EPIDEMIC Podcast / S1E21: Are Antibodies the Holy Grail? / Kaitlyn Sadtler & Matt Memoli

I'm Celine Gander. And I'm Ron Klein. And this is Epidemic. Today is Tuesday, May 19th. I have to ask on behalf of a concerned globe: how are you feeling?

We are just fine, dandy.

That's actor Tom Hanks on a recent episode of the NPR podcast Wait Wait Don't Tell Me. Hanks and his wife, actress Rita Wilson, contracted COVID in early March.

We had all of the flu-like symptoms. My wife Rita was a little worse off than me. She had a very high temperature, and we were isolated so that we would not give it to anyone else.

Hanks and Wilson made a full recovery, and ever since they've asked the same question: now that you've had it, aren't you supposedly like immune? You're superheroes, you can walk amongst us and be immune? Or is that just nonsense? It would be nice, wouldn't it, if battling a COVID infection made you immune to reinfection. Hanks and another 1.4 million fellow Americans would indeed be modern superheroes. In recent weeks, thousands of people have taken antibody tests. If the tests detect COVID antibodies in their bloodstream, they can accurately say they had COVID and they beat it, even if they never had symptoms. But can they say they're now immune? Not quite.

When it comes to an infection, we don't know exactly what our immunity is from this infection yet.

This is Caitlyn Sattler. She's an investigator at the National Institutes of Health.

Mainly we just need to learn a little bit more on the research side before saying that somebody that has tested positive is considered immune. We need to figure out how much antibody you need and how long that immunity might last.

In this episode, we'll look at how our bodies fight off infections. We'll ask: how do we build immunity to future infections, and how are scientists determining how long that immunity lasts? We'll look at how they're studying COVID antibodies and how their work will bring us closer to returning to normal. Popular belief holds that once your body has beaten a particular virus, you become immune to it. Well, that's not exactly true, and we'll explain why. But first, we need to understand how the immune system responds to an infection. There's a lot of parts to our immune system. The innate immune system is the early acting part; they're the first responders and help communicate with the adaptive immune system. The adaptive immune system learns and adapts to the type of pathogen that invades. You've probably heard about antibody tests. Antibodies are produced from the adaptive immune system. Why are we so focused on antibodies? Antibodies themselves are very important in controlling viral infection and preventing viral spread. They tag foreign invaders for destruction. So when the body goes to war with a foreign invader, it generates antibodies, which are specialized soldiers. Each organism has different antigens, and you can have different types of antibodies to each antigen. For SARS-CoV-2, the primary one is the spike protein. This is Matt Memoli, he's the director of the Lab of Infectious Diseases Clinical Studies Unit at the NIH, where he usually focuses on developing vaccines for influenza. Now, along with the rest of the world, he's shifted his focus to SARS-CoV-2.

Sure, so it's even more complicated than that.

Okay, so if we stick with the military metaphor, IgM is the first wave. It's the body's first attack on the virus. After this first wave, the body brings in reinforcements. These are the IgG antibodies that Matt was talking about. These guys hunker down for a sustained fight, like troops in a trench.

The antibodies keep firing until they defeat the infection, and then they do something even more important: they remember how they did it. The antibodies remember what it took to win the fight. That memory creates immunity, and it's the reason so many have been looking to antibodies as the holy grail for ending the pandemic. At the beginning of this episode, we promised to explain why that isn't necessarily true. The catch is that the length of that memory varies with every new virus. Sometimes it lasts for hours, sometimes forever, sometimes somewhere in between. Until researchers can really study a new virus like COVID-19, they don't know if the presence of antibodies actually indicates long-term immunity. In the case of some diseases, antibodies never give you immunity. If you have HIV, herpes, or hepatitis C, your body produces antibodies but that doesn't mean you're immune. So far, there hasn't been enough time to study COVID antibodies, how long they last, and how effective they are in protecting us.

And that brings us to Matt and Katelyn's current research. This research study will let us know the extent of the spread of the coronavirus infection in the United States. It will help us with several things, one of which is understanding whether or not some of these antibodies are able to confer immunity. So Caitlyn, if you could explain, how do you even go about conducting such a study?

What we want is to be able to recruit 10,000 people that properly represent the population of the United States. We are looking for individuals who have not been diagnosed with the disease, because we already know those people have had it. By looking for antibodies, we can tell that there are people who never had symptoms, never went to the doctor, and were never diagnosed. That gives us a better idea of how many people actually have been exposed or infected compared to what we know about.

This part is so important because right now no one knows exactly how many people have been infected with COVID. Last week, the CDC posted a data set showing how many people have been tested. Nearly 11 million people have been tested, and 1.4 million tests were positive. But states are reporting different numbers, so it's tough to know anything about prevalence. And those are just the people who've been tested. How many of us have family members or friends who experienced symptoms but didn't get tested because testing was so limited? Right, these antibody tests will start to offer a more complete picture, but only when they produce accurate results.

Researchers like Matt and Caitlin have to be careful in designing the test, what we in the science community call assays, tests that only pick up COVID, not other coronaviruses.

To what degree are you characterizing? There are different kinds of antibodies, right? You have antibodies to different antigens, you have IgM, IgG, IgA. How are you trying to tease apart those details?

But unfortunately, historical data doesn't offer much else. Understanding a specific virus takes time, as Matt knows all too well from his research on influenza.

As with everything COVID-related, no one really knows. We're learning as we go.

By using large numbers of samples, both positive and negative, and running them through these various assays and testing them very carefully, she's developed an algorithm that will give us high sensitivity and specificity to make sure what we're getting is correct.

So what we understand is, what do we actually know about the extent of the spread of this virus? And pairing it with other analyses, starting to understand that idea of immunity.

Caitlin and Matt are among dozens of research teams attempting to understand immunity. Last week, a biopharmaceutical group in California announced it has identified an antibody that has 100% success rate in blocking COVID's spike protein from binding to other cells. These are neutralizing antibodies. If their results are accurate, it's a major breakthrough, but until replicated, no one can say with certainty that this is the key to immunity.

In the meantime, people are flocking to doctors' offices and labs to have their blood tested for antibodies. There are more than 120 antibody tests available, but they're not necessarily trustworthy. The American Medical Association recently warned that most tests have not been granted emergency use authorization by the FDA, never mind permanent approval. So these tests could be returning false positives, and even accurate results don't tell us it's safe for someone to be around others with coronavirus.

So is there any value then in getting one of these antibody tests?

But also, let's not count them out entirely, because they can tell us something about immunity.

You could look at the rates of infection in different states and the kinds of antibodies that are appearing. If one state has a spike after reopening and another doesn't, you could look to see which antibodies are present in the state with fewer cases. That might be a clue for which antibodies are most effective and which we should be testing for.

And so in answer to the question that everyone's been asking Tom Hanks and everyone else who's had COVID: 'Now that you've had it, aren't you supposedly immune? You're superheroes, you can walk amongst us and be immune? Or is that just nonsense?' Well, we just don't know for now.

That hasn't stopped officials in the U.S., UK, Italy, and Germany from floating the idea of special immunity passports for people who've already survived the virus. These passports would grant them permission to travel, dine out, go back to work, and enjoy a return to normal life.

In the meantime, if you think you've had the virus, the best thing you can do is to join legitimate studies to help researchers better understand immunity to COVID. If you do, you'll be in good company.

A lot of the question is: what now? What do we do now? Is there something we can do? In fact, we just found out that we do carry the antibodies, antibodies that might bring us one step closer to understanding immunity and developing a vaccine. We've not only been approached, we've said, 'Do you want our blood? Can we give plasma?' And in fact, we will be giving it now to the places that hope to work on what I would like to call the Hank scene.

There could be no better ending to this international catastrophe than if the cure turns out to be the blood of Tom Hanks.

We'll discuss other elements of the immune response and other uses for those donated antibody samples, and the big one: vaccines, in the coming weeks. Next Tuesday, you'll hear more about the immune response to COVID. It's about a whole lot more than antibodies. That's next week on Epidemic.

Epidemic is brought to you by Just Human Productions. We're funded in part by listeners like you. Powered and distributed by Simplecast. Today's episode was produced by Zach Dyer, Danielle Elliott, and me. Our music is by the Blue Dot Sessions. Our interns are Sonia Baradwa, Annabel Chen, Isabel Ricky, Claire Halverson, and Julie Levy. If you enjoy the show, please tell a friend about it, and leave us a review on Apple Podcasts. You can learn more at epidemic.fm. Just Human Productions is a 501(c)(3) non-profit, so your donations are tax-deductible. We release Epidemic twice a week on Tuesdays and Fridays. Please make a donation to keep this going. Check out our sister podcast, American Diagnosis, at americandiagnosis.fm. I'm Celine Gander, and I'm Ron Klein. Thanks for listening to Epidemic.