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JOHN WHYTE, MD, MPH: 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.
JOHN WHYTE: Let's start
with the basics.
What's the difference
between antibody testing
and diagnostic testing?
VINCENT RACANIELLO: 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.
JOHN WHYTE: 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.
JOHN WHYTE: 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?
VINCENT RACANIELLO: 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.
JOHN WHYTE: The first time,
yeah.
Mm-hmm.
VINCENT RACANIELLO: 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].
JOHN WHYTE: 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.
VINCENT RACANIELLO: Yeah
that's a really --
JOHN WHYTE: Is that good enough?
VINCENT RACANIELLO: -- 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.
JOHN WHYTE: Well, but why are we
talking about them then?
VINCENT RACANIELLO: Well,
that's --
JOHN WHYTE: It's good enough?
Are they good enough?
VINCENT RACANIELLO: [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.
JOHN WHYTE: But you might be
exposing people, um,
to infection.
If they're not truly recovered,
they could still be infecting
others, right?
VINCENT RACANIELLO: 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 --
JOHN WHYTE: Right.
VINCENT RACANIELLO: -- where you
might encounter other
infections.
JOHN WHYTE: 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?
VINCENT RACANIELLO: Well,
the neutralizing antibodies will
protect you.
But of course, these rapid tests
will not distinguish between --
JOHN WHYTE: No.
VINCENT RACANIELLO: -- 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.
JOHN WHYTE: Now, Dr. Fauci has
said we're going to consider
giving these certificates
of immunity to people.
VINCENT RACANIELLO: Mm-hmm.
JOHN WHYTE: 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?
VINCENT RACANIELLO: 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.
JOHN WHYTE: Yes.
VINCENT RACANIELLO: They're just
immunity.
Although, in some people's minds
--
JOHN WHYTE: That's what people
are assuming.
VINCENT RACANIELLO: Yeah, I
agree.
JOHN WHYTE: [INAUDIBLE]
VINCENT RACANIELLO: 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.
JOHN WHYTE: 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?
VINCENT RACANIELLO: 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?
JOHN WHYTE: Sure.
VINCENT RACANIELLO: [INAUDIBLE]
JOHN WHYTE: So why can't we
do that?
Is it just resource intensity?
How are we going to do 300
million tests?
VINCENT RACANIELLO: 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.
JOHN WHYTE: 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?
VINCENT RACANIELLO: 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.
JOHN WHYTE: 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?
JOHN WHYTE: 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 --
JOHN WHYTE: Mm-hmm.
VINCENT RACANIELLO: --
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.
JOHN WHYTE: So you do believe
that, once infected, you likely
develop some immunity
to COVID-19.
VINCENT RACANIELLO: 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.
JOHN WHYTE: So you think you're
protected.
VINCENT RACANIELLO: Yes.
JOHN WHYTE: So do we need
the quantitative tests?
VINCENT RACANIELLO: 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.
JOHN WHYTE: So we have these
point of care tests, which are
the pinpricks --
VINCENT RACANIELLO: Mm-hmm.
JOHN WHYTE: -- 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.
VINCENT RACANIELLO: That's
right.
JOHN WHYTE: How concerned do you
get when --
the public often --
we don't often understand
that tests aren't 100%.
VINCENT RACANIELLO: Mm-hmm.
JOHN WHYTE: 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?
VINCENT RACANIELLO: 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?
JOHN WHYTE: Yeah.
Mm-hmm.
Now, I don't have a wand.
But if I did, and I made you
the immunology czar --
VINCENT RACANIELLO: Mm-hmm.
JOHN WHYTE: -- 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?
VINCENT RACANIELLO: 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.
JOHN WHYTE: What
about diagnostic testing though?
VINCENT RACANIELLO: So --
JOHN WHYTE: Where does that go?
VINCENT RACANIELLO: 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?
JOHN WHYTE: Why does that help?
Why does that help you?
Why do you need
that information?
VINCENT RACANIELLO:
The quantitative tests?
JOHN WHYTE: No, even just what
percentage of people
of in the population
have antibodies.
VINCENT RACANIELLO: 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.
JOHN WHYTE: 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?
VINCENT RACANIELLO: 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.
JOHN WHYTE: 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.
VINCENT RACANIELLO: That would
be great.
Love to do it, John.
JOHN WHYTE: Dr. Racaniello, I
want to thank you again
for taking time to spend
with us.
VINCENT RACANIELLO: My pleasure.
JOHN WHYTE: Thanks for watching
Coronavirus in Context.
I'm Dr. John Whyte.
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