Emerging SARS-CoV-2 variants: genomic shifts, immune evasion, and therapeutic perspectives.

The COVID-19 pandemic, caused by the continuously evolving SARS-CoV-2 virus, has presented persistent global health challenges. As novel variants emerge, many with enhanced transmissibility and immune evasion capabilities, concerns have intensified regarding the efficacy of existing vaccines and therapeutics. This review provides a comprehensive overview of the current landscape of COVID-19 vaccination, including the development and performance of monovalent and bivalent boosters, and examines their effectiveness against newly emerging variants of interest (VOIs) and variants under monitoring (VUMs), such as JN.1, KP.2, and XEC. We also explore real-world vaccine effectiveness, antibody neutralization studies, and the latest updates from WHO advisory groups. Beyond vaccines, we discuss evolving treatment approaches, including the use of monoclonal antibodies (mAbs), small-molecule antivirals, and host-targeted therapies. As resistance to antiviral agents and mAbs continues to emerge, combination therapies and next-generation broadly neutralizing antibodies offer promising avenues. This review underscores the importance of ongoing surveillance, rapid vaccine reformulation, and the development of adaptive treatment strategies to mitigate the impact of emerging SARS-CoV-2 variants and protect vulnerable populations.