The Promise of Plasma in the Fight Against Covid-19

[MUSIC PLAYING] DAN GORENSTEIN: Hey, I'm Dan Gorenstein, host of the podcast, Tradeoffs. I've been reporting on health care for years, and here's what I know about our system. It's costly, it's complicated, and a lot of the time it's counter-intuitive, especially in the time of a pandemic. Each week, we look at the data the evidence with people who best understanding it and tell stories about some of the country's toughest health policy problems. Subscribe to Tradeoffs wherever you get your podcasts.

SARAH BALDWIN: From the Watson institute at Brown University, this is Trending Globally. I'm Sarah Baldwin. We last heard from physician and public health expert, Adam Levine, back in April when he was organizing a global remote training program for front line health workers.

Now he's working on a project much closer to home. Adam, who's a faculty fellow at Watson, is helping lead two studies in Rhode Island of the effectiveness of something called convalescent plasma treatment for people with COVID-19. This is when patients are treated with blood plasma from people who have already recovered from the disease. That blood is filled with antibodies, and those antibodies might help currently infected people fight off the virus. Depending on what the studies show, this could change the global trajectory of the pandemic. That's because the key ingredient in this treatment is, unfortunately, pretty easy to find.

ADAM LEVINE: Every country on the planet that has COVID-19 has convalescent plasma, because it just comes from people who've recovered from the disease.

SARAH BALDWIN: On this mini episode, I talk with Adam about the details of these studies and about what the results could mean in our fight against COVID. A thing to know before we start, Adam's team is looking for volunteers for both trials in Rhode Island and in many other parts of the country right now. We'll talk about it more in the interview, but be sure to check out the links in our show notes to see if you might qualify to be a part of it. As you'll hear, it's one of the most direct ways people can contribute to finding a cure. I started by asking Adam to describe the mysterious liquid at the center of this whole study. Here's Adam.

ADAM LEVINE: Convalescent plasma is actually antibodies that we take from the blood of patients who've recovered from COVID-19. People who've recovered from COVID-19 have all built up an antibody response to the disease, and while it varies from person to person, they'll have some level of antibodies against COVID circulating in their blood for many months, and perhaps years afterwards. We still don't know.

So when people who've had COVID-19 and recovered from it donate this plasma, we actually extract specifically the antibodies from their blood. So it doesn't include any of the red blood cells or any of the other components in the blood, and then we test it to see if the antibody titer is high or low. And if it's high, then we utilize it in this trial. And we actually have two separate trials going on. One of them is related to treatment of patients who are early in the course of COVID-19 infections, so within their first week of illness. And we are giving them a single transfusion of convalescent plasma to see if it can reduce the likelihood that their disease will become more severe and that they'll end up requiring hospitalization or other measures.

SARAH BALDWIN: You said you're doing two trials. Can you talk about the other one as well?

ADAM LEVINE: Yeah, the other one is what's called a post-exposure prophylaxis study. And so for this study, we're actually trying to see if we can prevent people from getting COVID-19 in the first place. So this is specifically targeting people who are at high risk for getting COVID-19, especially people who live in the same household as someone who has COVID. We know that this is probably the most high risk group for getting COVID-19. And the idea is that if we give you an infusion of this antibody, it will hopefully block the virus from being able to enter your body and for being able to take hold in your body and prevent you from getting infected at all with the disease.

Again, we're enrolling people for this study who are either household members of somebody who has COVID-19, or are in high risk professions, like health care for instance, who've had specific exposures to people who may have COVID-19. And we give people a single infusion of the convalescent plasma, and then we're following them over time to see if they end up contracting the disease or not. And we're hopeful that, for those who are randomized to getting the convalescent plasma, we'll see incredibly low rates of contraction of disease in that population.

SARAH BALDWIN: So can we just pause for a second and have you define what exactly plasma is?

ADAM LEVINE: Sure. Our blood contains a number of different components. It contains red blood cells, which are what carry the oxygen, and that's what makes the blood red. It contains platelets which help our body in clotting, when we get a cut or we have an internal bleed and we need to clot that blood. And then it also includes plasma, which is sort of the liquid in between the red blood cells and the platelets. And that liquid includes mostly antibodies. It includes different salts and nutrients, and it also includes some factors that are involved in the clotting of blood.

So when somebody donates plasma, we are removing all of the red blood cells and all of the platelets and only taking that liquid that remains, which includes the antibodies, and that's specifically what we want to give to patients. By removing the red blood cells and the platelets, we reduce any likelihood of transfusion reactions that can occur when you get blood. And so we make it safer. In addition to that, we concentrate the very specific thing we're looking for, which is the antibodies.

SARAH BALDWIN: Could you describe why an antibody approach is more effective than, say, a drug treatment?

ADAM LEVINE: Yes, so, I mean, an antibody approach takes advantage of our body's natural system that has evolved over hundreds and hundreds of thousands of years to fight disease. And so antibodies bind directly to the virus itself and neutralize it from being able to enter our cells and cause damage. You know, drug treatments work in a variety of different ways. Some of them block the virus from entering cells. Some of them attack the virus or the way it replicates in our body. But all of them are going to be limited in terms of their ability to completely neutralize the virus. We've also seen, just from other emerging infectious diseases, that antibody-based treatments often are more effective than drug-based treatments.

SARAH BALDWIN: I can imagine someone feeling hesitant about entering a trial that is using an experimental drug, but I can also imagine people hesitating to receive an injection or an infusion of someone else's plasma. Can you talk about the risks and the relative safety?

e outbreaks going back to the: 1918

And so we have lots and lots of evidence about its adverse effects. And we know that they are pretty rare. In particular, we have data from the Mayo Clinic now on over 50,000 patients who've received convalescent plasma for coronavirus disease during hospitalization. So these are really sick patients who got it as part of a expanded access protocol that allowed them to get access to this treatment. And the rates of complications from the convalescent plasma were incredibly low, less than 1 in 1,000 in general in this population in terms of severe adverse effects. So we think it's incredibly safe. And again, even though it's coming from someone else, the plasma is screened to ensure that the donor does not have other infections like HIV or hepatitis, et cetera. So it's completely screened to make sure it's safe before it's given to patients in the study.

SARAH BALDWIN: And Rhode Island's the smallest state. So I imagine that there are other sites to this study?

ADAM LEVINE: Yes, so this is a multi-center study. It's going on at almost 30 sites around the country. And so we're enrolling patients in places that are currently hotbeds of COVID, like California and Texas, in the Midwest, as well as places that are now seeing lower rates of COVID, like the Northeast for instance. However, the important piece about having a multi-center study like this is we have no idea where the virus is going to go. And so it could be that, in a couple months, the Northeast is, again, the hot spot and there are lower rates in other parts of the country.

And so we want to be prepared to enroll patients wherever they are around the United States. If we do find it to be effective, it will be the first randomized controlled trial showing that convalescent plasma is effective in the early treatment or prevention of COVID-19, which could really be a game changer in this fight, not only here in the United States, but around the world.

So if we can stop the virus in its tracks in the first week of illness while people only have mild symptoms, we can prevent them from developing worse disease, having to be hospitalized, having to receive oxygen, having to be intubated, and potentially dying as a result of the disease. Preventing all of those downstream complications not only saves lives, but saves health care dollars, prevents the health care system from being overwhelmed. And that's really important, because one of the big reasons that we're all stuck at home right now, because of this disease, is not only because of the high mortality, but because we have to protect our health care system from an overwhelming number of patients being hospitalized. And if we can stop this disease from hospitalizing people, then we can actually make it something that we can live with and go back to our lives with.

SARAH BALDWIN: That would be a game changer.

ADAM LEVINE: Absolutely. And that's true not just here in the United States, but around the world. The important thing about convalescent plasma is that every country on the planet that has COVID-19 has convalescent plasma, because it just comes from people who've recovered from the disease. So if you've had large numbers of people who've been infected and recovered, you have large capability to deploy this treatment to your population and prevent new infections or treat new infections early.

Unlike a drug, and unlike some of the other types of antibody treatments that are being developed which are sort of specific targeted antibodies that are being created in a lab, all of those are going to be patented, and they're going to be expensive. And so while we'll probably be able to afford them here in the United States, they probably will be too expensive for many poor countries around the world to afford in large quantities and deploy to their population. But every country in the world will have convalescent plasma that it can deploy for early treatment and prevention of COVID-19 in their countries.

SARAH BALDWIN: Well, if we find-- or if you find-- that this treatment approach works for COVID-19, would it be applicable to regular old flu?

ADAM LEVINE: Potentially, it would have to be studied in that setting. I think one of the tough things about influenza is that the virus actually changes every season, and so we have different strains of the virus, slightly different antibody responses, which is partly why the flu vaccine we got last year doesn't really protect us against the flu virus this year, and we have to get a new vaccine. So it may be a little bit more complicated to do with the flu, but potentially could be possible and be something that might be worth studying.

SARAH BALDWIN: It sounds like an amazingly logical and straightforward approach. And also, this study sounds like an amazing public service for the world if it turns out to prove that convalescent plasma treatment is effective for COVID-19, because everyone has access to it.

ADAM LEVINE: Exactly, and that's why I say to people, even individuals who are not so worried about their own health and also might be a little bit worried about enrolling in a clinical trial, this is actually a way that you can give back and help find a cure for this pandemic that has killed almost a million people around the world and shut down our planet. This is a way that everyday people who aren't doctors or scientists, but who happen to have been infected with the virus or happen to live with someone who's infected with the virus-- this is a way you can give back to your community here in Rhode Island, and also to the world. You can be an important part of the race to find a cure for this disease. And so that's why I really would encourage people who are hesitant to think about signing up for these trials if they're eligible.

SARAH BALDWIN: We'll include contact information for those who are interested in participating in the study in our show notes. But could you just say briefly what the qualifications are for each?

ADAM LEVINE: Yeah, so for our early treatment trial, we're looking for adults, so people over 18, who've been diagnosed with COVID-19 within the last week. For the second trial, it's anyone who lives in the same household as someone who has COVID-19 but is still asymptomatic themselves, so still hasn't contracted the disease or developed any symptoms. And it's that group of people that we really want to target to see if we can prevent them from getting infected. It would also include anybody who's had a high risk contact with someone with COVID-19. So that means anybody who's been in the same room as someone with COVID-19 for more than a few minutes without a mask on, or anybody who's actually directly touched or come in contact with someone with COVID-19 without proper protection.

SARAH BALDWIN: And there's compensation for participants?

ADAM LEVINE: Yes, there is compensation for participating in the study.

SARAH BALDWIN: Thank you so much, Adam, just for taking time out of your day with all you've got going on. I really appreciate your talking to us about this very promising trial, and I hope people will sign up.

ADAM LEVINE: Thank you so much. It's really been a pleasure.

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SARAH BALDWIN: This episode was produced by Dan Richards and Alina Coleman. Our theme music is by Henry Bloomfield. I'm Sarah Baldwin. You can find all the information about these trials, including if you might qualify for them, in our show notes. Subscribe to us on Apple Podcasts, Stitcher, Spotify, Google Play, or wherever you listen to podcasts. And if you like the show, leave us a rating and review on Apple Podcasts. It really helps others find us. For more information about this and other shows, go to watson.brown.edu. Thanks for listening. And tune in two weeks for another episode of Trending Globally.

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