Anti-SARS-CoV-2 serology based on ancestral RBD antigens does not correlate with the presence of neutralizing antibodies against Omicron variants

Abstract

Anti-SARS-CoV-2 serology was developed in 2020 in response to the COVID-19 pandemic to diagnose SARS-CoV-2 infection and monitor an individual’s immunity following natural infection or vaccination. Given the relationship between neutralizing antibody titers and protection against severe infection, many studies have evaluated the correlation between serology tests and neutralization assays in the pre-Omicron era. An important potential clinical use of serology, which explores binding antibodies, is estimating an individual’s level of protection against new infection, particularly in immunosuppressed individuals and those at risk of severe COVID. However, in the Omicron era, as new viruses evade the immunity induced by previous infections and vaccination, the correlation between binding antibody levels determined by serological assays developed from ancestral antigens and neutralizing antibody titers against new viruses should be re-examined in order to determine whether these assays should be optimized by adapting antigens to the circulating SARS-CoV-2 strains.