March 25, 2021

Why some experts say we can't give up on convalescent plasma yet

Daily Briefing

    Interest in convalescent plasma—once called a "breakthrough" Covid-19 treatment by the Trump administration—has waned in recent weeks, as some research suggests it's not as helpful as originally thought. But other experts caution that it's too soon to write off the treatment, particularly as new, more narrowly focused studies indicate it could be an effective treatment for certain patients, JoNel Aleccia writes for NBC News/Kaiser Health News.

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    A controversial treatment dims

    According to NBC/KHN, the use of convalescent plasma as a therapy for Covid-19 involves infusing blood plasma from people who've recovered from Covid-19 into newly infected patients in the hopes of bolstering their immune system. In August 2020, FDA issued an emergency use authorization (EUA) for Covid-19 convalescent plasma (CCP) as a treatment for hospitalized Covid-19 patients, overriding the concerns of federal government scientists, who said the therapy was still unproven.

    However, FDA scaled back its EUA this January, limiting the use of CCP to treat Covid-19 patients who had been hospitalized and were in the early course of the disease, as well as patients who had pre-existing conditions that undermined their immunity. FDA added that after May 31, providers could use as treatment only CCP with high concentrations of the antibodies that fight the virus.

    Shortly after FDA's revised EUA, in February, a large NIH trial of the therapy among high-risk patients admitted to the ED with mild to moderate cases of Covid-19 was halted. Researchers had determined that CCP—while not actively harmful to enrolled participants—did not appear to help them recover. And in that same week, a JAMA review of 10 convalescent plasma studies concluded there was no clear benefit to the therapy.

    Coinciding with the revised EUA, as well as the new research, the winter surge of Covid-19 began to abate, which sent demand for plasma plummeting, NBC/KHN reports. Hospital infusions of the therapy dropped from a high of roughly 30,000 units per week at the start of 2021 to about 7,000 per week in early March.

    In addition, NBC/KHN reports, the federal contracts that paid blood centers to collect CCP—totaling about $646 million—will soon expire. As a result, facilities around the country are reconsidering whether to continue collecting CCP.

    "We're not getting orders," Louis Katz, CMO at the Mississippi Valley Regional Blood Center, said. "I don't want to collect a product that is not going to get used and will cost me more money."

    The American Red Cross has also suspended direct collection of convalescent plasma, citing FDA's changed EUA for the therapy, as well as an "evolving" market. (That said, people who've recovered from the virus can still donate whole blood, which—if those units test positive for high levels of antibodies—could eventually be used as CCP, NBC/KHN reports.)

    Proponents advocate for continued research

    But amid all these setbacks, proponents of the therapy said declaring it ineffective with just a few months of research would be a "foolish overreach," NBC/KHN reports.

    In fact, according to NBC/KHN, the idea of using plasma from recovered patients to treat those recently made ill is a "century-old concept" that's been experimentally used amid several plagues, including the 1918 flu and Ebola. So rather than abandoning the therapy, researchers need to refine how and when they use plasma—as well as what they expect to happen as a result, according to Michael Joyner, principal investigator of a program, helmed by Mayo Clinic, that supplied convalescent plasma for more than 100,000 patients in 2020.

    As Joyner put it, "This is an unstandardized dose of an unstandardized product being given to all patients for a disease with variable progression. So, it is unrealistic to expect cookie-cutter results like you get for statin/heart attack trials."

    In support of the therapy, Joyner and other experts cited ongoing research, such as a study in Argentina that found giving CCP with high antibody levels within three days of a mild case of Covid-19 helped curb the disease's progression in older patients. Similarly, a study in mid-March, conducted by U.S. and Brazilian researchers, found that while CCP didn't help symptoms during hospitalization for patients with severe Covid-19 symptoms, it was correlated with a 50% decrease in death after 28 days—a finding the researchers said "may warrant further evaluation."

    U.S. oversight committees have authorized the continuation of two federally funded clinical trials of CCP. In one study, researchers at Johns Hopkins University are testing the use of CCP among Covid-19 patients who, although infected, were not hospitalized. In the other study, researchers at Vanderbilt University are testing high-potency plasma among hospitalized Covid-19 patients.

    "[A]ntibodies work against the virus," said David Sullivan, a professor of molecular microbiology and immunology at Johns Hopkins and principal investigator in the plasma trials. But it’s all about "dose and time," he explained, noting that giving high-potency convalescent plasma within the first few days of infection is critical.

    Separately, Michael Knudson, co-medical director of the DeGowin Blood Center at the University of Iowa Carver College of Medicine, said convalescent plasma's most promising use may come from so-called "super donors," people who've been infected with Covid-19 and were later vaccinated. Knudson said his research indicates that plasma from these super donors can provide between 5 and 20 times more neutralizing antibodies than plasma from people who haven't yet been vaccinated—a distinction that makes it an "almost…completely different product compared to what is used to date."

    Joyner and other experts agree that this "boosted" plasma could be helpful in early infection, much like how monoclonal antibodies—lab-made proteins designed to act like human antibodies in the immune system—are used. But unlike monoclonal antibodies, which at more than $1,200 per dose can be unaffordable in developing nations, this boosted plasma could be an affordable option.

    And more broadly, Claudia Cohn, CMO at AABB, an international nonprofit focused on transfusion medicine and cellular therapies, said, "I think that it would be a mistake to stop now. We have some evidence that it works and evidence that we can produce high-titer plasma. Let's see what we can do to keep people out of the hospital" (Aleccia, NBC News/Kaiser Health News, 3/21).

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