CCP May Reduce Mortality Risk in Mechanically Ventilated Patients With COVID-19-Induced ARDS

The administration of COVID-19 convalescent plasma (CCP) provided a 28-day mortality benefit for patients with COVID-19–induced acute respiratory distress syndrome (ARDS) requiring mechanical ventilation versus standard care, according to a study published in the New England Journal of Medicine. Earlier intervention provided an even greater benefit.

Mortality at 28 days was 35.4% versus 45% for patients receiving CCP compared with standard care. For patients who received CCP, 28-day mortality was 32.7% for those who underwent randomization in the first two days following the initiation of mechanical intervention compared with those who received CCP after two days on ventilation.

“Our interpretation of the benefit with respect to mortality is that [CCP] is directed against the cause of COVID-19–induced ARDS in patients receiving invasive mechanical ventilation. Convalescent plasma may reduce the quantity of virus alive in the lungs of patients who continue to shed the virus. It may counteract the delayed kinetics of neutralizing antibody production in these patients,” the researchers wrote.

For the study, conducted at 17 sites in Belgium, 237 patients were assigned to receive CCP with 171 undergoing randomization 48 hours or less after ventilation began; 238 patients received standard care with 171 undergoing randomization within 48 hours. Patients were included if they had been admitted to a participating ICU with a COVID-19–induced ARDS diagnosis, received invasive mechanical ventilation for no more than five days, and had a clinical frailty scale (CFS) score of less than 6 (range, 1 to 9, fragility increases with score).

Patients were randomized 1:1 to receive convalescent plasma with a neutralizing antibody titer against SARS-CoV-2 of at least 1:320 or standard care. A neutralizing antibody titer of1:160 was used when there was a shortage of plasma. As a result, CCP with a neutralizing antibody titer of 1:160, 1:320, 1:640, and more than 1:640 was administered to 17.7%, 38.8%, 31.9% and 11.6%, respectively. Titer did not appear to affect 28-day mortality.

Plasma came from donors who had been infected with SARS-CoV-2 and who had fully recovered between 28 days and 10 months earlier.

A total of 711 adverse events (AEs) were observed in patients who received convalescent plasma, of which 209 were considered serious; 184 were fatal. All AEs were attributed to COVID-19 or complications of organ support; none were directly attributed to CCP. Increased mean neutralizing antibody and total IgG titers to SARS-CoV-2 were seen in both groups after inclusion.

The researchers noted this trial differed from previous studies in three ways: CCP was selected for higher neutralizing antibody titers; patients had a greater severity of ARDS (mainly scores of 7-9 on the World Health Organization Clinical Progression Scale); and patients were included as early as possible after beginning mechanical ventilation to ensure a more homogeneous cohort.