ObjectivesThe SARS-CoV-2 Omicron variant is characterized by substantial changes in the antigenic structure of the Spike (S) protein. Therefore, antibodies induced by primary Omicron infection lack neutralizing activity against earlier variants. In this study, we analyzed whether these antigenic changes impact the sensitivity of commercial anti-SARS-CoV-2 antibody assays. MethodsSera from 37 unvaccinated, convalescent individuals after primary Omicron infection were tested with a panel of 20 commercial anti-SARS-CoV-2 immunoassays. As controls, we used samples from 43 individuals after primary infection with the SARS-CoV-2 ancestral wildtype strain. In addition, variant-specific live-virus neutralization assays were used as a reference for the presence of SARS-CoV-2-specific antibodies in the samples. Results 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. ConclusionsIn 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.

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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.