Global Emergence and Spread of the XFG SARS-CoV-2 Variant and Its Clinical Profile Among XFG Patients in Maharashtra, India

BACKGROUND: In early 2025, changing dominance among Omicron-derived lineages culminated in the emergence of the recombinant XFG variant. XFG exhibited a significant growth advantage, rapidly emerging as the predominant SARS-CoV-2 variant in India and globally, prompting its designation as a Variant Under Monitoring by the World Health Organization in June 2025. This study examines the spread of the XFG variant and describes its clinical characteristics in Maharashtra, India. METHODOLOGY: The dataset included 204,603 SARS-CoV-2 genomes from the Global Initiative on Sharing All Influenza Data (GISAID) and 1,089 XFG sequences from India (obtained from the Indian Biological Data Centre (IBDC)), collected between November 1, 2024, and October 31, 2025, to assess the temporal and geographic distribution of XFG in the context of global SARS-CoV-2 circulation. Telephonic interviews were conducted to obtain clinical information for the XFG cases in Maharashtra. All data were recorded and analyzed using Microsoft® Excel (Microsoft Corporation, Redmond, Washington, United States). RESULTS: Among 204,603 global SARS-CoV-2 genomes analyzed, XEC (20.4%) and XFG (18.8%) were the most prevalent lineages, with XFG emerging as a major global driver during mid-to-late 2025. XFG became dominant in North America, Europe, South America, and Africa, accounting for 66-83% of late-phase sequences, while remaining less prevalent in Asia and Oceania (