In New York and Houston, pints of straw-colored convalescent plasma have dripped into the veins of five U.S. coronavirus patients. Hundreds more there and across the nation are set to follow.
Whether the plasma, derived from the blood of people who have recovered from COVID-19, will help them fight off the devastating disease caused by the new coronavirus that has so far killed more than 5,100 Americans is still unknown. But, in less than three weeks, the effort to find out has gone from an idea to a worldwide program entirely self-organized by medical researchers.
Like so much about the desperate efforts to fight the COVID-19 pandemic, it’s seat-of-the-pants medicine. Doctors don’t know if it will work but are hoping to find out in weeks, not the years it typically takes for studies to yield answers.
“Our treatments began on Saturday,” said Ania Wajnberg, an internist at Mount Sinai Medical Center in New York City who is directing its Serum Antibody program.
It was only four days before that, March 24, that the U.S. Food and Drug Administration began allowing researchers to request emergency authorization to test whether the plasma will help.
Plasma is the almost clear liquid that remains after red and white blood cells and platelets are removed from blood. It contains antibodies that can fight disease.
“The Chinese paper came out days ago, but days are feeling like years to me right now,” Wajnberg said, referring to a paper published March 27 in the Journal of the American Medical Association that described a test of convalescent plasma on five critically ill patients in Shenzhen, China.
For Wajnberg and thousands of other doctors worldwide “nothing feels fast enough.”
Methodist Hospital in Houston began recruiting plasma donors on Friday and gave the first plasma transfusions to a COVID-19 patient the following day.
It’s a gamble of time, energy and money, said William Schaffner, a professor of preventive medicine and infectious disease at Vanderbilt University School of Medicine in Nashville, Tennessee.
Convalescent plasma therapy has a mixed history of success. It's also time-consuming, expensive and difficult to deploy on a large scale. Even so, he’s all in favor of it.
“Any port in a storm — and we’ve got one heck of a storm out there,” he said.
National COVID-19 Convalescent Plasma Project seeks donations
The project, dubbed the National COVID-19 Convalescent Plasma Project, already has posted a protocol for clinical trials on its website.
"The world is downloading it," said Arturo Casadevall, one of the project's organizers and chairman of molecular microbiology and immunology at Johns Hopkins Bloomberg School of Public Health.
The plasma is being collected from patients who have recovered from COVID-19. Each donates a pint of blood. The red and white blood cells are separated out and put back into the donor’s bloodstream while the blood plasma, rich with virus-fighting antibodies, is kept aside.
The donor and the patient must be from compatible blood types and the plasma is tested for multiple diseases including COVID-19, HIV and hepatitis to ensure it can’t transfer other diseases.
While convalescent plasma (from the blood of people “convalescing,” or recovered, from a disease) has been used successfully in outbreaks of other diseases such as polio, measles and mumps, it’s by no means a slam dunk.
“It’s been used for other viruses, some with efficacy and some without,” said Wajnberg.
The plasma showed promising results in the small Chinese study posted as a preprint on March 27. Another preprint, from March 16, about plasma treatment in 10 severely ill patients in Wuhan, China, found similar results.
Preprints are papers posted to online open-access sites before they have gone through the rigorous scientific peer review process, so information can be shared rapidly. During the COVID-19 crisis, they have been crucial in quickly disseminating essential data.
In both studies, almost all the patients also received antiviral and other treatments, making it difficult to know in a group of only 15 patients what specifically helped.
For now though, plasma therapy is one of few options for doctors when critically ill patients "don't have much time," said Eric Salazar, principal investigator in the Department of Pathology and Genomic Medicine at the Houston Methodist Hospital and Research Institute.
“Convalescent serum therapy could be a vital treatment route because, unfortunately, there is relatively little to offer many patients except supportive care,” he Salazar.
No one is anticipating the treatment will have a "Lazarus-like effect on the really ill," cautioned Michael Joyner, who has been working to set up trials at the Mayo Clinic in Rochester, Minnesota, where he is a professor of anesthesiology.
"What's more likely is that the slope of the patient's decline will gradually slow and that they can be weaned off of ventilation," he said.
Speedy science: From a published paper to reality in less than three weeks
The idea of giving desperately ill patients blood plasma from people who have recovered from the same illness is more than a century old and was first used to treat a German child suffering from diphtheria.
But using it to fight COVID-19 has gone from one paper published in the Journal of Clinical Investigation on March 13 suggesting the idea of a large trial to a broad program in fewer than three weeks.
It’s become an international effort, showing the ability of scientists to self-organize at a speed unimaginable even three months ago. As of Monday, more than 100 researchers and 40 large hospitals in 20 states are involved in the effort to bring survivor plasma to clinical trials, according to project leaders.
Other countries are joining what began as a grassroots endeavor by doctors and scientists.
"We brought in the United Kingdom over the weekend. Ireland, too," said Casadevall, who co-wrote the March 13 paper.
When a person is infected with COVID-19, the body creates blood proteins called antibodies to attack the virus, said Mark Slifka, a viral immunologist at the Oregon Health and Science University in Portland.
“When the body mounts an antibody response, it clears the virus and then you maintain that antibody response,” said Slifka, who studies the body’s immunological memory after vaccination or infection.
Depending on the disease, the body keeps making those antibodies for weeks to months to a lifetime. No one knows how long the antibodies against COVID-19 will stay in the bloodstream, but work on similar coronaviruses suggests it’s at least a year, he said.
COVID-19 Plasma Project matches donors with the sick through website
For now, the plasma is being taken from people who were exposed to or contracted COVID-19 about three weeks ago and have recovered. So far that seems to be the time the body requires to mount a strong immune response to the virus.
People who have tested positive for COVID-19 and fully recovered can register on the Plasma Project's website to see if they are eligible and if there's a plasma donation program near them.
When people learn they are positive for antibodies to the virus and eligible to donate plasma to the effort, almost all have offered to do so.
“That’s been a bright spot in all this, everybody wants to help. It’s nice to see,” said Wajnberg.
Patients are being given between one and two units of the plasma, about one to two pints. Doctors are hoping to find out quickly how much is required.
At Mount Sinai, a committee is deciding the right candidates for possible treatment. Only hospitalized patients with severe clinical disease are being considered. Those who get the plasma are being meticulously tracked to see its impact on outcomes.
If it does prove to help, scientists hope to build up a pool of plasma for all blood types that can be given to severely ill patients.
“Maybe in a few weeks we’ll be able to report our first 10 or 20 patients,” said Wajnberg.
Plasma Project's 'national distribution plan' is ongoing to find 'a lot of donors'
A big concern is whether the treatment is scalable. As it stands now, one donor’s blood is enough to give to no more than one to two recipients. “We will need a lot of donors,” said Wajnberg.
The Plasma Project is working on the problem and "a national distribution plan (for the plasma) is being worked on as we speak," said Joyner.
The effort is an example of how medical researchers are self-organizing in the face of the global COVID-19 pandemic. The project has proceeded with "terrific" help from the FDA, Casadevall said, but has no government lead.
"What hasn't materialized is a federal coordinator," Casadevall said.
Instead, the effort is being guided by an executive committee from Icahn School of Medicine at Mount Sinai, the Mayo Clinic School of Medicine, Washington University School of Medicine in St. Louis, Michigan State University and Johns Hopkins University. The group is convening meetings by conference call once or twice a week.
The project's unofficial motto reflects the doctors' drive to do everything they can to fight the virus: "Don't permit what you cannot do to interfere with what you can do."
Weise reported for USA TODAY from San Francisco; Johnson reported from Milwaukee for the Journal Sentinel of the USA TODAY Network.