Months before the US Food and Drug Administration authorized the emergency use of convalescent plasma for patients with coronavirus disease 2019 (COVID-19) last summer, the Mayo Clinic in Rochester, Minnesota, had been running an expanded access program to make it available to patients outside of clinical trials.

Naturally, doctors had a lot of questions about who should receive the antibody-rich therapy: What about COVID-19 patients who also had lymphoma or leukemia? So, many of these physicians called administrators of the national registry — one that eventually included more than 100,000 patients at 2731 sites — to ask for more information.

The steady flow of inquiries gave Mayo Clinic anesthesiology research fellow Jack Senefeld, PhD, the idea to comb the literature to learn of previous cases. He did this research “rather than tell people that we don’t know; [that] we more or less Googled it,” he said. “It was information that was widely available. We just collected it and made a one-stop shop for clinicians.”

The result of Senefeld’s work is a preprint that was published last month, which concluded that the use of therapeutic plasma for immunodeficient patients with COVID-19 was indeed beneficial.1 “It appears it’s safe and also appears to lower mortality,” said Senefeld. “The most surprising thing was the number of patients who rapidly improved after receiving this treatment.” (Because it is a preprint, it’s important to note that the work was not peer-reviewed, and, according to a caveat accompanying all medRxiv papers, the results “should not be used to guide clinical practice.”)

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Of particular interest were patients with hematological malignancies. Senefeld’s team identified 54 such patients in 18 peer-reviewed reports. In the largest cohort — 17 patients with B-cell depletion with secondary immunodeficiency due to treatment with therapies for lymphoma or leukemia who experienced severe COVID-19 symptoms — they found the majority “demonstrated improved clinical status and viral clearance” within 48 hours of receiving a convalescent plasma transfusion. Another cohort of 14 patients who received the treatment reported improvements in symptoms such as shortness of breath, fever and coughing, and a reduction in the need for oxygen.

“A lot of these studies included [fewer] than 10 patients, so it can be difficult to glean a bigger insight from just a few patients,” said Senefeld. “This collection of case reports provided more robust evidence that plasma represents a way to tip the scales against cancer and COVID-19.”

The review comes at a time when other research shows inconclusive results on the value of administering convalescent plasma to COVID-19 patients. For example, an Argentinian study of hospitalized adult patients with severe COVID-19 pneumonia randomly assigned 228 patients to receive convalescent plasma and 105 to receive placebo. The research that was published in late November 2020 in The New England Journal of Medicine found no significant differences in clinical status or overall mortality between the 2 groups. 2