Published on Nov 02, 2020

Video Transcript

[MUSIC PLAYING] JOHN WHYTE: Hi, everyone. I'm Dr. John Whyte, chief medical officer at WebMD, and you're watching "Coronavirus in Context."

Have any of you gotten a test for COVID? What type of test? How long did it take? Did you need a test? Should you have gotten one? To help provide insight into a lot of the questions that you all have around testing, I asked an expert today to join me. Dr. Geoffrey Baird is the interim chair of laboratory medicine at the University of Washington. Dr. Baird, thanks for joining me.


JOHN WHYTE: Let's start off with, there's basically two types of tests. There's the test that looks for genetic material of the virus. Those are those PCR tests that take longer. And there are some rapid tests. And rapid can mean different things, whether it's 15 minutes or 45 minutes. And it's not just antigen tests, but maybe some others.

But let's go back a couple of steps. And if you could give us a little lesson about testing for COVID-19, let's start off with those PCR tests that tend to be more accurate.

GEOFFREY BAIRD: Sure. Yes, so the coronavirus is a little tiny ball of protein. And we've all seen the pictures with the spikes on it, and those spikes are made of protein. But inside of it, the coronavirus has a genome, like you do. And its genome is made of genetic material. It's a slightly different type of genetic material than we have in our genomes. It's called RNA and not DNA.

And we have lab tests that allow us to identify a small piece of that RNA, convert it into DNA, and then amplify it. And by amplifying, what we do is, we have special chemicals that can latch onto a piece of the coronavirus genome and double it. So if there's one strand there, It can make two strands of the genome. And then we can double it again to make four, then to make eight, then to make 16. And we do that 20, 30, almost 40 times, and we can get billions and billions of copies of that. Those little tiny bits, we can then detect. We have a chemical that makes them glow in the dark or something like that.

So that that's generally how the PCR tests work, is that we can take a little bit of the virus, amplify it millions and millions and millions of times over and then we'll see a signal. And that's why the test is so, so, so sensitive, is that we amplify it so much before we try to detect it.

JOHN WHYTE: The challenge has been, they've been taking a long time to get back in certain cities, seven days, 14 days. Other places are doing it in three days. Is that accurate? Why is it taking so long?

GEOFFREY BAIRD: The answer is really just supply and demand. If there is a laboratory that has all of the setup ready to do 1,000 of those per day, they can do 1,000 a day.

JOHN WHYTE: Because they're batching them.

GEOFFREY BAIRD: They would batch them, or they could do them as they came in. But they would do 1,000 a day. Now, what happens if they get 1,500 that day? Well, they'll do the 1,000 they can do, and then the next morning, they'll have 500 left over. And then if they get 1,500 again, they'll do 1,000, but now they have 1,000 left over. And that backlog will just grow and grow and grow, and those samples just won't get run until they finally make it to the front of the line.

So that's the major problem, is that the supply of testing and all the equipment, the people, the test chemicals, the test supplies, the instruments that do it-- they're not sufficient to do the demand that we have for these things. And so we just have to get in line, oftentimes, and do that. And that's what is most of the cause for the wait.

JOHN WHYTE: So these are very sensitive, meaning they're accurately detecting positivity if you're positive. Correct? So if you have a positive test, and if you have a negative test, there's some certainty that those are accurate. Is that correct?

GEOFFREY BAIRD: Yes. Certainty is always relative. There's no absolutely perfect test that has God's honest truth every time. But with a high degree of certainty, I would say we have a lot of confidence in PCR results being positive reflecting actual infection and PCR results being negative reflecting no infection when you got that test.

Of course, however, there are caveats, and there are false positives and false negatives. They're just uncommon with PCR.

JOHN WHYTE: They may detect some fragments, correct?

GEOFFREY BAIRD: It could be fragments. There could be errors involved. So if a lab or a collection site makes an error and actually contaminates a sample by having a positive sample next to a negative sample, and maybe it splashes over, that's one potential route for having a false positive.

And then false negatives could happen where you could be infected, but maybe there's not enough in you to be detected. Those PCR tests, we said, are very sensitive. But that means that they can detect about 100 viruses on that swab. But if there's only 20 viruses on the swab, we might miss it.

JOHN WHYTE: If you get a positive test, though, we're not recommending with PCR testing that you get another test. Is that correct?

GEOFFREY BAIRD: We generally do not recommend that you get another test, with the caveat, though, that all tests need to be interpreted in the context of the patient who got them. And we have seen some false positives-- and every once in a while that makes it into the news. It's rare, but it has actually happened where there have been errors that we might not know about or whatever happened with that.

And so if the clinical intuition of the caregivers of the doctors and whoever it is that ordered that test is such that, that really sounds unusual, we should really think about that a lot harder, the recommendation might be to get another one. But for the overwhelming number of cases for a person, let's say, who's symptomatic, who has a cough and a fever, and who goes to a site to get tested, and that test is positive, that test result should be believed.

JOHN WHYTE: Let's turn to the rapid test, which is what everyone is talking about. There's a couple of different tests out there, whether it's in five minutes or 15 minutes. Let's start with the rapid tests that are antigen tests, that are looking for that spike protein that you reference. It's different. And that's important when we think about, how do we interpret the results, and who are they used for? So can you walk us through the rapid antigen tests for COVID-19?

GEOFFREY BAIRD: Yes. So the majority of the current rapid antigen tests out there-- they identify not the genome, like we talked about with PCR, but those proteins that are around. And sometimes they're the spike proteins on the outside. Sometimes they can be the proteins on the inside And what we do is, we look for those proteins.

And the technique that we use is pretty similar to the drugstore pregnancy tests that you're probably used to seeing that you could purchase, where you put a drop of urine on one end, and then it flows to one side, and you see one stripe or two, and that type of thing. So the tests that we have for coronavirus that work the same, we would get two stripes if there was coronavirus proteins there or not, and then one stripe if there wasn't there.

And those tests are either read by eye, meaning just like with drugstore pregnancy tests, we'd look, and we'd see a pink stripe, or they may actually be plugged into a special reader. And the reason for that is, our eyes are only so good. And if you put a reader, you can get a little bit more sensitivity by putting a really sensitive camera-like thing onto that to detect just a really faint stripe that maybe your eyes couldn't detect. So that's the general technology. It's very similar to the pregnancy test.

JOHN WHYTE: The results are back in about five minutes. Now, correct me if I'm wrong. When they applied for authorization or approval, the tests were designed for people that were symptomatic, or that you may have had some suspicion of COVID. Is that correct? So they were not designed for general screening.

GEOFFREY BAIRD: What I would say is-- and I can't read the minds of anyone who designed the tests, but the approval of the tests is--

JOHN WHYTE: Authorization. [INAUDIBLE] authorized.

GEOFFREY BAIRD: The authorization is entirely based on the performance of these tests in symptomatic people and not in asymptomatic people.

JOHN WHYTE: So why does that matter, though, when we're interpreting the test results?

GEOFFREY BAIRD: So what we believe, and now actually have some evidence to show, is that the viral levels in your nose, or really anywhere in your body right when you get infected, starts off very low, and then it rises. And then probably right around the peak is when you're probably feeling quite symptomatic. And then it goes away over time.

And the question is, where on that curve can you detect the virus? If you have a very sensitive test, you can detect it very close to the bottom of the curve. But if you have only a very insensitive test, you might only be able to detect it right at the top of that peak. And if you're below it, we might miss you.

And that is the major worry we have with the antigen test, is that they are insensitive to the degree to the levels that PCR can easily detect. And we don't actually know what the threshold is to determine if someone is contagious or not.

What we do know is that the antigen tests, when applied to symptomatic people who have high levels of virus, they are, I would say, OK. They're not great. They do miss some cases. But they detect the majority of people who are infected.

JOHN WHYTE: What does OK mean? I don't know what that means.

GEOFFREY BAIRD: 70%, 80%, 90%, somewhere around there. So they're still missing one out of five, maybe one out of four.

JOHN WHYTE: So we recognize there are going to be both false positives and false negatives on the rapid test, antigen testing. I did want to ask you, though, about-- because there is rapid testing for PCR, isn't that right? And it takes about 45 minutes. There's currently a test on the market.

GEOFFREY BAIRD: There are rapid PCR tests that are more rapid than the standard big laboratory instrument one. The fastest one probably is about 45 minutes, as you said. And some of the speed of those is that they may skip some steps in the process that are not as important for the accuracy of the test. And so they make a little bit of a sacrifice in accuracy for a big increase in speed. But what they don't really address is cost, and that speed comes at a great cost, too. So those rapid PCR tests are actually quite expensive.

JOHN WHYTE: So, Dr. Baird, you have a friend who's not a doctor, not an expert in laboratory medicine, and they come to you and they say, I'm going to visit elderly loved ones over the holidays. And I want to get a test, because I want to make sure that I don't expose family members to COVID.

So what do you counsel them? What kind of tests, when do they get tested, how do they interpret it? I know that's a lot of complicated questions, but I thought, let's make it real practical for people, because that's what our listeners really want to know. I'm sure their eyes are rolling when we're debating sensitivity and accuracy. They just want to know, what do I do, Dr. Baird?

GEOFFREY BAIRD: It may not surprise you that I've been asked that question a bunch of times. I know

JOHN WHYTE: You have.

GEOFFREY BAIRD: And actually literally that-- not a hypothetical, but literally that exact question. And so here are my thoughts on that.

The first thing to remember is that testing is an adjunct to all of the behavioral interventions that we're doing right now to slow or stop the spread of COVID, so masks, social distancing, avoiding gatherings, et cetera. Those are the important things. And testing adds marginal safety on top of that, but testing in and of itself does not actually do something.

If you-- if you test and then behave in ways you shouldn't by going to a large gathering without a mask, we saw what happened recently at the White House, where they had large gatherings without a mask. And that was what was called a super-spreader event, where many, many cases were done. Very few masks. Even though there was some testing, the testing was really sort of the icing on the cake there, but there was no cake.

JOHN WHYTE: And that was rapid antigen testing, is my understanding.

GEOFFREY BAIRD: That was rapid antigen testing, yes. But still, there were baseball teams early on in the season in baseball that had outbreaks, too, even despite PCR testing, when folks weren't doing this thing.

So the first thing I tell folks is, listen. The most important thing is your behavior before visiting your in-laws, and then your behavior after you get the test, and then when you go there. Because any test is really just a point, a point in time. And if you get a test, and you're dead negative, and then you go and get exposed to it and get positive, that negative test isn't relevant anymore.

So what I recommend to folks to do is to be cognizant of what they're doing. You have to ask about if you've had exposures. If you've been recently exposed, you do have to wait some number of days to see if that exposure leads to an infection. So if you were exposed today, it would not be helpful to get a test tonight, because the natural history of the disease is such that you would most likely have detectable virus in three to five days. And so you have to wait a few days to then get your test so that--

JOHN WHYTE: Quarantine yourself in the meantime.

GEOFFREY BAIRD: Quarantine yourself in the meantime, for sure. And then you can get that test. And again, for this purpose, I would heavily recommend getting a PCR test from a nasopharyngeal swab. So that's the deep one in there. That is the most sensitive we have, meaning it's least likely that we'll have a false negative. It's least likely that we're going to miss it if we're actually there.

JOHN WHYTE: [INAUDIBLE] no exposure, though, or no known exposure, and I'm not having any symptoms. What test what I do then?

GEOFFREY BAIRD: I would, again, say that I would heavily recommend getting a PCR test. Even if it's a little bit more difficult to find or maybe a little bit more expensive or a little bit slower to get back, that PCR result will be very helpful if it is negative. Or if it's positive, obviously, too. If it's positive, that's another question we're not going to talk about right now.

But that negative value just has more-- it's more worthy. It has more worth to it than a negative antigen test, because a negative antigen test has a much higher likelihood of being a false negative.

JOHN WHYTE: All right. So what's the role of the rapid antigen test?

GEOFFREY BAIRD: That's a really good question. So one of the major problems we have with rapid antigen tests is that the limitation on their sensitivity is sort of baked into the way that we do it. So it's never going to get to the point where they're equivalent. And to tell you the truth, we don't really use influenza rapid tests much at all for antigen, because we know that they're so insensitive. So we've known it for a long time with the flu.

But honestly, one of the reasons that we're thinking about it right now-- I hesitate to use the word, but it's the most appropriate-- is desperation. I think people are worried that we don't really have anything else to do, so we might as well do this, even though it's not that great.

So what I think the best use of the antigen tests will be is in a coming-- and I believe it's going to happen-- surge of symptomatic cases over the winter, because this is likely to have a seasonal surge that we're seeing right now.

I think in urgent cares, emergency rooms, et cetera, where there just isn't any PCR capacity whatsoever, the PCR test just isn't available, it's better than nothing in symptomatic people. But in asymptomatic people, I think it's yet an unsettled question whether or not it is better than nothing at all. It might be worse than nothing by giving people the wrong answers.

JOHN WHYTE: Any role for antibody testing?

GEOFFREY BAIRD: So antibody testing is a third test that we didn't talk about so far, and that is measuring the body's response to it. So antibody testing has one half-interesting historical role, which is, we can tell if you were exposed three weeks ago or four weeks ago. About 100%, very close to 100% of people who are infected will have antibodies, showing that their body made an immune response in about three weeks.

JOHN WHYTE: Depending upon your level of disease? There's some data that says, perhaps if you had mild symptoms, very mild, you may [INAUDIBLE].

GEOFFREY BAIRD: My next sentence was the caveat-- unless you have perhaps mild disease or even asymptomatic infection, it's harder to find people who didn't know that they had the disease to then go and do the test on them. But we have definitely seen people who have both not made antibodies because they had very, very mild disease, or they had antibodies and they might have gone away in two or three months. So it's not a perfect test.

But the second, and most useful, I think, context for antibody tests will be, once we finally have more information, largely coming from these vaccine trials, of whether or not the antibody test will tell us if we're protected. And then once we know that, which we don't really know, right now-- and there's a bunch of different antibody tests. It might be one of the tests versus the other tests that is better at telling us this.

What we would really like to have is a test that says, yes, you have antibodies, and that means that you're protected. You can't actually get COVID now. That would be a great thing to have, but we don't have the data to tell us right now. We have inklings we have a lot of support for-- certain anti-spike antibody tests are quite closely correlated to the results of neutralizing antibody tests, which are probably the best surrogate for whether or not it's going to be protective or not.

But again, we'll know a lot more after the vaccine trials are out, because we're going to see. There'll be a bunch of people who have antibodies, and then some people will get it, and some people won't. And so we'll know how protective these antibodies are as assessed by these tests.

JOHN WHYTE: So despite the fact that there's going to be a lot of rapid testing that seems to be coming online, we still need some more iteration and development of the sensitivity of those test, do you think?

GEOFFREY BAIRD: The normal order of events in laboratory medicine, and to tell you the truth, medicine, would be first to do a trial to see if something works and then to do it. And what we're doing now is, we're doing it, and then I think some people are trying to do trials to figure out, did that have any chance of working?

As I said, the limitations of the antigen testing are really intrinsic to the math, chemistry, and physics that underlies how these tests work, how easy it is to see 100 viruses with a PCR test, versus a traditional drugstore or pregnancy test. You need a billion molecules of HCG to see that stripe on a pregnancy test.

So in one technology, we need a billion of something. And maybe we can make it a lot better and only need to see a million, but still, it's millions or billions of things to see it in one, technology versus 100 with PCR. So there's this chasm of sensitivity that we're not going to be able to bridge. No one is going to be able to make an antigen test that outperforms or has completely equivalent performance to a gold-standard PCR test, at least not until we're all vaccinated.

And so we have to question, as a matter of public policy, is it most important to be focusing our energies on distributing a vaccine to everyone, which could be a definitive end to this, or to purchase a bunch of antigen tests that we know already don't work very well, and may not or might only have a moderate affect or a mild effect of helping things?

JOHN WHYTE: Well, the vaccine is going to be a whole other day that we'll talk about. But I want to ask you one final question. What about some of these-- there's limited at-home tests, that people can request a test. Many of them still require some doctor-- it might not be your primary care doctor-- approve it for your use. And then you collect it on your own and send it back. What do you think of those tests?

GEOFFREY BAIRD: So the performance of most at home tests is actually-- the performance of the tests, the machines and the instruments that do it, is in the lab. And so the at-home part is simply the nose swab, and then you mail that in. So the test technology is oftentimes the same as what we've been talking about.

JOHN WHYTE: But it's PCR? Are they PCR?

GEOFFREY BAIRD: It is oftentimes PCR. So the major lab vendors that do that, they're just doing a mail-in version of their current assay that they're doing.

Now, the problem then becomes the specimen collection, and how good is it? One of the things that we know when we go to-- for example, at our city of Seattle, we have multiple sites all around town that you can drive through. And our wonderful folks at Seattle Fire Department have hired a bunch of people, trained them to do these deep nasal swabs, and [INAUDIBLE] NP swabs. They're very, very good at it.

The home tests are usually, the anterior nasal swabs, because no one at home wants to stick something that far into their nose. So that's sort of the same motion as picking your nose, that sort of space, just in the front of your nose. People can do that.

But what if someone is too ticklish, and they just maybe rub their whiskers a little bit, or just sort of sneeze on or spit on it, or maybe lick it or stick it in their ear? We don't know any of those things in the laboratory when we get that sample. All we have is a swab, and we're going to test it as if it was perfectly collected.

So the problem with home testing is the variable nature of what we're getting. Some people can follow the direction. Some people, it's very difficult. For someone, let's say, who had some other disorder-- let's say they had a movement disorder and couldn't hold something well with their hand. How easy could it be for them to get a good sample in their nose? Those are all things you have to start thinking about when you approve and then move towards at-home testing.

JOHN WHYTE: Why aren't we doing more rapid PCR testing? So you note the challenges the rapid antigen testing, but we talked about, there's rapid PCR, which might be able to be done in 45 minutes. Why aren't we investing more in that as a potential?

GEOFFREY BAIRD: The 45-minute test, the vendor that makes one of the 45-minute tests that is frequently deployed in hospital settings-- I can tell you, because we have multiple instruments that can do that at our different sites.

My hospital system has three large hospitals, a big cancer center, a bunch of stuff. We get 20 total tests per day for a system that has two 450-bed hospitals, another 200-bed hospital like that. We get 20 tests a day. That's not even enough for all the people who come in and need testing to our emergency rooms. So there's just not enough of that technology out there. That company is 24/7 cranking out test cartridges to mail out to all of us, and they can't make them.

Now, there have been other homebrew attempts to make tests. Yale, in their department of pathology and their public health group, has made a saliva test. And any number of folks have made their own homebrew tests for these things. But they're not usually that rapid. That's the problem. So you can get PCR, or you can get rapid, but it doesn't mean that it's necessarily-- PCR is always going to be the most rapid.

JOHN WHYTE: How's the saliva test done?

GEOFFREY BAIRD: Saliva is another thing that is a great hope. Saliva is one of these things where it works, again, OK. It's not probably as high quality as the deep nasal swab, the NP swab. The results have been somewhat variable. You can find studies where people have been positive in their nose and negative in their saliva, positive in their saliva, negative in their nose.

Overall, the results have been variable but mostly centered around the fact that, again, saliva is just a little worse than NP. So if you could do an NP swab, you should do that, because that's probably the closest we have to a gold standard test.

And then on my side-- this isn't your problem or the patient's problem, but on my side as a lab director, saliva can be quite challenging to deal with. Some people have very viscous saliva, and some people have very liquid saliva, and that clogs up our instruments.

And we're doing 8,000 tests a day now. I can't afford to have the instrument fall apart or get clogged and then have to take it down, because then I delay everyone's samples by two to four hours, and that just makes the turnaround time worse.

So the most promising thing coming, I think, from saliva might actually be the idea of swishing with something. So that helps us get away from some of the viscosity issues, those swish scope or swish saline-- probably not water, but it's the, swish something and then spit that out, and then we'll test the swish spit stuff, which will probably be more of a standard, regular type of substance that we could test.

JOHN WHYTE: Well, Dr. Baird, I want to thank you for sharing your insights about the different tests that are currently available, as well as reminding us that testing is an adjunct, that we still need to utilize all those public health safeguards that we've been trying to do over the last few months. So thank you for taking the time today.

GEOFFREY BAIRD: Thanks for talking with me.

JOHN WHYTE: And thank you for watching "Coronavirus in Context."