A high-throughput liquid bead array assay confirms strong correlation between SARS-CoV-2 antibody level and COVID-19 severity

Abstract

A detailed understanding of the adaptive host response to SARS-CoV-2 infection in humans is urgently needed. We developed a sensitive, high-throughput, and efficient assay using liquid bead array technology. We observed advantages over traditional ELISA for the detection and quantification of binding IgG against the receptor binding domain (RBD) of SARS-CoV-2. To determine whether COVID-19 symptom severity correlates with SARS-CoV-2 IgG, we measured anti-RBD IgG levels from 67 subjects recovered from PCR-confirmed COVID-19. We found that COVID-19 symptom severity strongly correlated with RBD IgG level (p < 0.001). These findings have substantial implications for public policy surrounding assessments of antibody responses and possible immunity, as not all cases of COVID-19 can be assumed to generate a protective antibody response, and mild disease in particular is capable of generating very low-level anti-RBD IgG levels. These findings also have important implications for the selection of donors for convalescent plasma to be used therapeutically.

Keywords: Biological Sciences; Microbiology; Viral Microbiology; Virology.

Graphical abstract

Figure 1

Liquid bead array assay performs favorably in comparison with standard indirect ELISA Standard curves were generated by 4-fold serial dilutions of a cross-reactive SARS-CoV-1 monoclonal antibody known to bind SARS-CoV-2 RBD. Both the bead array and standard ELISA generate valid binding curves, although the bead array exhibits higher accuracy (defined as percent recovery against known antibody concentrations) and greater sensitivity with a lower limit of detection.

Figure 2

SARS-CoV-2 receptor binding domain IgG levels are strongly correlated with COVID-19 symptom severity Partial effect plot of log antibody measurement (EU/mL, calculated via liquid bead array normalized to a monoclonal standard) of binding IgG against SARS-CoV-2 RBD in samples obtained ~6 weeks post-COVID-19. Increasing symptom severity is strongly associated with increased anti-SARS-CoV-2 RBD IgG (p < 0.001, see Table 1). Measurements were performed in duplicate, with a triplicate value obtained if the duplicate values differed by >15%, and the repeated measures were accounted for in the model by compound symmetric correlation. Gray region indicates point wise 95% confidence interval limits. Red points indicate IgG values from subjects hospitalized for COVID-19.