From Pandemic to Persistence: Obesity, Immunity, and Next-Gen COVID-19 Vaccines

The COVID-19 pandemic, though no longer classified as a global emergency, persists as a major public health challenge in 2025 due to the continued emergence of SARS-CoV-2 variants with enhanced transmissibility and immune evasion. This paper reviews the evolving epidemiology of COVID-19, the critical interplay between obesity and disease severity, and advances in precision vaccination and therapeutics. Epidemiological and meta-analytic evidence highlights obesity as a significant independent risk factor for infection, hospitalization, ICU admission, mechanical ventilation, and mortality, underpinned by mechanisms such as immune dysfunction, chronic low-grade inflammation, and obesity-related comorbidities. Moreover, obesity is shown to impair vaccine-induced immune responses, complicating long-term protection. In parallel, updated mRNA and protein-subunit vaccines, alongside emerging monoclonal antibody and antiviral strategies, reflect the shift toward precision medicine tailored to vulnerable populations, particularly the immunocompromised. While monoclonal antibody efficacy has been undermined by viral evolution, novel agents such as pemivibart and vilobelimab demonstrate promise in targeted settings. Collectively, the findings underscore the importance of sustained surveillance, equitable vaccine distribution, integrated obesity prevention, and personalized medical interventions. As SARS-CoV-2 continues to adapt, long-term mitigation will require scientific innovation, public health vigilance, and commitment to global health equity.