Investigating Convalescent Plasma as a Treatment for COVID-19

One of the ways our immune system fights infections is by making antibodies, a protein found in the liquid part of the blood called plasma.

By Barbara Drosey

Sometimes treating a modern disease requires a line of investigation that takes cues from the past. David Teachey, MD, and colleagues are doing just that by exploring convalescent plasma as a treatment for COVID-19, the disease caused by SARS-CoV-2.

Dr. Teachey, who co-leads the Immune Dysregulation Frontier Program at Children’s Hospital of Philadelphia and is an associate professor of pediatrics at the Perelman School of Medicine at the University of Pennsylvania, explained that the concept of using the plasma of recovered patients to treat disease goes back to the 1890s, and it has been used to treat diphtheria, rabies, and the Spanish flu.

“This treatment is experimental and requires cautious interpretation,” Dr. Teachey said. “It's been done for other coronavirus infections like SARS with some success, and there are some early data and anecdotal reports from around the world suggesting there may be a benefit.”

One of the ways our immune system fights infections is by making antibodies, a protein found in the liquid part of the blood called plasma. Treatment using convalescent plasma takes the plasma of a person who has recovered from an infection and, in theory, should contain antibodies against that infection. Transfusing plasma from a recovered person to a patient who is sick with the same infection has potential to help the sick patient to also recover by enhancing their ability to fend off the virus. The American Red Cross is currently collecting plasma from individuals who have recovered from COVID-19.

The U.S. Food and Drug Administration issued guidance for the use of Investigational COVID-19 Convalescent Plasma. While the therapy has shown promise in the treatment of other respiratory infections, it has not yet been shown to be safe and effective as a treatment for COVID-19. As such, the FDA recommends three pathways for the administration or study of COVID-19 convalescent plasma: clinical trials, expanded access through the National Expanded Access Treatment Protocol, or a single patient emergency investigational new drug (IND) application.

In the case of one critically ill patient, a CHOP-Penn team worked with the American Red Cross, CHOP’s transfusion medicine, infectious disease, critical care, occupational health, the immune dysregulation teams, and the oncology protocol support office, who handled the regulatory paperwork to get approval from the FDA to administer convalescent plasma as an emergency IND.

When a patient is in dire need, clinicians may write to the FDA for approval. To give a sense of the current state of urgency, Dr. Teachey shared the FDA is working around the clock. “We wrote the FDA on behalf of our patient at night, and [the FDA] signed off on the paperwork at 3:00 in the morning,” he said.

At the time of publication, Dr. Teachey shared that four patients have now received treatment with convalescent plasma, although he did not have consent to elaborate on their conditions.

Not All Antibodies Are Equally Protective

As with any medical treatment, there are inherent risks – in this case, there is the potential for an allergic reaction and, though rare, infection and possibility of lung damage. When the body’s immune system creates antibodies to a virus, it can make two kinds of antibodies: neutralizing antibodies (IgG), which neutralize the virus so it doesn't cause harm; or antibodies that find the virus, pull it into other cells, and eradicate it within the body (IgM).

“Depending the type of antibodies, the treatment can actually make the infection worse,” Dr. Teachey explained. “For example, if a patient receives convalescent plasma from a person who produced ineffective antibodies, those antibodies would just coat the virus, making the patient’s own immune system unable to recognize the virus, and therefore their immune system would not make antibodies against the infection.”

With that in mind, this experimental treatment is reserved for those who are critically ill, not individuals experiencing mild or moderate symptoms of COVID-19.

What Can Children Teach Us About COVID-19?

As researchers investigate how convalescent plasma collected from those who have fully recovered from COVID-19 may benefit people who become severely ill and aren't helped by other treatments, they also are studying why COVID-19 tends to take a less threatening course in children. When considering infections in adult versus pediatric patient populations, it’s quite common for pediatric patients to fare better with recovery, even if they become critically ill. While there are exceptions, children simply tend to be more resilient.

“We have kids who are immunocompromised, and they are getting COVID-19, but not getting sick like adults are,” Dr. Teachey said. “Of course there are exceptions, and there have been critically ill children and children who have died in the United States as a result of COVID-19; but the odds of that happening are much less than with adults. Scientists at CHOP and other institutions are trying to figure out why. It's important to get across how much of a team effort this work is, and all the people who are involved to make this happen.”

Among his colleagues contributing to the effort are Deborah Sesok-Pizzini, MD, MBA, medical director of Blood Bank and Transfusion Medicine; Edward Behrens, MD, chief, Division of Rheumatology and co-leader, Immune Dysregulation Frontier Program; Kathleen Chiotos, MD, Pediatric Sepsis Program; and Hamid Bassiri, MD, PhD, in the Division of Infectious Diseases; all of whom hold faculty positions at the Perelman School of Medicine at the University of Pennsylvania, as well as Caroline Diorio, MD, FRCPC, FAAP, fellow with the Cancer Center at CHOP.

A protocol is open at CHOP to collect blood from consenting patients who have COVID-19, and work with the adult group at Penn to compare the blood of adults and children to gain an understanding of why kids generally do not become as critically ill.

Collaborative CHOP-Penn research is also underway to help determine what percentage of patients who get coronavirus make effective antibodies against it and if those antibodies confer lasting immunity.

There are some viruses people contract once, recover from, and never get again for the rest of their lives. If that's the case, by the time a COVID-19 vaccine is available, a large portion of the population will have already contracted the illness and achieved full immunity. But if this virus turns out to be similar to influenza in that it can mutate just enough for people to get it each year, then we may be looking at a future where every year we get a flu shot and a coronavirus shot.

“I think a vaccine is going to be important either way, but we'll have to see what the odds of people getting it twice are to understand just how important,” Dr. Teachey said.