UW-Madison will be a clinical trial site for a coronavirus treatment that uses plasma from recovered patients

What began two weeks ago with a pair of scientists urging the use of plasma from recovered COVID-19 patients to rescue the sick has blown up into a national movement.

Today 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.

The University of Wisconsin-Madison this weekend joined the National COVID-19 Convalescent Plasma Project, which has a website and intends to launch clinical trials as soon as it receives approval from the U.S. Food and Drug Administration. The group is also collaborating with the American Red Cross, blood banks, Amazon and Federal Express.

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The project centers on organizing and fast-tracking clinical trials at various institutions, a process that could take several weeks or more to begin.

"They're hoping to take this nationwide sooner rather than later," said Michael J. Joyner, who has been working to set up trials at Mayo Clinic in Rochester, Minnesota, where he works as a professor of anesthesiology.

"Everybody is on the same page."

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 Arturo Casadevall, one of the project's organizers and chairman of molecular microbiology and immunology at Johns Hopkins Bloomberg School of Public Health.

The project has already posted a protocol for clinical trials on its website, Casadevall said, adding, "The world is downloading it."

Preliminary results soon

Joyner stressed that researchers will see some preliminary results on the effectiveness of plasma well before clinical trials actually begin, possibly within 36 to 48 hours.

These early results would not come from trials but from the emergency compassionate use of survivor plasma in hospitals, a measure the FDA approved a week ago. Methodist Hospital in Houston has already started using the plasma for some of its COVID-19 patients.

Joyner said doctors and researchers are already collecting data from the emergency use of plasma and are attempting to analyze its performance "in close to real time." While compassionate use of plasma can be studied, it cannot substitute for randomized clinical trials.

The work in Madison will be led by William Hartman, UW Health assistant professor of anesthesiology and a former colleague of Joyner's at Mayo Clinic. Hartman said Madison will be one of the clinical trial sites, though he could not say how many patients will participate.

"We just had a meeting the last hour on this," he said. "The goal obviously is to treat as many as we can."

He said at least five other UW doctors will be involved, covering infectious disease, transfusion medicine, critical care medicine and internal medicine.

Using plasma from those who have recovered from a disease to treat those still sick with the illness is a technique that goes back more than a century to the treatment of a German child suffering from diphtheria.

Since then, the method has been used "to stem outbreaks of viral diseases such as poliomyelitis, measles, mumps and influenza," according to a paper two weeks ago in The Journal of Clinical Investigation.

Rich with antibodies

The plasma is rich with virus-fighting antibodies, but it does carry potential side effects, including fever, allergic reaction and a very small risk of infectious disease transmission.

It is unclear how far the plasma will go in saving people with advanced cases of COVID-19 and ultimately in slowing or ending the pandemic.

"I'm an optimist by nature. I think this is a human calamity and I think science and medicine will find a way out, but before they do we will lose a lot of people and see a lot of suffering," said Casadevall at Johns Hopkins, a co-author of the paper in The Journal of Clinical Investigation.

At UW, Hartman expressed faith in the use of plasma, saying, "I think we can be very hopeful in that it has exhibited success with previous coronaviruses including SARS (Severe Acute Respiratory Syndrome)."

The plasma also showed promising results in a small Chinese study of five COVID-19 patients, published a few days ago in The Journal of The American Medical Association. The five patients, ranging in age from 36 to 65 were all on mechanical ventilation when they received the plasma. Four recovered from acute respiratory distress syndrome.

At 37 days following the plasma infusion, three of the five patients had been released from the hospital; the other two were in stable condition.

"Nobody anticipates a Lazarus-like effect on the really ill," Joyner cautioned, referring to the biblical figure raised from the dead. "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."

The later stages of COVID-19 produce pneumonia-like symptoms including severe difficulty breathing.

Major challenge

Collecting plasma from recovered patients on a national scale will present a major challenge.

Of the nation's 160,000 COVID-19 patients, only 5,600 have recovered. To be considered recovered from the virus, patients have to be symptom free for at least 14 days.

Nonetheless, Joyner said, "a national distribution plan (for the plasma) is being worked on as we speak."

Federal Express will be working with the blood banks including The New York Blood Center. Amazon Web Services and Michigan State University Information Technology developed the project's website.

The national effort to use survivor plasma began coalescing with the publication of a journal paper on March 13 by Casadevall at Johns Hopkins and Liise-anne Pirofski of the Albert Einstein College of Medicine in New York.

Joyner said clinical trials will likely begin at different times at different sites as the pandemic moves across the U.S.

Federal Express is working with the blood banks, which will need to test any plasma to ensure it is not tainted by Hepatitis B, HIV or other viruses.

The clinical trials would test at least three distinct groups of people: those who have been exposed to the virus that causes COVID-19 such as doctors, nurses, first responders and family caregivers; patients already hospitalized with the disease who have continued to grow sicker; and severely ill patients.

In addition to approval from the FDA, trials will require approval from the Institutional Review Boards at each site. These boards are tasked with protecting the rights of human subjects used in research.

Organizers cannot say exactly when the clinical trials will begin. Joyner said he hopes that by the end of this week or early next week doctors will have gathered some of the plasma required.

"What hasn't materialized is a federal coordinator," Casadevall said, explaining that the project has proceeded with "terrific" help from the FDA, but with no leader from the federal government.

Instead, the effort is being guided by an executive committee including Casadevall; Joyner; Pirofski; Benjamin Chan, a doctor at Mount Sinai School of Medicine; Jeffrey Henderson, a doctor at Washington University School of Medicine in St. Louis; Nigel Paneth, a doctor at Michigan State University; and Shmuel Shoham, a doctor at Johns Hopkins University. The group is convening meetings by conference call once or twice a week.

Joyner praised the doctors, nurses and respiratory therapists who have been working to save lives across the country, while researchers have searched for a treatment.

"They become sort of like the Packers offensive line," he said.

"As devastating and as scary as this pandemic is, it is important for the general public to have confidence that we are doing our very best."

He said the project's motto is: "Don't permit what you cannot do to interfere with what you can do."