You’re listening to a press conference from the Harvard School of Public Health with Michael Mina, assistant professor of epidemiology and a faculty member in the Center for Communicable Disease Dynamics. This call was recorded at 11 a.m. Eastern Time on Friday, March 5th.
MODERATOR: Dr. Mina, do you have any opening remarks?
MICHAEL MINA: No, I’ll take questions.
MODERATOR: OK, first question.
Q: Great, thank you, Dr. Mina. My question is about a tweet that Julia Marcus, your colleague, had put up a few days ago and it got some attention in the Boston Globe. It was about the J&J vaccine and how its efficacy continued to improve through well beyond fifty-six. Obviously, that got some attention for reasons beyond just the data. But I wondered if you could comment on the data portion of it. I’m interested in the way that the efficacy is measured, and you know, especially since at some point it seems to rise above the 90 percent threshold, which would make it more comparable, I guess, to the Moderna and Pfizer vaccines. Thanks.
MICHAEL MINA: Yeah, I think that that tweet certainly got a lot of attention not having anything to do with the rising efficacy. But I mean, the data is extremely interesting and frankly fits with a lot of what we know about immunology again. And we know that immunity improves after an exposure. We have affinity maturation. Truly, the immune cells that are responding to the pathogen can continue to mature over time. And that happens over many weeks, which is exactly, I think, what is being detected there. You have this maturation of the immune protection and it is a long continuum. So you can have sort of a very, very fast immunological response, which does concern me about the mRNA vaccines to a certain extent, is we saw this very, very swift rise in efficacy, up to about 90 percent within the first couple of weeks. And then, of course, the extra booster kind of pushed it a little bit over that as well. With the J&J vaccine, we saw this kind of very gradual increase in effectiveness in these inefficacies and in the clinical trials. And that’s essentially determined by looking at essentially stratified analysis but looking at how what are the rates of infections and disease that occur over time when you’re setting sort of time point zero as the time that you get the vaccine.
And so I think that this is really a reflection of the basic properties of the immune system. It’s important to remember that we might also see this with the other vaccines. For example, we made the twenty-one-to-twenty-eight-day time window that has been discussed so much for the mRNA vaccines wasn’t based around a good biological reason, it was based around accelerating the time, of course, needed to run the clinical trials, which was unfortunate because then everyone kind of became glued to this idea that twenty-one and twenty-eight days was essential or even optimal and there was no evidence to suggest that it’s optimal. It was just to speed things up. Had we waited, for example, and given a booster shot at two or three months, maybe that would have been even better, which is what the AstraZeneca vaccine is doing. And so I think that this is consistent with biology.
Q: I did have one follow up question. Bruce Walker had said during a talk of the Mass Consortium on Pathogen Readiness that the J&J vaccine also was showing evidence of T cells. And he suggested that those were not being seen with the other two vaccines and furthermore, that that T cell might be providing a broader type of protection against potential future variants that had not yet arisen. How does that work? Is that does that jibe with what you know? Does that make sense to you? And have you heard anything about T cells appearing after administration of either the Pfizer or the Moderna vaccines?
MICHAEL MINA: So the way that the T cell response works, essentially T cells are slightly different than an antibody response. An antibody response, you essentially have a piece of a protein that gets recognized, but it’s usually in sort of a confirmation all shape. And so this is a protein and it may be an antibody comes in. On the other hand, a T cell. What happens is once a virus is infected, the cell, waves a little white flag and tells the T cell to come in, eat it, and so the T cell goes after the cell that’s infected and not the virus itself. But the reason I bring that up is what happens inside the cell is very important. The cell chews up that protein. So you have this protein in the cell like chews it up and then displays just a little piece of the protein, just a little 9 amino acid piece, usually maybe 12. And that just sits on something called MHC. Why that’s important is because what it means is that if you have a big protein, you may have a lot of different epitopes on that protein once it’s chewed up and kind of split into all these little bits, any one of those might become a T cell epitope and those little bits can be conserved across various mutants. And so that’s why there is this potential and that’s why there’s a lot of fervor around T cell immunity. I think that it’s a little bit speculative to suggest that it’s going to be make a massive difference, and I don’t think Chris was making that speculation that it’s going to be a massive difference. But there is some thinking that because it’s really recognizing these much smaller little bits that you could potentially have a sort of broader response. To be honest, I haven’t kept up with the J&J vaccine T cell literature enough to comment one way or the other. If I feel that this is really going to be, I’ve seen the data that this is really going to be a major overhaul with this vaccine and if it’s necessarily responsible. But T cells are something that have always been around. They’re not a new thing for this virus. They’re a new discussion during this pandemic compared to others, because really a lot of the T cell biology and tools to study T cells in high throughput and in larger numbers have really only been developed in the last half a decade. And so they just haven’t been as much a part of the discussion compared to serology and antibodies which go back many, many years.
Q: Thank you.
MODERATOR: Next question.
Q: Hi, Dr. Mina, thanks a lot. I’m calling about the Broad Institute. It seems that they changed their protocol at the end of January in terms of testing and what is deemed a positive test, and it changes it. So there’s fewer tests that are deemed positive, a very small proportion of fewer tests. And I know you’ve said before the problems with the PCR test for controlling outbreaks. So could you comment on this?
MICHAEL MINA: Yeah, this is part of a slightly larger discussion across the globe, which is a recognition, as I and many other people have said, is that using a test like PCR can be so sensitive that we are. Potentially able to get false positives and we’re potentially able to detect true positives for a very long time. And this is a way to balance those measures up, there’s always this balance between sensitivity and specificity. We want to limit false positives as much as possible while still maintaining relevant high sensitivity. The CDC assay, which is the base assay that the Broad uses and many, many PCR assays around the world usually use a CT value of PCR, a threshold of around 40 to call something positive. Meaning below 40 you’re positive, above 40 you’re negative, but that is a lot of cycles that’s potentially amplifying a single molecule a trillion times just to get a signal. And theoretically, that means you have essentially one molecule. If you’re going to go all the way up to 40 cycles to get a positive, you might have just one molecule in the reaction or you have no molecules. And it’s a false positive due to any number of mechanisms that can cause a reaction to falsely term positive when you go out to that many cycles. So this is an effort to improve the specificity. It is not suggestive. I think a lot of people have confused that this whole discussion, assuming that the majority of PCR values are false positive, that’s not true. But I would say that we never needed to go to such high sensitivity on these PCR tests. That just wasn’t a necessary thing. It’s one thing if you’re testing for HIV and you want to really be monitoring people’s viral loads and to know if they are if their virus has mutated to get it away from their HIV therapies. But for an acute respiratory virus which grows from, you know, a few viral particles to a trillion in a day, we don’t really have to worry about the few most of the time when you’re just measuring a few of your way post infection. And so this is in an effort to sort of limit potential of false positives and keep sensitivity and keep the relevant sensitivity very high still.
Q: I just have one follow up. Do you know of other labs that process a large number of tests that have done this?
MICHAEL MINA: I’m sure that there are. I don’t know of any labs that have sort of changed their major process midstream so far. But I’m sure that they have plenty of labs that have been tweaking their assay since starting it in the middle of last year. But I don’t know which ones they are. I know that Curative is one of the major labs that isn’t Lab Carquest. Curative is a little different. It’s working and across many, many different physical laboratories. But I know that they’ve been advancing their own technology, using sort of mouth swabs and such, but I’m not sure I have any others that have specifically done this.
Q: Thank you very much.
MODERATOR: Next question.
Q: Hey, Michael. Thanks, Nicole. Hey, so the biotech sector is really just blowing up here. So on your rapid test in the past, you’ve sort of discouraged us from thinking about it. I mean, you used the phrase license to party, which is maybe a little bit cynical. But I think there are settings where, you know, you might have a chance to meet somebody you haven’t seen for a long time and, you know, just to test out so you can know whether you can hang out or not, particularly if you’re in an at-risk category. I wonder if you might consider kind of re-pitching your idea and maybe emphasizing that angle a little bit more. And if not, why not? And the reason is like for us, that has a lot of appeal on that level. So if you generate an interest in the public, that might also capture the attention of politicians.
MICHAEL MINA: Yeah, it’s a somewhat fraught question, and I completely agree with you on the one hand. Now, from an epidemiological perspective, I think that the best, most powerful use of these tests is to have just the population using them twice a week on an ongoing basis just to keep our below one and stop outbreaks from happening. Don’t change anything if you’re negative, but if you are positive, you stay home and isolate. That’s a very, very powerful epidemiological approach, is just mass distribution. Don’t worry too much about the individual metrics, but if you are positive, don’t go out. That alone, if we could get enough test out to the community, that would stop these outbreaks. That would have stopped the outbreaks that ultimately happened in the fall and winter. But, you know, we are in a different time now and people are no longer asking the question, can we stop the outbreaks? Now, people are really asking the question, can we gather again? And so I think your point is very well taken. The issue with the rapid antigen test is that, as I’ve said many, many times, it is positive when you’re infectious. And that’s great. That’s very good. But it is going to be negative until are infectious. And so the concern is that and what I’ve seen happen, even with PCR, this is happening all over the place, is that people get a test at one period of time and then you don’t have a good sense of how long they can kind of consider that test to be a sort of valid as reflecting that they’re likely not infectious. My personal feeling is you take a high-quality test like a BinaxNOW or one of these other rapid tests. Take one of the good ones. And if you’re negative, you’re very, very unlikely to be transmitting, at least for the next following hours. So could you have a party where everyone shows up and tests negative? Probably. Overall, it’s a whole lot safer to have one hundred parties where everyone tests negative right before walking in the door than to have 10 parties where nobody tests before walking in the door. It’s a lot safer to the hundred with tests than the 10 with no tests. So I think that if it’s a way to get people to test and kind of get socialization back into our culture and society, I think that at the end of the day, it’s going to be a net benefit. The problem? The real problem is, frankly, the media attention and how events are covered, and it’s really difficult in public health to keep a balanced discussion going. Let’s say you have hundred parties, and everyone tests negative before the party, but you end up getting an outbreak in one of those parties. But you have a positive person who’s getting filtered out in every single one of those hundred that otherwise would have walked in. You’ve just prevented ninety-nine outbreaks. One goes through, but that one is the only thing that’s going to get reported on. And so it gives this false denominator for the population, so people then lose confidence in these tests. So how to balance that? That’s a really hard question. And so in some ways, from my perspective, this is not a this isn’t a problem of the media. This is a problem of everything of the biases in medical science, we always focus on the bad and we never report just the daily grind of good and positive benefits. Same thing with the Rose Garden event, for example. So how to keep the confidence high while saying people can go socialize while knowing that there is going to be a breakthrough outbreak every now and again, it’s almost easier for somebody like me to sit here and say, well, that’s not the appropriate use of these. You know, I’m calling for something else versus if I say I’m calling for a reference for people to use this as a tool that can allow them to socialize, probably the net benefit is absolutely there. But it’s going to be a snowball effect of the few outbreaks that do occur despite the tests are going to be the news and it’s going to cause a lack in public confidence. And so from my position, I have a very difficult time trying to figure out how to weigh these competing forces. I know mathematically very well that the competing forces fall on the side of its better if you’re going to go socialize, use this as a green light test. But from a preservation of the discussion, in some ways, it’s better to call this a red light to us than if people choose to use it as a green light test, so be it. That’s an honest answer, I suppose.
Q: Well, yeah, it is. I think you have a really compelling idea and I think you’re thinking about a big picture, which is how you think. And there’s nothing wrong with that. But, you know, most people think only about their own self-interest. So from a public health perspective, I get your point. But from a political perspective, if you sold it as an idea that allowed people to, you know, to get a green light ahead of a dinner gathering or something like that, I don’t know. I just I think I would make a lot of sense in terms of like reaching your objective of getting this accepted and getting the media board. That would be really appealing concept. I think so, anyway, thank you.
MICHAEL MINA: Just to follow up that, I do completely agree. But also, if I and the media and the policymakers say use this to help you socialize as a green light test, just imagine what happens when the media then says, just kidding, this didn’t work. And no media is going to pay attention to the millions of gatherings that go on where no outbreak happens. Media, it’s just not going to care. That’s going to be no media around the outbreaks that don’t happen. But the message is going to be all about the few times that it does happen. The public loses confidence very, very fast. So I don’t personally know how to control the media enough to counter those. How do you get a media infrastructure that is focused on negative outcomes and news to care about non news, to care about reporting on all of the parties that are happening where no outbreaks happen because of rapid tests? You know, it wasn’t done in the White House. The biggest news item around testing in the White House was the one day there was an outbreak, no media attention to the two hundred and fifty days where there was no outbreak. And that one event alone caused a massive reduction in confidence in the public globally about the use of rapid tests. We just saw another one with some guy from XPRIZE talking about a bad experience, these rapid tests poorly. But, you know, there was one event and that went viral. So I don’t really know how to message this in a way that I think that they can be most positively used, which is exactly what you’re describing, without also trying just battle this never ending fight of explaining the way these few the few outbreaks that do happen that become the center of attention. So it’s a really difficult thing in public health, always.
Q: Yeah, that’s interesting because when the plane lands safely, we don’t cover it. OK, thank you. Thanks very much.
MODERATOR: Next question.
Q: Hello, again. I have a question on the efficacy against the variants which some of vaccines have shown. So I’ve had some publications about Novavax which, according to the publication, the highest, basically and highest rates of efficacy against the variants. And I asked this question also to other experts who told me that the subunit can target a wider audience without actually telling me why. So I would like to ask you if you agree with that and if you agree for which reason this everybody should be more effective against violence.
MICHAEL MINA: Yeah, certainly, I mean, I think the subunit vaccines are potentially very, very important. It’s using updated understanding of biology and understanding of how the immune system works, rather than just taking the natural response to a spike protein, for example, or the natural spike protein and trying to just repeat what nature would normally have happen, subunit vaccines are a slightly different attempt to say, look, we can actually go a little bit rogue here. We can control. We can tell the immune system exactly what we want to see rather than hoping that it sees what we want to see. We’ve done that a little bit with the mRNA vaccines and all of the vaccines which are presenting the Spike protein. But you can then take that and go even further, and you could say, look, we’re actually not going to do even a full spike, we can actually pick and choose what subunits from this virus we want to put in and we can make a whole variety of them. We can decorate a nanoparticle with a whole bunch of different subunits if we want, and essentially to give somebody the experience of responding, getting to know and recognize all of these different proteins and pieces of proteins without actually having to give them a live attenuated or killed virus. And so in some ways, I mean, the mRNA vaccines could technically do very, very similar things where we could plug in multiple RNA strands into a single vaccine, into a single lipid capsule. But that would actually recommend that we consider doing that. I’m sure Moderna is thinking very hard on it. But that’s essentially, I mean, if this makes sense, this is taking an even more informed perspective as to what are the most likely subunits that people will respond to that could create immunity and placing them in and it can create more of a diverse immune response. My real major concern about all of the major vaccines, Novavax excluded, is that they are all giving the human body an introduction to the same protein, there’s very little diversity. There is some diversity because we can respond to all different parts of the protein. But there’s generally not a lot of diversity in the response. It’s all against the spike and they’re providing demand in other places. And so this is a way to give people more diversity and hopefully not lock them into a specific immune response in the future.
Q: Follow up question, given what you said, should we consider that the best strategy against the variants would be repurposing the subunit vaccines rather than mRNA vaccines, which are more complicated to manufacture because the world, which is because of the cold chain logistics?
MICHAEL MINA: Well, I don’t know. I think that they can all be used similar, like you could take any of these different vaccines and make them have multiple proteins. Novavax just as a technology that makes that it’s very explicit in the technology that you have a subunit vaccine, you can put multiple subunits on it. So I don’t know that it’s better or worse. It is showing that I think the diversity and the subunit approach is really honing in. We could do the same thing with the mRNA vaccines. There is some difference where the mRNA vaccines, you need to make sure that the proteins are going to fold appropriately, which is why your kind of stuck. But in giving whole protein and for the most part, not always, you could find different pieces of RNA. That alone will create a nicely folded part of that, like the receptor binding, given it’s very stable, even if you’re just making the receptor binding domain the spike. But to do that at scale, it just takes a little bit more finagling to ensure that the RNA strands that you’re putting in are going to fold appropriately into something that conforms to what’s naturally on the virus, whereas the Novavax that’s just already preprogrammed into their design of it.
Q: And the question about the drugs, so I was told that way back to talking about the concept of bio domain, which is the definition of variants, which is subject to mutation and variants, drugs, and actually target the default, which is more conservative, where the general genomics concept and actually, yeah, the antibodies produced by the vaccine cannot actually penetrate and target the proteins while actually the drugs can do it, killing the virus inside the cells after that completely. So why do you think that there is not enough effort on drugs as a future preventive measure? Or you think there is enough, but just that they cannot be developed as fast?
MICHAEL MINA: I think that there is a major hunt for small molecules for this virus. You know, but at the end of the day, drugs are great, but they require you to get infected to be beneficial. So certainly, all of the effort has been on the vaccine for and whether that’s the right approach or not is a slightly different question. But I think that vaccines, it’s just we know a little bit more in a way to really find a good small molecule, a therapeutic is going, you just have to hunt for it. You can use it. You can use educated guesses and what you should be hunting for. But the vaccine was just a little bit more straightforward to build. We had the technology is already there, and essentially DMORT vaccines in particular were essentially as simple as taking a sequence and plugging it in. So I think that it’s just the speed more than anything else. It’s also easier potentially to look at efficacy from a vaccine. I mean, you can do it with a drug trial, but then there’s so many biases that happen once you’re evaluating people who are already in the hospital, it’s a little bit more difficult to really see a beneficial effect relative to just preventing infection altogether.
Q: OK, thanks a lot.
MODERATOR: Next question.
Q: Hi, Dr. Mina, thanks for taking questions today. Here in Ohio, the J&J vaccine has gotten distributed out to community pharmacies, which tend to be in a far-flung corner of the state. And as you know, the original top line efficacy numbers for J&J as opposed to Moderna and Pfizer didn’t look as good. I realize there’s more to the picture than that. But the pharmacists I’m speaking to say that there’s a notion abroad that second rate vaccine is getting sent out to the sticks. How do you suggest pharmacists communicate with their patients to let them know that that’s not the case?
MICHAEL MINA: Well, the honest answer is we have to create more science. We need to continue to show data like we were discussing before that, hey, look, this isn’t a second-rate vaccine, that the data shows that this vaccine is working essentially as well. There’s a chance that it will actually work better. But there is so much fanfare around this, 94 percent in the acute phase after vaccination, which may not in the long run, might not last as long. I think that the best thing that pharmacist can do, and this is the same question is coming to me all the time now, should I get a second-rate vaccine, or should I wait for an appointment for Moderna or Pfizer, and I’m recommending get the J&J vaccine. And I actually think it might be better in the long run. I think the best thing to do is to, you know, depending on how savvy the person is that you’re talking to. Some people respond really well to data show that chart show, although the initial vaccine trials were not as encouraging, the real-life data, the field trials, you know, we’re starting to see benefit as we go further and further out in time that actually we were mistaken at the beginning in terms of the trial data, for example. But it is going to be a pretty hard message to confront because the J&J vaccine, specifically because it doesn’t have the same freezer requirements, it’s going to go to lower income areas. It’s going to go to places that don’t have minus 70-degree freezers at their disposal. So there’s going to be this very clear dichotomy in terms of where this particular vaccine is going and when you couple that to the message that it’s less effective. That’s a pretty hard pill to swallow. It’s a pretty hard thing to change and to clarify and to say no, I know we said in the trials that it’s less effective, but it’s actually more people are going to be skeptical. And that’s why I think we just have to keep creating more data, keep doing the post market evaluations. And this is a good place for the media to really, again, put a positive media, say, look, this is actually working really well, this is exceeding expectations, whereas maybe some of the other vaccines might be slightly not exceeding expectations, for example, the trials. And so I think that it can be balanced, but it is going to be a I think it’s going to take a lot of messaging.
Q: OK, thank you.
MODERATOR: Next question.
Q: Hi, Dr. Mina, thanks again for doing this. My question, I have two questions, actually. My first is, can getting the COVID-19 vaccine cause you to test positive on a COVID test, why or why not? And I guess differentiate between the diagnostic and the antibody test. And then I’ll ask my second question when you’re done.
MICHAEL MINA: It will not cause you to be positive on a viral test. The vaccines are giving us shots and there’s really no reason for the protein mRNA to make its way up into the nose where we’re sampling, for example, the antigen test, that’s just a different compartment and most of the tests don’t look for Spike, are looking for different parts. So there’s essentially no way that the current vaccines would cause somebody to turn positive. Of course, if it was a flu mist kind of spray vaccine for a coronavirus, that would be different. But that’s not what any of these are. For the serologies, that’s really important. And this is going to be a pretty difficult thing. I think that for the sake of the physicians, most physicians in the world don’t really understand this stuff. And it’s confusing to most people, so what I think we should start doing is label antibody test. Antibody test will turn positive after somebody gets a vaccine, if they’re looking for antibodies against the spike protein or any of the other subunits and proteins that are in the vaccine. But they will not turn positive if it’s an antibody looking for nuclear capsid, which a lot of them are. So this is going to lead to a massive amount of confusion, I think, where doctors are going to go and order an antibody test for a patient or patients going to do is to direct to consumer antibody test. They might be looking for antibodies against nuclear capsid. They’re going to say, what the heck, I just got vaccinated two months ago. I can’t believe I’m not protected anymore. But really, they’re just looking for antibodies against the wrong protein. And so probably what we should start doing and maybe it’s already being done, I’m not sure is the labeling the like will not detect a response against X, Y and Z vaccines that should be plastered on the ordering farms and very, very clear on the box because it is a confusing issue for many people.
Q: Thank you for explaining that. Appreciate it. My second question was, is it safe to get the COVID vaccine if you’ve recently been vaccinated for something else like shingles, influenza, should you kind of plan those other vaccines around when you get your vaccine?
MICHAEL MINA: Well, I would say we certainly don’t have the data to back up one answer versus the other, it’s something that I actually study in my laboratory is how do immunological responses to one thing impact one vaccine impact another? Sometimes it’s actually beneficial, sometimes it’s not. And I would say in this case, it’s generally my expectation, which isn’t backed by data, but it’s backed by knowledge of the immune system and started doing this for other pathogens and responses, is that there won’t be a major impact, that there won’t be a massive reduction in your ability to respond to coronavirus vaccine if you’ve just gotten rubella vaccine or something like that or flu vaccine. Sometimes they actually bolster each other. You have an immune response that stimulates all the machinery, and the machinery is shared between the responses. So you can actually get a synergistic effect. And so I don’t think that it should be top of mind for people. But also, I wouldn’t necessarily recommend somebody go in on day one and get one vaccine and then go in on day two like, give if you do that, maybe give your immune system a week in between or something along those lines to just kind of reset that is completely without data to back it up. May as well just kind of play it on a slightly more conservative end of things, but my expectation is there would be a massive degradation and response.
Q: All right. Thank you.
MODERATOR: Next question.
Q: Thank you, Nicole. Thank you, Dr. Mina. What I would like to ask about is I’m working on a story to explain to the public what is the current state of the pandemic here in the U.S.? So we’ve been hearing about cases dropping, vaccination accelerating. And what I would like to ask you is if you believe that you are more optimistic about the state of the pandemic today in the U.S., if we are looking at better days ahead in the country or if you expect another wave?
MICHAEL MINA: I mean, relative to where I was at this time last year. Hugely optimistic. Relative to where I was in November of last year, hugely optimistic. Overall, I would say, you know, I’m a little bit depressed about our general response, with the single exception of the vaccine response, and I’m frustrated with the global inability to really. You know, not every country, but many countries inability to deal with this virus in an updated way, but I think moving forward, we should all be pretty darn optimistic that the vaccines do seem to be working. They’re not going to be the end of this. But we never thought that we are just going to end this pandemic. We’re going to see a decline. We’re going to then see new cases emerge again in the fall. And in Brazil, the seasonality is a little different, but we will probably continue to see outbreaks. But I do believe that the worst part of it is hopefully behind us, of course, the major combat is, and I have been and remain concerned that that a big mutation could happen, where that kind of makes the virus seem slightly blind to the immune system. And if that happens, even if the mortality and hospitalization is much less, I think the population is fatigued. People just want this to be over. So even small blips are going to be big knocks and people’s confidence. But I do think that we’re at a point now where we can be optimistic that at least probably the true worst of it is over. And now we’re kind of in this long haul of just becoming accustomed to it, getting enough people immune. The virus isn’t going to go away, but it will begin to do less and less damage because people are going to be immune. So even if they get sick, they’re not going to die. For example, even if they get infected, they won’t end up in the hospital. But I do think that we don’t want people just to think, hey, this is going to be done by April. It’s just not. The virus is going to continue transmitting all across the globe. We’re going to continue seeing mutations. It’s still going to be front page news for a long time. People are going to still be tired and worn out by it. But hopefully we can look at the vaccines and we can really start taking a very measured approach to it, where we take a big step back and we say, what is our goal with this virus? Is our goal to get to zero or is our goal just to stop hospitalizations and deaths or decrease them to a level that is sufficient to get society back and running? And ideally, get us into a pattern that’s a little bit more endurable than we have been. And so I’m optimistic, but also recognizing very much that this isn’t the end of it.
Q: And just a quick follow up question, you mentioned the mutations. Is the mutation that came from Brazil something that you are most worried about? Is this a special source of worry for you?
MICHAEL MINA: I want to be really clear that while that particular mutation seems worrying, yes, I do not want it to be considered a Brazilian variant or Brazilian mutation, for example. There is convergence where that mutation is popping up elsewhere. The more we sequence, the more we find similar mutations. I think we should be very cognizant that probably the US may have been the greatest hotbed for these mutations. We just weren’t we just weren’t sequencing to look for them. But yes, I mean, the short answer is that that mutation, which is which arose in Brazil, that arose elsewhere in many different places, I think is of concern because we do see that it is impacting immunity. That particular one isn’t my greatest concern. But my concern is that that we might have only seen the beginning of what these mutations are capable of. Will we see in the next six months a new suite of mutations that build off of the current ones that really do greater damage to our immune system’s ability to recognize the virus? That’s what I’m concerned about. I sure hope it doesn’t happen. But I think that this should be considered some bit of foreshadowing for what might come.
Q: Thank you, Dr. Mina.
MODERATOR: Next question.
Q: Actually, I wanted to build on that previous question, you know, the Minnesota Department of Health sequenced the first P1 case in Minnesota and they had a right up first case in the states and they had a write up about it in MMWR this week. And one thing I wanted to ask you about is one thing that becomes pretty clear if you read the write up is the sequencing doesn’t happen quick. Like, that patient was hospitalized nine days, but for nine days, and the sequencing was after that even. I mean, all of which kind of underscores that, like, to someone like me, who knows not a lot, I might think, oh, you know, more contagious thing, public health is going to be running these sequences. And if they figure out, I’ve got P1 one, they’re going to give me a call and say, hey, you really need to stay home. But I gather that’s not how this works. And I wondered, given what you just said about the concern going forward about even worse variants, if they ever were to happen, what’s the utility, is there ever going to be utility of sequencing for, like containing or is sequencing just about knowing?
MICHAEL MINA: Yeah, your question is one of the most important ones, and it is, it’s an updated version of the same thing that I’ve been talking about for a year. Which just without going into the whole issue of rapid tests, what I have been trying to suggest is for a long time at the beginning, PCR was just so slow and remains too slow to really be able to act to block transmission, especially when it was seven days people were ordering PCR tests and the result was not coming back. And what I would consider to be an actionable timeframe. Even with the improvements in PCR testing, most tests are still not coming back with what I deem to be an actionable timeframe to stop transmission. It’s why I’ve been pushing these rapid tests so much, because they are an actionable timeframe. The sequencing issue and the mutations just steps it up a notch. Not only are we getting people results back in what it’s really an actionable timeframe and getting them results with enough frequency so that we’re actually catching them before they transmit. Now it goes another step or saying we don’t just need to know who is positive, who is potentially transmissible, but we want to know who to prioritize and really work on those people to help them not transmit because they have this dangerous strain that’s even worse than the first one. We’re not even close to that, not even close. So the best we can do at the moment is either build newer technologies that will detect the mutations that are important right there in the test itself so we don’t have to sequence and then do sequencing in the back end to make sure we’re not missing anything. That would probably be a good way, but we don’t know the technologies and tools authorized yet to really make that a reality. I do think, though, that your question is absolutely crucial. We should be figuring out many new ways to be able to identify people, especially prioritize those people who need to be prioritized to tell them not to transmit. This also happened, for example, early on, back in April or May, I was talking to the CDC and I said, look, we should really be prioritizing contact tracing to those people with really high viral loads because that’s the best bang for your buck to stop transmission. But even that was too much. You know, we haven’t prioritized contact tracing based on viral load. And so I think while I would love to see sequenced to get to a speed that it can actually be actionable, we’re nowhere close to it. But we do see, you know, we have these new sequencing devices like Oxford Nanopore, and you can do sequencing practically on the spot so that there is actually a reality of a world where we could potentially do this. But it’s not happening at scale at the moment.
Q: Sorry, just really quick, what was that last technology you mentioned or compelling?
MICHAEL MINA: I’m sorry, it’s something it’s a company called Oxford Nanopore. It’s a sequencing device. I don’t have one around here, it’s in my lab. But it’s like the size of an iPhone and you just put a sample straight on to it and it can sequence in real time. So you could envision if let’s say you had a rapid testing program set up on the street and you wanted to test people rapidly, you could actually find somebody who is positive and sequenced them all within a matter within a very, very short timeframe. You take the positive specimen, you put it straight onto the nanopore sequencing device and you’d have a result potentially very, very quickly. So there’s a lot that we could do, but it’s not quite as simple as just kind of one to the next. The sequencing still takes a step, but there is there are ways that we could be able to do this in a much faster fashion and then we generally are doing it. It’s part of what I would consider if we were to try to prepare for the next pandemic and try to actually use the tools of the 21st century, you know. These are the kinds of tools we would want to be building on, we would want to be thinking, what do we have at our disposal? That’s fast and frequent and accessible, including sequencing and really rise to the occasion and the challenge of this pandemic, which I would say biometrics we haven’t done specifically in the testing space, we really haven’t done one bit.
Q: OK, thank you.
MODERATOR: Next question.
Q: Hi, thanks. I want to ask what the latest we know on how much the vaccines cut transmission of the virus? My understanding is we know it cuts it a lot, but it doesn’t cut it down to zero percent chance that you would spread it to somebody. I mean, is that right? And what do you think the implications for even after you’re fully vaccinated? Is there some period of time where you should keep wearing a mask when you’re like on the subway or around a group of people who might not be vaccinated?
MICHAEL MINA: Yeah, it’s a great question, it’s one of the most important and again, one that we should have paid attention to when we started the vaccine trials. One of the best ways that we have to look at this is purely just to look at how many people have detectable virus regardless of symptom onset or anything, how many people have detectable virus over the duration after they get vaccinated. And what do those titers look like when they do get it? What we’ve seen in the data, which all of which has potential for massive bias, is right now. But in the data that we do have, we see around three to four or five CT value difference. We’ve seen that some people can still get to decent titers of virus using viral loads even after being vaccinated. But we do believe with intuition and, you know, would essentially suggest that if people aren’t getting sick, they’re probably not going to transmit as much. I don’t think there’s a lot of question about that. But does it go to zero? Probably not, no. As we start to see antibodies decay more and more after people get vaccinated, a natural process, normal, will we end up seeing transmission start to get increase even more again? So we kind of see a lull after people get back to the transmission and start increasing again from people that may very well happen. It’s actually pretty hard to ensure that you have enough antibodies right there to stop any replication. You might be able to stop the disease inside of you, but to stop all replication and stop all transmission is difficult. You need antibodies kind of sitting there at the ready to go all the time. Once your plasma blast will die off after a few months, your antibodies go way down. And whether or not you have enough in your mucus to really prevent any replication, it’s a question that we’re waiting to see the answers to. So I think that we’re going to see a large reduction, though, but I don’t think we should feel that we’re in the clear for no transmission after vaccination.
Q: So I mean, it is just a personal choice, but I mean, does that delay our, quote unquote, return to normal if we still need to be worried some about transmission?
MICHAEL MINA: Well, that’s kind of gets to what I was saying earlier, where we really have to ask the question, what’s the goal here? And what is our end game? Is our end game to stop all cases? Or is our end game to stop all hospitalizations and deaths? There’s nothing wrong with people getting respiratory virus infections if they’re not killing you and if they’re not sending you to the hospital. It’s part of our natural evolution, usually unfortunate starts as babies. And so by the time you’re an adult, you have built up enough immunity that it really isn’t a big issue anymore for that particular virus. In this case, that didn’t happen. And so there’s a part of me, actually, if I take a big step back and this is a little bit controversial for a lot, maybe we actually want to do something totally different. And we say, OK, people who are vaccinated, we actually want some amount of transmission to continue to persist so that people continue to get naturally boosted and keep their immunity and keep kind of boosting their immunity. As long as we have enough of the vulnerable people protected. That massive outbreaks don’t happen if people don’t end up in the hospital. It’s OK to have the virus transmit and continuing to boost the immune system over and over. We’ll just set us up for our future selves to be in even better shape. So how to balance that? That’s a lot of the kind of work that we try to look at to say what would be the consequences of one versus the other over a multi-year period of time using mathematical and epidemiological models.
Q: Thank you.
MODERATOR: Next question.
Q: Hi, thank you, there has been some anecdotal chatter that perhaps people with so-called long COVID or post-COVID may feel better after the vaccine. I’m wondering if, you know, if anyone is actually studying that in a formal way and or if it’s more likely just a placebo effect?
MICHAEL MINA: Great question, I wouldn’t want to say it’s a placebo effect right now. I think that there are reasons to believe that it could be that that kind of benefit could happen. You know, there has been some suggestions that maybe you’re distracting the immune system and like pulling some of those inflammatory cells that would otherwise be attacking, causing long COVID, which you don’t fully understand yet, to sort of divert their energy and attention to something else for a little while. So you might see a brief reprieve. Or maybe there is some viral reservoir that’s actually sticking around for a little while and you’re boosting the immune system to really knock it out. It hasn’t been clear. But I do think that there’s a likelihood that that this is a real phenomenon where we’re giving vaccines could boost your recovery from long COVID. I don’t think this formally studying it at the moment, but I wouldn’t be surprised if there are people doing formal trials.
Q: Thank you.
MODERATOR: And it looks like that is our last question. It’s also about 12:30. Do you have any comments you like to make before we wrap up today?
MICHAEL MINA: No, I don’t today. I think this was a nice reprieve from talking about rapid tests today, and my love is immunology and vaccines, so I’m happy to take those kinds of questions any time.
This concludes the March 5th press conference.