COVID-19 Testing: Eric Topol, MD, On Getting It Done

John Whyte, MD, MPH;  Eric J. Topol, MD


April 22, 2020

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This transcript has been edited for clarity.

John Whyte, MD, MPH: You're watching Coronavirus in Context. I'm Dr John Whyte, chief medical officer at WebMD. Everyone is talking about testing as a solution to get back to work and reopen the country. But is testing all it's cracked up to be? What are the challenges? To answer these questions is my friend and guest, Dr Eric Topol. He's the executive vice president of the Scripps Research Institute and editor-in-chief of Medscape. Dr Topol, thanks for joining me.

Eric J. Topol, MD: Great to be with you, John.

Whyte: Everyone is saying that we need to do more testing, whether it's diagnostic testing or antibody testing. What are your thoughts about the role of testing? You've been somewhat vocal about it.

Topol: I think it's clear that we do need an exponential jump in testing. I was part of the Rockefeller Foundation report that was just issued yesterday where we actually called for scaling up from 1 million to [3 million] and then to 30 million tests a week.

Whyte: Three million by June, which is not far off.

Topol: Right. We have barely done 1 million since starting, so we're far behind. And this is a big problem. Even the 30 million a week is a compromise because you have 330 million people. And you can't just think that you're going to do it once. A lot of people are going to come out with a negative test, but they could subsequently become positive, whether it's for the virus or for the antibody. We have a problem with not being able to reach a large number of people, and on a frequent basis.

The other thing is that the tests are not as good as we'd like, for accuracy. We have a false-negative problem with virus testing. We have a false-positive problem with antibody testing. There's false everything, for both of these tests.

Whyte: How bad is it, do you think? Is it based on the prevalence of the disease in the population, in terms of its positive predictive value and negative predictive value—those people who test positive who are truly positive, etc.? What do you think the number is? Some people are saying it's 70%. Is it that low?

Topol: You're bringing up a really important point for the seropositive antibody test. Because the prevalence is so low—probably 2% or lower—their chance of getting false positives is higher. For the virus, the RNA test, the false-negative rate could be as high as 25%-30%.

The other key point about testing is that there are so many different tests. Today we've learned from Yale of a saliva test that would be much more palatable than a nasopharyngeal swab. It looks much better, but obviously we need more data.

There are more than 90 antibody tests, and many of these are getting emergency use authorization from the FDA with limited data, and that doesn't help. The key point there is that we have too many people spread out all over the country. We have to test them frequently, but we have shakiness in the tests.

We need another plan. We can't rely on testing. In the Rockefeller report, there were three big initiatives. One is testing. The second is contact tracing. We don't have the labor force to do that, but we need to have that. The third is digital surveillance.

The idea here is to use a smartwatch, for example. We have a successful app called Detect, which we launched a few weeks ago. We have many thousands of people on it, and we're collecting resting heart rate.

Now, resting heart rate goes up before fever. We had already published in the Lancet Digital Health Journal earlier this year that we could predict the flu before the CDC could, and at least as accurately. The point is that resting heart rate is a really valuable marker, and over 100 million Americans have a smartwatch or wrist heart rate detector. So if we got a large number of people opting in through the Detect app, we could really get our arms around this. And that's just one tool. You could also go for body temperature.

Whyte: You mentioned contact tracing. There's talk about hiring 100,000 workers to do contact tracing. Is that realistic? You've been a big proponent of tech. How does tech play into this? I mean, it's not one or the other, but where do you think we're going to get the biggest bang?

Topol: Well, digital contact tracing is attractive. It uses smartphone chirps to alert people that they've been in contact. Singapore has the most experience so far, but even with the instruction from the leadership of the country, there's relatively limited use, and it isn't clear that it's as good as human contact tracing. We want to see that work well. We've got this thing for the next year and a half or 2 years, and we need methods that don't rely on slowness and don't rely only on the human labor force, because that takes a while to develop and it's very expensive.

The Google and Apple program for digital contact tracing, which is supposed to start in May, needs to get validated. We have to do paired studies to show that it comes up with accuracy as good or better than human contact tracing, which is the gold standard.

Whyte: But don't we also have to get 60%, 70% plus to opt in? That's hard to do for any type of app.

Topol: Yes, you need a large proportion of people willing to do it. It's not something you can mandate. There are obviously legitimate concerns about privacy, especially when you bring in the tech titans on something like this. But I think it's worth emphasizing that if it's validated, people might trade off some temporary privacy compromise in order for everyone to try to restore the way life used to be, the chance of being able to get back to work in a pre-COVID world.

So these are the sorts of things we have to think about. We're not prepared for tracing at all, as you've pointed out, John. Testing, we're not prepared for, and tracing, we're not prepared for. The only thing we're prepared for is that we've got 100 million people out there with a smartwatch.

And all they have to do is get on the app and start to donate their data, and we can likely—I mean, we have to prove it—but we can likely pinpoint where clusters of people with resting heart rate elevation are starting to appear before an outbreak has gotten to any significant level.

Whyte: Dr Topol, what are other countries doing better? You've been tweeting a bit about what's happening in Germany. What are the differences?

Topol: It's actually pretty remarkable, John. In Germany, they read our paper in Lancet about the ability to predict flu from resting heart rate from a smartwatch. So they initiated a program, and within a matter of days they now have over 300,000 German citizens who have donated their heart rate data continuously. And they're extremely happy with this ability—at essentially no cost—to have digital surveillance throughout Germany.

And they're going to keep building the number of people on it. This is a very attractive, alluring way that we can get our arms around it. If it happens immediately in the US, we're fortunate. Over 100 million people have a smartwatch or a wristband that gets heart rate data. It could be quite valuable for us.

Whyte: Can we add a pulse ox to that so we get some sense of oxygenation? Is there value there? Some of them are, you know, in terms of where we are in technology, amazing.

Topol: You're right. Good point, John. Some of the newer Fitbits and other watches do have an oxygen saturation capability, and some have validation. The problem is that if you start having drops in your oxygen saturation, you're much more likely to be symptomatic and have already had some medical contact. We're trying to pick things up really early.

But you're also bringing up another point, which is using digital surveillance to keep people out of the hospital. And we need to be thinking about that too, because a hospital is not a place to go unless you are pretty darn sick. The problem with that, just to be clear, is that we don't have algorithms to say it's safe to stay at home. Sometimes, as Medscape has covered, there can be sudden demise. So we've got to also make sure we have that nailed.

Whyte: Eric, where do you feel we are on antibody testing today? You referenced it a little earlier. The challenge, as you pointed out, is their emergency use authorization—not a true approval for most tests. There are only about three or so that have truly been approved. They have lower standards of accuracy. So are we there on antibody testing, or should we not get too excited about it right now? What about these "certificates of immunity" that some people are talking about?

Topol: That goes back to Germany—the immunity certificate. But that is flawed to some extent. The first point is that no one has a good serology test that's been fully validated. The problem is that there are four other coronaviruses that can cause common colds, and some people have high titers of IgG antibodies to those coronaviruses that cross-react with the coronavirus of interest, COVID-19. So we have problems with false positives. It's a delicate assay. There are more than 90 of them, and none have had validation at scale.

There's another issue. Let's say you have a test that's 100% accurate, which doesn't exist yet. Then how long does that protection last? If you have antibodies, could you still spread? Might you reactivate or potentially even have reinfection? That hasn't been clearly demonstrated.

So even if we had assurance that the test was fully accurate, we still have lots of unknowns. And we have to fess up about it. Just because you say, "Oh, you have a positive antibody test," well, it's not just 0 or 1. Some people have low levels of IgG against COVID-19, some have very high levels. So this is full of holes right now.

Whyte: And you're always very practical. So let's be practical for our last minute. In the Rockefeller report, you talk about how we need to do more testing and better testing, whether it's antibody testing, diagnostic testing, whatever. We need to do better contact tracing, whether it's hiring people or using tech. And then we need to have these digital tools, which in some ways is for surveillance, and also to help with diagnosis.

We can't do all three well, and there's some element of [limited] resources. So where do we need to be spending more of our efforts? Not that the other two aren't important, but if you had to focus more on one, where would it be? Would it be on these digital tools?

Topol: Yeah, I think they've been grossly underemphasized. And the reason I say that is, in the Rockefeller panel of 20 or so experts, none of them were particularly interested in the digital side. They were just arguing about how many tests. But frankly, we recognize that it would take 6 months to get to 30 million tests a week.

We can do the digital surveillance tomorrow if we had national support. It's relatively cheap, and heart rate by smartwatches is quite accurate. Again, it isn't at the individual level. We're looking for clusters of people whose resting heart rate is changing. So I am a proponent of that, but I don't want to dismiss testing at scale, frequently, both antibody and virus, and the contact tracing. These are all important.

The critical issue is that we got so far behind this pandemic in the US and now we're playing catch-up. And there's no great strategy. All the things we're talking about are really difficult. The easiest one is, "Hey, you've got a smartwatch? If you don't have one, we'll send you one. Let's get that heart rate data." It works quickly. It's passive. There's nobody sticking a swab up your nose. It's pretty straightforward.

Whyte: And it's a good point. Thank you, Dr Topol.

Topol: Thank you. It's great to talk with you again, John.

Whyte: Thank you for watching Coronavirus in Context. I'm Dr John Whyte.

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