Podcast: Can plasma from COVID-19 survivors help others battle the disease?

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Jim Dryden (host): Hello, and welcome to Show Me the Science, a podcast about the research, teaching, and patient care, as well as the students, staff, and faculty at Washington University School of Medicine in St. Louis, Missouri. The Show-Me State. My name is Jim Dryden, and I’m your host this week.

At present, we’re focusing these podcasts on COVID-19. Doctors and scientists all over the world have been scrambling to understand how the novel coronavirus affects us and to develop therapies. With no drugs or vaccines yet approved for COVID-19 and with the number of cases increasing daily, some doctors are looking to bring back a very old therapy. They want to transfuse antibodies from the blood of recovered patients into patients who are sick.

Jeffrey Henderson is one of the leaders of an effort to do the same thing now. He’s an associate professor of medicine and of molecular microbiology at Washington University School of Medicine in St. Louis. And he’s teamed up with colleagues at Johns Hopkins and at Mayo Clinic to launch a clinical trial. That trial was approved by the Food and Drug Administration, and in an unusual move, FDA also announced it would provide access to the experimental treatment for critically ill patients while the clinical trial is underway, expediting what’s known as emergency investigational new drug applications. As a result, the strategy is already being employed in several settings, including in New York. We asked Dr. Henderson about the goals of the study.

Jeffrey P. Henderson, MD, PhD: Convalescent plasma therapy has really a long history. And in this case, we’re using it as a potential therapy that we can quickly mobilize for a new viral disease.

Dryden: The idea is that you are collecting plasma from folks who’ve already had this, with the theory that they would’ve somehow built up some immunity in order to get better themselves.

Henderson: Yeah. Well when any of us experiences a viral illness, our immune system generates antibodies that show up in our blood, usually within a couple weeks of having the illness. These antibodies recognize a virus and then if that virus is encountered again, the immune system can quickly eliminate it. We can take advantage of this by purifying out the part of the blood that contains antibodies, which is the plasma, in somebody who’s recovered, and giving that plasma to somebody who either has been recently exposed or is in their early stage of illness where they haven’t yet developed their own antibodies.

Dryden: So what potential advantages, maybe some disadvantages, are there to using this type of an approach?

Henderson: Well, I think an advantage to this approach right now is that it takes advantage of something we already have in this country which is a very advanced blood banking system with lots of capacity and many decades of safety procedures built in. So that means we’re already equipped to take plasma from donors and safely administer that to patients. So that’s a big advantage of this approach right now. Because it’s a new virus, it’s going to take us a while to develop things like vaccines or antivirals that are effective against it. Until those things become available, it’s something we can use now.

Dryden: Are there any dangers or problems that could be linked to trying to do something like this?

Henderson: Generally speaking, plasma transfusions are quite well tolerated. It’s difficult to do studies with these because if you look back over the history of convalescent plasma as a therapy, it has generally been deployed almost as a last-ditch measure when people are kind of desperate for something. In those circumstances, people aren’t necessarily thinking about setting up the best possible study. They’re thinking about mobilizing whatever they can as a treatment.

Dryden: This type of treatment was tried back in the early 2000s in patients who were infected with SARS because that’s a virus from the same family as this novel coronavirus. How did it work in those patients?

Henderson: They weren’t particularly large studies, but when people have taken the individual studies and put big data together from those, the indications are that that was a successful therapy or in many cases helped improve symptoms or even survival from SARS.

Dryden: Part of my understanding of why COVID-19 is such a problem, is that none of us currently have any of this immunity. I mean, aside from those few people who have gotten the virus and gotten better.

Henderson: Right. That’s a remarkable thing about this. When it’s a new virus it’s quite readily transmissible. And you have a whole world population that is immunologically naive to it, which is what you’re describing. They haven’t seen a virus like this before. Their immune system hasn’t been trained to recognize it by either prior exposure or by a vaccine. And so yes, that’s part of the problem.

Dryden: Now, the people who have made these antibodies have recovered. Are they now safe do you think? Do they not really have to worry very much about getting this virus again?

Henderson: This is a burning question in the field. And of course we have no idea. It’s such a new virus. Nobody has been infected — that we know of — for long enough to answer that question. What we do know so far is that a month out from infection, people still have high titers of antibody in their system. But we don’t know how long that will last. We’re hopeful that that’s a lasting immunity and that reinfection would be a rare event, but time will tell.

Dryden: Now, how do you go about getting the plasma from these people who have recovered? And do you do anything to it or to the antibodies perhaps to increase the number of antibodies in a given dose or to spread them around so maybe a single donor could help multiple patients?

Henderson: Well, part of the beauty of this approach right now is that it is basically standard plasma collection and a transfusion. Just the same way we do that procedure and have done that in medicine for many years. So it’s really nothing new as far as a procedure. The only thing that’s different about it is that the donor will have recovered from COVID and the recipient has COVID. So those are the different parts about this. With that said, there will be refinements on this. There are those that are looking to purify out antibodies that are reactive to the virus and to be able to give those to patients or to those at a high risk of exposure. And those efforts are underway, but that requires a longer period of time to gain approval and to make sure it’s safe. So refinements on this convalescent plasma therapy will be forthcoming, I would imagine, as soon as potentially this summer or fall.

Dryden: How would you now use the plasma? Do you want to do it early in the course of the COVID-19 illness to keep infected patients from declining? Do you use this in the sickest patients who need the most help? How is that going to be worked out?

Henderson: The best scenario that we’re aware of based on our past experience, is that plasma donation or what we sometimes called passive immunization works best when given at an early stage in the disease. In the 1930s it was given to stop measles outbreaks by giving kids who were known to be exposed to measles, which of course is highly transmissible. And it probably stopped a number of outbreaks in school settings back in the ’30s. There’s been data over the years to indicate that it’s effective early on in an illness, in that window of time when the patient hasn’t yet developed their own antibody response. The track record, as you get into severe illness, it varies a lot. In general, it appears to be less effective. But there can be differences depending on exactly what virus we’re treating. And so we really don’t know yet for COVID whether it would be effective, say, in a ventilated patient with severe disease or not.

Dryden: What about Washington University and your other institutions that you’re working with at Mayo and Hopkins? Is there something special at those places that put you in a position to do something like this? Is there any evidence that similar approaches have been tried in other parts of the world so far?

Henderson: The effort in the US, in this network, started small. And it was just a discussion between friends and colleagues at Johns Hopkins at Mayo and myself at WashU. And Arturo Casadevall from Johns Hopkins floated this idea of convalescent plasma therapy. And we recognized or felt like this was actually a really good approach to try for something like COVID.

Dryden: But this is not the kind of thing that you normally work on, correct?

Henderson: I think notably perhaps here, I am not a virologist. I am not an immunologist. And perhaps notably, the other two people I’ve been working with would not identify as that either. One is an anesthesiologist at Mayo. And then Arturo Casadevall is also an infectious diseases physician-scientist who studies pathogenic fungi. So sometimes we get raised eyebrows that we’re engaged in this project outside of our kind of classical specialties. I think just when you recognize that there’s going to be an imminent need and feel that you’re well-positioned to make it happen, you change gears quickly. It built into a network, to a nationwide network of over 100 people, who’ve been engaged in one manner or another at all sorts of academic institutions. We’ve looked to see where else this has been tried. It’s been tried on a smaller scale in China that we’re aware of. Reports of their work with this are just kind of coming out, and it appears to have been successful in hospitalized patients there. Or have some benefit.

Dryden: Right. Now, you talked about just those Chinese studies though in hospitalized patients. I’m guessing that just because of our testing restrictions at the moment, it’s not like you’re going to be able to find somebody who has just become symptomatic because they might not be able to get tested at the present time.

Henderson: Right. The testing slowdown certainly is a challenge that has improved. And I think that right now, the FDA approval for convalescent plasma is for patients with relatively severe disease who’ve had some kind of respiratory compromise, weren’t breathing well. Part of the rationale for that is that if there’s little else of known value to offer these patients and medical judgment says this has a reasonable potential to help, then it will be made available. It is not going to be part of a rigorously designed clinical study, but that doesn’t mean we can’t learn something based on how these patients respond.

Dryden: Now, you’ve said that several scientists, including you here at Washington University, think this approach shows some promise. I wonder about the potential for using something like this as time goes on like recombinant DNA technology, so that once you get plasma from some of these donors it might be possible to ramp things up so that the antibodies could be produced on a larger scale the way something like insulin is produced. I mean, is that a long-range goal for this strategy if it works?

Henderson: Yeah. Absolutely. And I think scientifically, all of these efforts are poised for a nice hand-off from a more primitive technology like convalescent plasma handing off what we learn from there to what you’re describing which is recombinant protein technology. In that case it’s — we already know how to manufacture antibodies, humanized antibodies, to different antigens. They’re already on the market as a number of diseases for arthritis and so forth. What would be done here is if we can identify the parts of the virus that should be recognized by the immune system, those parts can be engineered into these antibodies. They can be grown in large amounts and administered to patients in a more controlled fashion than convalescent plasma.

Dryden: Now, if someone who’s listening to this did have COVID-19, has recovered, what steps would he or she take?

Henderson: Right now, I think plasma donors will be very important in getting this approach off the ground. The donation pipeline at the moment, donors of COVID immune plasma have to have had a previously positive COVID test. They have to be 14 days or more away from the end of their COVID symptoms. And of course, they have to be cleared to leave quarantine by public health. In this case, of course, they also have to be good candidates for plasma donation.

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Dryden: Jeffrey Henderson is an associate professor of medicine and of molecular microbiology at Washington University School of Medicine in St. Louis. He is collaborating with Arturo Casadevall at Johns Hopkins, Michael Joyner at Mayo Clinic, and others, to launch a clinical trial using antibodies in the blood plasma of COVID-19 patients who have recovered, in order to aid the immune systems of COVID-19 patients who currently are sick.

Show Me the Science is a production of the Office of Medical Public Affairs at Washington University School of Medicine. The goal of this project is to keep you informed and maybe teach him some things that will give you hope. For the foreseeable future, we’re focusing on the immediate threat from COVID-19 and ongoing efforts to treat it and stop its spread.

Thanks for tuning in. I’m Jim Dryden. Stay safe.

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