Rethinking Our COVID-19 Testing Strategy
This story is a part of Science Friday’s coverage on the novel coronavirus, the agent of the disease COVID-19. Listen to experts discuss the spread, outbreak response, and treatment.
Throughout the pandemic, testing has continued to be one of the biggest issues, particularly in the United States. Some scientists say that the solution is to rethink our COVID-19 testing strategy, focusing on making faster, cheaper tests. While these more cost-effective tests may be lower in sensitivity than the PCR tests and perhaps not as accurate, they would allow for more people to get tested and receive faster results. The system can also help improve case tracking—which is essential as more people return to work, school, and daily lives. Eric Topol, the founder and director of the Scripps Research Translational Institute, talks about how these tests can look ahead for infectious patients rather than those already infected. Plus, epidemiologist Anne Wyllie walks us through what the process would look like to develop a rapid test.
Update: The SalivaDirect research group is awaiting Emergency Use Authorization from the Food and Drug Administration for the test, not approval as stated in the interview.
*Editor’s Note 8/14/2020: This page has been corrected to fix a misspelling of Anne Wyllie’s name. We regret the error. Clarification has also been added on the status of the SalivaDirect research.
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Eric Topol is the author of several books, including Deep Medicine: How Artificial Intelligence Can Make Healthcare Human Again (Basic Books, 2019) The Patient Will See You Now: The Future of Medicine is in Your Hands (Basic Books, 2015), practicing cardiologist at the Scripps Clinic, and a genomics professor at the Scripps Research Institute in La Jolla, California.
Anne Wyllie is an associate research scientist in Epidemiology at the Yale School of Public Health in New Haven, Connecticut.
IRA FLATOW: This is Science Friday. I’m Ira Flatow. Throughout the pandemic, one of the big issues has been, of course, testing. The main test used to detect COVID-19 infections are polymerase chain reaction tests. These PCR tests are highly accurate and reliable, but they have been hampered by all sorts of issues– not enough of them, taking too long for results, for example.
Some scientists are saying that the solution is rethinking our testing strategy, make faster, cheaper tests. And while they may be lower in sensitivity than the PCR tests and perhaps not as accurate, they would allow for more tests, faster results, and better tracking. So is the trade-off worth it? What are some of the possibilities, and advantages, and disadvantages? And how should we rethink our testing system?
My next guest is here to speculate with us, Dr. Eric Topol, Founder and Director of the Scripps Research Translational Institute, Professor of Molecular Medicine, Executive Vice President of Scripps Research in La Jolla, California. Welcome back, Eric. Always good to have you.
ERIC TOPOL: Oh, same here, Ira. Great to be with you.
IRA FLATOW: Let’s first talk about the PCR test. They have been the go-to test to determine if you are infected with COVID-19, but you say the tests have a different mission. Tell us what’s wrong with these tests.
ERIC TOPOL: Well, you covered, of course, the practical aspects, that they’re hard to get, and they’re taking too long to get the results back. But the bigger problem is that they test whether someone is infected, and that’s not what we really are interested in. Our exit strategy from where we are right now is predicated on knowing if someone is infectious. So all–
IRA FLATOW: The difference being? The difference?
ERIC TOPOL: So the difference is there’s a lot more viral load, a lot less– a lot more likelihood that you could spread an infection. So just because you have some RNA nucleotides picked up by a PCR, which, as you said, is pretty darn sensitive, we don’t need to know about that. We need to know whether you can transmit the infection. Because if you can’t transmit, then you’re good to go.
IRA FLATOW: So what will tell us– what kind of test would tell you if you’re infectious?
ERIC TOPOL: Well, there’s 20 different companies working on this and lots of different academic labs around the world, and so there’s lots of different solutions. Most of them are using the so-called RT-LAMP assay. But what it does is gets the results within 20 minutes, 30 minutes, at most.
It’s very inexpensive. And it’s pretty darn sensitive, but not as sensitive– and that’s good– as the PCR test, which is the standard today, which isn’t perfect, by the way. The PCR still has a 10% gap of missing false negatives.
IRA FLATOW: So if you had a test that was not terribly accurate, I mean, not 100% or maybe not even 75%, let’s say 50%, a quick, easy test, cheap, 50% accurate, is that still a useful test?
ERIC TOPOL: Well, firstly, that 50% is using the wrong benchmark because that’s against PCR. What you really want is, is it picking up infectious, the person is infectious accurately? That could be 90% or 100% if we get the right threshold. How many copies of virus? How much viral load?
So that’s what’s great about this is that it’s a whole new path. And the problem, of course, is it hasn’t been recognized. And it’s vital that we get behind it, because it’s really a practical way that could be done by anyone in the home or any environment and get an answer quickly.
IRA FLATOW: Why has it not been recognized?
ERIC TOPOL: Well, there’s three major reasons. One is that because it goes through the regulatory path of FDA and they’re still holding PCR as the standard, they haven’t recognized this as an independent new pathway, and so that’s a problem. The second thing is, as you well know, you need millions, millions, tens of millions of these tests to be manufactured. And these are largely startup companies or academic centers, and they don’t have the means, they don’t have the funds to do that, so it’s a catch-22.
If they can’t get FDA clearance, they sure can’t go into high production. And that gets us to the fact that the government has not gotten behind this like it has for vaccines. In fact, none of the rescue PPP funds have been going to this diagnostic rapid home testing.
So this is a real problem. It’s a lack of financial support, a regulatory pathway that hasn’t been established, and finally, the fact that you have to prove it, that is, all this makes a lot of sense, but you have to show that when you use these tests at scale you don’t have infections that get spread. So that’s the one other piece that has to get validated.
IRA FLATOW: Mike DeWine, the governor of Ohio, tested positive with a rapid test, but then he tested negative with two different PCR tests. Are we risking having more false positive tests?
ERIC TOPOL: Well, actually, the good part is the false positives are not the worry here. The problem, even with some of the tests that are used today that are so-called rapid, they’re requiring very expensive machines. They can’t be done at home or at scale, and they do generate false negatives. For example, the ones that are used at the White House and many other places where– the Abbott ID test, for example, is notorious for having a sensitivity problem. So that’s why this whole new path, this whole new type of testing has a lot of appeal.
IRA FLATOW: Let me bring on somebody who is developing a whole new type of testing, who is part of a team developing a rapid test called SalivaDirect. And as you can guess, it uses your saliva. The test is currently in the process of being approved by the FDA. Anne Wyllie is an Associate Research Scientist in Epidemiology at Yale School of Public Health in New Haven. Welcome to Science Friday, Dr. Wyllie.
ANNE WYLLIE: Thank you.
IRA FLATOW: Tell us a little bit about how your saliva test works. And what part of the virus is it testing for? Why is it rapid– give me the ABCs, please.
ANNE WYLLIE: So what we’ve done with SalivaDirect is we were wanting– it is still, as you say, a PCR-based method. We are still relying on laboratories for testing it at the moment. But we saw early on in the pandemic that saliva was giving us comparable results to the nasopharyngeal swab, but it had the benefit of not needing that deep brain swab.
It wasn’t relying on swab kits that were in short supply. It had less risk to health care workers. It could be easily collected by just about anyone. And we realized that as this was going forward, we were going to start to see a shift and needing to move away so much from the diagnostic test, but to ongoing screening and surveillance as we start to reopen our communities.
So we really wanted to make a test that was a lot easier to take, a faster turnaround time. And we had seen others taking their swabs and testing them, almost directly, into PCR, so we decided to see if we could do the same with saliva, and we have been able to. We do a very minor workup, and we take away the RNA extraction step. Taking away that RNA extraction step saves a lot of time, but it also saves a lot of money in terms of the resources needed to do the RNA extraction and the hands-on time of people to do that test.
IRA FLATOW: So how quickly can you turn a test around? How cheap is it? And how accurate is it?
ANNE WYLLIE: We’re using the CDC N1 primer, so this is a primer that’s being used in tests all across the country already, which has shown to be very specific for SARS-CoV-2. I mean, we are still relying on a PCR, so this is still something that has to be done in the lab. But by removing that RNA extraction step, it is only– we can get results in about two to three hours.
But this is– so that doesn’t seem like rapid for an individual test. But these plates can hold up to 90 samples on a– in a reaction. So we can test 90 samples in perhaps less than three hours, so this is a much faster turnaround time than what we are seeing otherwise.
IRA FLATOW: And the price point we’re talking about?
ANNE WYLLIE: We’re looking at anywhere between $1.50 and $4.50 per test, depending on what reagents you use.
IRA FLATOW: And as you said before, the reagents are quite commonly available. We don’t have to go out and get some exotic stuff.
ANNE WYLLIE: That’s right. And what we’ve actually done without FDA EUA is that we’ve validated reagents from a wide range of suppliers and different manufacturers with this idea that different labs will have connections with different suppliers. We also want to circumvent any supply chain issues with demand. And we’re also hoping that by having reagents available from different suppliers will help keep costs down and not have a single company jack up their prices in response to a recommendation from us.
IRA FLATOW: Of course, one of the issues with new tests is that you need to test them, and you have studies to see how effective they are. I understand that to do this, you’ve partnered with the NBA. Are you testing the NBA players?
ANNE WYLLIE: We have. It’s a very interesting scenario to find ourselves in, but indeed. And the NBA reached out to us earlier in the year because they had seen our work with saliva, and they realized– same as everyone else, you know– they would much rather be taking a daily saliva sample than taking a daily nasopharyngeal swab, or any other swab, for that matter.
They could have reached out to anyone of the industry partners out there and just bought some rapid tests for them to test with. But they really wanted to help support research, and after discussing with them, we realized that our ideals quite aligned. We wanted to make testing more accessible at price points that could reach right across the community.
And so they really helped us to continue our research into saliva. And indeed, we do need to validate this myth on asymptomatic individuals to show that this can be worked in a screening manner for healthy people. And the time and resources to set a study like that up by ourselves when we have been so stretched thin responding to this pandemic would have been near impossible.
So we know to piggyback on their resources and have them send us saliva samples. We receive them blinded. We don’t know who they are or who they’ve come from. But we’re comparing them to their true diagnostic test that they’re having taken by Quest or Bioreference. So it’s been a incredible opportunity to validate our method and in a healthy asymptomatic population.
IRA FLATOW: How close are you then to doing a home test that you could send a tube or people can get a tube, put their saliva in, and how close are you?
ANNE WYLLIE: So at the moment, our FDA EUA will be for a saliva collection under the guidance of another individual. Going into the home and getting home tests is where the regulations are still really tight at the moment. We are working on that. We’re looking into things.
We’re seeing that you don’t need really expensive collection tubes to take saliva samples. You can just almost spit into a very simple plastic cup or plastic container, which also helps keep prices down. We’re going to see what we can do.
But I think one of the things I’m most excited about for our FDA EUA is that our SalivaDirect is not only the rapid fast point-of-care possible test that’s out there. There’s so many others that have been developed. And I just hope that us giving our EUA will really help pave the way for other tests to also get the EUA more easily through the FDA, and we can just open up testing right across the board.
IRA FLATOW: Eric Topol, how close do these tests that she’s talking about come to the kinds of tests you’d like to see?
ERIC TOPOL: Well, I think what the innovation that Anne and her colleagues at Yale did is just terrific. The problem, though, is we need to get the results for home wide-scale use even quicker, that is, the 20, 30-minute, or even shorter. So a lot of these tests that are now in ready mode for scale production and testing are paper strips or change in color of liquid that you can get in 20 minutes and are very inexpensive, like what Anne described, even at the level of $1 per test.
So the frequency of the tests is really important. And I think you mentioned that, Ira, at the outset, that if you do this test that’s done on a frequent basis, like every day, that’s where you’re making a big difference. And so I think they’re very different– the path of these rapid inexpensive frequent testing, whether it’s for the antigen, that is, a protein of the virus, or the virus per se, is different than trying to get a plate of a large number of samples in a two or three or four-hour period. So we need for speed and frequency, and, of course, the accuracy of infectiousness. Those are the things that need to be emphasized.
IRA FLATOW: I’m Ira Flatow, and this is Science Friday from WNYC Studios. And how do we scale-up to get a test that costs about $1 and can get out to everybody and get to the point where you would like to see it? What kind of revolution do we need in the testing business?
ERIC TOPOL: Yeah, well, as Anne alluded to, we need to get the FDA to buy into this, and quickly. They’re months behind. Anne’s paper was published months ago. Harvard, Heidelberg University, so many academic groups have been on this, but the FDA has not yielded.
Even though they made a statement recently that said they think this is the future, they haven’t changed from the PCR current standard. And that will unlock some funding, but also the government should get behind this. It isn’t just about vaccines, which still, that’s going to take time, and there’s a lot of uncertainties.
And the problem really is, Ira, when you get down to it from the bigger picture in medicine, diagnostics are like the Rodney Dangerfield. They don’t get any respect. But here, they are the way we see the virus. So we really need government and funding. If they put some of the rescue funds towards this, it would really help.
IRA FLATOW: Are there other countries that we can look to that have rethought this testing strategy, Eric, and have come down to your way of thinking?
ERIC TOPOL: Senegal in Africa, they’re capable of doing two-to-three-hour tests. In the UK, they’re adopting that right now. So that’s good. That’s a definite step, enormous step in the right direction when you think that people are waiting many days to get their results back now. So there are some efforts around the world. South Korea, early on, switched from the conventional PCR to one that was in the two-to-three-hour range. But even that is not ideal when you’re trying to make a decision when you wake up in the morning, am I good to go somewhere?
IRA FLATOW: And that’s the point, Eric. If you can test every day, it doesn’t matter if the test is not totally sensitive. By testing every day, you will eventually find out how infected people are.
ERIC TOPOL: Exactly. As you’re familiar with, Ira, there are many people who, once they get an infection, they can be PCR positive for weeks, but they’re not infectious. And that’s basically the story. We just want to know about the ability to spread an infection.
And so the whole idea is it’s a different threshold, a lot more virus load. And so that has to be established and proven. But this is something that’s very appealing when we otherwise don’t have an adequate alternative.
IRA FLATOW: Are you hopeful that the FDA might come around to your way of thinking?
ERIC TOPOL: Well, they’re certainly starting to get some pressure. I sure hope so. But of course, it’d be nice if we not only had that, but we also had a national coordinated plan to emphasize that this is worthwhile, that this is a way to get– for example, as you know, the school controversy is ongoing now.
But if we had each teacher, and child, and staff people, bus drivers, if they were being tested every day, we’d be potentially much more comfortable about opening schools in regions where there’s low spread or well-suited for this. So no matter what scenario you look at, this is a very promising path.
IRA FLATOW: Well, I’d like to thank both of you for taking time to be with us today. Anne Wyllie, Associate Research Scientist in Epidemiology at the Yale School of Public Health. Eric Topol, Professor of Molecular Medicine, Executive Vice President of Scripps Research, and Director of Scripps Translational Science Institute in La Jolla, California. Thank you both for taking time to be with us today.
ANNE WYLLIE: Thanks for having us.
ERIC TOPOL: Thank you.
IRA FLATOW: Good luck in your work.