It was late March when Scott Lederer, of New Windsor, began experiencing symptoms of COVID-19. He had an existing cough that was soon joined by fever and chills and body aches.
“My sister happens to be a nurse and so I called her and she recommended I call the Carroll County COVID-19 hotline about maybe getting testing,” Lederer said. He was directed to the Carroll Hospital drive-thru testing location on March 30. “They said I would get the results in about a week.”
And so he did. On April 6 the results came back positive, and while Lederer was beginning to feel better by that point, it was a rough journey.
“The fever was the worst, I think I had chills,” he said. “My fever was 102.5 for about three days. And then the body aches, just severe joint pain. Pretty much lost my appetite and my taste; I really couldn’t taste food.”
So when Lederer learned there might be a way he could help other people avoid that same experience, or worse, just by donating his blood plasma, he was all in.
“I’ve given blood in the past and I have no problem doing that,” he said. “I would have no problem donating plasma for somebody that might need it that’s in the hospital.”
Plasma therapy for COVID-19
The donation program Lederer had learned about is part of an initiative at LifeBridge Health, of which Carroll Hospital is a part, which is joining numerous hospitals and universities around the country in exploring the use of convalescent blood plasma as a therapy for people suffering from COVID-19.
It’s a method of providing instant immunity to patients by transfusing a blood product taken from people who have already recovered from a viral disease, according to LifeBridge Health Chief Innovation Officer Dr. Daniel Durand, and one with a historic pedigree.
In the early 20th century, when physicians were faced with outbreaks of viral diseases such as measles, polio and the 1918 Spanish flu for which they had no vaccines available, “They noticed that if they took blood from somebody who recovered and they isolated part of the blood, the clear part, called the plasma, that there was something in there that could be infused into somebody else and help them fight the disease,” Durand said. “Another word for recovered was convalescent — they used to have convalescent homes, so this is a historical word we don’t use much anymore — and this is called convalescent plasma.”
So far, Durand said, LifeBridge has infused 15 patients with plasma at Sinai hospital. There are no results yet on their condition, but the therapy could be expanded if all goes well.
As of April 23, LifeBridge Health had tested around 7,900 people for COVID-19, with just more than 1,400 testing positive. according to Durand. And the good news, he said, is that like Lederer, most of those people will recover, making them potential resources — Lederer is one of six people who tested positive at Carroll Hospital who have recovered and have applied to become plasma donors, according to hospital Spokesperson Simone Lindsay.
“We absolutely would love to have folks from Carroll County, and all the places that LifeBridge works with, to have the opportunity to donate plasma for this,” Durand said. “Anybody who is known to have been positive who has recovered should give us a call if they have interest.”
Those interested should go to lifebridgehealth.org/plasma to learn more.
What follows is a screening process over the phone, Durand said, and then a blood test to ensure the donor is, in fact, recovered from COVID-19 and their blood is tested for other blood-borne pathogens before being separated into the plasma and red blood cell components of blood.
The separated plasma is sorted by blood type and then is available, for a limited time — “Just like regular blood products, there is an expiration date,” Durand noted — to be intravenously infused in patients the same way saline might be administered.
“It’s a pretty straightforward administration process," he said. “It doesn’t require many bells and whistles.”
And while it would be not as universally protective or available as a proven vaccine, Durand noted that plasma therapy could potentially be available for those who need it most in a matter of months — something that cannot be said about any of the vaccine candidates.
“People want to say we might have it in a year, but I think the truth is, you might have something to be proven to be helpful — if you’re lucky — within a year,” he said. “Then you probably have another year of manufacturing and scaling and making sure it’s safe. There is just no way around the 12- to 24-month timeline for those things.”
Back from the past
While there are always risks associated with any treatment, plasma therapy has a long record of being well tolerated when used for a variety of viral disease, and there have been no reports of bad reactions from the 1,000 or so U.S. patients that have received plasma therapy for COVID-19 so far, according to Dr. Arturo Casadevall, a professor of medicine at Johns Hopkins, where he is helping to coordinate efforts to study plasma therapy. He was one of the authors of a March 13 paper in The Journal of Clinical Investigation that raised the idea of using plasma therapy to fight COVID-19, noting its use as early as the 1890s to combat diphtheria.
The treatment fell out of common use with the advent of better treatments and vaccines for known diseases, but Casadevall said there is reason to believe plasma therapy could be applied more safely and effectively today than in the past.
“In the mid-20th century we did not know about bloodborne pathogens like hepatitis. Today, plasma is collected and prepared under the most regulated medical industry, which is transfusion medicine,” he said. “It’s an ancient therapy, but it’s being done with all the modern technology that’s been learned.”
Will it work?
Plasma therapy is being given to patients sick with COVID-19, such as those at Sinai in the LifeBridge program, under “compassionate use," according to Casadevall, following the FDA’s emergency Investigational New Drug status for the therapy in early April. But these are not clinical trials, where those being given the therapy are balanced by a control group, he noted, which is why Johns Hopkins and other institutions are launching clinical trials now.
Casadevall’s colleague at Johns Hopkins, Dr. David Sullivan, for instance, is running the first randomized clinical trial anywhere on the use of convalescent plasma therapy in “ambulatory” COVID-19 patients, that is, those who have tested positive but have not yet become ill enough to be hospitalized.
“One of the rules of antibody therapy is, it always works best if given early,” Casavedall said. “If you give them plasma before they get really sick, can you prevent hospitalization? If that works, it would be a major advance. ... You head the disease off at the pass.”
Sullivan’s study will compare the effect of giving COVID-19 plasma therapy to patients who test positive but are not yet in the hospital to a randomly assigned control group of the same types of patients, who will receive blood plasma donated in 2019, before donors could have acquired immunity to COVID-19.
About 20 percent of people who test positive for COVID-19, especially older age groups, go on to get hospitalization, Sullivan said.
“Our endpoint is hospitalization, so it’s a nice, defined, hard cut — you’re either hospitalized or not,” Sullivan said, describing the goalpost for the trial.
While patients who are willing to receive plasma in Sullivan’s trial will be identified through Johns Hopkins and the other institutions participating across the nation, those who wish to donate plasma can send email to JHUcovidplasma@jhmi.edu to begin the screening process.
If it’s shown to work and significantly reduce the number of infected people who wind up needing hospitalization, Sullivan said, plasma therapy could be given to those at high risk, such as nursing home residents in an outbreak, the immunocompromised or those at higher risk in a household where someone may have been in contact with COVID-19, such as elderly parents.
But there is always that “if.”
“Here is the thing: this is not guaranteed to work,” Durand said. “Convalescent plasma is known to be helpful for some viruses, and not for others.”
There’s no evidence so far to suggest the therapy will not work, Sullivan noted, but “If this doesn’t work, I’m not so certain vaccines will work. I mean, the whole purpose of vaccine is to stimulate antibodies,” Sullivan said. “Then we focus on antivirals.”
Clinical trials for antiviral drugs such as Gilead’s remdesivir and the repurposed malaria drug hydroxychloroquine are ongoing, but results so far are mixed, according to Sullivan, and their deployment could still be a long way off.
How soon is soon?
But if plasma therapy could be available sooner than other treatments if shown effective, how soon will scientists know if it’s effective?
If things go really well, according to Casadevall, "I think we’ll know by early summer, which is not that far away from now,” he said. “But remember, this is not going to be a pharmaceutical product, because this is donated units from people.”
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If the plasma therapy trials work out, the next step would be to formulate antibody preparations from donated plasma, known as gamma globulin or immunoglobulin, which would provide consistent and concentrated doses of antibodies to patients without the variation inherent to donated plasma.
“As of right now these units differ,” he said. “Some people have a lot of antibodies and some people don’t have as much.”
Such a product is already being researched at multiple drug companies and could be available later this summer, Casadevall said.
Beyond that, according to Sullivan, the next step would be to use antibody producing cells to create antibodies to COVID-19, known as monoclonal antibodies, and to do so at scale in a laboratory.
“That’s the way we can mass produce this antibody, and then give it to people,” he said. “We don’t have to harvest it from anyone.”
And that’s the point, Sullivan said, where the plasma infusions given to just 1,000 people to date could lead to a much broader impact.
“If people knew they could get a test, and they knew they could get therapy if they got the virus, then we get back to a functioning society. Period. That’s the big idea,” he said. “This is something that we can do quickly and find out yes or no, and then implement it.”