ABSTRACT
Background/Case Studies: Convalescent plasma mediates passive immunity through the transfer of protective antibodies. It is an inexpensive and readily accessible therapy whose efficacy is unknown in the current COVID-19 pandemic. COVID-19 convalescent plasma (CCP) with high neutralizing antibody titers may have a greater likelihood of efficacy than low titer CCP. Study Design/Methods: The Passive Immunity Trial for Our Nation (PassITON) is a multicenter, blinded, placebo-controlled, randomized clinical trial. The studyâ ™s purpose is to evaluate efficacy of convalescent plasma containing neutralizing antibodies to COVID-19 in moderate-to-severe hospitalized adults with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV- 2). Unlike other published CCP studies, this study quantified SARS-CoV-2 antibody titers and screened CCP units for neutralizing SARS-CoV-2 antibodies with binding assays. Serum samples obtained from CCP donors were first screened by the Abbott TM ARCHITECT TM IgG qualitative platform for the presence of detectable antibody against SARS-CoV-2. Positive samples in the Abbott assay were quantified for IgG binding against the RBD of SARS-CoV-2 using a liquid bead-array (RBD Luminex). Units with a mean fluorescence intensity (MFI) of 8000 U/mL or greater were then assessed for neutralization using a VSV-SARS-CoV-2 chimeric virus neutralization assay. Units were deemed eligible for transfusion if they met a threshold of neutralization (50% neutralization titer (NT50) > 1:50). Both cutoffs were determined by screening a subset of samples for neutralization using a traditional live-virus plaque-reduction neutralization titer (PRNT) assay. Results/Findings: A total of 429 donors donated over 1200 CCP units for screening between April 22, 2020 and January 29, 2021. Initial studies of approximately 60 donors samples were used to create a cut off for the RBD binding assay;the vast majority of samples with RBD < 8000 IU/mL did not demonstrate neutralization activity of NT50>50. Ten samples were used to demonstrate a tight linear relationship between the NT50 and PRNT50. Using these cut-offs approximately 25% of the plasma donations in this program met or exceeded the minimum thresholds during antibody screening and were selected for use in the trial. Twenty-seven institutions participated in the study, representing all census regions in the United States (Figure 1). Presently, 837 patients have been randomized for the study. Conclusions: While the efficacy of CCP is unknown given the variable results that have been published to date, the PASSITON study design optimizes the efficient procurement of CCP with high levels of neutralizing antibodies.