Plasma From Covid-19 Survivors Could Be a Lifesaving Treatment
Medical experts discuss the risks and benefits of using donor plasma from Covid-19 survivors—a treatment known as convalescent plasma therapy— to help the very ill recover.
Calling all Covid-19 survivors: Health experts believe that if you donate your blood, it might help save the lives of people infected with the coronavirus.
If you’ve tested positive for Covid-19, the disease caused by SARS-CoV-2, and you’ve now recovered and are symptom-free, you may be able to help others by donating plasma. This is the liquid part of your blood that contains antibodies that contribute to your immune response.
At least that’s the hope pinned on so-called convalescent plasma therapy, according to infectious disease and public health experts.
What is convalescent plasma therapy?
Convalescent plasma therapy involves taking donated blood from people who have recovered from Covid-19, and spinning it in a centrifuge to separate out the clear watery plasma that contains infection-fighting antibodies. Then, the plasma (after it is screened for other infectious agents) is infused into very sick Covid-19 patients. Clinical studies are underway, and the U.S. Food and Drug Administration (FDA) is removing some hurdles to make it easier for doctors to treat severely ill patients with this therapy. (Here are the ways to stop coronavirus from spreading at home.)
And there is reason for optimism. For starters, this is not a new treatment. It has been used for more than a century—and particularly before there were vaccines—to confer protective antibodies from one person (or animal) to another. This type of therapy was used during the 2009-2010 H1N1 influenza virus pandemic, 2003 SARS-CoV-1 epidemic, and the 2012 MERS-CoV epidemic. Also, there’s a lot of anecdotal evidence that suggests it works and is safe for Covid-19. (Here’s what else SARS, MERS, and Covid-19 have in common.)
Building the case for plasma therapy
A small study in the March 27 issue of the Journal of the American Medical Association (JAMA) looked at the use of this technique in five severely ill Covid-19 patients in China who had severe respiratory failure and were on ventilators. The researchers found it worked. Fever returned to normal in three days in four of the patients. Viral loads were negative in all five patients within 12 days of the plasma transfusion. What’s more, researchers reported an increase in the SARS-CoV-2–specific and neutralizing antibody titers in the treated patients after transfusion.
Calling the study findings “compelling,” John D. Roback, MD, PhD, and Jeannette Guarner, MD, of Emory University School of Medicine in Atlanta, point out that there was no comparison group of individuals who did not receive this therapy. So, it’s possible that these patients would have recovered on their own. In addition, the patients were also receiving other therapies. Therefore, it’s hard to tease out the effect of the donated plasma.
“If the results of rigorously conducted investigations, such as a large-scale randomized clinical trial, demonstrate efficacy, use of this therapy could help change the course of this pandemic,” Dr. Roback and Dr. Guarner write, in an accompanying editorial in JAMA.
What the experts say
Miriam Smith, MD, chief of infectious disease at Long Island Jewish in Forest Hills, New York, is cautiously optimistic about the potential of this therapy. “The concept is sound,” she says. “You sort out patients with high antibody who have recovered and process the serum to extract plasma and put it into patients who are critically ill for an immune boost.”
Still, more research is needed. It’s unknown when would be the best time to extract blood and infuse it, and how much is necessary to see improvement.
We are on the clock, says Edward Snyder, MD, professor of laboratory medicine and attending physician in transfusion medicine at Yale New Haven Hospital in Connecticut. “This is a viral infection for which we have no immunity because we have never seen this virus before,” Dr. Synder says. You can develop immunity from exposure to an illness or through vaccination, he explains. “Right now, we have no way to protect against Covid-19.”
The plasma technique is the most promising because it is easy to bring to the bedside, he says. “If you take plasma from one person and give it to someone else, you can do it in a day or two,” he adds. “It’s immediately available and all you need is the FDA’s blessing.”
And doctors now have that blessing. The FDA will allow treatment on a case-by-case basis in extreme cases. Doctors must identify and qualify donors who meet the proper criteria and request permission to proceed from the FDA.
Another potential plasma-derived therapy
Vaccines for Covid-19 are being developed, but realistically they are at least a year and a half away, Dr. Synder says. Another form of treatment that uses plasma is hyperimmune globulin (H-IG). This process involves collecting plasma from a large number of individuals, extracting the antibodies only, and preserving them in a bottle. The manufacturing process is much more involved and takes a lot longer, Dr. Snyder explains.
“If we could get H-IG or a vaccine in a few weeks, we wouldn’t be doing convalescent plasma therapy, but this is the best we can do and the quickest we can do it.” (These are the people at highest risk from Covid-19.)
Convalescent plasma therapy dates back to the late 1800s and early 1900s. This is when Adolf von Behring received the Nobel Prize for using blood from immune horses as a method to cure and prevent diphtheria, according to Dr. Synder.
Still, there are questions that remain about the use of this therapy. “We don’t know the dose or concentration of the antibody that is most likely to be effective, and we don’t know at what point patients should be infused,” he says. “We need data.”
Dr. Synder likens the use of convalescent plasma therapy today to the early days of bone marrow transplantation for people with advanced cancer. “We gave bone marrow to the sickest people and they didn’t survive, but now we know that if we give it early in the disease, it is lifesaving,” he says.
Risks of donating plasma
But of course, there are risks, when it comes to donating plasma, Dr. Synder cautions. The donated plasma could trigger the recipient’s immune system and they could get sicker. Industry is diving in, he says. Cerus, a blood products company, is using a technology that they developed to clean the plasma so there aren’t elements of other viruses left behind. The company also formed a collaborative research group to identify key characteristics that influence the efficacy of convalescent plasma. This includes the level of anti-Covid-19 antibodies, optimal timing for donation, dosing, and how these factors influence responses to the therapy regimen.
Collecting plasma from survivors
In New York, the epicenter of the Covid-19 outbreak in the U.S., doctors at Mount Sinai Hospital in New York City are actively starting to collect plasma from survivors. “We are trying to find patients with high antibodies in their blood and have them donate plasma to be transferred into patients with the virus to help treat it,” explains Daniel Stadlbauer, PhD, a post-doctoral fellow in Mount Sinai’s Krammer Lab that developed one of the first antibody tests for Covid-19. Currently, Stadlbauer and colleagues are working with the FDA to get this lab test approved for use. Then, they will be able to bring it to the bedside.
Recruiting Covid-19 plasma donors
A program to recruit Covid-19 convalescent plasma donors is in the works at Northwell Health in New York. The product should become available to treat Covid-19 patients in April under the FDA’s guidance.
“We are getting ready to do it,” says Alexander J. Indrikovs, MD, senior director of transfusion services at Northwell Health in Manhasset, New York. “There are several published reports on the use of convalescent plasma in a small number of patients with a variety of viral diseases that have shown some improvement in patient outcomes,” Dr. Indrikovs notes.
Programs at other healthcare institutions will look at whether convalescent plasma can be used to prevent people from becoming sick.
“The optimism is high especially when there are so many people with bad complications from Covid-19 and so many people who are dying.” Dr. Indrikovs says.
- JAMA: "Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma"
- Recent Patents on Anti-Infective Drug Discovery An augmented passive immune therapy to treat fulminant bacterial infections.
- Blood Transfusion Convalescent plasma: new evidence for an old therapeutic tool?
- JAMA: "Convalescent Plasma to Treat COVID-19 Possibilities and Challenges"
- Miriam Smith, MD, chief of infectious disease, Long Island Jewish, Forest Hills, New York
- Edward Snyder, MD, FACP, professor of laboratory medicine, attending physician in transfusion medicine, Yale New Haven Hospital in Connecticut
- FDA: "Investigational COVID-19 Convalescent Plasma - Emergency INDs"
- Cerus: "Cerus Forms Group to Research Optimal Production of COVID-19 Convalescent Plasma"
- Daniel Stadlbauer, PhD, a post-doctoral fellow, The Krammer Lab, Mount Sinai Hospital, New York City
- Alexander J. Indrikovs, MD, senior director of transfusion services, Northwell Health, Manhasset, New York