Rapid and Quantitative Detection of Human Antibodies against the 2019 Novel Coronavirus SARS CoV2 and Its Variants as a Result of Vaccination and Infection.

Measuring the antibody response to 2019 SARS CoV2 is critical for diagnostic purposes, for monitoring the prevalence of infection, and for gauging the efficacy of the worldwide vaccination effort for COVID-19. In this study, a microchip-based grating-coupled fluorescent plasmonic (GC-FP) assay was used to measure antibody levels that resulted from COVID-19 infection and vaccination. In addition, we measured the relative antibody binding toward antigens from the CoV2 virus variants strains B.1.1.7 (Alpha) and B.1.351 (Beta). Antibody levels against multiple antigens within the SARS CoV2 spike protein were significantly elevated for both vaccinated and infected individuals, while those against the nucleocapsid (N) protein were only elevated for infected individuals. GC-FP was effective for monitoring the IgG-based serological response to vaccination throughout the vaccination sequence and also resolved acute (within hours) increases in antibody levels. A significant decrease in antibody binding to antigens from the B.1.351 variant, but not B.1.1.7, was observed for all vaccinated subjects when measured by GC-FP compared to the 2019 SARS CoV2 antigens. These results were corroborated by competitive enzyme-linked immunosorbent assay (ELISA). Collectively, the findings suggest that GC-FP is a viable, rapid, and accurate method for measuring both overall antibody levels to SARS CoV2 and relative antibody binding to viral variants during infection or vaccination. IMPORTANCE In this work, a novel biosensor technology was used to measure antibody levels that resulted from vaccination against COVID-19 and/or from infection with the virus. Importantly, this approach enables quantification of antibody levels, which can provide information about the timing and level of immune response. Due the multiplexed nature of this approach, antibody binding to both the original 2019 SARS CoV-2 strain and variant strains can be performed simultaneously and in a short (30-min) time frame.

Serological analysis reveals an imbalanced IgG subclass composition associated with COVID-19 disease severity.

Coronavirus disease 2019 (COVID-19) is associated with a wide spectrum of disease presentation, ranging from asymptomatic infection to acute respiratory distress syndrome (ARDS). Paradoxically, a direct relationship has been suggested between COVID-19 disease severity and the levels of circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies, including virus-neutralizing titers. A serological analysis of 536 convalescent healthcare workers reveals that SARS-CoV-2-specific and virus-neutralizing antibody levels are elevated in individuals that experience severe disease. The severity-associated increase in SARS-CoV-2-specific antibody is dominated by immunoglobulin G (IgG), with an IgG subclass ratio skewed toward elevated receptor binding domain (RBD)- and S1-specific IgG3. In addition, individuals that experience severe disease show elevated SARS-CoV-2-specific antibody binding to the inflammatory receptor FcÉ£RIIIa. Based on these correlational studies, we propose that spike-specific IgG subclass utilization may contribute to COVID-19 disease severity through potent Fc-mediated effector functions. These results may have significant implications for SARS-CoV-2 vaccine design and convalescent plasma therapy.