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Infusing hospitalized Covid-19 patients with blood plasma from people who recovered from the disease had no effect on whether patients got sicker or died, according to the first completed randomized trial of the treatments.

The study, published Thursday in BMJ, could re-energize the debate over whether blood plasma is an effective treatment for the disease. An earlier analysis, run by the Mayo Clinic, showed blood plasma did yield some benefit, leading the Food and Drug Administration to grant emergency access to the therapy in August. That research, however, did not have a control arm.

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“My guess is that this will diminish enthusiasm for this,” said Susan Ellenberg, professor of biostatistics in and epidemiology at the Hospital of the University of Pennsylvania. “I don’t know whether it is enough to lead the FDA to withdraw its authorization for this, but it certainly suggests it’s not the lifesaver that people thought it would be.”

Other researchers said it was too soon to cast aside so-called convalescent plasma as a treatment option. In the study, which enrolled 464 adults at 39 hospitals in India, more than 80% of patients had already developed their own antibodies against Covid-19, suggesting they had contracted the virus a week or more before treatment. That’s likely too late to benefit from convalescent plasma, said Arturo Casadevall, an infectious disease expert at the Johns Hopkins Bloomberg School of Public Health, citing earlier studies in which patients appeared to improve after receiving infusions within a few days. 

“To me this is inconclusive,” Casadevall said. “We already know you need to give it early.”

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Michael Joyner, a Mayo Clinic anesthesiologist who led the large convalescent plasma study cited by the FDA, agreed the trial would have reached a more meaningful conclusion had it treated patients early in their course of disease. But in the study’s defense, Joyner said, researchers knew much less about how to treat Covid-19 when the trial began in April.

“I think these guys deserve incredible credit,” Joyner said. “All of the good things about clinical trials are shown in this study, but all of the limitations of clinical trials in a pandemic are shown, too.”

Joyner and Casadevall both said that the antibody levels in the plasma given to patients also needed to be higher. The researchers conducting the study did not measure the levels of neutralizing antibodies before giving plasma to patients. In analyses done after the fact, those who received higher levels of these antibodies did not seem to do better. But Joyner and Casadevall believed making sure that levels of neutralizing antibodies in the plasma are high enough beforehand might make a difference.

The median patient age in the trial was 52, and more than 75% of the trial participants were male. The researchers did not disclose racial and ethnic data on patients.

Some experts worry about the practicalities of treating patients with convalescent plasma. It’s difficult to administer and in short supply; researchers, they say, are  testing other treatments that may have a greater societal impact, such as the monoclonal antibodies being developed by Regeneron and Eli Lilly.

Luciana Borio, a former acting chief scientific officer at the FDA, is among the skeptics. “We should not be using convalescent plasma,” she said. “It has not been shown to help patients.”

But more than that, she said, she worries that the availability of a treatment that has already been authorized is making patients less willing to enroll in clinical trials that represent the path to finding a therapy that saves lives.

It’s not impossible for clinical trials to deliver conflicting results. Ellenberg, the statistician, notes that has been the case with remdesivir, another Covid-19 treatment developed by Gilead Sciences. One study, conducted by the National Institutes of Health, showed a benefit for the drug, and served as the evidence for the FDA’s decision to grant it full approval on Thursday. But another, even larger, study conducted by the World Health Organization unveiled last week found no benefit.

“Randomized trials don’t always agree with each other and it’s not always possible to find an explanation,” Ellenberg said.

Correction: A previous version of this story incorrectly referred to the Mayo Clinic analysis as a clinical trial.

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