Tatiana Prowell knew it was a long shot, but she didn’t know what else to do. Her brother-in-law’s father, the man she knew affectionately as “Papa Doc,” was in the ICU with COVID-19, and things were not looking good. “HELP!,” she tweeted late on Wednesday night: She needed to find someone who had recovered from COVID-19, and then ask for their blood.
The day before Prowell tweeted her plea, the Food and Drug Administration began allowing doctors to use plasma, the yellow fluid in which blood cells are suspended, as a Hail Mary to treat very ill COVID-19 patients. The idea of using plasma from survivors, also known as convalescent-plasma therapy, dates back to the late 19th century. Doctors have transfused the blood of recovered patients into those still sick with the 1918 flu, measles, polio, chickenpox, SARS, and Ebola—to varying degrees of success. Given the dearth of treatments for COVID-19, convalescent plasma has gained new prominence. The blood of survivors, the thinking goes, contains proteins called antibodies that can neutralize the coronavirus. Early data from very small numbers of COVID-19 patients in China show some promise. But the first hurdle is finding the recovered patients who can give plasma.
“We can’t go to that warehouse and get the 100 bottles on the shelf,” says Liise-anne Pirofski, the chief of the infectious-disease department at the Montefiore Medical Center, in New York. So doctors, scientists, blood banks, and government agencies have begun mobilizing to collect, distribute, and study plasma from COVID-19 survivors. The advantage of plasma is that you don’t need to develop a vaccine or treatment from scratch. But in these early days of the pandemic, when the number of recovered and confirmed patients is still relatively small, finding them will take time. The irony is that the bigger the pandemic gets, the easier finding donors will be.
Prowell, who had been following the prospects of convalescent plasma closely because she is also a doctor at Johns Hopkins University, was overwhelmed—in a good way—by the response to her tweet. She got hundreds of replies from people who offered to donate or knew someone who might. “That’s very powerful, but it’s obviously not the right way to do this at scale,” she told me. “We’re going to have millions of cases.” The family is still looking for a donor who fits all the criteria.
The way to do this at scale is a national network that connects donors, patients, and their doctors. Such an effort began in late February, when Arturo Casadevall, an immunologist at Johns Hopkins, published an op-ed in The Wall Street Journal suggesting the use of convalescent plasma for COVID-19. He started connecting interested doctors, virologists, immunologists, and blood-banking experts, who all came together to launch the National COVID-19 Convalescent Plasma Project.
The movement has gained traction. This week, New York announced that it would be the first state to try convalescent-plasma therapy, and the New York Blood Center, a major blood bank, began collecting plasma from people who have recovered from COVID-19.
For now, this plasma is going to hospitals in New York, which are using it on a case-by-case basis. A spokesperson at Mount Sinai told me that the hospital expects to transfuse its first patient this weekend. Mount Sinai’s call for donors got thousands of responses, which an army of medical students is now sifting through.
A single plasma donation from a COVID-19 survivor could go to multiple patients. Donating plasma is similar to donating whole blood, except the red blood cells are separated out by a machine and returned to the donor. “We can do two to three people from one donor,” says Bruce Sachais, the chief medical officer at the New York Blood Center. But the majority of these interested donors will not be suitable for one reason or another: The criteria, set by the FDA, suggest that donors should have had no symptoms for at least 14 days. They should have had a lab test confirming COVID-19, which is hard to get now and was even harder to get when the donors would have first gotten sick, several weeks ago. And, as with normal blood donation, patients and donors have to be matched by blood type. Prowell, for example, is looking for someone who is A-positive or AB-positive for Papa Doc.
In addition to using plasma on a case-by-case basis for very ill patients, doctors are also planning to study convalescent-plasma therapy for COVID-19 more systematically. Soon, the New York Blood Center plans to send out plasma for clinical trials at several hospitals, such as Johns Hopkins, the Mayo Clinic, and Montefiore Medical Center. To help find the right donors for the trials, Shmuel Shoham, an infectious-disease doctor who is involved in the Johns Hopkins trial, told me he leaned on a friend who is an organizer in the Orthodox Jewish community. Orthodox Jews in New York were at the center of an early coronavirus outbreak, which means those who have recovered could become donors right now.
Michael J. Joyner, a doctor at the Mayo Clinic, likened this phase to the “craft brewing” of convalescent-plasma therapy. It’s available at only a few academic centers, and doctors are reliant on personal connections to recruit donors. Getting to the “national-brewery model,” he says, requires involving bigger players. The FDA could help identify donors, and a network of national blood banks could send COVID-19 plasma to hospitals in small cities and towns. Eventually, pharmaceutical companies might be interested in pooling and purifying plasma down to a concentrated dose of antibodies—at which point convalescent plasma truly would be a standardized product you pull off the shelf.
All of this, of course, is contingent on plasma actually working against COVID-19. The clinical trials that are planned in the U.S. will focus on patients who are less ill—ideally those not in the ICU. Some evidence suggests that the antibodies in plasma are useful early on in the immune response, but less so once a patient has reached the stage of organ failure that requires hospitalization. No one knows why, Pirofski told me, but one reason could be that antibodies help prevent the virus from spreading from the nose and throat into the lungs.
At Mayo and Montefiore, the trials will be focused on people early into their infections. The Johns Hopkins trial will enroll people who have been exposed to COVID-19—maybe because a family member tested positive—but who do not yet have symptoms. If plasma can lessen the severity of COVID-19, it could be key to alleviating the strain on hospitals. “The idea is if we give this to people who have respiratory symptoms like cough and chest pain, maybe they won’t require supplemental oxygen, won’t require intubation,” Pirofski said.
Papa Doc has gotten slightly better in the days since Prowell tweeted for help. But he’s still sedated and on a ventilator; no visitors are allowed, due to the risk of infection. “That is so emotionally excruciating,” says Jason Constantine, Prowell’s brother-in-law. His father doesn’t know that they are trying to find him a plasma donor or that hundreds of strangers have taken an interest in him. But they are still looking for the right stranger who might be able to help.