High-Titer Plasma Beneficial in Less Severe COVID

Treatment with convalescent plasma with higher COVID-19 antibody titers was associated with a lower risk of death in hospitalized patients versus those receiving lower-antibody titers, researchers found.

Patients receiving plasma with high antibody titers had a lower relative risk of death within 30 days after transfusion compared with patients in the low-titer group (relative risk [RR] 0.75, 95% CI 0.61-0.93), reported Michael Joyner, MD, of the Mayo Clinic in Rochester, Minnesota, and colleagues.

Mechanical ventilation status appeared to impact these results: patients in the high-titer group who were not mechanically ventilated prior to transfusion had a lower risk of death than patients receiving lower-titer plasma (RR 0.66, 95% CI 0.48-0.91), the authors wrote in the New England Journal of Medicine.

Interestingly, there was no difference in mortality for patients who received high- versus low-titer plasma who were already intubated (RR 1.02, 95% CI 0.78-1.32), they noted.

It’s been a rocky road for convalescent plasma for COVID-19 in the U.S., starting with its expanded access use and culminating with the FDA authorizing its use under the specter of controversy. Not only did its emergency use authorization come after a nudge from President Trump, but FDA commissioner Stephen Hahn, MD, spoke extensively about its benefits based on nonrandomized trial data.

MedPage Today Editor-in-Chief Marty Makary, MD, of Johns Hopkins University, interviewed Joyner in September about research published the previous month as a preprint on medRxiv. Data from the entire cohort were never published in a major journal, though Joyner told Makary that one major journal discussed “significant” editorial changes to the study. It is unclear whether NEJM was the journal in question; however, the journal’s publication reports results from fewer than 10% of the 35,322 patients included in the preprint analysis.

Separately, exploratory analysis of a randomized trial of older patients in Argentina published last week found a dose-dependent IgG effect, where plasma from “super donors” was associated with a reduction in severe respiratory disease and a lower number needed to treat when these patients were treated earlier in their disease course.

Here, Joyner’s group examined data from a subgroup of hospitalized patients in a U.S. registry of 680 acute care facilities, enrolled through July 4, 2020, from which data on antibody levels in those transfusions, as well as 30-day mortality data, were available.

There were 3,082 patients available — 561 in the low-titer group, 2,005 in the medium-titer group, and 515 in the high-titer group. Overall, 61% of patients were men, 37% were Hispanic, 23% were Black, and almost 70% were younger than age 70. Two-thirds of patients received transfusions prior to invasive mechanical ventilation.

About 27% of all patients receiving convalescent plasma died within 30 days after infusion: about 30% in the low-titer group, 27% in the medium-titer group, and 22% in the high-titer group.

An exploratory analysis found that timing also played a role, with lower unadjusted mortality within 30 days after transfusion for patients receiving the transfusion within 3 days of diagnosis (point estimate 22.2%, 95% CI 19.9-24.8%) compared with those who were treated 4 or more days afterwards (point estimate 29.5%, 95% CI 27.6-31.6%).

“These data were consistent with a mortality benefit associated with high-titer plasma administered earlier in the course of disease,” the authors wrote, noting that their findings paralleled a trial involving remdesivir in which patients not receiving advanced respiratory support benefited, and those who required this support did not.

They also noted that their findings were “an important component” of the FDA’s decision to issue an emergency use authorization for convalescent plasma, and that other countries have since approved or conditionally approved its use since then.