Reduced sensitivity of commercial Spike-specific antibody assays after primary infection with the SARS-CoV-2 Omicron variant

Abstract

The SARS-CoV-2 Omicron variant is characterized by substantial changes in the antigenic structure of the Spike (S) protein. Therefore, we analyzed whether these changes impact the sensitivity of commercial anti-SARS-CoV-2 antibody assays. Sera from 37 convalescent individuals after primary Omicron infection were tested with 20 commercial anti-SARS-CoV-2 immunoassays. As controls, we used samples from 43 individuals after primary infection with an ancestral wildtype strain. Notably, in Omicron convalescents, there was a statistically significant reduction in the sensitivity of all antibody assays containing S or its receptor-binding-domain (RBD) as antigens. Furthermore, antibody levels quantified by these assays displayed a weaker correlation with Omicron-specific neutralizing antibody titers than with those against the wildtype. In contrast, the sensitivity of nucleocapsid-protein-specific immunoassays was similar in wildtype and Omicron-infected subjects. In summary, the antigenic changes in the Omicron S lead to reduced detection rates in commercial S- and RBD-specific antibody assays, impairing their diagnostic performance.