A randomized clinical trial in Belgium finds that convalescent plasma reduces death rates by about 10% in COVID-19 patients requiring invasive mechanical ventilation.
University of Liege researchers led the open-label study involving 17 intensive care units (ICUs) in Belgium from October 2020 to March 2022, largely pre-Omicron strain. The results were published today in the New England Journal of Medicine.
A total of 475 COVID-19 patients with acute respiratory distress syndrome (ARDS) were enrolled in the study, with 237 receiving convalescent plasma within 5 days after initiation of mechanical ventilation and 238 receiving standard care.
Owing to a shortage of convalescent plasma, ICUs had access to plasma with high levels of SARS-CoV-2 antibodies (1:320) for 82.3% of patients, and the remaining 17% received plasma with a concentration of 1:160. Nearly all patients (98.1%) received glucocorticoids.
SARS-CoV-2 antibody-rich convalescent plasma is taken from donors recovering from COVID-19 infection and given to currently ill patients as a means of passive immunization.
Early treatment appears superior
At study enrollment, 9.9% of patients had mild ARDS, 57.7% had moderate ARDS, and 32.4% had severe ARDS. In total, 72.0% underwent randomization within 48 hours after mechanical ventilation was initiated, and 28.0% did so after more than 48 hours. Overall, 197, 163, 99, and 16 patients were infected during waves dominated by the wild-type virus and the Alpha, Delta, and Omicron variants, respectively.
Death rates at 28 days were 10% lower in convalescent-plasma recipients than in standard-care recipients. Overall, 35.4% of patients who received convalescent plasma died, compared with 45.0% of standard-care patients. The effect was especially pronounced in those given convalescent plasma within the first 48 hours of mechanical ventilation (32.7% vs 46.8%).
For the first time, we have demonstrated the therapeutic value of convalescent plasma in improving the very poor vital prognosis of these patients.
The median time between SARS-CoV-2 infection and development of ARDS was 12 days. Antibody concentrations in the convalescent plasma were not associated with death. Rates of serious adverse events were similar in both groups.
Mechanism of convalescent plasma unclear
The study authors called the study the first to examine the use of convalescent plasma in patients requiring mechanical ventilation. "For the first time, we have demonstrated the therapeutic value of convalescent plasma in improving the very poor vital prognosis of these patients," lead author Benoit Misset, MD, of the University of Liege in Belgium, said in a university press release.
The researchers said that the mechanism of convalescent plasma in COVID-19 patients is unclear but that it may reduce the volume of live virus in the lungs of patients shedding the virus.
"It may counteract the delayed kinetics of neutralizing antibody production in these patients, a phenomenon that was observed in a placebo-controlled trial," they wrote. "A decrease in viral load might reduce inflammation, as we observed in our convalescent-plasma group."
They called for future research in ARDS patients infected with different SARS-CoV-2 variants than those studied. "Confirmation could be accomplished by continuing collection campaigns and delivering the most recently collected plasma available," they wrote.
