Use of a Novel Liquid Bead-Array Assay to Determine Correlation between SARS-CoV-2 Binding Antibody Level and COVID-19 Disease Severity

Abstract

A detailed understanding of the adaptive host response to SARS-CoV-2 infection in humans is urgently needed, as questions abound regarding serologic responses and the development of antibody-mediated immunity against COVID-19. We developed a highly sensitive, high-throughput, and efficient assay using liquid bead array technology. We observed advantages over traditional indirect ELISA for the detection and quantification of binding IgG against the receptor binding domain (RBD) of SARS-CoV-2. Using this sensitive and highly reproducible assay, we sought to determine whether the severity of COVID-19 symptoms is correlated with SARS-CoV-2 binding IgG level. We measured SARS-CoV-2 RBD IgG levels from 67 subjects who had recovered from PCR-confirmed, symptomatic COVID-19. Samples were obtained approximately 6 weeks post-symptom onset. We found that COVID-19 symptom severity, assessed on an 8-point severity scale, strongly correlated with RBD IgG level (p<0.001), with and without adjustment for covariates of age, sex, and time from symptom onset. 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 as a therapeutic, and other scenarios where antibody level, rather than mere presence or absence, is relevant.