RESUMEN
BackgroundWith no vaccine or treatment for SARS-CoV-2 and its associated disease, COVID-19, convalescent plasma from recovered COVID-19 (CCP) patients offered a potential therapy. In March of 2020, the United States (US) Food and Drug Administration (FDA) authorized CCP under emergency Investigational New Drug (eIND) exemption and an IRB-approved Expanded Access Program (EAP) to treat severe COVID-19. Hospital demand grew rapidly in the Southeastern US, resulting in backlogs of CCP orders. We describe a large US blood centers (BC) rapid implementation of a CCP program in response to community needs. Study Design and MethodsFrom April 2 to May 17, 2020 CCP was collected by whole blood or apheresis. Initial manual approaches to donor intake, collection and distribution were rapidly replaced with automated processes. All CCP donors and products underwent FDA-required screening and testing. Results619 CCP donors (299 females, 320 males) presented for CCP donation [161 (25.6%) whole blood, 466 (74.1%) plasmapheresis] resulting in 1219 CCP units. Production of CCP increased as processes were automated and streamlined, from a mean of 11 donors collected/day for the first month to a mean of 25 donors collected/day in the subsequent two weeks. Backlogged orders were cleared, and inventory began to accumulate 4 weeks after project initiation. ConclusionThe BC was able to implement an effective de novo CCP collection program within 6 weeks in response to a community need in a global pandemic. Documentation of the experience may inform preparedness for future pandemics.
RESUMEN
BACKGROUNDEfficacy of COVID-19 convalescent plasma (CCP) to treat COVID-19 is hypothesized to be associated with the concentration of neutralizing antibodies (nAb) to SARS-CoV-2. High capacity serologic assays detecting binding antibodies (bAb) have been developed, nAb assays are not adaptable to high-throughput testing. We sought to determine the effectiveness of using surrogate bAb signal-to-cutoff ratios (S/CO) in predicting nAb titers using a pseudovirus reporter viral particle neutralization (RVPN) assay. METHODSCCP donor serum collected by 3 US blood collectors was tested with a bAb assay (Ortho Clinical Diagnostics VITROS Anti-SARS-CoV-2 Total, CoV2T) and a nAb RVPN assay. CoV2T prediction effectiveness at S/CO thresholds was evaluated for RVPN nAb NT50 titers using receiver operating characteristic analysis. RESULTS753 CCPs were tested with median CoV2T S/CO of 71.2 and median NT50 of 527.5. Proportions of CCP donors with NT50 over various target nAb titers were 86% [≥]1:80, 76% [≥]1:160, and 62%[≥]1:320. Increasing CoV2Ts reduced the sensitivity to predict NT50 titers, while specificity to identify those below thresholds increased. As the targeted NT50 increased, the positive predictive value fell with reciprocal increase in negative predictive value. S/CO thresholds were thus less able to predict target NT50 titers. CONCLUSIONSelection of a clinically effective nAb titer will impact availability of CCP. Product release with CoV2T assay S/CO thresholds must balance the risk of releasing products below target nAb titers with the cost of false negatives. A two-step testing scheme may be optimal, with nAb testing on CoV2T samples with S/COs below thresholds.