Zesuliwe Jule, Cornelius Romer, Taskeen Hossen et al.
medRxiv, vol. , , 2025
10.1101/2025.10.28.25338622
Abstract
The SARS-CoV-2 Omicron subvariant BA.3.2 descends from BA.3. It emerged 2 years after BA.3 ceased to circulate and differs by 39 spike mutations from BA.3. Similar to BA.2.86, which circulated at low levels before giving rise to JN.1, BA.3.2 shows a low but persistent circulation globally. Here, we characterize the phylogenetic origin, infection in cell culture, and neutralization of BA.3.2 using live virus and blood plasma samples collected in South Africa at different stages of the Covid-19 pandemic. Like the Omicron BA.2.86 subvariant, we find that BA.3.2 likely emerged in Southern Africa. We also find that in almost all BA.3.2 sequences to date, an 870 base pair deletion removes ORF7 and ORF8. In cell culture, BA.3.2 has lower cytotoxicity measured as plaque area compared to ancestral SARS-CoV-2, the Delta variant, and Omicron BA.1, but similar to the co-circulating LP.8.1 Omicron subvariant with whom it also shares similar replication in H1299-ACE2 cells. BA.3.2 and LP.8.1 exhibit complete escape from neutralization from pre-Omicron collected plasma samples, have low levels of neutralization by plasma collected in 2024, and higher neutralization by plasma collected in 2025, with BA.3.2 having moderately higher escape relative to LP.8.1. The emergence of long branch subvariants like BA.3.2 without intermediates likely indicates that unmonitored persistent infections continue to drive large evolutionary shifts in this virus.