Hospitalized COVID-19 patients treated with high-titer convalescent plasma showed no survival benefits or clinical improvements compared to patients only receiving usual care, according to data from the U.K.'s RECOVERY trial.

Both groups had a mortality rate of 24% at 28 days (RR 1.00 95% CI 0.93-1.07, P=0.95), reported Peter Horby, PhD, of the University of Oxford in England, and colleagues.

There was also no difference between groups in hospital stay duration or chance of disease progression, the authors wrote in The Lancet.

"This study is significant since the Recovery Collaborative Group organized the largest randomized trial in reporting COVID-19 convalescent therapy mortality results," Horby and colleagues wrote.

Convalescent plasma has been used as a "passive immunotherapy" in treating influenza pneumonia and for SARS-CoV-1, the authors explained. Previous studies examining convalescent plasma's ability to reduce mortality in severe COVID-19 and other respiratory infections (influenza and Ebola) have been of poor quality, or reached limited or inconclusive results.

In February, the FDA limited the use of high-titer convalescent plasma, used under emergency use authorization, to patients early in their disease course and for those with impaired humoral immunity.

"The often unpredictable disease course of COVID-19 creates a substantial challenge for clinical researchers when identifying ideal patient populations who might benefit from investigational interventions," wrote Sean Liu, MD, PhD, and Judith Aberg, MD, both of the Icahn School of Medicine in Mount Sinai in New York City, in an accompanying editorial. "Special populations, such as patients with impaired humoral immunity, who were not actively considered in this study, might still benefit from convalescent plasma when admitted."

The U.K.'s Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial is coordinated by the University of Oxford in the Nuffield Department of Population Health, at 177 U.K. hospitals. From May 28, 2020, to Jan 15, 2021, 11,558 (71%) of the trial's 16,287 patients were eligible to receive convalescent plasma and were randomly placed in a "usual care" group or a "usual care plus high-titer convalescent plasma" group.

The primary outcome was 28-day mortality, as analyzed on an intention-to-treat basis. Secondary outcomes were hospital discharge time and among patients not on ventilators, a composite endpoint of progression to invasive mechanical ventilation or death.

Mean patient age was about 64, roughly two-thirds were men, and 77% to 78% were white. Median time to symptom onset was 9 days.

At randomization, 5% of patients required invasive mechanical ventilation, 87% received oxygen-only therapy, and 8% of patients received no oxygen therapy. Corticosteroids were taken by 92% of patients at randomization.

There was no difference in 28-day mortality in any subgroup, including age, sex, ethnicity, duration of symptoms before randomization, level of respiratory support, or use of corticosteroids.

Convalescent plasma therapy didn't affect the number of patients discharged within 28 days; both groups showed a 66% discharge rate (RR 0.99, 95% CI 0.94-1.03, P=0.57). Regardless of not being randomly placed on a ventilator, 29% of patients in each group still experienced disease progression resulting in ventilator intervention/death (RR 0.99, 95% CI 0.93-1.05, P=0.79).

In the convalescent plasma group, the median time to discharge was 12 days and for the usual care group, 11 days.

The authors mentioned limitations, including that "disease stage could impact the benefits of convalescent plasma." This study only assessed admitted hospital patients with a long median time (9 days) from symptom onset to randomization, and patient ethnic diversity was underrepresented.

Researchers highlighted the need for additional trials to study convalescent plasma therapy for COVID-19 in other patient groups.

"Future ambulatory trials with convalescent plasma might need to be matched against monoclonal antibody therapies or hyperimmune immunoglobulin, eligibility criteria must include tightly defining the population most likely to benefit," wrote editorialists Liu and Aberg.