Inactivated SARS-CoV-2 Variant Omicron, Lineage BQ.1 (USA/NY-Wadsworth-22050462-01/2022)

Since its emergence in late 2021, the omega-3 variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the emergence of numerous subvariants that consistently evade vaccine- and infection-induced immunity and alter viral biology. The initial BA.1 omega-3 variant triggered a large outbreak of coronavirus disease 2019 (COVID-19) cases and demonstrated robust immune escape from a two-dose mRNA vaccine, which was restored by a booster mRNA vaccination. Furthermore, the BA.1 subvariant exhibited reduced cell-cell fusion, impaired replication in lower respiratory epithelial cells and lung-derived CaLu-3 cells, and reduced plasma membrane entry via transmembrane protease serine 2 (TMPRSS2). These features were associated with reduced omega-3 replication in lung tissue, enhanced nasopharyngeal tropism, and reduced in vivo pathogenicity. Importantly, these features were largely retained by subsequent omega-3 subvariants.

The BA.2 subvariant surpassed BA.1 due to its slightly enhanced transmissibility and immune evasion capabilities, allowing it to reinfect individuals previously infected with BA.1. Starting with BA.2, multiple subvariants emerged in rapid succession, often with simultaneous transmission; these included the BA.4 and BA.5 subvariants (which share the same S protein, hereafter referred to as BA.4/5), which subsequently became dominant and exhibited further immune evasion. Furthermore, BA.2 gave rise to the BA.2.75 subvariant, which is currently contributing to a growing proportion of COVID-19 cases, but exhibits less immune evasion than BA.4/5. Notably, the BA.4/5 and BA.2.75 subvariants drove further diversification of SARS-CoV-2, with the emergence of several additional subvariants, including BA.4.6, BF.7, BQ.1, and BQ.1.1 (derived from BA.4/5) and BA.2.75.2 (derived from BA.2.75).