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

backgroundIn 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).

resultsAmong 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 (<20%). Globally, the distribution of XFG sublineages was dominated by the parent lineage XFG (71.1%), followed by XFG.3 (12.6%), XFG.1 (5.8%), XFG.3.4.3 (5.4%), XFG.3.4 (3.3%), and XFG.2 (1.8%). In India, among the 1,089 XFG sequences, 27 sublineages were identified, predominantly XFG.3 (45.27%) and XFG.4 (41.78%), with the highest contributions from Gujarat, Maharashtra, West Bengal, and Rajasthan. Maharashtra reported its first XFG detection in early January 2025, followed by a sharp surge during May-June 2025. Clinical evaluation of 99 laboratory-confirmed XFG cases from Maharashtra showed that most patients were symptomatic (92.93%) but experienced predominantly mild illness, commonly presenting with fever, cough, cold, body ache, fatigue, and sore throat. Comorbidities were present in 31.31% of cases, most frequently diabetes mellitus and hypertension. Most patients were managed at home (68.69%), while 31.31% required hospitalization; among these, 61.29% received conservative care, and 38.71% required predominantly non-invasive oxygen support. Vaccination coverage was high (90.91%), with all unvaccinated cases occurring in children aged 0-9 years. Overall outcomes were favorable, with a recovery rate of 95.96% and low mortality (4.04%), confined to elderly patients with significant comorbidities.

conclusionThe XFG variant emerged as the dominant SARS-CoV-2 lineage globally during late 2024-2025 and circulated widely across India, with a brief mid-2025 surge. Despite reduced clinical severity, XFG's rapid spread and diversification highlight ongoing viral adaptability and the need for strengthened, complementary surveillance to detect emerging variants early.