Worldwide emergence of SARS-CoV-2 NB.1.8.1 sublineage with spike 420N and 478 T dual substitution

BACKGROUND: After a year of quiescence, SARS-CoV-2 activity increased rapidly in Hong Kong since June 2026. We sought to characterize the genomic profile of SARS-CoV-2 driving this COVID-19 surge in Hong Kong and to examine the global dissemination of the identified circulating lineages. METHODS: We performed SARS-CoV-2 whole-genome sequencing on archived respiratory specimens collected at Queen Mary Hospital, Hong Kong, between January 2025 and July 2026. Viral lineages were assigned via Nextclade. Global SARS-CoV-2 metadata downloaded from GISAID as of July 2026 were analyzed to track global evolutionary trends. RESULTS: Among 615 successfully sequenced strains, the XDV descendant NB.1.8.1 was the predominant lineage. Between April and July 2026, NB.1.8.1 descendants accounted for 95.6% (108/113) of sequenced strains, dominated by PQ.16.1.1 (81.5%). Spike substitutions 420N and 478 T emerged rapidly. While 478 T increased gradually throughout 2025, 420N emerged in April 2026 and reached 98.0% by June-July 2026. Strains harboring 420N-478 T dual substitution arose independently across distinct NB.1.8.1 lineages, accounting for 94.4% (102/108) of NB.1.8.1 descendants in Hong Kong during this period. Globally, the prevalence of NB.1.8.1 strains with 420N-478 T dual substitution increased from <1% before April 2026 to 50.7% by mid-July 2026, with the highest prevalence observed in Southeast Asia and Australia. CONCLUSIONS: The 2026 COVID-19 surge in Hong Kong was driven by NB.1.8.1 descendants harboring spike 420N and 478 T substitutions. The rapid worldwide expansion of these dual-substitution lineages highlights their competitive growth advantage and underscores the need for continued global genomic surveillance.