Vaccination, human mobility, and COVID-19 health outcomes: Empirical comparison before and during the outbreak of SARS‐Cov-2 B.1.1.529 (Omicron) variant

•Disentangling the relationships among vaccination, human mobility, and COVID-19 health outcomes.•Examining differences in COVID-19-related outcomes before and during the Omicron surge.•Controlling for effects of socioeconomic, demographic, racial/ethnic, and partisan disparities.•Developing a time-varying mediation analysis to understand the temporal evolution of relationships. The B.1.1.529 (Omicron) variant surge has raised concerns about the effectiveness of vaccines and the impact of imprudent reopening. Leveraging over two years of county-level COVID-19 data in the US, this study aims to investigate relationships among vaccination, human mobility, and COVID-19 health outcomes (assessed via case rate and case-fatality rate), controlling for socioeconomic, demographic, racial/ethnic, and partisan factors. A set of cross-sectional models was first fitted to empirically compare disparities in COVID-19 health outcomes before and during the Omicron surge. Then, time-varying mediation analyses were employed to delineate how the effects of vaccine and mobility on COVID-19 health outcomes vary over time. Results showed that vaccine effectiveness against case rate lost significance during the Omicron surge, while its effectiveness against case-fatality rate remained significant throughout the pandemic. We also documented salient structural inequalities in COVID-19-related outcomes, with disadvantaged populations consistently bearing a larger brunt of case and death tolls, regardless of high vaccination rates. Last, findings revealed that mobility presented a significantly positive relationship with case rates during each wave of variant outbreak. Mobility substantially mediated the direct effect from vaccination to case rate, leading to a 10.276 % (95 % CI: 6.257, 14.294) decrease in vaccine effectiveness on average. Altogether, our study implies that sole reliance on vaccination to halt COVID-19 needs to be re-examined. Well-resourced and coordinated efforts to enhance vaccine effectiveness, mitigate health disparity and selectively loosen non-pharmaceutical interventions are essential to bringing the pandemic to an end.