Coronavirus in Context: Immunology Expert Discusses Testing, Antibodies, and More

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Welcome to Coronavirus in Context. I'm Dr. John Whyte, Chief Medical Officer at WebMD. Everyone's been talking about testing.

First, we talked about diagnostic testing. Now we're talking about antibody testing. But is that really the way that we're going to get back to work and open up the country?

My guest today is Dr. Vincent Racaniello. He's professor of microbiology and immunology at Columbia. Thanks for joining me, Dr. Racaniello.

VINCENT RACANIELLO, PhD: Good to be back, John.

Let's start with the basics. What's the difference between antibody testing and diagnostic testing?

So a diagnostic test will tell you if you're infected at the moment the test is taken. You typically give a nasopharyngeal swab. They look for -- in the lab, they look for nucleic acid of the virus by an amplification method called PCR. And that tells you if you're infected. But of course, it only works as long as the virus is in you.

Mm-hmm.

VINCENT RACANIELLO: And an antibody test will tell you if you were infected last week, last month, or even last year, or 10 years ago. So it's a permanent record of the infection, long after it's over.

So I'm going to come back to that -- whether it can tell if you are immune from a week ago. Because there's some issue of -- of timing. But let's talk about how these tests are done.

And there's different strategies. And we hear a lot about these "point of care" tests that you would do with a fingerprint. And, um, I saw a memo recently that talked about these tests are actually authorized by the FDA, not approved. So there's a lower standard of accuracy. Is that right?

That's right. These rapid tests, which you do with a little bit of blood from a pinprick on your finger, they work in about 15 minutes. They're dipstick tests, sort of like a pregnancy test that you put some urine on.

The first time, yeah. Mm-hmm.

They develop rapidly. And they can give you an answer. But they're not hugely accurate. They're good for a broad swath of what's going on out there. We have them for influenza virus infection [INAUDIBLE].

Yeah, but those have been approved outside of a public health declaration. And the FDA commissioner, just a day or so ago, said there are a lot of inaccurate tests out there which could give people misinformation. Now, what about the fact that these are qualitative tests? Are they not the ones that we're currently talking about -- either you have antibodies or you don't? And that's good enough.

Yeah that's a really --

Is that good enough?

-- really, really important point. It will just tell you yes or no, not how much immunity you have, right? So it won't tell you if you're protected from another infection and whether you're safe enough to go back to work. It's just going to say yes or no.

Well, but why are we talking about them then?

Well, that's --

It's good enough? Are they good enough?

[CHUCKLES] That's a great question. I think it's good to know who's been infected. Essentially, we're going to take a chance.

These are the fastest tests we can get out there. We can test the most number of people with them. Because the alternative is a lot more time-consuming. And we're going to see if that's good enough to tell us whether you can go back to work or not. Because that's really the goal.

But you might be exposing people, um, to infection. If they're not truly recovered, they could still be infecting others, right?

I'm not so concerned about that. I think, if you wait long enough after the end of illness -- of clinical illness -- you know, if you wait a certain amount of time, you're probably not shedding. You know, this infection peaks in a healthy person with an uncomplicated illness in about seven to 10 days. And so I think, after two weeks or so, you're not shedding that much.

The real concern here for me is whether you're really OK to go back in the workforce --

Right.

-- where you might encounter other infections.

Now, without giving us an immunology lesson, you know, is there some data that says -- you know, there's IGM, there's IGG, there's IGA, which, you know, we can send people to to find out more. But is it really you have to wait 20, 28 days after you've been infected to find these neutralizing antibodies, which really are what we need? Isn't it?

Well, the neutralizing antibodies will protect you. But of course, these rapid tests will not distinguish between --

No.

-- those and any other antibody against SARS-CoV-2. But you do start making these antibodies seven to 14 days after you're initially infected. And IGM, as you mentioned, they come up first. They last about two months.

And then IGG are the long-term-lasting ones. And that's another issue. The IGM can cross-react with other coronaviruses. So if you're just looking for that, that's not a good test. You have to look for both.

Now, Dr. Fauci has said we're going to consider giving these certificates of immunity to people.

Mm-hmm.

Is -- are they going to be valuable at all? Will that really tell us? Because aren't what we really saying is, they are not going to get re-infected, because they have immunity? But are you sure that's true from these tests that we're currently talking about primarily?

Well, if, by immunity -- I mean, it's a -- it's a word that can mean two things. It could mean -- it can mean any antibody or any immune response against the pathogen versus protection. So notice, they're not certificates of protection.

Yes.

They're just immunity. Although, in some people's minds --

That's what people are assuming.

Yeah, I agree.

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But I -- I don't think you can say that you're immune. Because you're not quantitating how much antibody. It's all or none, right? And some people are going to have very low amounts. They may not be protected.

Should we really be doing, then, a serum test to get that quantitative amount to know for sure? Let's assume you had unlimited resources. What test, Vince, would you do to tell us that you're immune from getting re-infected?

Oh, I would take a tube of blood from you, from your arm vein, first of all -- not just a little bit. And then you bring that to a clinical lab. And then you do a quantitative test, where you make dilutions of serum against a fixed amount of virus protein. And you can tell exactly what levels of antibody you have. And if you even wanted to do better, if you wanted to know protection, you would have to know about neutralizing antibodies, right?

Sure.

[INAUDIBLE]

So why can't we do that? Is it just resource intensity? How are we going to do 300 million tests?

Yeah, we -- we can't do that, right? We can barely do 300 million rapid tests. That's why we're doing the rapid test, because we can do them quickly and they'll give us an idea. But they're not definitive in terms of protection, by any means.

But are we then taking time away from the diagnostic tests, right? Don't we still want to rapidly build that up? We're roughly only over 2 million diagnostic tests. How are we going to do millions of diagnostic tests, and now we're going to ramp up millions of antibody tests?

Well, I think that these "point of care" tests are not going to tax the clinical laboratory capacity of the US. And I think, at the same time, they need to be developing the quantitative assays. And we should start ramping that up. I'm hoping that's happening behind the scenes, you know, and they're not -- we're not being told about it. But that absolutely has to be done at the same time, for sure.

And what about this issue of reactivation? We talked about that on a previous interview. Some people are saying that they recovered. Uh, and then they tested positive again.

There's even some people that are saying this is like herpes, a DNA virus, instead of an RNA virus. What's going on here with reactivation? Could they have been immune and then get the infection again?

I don't think so. I think what happened is they, uh, recovered, and then the tests -- you know, the tests that were done -- the diagnostic tests were wrong. And so then, at some later time, they tested them again, and they saw they were positive again.

But I don't think, at that point, they're actually shedding virus. They're probably shedding pieces of nucleic acid. And so I'm not worried that this is, uh, a persistent virus --

Mm-hmm.

-- that's going to come and go over and over. This is a virus that gets you, you get immune. And then later, if you get another infection, it's going to be much milder. So I'm -- I don't put much stock into those reports.

So you do believe that, once infected, you likely develop some immunity to COVID-19.

Absolutely, some immunity. And if you are re-infected at a later date -- let's say, in the winter, when the virus is coming back -- you might not even know it. You could get a mild disease with few symptoms, because your immune response is protecting you.

So you think you're protected.

Yes.

So do we need the quantitative tests?

I think the quantitative tests, at least initially, would give us an idea of whether the rapid tests are telling us about just general immunity or protection. So it's kind of a research question. Can we depend on the rapid tests, and so, in parallel, we should do rapid and quantitative, and say, oh, yeah, everyone that has a rapid positive is protected? That would be great information to have.

So we have these point of care tests, which are the pinpricks --

Mm-hmm.

-- for which we have perhaps greater capacity. And then that quantitative test is, we would do a lipid, or, you know, a CBC, or anything like that.

That's right.

How concerned do you get when -- the public often -- we don't often understand that tests aren't 100%.

Mm-hmm.

And folks tend to believe the test result, whether it's a diagnostic test, whether or not you have coronavirus, or whether or not you have antibodies. What -- what are your thoughts on how we educate folks more about, tests aren't 100%, and, sometimes, you have to go back the old-fashioned way, to symptoms and ruling things in or out?

Well, you're right about tests. And often, in a clinical setting, as you well know, when a physician sees a test, and it doesn't look quite right, what do you do? You do it again. And usually, it's not going to be wrong twice in a row. And so if someone has had symptoms of COVID-19 -- they had a diagnostic test which said they were infected -- -- if you now do a -- a rapid antigen or antibody test, and it's negative, then you should do it again. Because if that person was infected, they should have an immune response. So I think that's really important, especially at this early date, when, as you said, a lot of the tests are not quite fully baked yet, right?

Yeah. Mm-hmm. Now, I don't have a wand. But if I did, and I made you the immunology czar --

Mm-hmm.

-- what do we have to do over the next week or two to get to where you think we need to be to start thinking about opening up the country a month, two months from now -- whatever that time may be?

So I think what we need to do is what many people are talking about. Start testing as many people as possible for antibodies to the virus, to SARS-CoV-2. And at the same time, a fraction of those should be compared in -- in a clinical lab test -- quantitative antibody tests, to see if the rapid tests are giving us the right information.

What about diagnostic testing though?

So --

Where does that go?

So to these people who are infected and have had symptoms -- so we have two sets. We have -- some people are in hospital. And they've obviously had diagnostic tests to show that they're positive. And then there are others who are not. And maybe they have had symptoms. They're never going to have a diagnostic test, because their infection is over. But now, we ask, do you have antibodies? We would like to know, in the general population, what fraction of people have antibodies to the virus, not just by a rapid test, but-- but spot-checking some of those with quantitative tests?

Why does that help? Why does that help you? Why do you need that information?

VINCENT RACANIELLO: The quantitative tests?

No, even just what percentage of people of in the population have antibodies.

Because we know, with this virus, somewhere between 50% to 70% of the population being immune will stop spread of infection. So if you have a city somewhere in the US, and you find that half of the population is antibody-positive, they can probably resume their normal lives at this point.

And then how long do you have to wait after symptoms to take an antibody test? You shouldn't take it while you're having symptoms, correct? So how long? Is it a week, two weeks? Does it matter?

So if if you have onset of symptoms with this virus -- remember, the incubation period can vary from one to 14 days. And usually, we say the antibody response kicks in a week or two after the virus starts to multiply in you. So I would say a week or two after symptom onset is probably the safest time to start doing the antibody tests.

All right. Well, that is great information. We'll see what happens with our capacity over the next few weeks. And perhaps we can have you back to critique how well we're doing.

That would be great. Love to do it, John. Dr. Racaniello, I want to thank you again for taking time to spend with us.

My pleasure. Thanks for watching Coronavirus in Context. I'm Dr. John Whyte.

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