Abstract
Background and objectives The NB.1.8.1 Omicron subvariant has demonstrated notable epidemiological relevance in India, though without evidence of a marked increase in severity compared to prior Omicron waves. Understanding its genomic trajectory and policy implications is critical. Methods This was a retrospective convergent mixed-methods study integrating genomic sequencing (GISAID, INSACOG), epidemiological counts (ICMR, WHO, CDC), and policy/advisory analysis (MoHFW, WHO-SEARO). Data were analysed across January-May 2025 using prevalence tracking, hospitalisation comparisons, and thematic policy review. Results Genomic analyses showed NB.1.8.1 carrying lineage-defining spike mutations (A435S, V445H, T478I) linked to transmissibility and immune escape. While prevalence rose in China, India reported <5% share. Hospitalisation burdens remained lower in India than in China. India's policy response showed increasing alignment between genomic surveillance outputs and subsequent public health advisories, with targeted booster promotion and enhanced surveillance in high-incidence States. Interpretation and conclusions NB.1.8.1 illustrates the dynamic evolutionary trajectory of SARS-CoV-2. India's adaptive genomic surveillance and flexible public health frameworks contributed to mitigating clinical severity, though surveillance gaps and rural under-reporting remain concerns. Sustained genomic tracking, booster equity, and real-time advisory mechanisms are needed to strengthen preparedness.