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Serology 101: Pathogens, Antibodies & Immunity

False-color rendering of SARS-CoV-2 virus.
Centers for Disease Control
A rendering of the coronavirus that causes COVID-19. The University of Vermont's Dr. Clayton Wilurn explains how serology works.

Understanding the science behind the COVID-19 pandemic can be complicated. Recently, there has been discussion around the use and accuracy of serological tests for the disease, tests that detect the presence of antibodies for the pathogen that causes COVID-19.

To explain some of the terminology and concepts at issue, VPR's Mitch Wertlieb spoke to Dr. Clayton Wilburn, medical director of clinical chemistry, immunology, and point-of-care testing at the University of Vermont Medical Center.

VPR's Mitch Wertlieb's interview with Clayton Wilburn is below. It has been edited and condensed for clarity.

Mitch Wertlieb: Let's start with the term "serology." What does that mean?

Dr. Clayton Wilburn: Serology is the specific study of particularly a portion of our blood that we call the serum, which is all of the fluid that is surrounding our red blood cells and our white blood cells. And when we talk about serology, what we're really trying to focus on is the antibodies that would be present in that serum.

How do they fight disease?

Antibodies are a protein that our immune system makes. They're made by something called plasma cells. And those cells, when they are exposed to a pathogen, they make a protein that is designed to attach to parts of that pathogen that are essential for its replication in the body or infecting you.

These antibodies would bind to that pathogen and prevent it from either being able to infect you or tagging the pathogen, or cell that it unfortunately got infected, that it needs the body to take care of it and remove it to further protect you.

Do we all have these antibodies, do some of us have more than others? Do they differ in quality and strength, that kind of thing?

Yes, everyone does have antibodies and everyone has different levels. Each antibody is specific in terms of what it's targeted against and how well it'll work against that target. Those are all things that go more into the nuances of antibody testing.

How do tests for antibodies work?

The best way I could explain it is it's really like fishing. It's all about using the right bait. And the bait is what we refer to as an antigen, or it's the protein from a pathogen that the antibody was designed to attach to or work against. We are selecting the antibodies. We're trying to see if the patient has to bind onto those.

Now, unlike fishing, antibodies are really small. So we have to have another mechanism that we add into the test, another marker that will turn the antibody and put a light marker on it. And then we measure how much light is produced inside of that test to give an idea of, did we actually see the antibody we were looking for, or did we not see them at all?

Well, that's interesting because we've been hearing a lot in the news about issues with false negatives, poor accuracy in some serology tests for COVID-19. I'm wondering if this is something that's fundamental to antibody tests in general?

This is actually something that is part of antibody and serology testing and affects every test that we do. When someone says "false negative," it would say that you didn't have antibodies. But the truth is, is that you really did. The other problem that we have is false positives. A false positive would mean the test told us that you have antibodies, but you really didn't.

There's some uncertainty around whether or not people are immune to COVID-19, after having it and recovering. Why is there so much uncertainty about that question?

It's really due to the fact that this is a novel disease. We don't really have a good idea of how much these antibodies are able to neutralize the the virus yet without further studies. Or if they are able to neutralize, how long does that last? Does it just give you a few weeks? Is it going to get you through the year, or is it going to be something like with hepatitis when you get immunized that can last for several years. Time will tell is really what we're looking at right there.

What about using antibodies as treatment, using human antibodies from people who maybe have recovered from the disease? Do we know if that works or what other issues there might be?

Sure. So one of the terms that your listeners have probably heard thrown around a lot is convalescent plasma. The use of convalescent plasma im medicine actually dates back over 100 years. And there are ongoing studies. There have been a lot of case studies, especially out of China, initially, that did show some possible benefit.

But the truth be told is, there's a lot of ongoing studies. So the best quality evidence you can get is from what we refer to as a randomized controlled trial, or an RCT. There's over 22 different randomized controlled trials ongoing throughout the world right now, where they're looking into convalescent plasma treatment for COVID-19.

Can I ask you about one of those trials specifically? Research showing that nanobodies from llamas seemed to neutralize the corona virus.

I have actually looked at the article to which you're referring. My basic understanding is that nanobodies are a type of antibody that are produced by llamas and related sepcies that are smaller than the antibodies that we have, but work in the same way.

The thing that can be hard and get confusing for folks is the differences between vaccine and something like the nanobodies. A vaccine is something we're using to help you yourself make antibodies to it, whereas in things like these nanobodies or the convalescent plasma, somebody or an animal is donating those antibodies to you for their use immediately. But they're not going to stick around forever.

It would be a treatment, not a cure. We do that with hepatitis and newborns that haven't been immunized yet. If there's exposure to hepatitis, we can actually give antibodies that are against it to help prevent them becoming infected. But it's a treatment. It's not something that's going to be with them for all time.

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