Temporal Analysis of COVID-19 Convalescent Plasma Donations Reveals Significant Decrease in Neutralizing Capacity Over Time (preprint)

ABSTRACT

COVID-19 convalescent plasma (CCP) received approval for use under an Emergency Use Authorization by the FDA for treatment of seriously ill patients. Use of CCP units with a signal-to-cutoff ratio of [≥]12 using the Ortho VITROS SARS-CoV-2 IgG test (OVSARS2IgG) is authorized. Little is known about the relationship between this ratio and the neutralizing capacity of plasma/sera against genuine SARS-CoV-2 virus. We measured the neutralizing capacity of 981 samples from 196 CCP donors 7-119 days post initial donation (DPID). Neutralizing capacity was assessed for 50% (PRNT50) and 90% (PRNT90) reduction of infectious virus using the gold standard plaque reduction neutralization test (PRNT). Importantly, while 32.7%/79.5% (PRNT90/PRNT50) of donations met the FDA minimum titer of 180 initially, only 14.0%/48.8% (PRNT90/PRNT50) met this cut-off [≥]85 DPID. A subset of 91 donations were evaluated using the OVSARS2IgG and compared to PRNT titers for diagnostic accuracy. The correlation of OVSARS2IgG results to neutralizing capacity allowed extrapolation to CCP therapy efficacy results. CCP with OVSARS2IgG ratios in the therapeutically beneficial group had neutralizing titers of [≥]1640 (PRNT50) and/or [≥]180 (PRNT90). This information provides a new basis for refining the recommended properties of CCP that is used to treat severe COVID-19.