Plasma Technologies LLC has signed a defense contract worth $750,000 to develop scaled-up Covid-19 convalescent plasma technologies, according to an announcement on the Department of Defense website Monday.
It’s the latest development in the effort to use a 19th century treatment to help 21st century patients.
The contract with the DoD’s Joint Acquisition Task Force is to develop a new convalescent blood plasma process that makes more serum-derived products, and faster.
President Donald Trump and US health leaders have done a full court press to encourage people who survived Covid-19 to donate plasma to help those who are sick.
Two weeks ago, on a tour of the Red Cross, Trump implored people to volunteer to donate plasma “as soon as you can.”
“We have a lot of people that would heal, would get better. As soon as you can, please,” Trump said.
While nearly 67,000 people have been infused with the treatment and nearly 14,000 physicians are using it, according to UScovidplasma.org, it’s still not clear if it works. Several studies are under way.
A Victorian solution to a modern problem?
Convalescent plasma is a treatment created out of blood from people who have recovered from an infection such as Covid-19. Plasma is the liquid portion of blood containing immune cells and antibodies – proteins the body makes to fight infection. The plasma can be infused into a sick person to help recovery.
Since the Victorian era, doctors have used this treatment to fight severe cases of the flu. The treatment has also shown success with two other deadly coronaviruses - MERS and SARS. Yet it will take studies to prove that it works to treat Covid-19. Absent other treatments, doctors have opted to use the treatment as it was still being studied.
Doctors try the old treatment
When the Covid-19 pandemic hit New York City hard in March, doctors desperate to save patients weren’t sure what might help. Plasma from recovered Covid-19 patients showed some early promise. For professionals used to relying on scientific evidence and established facts, there was – and still is – little to work with.
“It was sort of like learning to fly the plane when we were in midair,” Dr. Nicole Bouvier, an infectious disease specialist at Mount Sinai, said. “There are basic things that you know about human physiology, but you don’t necessarily know how this particular virus is going to behave and what the best treatments are,” she said.
“We probably changed what we were doing on a daily basis.”
To see what worked, Bouvier and team did a retrospective analysis on data collected from 39 patients.
Even in that small group, convalescent plasma stood out.
Bouvier published the results in a small pre-print study, meaning it isn’t peer reviewed yet, in May. Patients treated with convalescent plasma improved more than those who were not transfused, and more patients survived.
“We don’t have definitive answers yet, but we are on the way to getting definitive answers and, I would say, that the evidence, while imperfect, is promising,” Bouvier said.
Dr. Janet Woodcock, who’s heading up the therapeutic efforts under Operation Warp Speed as the director of the US Food and Drug Administration’s Center for Drug Evaluation and Research, recently called vaccines the “permanent hope,” but she said vaccines are not the only approach that will get this country out of the Covid-19 pandemic.
Convalescent plasma, Woodcock said, is an option that can be “feasible fairly quickly.” Woodcock, said it’s a treatment the government is trying to accelerate, even before the government knows if it works.
Early results in China
Early on, a handful of small studies in China looked promising.
A small study published in JAMA in March showed four of five patients given convalescent plasma improved. A second small study of 10 Chinese patients published in May in the journal PNAS saw improvement in patients treated with convalescent plasma, with no safety issues. Two other small pre-print studies from China showed similar results.
One additional observational study from Chinese researchers published in June did not see an improvement in the mortality rate among six critically ill patients, but the authors did not dismiss convalescent plasma completely. Instead, they suggested it may work if patients were treated earlier.
Trying the treatment in the US
The US Food and Drug Admnistration has not yet approved its use for the treatment of Covid-19, but at the end of March, the FDA created a pathway for scientists to try convalescent plasma with patients and study its impact.
Doctors at Houston Methodist immediately performed what it says were the nation’s first plasma transfusions. They published their results in the American Journal of Pathology in May.
Among 25 hospitalized patients with Covid-19, seven days after the convalescent plasma treatment, nine showed some improvement and seven were discharged from the hospital. By day 14, 19 had improved and 11 were discharged. There were no safety issues.
Still, it’s not clear if the treatment was the reason these patients improved; the study results would need to be reproduced in a larger group of patients.
As evidence mounted that it had shown some success, the FDA put out a call in April to urge recovered patients to donate plasma. The government launched a website instructing Americans on how they could donate, as did the American Red Cross.
First ‘maybe,’ then ‘possibly,’ now ‘probably’
In June, a larger study of 5,000 hospitalized patients published in the Journal of Clinical Investigation showed that the treatment was safe.
Dr. Arturo Casadevall, one of the researchers, called convalescent plasma the “good news story” of the pandemic.
The chief of molecular microbiology and immunology at Johns Hopkins Bloomberg School of Public Health, Casadevall thought the practice held promise and helped spearhead the national push to understand if this therapy works in March, when he and a colleague wrote about its possibilities in the Journal of Clinical Investigation and created the National Covid-19 Convalescent Plasma Project. It’s a national network of providers at 57 institutions in 46 states. More than 100 people joined the group’s first conference call.
The organization quickly published a guidebook of convalescent plasma best practices for physicians. It created a website collecting the latest science. The physicians started clinical trials. One that’s underway looks at the impact of the treatment on health care workers. Another is looking at the effect of convalescent plasma on patients who have not been hospitalized.
“When we first started this effort if you had asked ‘do you think it’s going to work?’ I would have said ‘maybe,’” Casadevall said. “Since then I progressed to ‘possibly,’ and now, I am at ‘probably.’”
Casadevall wants more research to prove it works.
“To really be certain you need to complete the randomized clinical trials,” Casadevall said. “But the good thing has been that there have been multiple reports that have been encouraging, including my clinical trials from Wuhan that had to be stopped prematurely.”
That trial was stopped when the flood of patients slowed to a trickle and there weren’t enough patients to test the therapy.
The number of cases can also impact how much of the therapy is available. Unlike with a monoclonal antibody therapies that can be made in the lab, this treatment relies on volunteers.
“It is a limited resource,” Woodcock said Monday. That’s why there has been a concerted push to get more donors. Even Dwayne “The Rock” Johnson has been enlisted to urge people to donate.
Typically, one donor’s plasma can treat two or three people and the original donor can come back and donate again within a couple of weeks.
But there are only so many donors, Woodcock said, and scientists are starting to think there is only a month-long window in which people have enough antibodies in their blood to help someone else fight the disease. But again, they need more research to know for sure.
An August study of 35,000 patients that has not yet been peer reviewed found that giving people the plasma treatment early seemed to reduce deaths more. People who got the transfusions within three days of diagnosis had a seven-day death rate of 8.7%, while patients treated four or more days into the course of illness had a 11.9% mortality rate.
But there was no placebo group. Without that comparison, it’s hard to know if the treatment made the difference.
The treatment be a difficult one to get right. Monoclonal antibody treatments, by contrast, are made by scientists in the lab. They pick the antibody that works best in the lab to neutralize the virus and reproduce it in the lab. Such Covid-19 antibody therapies are in clinical trials now, too.
With convalescent plasma, patients get all the antibodies in that plasma, not just those carefully engineered to fight the virus. Every donor’s plasma is a little bit different and some may have more antibodies that protect against the virus better than others.
“Convalescent plasma, I think we need to have more caution about that,” Dr. Anthony Fauci said recently. “You want to make sure you do it right.”
Even before scientists know for sure, the US Department of Defense said it wants to collect 8,000 units by the end of September. Casadevall said the government is also stockpiling 200,000 units, something he says is a sign that the experimental treatment is here to stay. Plasma can be stored frozen for about a year.
Woodcock, who said the US government is trying to accelerate these plasma drives, thinks there may be an additional benefit to convalescent plasma that goes beyond treating someone’s symptoms.
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“I think people feel very helpless in the face of this,” Woodcock said. “This is something that everyone can contribute who’s been infected.”