An old idea for fighting infections — an approach most physicians know about only from medical lore — is being revived as people wait for drugs and vaccines to thwart the novel coronavirus. If it works, the blood plasma of people who have recovered from covid-19 would be used to protect health-care workers and help sick people get well.
The possible therapy is based on a medical concept called “passive immunity.” People who recover from an infection develop antibodies that circulate in the blood and can neutralize the pathogen. Infusions of plasma — the clear liquid that remains when blood cells are removed — may increase people’s disease-fighting response to the virus, giving their immune systems an important boost. The approach has been successful against polio, measles, mumps and flu.
“The recovered people could have in their blood something that could be very useful,” said Arturo Casadevall, chair of molecular microbiology and immunology at Johns Hopkins Bloomberg School of Public Health. “The history is this has been used in 120 years in medicine, and it’s well-known.”
Casadevall is hopeful the treatment, called “convalescent plasma,” could provide short-term relief to a medical system that faces a surge of patients, with no approved drugs or vaccines. But he and colleagues face regulatory, logistical and scientific challenges to set up a process that will ultimately be limited in how many people it can treat. Researchers must collect blood plasma from people after they’ve recovered, then test it to determine if it is likely to be potent against the disease and deliver it to patients.
Infectious disease specialists are sharing information through grass-roots networks, helping each other with clinical trial designs and ideas on how to screen plasma for virus-fighting antibodies.
New York Gov. Andrew M. Cuomo (D) announced his state would begin trying the treatment in patients stricken with covid-19, the disease caused by the coronavirus. The Food and Drug Administration announced Tuesday it was helping facilitate access to the experimental treatment, while underscoring the need to establish safety and effectiveness. Mount Sinai Health System in New York announced this week it plans to begin transfers of antibody-rich plasma from recovered patients to people who are severely ill.
“We get really hung up on always trying the newest, latest, greatest thing. And sometimes the classics are good, too, and they tend to be ignored,” said Jeffrey P. Henderson, an infectious disease specialist at Washington University in St. Louis, who is working on the project.
First, experts must develop tests to measure the levels of antibodies, and then use those to identify donors whose plasma is rich in antibodies that could help others battle the illness. Then, they have to deliver the plasma to patients — most likely in clinical trials designed to measure whether it works. The plasma must be safe and disease-free, not only from other blood-borne pathogens but also from the novel coronavirus.
Plasma could be used to treat people who are sick and to prevent illness in health-care workers, Casadevall said, especially those at greatest risk for developing the illness because of repeated exposure.
“Convalescent plasma has a real role — this has been going on for over 100 years. We know this stuff works,” said Wayne A. Marasco, an infectious disease physician at Dana-Farber Cancer Institute in Boston. “If you do this right and harvest plasma from someone who has undergone infection, you can get protective antibodies that can be infused in other people.”
Access to the therapy is likely to vary. Many hospitals are racing to set up clinical trials that would be open to patients who meet specific criteria. The FDA has also created a track for “emergency use” — a way for people with serious or immediately life-threatening disease to gain access to the treatment. But many logistical questions need to be solved, including the question of who will pay for the experimental treatment.
Michael J. Joyner, an anesthesiologist at the Mayo Clinic, said that, so far, he has been repurposing resources — redeploying about 20 people — to work on the project full time.
“For specific services, I am charging my endowment funds. The resources will catch up. If they don’t catch up, that is life,” Joyner said.
But the research into plasma is only one part of a broader effort to learn from people’s natural immune response to unlock secrets to treatment. In the longer term, Marasco and other researchers plan to develop drugs based on coronavirus-fighting antibodies. Marasco has a library of 27 billion antibodies from 57 donors that he plans to screen, looking for ones that are active against the new coronavirus.
Rockefeller University immunologist Michel Nussenzweig and his colleagues launched a study of people who have recovered from coronavirus infections this month — a study that also focuses on antibodies.
Nussenzweig searches for people who, as he described it, have “exceptional responses to viral infections.” In the past, he has studied patients with HIV, hepatitis B and C and other viruses. The approach worked most clearly with HIV. “There are just a small number of individuals that are infected that develop broadly neutralizing antibodies” to the virus that causes AIDS, he said, and their antibodies can be cloned, and, in theory, turned into therapies.
“It’s hard to tell in this exceptional time,” Nussenzweig said. “Normally, this is something that would take a year and a half. I don’t know exactly how much it can be accelerated.”
The convalescent plasma approach is appealing because it could provide a shorter-term option than an antibody therapy, which is also being pursued by drug companies. But even those who are working to make the treatment possible acknowledge it is just a bridge to a better, and more broadly accessible, solution.
“None of us sees this as a long-term solution. This is a stopgap, pending availability of more definitive interventions,” such as a vaccine or antiviral drug, said Evan Bloch, associate professor of pathology at Hopkins.
To give the treatment the best chance of succeeding, the researchers want to make sure they provide patients plasma that contains lots of antibodies — and design trials that can rigorously demonstrate whether it is working.
Ashoka Mukpo, a freelance journalist infected with Ebola in 2014, received plasma from a recovered physician after being evacuated to Nebraska Medical Center. He said he received the treatment at the height of his illness and recovered, but it is hard to know whether to attribute it to the treatment.
“I did have an adverse reaction — my heart rate dropped to 40, and they had to stop the transfusion briefly before resuming it,” Mukpo said in an email. “It was a very unpleasant experience, but I did feel better the next day. It’s hard to say whether that was because of the transfusion or just my body finally getting over the hump.”