Researchers in Belgium have published the findings from a randomized trial that explored the impact of COVID-19 convalescent plasma (CCP) in ventilated COVID-19 patients. Specifically, the study explored the impact of CCP as a treatment for COVID-19 patients on mechanical ventilation from acute respiratory distress syndrome (ARDS). The data has been reported in the New England Journal of Medicine. The authors explained that the, “randomized, two-group, open-label trial was conducted at 17 [Belgian] sites.”
The researchers also noted that, “[w]e encouraged inclusion soon after the initiation of invasive mechanical ventilation and stratified the randomization according to the delay between invasive mechanical ventilation and inclusion (≤48 hours vs. >48 to 120 hours).” To examine the potential benefits of convalescent plasma for ventilated COVID-19 patients, the authors “assigned patients in a 1:1 ratio to receive either CCP with a neutralizing antibody titer against SARS-CoV-2 of at least 1:320 or standard care.” They included adult patients, “who had a score on the Clinical Frailty Scale of less than six (range, 1 to 9, with higher scores indicating greater frailty), who had been admitted to a participating intensive care unit (ICU) with a diagnosis of COVID-19–induced ARDS, and who had received invasive mechanical ventilation for a maximum of five days were assessed for eligibility.” CCP was collected from adult donors who had been diagnosed previously with SARS-CoV-2 but had since recovered, “between 28 days and 10 months earlier.”
The authors explained that the study’s, “primary outcome was death by day 28 after randomization. Secondary outcomes included adverse events, inflammatory and anti–SARS-CoV-2 antibody responses, the Sequential Organ Failure Assessment (SOFA) score, the use of organ support, the length of hospital stay, and death by day 90 and 365.” The trial included 475 patients from September 2020 to March 2022 who had COVID-19-induced ARDS. According to the researchers, “[a] total of 237 patients were assigned to receive CCP, and 238 patients were assigned to receive standard care.”
Seeking to understand the benefits of convalescent plasma for ventilated COVID-19 patients, the trial found that, “[a]t day 28, mortality was 35.4 percent (84 of 237 patients) in the CCP group and 45.0 percent (107 of 238) in the standard-care group. (P=0.03, before and after adjustment for the stratification factor). These values were 32.7 percent (56 of 171) and 46.8 percent (80 of 171), respectively, among patients who underwent randomization 48 hours or less after ventilation initiation and 42 percent (28 of 66) and 40 percent (27 of 67), respectively, among those who underwent randomization more than 48 hours after ventilation initiation. The survival curves in the CCP and standard-care groups separated at approximately day 17, and the difference in restricted mean survival time (CCP minus standard care) at day 28 was 0.33 days (95 percent CI, −1.27 to 1.92). The neutralizing antibody titer of [infused] CCP was not associated with mortality.” The authors also noted that no adverse events were, “directly attributed to [CCP].”
The researchers concluded that convalescent plasma for ventilated COVID-19 patients could lessen the risk of mortality. “The administration of plasma collected from convalescent donors and documented to have neutralizing antibody titers of at least 1:160 to patients with COVID-19–induced ARDS within five days after the initiation of invasive mechanical ventilation significantly reduced mortality at day 28. In a prespecified analysis, this effect was mainly observed in the patient group that underwent randomization 48 hours or less after the initiation of invasive mechanical ventilation.” The authors also noted that limitations of this trial included, “it was not blinded…[CCP] was obtained between April 2020 and May 2021, when the ancestral virus and then its alpha variant were predominant in Belgium, and their neutralizing antibodies might have been less active against subsequent variants…[W]e have not standardized our in-house neutralizing antibody titers against an international standard…[D]ata were missing for a substantial number of quantitative nasopharyngeal PCR and antibody measurements.”
The U.S. Food and Drug Administration previously updated guidance regarding CCP. America’s Blood Centers and its member blood centers supported COVID-19 response efforts throughout the COVID-19 pandemic.
Citation: Misset, B., Piagnerelli, M., Hoste, E., et al. “Convalescent plasma for COVID-19–induced ARDS in mechanically ventilated patients.” 2023. NEJM.