Beginning early on in the coronavirus pandemic, some researchers looked to experiences of past outbreaks for lessons, proposing that some patients might be saved by a decidedly old-fashioned remedy: plasma taken from people who’d recovered from the disease in infused into patients. The idea is that such plasma contains antibodies against SARS-CoV-2 that can give patients’ immune systems a boost in fighting the disease. The approach caught on. Presently, about 1,500 patients a day are receiving this treatment in the US, Buzzfeed reports—but convalescent plasma’s very popularity is making it difficult to get solid answers on whether the remedy really works, and for whom.
“Without a randomized control trial, it’s very difficult to be certain that what you have is meaningful,” epidemiologist W. Ian Lipkin of Columbia University tells The New York Times. Lipkin had been conducting such a trial, in which patients are randomly assigned to receive either plasma or a placebo, but the outbreak in New York died down before the trial had enrolled enough participants. Lipkin says he looked for partners in other areas of the US to help continue the study, but had a hard time finding them because patients and their doctors are reluctant to participate knowing they might receive the placebo.
Since early April, many patients have been receiving plasma outside of clinical trials through a Food and Drug Administration (FDA)–sanctioned program run by the Mayo Clinic. That initiative had published a preprint last month indicating that the plasma treatment is safe, and this week it put out further results on 35,322 treated patients indicating that those who received infusions with a greater concentration of antibodies, and those who received the treatment earlier in their illness, were more likely to survive than patients who received less–antibody-rich plasma or received it later.
But the Mayo study does not include a control group, and randomized controlled trials that have been completed on convalescent plasma for COVID-19 have been much smaller. In one study published in JAMA in June, researchers based in China reported that they did not find a statistically significant difference in recovery within 28 days for patients who received the treatment, but they had only managed to enroll 103 patients in the trial and they wrote in their report that it “may have been underpowered to detect a clinically important difference.”
Trials in the US have similarly stalled due to an inability to recruit enough patients, the Times reports, and meanwhile, its sources say that the FDA is preparing an emergency use authorization for convalescent plasma that could further expand its use.
The Mayo Clinic’s new study “raises the question of what strength of evidence is necessary to treat during a pandemic,” says Harlan Krumholz, director of the Center for Outcomes Research and Evaluation at Yale New Haven Hospital, in comments to STAT. “The problem is we have yet to resolve what is sufficient evidence to change the treatment paradigm.”
Even if convalescent plasma has benefit, it “was never intended to be the final treatment for a disease,” infectious disease expert Nicole Bouvier of the Icahn School of Medicine at Mount Sinai who is involved with the Mayo study tells BuzzFeed. “It gives us more time to work on making other therapeutics.”