COVID-19 Serology Data Provide Guidance for Future Deployments of Convalescent Plasma

Abstract

Measurement of antibody content and function after a viral illness is important for diagnosis and selection of the best convalescent plasma (CP) units for passive immunization. Zhang et al. (mBio 14:e03523-22, 2013, https://doi.org/10.1128/mbio.03523-22) analyzed over 19,000 coronavirus disease 2019 (COVID-19) CP (CCP) samples from the early days of the COVID-19 pandemic and reported a moderately strong correlation between antibody amount and neutralizing titer. Strikingly, about one-third of the samples had little or no neutralizing activity. The results provide a detailed glimpse of the humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in immunologically naive humans and reveal major differences in the quality of CP units collected for passive therapy before antibody screening. Heterogeneity in CCP quality undoubtedly contributed to the variable therapeutic efficacy. Analysis of the COVID-19 serology data suggest that, for the next infectious disease emergency, the best approach after quick establishment of methods for robust antibody-level stratification would be to use CP units in the top quintile of antibody content and neutralizing capacity.

Keywords: COVID-19; SARS-CoV-2; convalescent plasma.

FIG 1

Scheme for using CP in a future infectious disease emergency. (A) Deployment of CP in the absence of assays to measure the antibody concentration and neutralizing activity. In the absence of assays, CP can be deployed based on clinical history of having survived the disease, as was performed early in the COVID-19 pandemic in the United States. In that situation, samples of transfused CP should be saved for later analysis to correlate antibody amounts with clinical efficacies. Transfusing 2 units increases the likelihood of administering 1 unit with high antibody content. The alternative of pooling units is not feasible without regulatory changes and brings possible complications with regard to blood group matching. (B) Deployment of CP when assays to measure the antibody concentration and neutralizing activity are available. In this situation, it should be possible to measure the antibody contents of several hundred units to establish the range of antibody concentrations and then pick the top quintile for clinical use. In both types of situations, registries can be used to obtain evidence for safety and efficacy.