Temporal Analysis of Serial Donations Reveals Decrease in Neutralizing Capacity and Justifies Revised Qualifying Criteria for COVID-19 Convalescent Plasma.

BACKGROUND: COVID-19 convalescent plasma (CCP) received an Emergency Use Authorization by the FDA. CCP with a signal-to-cutoff ratio of ≥12 using the Ortho VITROS SARS-CoV-2 IgG test (OVSARS2IgG) is permitted to be labeled "high titer". Little is known about the relationship between OVSARS2IgG ratio and neutralizing capacity of plasma/sera against genuine SARS-CoV-2 virus.

METHODS: 981 samples from 196 repeat CCP donors 0-119 days post initial donation (DPID) were analyzed. Neutralizing capacity was assessed for 50% (PRNT50) and 90% (PRNT90) reduction of infectious virus using the gold standard plaque reduction neutralization test (PRNT). A subset of 91 donations were evaluated by OVSARS2IgG and compared to PRNT titers for diagnostic accuracy.

RESULTS: 32.7%/79.5% (PRNT90/PRNT50) of donations met a 1:80 titer initially but only 14.0%/48.8% (PRNT90/PRNT50) met this cut-off ≥85 DPID. Correlation of OVSARS2IgG results to neutralizing capacity allowed extrapolation to CCP therapy results. CCP with OVSARS2IgG ratios equivalent to a therapeutically beneficial group had neutralizing titers of ≥1:640 (PRNT50) and/or ≥1:80 (PRNT90). Specificity and positive predictive value of the OVSARS2IgG for qualifying highly neutralizing CCP was optimal using ratios significantly greater than the FDA cut-off.

CONCLUSIONS: This information provides a basis for refining the recommended properties of CCP used to treat COVID-19.