is in contrast to vaccination, where we basically get a response only against the spike protein, with very high neutralizing antibody titers. In healthy adults, the responses are very homogeneous — everybody is high. But you're lacking on the mucosal immune response to a certain degree, and your T-cell response is only focused on the spike protein because that's what's in the vaccine. So there are differences, and this might lead to different types of protection.

    If you had an infection, I would still recommend that you get vaccinated because people who had an infection have variable titers. If you get vaccinated on top of natural infection, you bring these titers very high. Actually, people who were infected and then got vaccinated have a very broad and very high antibody response, even better than people who just got vaccinated.

    The Truth About Antibody Tests
    Topol: Getting a little bit more into the antibodies, is there a test that would show whether someone had prior COVID? Approximately 40 million Americans have had COVID infection, as confirmed by PCR or some other test, and probably another 90 million Americans were infected but didn't have a confirmatory test at the time. Could you differentiate a natural immune response from a vaccine response by testing, let's say, for a nuclear capsid protein antibody? Would that help? Also, could you respond to the idea that a lot of the antibody tests are for IgG and not for neutralizing antibodies per se, so they might not be a good correlate for protection?

    Krammer: There are two targets for antibody tests out there. One is the nuclear protein, which you would only make antibodies against if you were infected with the virus or if you received one of those whole-inactivated virus vaccines that are used outside of the United States. But that vaccine is rare to find here; some people who travel might have gotten it, but basically a very small percentage. So if you have antibodies to a nuclear protein, that suggests that you had an infection. If you have antibodies to the spike protein, it could be from an infection or from vaccination. Of course, if you've been vaccinated, you know that you've been vaccinated. If you haven't been vaccinated and you have spike antibodies, it's probably because you were infected. But antibodies against the nuclear protein vs spike protein let you differentiate.

    In terms of what we're measuring, some antibody tests give you a yes-or-no response. That is okay to figure out if you had an infection or not, or if you made an immune response to the vaccine. But that's all it can tell you. Then there are antibody tests that are semi-quantitative or quantitative, that tell you what level of antibody you have now. It's correct that these antibody tests are not measuring neutralizing antibodies; they're measuring binding antibodies. But what we have seen in general is that there's a relatively good correlation between neutralizing and binding antibodies. In fact, studies coming out recently from Moderna and from David Goldblatt's lab have begun to establish a number that is connected to protection. There isn't really a single number above which you know you're protected, and below it, you're not. This looks very different; it's usually a probability. Typically what is established with a correlation is a titer of antibody that reduces your chance of getting an infection or disease by 50%. Those values are starting to come out in scientific papers.


    The problem right now is that these tests are reported in international units — or if it's a binding assay, it's BAUs — but a lot of tests available today in the US have not been standardized to international units. So if you get an antibody test back from the lab and you have a certain number and you want to compare that to a paper that gives you a correlation for protection, you might have a hard time because that lab might not report that type of unit and you cannot directly compare. It's still very complicated. But on the other side, we see more and more that antibodies do correlate with protection and that determining a 50% protective titer is possible.








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    Verghese: I have to confess that — like many physicians listening to this, I suspect — I got the antibody test and it came back negative, and I realized I had no idea what they were testing. There was no way to do anything with the information. I sheepishly talked to a few colleagues only to find that many of them had done the same thing, and 50% or so had the same awkward realization that they had no protection. But we don't know what we were measuring. We don't know that it mattered. And ultimately, we all concluded that in the absence of standardization, we just needed to ignore this. The bottom line is we shouldn't have done the test.

    Krammer: Once the vaccine started to be rolled out, I got a lot of emails from people who had gotten tested and were negative after vaccination, and in 100% of cases, it turned out that they had done nuclear protein tests. So they were upset that they didn't make a response. But then it turned out that they were just measuring the wrong antibody response.

    Topol: And you have published how virtually everyone who gets vaccinated has at least some antibody response, even among people who are immunocompromised, although perhaps not as high a level.

    Should Prior COVID Be Counted as a Vaccine Dose?
    Topol: Prior COVID doesn't get much respect. If you get a vaccine card, there's no entry for prior COVID. Do you think that should count as one dose? In many other countries, perhaps in Austria, but in certain countries in Europe and Asia, confirmed prior COVID is counted as one dose of vaccine in terms of your vaccine status. What are your thoughts about that?

    Krammer: Absolutely. There is a nice preprint out there in which they assessed vaccine effectiveness against Delta with AstraZeneca, Moderna, and Pfizer-BioNTech vaccines. But they also looked at prior infection, and prior infection is pretty much as good as what they see with the vaccines, in the range of 70%-80% protection against reinfection with the Delta variant. So just to assume that somebody who had an infection has no protection is wrong. Those people have substantial protection. They have variability in their response. Some might get reinfected and are less protected than others, but they certainly have a degree of protection. You might not want to consider them fully vaccinated; you can argue about that, but at least a one-dose equivalence from a scientific perspective is justified.


    Topol: Any time cut-off on that within a year or 6 months, when you say "prior COVID"?

    Krammer: The initial studies that came out that showed that previous infection is about 80%-90% protective against reinfection — we're talking about infection, not disease; protection against disease was higher. Those studies were done mostly in December 2020 or January-February 2021.

    There was a lot of talk about waning immunity in the beginning, and we hear that again now about the vaccines. But people don't realize that those are normal responses. What we see is that the antibody response — I didn't look at the T-cell response — but the antibody response after natural infection does stabilize over time. We have been following a cohort of people with Viviana Simon at Mount Sinai since the spring of 2020. Of course, we have fewer data points now because a lot of people got vaccinated. But for the people who got infected and did not get vaccinated, the antibody titers are now pretty stable. Even a longer time out, I think protection would still be there. It's not 100%, but there is certainly a good amount of resistance to infection.

    To Boost or Not to Boost
    Verghese: Which leads us into the discussion of the booster doses. What are your thoughts on the timing of the booster, the particular booster to use, and so on?

    Krammer: There are a lot of things that you have to consider when you think about booster doses, waning immunity, and Delta. First of all, we have to be very careful when we talk about waning immunity and reduced effectiveness. You see a lot of newspaper reports out there that compare the efficacy of the vaccine against disease, measured in clinical trials, with the effectiveness against infection, and those are apples and oranges. You cannot really compare them.

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    But even if you look at the efficacy data — Pfizer, for example, has data from 4-6 months, and they do see a drop. It makes sense because there is some waning of immunity initially. In addition to that, we have a variant circulating right now that seems to grow to higher titers. It's more infectious. It might have a couple of tricks to evade immunity in general a little bit better, not just adaptive immunity. Now, the question is when vaccine efficacy or effectiveness falls to levels like 80% against disease (and I'm not talking about infection; I don't care about infection that much at this point), is it time to give a booster shot or are we still good? And how do the levels against severe disease and hospitalization look?

    Also, we need to look at the populations we want to give a boost to, such as those who are immunocompromised or older individuals who did not respond well to the vaccine. I think a booster dose makes a lot of sense. There was already a recommendation for certain groups who have issues with their immune system, which makes sense.

    Does it make sense for the general population to just, as a blanket policy, say, "Oh, you should get a booster"? I'm not sure that's justified at this moment in time. We'll see how the FDA and the CDC see that in the end. But you need a lot of data to support that. We do see some waning of vaccine effectiveness. Yes, the data go down with time a little bit, but we already see that titers after natural infection start to stabilize; typically there are no differences between 7- and 8-month titers. The question is where you end up. If you end up at the 85% effectiveness against disease, that's probably okay. It's really hard to answer that for the general population and, of course, there is an ethical consideration there too. We're now talking about giving booster doses potentially to people who don't need them, while a large proportion of the globe has no access to any vaccines. That's also something that we should take into account.

    Topol: I want to make sure our listeners understand the differentiation between infection and disease, because in the middle there is symptomatic infections, which can be pretty severe — just short of winding up in the hospital or needing monoclonal antibodies because they're quite ill and they're starting to manifest signs of lung or other organ involvement. Do you consider symptomatic infection disease?

    Krammer: Yes, I do consider that disease. I like the definitions that were used in the initial vaccine trials for the mRNA vaccines, which is basically a positive PCR to show that it's really SARS-CoV-2 causing the infection and at least one symptom. That's symptomatic infection.


    Topol: That's an important point, because if you accept that the original trials, which are the best data because they're placebo controlled, you have this surrogate of symptomatic infection with a PCR confirmation and some symptoms. The trials didn't use the endpoints of hospitalizations and death because that would have taken tens of thousands more participants.

    Comparing mRNA Vaccines
    Topol: I want to get into the Pfizer-vs-Moderna data, because I know you're familiar with this controversy. We have differences in spacing with Pfizer and Moderna: 3 weeks vs 4 weeks. Other countries that have seemed to do very well have used 8- to 12-week spacing of all the vaccines rather than the initial protocols. We also have this period of time, either 6 or 8 months of follow-up, which is different, with Pfizer getting out of the block first and then Moderna. And then we have the factor of time itself when you look at the initial placebo trials. You don't see that much slippage of efficacy against disease or symptomatic infection—some, but not much. How do you put all of this together? Are there differences with the vaccines? What about the spacing? If you see drop-off in symptomatic infection effectiveness, aren't you going to also see some slippage in protection from hospitalizations and deaths?

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    Krammer: Those are all good questions. It's a mess right now, honestly. First of all, a lot of what you see is people talking about or comparing vaccine efficacy against symptomatic infection as defined by the initial clinical trials, with vaccine effectiveness against any infection. And sure, those drops look big. It's very likely that you also see some increase in hospitalization if the effectiveness drops. So the question is, how big is that going to be? There are studies that suggest that the drop is not that big.

    There are also datasets that tell different stories. If you compare the UK with Israel — and to my knowledge, there's no good scientific study out of Israel yet but there are a couple from the UK. In the UK, the Delta wave was massive, but the deaths associated with the Delta wave were very low. They had very few deaths compared with the Alpha wave; it's night and day. In Israel, that doesn't seem to be the case. So the question is whether this is vaccine breakthrough and does the vaccine just not work that well in Israel, or is it that unvaccinated people are affected? If it is among vaccinated people, then that brings up the difference in spacing between the first and the second dose of the vaccine. Typically, we know that vaccines work better when you leave more time between the prime and the boost. Of course, between the prime and the boost you also have more vulnerability to become infected because your protection is not optimal yet. In a pandemic, you want to have a very small window. The UK had a different strategy. They had a very large window, and that might in the end have produced a better immune response.

    But those are hypotheses that have not been confirmed. Right now it's relatively messy when we look because so many things come together: a more infectious variant, waning immunity in some subjects, and the fact that many places no longer have restrictions. During the winter waves, we still had restrictions in many countries. Now we don't, and that also comes into play here. It's very difficult to disentangle all of that.

    Topol: What about Moderna vs Pfizer?

    Krammer: That's one of my favorite topics. There are differences between the vaccines. They're minimal, but there are differences that start with the formulation. The lipid nanoparticles are different, the scientific profile is different, and the dose of RNA that is delivered is different. The sequence is basically the same. The Moderna vaccine has 100 µg of RNA; the Pfizer vaccine has 30 µg. So there are differences.

    In terms of the immune response, there's not much difference. There might be a minor twofold difference between Moderna and Pfizer. Some studies suggest that, but we actually don't see that when we compare them. Studies from Qatar and the Mayo Clinic suggest that the Moderna vaccine holds up much better than the Pfizer vaccine. For the Qatar study, there might be a bias about when people were vaccinated, whereas the Mayo Clinic study controlled for that. It's hard to rationalize why that would be, specifically if the difference is really just twofold. We'll have to wait until these findings are confirmed. The Mayo study was already relatively large, so it wasn't a small dataset, but it would still be nice to see that comparison from other places too.

    One problem is that Moderna was used later in many places. It was licensed in many countries later and then a smaller proportion of people were vaccinated with it. There's a nice preprint out from Canada that has data for Pfizer against Delta after the first and second vaccinations. For Moderna, we only have data for the first vaccination so far. The data will trickle in. If there really are differences — and I'm still skeptical about this — then it might actually make sense, if you really go for booster doses, to preferentially use one of those vaccines. We need hard data and confirmation that this is really the case.

    From Glycoproteins to Science Twitter
    Verghese: You've done a lot of work on glycoproteins. For those of us who are not biochemists, help us understand the fundamental role of glycoproteins in everything we've been talking about.

    Krammer: Many viruses have glycoproteins on their surface, and those proteins are basically the part of the virus that binds to our cells and then facilitates entry of the viral genome into the cell to start to replicate the virus. Many viruses have glycoproteins; some have surface proteins that are not glycosylated. I started out working on influenza, which has two glycoproteins: hemagglutinin and neuraminidase. SARS-CoV-2 has only one bona fide glycoprotein, the spike protein; although the E protein, which is an ion channel, is also glycosylated. It has one glycosylation site, but it doesn't play a big role in virus neutralization. Typically when you make an antibody response against those glycoproteins, these antibodies can either stop the attachment of the virus to your cells or that fusion mechanism that neutralizes the virus. That's why I'm interested in that process.

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    Some of these glycoproteins are relatively simple, like the hemagglutinin of influenza. I wouldn't say the spike protein is that simple, but it's one of the simpler ones. And then you have very complex ones. For example, with the glycoproteins of hantaviruses, we are not really clear about the details of the mechanism. A lot of things still need to be explored. You have these little glycoprotein machines that are used to enter cells, the antibodies that people make, and the interaction of the antibody that stops the glycoprotein. I think that's very fascinating. That's the core of what my lab is doing for four different viruses.

    Verghese: We've had a surge in medical school applications because of COVID, and I suspect we'll probably have a lot more people going into virology, which I'm sure must gratify you. But during the pandemic, many virologists have been forced to take on important social roles. You have a very large Twitter following, and I love the banner on your Twitter page: "Mask not what your country can do for you. Mask what you can do for your country!" So this is an interesting transition in your life. Talk a little bit about your social activism around masking. It's not all viruses; it's also human behavior, as you correctly point out.

    Krammer: I'm not really good at science communication. I was on science Twitter, which was a really nice tool to exchange information with other researchers, mostly flu virologists. But in the beginning of 2020, there was a vacuum in terms of information. The CDC did some communication but they were shut down relatively quickly. I just started to spread information. When the vaccines were developed, I started to spread information about vaccines. People who are hungry for very high-quality information about these things found me. And then I started to interact with the media. This actually makes me very nervous. I'm not a person who likes to interact with the media, and when The New York Times called me the first time, I was really shaking. But then you get used to it and it's nice to have these interactions.

    There were many people on Twitter who did really good science communication during the pandemic. It's nice because you get a lot of positive feedback. It's not just Twitter trolls. There are also a lot of people out there who appreciate what you're doing and let you know that they appreciate it. It also has downsides. When I was on Twitter and had 500 followers, I could make all kinds of snarky comments about politicians or other people. I cannot do that anymore or I get a lot of bad feedback. I have to really watch what I'm saying. That's the downside of it.

    Verghese: It doesn't always stop my co-host. He carries on whether he's got a million or 10 million followers.


    Mix or Match Vaccines?
    Topol: I've learned so much from you throughout the pandemic. You've been a great instructor and explainer. I have two other questions I want to get to before we wrap up. First, there's a lot of interest in the mix and match of vaccines; the fancy medical word is "heterologous." The whole idea is that if you give a vaccine with the adenovirus vector first and then give an mRNA vaccine, that seems to be the second best in terms of a potent immune response after prior COVID and a vaccine. But it doesn't seem to work as well the other way around, if you give the mRNA vaccine first. But the mixing appears to work better than two mRNA vaccines or two adenoviruses vaccines. Can you explain why that is, and should we be exploiting that information?

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    Krammer: To explain in terms of the actual mechanism is hard. We have observed for influenza and HIV that a lot of the HIV trials, even if they were not successful in the end, they were successful in inducing strong immune responses when they used different vaccine platforms in combination, such as vaccinating first with a virus vector and then with a recombinant protein vaccine. These types of combinations also worked very well for influenza; Kanta Subbarao did a trial with H5 vaccines, where she gave a live attenuated H5 flu vaccine (which is basically like a viral vector; it's a replicating virus), and then she boosted with an inactivated vaccine. That worked much better than giving the inactivated vaccine twice. So it seems that all of these platforms stimulate the immune system slightly differently, and if you combine these stimuli, the immune system actually makes a better response. That could be a longer-lasting response, a stronger response, or in some cases, a broader response.

    When this question came up for SARS-CoV-2, the speculation was that it would work and most likely was going to be better than just giving the same vaccine twice. We have some indication from studies specifically from Europe that AstraZeneca followed by an mRNA vaccine might be a pretty good strategy. Some of these studies report that it works better than giving two mRNA vaccines. And the side effect or reactogenicity profile is actually not much worse or not worse at all. Only one study had a little bit more reactogenicity. So that might be a good way to induce strong immune responses.

    The question is really in the United States. We will need bigger studies to look at Johnson & Johnson and the mRNA vaccines because AstraZeneca is not licensed here. The question is also what Europe is going to do. They had clinical studies to evaluate that, which was partially just a practical decision, because in Germany, AstraZeneca was initially given but then they said that it should not be given to females under a certain age. The people who had already gotten the AstraZeneca vaccine then got the second dose with the mRNA vaccine because of that change in recommendation. So a lot of people got these regimens in Europe, and it looks like it gives a slightly better immune response. There is one preprint from David Ho's Lab, where they gave — and I don't know the reason why this was done; it might have been by chance — mRNA vaccine twice and then Johnson & Johnson; that seems to induce a nice boost. But it's not the same as giving one vaccine followed by another; it's twice the same vaccine and then the boost with a third. It was also only a few people, four or so, but it induced a nice boost.

    A Pan-Coronavirus Vaccine
    Topol: We're giving the same vaccine as a booster and we don't have a Delta multivalent vaccine. We know that the evolution started with this N501Y signature and the Alpha, Beta, and Gamma variants, but Delta took a detour. It's substantially different and it's not following the earlier variants of concern. So wouldn't we be better off having a Delta vaccine? Also, you have worked on universal vaccines for influenza; wouldn't the SARS-CoV-2 virus be the ideal target for a pan coronavirus, at least betacoronavirus, vaccine? Why aren't we putting full priority on that?

    Krammer: Trials of mRNA vaccines against the Beta variant (B.1.351) are being done in people who got the regular mRNA vaccine first. Some of these studies also have arms in which the same vaccine was given a third time, and it look like that gives you as much protection or as-good antibody levels against Beta, but also against Delta, as the switched vaccine. So right now, it's not clear whether there is even a benefit in changing the vaccine strain. If Delta keeps dominating, that might be a consideration at some point in time, which would be relatively easy, especially for the mRNA vaccines.


    The situation with Delta is a little bit different from before, because Delta is now very prevalent. In the United States, it's way above 90% of all variants that are circulating, whereas before it was more mixed. If you do a strain change, say to Beta, will that help you against Gamma as much as the wild-type vaccine? You have to be careful when you're choosing new vaccines to make sure that that is actually representative of what is circulating. Maybe for Delta that is easier, but right now it doesn't look like it's necessary.

    The question about the universal vaccines is super-interesting. We have done a lot of work for flu and there are clear targets for influenza virus that can lead to broad protection — the stalk domain, partially the neuraminidase to the ectodomain of the ion channel, and so on and so forth. For SARS-CoV-2, it's not clear yet. There are some antibodies against the S2 subunit of the spike, which is more conserved, that are neutralizing antibodies but they are not very strong. That doesn't mean that a vaccine based on that subunit won't work. We'll have to see about that. But there are now a lot of initiatives that are pushing toward a universal coronavirus vaccine.

    But as you said, we have to also be careful what we're talking about and how we define that. Some people, when they talk about the universal coronavirus vaccine, they mean something that would work against all the SARS-CoV-2 variants. That's easier to do than a vaccine that protects against all betacoronaviruses. If you're talking about a vaccine that protects against all coronaviruses, that gets really tough; you would have to cover a very high diversity. But I think even that is worth trying.

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    9
    We have to keep in mind the typical pipeline duration for vaccine development, despite how quickly these SARS-CoV-2 vaccines were developed. In addition, for a universal coronavirus vaccine, a substantial amount of time would be needed to design it and find targets and so on. I think it's possible to make a vaccine for all the SARS-like viruses. It's possible to make a vaccine against all the SARS-CoV-2 variants, and it might be possible to make a betacoronavirus vaccine. It might even be possible to make a broader one, but it will take a lot of time.

    A Virologist's Nightmares
    Verghese: I can't let you go without quickly asking you about Nipah virus, because it's happening in Kerala, where my parents are from. They're struggling with that outbreak and with SARS. Any closing thoughts on the Nipah virus?

    Krammer: I give a lecture on emerging viruses and the two examples that I usually talked about before the epidemic that I found scary were SARS coronavirus and Nipah virus. That was one of the reasons why I jumped onto SARS-CoV-2 research so quickly, because I was actually scared of that virus. But the other virus that I find problematic is Nipah, for a number of reasons. We have seen Nipah virus outbreaks in Bangladesh where there was human-to-human transmission and where it had a respiratory phenotype. Of course, you get very concerned when you see something like that, specifically with a virus that also causes encephalitis and has a case fatality rate, depending on the outbreak, higher than 50%. I have no doubt that the current outbreak in India will be brought under control. But I think it will be good in the future to have a Nipah virus vaccine ready for use if we need it so that like with Ebola, if there is an outbreak and we see human-to-human transmission, we can vaccinate really quickly. Nipah is a virus that has a lot of potential, and with that case fatality rate, it's one of my nightmares.

    Topol: Florian, we really appreciate this conversation with you. There's no question this virus has humbled us. We have many mysteries still out there, whether it's the messy interpretation of breakthroughs, or why, in certain countries, the Delta variant behaves so differently from others, or why it goes down rapidly or goes back up. There's so much we don't yet know, and we will continue to turn to you for guidance. And we encourage everyone who's listening to us to realize that you're a great resource. Thanks so much for being with us, and we'll stay tuned for your very helpful interpretations throughout the pandemic.

    Eric J. Topol, MD, is one of the top 10 most cited researchers in medicine and frequently writes about technology in healthcare, including in his latest book, Deep Medicine: How Artificial Intelligence Can Make Healthcare Human Again.


    Abraham Verghese, MD, is a critically acclaimed best-selling author and a physician with an international reputation for his focus on healing in an era when technology often overwhelms the human side of medicine.

    Florian Krammer, PhD, graduated from the University of Natural Resources and Life Sciences, Vienna, in 2010. He currently holds a position as a professor of vaccinology in the Department of Microbiology at the Icahn School of Medicine at Mount Sinai. Follow him on Twitter at @florian_krammer

    This podcast is intended for US healthcare professionals only.

    Follow Medscape on Facebook, Twitter, Instagram, and YouTube

    0 Read Comments
     
  24. ashy larry

    ashy larry from ashy to classy
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  25. Tobias

    Tobias dan “the man qb1” jones fan account
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    highlights include:

    -no discussion of the mandate
    -one employee asking if it would be better to not get vaccinated because if the vaccine hides symptoms, it would be better to have bad symptoms so you know you have it and can't spread it. the health department lady didnt really push back on how dumb this is and just recommended the vaccine
    -same employee was worried about the stat she showed of 50% of people have mild side effects for 24-72 hours. great job making that possibility look scarier than it is
    -one employee asked about preventative measures you could take such as taking vitamin d supplements and "other stuff that isnt being discussed". she said its good to be healthy and never mentioned that the vaccine is quite literally the best preventative measure
    -another employee had never head of guillen barre syndrome but now is worried. the slide showing how rare that is in vaccinated people had the opposite effect because now there is another reason to not get vaccinated

    real tour de force of stupidity all around
     
  26. Tobias

    Tobias dan “the man qb1” jones fan account
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    also we had a moment of silence for an employee's wife who died of covid and also 9/11 (which the plant manager went on an extended speech about never forgetting)

    the moment of silence came to an end when the "mild symptoms are bad" big brained genius had his text message ringtone go off (sound of racking a shotgun and shooting it)

    it felt like a skit from i think you should leave. i had to struggle to not laugh out loud at the absurdity of it
     
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  27. rulethirty

    rulethirty UCF and Alabama are basically peers.
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    fwiw, i do think you should leave
     
  28. Tobias

    Tobias dan “the man qb1” jones fan account
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    there actually is a pretty strict mask policy and i am never close enough to any of these people to worry. really gonna enjoy their ultimate demise
     
    rulethirty likes this.
  29. SD_Irish

    SD_Irish El Mas Chingon
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    Do you by chance work in a glue making factory?
     
  30. ned's head

    ned's head Well-Known Member
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    Would be amazing if this timeline hit

     
  31. Can I Spliff it

    Can I Spliff it Is Butterbean okay?
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    Get a job, welfare queens
     
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  32. Tarpon Nole

    Tarpon Nole Well-Known Member
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    If I am able to get both of mine by end of year, I'm happy
     
    ned's head likes this.
  33. Sub-Zero

    Sub-Zero ALL THE TOSTITOS!!!
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    Finally I can go back to teaching my kids how to properly lick doorknobs
     
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  34. Prospector

    Prospector I am not a new member
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    liked for the sneering "these people" instead of co-workers
     
  35. Can I Spliff it

    Can I Spliff it Is Butterbean okay?
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    Poor russia cant sell their vaccine
     
  36. Can I Spliff it

    Can I Spliff it Is Butterbean okay?
    Donor



    Wonder how those stands are looking
     
  37. AUShyGuy

    AUShyGuy Unbridled Enthusiasm
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    How long we thinking the EUA takes to approve?
     
  38. pperc

    pperc Well-Known Member
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    First group Walensky said end of year which is awful
     
    Keef likes this.
  39. Pile Driving Miss Daisy

    Pile Driving Miss Daisy It angries up the blood
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    Others, like Gottleib, have said it could take 3-6 weeks.
     
  40. ashy larry

    ashy larry from ashy to classy
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    [​IMG]
     
    AUShyGuy likes this.
  41. PeterGriffin

    PeterGriffin Iced and/or sweet tea is for dirty rednecks.
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    upload_2021-9-14_15-22-26.gif
     
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  42. Andy Reocho

    Andy Reocho Please don't get lost in the sauce
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    lol
     
  43. bro

    bro Your Mother’s Favorite Shitposter
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    I don't care what the haters think.

    also I am melting down for 2 straight days on the internets
     
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  44. a.tramp

    a.tramp Insubordinate and churlish
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    I can’t tell if this is you posting as Nicki or you posting as you.
     
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  45. beerme

    beerme Well-Known Member
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    he definitely could’ve pulled this off
     
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  46. PeterGriffin

    PeterGriffin Iced and/or sweet tea is for dirty rednecks.
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    This is posted in the right thread, for those confused.
     
    #91699 PeterGriffin, Sep 14, 2021
    Last edited: Sep 14, 2021
  47. JacobPalmer

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    I was charge nurse on our covid unit the last couple days so I got to sit around and answer a lot of phones. Multiple family members calling telling us 1. We need to start on ivermectin 2. We need to stop the remdesivir 3. We need to extubate.

    Again, I like to stir the pot a little so these people don’t know how much I enjoy this part of the job. It’s like an episode of Crank Yankers only they’re calling me. The last call today it was obvious I was on speaker phone and towards the end I heard a lady yell, “The nurse is just fucking with you Larry!”
     
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