Determining the Optimal Level of Neutralizing Antibodies Key for COVID-19 Plasma Therapy

Closeup of male lab technician holding a vial with a blood sample of a patient infected with coronavirus. Staged shot, safely executed.
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While sera with high severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody levels showed maximal activity, not all high titer sera contained neutralizing antibody titers recommended by the US Food and Drug Administration (FDA), highlighting the need to characterize neutralizing activity before using convalescent plasma for coronavirus disease 2019 (COVID-19), according to study results published in the Journal of Infectious Diseases.

This serologic study used data from 2 COVID-19 plasma donor screening programs in New York to identify sera that met the FDA recommended or minimal titers for convalescent plasma (160 and 80, respectively) using plaque reduction neutralization tests (PRNT) at 50% (PRNT50) and 90% (PRNT90) neutralization levels.

An analysis of 159 sera between enzyme-linked immunosorbent assay (ELISA) and PRNT titers showed a significant, positive correlation between ELISA titers neutralizing activity at the PRNT50 level (Spearman r = 0.4315; P <.001) and at the PRNT90 level (Spearman r = 0.4057; P <.001). Data showed that while 84.1% of sera with an ELISA titer of 2880 was predictive of neutralizing activity at 160 with PRNT50, only 50% of these high ELISA titers reached the 160 titer recommendation at the PRNT90 level.

When researchers examined approximately 300 sera to determine neutralization titers over different time periods, they found that neutralization peak was between days 31 to 35 after symptom onset. Approximately 93% of sera had at least 160 PRNT50 titers, and only about 54% of sera had at least 160 PRNT90 titers. The number of sera that had high PRNT90 titers decreased significantly after 35 days.

“Better definition of the optimal time period between symptom onset and serum collection and baseline PRNT titers will improve the quality of sera and render convalescent plasma therapy a more effective tool in the COVID-19 treatment arsenal,” the researchers concluded.


Lee WT, Girardin RC, Dupuis II AP, et al. Neutralizing antibody responses in COVID-19 convalescent sera. J Infect Dis. Published online October 26, 2020. doi: 10.1093/infdis/jiaa673