Coronavirus in Context: Treating COVID-19 with Convalescent Plasma

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You're watching "Coronavirus in Context." I'm Dr. John Whyte, chief medical officer at WebMD. We've been hearing a lot about different treatments-- potential treatments-- for COVID-19. One we haven't heard that much about lately is convalescent plasma, so I've asked Dr. Peter Hotez. He's the dean of the National School of Tropical Medicine at Baylor College of Medicine to come by and tell us the latest. Dr. Hotez, thanks for joining me.

Thanks for having me.

Can we start off by explaining to viewers-- what is convalescent plasma?

Well, the idea is if you become infected with a virus agent, such as the virus that causes COVID-19, the SARS-2 virus, you become infected. And then, more often than not, you develop an antibody response. And that antibody response is one of the reasons why you ultimately clear the virus, and also can protect you against getting re-infected. And that's the basis for a lot of our vaccine strategies.

But that-- and those antibodies themselves could be used as a therapy. And this idea is more than 100 years old. It was actually used during the 1918 flu pandemic, even though they didn't know exactly what the basis was. But the idea is if somebody is recovered from the virus, they'll have antibodies. And you remove the blood, and now we can actually give back red blood cells through an apheresis process.

But then the plasma, or the serum, could be used as a therapy. And this actually was looked at very closely after the first SARS epidemic. So 2003, if you remember, SARS emerged out of southern China, and infected Toronto. And there were a number of studies, and there is now a pretty good sized meta-analysis, showing that it actually worked.

So when we started seeing COVID-19 coming out of China, and there was a lot of worry that this could be a big problem in Europe, or even in the United States, a group of physician scientists actually mobilized to see if we could scale it up here in the United States.

Now, it's not a simple procedure, correct? Obviously, it's not like taking a pill. It's not getting an injection through the muscle. There is some labor associated with there-- is it not-- in terms of to do this. And most of the studies have primarily been in hospitalized, critically ill patients. Is that correct?

Yes, that's right. So the idea-- the one who has really been pushing hard on this is the group at Johns Hopkins, and at Albert Einstein, led by Arturo Casadevall. And now, Mayo Clinic is having a major role. And Duke's a part of it, as well as some of the hospitals here at Baylor College of Medicine and Houston Methodist Hospital.

And the idea would be that-- it would require you to have a high functioning and well regulated blood bank, a transfusion bank, whereby you would remove blood, give back the red cells, possibly through an apheresis process. And then, after you take that plasma that has antibody, you want to measure it. So you want to usually measure high-- you want to usually look for plasma that has high titers of antibody, because if it just has a little bit of antibody, that probably may not be effective.

And then you need to inactivate any potential contaminating viruses, because plasma, in theory, could have the HIV virus, the AIDS virus. It could have hepatitis. There are different types of hepatitis virus, so you inactivate it. In China, they were using an agent called methylene blue. The older one is gentian violet, I think, here in the US. They're looking at psoralen, maybe other inactivating agents. And you administer it.

And I think, you know-- I think it's really important to remember that this kind of antibody therapy, usually, it tends to work earlier on in the course of the infection, rather than later. Because if you think about what's going on in COVID-19 patients-- we still don't have a lot of data on this, but the supposition is that the early stages of the infection are due to virus invasion, and the later stages are due to some type of post-inflammatory or cytokine response.

So you want to get those antibodies in early to prevent binding of the virus to the receptor, and be able to neutralize the virus. And that's where some of the confusion comes in, in terms of clinical trials and studies, because you have to control for when you're timing those antibodies. And that's being done, I think, in at least 20 academic medical centers.

I was in contact with Arturo and others-- Dr. Casadevall and others, and Shmuel Shoham as well. And they informed me now that more than 4,000 people have been treated with plasma across the US. And these are part of an expanded access programs. And so far, it looks like it's safe. And one of the problems is whether it actually works. It's a bit difficult to discern, because there's no comparison group.

And what the team at the Mayo Clinic is doing is they're looking at a big data project to see if they can derive some clinical trial comparisons. The anecdotal information is it's working, but we're going to need to scale up that information.

What role do you think this will end up playing, say, three months from now, in the different treatment options. Is it going to be considered one of the first line therapies, or you think it'll be kind of more those therapies that we consider after different options have not worked?

Well, it's a bit limited, isn't it, because you have to have convalescent patients. And they have to have a high enough antibody titer. So I think the idea is this is version 1.0. Version 2.0 is maybe you could pool a lot of those antibodies, and concentrate that, and make a commercial hyper immunoglobulin. This is what we do for rabies-- right, rabies immunoglobulin.

Or, as a step better, in terms of mass production, is to clone antibodies from infected patients and scale it up as a monoclonal antibody therapy-- like, you would say Humira, or other antibodies to interleukin receptors, but do this for the virus. This was done, if you remember, for Ebola-- if you remember back in 2014, we had ZMapp, the ZMapp monoclonal collection of monoclonal antibodies.

And I would envision that something like that eventually will be produced. And it has a good potential for success, provided we can get to patients early on, before they're developing a pretty aggressive cytokine inflammatory response.

And you mentioned antibodies throughout. So I want to ask you, because there's so much discussion about antibody testing, and whether the presence of antibody on a test affords protection. That's really what people want to know-- associating with immunity. So what are we learning, though, from convalescent plasma? Does that give us any more data? Are we able to make more inferences, based on what we're learning with convalescent plasma, relating to antibody testing, and whether or not that'll protect people?

Yeah, I mean the fact that patients seem to be responding to it is a good indication. You know, if you look at the early SARS literature back in 2003, those patients who developed a convalescent antibody, they were generally pretty sick patients, also, because SARS-1, you didn't have this situation where you had asymptomatic patients, or people with low grade symptoms. If you had SARS, you were pretty ill, generally speaking.

And they developed a pretty robust antibody response, including antibodies to the receptor binding domain of the spike protein. With the COVID-19 virus, the SARS-2 virus, I think the situation is going to be that most patients do develop a pretty vigorous antibody response. But there's an emerging story now about a subset of patients, maybe those with mild symptoms, or maybe asymptomatic individuals, who may either develop no antibodies or low titers of antibodies.

And we really don't know what the situation with those individuals are. There is one study with a handful of rhesus macaques in China that's been put up. I forget if it was on bioRxiv, or medRxiv, or preprint server, showing that you infect them, they develop antibodies. And those rhesus macaques are resistant to reinfection. So I think the trend is clear, clearly, that the antibodies will be associated with protection. But you do have a subset of individuals, that may not be the case. Likely, those are those with low titers of antibodies.

But we'll learn a lot more in the coming months. Then, of course, you have the other complication-- is you've got a wide range of antibody tests. And we're getting false positive--

I was just going to ask you, does that--

Trying to sort through that is going to be mess, also.

Does that mean less focus on point of care testing, which is a qualitative test, and more so-- I'm thinking about, you know, a serum draw, trying to look at titers, or other elements?

Well, remember how this works in the US. The reason you might want to know if you're antibody positive is because you want to know whether you can safely go back to work if you're exposed to asymptomatic people at the workplace that are shedding virus. And I think right now, it's not a huge factor, as many are making it out to be.

And the reason I say that is because I think probably less than 10% of the US population is antibody positive at this point. But overall, the vast majority of Americans are still going to be serum negative to this virus. Now, if we see repeated waves, and we move closer to a higher percentage, this may become more relevant.

Well, Dr. Hotez, I want to thank you for sharing your insights today.

Thank you so much.

I want to thank you for watching "Coronavirus In Context."