Using plasma of patients convalesced from COVID-19, whose blood contains antibodies against the disease-causing SARS-CoV-2 virus, has been touted as a promising treatment for some patients with signs of infection.
UMass Chan Medical School’s Jonathan M. Gerber, MD, the Eleanor Eustis Farrington Chair in Cancer Research, professor of medicine, chief of the Division of Hematology/Oncology and medical director of the UMass Cancer Center, was the first in Massachusetts to successfully treat a seriously ill COVID-19 patient with convalescent plasma, in April 2020. He co-authored a recent report on a multicenter clinical trial from Johns Hopkins Medicine, posted on the preprint website MedRxiv, which found convalescent plasma is effective as an early treatment.
Dr. Gerber explained convalescent plasma and what researchers have learned in the past two years about its use in treating COVID-19. The interview has been edited for clarity.
What is convalescent plasma and how does it work?
Jonathan Gerber: Convalescent plasma is plasma directly collected from the blood of somebody who has recovered from an infection, in this case, COVID-19, and it should be chock-full of antibodies against COVID. By transfusing it into the recipient, you can actually give them somebody else’s antibodies to fight off the infection.
And it’s contingent on a couple of things. Number one, the antibodies have to be at a high enough level. The second piece is that the antibodies have to be of good quality. And that’s where the variants and things like that come into play, in that you’re looking for collecting plasma from a group of donors who will be representative of the infections that you’re currently seeing.
What are some of the COVID-19 convalescent plasma studies involving UMass Chan researchers?
JG: We participated in two trials spearheaded by the team at Johns Hopkins and funded by the Department of Defense. These focused on the outpatient side. The one we recently reported was used for early treatment of COVID. So, these patients were known to be positive. They were still within basically the first week after the onset of symptoms. It was roughly 1,100 participants, in a placebo-controlled, double-blinded, randomized trial, which is the highest quality type of trial that you can do in this.
What we found was there was a 54 percent reduction in the risk of needing to be hospitalized for the patients who received the convalescent plasma versus regular plasma.
The nice thing about the Hopkins trial is that it was run head-to-head against regular plasma, which had been confirmed to be devoid of COVID antibodies. And once again, consistent with the results of other studies, the trial we’re reporting now showed a good safety profile.
We’ve had our own protocol on the inpatient side. We treated almost 500 inpatients with plasma and we’re unraveling a lot of different things. We’re trying to both look at the dose that we deliver to people, sifting out low versus high titers of antibodies and seeing if there was a dose response.
The second thing that we’re looking at is the antibody levels of people who receive the plasma. The presence of antibodies of their own suggests that the virus may have been incubating for a while and that the patient may be beyond a time where convalescent plasma can help. The second part of measuring the antibody levels is that if they already have antibodies of their own, it doesn’t exactly make sense that giving them more antibodies is going to solve the problem.
So two lessons learned in our early experience: If you don’t give enough antibody, you’re not going to see an effect. And if you wait too long, or the disease is simply too far along, it’s not going to work either.
I would look at plasma as a fire extinguisher: You need to get in early and shut the infection off, and you need to get it in sufficient quantity that it can work.
We’ve also participated in a National Institutes of Health trial on a related product called hyperimmune globulin, which is ongoing.
Convalescent plasma is a therapy that has been around for at least a century. What have been some of the hurdles applying it to COVID-19?
JG: One of the main issues has been collecting convalescent plasma in reasonable quantities. In the first year of the pandemic, a government organization called BARDA [Biomedical Advanced Research and Development Authority] had been funding collection and distribution, so the American Red Cross and other blood centers were able to provide it.
But as the pandemic wore on, other treatments emerged and became more favored. We’ve seen a lot of success with monoclonal antibodies and now we’re seeing some antiviral oral agents that are effective, as well as the IV antiviral remdesivir. So, along with some other reasons, plasma collection really tapered off.
There were also two big restrictions on emergency use authorization by the Food and Drug Administration for plasma. One, it was restricted to inpatient use, and here we are talking about an outpatient trial that was very effective.
The FDA is reconsidering its position on things and a few weeks ago, for the first time, authorized outpatient use. They’re limiting it to immunocompromised patients, but they haven’t clearly defined what that means.
The second was that it can only be collected from individuals who had actually recovered from COVID. But we have a unique situation of vaccinating people. And it’s a shame because the vaccinated individuals have really sometimes sky-high levels of antibody, which should be effective; but we haven’t been able to take advantage of that donor pool.
We would like to mobilize the plasma collection again. And certainly, people donating plasma is a key thing.
How well does convalescent plasma work against new virus variants?
JG: Most of the patients in plasma trials haven’t been classified as to what variant they had, but our trials predated the emergence of the omicron variant.
But unlike manmade monoclonal antibodies which target a specific area, typically only a specific part of the spike protein, the nice thing about convalescent plasma is that it contains antibodies that are polyclonal—attacking many targets on the virus. Even from a vaccinated individual, they will have antibodies against multiple areas on the spike protein. And some of those are mutated in the variants and some of those aren’t.
And then when you transfuse convalescent plasma into people who have the infection, they’re going to receive antibodies not just against the spike protein but against other proteins and other areas of the virus as well, so you have potentially even more comprehensive coverage.
There’s a lot of variability in how good those antibodies are at clearing out and neutralizing the virus or activating components of the immune system. But one of the pluses of that variability is that you do probably get activity against variants. If you do real-time collection of plasma throughout the pandemic, you’ll start to get a representation of whatever variant is circulating in the community.
How do you see convalescent plasma’s role in controlling COVID-19?
JG: We don’t really look at it as the definitive treatment long term. But because of that ability to really leverage the human body and its ability to evolve in this arms race, as the virus is evolving, and keep pace—it’s a great stopgap measure as a bridge to vaccination and other treatments. It’s a great thing to be able to use quickly, and to mobilize large scale in countries that are less well-resourced than our own.
Related UMass Chan news stories:
Early use of convalescent plasma treatment for COVID-19 helps avoid hospitalization
UMass Medical School researchers ramp up COVID-19 convalescent plasma study
LISTEN: Jonathan Gerber on next-generation therapies to fight cancer
