You’re listening to a press conference from the Harvard T.H. Chan School of Public Health with Michael Mina, assistant professor of epidemiology. This call was recorded at 11:30 a.m. Eastern Time on Monday, May 18.
Previous press conferences are linked at the bottom of this transcript.
MODERATOR: Alright. Dr. Mina, do you have any opening remarks for today?
MICHAEL MINA: I don’t. I’ll just take questions.
MODERATOR: Alright, then we’ll get straight to it. First question.
Q: Yes. Good morning. Can you hear me OK?
MICHAEL MINA: Yeah.
Q: Great. So, my question has to do with serologic test. And I understand from some sources that the FDA, NIH, CDC and BARDA are working on an independent evaluation of what they’re calling mainlines serologic test, Abbott, Roche, those companies. I would like to know if. – first of all, I’m assuming some familiarity with this on your part, but how this is going to work with the FDA data that they’re requiring from these companies? And then the second part of that question is, have you heard when the data, the results are going to be released? Because I know a lot of states and labs are waiting on that information.
MICHAEL MINA: So, I don’t know how it’s going to interact with the data. I can only, my anticipation of that is that it’s mostly going to be an evaluation that will come out with some report, not so much something that’s going to be legally bound by the FDA, for example. But I don’t actually have much additional information. I definitely don’t know when they’re planning to have the results out. I think it’s, my feeling about it is that it’s something that is necessary at this point time.
And, you know, it’s the type of the type of coordinated effort that I think really does need to be happening to ensure that these houses are all working as anticipated or at least as reported by the companies themselves. So, I think given their reach, it’s extremely important to have good quality metrics rather than just the metrics that the companies actually provide to the FDA because they’re oftentimes best-case scenario, if you will. So, but otherwise, I don’t actually have a lot more information on this.
Q: Just to clarify, are these like CDC and NIH – are they running their own tests on them? Is that how that works, to provide that extra layer of protection that you’re talking about?
MICHAEL MINA: Well, the idea would be that they would have – I believe this is how it’s working, but I don’t have all the details is that they would have samples that are consistent, the same samples essentially, and running them on distinct platforms to understand how they compare across each other and then to try to find a good panel of samples that will actually be known to be positive or negative. And you can work with those to do some sort of coordinated assay trialing and you’re able to actually compare apples to apples.
Whereas most of the time, iif you’re taking all different assays and everyone’s using their own sample set, you really don’t know which ones are the positive and negative ones, it’s very difficult to really compare them in any useful way while still being able to say with clarity what the real sort of ground truth is. I think a coordinated effort where you have a set of samples that can all be used is the approach.
Q: Thank you.
MODERATOR: Next question.
Q: Hi. Thanks very much for doing this. So, I have a question about immunity and the ongoing question of whether initial infection confers immunity. And I guess I’m – how do you know what immunity looks like? Like if you’re looking at cells or blood or like how do you know what immune response is actually protective?
MICHAEL MINA: Well, so that’s the million dollar question at the moment and the way that you do that, usually, in this case you have to have pretty large studies, to be honest, to find what you’re what I believe you’re asking about is how do you know, let’s say an ELISA-based test for an antibody. You need to, you want to ideally find out, is there a value that can reasonably, that when somebody is above that value, you can reasonably say with confidence that they are protected from further infection. And so to really get at that question, you have to do population studies where you follow people over time and and you say this group of people has an antibody test which says that they’re above a certain number and these people are still positive, but are below a different number. And can you find a threshold number that will suggest that people are immune and not able to get the infection?
So one way to do it would be, and this is what we’re doing here and other groups are doing around the country, is to follow health care workers or other people who might have a decent risk of exposure and are also able to participate in these studies. You’d follow them over time, find the people who are positive having been recovered from the infection and then follow them to see and do some of them become ill again. Do some of them not become sick again? And you also want to be swabbing them on a regular basis to see do some of them become colonized asymptomatically? And if so, do the viral titers that they become colonized with get to levels that we would be concerned that they would become onward transmitters of the virus?
So those who you just have to kind of wait and see in the absence of doing clinical studies where you actually challenge, you give people the infection. And I don’t believe that with this virus, we are anywhere near doing that. But that’s certainly, there is a whole ecosystem of research that actually performs human challenge studies where you try to answer these questions by actually giving somebody pneumococcus or influenza or something along those lines. But with this coronavirus, we’re not currently doing it.
Q: And you do you need to know that, I guess what sort of what the immune response looks like that confers protection in order to know if like the immune response generated by a vaccine is protective? Like, do you need to have that established first?
MICHAEL MINA: Absolutely. It’s the same idea with the vaccine. You would – it could be different with the vaccine, because if you have a very targeted vaccine in terms of the protein that the vaccine is encoding, you might have as protective or more protective a response, but ultimately potentially a lower, titer on an ELISA. And that gets into the nuances of how we measure antibodies and how you can interpret a titer of an antibody test. But yes, the short answer is that’s how efficacy trials work. So, we give people vaccines, the primary endpoint is usually if you’ve had the vaccine, do you get the infection later on? But then secondary endpoints might aim to explore the quantitative details surrounding that protection.
Q: Thanks very much.
MODERATOR: Next question.
Q: Morning, Dr. Mina. Thank you once again for all this perspective. It’s been a while since I’ve asked this question and I guess we know a little more now. If you could for laypeople, what’s your best guess now on both the infectiousness and the death rates of COVID-19 compared to seasonal flu? And I ask because people are still trying to make that comparison and use it to, you know.
MICHAEL MINA: I do think that this is spread more broadly than we’ve recognized from testing, of course. And I think New York City is probably – my guess is that of all the major cities, New York City is certainly where it’s been hit the hardest. And a couple of weeks ago or a few weeks ago now, it was about 20 percent seropositivity. It might be maybe as much as 30 percent at the moment and I do think it’s able to, it has shown that it is an extremely transmissible pathogen in the right environments.
And so that is, you know, whether it’s an R0 of two to three or an R0 of five, I think that is going to really depend on the ecosystem and the environment that it’s in in terms of its transmissibility and how much it’s spreading. Where we might expect, for example, that rural areas, it might spread to fewer people in the very high dense places like New York City, it might just be structurally at a disadvantage in terms of being able to contain and control the virus.
In terms of mortality, I am certainly going to refrain from giving, from even attempting, a mortality rate per say, but I will continue to drive home the message that there’s not a mortality rate associated with this virus, there’s a spectrum. So statistically, anytime we see epidemiologically, if we see a distribution that is highly skewed, in this case the skew is towards the older age groups in a very profound way, we don’t usually want to take an average mortality rate because it doesn’t actually represent the average across the population. And so we know that the average mortality rate is going to be very different and driven primarily by the deaths happening in the very old age classes, so those 75 and older, many of whom, for example, are hospice patients, and if that turns out to be point five or point eight percent mortality, that doesn’t on average across the whole population, and it doesn’t mean that a 15 year old has point five percent risk of dying if they become infected. It’s very, very skewed. And we know that that average is driven entirely by the upper age brackets.
So I would say in general with this virus, it could be that, and I do think that this will become the case once the dust settles and we get good seroprevalence, I think for the very young age classes, this is going to potentially be lower mortality than the flu. That’s especially in very young that that’s likely the case. And then in the very old age classes, I think that it probably will be higher than the flu. So it will cross that threshold at some point during age and that makes it a unique virus compared to influenza.
I do think that there’s something else that – it’s interesting I’ve been thinking a lot about this in the context of seasonal coronaviruses, the ones we see every year. We don’t know if this virus is actually that different from those seasonal coronaviruses in many ways, because we’ve never had – if we dropped one of those, if we had another earth and we had a whole group of humans who had never seen HKU1, one of those seasonal coronaviruses, and we dropped that seasonal virus, which current day we don’t really care too much about it and infects people and they get over it, if we dropped it on a whole naive population across the whole age spectrum, would we see a similar effect as we’re seeing with this virus? It could be because essentially by the time you become old in our population, you’ve already seen these seasonal coronaviruses many times so you’ve built up immunity. So that’s a different story. But I think the case fatality or the infection fatality rate is going to be not just linked to age, but also to preexisting immunity, which in this virus we don’t have any. But we anticipate that in the future there is not just sort of one set infection fatality rate. It really depends on how many times you maybe have seen the virus over the course of your life.
Q: Quick follow, because you brought this up and my apologies to my colleagues with all their hands up. You said this virus may not be all that different from common coronaviruses that cause the common cold. What do you mean by that, not that different?
MICHAEL MINA: Well, we know that this virus isn’t killing kids in very high numbers, you know, barely at all for the youngest. And we know that with the regular seasonal coronaviruses, people get exposed to those when they’re babies. We measure that all the time. And so the question with a regular seasonal coronavirus, if you actually could find somebody on Earth who was eighty five years old and had somehow managed to go their whole life without seeing a coronavirus, and you gave them one of the regular seasonal coronaviruses that we don’t normally think much of, it could be that their risk of mortality from that regular seasonal coronavirus could be just as high as this novel one. So the thing that could be making this novel one so deadly to elderly people, for example, is really just the complete lack of preexisting immunity and not having had potentially hundreds of exposures to the virus over the course of a lifetime by the time somebody is 65 or 70. So that, you know, we just don’t know that, I would say.
So, it could be that this is a very distinct virus in the way it’s infecting people and that it’s very unique in that sense. But in general, I think what one of the main things we don’t know is how unique is it in terms of its biology or is it really the host biology and the lack of exposure history that’s really driving the deaths?
Q: Fascinating. Thank you.
MODERATOR: Next question.
Q: Thank you very much for doing this. A question that was sort of related to make antibodies, but on the other side, there’s been a lot of companies working on neutralizing monoclonal antibodies in the lab. There was actually one last week on Friday that claimed that they had developed a cure based on this method. And what they had really done was made one antibody and shown that it worked in vitro and not sort of in any animal models or humans either. I was wondering if you could just sort of talked a bit about what the difference is between showing an antibody works in vitro and actually something you can bring the clinic versus something that would actually have an impact sort of on the illness in patients.
MICHAEL MINA: Yeah, it’s a great question. So that has to do a lot with a number of things. You know, how the antibody distributes through the body and once it gets in. So, it’s not – I would say that we have to take most early findings, in vitro findings with a little bit of a grain of salt. Well, with a lot of a grain of salt. For example, and not to you know, a few weeks ago, Trump said to pour bleach into your body or I forget what he said, but the idea that just doing it in vitro, we can pour bleach onto a petri dish and certainly kill all the virus that’s on it. But that doesn’t mean that we can use that as a treatment. And the same thing for monoclonals. We have to be very careful how we interpret any therapeutic data, especially in the pre-animal model data, because you can give it at very super physiological concentrations in vitro. And the question is, will it still have that type of profound neutralizing capacity once you’re giving it in a way that’s tolerable and it distributes throughout the human.
So that’s just something to keep in mind. And to really be able to understand that, we do have to do first animal studies to see if it can distribute appropriately and prevent a natural or an infection in animal models. And then we can give it to humans as long as it appears safe. We do Phase 1 and 2. And the nice thing is a lot of the core technology for some of these monoclonal therapeutics has been created and we give monoclonal antibodies for all sorts of things currently, whether it’s for cancer or arthritis or infectious diseases. And so, we know how to produce them in a safe way. And so, then the question is, can they at the concentrations we can give them safely, will they still neutralize and actually reach the compartments that they need to get at the virus?
So, I think the data that came out last week. It was way overblown. It was an overblown headline, I think, and saying that something neutralizes a virus in vitro is very, very different from suggesting that it’s going to be useful in humans. But at the very least, it does show – one of the big barriers in terms of monoclonal antibody production and development research is finding the monoclonal that can actually bind to the pathogen in a way that will be neutralizing. So, it’s not an insignificant step that they took. It’s just not correct to say that it’s curing the virus from a petri dish. That’s a weird way to put it. But it did seem to bind and neutralize, which is a great first step. And then we’ll be excited to see what happens in the animal models.
Q: And just quick follow here, how confident are you about sort of the antibodies being made by some of the bigger companies that they’re going to have an impact on this virus?
MICHAEL MINA: If I were putting my money somewhere, I’d put it on monoclonals as a very good therapeutic. I think I’ve said that to somebody months ago and I still feel that way. I think that we can essentially use what humans are doing anyway, we don’t have to go out and find only synthetic compounds of small molecules. We collect a whole bunch of plasma cells from people who have been able to clear the virus. We screen those plasma cells, we collect them, we sequence them, we produce the antibodies that those plasma cells that nature was essentially producing or evolution was producing anyway, and we can copy it. And as far as I’m concerned, one of the best ways to find new therapeutics is to just copy what evolution has trained us to do.
MODERATOR: Next question.
Q: Hi. I wanted to ask on getting to this reopening question. We’ve still seen, you know, we’ve seen several states, you know, with still record high, you know, new cases per day that are in various stages still up starting to reopen. So, I wonder if that’s a concern to you. Does that mean they’re starting to reopen too soon? And does that – and how does the testing factor into that? I’ve seen some of the governors are saying, oh, well, that’s only because we’re testing more, so now we’re picking up new cases, so that doesn’t necessarily mean it’s a warning sign that our numbers are going up. So, what do you make of that argument?
MICHAEL MINA: Yeah, I think I very much understand the need to be opening right now, and I know we’re starting to open up here and everywhere else in the country is opening up. And I get very, very – I think myself and many of my colleagues are very nervous about this idea of opening up this early without the right pieces in place.
But it does need to happen in a way and whether we’re doing it correctly or not. Certainly we are on the brink of sort of, I think, societal collapse, if we don’t start doing, if we don’t start figuring out how to get things in order so we can open up safely very soon anyway. So, I do believe that this is something that needs to go forward. I might have missed the actual question.
Q: Oh, yeah. I mean, if they say, oh, well say you have a record daily number of new cases, but you say, oh, well, our testing is we’ve really ramped up our testing, so that explains it. I mean, is that a good explanation or not?
MICHAEL MINA: No, I would say there’s a very complex dynamic between testing and the number of cases that are coming in, and some places you will start, as long as you’re really increasing testing, you’ll probably continue to find more cases. So we really have to be looking at the ratio or the percentage of positives. But we also have to do that in light of who we’re testing. If we continue to only test hospitalized patients, for example, then that’s not going to give us a good representation of what’s happening in the community.
But I do think a lot of the increases in numbers that have been happening are probably very likely attributed to increased testing, which I think is a good thing. We can look at the fraction positive and we see that going down. So it does suggest that that’s happening, but we may very well – we need to figure out how to interpret this data really soon, because we’re about to see increases in cases again as everyone opens up. And I think we need to better understand all the nuances of the testing that is going on. I think it’d be great, for example, to have a database to know for every test that’s being taken, it should be associated with some sort of metadata that suggests why it’s being taken. And that could be reported to states. Is this somebody who’s healthy that’s coming in and just wanting to be screened, or is this a drive thru site that’s really focusing on sick people?
And so if we were collecting – we’re not generally collecting that metadata. We should be nationally and then we would actually be able to interpret the changing numbers in a really robust way. But all this is wrapped up in the sense that the US really has no sense of how to do public health in practice. We have some of the best experts in public health in the world, but they’re wrapped up in the academic or world in large part and some other agencies. But we don’t have sort of the infrastructure built, of course, to do these types of things. But I think we can work towards it. And part of it would be collecting a different type of data from these people.
Q: Would you still like to, I mean, it would still be a better sign if the new cases per day were declining, right? I mean, that would be more confidence inspiring about this.
MICHAEL MINA: Absolutely. Yeah. If if the new cases per day as long as the – especially if the test numbers are going up and the absolute number of new cases are going down, then absolutely. I think that that would be terrific if we could see that and we are seeing that in some places, but some places we’re seeing them go up. And yeah, we would like to see absolute numbers go down as long as it’s not a reflection of reduced testing.
Q: Mm hmm. Thanks.
MODERATOR: Next question.
Q: Thank you very much. Hi. You probably heard Moderna put out some results today on their vaccine candidate, and I’m just, it has me wondering what is realistic to expect of a COVID-19 vaccine, you know, respiratory pathogen vaccine? Do you think that we’re going to be able to get vaccines that prevent infection entirely or vaccines that prevent severe infection?
MICHAEL MINA: I don’t think that this is going to be a virus that’s going to be easily, that’s going to be easy to vaccinate with the goal of sterilizing immunity and complete protection. If natural coronaviruses don’t do it, I don’t think that we should necessarily expect or have the anticipation that we’ll be able to get there with the vaccine. However, if we can create a vaccine that maybe doesn’t give you complete protection from colonization of the virus, but that does give you protection personally, then in some ways, that might be enough because we might still be able to transmit it to each other, but if we’re transmitting it to other people who have already had the vaccine as well, then they probably won’t get sick. And if anything, what we see with a lot of infectious diseases, for example, is you can actually get natural boosting.
So in some ways, it might actually be better to create vaccines that don’t necessarily give complete protection, because then you don’t necessarily have to keep going and getting a vaccine every year. For example, you could rely on some level of natural exposure as long as all the people who are at particular risk have been given the opportunity to get vaccinated as well. So there is a tradeoff there. But I could see that happening as something that would actually be, you could see the silver lining, I suppose, in having a vaccine that doesn’t give complete protection.
And, you know, for example, we see the downfall of a vaccine that does cause- it’s not really the downfall, but measles vaccine or mumps vaccine causes very high levels of protection for some amount of time, as does chicken pox and chicken pox is actually a good example. People can relate to it. We’ve gotten rid of chicken pox and largely gotten rid of chicken pox transmission in the population. But we are seeing a slight downside of that with increased shingles was anticipated. So, there’s actually some benefit of having, if you can keep transmission in a population at very low levels without people getting sick, there can be benefit for the durability of immunity.
Q: Thanks. Can I ask a follow up question? OK. The Moderna results. They have just a very little bit of data and for people with neutralizing antibodies and the 25 microgram and one hundred microgram doses. But then they should have essentially tried to suggest that they also probably could conclude that all forty five people for whom they currently have data are protected because they said the others had binding antibodies and after a point, binding antibodies and neutralizing antibodies apparently correlate on a linear basis. Is that true?
MICHAEL MINA: That generally is true. And we see that and that’s one of the things we look for. So if we take, I’m just thinking, the last we did it for was rubella. If you plot out rubella antibody titers against neutralization above a certain level, you do start to see decent correlation. And we can use the strength of that correlation. And part of it is because just looking at binding antibody titers, you might be getting an average of a whole bunch of different antibodies, some of which might be neutralizing, some of which might be just bystander antibodies that are doing nothing but they’re adding to the antibody binding signal. But above a certain level, you assume that the average person who has that level of binding antibodies, on ELISA for example, will have wrapped up in their binding antibodies, neutralizing antibodies. So that’s something we see and we tried to design vaccines in order to elicit those neutralizing antibodies.
We could go in a different way. If we designed vaccines that only elicited non-neutralizing antibodies, then I don’t think we would see that type of correlation. But as long as we’re trying to design them specifically to derive neutralizing antibodies by cutting the epitope that would be bound to neutralize the virus as part of the vaccine, then we actually can get a pretty good signal that correlates. And then just one more step is what needs to be taken to figure out, now you have this nice correlation between binding and neutralizing so when you go to the big population studies, you don’t necessarily need to look for neutralization once that correlation has been met. You then just need to find the threshold of protection for a binding signal to start getting and what threshold will actually lead to protection will be the next step that has to be taken.
Q: Would that be considered parts of the correlates of protection?
MICHAEL MINA: That’s exactly what that is.
Q: Thanks much.
MODERATOR: Next question.
Q: Doctor, thanks for doing this. Appreciate it, as always.
MICHAEL MINA: Sure.
Q: You mentioned a few minutes ago that you and your colleagues are nervous about reopening without the proper pieces in place. What are those pieces?
MICHAEL MINA: Well, I’m not sure. I think the pieces I think would be a) a really clear plan for how we’re monitoring for outbreaks. I would say that we don’t have a good plan. Even in the nursing homes, we don’t have a good plan. And so that for me is step number one. What is the plan? What are the measures? What are the metrics we’re looking for? I would like to see us open up in a way that we learn from vaccine trials and we learned from therapeutic studies and biological research where there are risks involved, we usually have a very clear plan. And that plan usually includes some data, some group of people that monitor for very specific outcomes and they stop a trial, for example, if those outcomes are met and those could be negative or positive.
And I think, you know, there’s no reason why we shouldn’t be treating the reopening of society somewhat as an experiment. Not that we should be experimenting on people in the population, but that we should be using it as an opportunity to take a really data driven approach to understand what it is we’re doing, because it’s very likely that we will have second waves of this infection of this virus, and we might find ourselves having to repeat. So it means we’ll learn as much as we can at the moment and also have as much set in place early on so that if there was some sort of data monitoring board, if you will, public health monitoring going on and we had a very clear metric that would say to a governor or a mayor, hey, you’ve hit this threshold, your city is about to experience a large outbreak if you don’t slow things down.
But so far, I haven’t seen anyone come out with very clear plans and clear, well-thought out descriptions of what those might be. I know that, you know, we are opening or starting phase one of opening up in Massachusetts and Boston today. And I don’t know that here we necessarily have those plans in place. Some of us are working on developing them in conjunction with various policy makers and such. But across the whole country, I don’t think there’s robust plans. So some of that might be testing, some of that might be partnering with companies that monitor people through mobile apps, that might be partnering with school systems and nurses, and it could be any number of different approaches. But having a plan anyway and a way to recognize that danger is upon us, I think is the most essential piece that I see missing.
Q: There has been talk of testing people as they go back to work, that maybe companies should be tasked with the job of testing people. Would that be part of what you would see as a good plan?
MICHAEL MINA: Absolutely. And I think it could very well be in particular colleges and universities, laboratories, companies. I think that, you know, especially places where outbreaks are potentially likely, I think that testing should be part of the plan. The problem at the moment is that testing is still extraordinarily difficult for the average person or the average company to get in any volume. We can barely do it in Boston and we have one of the highest throughput testing facilities in the country. We have two in the immediate vicinity of Boston between Quest and the Broad, and just getting the supplies to do the testing has proved extremely difficult. I spend my life these days trying to do a lot of this.
And so, I think that while I would like to see companies be able to incorporate testing, I don’t think there is yet a good model for how to do it. Some of the things that I’m thinking about are could we actually have everyone do daily testing but pool their samples together and, you know, have some sort of stat test that you could perform on a pool of samples, and very quickly, you know, it’d still mitigate transmission either for that day or definitely for the next day. You would be able to find out that there’s a pool of 10 or 15 people who are one of those people maybe is positive, you take all of them out, tell them all to go home and then you kind of deconvoluted and figure out who the positive person is. So, there are some ways to improve efficiency in testing for this type of purpose. If we have to do it every day, we might lose some sensitivity, but what we would gain is frequency of testing and that would be, you know, one structure.
But there’s a lot of different iterations that you could think of and some of it will really come down to what tests become available in the coming months as well. I think that there is going to be a big shift in the type of test that is available to people. And then additionally, you know, as an integral part of this, I think serological testing is one of the most powerful tools we have, not for a day to day test, but to understand where are the immunity gaps and where are there a lot of people who are immune, so could you allocate resources in certain ways? You know, in a lot of settings, especially in health care, we could think of ways to do that. But also just in the regular workplace, could you know, who are your staff who have at least experienced this virus?
Again, we don’t know how immune they will be, but at least we can take an educated guess from everything we do know about viral immunology and assume that people will have some level of protection. And that might be a way to allocate resources towards or away from certain populations and really use the limited resources we do have to best improve how we open up most safely. So short answer is testing should be part of a plan.
Q: Thank you.
MODERATOR: Next question.
Q: Hi. Thank you, Dr. Mina, for taking this time to speak with us. My question really relates to the number of serology tests that are on the market, the self-reported performance characteristics and the validation of those results by independent researchers and the FDA. And I was wondering if you can point us to any good studies on serology tests that are on the market, because we wrote about one that’s being used in Miami. It’s a lateral flow test manufactured by Hangzhou Biotest Biotech. And we cited a study in California by the University of California, San Francisco and Berkeley and I think Massachusetts General, and the distributor fired back, saying their customers were happy. And they presented two letters from a researcher at John Hopkins who apparently did his own evaluation. And I was just wondering if you can help us navigate this minefield.
MICHAEL MINA: Well, it is a minefield. I think there’s a few – I can’t point you at the moment to any published papers that I would point to off of my head, but there are a lot of different validations and different labs doing the work to try to understand what the metrics are of these serological tests. Some of them are point of care. Some of them are a laboratory. We’re doing a lot, for example, at Brigham and Women’s Hospital to kind of to try to test different assays, different tests and see which ones are the most accurate or the least. And there might be some tradeoffs that are okay to make.
But at the moment, it is a little bit like the Wild West. These things flooded the market, of course, and now there’s a big effort to hold some of them off the market. And whether individuals like the test is, that’s not how this works in terms of consumers. It’s much more about, you know, if you know that you’re positive – we have to do population studies. We’re looking for, you know, is 1 percent a reasonable lack of specificity if there some benefit that you’re gaining? And I don’t know that there is. But, for example, we have different combinations of tests that we normally do, you know.
Right now, the ecosystem surrounding serology is now being driven by people who don’t normally practice serology as their day job, if you will. And so false positives are a known phenomena in antibody testing. So it’s not so much – and that’s because antibodies are sticky little molecules. They’re designed to stick to things and likely hopefully specifically, but also sometimes known specifically. A whole part of my research program at Harvard is focusing on the nonspecific finding of antibodies. So it’s a normal, natural process. So you need to kind of maneuver away from that.
But you can also use that as a very powerful component of antibody testing if done appropriately. So, for example, you can bank on improving your sensitivity of an antibody test by allowing false positives to show up with the benefit that may be you’re capturing nearly 100 percent of all positives, but then you also get a lot of false positives and then you have to follow it up with a confirmatory test, which would be maybe less sensitive, but much more specific. So, the antibody landscape has got a lot of bad press lately because, I think because people aren’t really comfortable with how to interpret these types of tests. What is a false negative is another question. I’ve been getting a bit frustrated at this notion of a false negative test for antibodies when somebody is still virus positive.
Nobody ever nobody ever made the rule that antibodies need to be there when you’re positive. In fact, usually it’s assumed that, you know, antibodies come up shortly after you’ve been sick with an acute viral infection. So a lot of people have been reporting false negative results and saying, oh, this diagnostic didn’t work. But really, antibodies are, having them come up and become present two weeks later is pretty normal.
I liken it to saying if you have a pregnancy test and if you get pregnant today and then you go and use a pregnancy test tonight, that’s not a false negative. If that pregnancy test shows up negative, that’s not a false negative. It’s just an inappropriately timed use of the test. You have to wait a few more days. And so that’s very similar here. So I think that the whole discussion needs to be wrapped up in more nuance and more getting people who are experts in immunology and serology to really be the ones talking about some of the metrics here and laboratory medicine, pathologists who do this quite frequently.
So I think, you know, that’s a long winded way of saying that some of the some of the press that’s been out about the antibody testing has been, I think, a little bit overblown in terms of being a lot of negativity attributed to the use of serology in general. But I think what’s really going on is that people are inappropriately using the tests. It’s not so much that serology in particular is not a useful public health tool. I do hope, I would say that these point of care instruments, I personally don’t – I don’t think of serology as a tool that most benefits the individual. For example, I think if you can make a point of care test where somebody could take a paper strip unless they have the virus in them, that’s useful. That’s hugely useful. They can act on that immediately.
The antibody test really is a powerful public health tool as much as it is an individual level health tool. And because of that, I actually think we should really be focusing on not having these point of care instruments, but we should really be focusing on tests that go to a laboratory that can feed into public health systems so that the public health systems can know how to allocate population resources and public health. And I feel very strongly that that’s where the effort should be going when we’re developing antibody tests. They should be laboratory-based tests or at least some way to ensure that when somebody does that test at home, that the result goes to the public health lab. And I find that to be a pretty difficult feat to accomplish if it’s something at home.
Q: Just quickly, if I could follow up. You said that what’s really going on is people are inappropriately using the test and I’m wondering I’m sure there are many ways it could be used, inappropriately. What are you seeing? Because what we’re seeing here was a sort of on an individual level, combined with a telehealth visit that appeared to be just an entrepreneurial opportunity to build people’s health insurance. I don’t know if that’s inappropriate or not I’m not a medical professional.
MICHAEL MINA: Well, for example, using a – I would say that if you have a serology test that gives you two percent false positives, well, you just have to know the metrics that you’re working with. So doing a serosurvey in a population that is one percent seropositive with a test that has two percent false positives is probably a bad idea because you really don’t know what the population prevalence is. So, in that sense, I would say that’s an inappropriate use of a low-quality test.
But if you have a virus that, if you have a seroprevalence of thirty five percent and you want to roll out that test to individuals and you can deal with a two percent false positivity, that’s something into the world. You build it into your calculations when you’re getting at seropositivity in the population. So I guess that’s what I’m referring to is we just need to know what the metrics are and they have to be used appropriately. We’ve seen a lot of people who don’t normally do test both for a virus and for serology using things inappropriately. It’s kind of – I’ll give you a different example that should make a lot more sense. We know, for example, that if we’re checking somebody for lung cancer, but it’s just a screening test, we might do a chest x ray first versus going straight to a C.T. scan or an MRI. We all know that a chest x ray isn’t as useful or sensitive or specific as a C.T. scan or MRI. But nobody discounts the utility of a chest x ray. We just have to use it in the appropriate setting and the appropriate way.
And this is why medicine is a practice. It’s why we have physicians who make these decisions about when is the right way to use a test and when is the wrong way, and all tests have their benefits and their drawbacks.
Some of the drawbacks for some of the tests we’re talking about here are cost and time to get a positive result, or time to get a result. So, I think that that’s what I mean. I mean that there’s a lot of people jumping into the space in a kind of a cowboy way or a cavalier way, when really I think most studies that are going on should really do their due diligence to think through with experts on how they’re using it in the same way that that, you know, a surgeon or an oncologist will know when to use a chest x ray and when to use an MRI. They each have their benefits and drawbacks, but doesn’t mean that a chest x ray isn’t useful.
Q: Right. But then they might miss out on the gold rush, I guess, if they don’t rush out with these tests and offer them to a bunch of people. So, thank you very much.
MICHAEL MINA: And that’s a big problem. I completely agree – we’ve commoditized medicine in this country.
Q: Thank you.
MODERATOR: Next question.
Q: Thank you so much for your time. You mentioned just a few minutes ago that we can assume people have some level of protection if they’ve been exposed to this virus, recover from this virus. And I guess based on what we know about other coronaviruses, would you be surprised if there was no level of immunity at all?
MICHAEL MINA: Well, we know that there is immunity. I keep saying that. I feel like this isn’t going to be the virus that breaks the immunology textbook. You know, HIV did that, this is not HIV. This is a virus that we know people are – we’re seeing the virus grow rapidly in people and then decline as a result of their immune system. They develop plasma cells, t cells, neutralizing antibodies, all the rest. So just because we don’t have the studies yet that show how protective it is, we know just from looking at the viral kinetics within a person that people are developing immunity. How durable that immunity ends up being and how protective it ends up being, that’s what we need to figure out. But we absolutely know that this virus leads to immunity in most people. We just now need to figure out what that level of immunity really looks like.
Q: And just as a follow up, I guess, I mean, it would probably be hard to tell when the timeline would be that we would have these answers. But is there any guess you might have as far as when we might know this?
MICHAEL MINA: Well, yeah, we can focus on looking at populations at high risk and we can hope to find – I mean the short answer is we might have some results within the coming months and that would be by, for example, taking people who have antibodies and just people who have different levels or no antibodies and seeing what does their risk of colonization or infection look like over the next couple of months. These studies are going on now, so we might have some preliminary data. But some of the questions that we’re trying to ask are how durable is the immune response? Do we still have good proper immunity after a year of getting infected? So for that answer, we’ll have to wait a year from the first infection that we’ve followed. So I think we’ll see a gradient of studies that come out. Some will look initially at does the acute immune response to the infection prevent re-infection?
And those are those are going to be the first studies that come out. And then the next ones, it’s going to be phased. It’s going to be six months after patients got infected, did they this many got re-infected, et cetera. And then one year and three years. And I have a feeling that this will become that there will be a long, drawn out studies. We’re doing it ourselves. We have studies that are getting started now following – we anticipate that people get infected and so we’re following populations for a minimum of a year through longitudinal population-based surveillance that we’re rolling out in Massachusetts and elsewhere. So, we’re looking at the long term though. We’re saying, you know, will we have results in a year from now to understand what their risk level looks like in a year from now. So, it will be a long gradient.
Q: Great, thanks so much.
MODERATOR: Next question.
Q: Hi, doctor. Thanks so much for taking our call. Appreciate it. Quick question for you. So when you were talking about the reopening and the concerns with nursing homes, we have several, more than five, that have seen major outbreaks. And by that I mean more than 160 cases, more than twenty five deaths at one facility, 24 deaths at another 16 at another. We have probably five at least that have had major outbreaks. And then also we have a pork processing facility in the panhandle of our state where they’ve had more than 200 cases. And I just looked at today’s numbers that just came out and they’ve got 64 percent of our positive cases today. What is your concern? Our state was among the first. We were in a race with Georgia to reopen and get salons open first in that type of thing. What is the concern when you were talking about nursing homes specifically and some of those areas or processing plants, those types of places?
MICHAEL MINA: My major concern is that during a period of serious and severe social distancing, we didn’t figure out how to protect the nursing homes. And like you said, we’ve had huge outbreaks across the country. I know that in Massachusetts, we’ve had enormous and horrific outbreaks that have killed 50 plus people, 25 percent of the census of one nursing home. So it’s devastating. And the problem that I have with this is that if we couldn’t figure out how to keep this virus out of nursing homes in a period of really restricted transmission through social distancing, I haven’t really seen a lot of effort being put in place to really, truly, structurally change something about the nursing homes to prevent transmission from entering, from preventing the virus from continuing to enter.
And unfortunately, you know, on the one hand, we can say nursing homes might reach herd immunity. You have 70 percent positive in a lot of nursing homes now. But unlike the rest of society, nursing homes are a little bit more like they have a constant replenishment of susceptible is into them. So this is going to be a problem that will persist long term for nursing homes.
And I want to see, rather than just going out and testing every nursing home once and spending tens of millions of dollars on it in certain states, no, I would want to see instead some of that money being put into structurally changing the nursing homes to make them safer. I don’t have exactly what that looks like, but I think that there should be real serious effort to put infrastructure changes in place to ensure that these things don’t continue to go. And at the moment, we open up if we do start seeing more cases again, which we anticipate will happen, whether it’s in summer, the fall, those cases will flow into the nursing homes.
Q: I appreciate that. Thanks for the insight. Also, just to follow up with something that you had mentioned earlier, you were talking about how the antibody testing can be a powerful public health tool and that you would like to see the effort to get them into public health labs. Can you expand a little bit about how they would be able to use that information? Because I think, like you said, we don’t sort of see any organized effort happening right now other than just a lot of new up and coming antibody tests happening, as well as the labs that we’ve been seeing, you know, some of our bigger labs. But what would you like to see happen with that public health lab angle of it?
MICHAEL MINA: Yeah. So knowing, for example, nursing homes are a great a great setting where that could be employed or university places where people are close together. For example, if you can take, if you know who is who is immune or at least who has antibodies and has been exposed, and you could assume, you can layer on top of that an assumption that those people will have a lower risk of re-infection and probably if they do get re-colonized, they will have a lower risk of transmitting it onward. You can start thinking more creatively about how to use that to your benefit to both allocate resources if you’re testing people, but also physically where to put people.
In nursing homes, for example, maybe you actually don’t want to just cohort nursing home residents who have had the virus away from people who haven’t had the virus. In fact, you probably want to do the exact opposite and you might want to be mixing people who have had the virus with pools of susceptible who have not to really mitigate transmission. So you need to have serology to understand that, because we know that there are a lot of asymptomatic people and there’s a lot of people who did not get tested and are not sure. So, serology is the really only the way to do that.
And then at a population level, really understanding where to allocate resources. If you’re if you’re an institution or a city that has had 40 percent positivity, you know, at the end of this, in the near future, maybe New York will be there. Maybe New York is actually one of the safer places to go in terms of major metropolitan cities in the near, you know, come next year. And that is, there’s just important information there to know. And if we don’t know, serology is really the tool that we use in public health to know where we’re at in terms of epidemics and including seasonal infections, too.
It can give you a lot of information on when pathogens are starting to transmit in a way that is much more powerful than just using the virus, because it’s hard to find somebody out in the population who happens to have flu at the time you’re testing. But it’s easy if you’re following people longitudinally to test them on a monthly basis and you don’t have to catch them in the five-day window when they’re positive for flu. You can know that, OK, they were negative, negative, negative, and now this month are positive. And so you’d know that somehow and in the interim that they got infected. So it’s a very nice, convenient proxy. And if you do that for enough people, you can really monitor pathogen transmission at the population level in near real time in a very powerful way. So that’s why I’m a huge advocate of setting up surveillance systems at the national level based around serology.
MODERATOR: Next question.
Q: Hi. Thanks for doing this with the news from Moderna about the vaccine. There’s been a lot of talk about timelines. Just in your view, what’s the biggest hurdle to getting a vaccine out there for mass use? Is it just making sure that it’s safe or is it more production scale so that there’s equitable distribution, that kind of thing? What’s the biggest hurdle here?
MICHAEL MINA: Timewise, I think between now and when it gets approved, it’s going to be efficacy studies. I might get some emergency use, compassionate care use early indications, that could very well happen and we might see that occur where some people are actually getting it early. For example, if you’re in a nursing home and there is a major outbreak happening, I could see some world where we start giving early phase vaccines to people. But in general, I think that to really get out to the masses, you’re going to need to have the Phase 2 and 3 trials, the efficacy studies really pinned down to show that it’s actually protecting.
And again, the way that you do those, you have to wait to see that people, you have to let people get exposed naturally and do the efficacy studies to see that they’re not getting infected. And that just takes time. In particular, it’s going to take an increasing amount of time now that social distancing has brought the virus to lower numbers. Of course, now that things are opening up. We might those studies might be able to be accelerated once they start.
We saw, for example, Zika by the time Moderna got a Zika vaccine ready to be in studies, Zika was pretty much gone. And so those Phase 3 efficacy trials never really materialized. And so I don’t think that’s going be the case here. But that’s a pretty that is a very big hurdle to get over. And then scaling up the vaccine, and I submit the Moderna vaccine as it can be scaled in a way that other vaccines, more traditional vaccines can’t. And so that’s a benefit. But I think that given the major interest in this vaccine and demand, I think they’ll have trouble initially once they get approval to really scale it up that huge numbers.
Q: Thank you.
MICHAEL MINA: Sure.
MODERATOR: Next question.
Q: And so I was wondering, given what you said today, what you mentioned, you know, the lack of a benchmarks to know when things are not going well, how – I mean, with that data that we have right now, the number sick or the number of cases and the number of people dying each day, how come we know at least with that if things are really going bad after reopening, is there any way?
MICHAEL MINA: I think it needs to be very localized. We need to have local governments, mayors and such really working on ensuring that they have stood the public health infrastructure, departments of public health and states really measuring and doing good surveillance at a very geographically small scale so you can find outbreaks when they start to occur and squash them down.
And I think until we have those types of networks set up across the country where we’re able to detect small outbreaks when they’re getting going, I think we run the risk of small outbreaks becoming big outbreaks. So I would really push for this to happen at a very local level, but coordinated at the state and federal level to have the right expertise. There’s actually ways to make surveillance more powerful if you design the studies well and if you design the surveillance networks well. And that’s where enlisting the help of experts who do these types of things can be very powerful.
And I would advocate, for example, for the federal government to really put guidelines together for how localities can survey and do their due diligence to ensure that they’re protecting their constituents from outbreaks. This might even be at the individual company level, whether it’s, you know, Harvard and M.I.T. or huge, massive companies like Amazon or whatever it might be. I could see it. It has to happen at all levels in the same way that we would focus on it in our own home. If we know that we’re sick and we live with an elderly person, we are going to do everything we can not to be around that person and recognize that we’re sick. And we have to just scale up that mentality to different levels locally. If we go too big, then we really run the risk of not being able to detect these things when they’re happening and people die at a local level. They don’t die at the national level.
Q: How long do you think it’s going to take before we see the impact of reopening?
MICHAEL MINA: Probably – well, let’s hope it takes forever and we see cases continue going down, but I think in general we won’t see, if we ever reopen today, for example, we’re not going to see it tomorrow. I think without really robust surveillance networks in place, I think we’re probably talking a few weeks at least before we really start to see a signal that is clear. And it could be the fall if the summer really does turn out to help us out. We’re not sure. So, I would say we shouldn’t get – I guess the point there is we shouldn’t get too excited because we don’t see anything happening tomorrow. We should really be patient and be very careful and continue watching for weeks and then months.
MODERATOR: OK, I think the last question.
Q: Yeah. Thanks so much. Really appreciate taking the last question here. My question’s on serology. I guess this has been done to an extent in New York where we’re seeing you were saying 20 to 30 percent of people may have that. What about other states like Massachusetts? And what does it take for, you know, that mass testing to be done?
MICHAEL MINA: Well, I think it takes a few things. It takes a public health laboratory for one and by that, I mean we can’t count on clinical laboratories that are used to doing clinical sample testing because those tests require, for example, whole venous blood, venipuncture, and like sticking a butterfly needle into somebody’s arm and taking a whole tube of blood. That is not an acceptable specimen type for real public health testing, where you need may be hundreds of thousands or millions of tests to be performed. You can’t have everyone going to a phlebotomist every day.
So I think we need a new laboratory system where we can actually process. For example, fingerprint blood spots. You prick your finger and you put it onto a dried blood spot filter paper and you mail in that filter paper, you close it up in an envelope, mail it into a laboratory with your address, your zip code or whatever it might be. And that information gets fed a) back to you, just since you’re contributing, but also to the Department of Public Health to monitor.
And that is what I think we should really be striving for in this country, to develop a network of laboratories that are able to handle huge capacity, huge volume and to do so with acceptable sample types like dried blood spots from a finger prick, maybe even saliva has a lot of antibodies in it. And so I think that those are the types of things I want to see happening and the benefit – it’s a large upfront cost because we’ve let our public health infrastructure degrade for so many decades that these just don’t exist today in the US. But what it would allow is in the future will allow the development of much larger networks to really monitor for other infectious diseases.
So, what I want to see happen in the near future, and we’re working on this now, is I want to see a weather system equivalent for infectious diseases. I want somebody to be able to log into their computer and type in a zip code and ask what’s the coronavirus situation look like today? What did it look like yesterday and what is the rhinovirus, or adeno, or influenza? And be able to actually create a true a true surveillance network for many pathogens. So that would be of interest to people. But also, it would really start to develop a notion of public health and a way that we can use public health to really monitor, detect and predict outbreaks in a way that we currently don’t have. So, I think that that’s something I want to see continuing to occur and build up. And I think that that’s the type of infrastructure we need.
MODERATOR: Did you have a follow up?
Q: No. No. That was very – thanks very much. I like that. I guess, do you see that happening? I mean, DC I guess you see it in New York but do you see that maybe extend? I don’t know, do see that anywhere else?
MICHAEL MINA: I don’t see it happening on the federal level, per say. I think it’s going to happen – I think that it can happen, but it’s going to take a huge amount of effort by probably academics and people who are interested in public health in a way that won’t probably be driven by governors or maybe it will be driven by governors, I don’t know. I hope. But I don’t anticipate that it will really be driven by government as much as it will be maybe a commercialized sort of a public private partnership situation where there needs to be some commercial entity just to keep these things afloat because we can’t bank on just always having taxpayer dollars, you know.
I think we should, but we don’t have a population that’s really willing to do that. But it could be some public private partnership to really make these things happen. And have networks have labs that are willing to contribute to the public health ecosystem in a way that we don’t currently get.
Our entire laboratory testing ecosystem in the United States is nearly 100 percent wrapped up in clinical care. And so, we don’t even have the instruments or the capacity or anything to really do public health type of work. They just need to be different design and reimagined. So, I think it will happen. We’re certainly working on it and it just is going to take some investment that probably will end up being private investment because there’s not a lot of public, even in the current state, there’s not clear avenues to get the right public investment.
This concludes the May 18 press conference.
Michael Mina, assistant professor of epidemiology (May 15, 2020)