Emergence of the BA.2.87.1 lineage of SARS-CoV-2 in South Africa, a highly diverged BA.2-related lineage.

The emergence of various SARS-CoV-2 lineages with adaptive mutations is of significant concern worldwide, especially when these mutations enhance the virus's ability to either evade immune responses or transmit more efficiently. Between September and December 2023, a highly diverged BA.2-related lineage, designated BA.2.87.1, was detected through diagnostic testing, syndromic surveillance, and wastewater surveillance in the Limpopo, Mpumalanga, Western Cape, Eastern Cape, and Gauteng provinces of South Africa. This lineage harbours 20 amino acid substitutions in Spike protein relative to baseline BA.2, including at antigenic sites of the receptor-binding domain (including N417T, K444N, V445G, L452M, N460K, K478T, N481K, and R493Q) and, most strikingly, large deletions of the N-terminal domain (NTD) residues 15-26 and 136-146. Such large NTD deletions have never been observed in circulating lineages but do sometimes occur in highly mutated sequences originating in chronic infections. Phylodynamic analysis supports the possibility that the BA.2.87.1 lineage originated in a chronic infection in that the nearest known ancestor of this lineage last circulated at least 18 months prior to its first detection. Although BA.2.87.1 had immune evasion and/or transmission potential, its detection was not associated with a surge of infections and it was displaced by the globally dominant BA.2.86 lineage, JN.1, in the last few weeks of 2023. Our findings further strengthen the case for genomic surveillance through clinical and wastewater surveillance systems. SARS-CoV-2 continues to circulate and evolve within the global population. Multiple divergent Omicron lineages such as BA.1, BA.2, BA.3, BA.4, and BA.5 that have emerged from the southern African region have had a major impact on the epidemiology of the virus worldwide. This is likely driven by the large population of immunocompromised individuals due to the high burden of HIV/AIDS and TB in the region that facilitates long-term chronic infections. This article provides insights into the emergence of the BA.2.87.1 lineage, which briefly circulated in South Africa. The lineage displayed a unique mutational profile, including major substitutions in the receptor-binding domain and N-terminal domain deletions. The study also highlights the critical role of syndromic and wastewater surveillance in monitoring the circulation and evolution of SARS-CoV-2.