Developments in Antibody Tests for Convalescent Plasma

Convalescent plasma therapy recently received EUA from the FDA for the treatment of hospitalized COVID-19 patients. Although the efficacy of this treatment is still not well understood and clinical trials are ongoing (read more about the current standing of this therapy on our blog’s clinical trials page), identifying possible plasma donors who may have sufficient antibody levels is an important aspect of this therapy. 

The FDA threshold value of virus-neutralizing (VN) antibody titer for plasma donations is 1:160, meaning that a 1:160 dilution of a given unit of plasma has activity against the virus. However, this level is currently not typically known in most donor plasma because the neutralization assays necessary are labor intensive, time consuming, and require a biosafety level 3 lab (Salazar et al, 2020). Most donated plasma samples are rather tested using IgG antibody tests and given a high or low antibody titer designation based on signal-to-cutoff values. 

A study recently published in the Journal of Clinical Investigation tested the hypothesis that IgG antibodies that target the ectodomain (ECD) and receptor binding domain (RBD) of the spike protein are strongly correlated with overall neutralizing antibody level, and thus could be used as a surrogate marker to identify plasma donors with titers above the FDA threshold of 1:160 (Salazar et al, 2020). The study utilized an ELISA assay to compare anti-ECD and anti-RBD IgG titers to virus-neutralizing (VN) titers in samples from 68 patients. The authors  found that greater than 80% of donors who had a VN titer above the FDA threshold also had serum anti-RBD and anti-ECD titers 1:1350 or higher, thus highlighting the strong correlation between VN titers and ELISA IgG titers. This finding suggests that ELISA tests, which are much more accessible and easy-to-use, could be used as a quantitative tool to confirm sufficient antibody levels in plasma samples for possible use in patient transfusion. 

The researchers in the study also sought to understand the donor characteristics that may be associated with higher antibody levels. They categorized each assay’s titer with patient characteristics of dyspnea, hospitalization, and severity and found that these were all positively and significantly correlated with higher antibody levels. Overall, dyspnea was the best symptom to discriminate the presence of an adequate IgG antibody titer, and duration of symptoms was found to not be associated with titer. 

Although more research is needed to understand the efficacy of convalescent plasma therapy for COVID-19 patients, the results from this study correlating the titer levels from spike protein anti-ECD and anti-RBD IgG with virus neutralizing antibodies utilizing an ELISA assay is a positive step-forward to understand how to easily identify individuals with neutralizing antibodies against SARS-CoV-2.