At-Home Rapid Testing, Interview with Professor Michael Mina, MD

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    Our latest update in the COVID-19 Explained Clearly series is an in-depth interview with Professor Michael Mina, MD from the Harvard School of Public Health. As a major advocate for at-home, rapid testing, Dr. Mina explains how a $1 test could potentially curb COVID-19 spread in the United States and worldwide. In addition, he describes current barriers to making at-home rapid tests available, breaks down the futility of comparing rapid tests to PCR tests, and explains how a vaccine won’t make frequent, rapid testing any less important for COVID-19. 

    Watch the full interview here, or read through the interview transcript below. 

    See Professor Michael Mina, MD’s bio here: 

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    Kyle Allred (MedCram Producer and Co-Founder): Dr. Mina, over the past several months, you’ve really been the leading advocate for a new testing strategy in the United States and abroad, and you’ve made a strong case that the technology already exists for inexpensive, convenient tests that people can use in their homes, and that potentially the widespread use of these tests can be even more effective than a vaccine program. I spoke with you here on MedCram about four months ago, and for viewers that are new to your research and your message, what is your central message about testing?

    Dr. Mina: The basic message is that the way that we stop a pandemic is we stop it from spreading. Vaccines do that by eliciting herd immunity by stopping the spread from people who get vaccinated onwards to other people. But, we can do the same thing without a vaccine, and we can do it today. We could have done it six months ago. And that’s with small, paper-strip, rapid antigen tests. These are tests that we can get out to everyone’s home. We can build them; we can get them into people’s homes and they can use them. Say, right after you brush your teeth, you use a rapid antigen test, and it tells you if you have COVID and if you are transmissible with it. So, it allows people, in the comfort of their own home, without having to go to a doctor, without having to make an appointment, spending hundreds of dollars on these PCR tests that then take days, if not a week, to get results back. It gives people knowledge whether or not they are at risk of spreading a virus to their loved ones or their family or friends or coworkers, and that’s how we can stop spread. It’s really not a difficult concept. The tools exist. This is one of the tools right here. It’s a rapid antigen test. These now exist all over the world. We just don’t have them widely available at all, really available at all, in the United States today to the average person. And if we could get people, get enough people in the U.S., to know that they can get to know their status of whether or not they have the virus in them and whether or not they’re transmitting the virus at the moment, then they could make very educated decisions — not go to that Thanksgiving dinner, for example, or Christmas dinner, whatever it might be — and really it can be used as a way to let people know, more than anything else, when not to do something. Everything else, they should do the same. If it’s a negative result, you keep going about your day the same for the time being, and after just a few weeks, we would see the incidence of this virus, because spread would start to stop. We’d start to see the population prevalence, the number of cases, just start to plummet after just a few weeks of using these tests at the community level. 

    Kyle: Are there any other countries that we can look to for examples of how this has been done successfully?

    Dr. Mina: Yeah, well, the best example right now is Slovakia. And Slovakia rolled this out, really the exact same plan that our science tells us that would work, and that’s to get people to use these tests once or twice every week, and get about half of the community to use them. So in the United States, we could actually do it with about 20 million tests per day — 20 million of these little tests. You know, we make more bags of Doritos every day that that in the United States, probably. And so Slovakia did it, and very quickly, within about a week and a half to two weeks, they went from exponential increase in their epidemic to a collapse of the epidemic, and it’s really tumbling down in the best of ways. It’s really a very powerful public health tool, and we’re starting to see more countries. Austria is about to roll it out, Poland is about to do this. And so I’m really hoping, for example, that the United States gets on board as well. 

    Kyle: You have a popular Twitter account that a lot of leading experts from all over the world follow, and one of your recent Tweets really hit home for me, in that rapid testing is something, by and large, people really want. People don’t want to wear masks; people don’t want to have to physically distance from their friends and loved ones. People certainly don’t want schools to be shut down and their workplaces to be shut down. So since rapid tests are something that we really want, and your research has really shown that they can be effective and now we have examples from other countries that these can be effective, what is the hold up at this time?

    Dr. Mina: Yeah, the hold up… Well, I want to mention quickly that I think it’s important to recognize that I’m not advocating, for example, for the use of these instead of all the other things, but really to be an adjunct. And the reason that I think that what you just mentioned is so powerful is, you know, people don’t want to wear masks, but a lot of people will, reluctantly, but will, because, you know, it’s a pandemic. Nobody wants to social distance. At least, very very few people actually want to be having to social distance in the ways that we’re asking people to, but they will. These are a different thing. These are things that people actually want to use. They wish that they had them in their house right now. So it’s amazing to me that it’s the one product that isn’t available to people, but really could be. But there’s regulation and there’s a lot of naysayers who really, I think, put the public down and say the public can’t handle the information that they’ll get from one of these tests. And you know what, I just think that that is such a cop-out of a reason not to get these out to the communities. Every time we try to let anything that’s remotely like this into people’s homes, people get up in arms. The professionals, the medical and public health professionals, say “no.” You know, this was the case with pregnancy tests. For decades, doctors really fought against pregnancy tests going into people’s homes, saying “God no, how could a woman handle that data, the information about their own body, without a physician telling them what to think.” And then HIV screening was the same thing: “How could somebody possibly get an HIV screening on their own?” And this is now just the newest iteration of this concern. But the other concern, or the other barrier, is there’s an FDA barrier, and this is that the FDA is not approving or authorizing these tests for home use, because they keep comparing them to medical tests. They keep thinking of this as a medical test and keep saying, “well what’s the sensitivity and specificity?” All of the data now suggest that the sensitivity, when somebody is infectious, is greater than 95 percent, or probably greater than 99 percent, sensitivity, meaning it will catch you if you’re infectious. And specificity is greater than 99.2, 99.3 — it’s like one in a few hundred to one in a thousand will be falsely positive. But there’s ways to get around that. We couple them; we have a whole program around these tests where you get 10 of these tests and two of these very similar looking tests, but that are slightly different model, and they would be falsely positive for different reasons. So it’s an algorithm: if you turn positive on this one, you take this one. And so there’s really very simple solutions to pretty much all of the hurdles. We just have to have a regulatory agency that can have the sort of window to see this as a public health tool and to allow people to have these in their homes, to allow the U.S. government to produce them and get them into people’s homes. And then, finally, we need the manufacturing capacity. Because these haven’t been built yet in the type of scale that this kind of program would demand, say 10 to 20 million a day in the U.S., we don’t have the scale, but they could be scaled easily. They really can. In World War II, we created B-24 bombers every 63 minutes. You know, we can mobilize. And these are easy to produce. We don’t need big factories to do it, just a few factories would be able to scale to a very high number, very easily. A lot of leaders, I think, in this country have forgotten that they are our leaders. They ask me a lot — these are governors, senators, and other people in the administration — everyone always says, “Well, you know, why hasn’t anyone else done this yet?” And I say, “Well, a lot of countries are starting to do it, but in the U.S. nobody’s done it, because that’s you. You are our leaders, and somebody has to take the reins and try to control the virus. 

    Kyle: I know you saw this video. I’m going to play the audio for it of Dr. Fauci in a recent interview. 

    (From News Clip) Dr. Fauci: You know what I’d like to see — and I would push for this very, very hard — in addition to the standard, highly specific, highly sensitive tests that you do if you want to know that this person is infected, you want to do identification, isolation, contact tracing, that’s good. I like that. But the thing I would be pushing for is something that’s a home test, that’s point of care, that you can do yourself. Because, if you can do that, you can get a situation where someone would know whether or not they’re infected or whether or not the family they’re bringing over for dinner is infected.

    Kyle: Even he is advocating for these, but it seems like it just keeps falling on someone else. So, from all of the research, all of the conversations you’ve had with different leaders, both here and abroad, I guess, specifically for the United States in this question, whose job do you think this is to really make this a reality?

    Dr. Mina: Well, I think it was the Trump administration’s job to do it, and it was Congress’ job to appropriate the funds to do it. We’ve seen the RADx program, and that was an attempt. RADx, in my opinion, has not failed, but it has not produced the type of tests at the speed we need to actually make a dent in this pandemic. And so I think it’s led to some innovation. RADx is this program that the NIH put together to help fund new innovation in testing. But, what we need is we need to forget about all the really new fancy innovation and recognize that we have a paper strip test that works really, really well right in front of us. We don’t need to be scaling up mega-laboratories that are going to require tons of logistics and all this stuff. We just need to create these. And I think that it really falls, in this case, on the federal government. The states — I mean, I would love it if some states, especially the wealthier ones, like California and New York, could get on board to build these themselves. Certainly, they have the capital to do it. To really do this, it’d probably cost 300-400 million dollars to get the capacity up, and then maybe a couple billion or a few billion to really produce tests enough for the country for the next six months or year. So it’s really very, very cheap. That’s less than 0.1 percent — less than 0.1 percent — of what we’ve spent so far on this virus directly. So this is an extremely cheap, practically risk-free, endeavor that could have profound effects as great, if not better, than a vaccine program, and certainly quicker. The only action that we’ve seen is sort of these much more traditional efforts, like infrequent surveillance testing at drive-thrus with a three-day delay to get results back, and then contact tracing. Every shred of evidence we have shows that it doesn’t work. But we keep doing it because it’s “what we do for a pandemic.” You know, it’s just we have to get bold leadership, and I think, it’s gonna land now, really, on Biden’s task force. I think that they are going to be the ones to give the President-elect information. But, unfortunately, that can’t really be acted on too heavily until the end of January. Meanwhile, we’re in a crisis.

    Kyle: Something that’s been in the news a lot lately is this first FDA-approved at-home test, and since I just showed a clip of Dr. Fauci, I’m going to play one more that you’ll hear the audio on, and then I want to hear your thoughts on this new test that’s been approved. 

    (From News Clip) Dr. Fauci: That’s something that’s just the first step. You want to be able to do it, it requires a prescription. I’d like to see one where you don’t even require a prescription. That’s what we need. Sensitive.

    Interviewer: How do you do that?

    Dr. Fauci: Well, you just develop it. You get the companies to go ahead and do it and say this is something you really need. 

    Kyle: So what are your thoughts on this test from Lucira that’s been approved by the FDA?

    Dr. Mina: Yeah, it’s, it’s not the test that I’m talking about. It is very much a medical device. It’s got batteries and wires, and it’s a disposable little laboratory. So it’s very expensive, relative to this. This is what it looks like without the plastic case. It’s just a piece of paper, essentially, with the antibodies printed on it. And that’s a device, it’s going to be expensive; it can’t be scaled; it needs a doctor’s note. All of these things, it continues to… it, to me, represents what’s wrong with our response to this pandemic. We keep trying to shove a public health approach through a medical lens, and that’s the thing that comes out the other end: something that can’t work for the population; something that, you know, is innovative, but won’t work, won’t make a dent. It won’t even come out until April for most people, and most people will not be able to get it, because there’s no way it’s scaling to tens of millions a day. It’s not going to help. It’s going to be a luxury item that, uh, maybe some people will grain access to. It really worries me, actually — I don’t want to bash the test, I’m sure it’s a very good test — but we are not in a medical crisis. We are in a public health crisis. We need to use public health tools to combat a public health crisis, and then the medical problems will resolve. We can’t try to claw out each medical problem and hope to contain an escalating public health pandemic. It just doesn’t work that way. We have to focus on the tools for the public health problem, and then we will take care of the medical problems, [they] will resolve, because we’ll get cases to be low enough. You know, what I’d love to see is for Elon Musk to get into this and use a few of his really good engineers; he loves to do things at scale, build things in brilliant ways. Let’s get Elon Musk. I’ll talk to him, and, you know, explain what we need, and I’m pretty sure that he can change — he can singlehandedly, if he wanted — change the face of this pandemic. So, if it’s not going to be government by now, we have a lot of very innovative companies and people that have the means to actually do something. You know, I can build the science, but I can’t build the tests, you know, but the country does have all of that right here on our soil. Frankly, there isn’t really another option on the table that’s politically palatable, economically feasible, and that would do the least, as little damage as these little rapid tests to really control this virus. 

    Kyle: You’ve been in the New York Times a lot, Dr. Mina, and several articles have been written about rapid tests in the New York Times and other publications, and there was one that caught a lot of people’s attention that had, in your opinion, and I definitely agree with you, a misleading title. It said: A Rapid Virus Test Falters in People Without Symptoms, Study Finds. Can you unpack that for people so they understand why this was probably an inappropriate title? 

    Dr. Mina: So, we keep comparing antigen tests, these rapid antigen tests to PCR. These are two totally different technologies that look for two totally different things. This [rapid, at-home test] looks for proteins of the virus; PCR, the laboratory test, looks for the RNA of the virus. The analogy that I like to give is: looking for RNA is very much like a detective looking for DNA at a crime scene. They go in — the crime is done, it’s complete, it could be going on still if the detective happened to be there at the same time — but oftentimes, more often than not, the detective doesn’t show up until after the crime has been committed. And then they’re trying to reconstruct the crime scene, and so they use DNA and PCR to do that. Well that’s the same thing with PCR for this virus. Most of the time that people have the RNA in their nasopharynx in their nose, you can think of this as the crime scene. The crime has already been committed, but that RNA lingers for a long time. There’s no more virus though. The RNA is just sitting there. So PCR will detect it really well, potentially for months after somebody’s been infected and infectious, contagious. These tests, on the other hand, will only be positive when somebody’s transmitting virus. You should think of these as contagiousness indicators. They are not the PCR test that’s going to reconstruct whether a crime has been committed. They are the test that’s going to, they’re more like the security guard. They’re there to take watch and note: is something happening right now? And not ask the question: did something happen last week or three weeks ago? And so these tests are very, very sensitive when people are contagious, but the problem is, because we continue to compare these erroneously, — and many studies have done this now — because people, unfortunately a lot of scientists aren’t familiar enough with the kinetics of how the virus grows and decays and then leaves its RNA at the crime scene. But when you start looking at it through this lens, which is the correct scientific lens, then 70 percent of the time that somebody is PCR positive, there’s no crime going on any more. So if you try to use one of these tests that looks for the infection itself, when somebody is just randomly PCR positive, it’s not going to work. There’s no virus left to find. And so, it’s only going to work during, the, say, 4-5 days when somebody is really infectious. Outside of that window, it’s not going to turn positive. So that New York Times article, for example, essentially said 70 percent of samples were falsely negative, were missed on this, when they went out to screen in asymptomatic people for PCR positivity. Well, that actually fits the theory exactly. We know that 70 percent of the time, somebody is PCR positive, but doesn’t have viral replication going on at the time and is not contagious, so sure if you go out into the street and you just start swabbing people looking for RNA via PCR, then you say “OK, all of those people who were PCR positive, did they turn positive on this?” 70 percent of them won’t be. And that’s correct. It’s not a bad aspect of these tests; you could even go so far — I try not to say this too much, because I don’t want people to misinterpret it — but you could go so far as to say that PCR is almost falsely positive 70 percent of the time, if your goal is to detect infectious people. It’s not actually a true false positive, because it is picking up the coronavirus RNA, but oftentimes the crime actually didn’t happen, but it doesn’t mean that it’s still happening, so we have to always interpret tests appropriately and unfortunately, then your Times piece is a very good example of inappropriately interpreting tests and it led to massive confusion amongst world leaders. I had lots of world leaders call me, or their teams, and say, “you know, we talked to you in the past, you advocate for these antigen tests, and now we see this that says that they’re not sensitive. They miss 70 percent.” And I’m always having to reeducate, because we just have so much misinformation, and unintentional misinformation, out there.

    Kyle: To build on what you just said, Dr. Mina, about what we really care about is a test that captures the contagious window for someone when they get COVID-19, you have a great graph that shows the viral dynamics and this huge spike. Could you explain that?

    Dr. Mina: Sure, so when we’re looking at the viral dynamics of this virus, we’re oftentimes representing it on what we call CT values. That’s the value that comes off of the PCR instrument, like how much virus is in the sample. Normally, it kind of looks like a nice triangle almost. And it looks like a pretty broad triangle, so it looks like you’d have a lot of virus at day like 8 to 15 post-infection, for example, and maybe a lot of virus at the beginning. But actually, if you change that graph and you take it off of a CT scale, which is technically what we call logarithmic scale, and you put it onto a linear scale, the difference being a logarithmic scale gives as much weight, for example, to the number, to a viral load up to a thousand as it does from a viral load a million to a billion. So we all know that a thousand viral particles is probably not the same as essentially a billion viral particles, but a CT graph actually gives those — well, visually — it gives them the same amount of weight. So it’s kind of like zooming in. The lower and lower you get of the viral load, the more you zoom into it, and so it’s really hard for somebody who’s not used to looking at these graphs to interpret these, and I think it’s led to actually a lot of confusion. People keep getting really concerned about, you know, “well are we catching the virus at 30 or 32 or 34?” But if you zoom out and you put it all on the right scale to actually indicate the true amount of viral load, all those differences completely fall away. The 30 versus the 34; even the 28 versus the 35s. You know, if you’ve been following the CT discussion, this is like asking the question, “well, when does transmission really stop?” The point isn’t to get exactly when transmission stops. That’s going to be different in everyone. It biologically just variable. The important thing is to know that you’re getting people when they have the most virus and not just when they might maybe kind of have some potential to transmit. From public health perspective, if we can find all of these people and we miss a few of these people, that’s OK because they’re really low virus anyway. So the point of this graph is that when you put it on the regular scale, the real scale that shows what the actual viral load looks like, then you see that you just have this really tight peak. It skyrockets hight and that’s because the virus grows exponentially, and that’s like what we’re seeing, for example, when you look at cases out in the community in a lot of places like the Dakotas, you can see that the cases were kind of going along and then they almost just started going vertical. That’s exponential growth. So to really start to see what’s happening, sometimes we put it on a log scale, but that gets confusing. And so when you put the viral load on this linear scale, it really drives home the message that almost all of the viral growth that happens in somebody is in a very short duration of time, say maybe like 2, 3, 4, 5 days max, and then you have just like the fringes where maybe you have some more virus on the edges. And primarily on the edges on the downslope of the virus, not on the upslope. When you plot it out like that, you can see why it’s so difficult to contain this virus, because it really transmits the most in this very, very short window of time, and then your body has to handle it. The reason, I mean just physiologically, your body can’t handle having exponential growth of a virus, once it gets to billions or trillions of viral particles per mil in your nose and in your lungs, it can’t deal with another two replication cycles. It would blow through your whole lung parenchyma and all of your tissues and it would land you in the hospital. So for most people who don’t get seriously ill, the body has to control the virus very, very quickly. And that’s what this graph really tries to demonstrate is just how much of the viral load is really concentrated in a short duration. 

    Kyle: And, what I take from that graph, too, is that these inexpensive antigen tests, that the technology already exists for, really capture that spike. 

    Dr. Mina: They do. They capture that spike nearly perfectly. That’s exactly right. You know, so we keep squabbling. The FDA is squabbling, people are squabbling with a lot of experts squabbling over “well, are we really catching the edges?” It doesn’t matter. You know, from a public health perspective, we want to know that we’re catching people at that point in time, and it’s even more important, people keep saying, “well, what if you miss somebody at the very beginning and PCR wouldn’t have missed them.” And so they say these tests are dangerous because they could miss somebody right as they’re coming up. Well, that’s not even a good comparison. Because if the PCR test takes three days to return, then by the time, you know, if you had just waited one more day and taken the rapid test the next day, it would definitely be positive, even if it wasn’t positive at the same time you took the PCR swab. And so the rapid test would turn positive potentially one day, two day and then only on the third day would you get the PCR test back. And so you have more time; it’s more sensitive, not less. And that’s what’s so incredible about rapid tests. It’s the power of getting the result immediately that gives you more time to act, not less. It gives you more sensitivity, not less. And I think that’s a hard concept because it’s looking at these tests through a public health lens versus a medical lens, where you kind of assume that the one swab you get is the only time you can possibly get it from that person. But at a public health perspective, you know, whether somebody comes in on day one or day two is random, and so the antigen test will actually be much more sensitive to find people, because it can tell you immediately. If you’re in that spike, it can tell you immediately, whereas a PCR test, so you get the swab at the beginning of that spike, you might miss the whole spike before you get the results, and that’s a real problem.

    Kyle: And to add to that, what you’ve advocated for from my understanding — correct me if I’m wrong — is that to take it a step further, we have the option to make these cheap tests actually available to people where they can use them in their homes, whereas most people, a lot of people that I know, haven’t even gotten one PCR test during this whole pandemic. And so it’s also comparing the practicality of what could be available at scale versus the PCR test or these more expensive at-home tests that have already been approved. 

    Dr. Mina: Yeah, that’s exactly right. You know, if this little test is sitting next to my toothbrush in the morning, I’ll take that. That’s the type of… If I could take that every Monday and Friday and have that really builds my confidence, or at least tells me, OK if I am positive, then I definitely don’t want to go out on Monday, Tuesday, Wednesday, Thursday. But if I’m negative, I’ll keep doing everything the same. But the only way I’ll do that every Monday and Friday is if I have something like this sitting next to my toothbrush. I brush my teeth in the morning and I take a COVID test. It takes literally 30 seconds to actually do the test. You let it just sit there and five minutes later, 15 minutes later, whatever it is, you’ll go back and read it and look for a line, just like a pregnancy test. 

    Kyle: I want to ask you about this new estimate by the CDC four days ago that 51-70% of COVID-19 transmission happens when no symptoms are present. So the presymptomatic or asymptomatic phase of the infection, if you will. What are the implications of this for rapid testing. 

    Dr. Mina: Well, the implications are really, it pushes towards the utility of frequent testing and rapid testing. I think what the conversation we were just having about the duration over which somebody’s actually peaking in their viral load, it’s so short. And unfortunately we keep having these discussions about, we,, when is most transmission happening? Is it symptomatic, asymptomatic, presymptomatic? The point is, with an infection like this, a lot of the symptoms actually come from the immunological response in the first place. So by the time you’re really having a robust immune response, you very well may have already passed the peak viral load, or you’d be right in the middle of it. So if it’s only then that you’d go get a PCR test and you find out three days later what your result is, then you’re already done transmitting, period. So it really suggests that having really ready access to a rapid test that gives you results in minutes can be one of the most powerful tools. And further, it really drives the message, the fact that so much transmission is happening in the presymptomatic stage, or just amongst people who are completely asymptomatic, drives the message that the only real way to catch people in the act of transmitting and to catch them early in their transmission cycle so that you can extract them out of the population and really kind of reduce the number of transmissible days that they’re mingling with other people is to be doing these tests frequently. And so if you’re doing it frequently, say twice a week, then you’re much more likely to catch somebody, say towards the beginning or mid-cycle in their transmission cycle. Sure, sometimes you’ll only catch somebody at the end as well, but maybe two out of three times you’ll catch somebody before they’ve actually done the majority of their transmitting. But unless you’re doing it every few days, it’s going to be really hard. You can do it weekly as well, but you’ll have lower probability of really removing people quickly in their infection. If it’s a four-day infectious period, for example, and you’re testing weekly, yeah, for a lot of people you will still catch them in the first day or second day or maybe the third day and cut off 25 percent of their infectious days. So it can still work, and it does still work, theoretically, but certainly twice weekly is much, much more powerful. 

    Kyle: And to pull off this twice weekly goal, you had a great opinion piece in Time Magazine recently — I think it was just last week — where you advocated for every person, every household getting a pack of 20 tests. And to deal with false positives and really help the tests be more sensitive and specific, including a few confirmatory tests in there, maybe made by a different manufacturer or looking for a slightly different antigen on the virus. Maybe you could explain that. But the follow-up question would be, do you know if any companies who are struggling to get FDA approval have actually thought about this strategy, maybe teaming up — maybe 3M and another company teaming up together — to say, “let’s combine your paper antigen test with ours” and try to run that through the FDA approval process?

    Dr. Mina: Yeah, well there’s not a lot of incentive for these companies to, and the FDA doesn’t even advocate for it. The CDC, you know, it’s really unfortunate. I spoke to people at the FDA and at the CDC months ago, and I said, “look, if we don’t have confirmatory testing for rapid tests, when we start rolling out rapid tests, people are going to lose faith in them very quickly, because they’re going to get a rapid test, and then they’re going to get a PCR to confirm it, and that PCR is going to come back three or four or five days later, and they’re going to find out then that they maybe were falsely positive.” That’s not OK. I mean, it’s OK if it happens rarely, but it’s not OK if it happens once every 200 tests. People will lost faith that it’s even working. We have to give a rapid test, a confirmatory test, with another rapid test. It needs to be very quick. And unless we do that, people will lose patience, and it doesn’t matter how much we tell them, “hey look, isolate during the three days after…” No, it’s just not the way to do it. So we have to get rapid tests confirmed with another rapid test. We actually do it in the hospital for HIV. It’s very common. It’s not a mind-blowing exercise, this is really normal endeavors with testing. And so, the companies, because these are all being approved as standalone medical devices, they don’t have any incentive to work together, to collaborate, and we have no tradition of that in this country to try to bring these companies together. We have, even for HIV testing, we have very clear algorithms where if you get a positive on this one, you take this test as well. But those are two totally different companies, approved totally independently, which I think is wrong. We should really be authorizing tests as a whole algorithm. But it’s not how our society really works in that regard. But I do think it falls then on the government to bring these companies together, to identify and say, “hey, Abbott and BD are working together. AccessBio and Quidel, you’re working together. And you have more ability to scale, so you make the primary test, and you have less ability to scale, so you make the confirmatory.” Super simple. I mean, we can do this as a government, if we want. And biologically it works. The reason, if you have two different tests from two different companies, for example, in general, the reason that one test will turn falsely positive is usually spurious; we don’t usually know. But the point is that it doesn’t turn falsely positive on the other test. So, you swab, you run it, you get a false positive on this one. You don’t know if it’s a false positive or true positive, you just take your second test out and you run it on the one that looks the same, feels the same, but it actually has different molecules on it, and it won’t turn falsely positive for the same reason. So that could be the policy. It’s very simple. It’s a 1, 2 punch. You take the first test every few days, and you’re hopefully always negative, but eventually, maybe once a year — I don’t think people need to be doing this for a year, but you know, one out of every hundred — so if you’re taking two tests a week, on average, most people wouldn’t have more than one false positive a year. And most people would have many fewer than one false positives per year. So most people never see a false positive. But if you get it, just pull out test number two and take it, and that’s the policy. I don’t think it’s too confusing for people. It will be rare; in fact, the newer tests like this that are coming out, especially the ones by Abbott and some of the others — Roche has a good one that’s sold internationally — they’ve gotten the false positive rate down to like — it’s correct when it’s negative like 99.5 percent of the time. So the false positive rate is just one in a few hundred tests, and it goes to one in a few thousand if you use this confirmatory test. 

    Kyle: You’ve made it clear that you don’t have any ties to these companies and that you really just want to see these tests get out there, and you’ve been an advocate for the government to really step in a work directly with these companies to try to get some programs going. That said, you mentioned Abbott, you mentioned Roche, what companies have a good, viable test right now that may be used internationally that’s not yet approved by the FDA?

    Dr. Mina: Yeah, so Abbott has the BinaxNOW; this is the card that is approved for medical use in the U.S. and has now been distributed. It’s not the right form factor for at home, because, for example, the bottle with the little buffer that you mix the swab into, it’s a bigger bottle, so one bottle is good for like 40 tests. So, it’s not packaged in the right way for home use. It could be. It definitely could be, but it’s just not, the way that they’re selling it. But Abbott actually has another test called the Panbio, which is one of these tests. It looks just like this; it’s got the plastic casing around it. But this is just, like, a case, you can reuse these things. The Panbio uses the exact same reagents and molecules such as as the BinaxNOW card that’s around the United States. But it’s really simple and it’s much more scalable. It’s not being sold in the U.S., probably having to do with trying to keep the market for the BinaxNOW and not flooding it with this other cheaper test, or I should say more inexpensive test, not cheaper. It’s inexpensive. But then there’s the Roche-SD Biosensor. It’s a great collaboration between Roche, the world’s largest diagnostic manufacturer and a company in South Korea to produce a test that looks just like this. There is AccessBio, it’s the one company that’s making these tests right on American soil. They’re in New Jersey. They have around 500,000 tests per day that they’re building now. They can scale up to a couple million, ideally, by early next year. But, you know, if this little company can scale to 2 million, the U.S. government could definitely scale to 20 million. This is a no-brainer. So there’s a number of companies, though. There’s a whole slew of additional ones, MyBio, and I don’t know, I lose track of all the names that are out there.

    Kyle: Is E25Bio still working on this, too? Because we spoke with them.

    Dr. Mina: E25Bio is right down here, right in Cambridge near me and they are still working on it. They have a contract manufacturer that they are trying to work with, and I believe that they have an approval waiting in the FDA. There’s a number of companies that are waiting for their authorizations. Now, as far as I’m concerned, there should be almost no wait time. This should be one of the highest priorities, but even E25Bio, because of the way that all of this is being authorized, they’re going for a medical claim. You know, you’re going to have to get a doctor’s note, it’s probably going to be a nasopharyngeal swab instead of a self-collected swab, and I don’t actually know exactly where they’re at. But all the companies are kind of going in that direction right now. And it’s a real travesty, because this is a tool that we want for public health, and we don’t want to isolate it to requiring a medical note to get this. I mean, just to put it really bluntly, this is illegal for me to use right now in my house. I mean, there’s a pandemic going on and I’m not allowed to know, in my house, on my own, if I have contagious virus in me. That’s insane. We should all be rising up and demanding that our politicians demand that these things get put out into the public domain. I mean, people want these tests. They want to know if they are infected and they don’t want to be footed with a $400 bill at the end of the day. I think that the government should just be making these for people, giving them for free, and allowing people to use them on their own. And, so I got off topic there a little bit, but [laughs].

    Kyle: And along those lines, just to be specific about it, if this COVID-19 task force that’s been newly appointed, is looking for a way to have these public health tools, as you’ve called them. They’re not medical grade diagnostic tests that you would use as a clinician in the hospital to confirm or rule out COVID-19 at the bedside, but they’re what we need for a public health crisis like we’re in. Should this fall under the CDC? Should the task force and the government create a whole new, kind of, entity to oversee something like this? What would you recommend?

    Dr. Mina: Well, I think… do we need a whole new entity? I think that we actually have all the institutes we need. One is, we don’t want these to be deregulated. That’s one of my fears. Because technically we could start skirting issues. We could use these and say, “oh, positive doesn’t necessarily mean positive. It means go get a confirmatory test.” You know, there’s ways to skirt around the regulation if need be. The companies aren’t really willing to take that risk and build them given that potential, but… I want them to be regulated because I want to make sure that the ones that are going out to Americans are good quality. Because we have good quality ones and then there’s a lot of bad quality tests, too. And antigen tests, in particular, can range just like those antibody tests ranged in quality early on. And so I want to keep these as regulated devices, but I want them to be regulated in a different way. I want the FDA to think about them as a public health tool and regulate them with that in mind. Don’t compare them to a PCR test, because that’s the wrong comparison. Like I said, 70 percent of the time that  somebody’s PCR positive, this is supposed to be negative, so that’s the wrong comparison to make. I do think we need kind of a dedicated team to just focus on, OK, how are we going to build them, where are we going to put the factory? OK, we found a factory space, now we’re going to get the instruments to go in there. And that could be done in a matter of weeks if the government wanted to. And then you have to have another group of people working with the U.S. Postal Service or Amazon or whoever it needs to be to figure out how to get these tests out into the households. We have the postal service; they go to every house in America, so we could do that. Package them up and pack little tubes of ten. Put them each in a tube, package them up and send them to all the households in America. We can do that. So, that would take another set of logistics, but not insurmountable at all. And then we have to work with messaging. We should get the news anchors on board and media. If this is really going out to every household in America, or every other household, it will become a national, it will gain national movement attraction by the media, so we could even ask the news anchors, “hey, do the test. You’re going to get one in your own house.” Do the test on TV. Let Americans know how to do it, and we can work with the media in new and innovative ways to tackle a pandemic that is truly harming everyone in this country. And then, finally, we can also work with the Apples and the Googles and Verizons and AT&Ts of the world to make reporting of these tests voluntary, but easy. A lot of people don’t want to get tested just because they don’t want to be monitored. They don’t want to get that call from somebody that says, “hey, you’re positive, you need to lockdown” and all this stuff. They want to do this on their own terms, and we have to, as public health professionals, recognize that that’s what people want. We have to meet people where they’re at. Anything else will not work. Forcing things on people is never a good idea. And it just isn’t going to work here, unless we’re planning to lock people up, which we’re not going to do. And rightly so, we’re not going to do that. So I think we need to meet people where they’re at, we need to recognize some people just don’t want to report their results, they don’t want to be part of the system, and so that’s OK. But they do want to know if they’re infectious so they don’t mistakenly go and kill their mom. Even the most ardent non-mask-wearers still I think do want to know if they’re infectious so that they can not expose the people they love and care about. And so we can make voluntary reporting a thing, and we can work with Apple and Amazon, whoever, to make — if I can order a new video camera for my computer with one click on Amazon, I’m pretty sure Amazon and Apple and Google can figure out how to make it a one-click reporting structure to just go straight to the CDC or your Department of Health and they’ll get the report. They’ll know where you are when you put in your zip code and however much information you want to about yourself, and boom, we actually have very much more public health information going to the officials than less, if we’re just getting a fraction of voluntary reporting, but of a huge number of tests being performed. It will really help public health, individual health, and we’ll see the pandemic subside in the United States. But I guess my point is, to answer your question, it needs to be coordinated. No one piece of this is that difficult — it’s really not — but it does need to be coordinated, so we probably need a team at the federal level to do that. 

    Kyle: You’ve used the analogy before that it should be like a war effort, and with the amount of people that are dying and getting infected, it certainly seems like it warrants that. Wars are expensive, you know, this type of testing that you’re talking about would have a significant cost associated with it. I noticed that you are a recent author on a paper about some of the economics of this type of testing. Could you briefly describe that?

    Dr. Mina: Sure. That was a paper with some other economists at Harvard, Jim Stock being the lead on that. So we asked a question, getting these tests out to every American isn’t going to be super expensive, but it’s not going to be free either. So what would be the economic gains of this? We used a very conservative approach. We overpriced what these would likely cost to make, and we undervalued how much we would probably save in economic recovery, for example, from getting rid of the virus. And what we found is the return on investment is huge. Even if we assume that these things are much more expensive than they are to build, and we put 50 billion dollars into this program — to build them, to get them out to places — I think probably the whole thing for a full year — and it won’t need to be a full year — it’ll be a few months of using them — can probably be done in under 10 billion dollars. But let’s say it’s 50 billion dollars. The return on investment is huge, if it means that we’re even just getting the virus under control, even just a week earlier, that pays for it all. Two weeks earlier, three weeks. But this could actually get the virus under control months and months and months earlier. Within weeks of rolling this out, we could actually start to see exponential growth across the population, fall into exponential decay of the prevalence of the virus, and so the benefits to society are, just from a financial perspective, are huge. We didn’t even really factor in the intangible benefits of being able to see your family again, of being able to go to a restaurant without a mask on, or go shopping. These are intangibles, but right now this virus is costing America billions of dollars daily. I don’t think people are realizing that. When they say “ooh, that’s a lot of money,” a few billion dollars, no, that’s not a lot of money. We spent something in the order of six trillion dollars at this point directly on this virus through the spending packages and interim — or it’s cost us six trillion dollars or so. Projections are that it will cost the country 16 trillion dollars when this pandemic is done for this country. And so this is less that 1/1000th of that cost to potentially save trillions of dollars. The financial question should not even be in the discussion. It’s so cheap compared to what the virus is costing us. 

    Kyle: Well, we’ve talked a lot about what should happen, and that there is bipartisan support for rapid testing. You’ve been advocating for this, experts around the world have been advocating for this, Dr. Fauci is now advocating for this, so hopefully we see it very soon. That said, currently, we live in this reality in this country of the testing we have, and Thanksgiving’s coming up, some of our U.S. holidays are coming up in December. What tips, if any, do you have for viewers about testing in general with what we currently have? For example, I know you’ve advocated to not get a PCR test if you know the turnaround time is going to be X amount of days. So what are some practical testing tips?

    Dr. Mina: Yeah, well, first, I guess just to answer it, follow the other precautions. Wear a mask as much as you can. Keep your gatherings small. Don’t stay home by yourself. I don’t want to advocate for people to get depressed, but keep your gatherings small. And try not to, if you’re going to work every day and you might be getting exposed, maybe it’s not the best time to invite grandma over. I really am a big proponent of “pods,” keeping a couple of neighbors or one family that you really stay with, but recognize what other pods they might be in so you can understand what the chains of transmission look like. When it comes to testing, though, there’s one thing that’s exceedingly important to know. And that is, don’t get a PCR test a week beforehand and think that it means anything for you by the time Christmas comes around. Even if you were positive! If anything, being positive a week beforehand means that you’re probably not transmitting by the time the holiday that you’re trying to attend comes around. Again, it’s a short window of time and so if you have access to a rapid test, say at a Walgreens drive-thru or something like that, then that’s one of the best ways to use a test. The closer you can get the test swab done and the report given before whatever it is you might be doing, the better. So, if you have an opportunity, if you are going to a gathering, either way, the best way to make it safe, besides all the other things, like masks and distancing and keeping your windows open and such, is to get a test right beforehand. A rapid test, 15 minutes before you walk into your family’s house is better than a PCR test taken two days earlier. It just is. And I could go through the math of it, but it just is. And so, if you’re worried about transmitting to other people, then try to get a test right beforehand. Most Americans, though, don’t have access to rapid tests right now. They just don’t exist in the United States in the way that I’m calling for. So, the closer you can get the swab taken, the better. Don’t mix up the time when you get the results for the time when you got the swab collected. If you get the results Thanksgiving morning, that doesn’t mean you are negative Thanksgiving  morning. That means you were negative or undetectable three days ago when you got that swab taken. It’s really, really, important to recognize that, so if you can find a quick turnaround way to get a PCR test, say 24 hours, that at least cuts your risk. It doesn’t eliminate it, but it does cut your risk of being highly infectious the next day. But, I’ll give a concrete example of why it’s so important to recognize this, because schools keep doing this, universities say we want to bring students back, but we want to get them tested in the week before they come back. Terrible idea. Let’s say somebody is on the upswing of their virus and they get a test at day minus seven before they go to school or they go home for the holidays. Let’s say you’re still negative then. By the time you get your test back, it will say that you’re negative, but you’ll actually be in the peak of your infectivity at the time you get that test back. So it’s very, very deceiving. And this is the whole problem with delays in testing and getting PCR results back three days later. But even 24 hours earlier, if you get a negative on a PCR but you happen to be in that upswing of the virus, then 24 hours later, you might be in the peak or near the peak of your infectivity 24 hours later. Meanwhile, an antigen test taken at that same time 24 hours later would be positive if you’re sort of near the peak. So PCR can be really deceiving and I think we’ve had a hard time in the medical community coming to terms with this. We continue to push it as the optimal test, but as long as there’s a delay, it’s frankly not an optimal test. 

    Kyle: Are there any other misconceptions that you commonly come across in conversations with leaders or people interested in these tests that we haven’t already covered that you want to speak to?

    Dr. Mina: No, I think the biggest thing is people just say — well, there’s a few things. It’s the accuracy. People think it’s inaccurate. It’s just not true and I hope that we covered that. When it comes to transmissibility, frankly, it’s more accurate than PCR. People say they don’t exist. They do. We just don’t have them in the U.S.. Let’s not be blinded here. They do exist and they can exist. This is a good tool that people — I have friends in Germany and Israel and all over and they’re using these all the time. They get them for five euros and its a no-brainer. They can just get it. It’s not a big deal. I want people to recognize that these exist. The only reason they don’t is because we haven’t had the political will or the strategy in America to do it. We haven’t had bold leadership to say, “I’m going to be the leader to do this.” We need some governor or senator or representative or president or anyone in between, but somebody, to say, “I’m going to tackle this. I’m going to be the first one to do this because nobody else is doing it in America.” There’s a lot of traction back in June and July for this, and then nothing really happened at the political level. But I hope that people will again really push their elected officials to push for this. Now, people have heard about it. This has been on the news, New York Times, NPR, every so often you’ll hear them talking about it. A lot of people have heard about it by now. And I know that the House of Representatives, the Senate and the President’s teams, they all know about it, too. So we can push on them to demand it. This is a tool that will keep people safe, and we should have access to it, not let this archaic view of what a test means in public health versus medicine be stopping us from having access to safety measures. 

    Kyle: And is the fact that we have a few now, vaccine candidates, that appear to be viable and appear to be close to getting emergency authorization, does that make rapid testing, at-home testing any less important?

    Dr. Mina: No, this is a huge misconception, too. People keep saying, “well, the vaccine’s a month away.” For one, the vaccine has been a month away for six months now. We don’t know what’s happening with this vaccine, but much, much more important than that, these tests are not instead of the vaccine, and a vaccine is not instead of these tests. That’s just not logical thinking. The vaccine, first of all, isn’t going to hit most Americans for months, probably not until the spring or summer. We’ll see very limited numbers of people start to get them maybe at the end of December, but that doesn’t account for most people. But there’s a few other things. The vaccine, we don’t actually know how good it’s going to be. The exceedingly high efficacy values are very, very encouraging, but there’s a lot wrong with the way that we’ve measured efficacy so far. We’ve measured — I don’t want to go into too much detail with this — but we’ve measured efficacy only in the short term after people get a vaccine. So right after you get a vaccine, you get a whole burst of plasmablasts, they’re called. These are antibody secreting cells, but they’re temporary. And they last for a couple of months. And those couple of months are exactly when we’ve measured the efficacy of this vaccine. But then those plasmablasts that are pumping out the majority of our antibodies during the acute phase after a vaccine for a few months afterwards, they die. By definition, they die. They go away. So, by measuring efficacy in the way we have so far is kind of like saying, “we’re in a war, we bring all of our troops to the frontline, and we have a 95 percent effectiveness to keep the enemy at bay.” But if we then withdraw all of those troops, it doesn’t mean we’ll still have a 95 percent efficacy to keep the enemy at bay, just because we have a few snipers up on the towers still. So that’s what we’re assuming that it would mean the same, but obviously anyone who knows anything about how people fight, if you remove the people, then the enemy has a much better chance of getting in. Same thing here. The plasmablasts will die off, and then you’ll have fewer antibodies being produces. And we just don’t know what it means at six months, for example, or even four months. That 95 percent efficacy or 94 percent efficacy could drop to 40 percent. We actually don’t know. And people haven’t really been willing to talk about this aspect of immunity and vaccines and viruses, but we should be. Because I worry very much that the vaccine is clouding our willingness to take controlled action in other ways. There’s two other pieces, too. One is that this virus, all the vaccines are generally clones of each other, in terms of the way that they’re presenting a protein to the immune response in terms of the spike protein. So they’re all generally the same. We don’t know what this virus is going to do once we start applying pressure to it, when we start vaccinating everyone. It just takes one mutation somewhere, out of the quadrillions of viruses that are forming and growing in people across the globe, it takes one, just one, to escape immunity of the vaccine at some point and start spreading again. And hopefully the vaccine will elicit enough immunity, so that we can ward that off, but we just don’t know. And it could very well start to escape immunity quickly, and then we’re back to the drawing board. I don’t think we’ll be all the way back to square one at the drawing board — our immune system will hopefully still hold some protective benefit. And then, finally, we just need contingency plans. The good thing about these tests is if the virus mutates, they’ll still work. For all kinds of things, these tests will still work. If a new virus comes around, a new pandemic, then we just change the ingredients of the tests and the tests work. So this is also pandemic preparedness for the next time, which will be in the next few years probably. We’ll have another flu virus, another coronavirus in the next 10 years. We don’t know, but we do know that more pandemics are on the way, and so we may as well prepare. And so this isn’t all for naught. 

    Kyle: And just to state the obvious, correct me if I’m wrong, adjusting a $1 paper antigen test is much easier than trying to adjust a vaccine to a mutation or a new virus.

    Dr. Mina: That’s exactly right. These tests — the safety profiles — there isn’t really a safety profile that we have to evaluate that’s unknown here. So it’s really easy to update a test for a new virus than to update the vaccine for a new virus. 

    Kyle: Well, Dr. Mina, thanks so much for this discussion and for being so generous with your time with this interview and all the other media appearances that you made in advocating for this. We really appreciate it. 

    Dr. Mina: Thanks a lot. 

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