The virology of Omicron: pathophysiology, immune regulation, and clinical impact of SARS-CoV-2 sub variants

Since its emergence in late 2019, SARS-CoV-2 has evolved into multiple variants with distinct genetic and clinical features. Among them, the Omicron variant (B.1.1.529) and its sublineages BA.2.75, JN.1.8, and KP.2 have shown enhanced transmissibility and immune evasion, while generally exhibiting reduced lower respiratory tract pathogenicity compared to earlier variants, thereby continuing to pose significant challenges to public health. In India, these variants have significantly shaped the trajectory of the pandemic, necessitating focused evaluation of their biological and clinical impact. This review aims to provide a comprehensive study on the virology, pathophysiology, and systemic manifestations of Omicron and its emerging subvariants upto July 2025. We discuss their mechanisms of entry and replication, interaction with ACE2 and TMPRSS2 receptors, and evasion of host immune responses. Particular emphasis is placed on multi-organ involvement beyond the respiratory system, including neuro-respiratory dysregulation, cardiovascular complications, hepatic injury, gastrointestinal disturbances, and renal dysfunction. Furthermore, we evaluate the effectiveness of available vaccines, antiviral therapies, and diagnostic tools, alongside emerging clinical strategies such as vagus nerve stimulation, thermal modulation, and respiratory muscle training. By integrating molecular insights with clinical outcomes, this review highlights the multifaceted and systemic nature of Omicron-induced disease. We underscore the urgent need for variant-specific immunisation, early intervention strategies, and robust genomic surveillance to mitigate long-term sequelae and guide preparedness for future outbreaks.