Socioeconomic determinants of COVID-19 vaccination and mortality: a cross-national path analysis

Numerous clinical and epidemiological studies demonstrated that COVID-19 vaccines and boosters reduce infection and mortality; however, the extent to which these effects vary across socioeconomic and political contexts remains insufficiently explained at the population level. Cross-national evidence remains fragmented, with many studies examining vaccination coverage and macro-structural determinants separately rather than evaluating how structural readiness, vaccination and booster coverage interact simultaneously to influence mortality outcomes, particularly during the post-Omicron phase. Consequently, it remains unclear how structural development and policy capacity are associated with differences in the population-level mortality impact of vaccination strategies.

This study tested an integrated cross-national structural model examining the interplay between COVID-19 vaccination strategies and country-level macro-structural indicators -the Human Development Index (HDI) and the Containment and Health Index (CHI)- and assessed whether these factors shape vaccination and booster uptake and subsequent COVID-19 mortality change across countries.

Using country-level data from 195 countries between March 11, 2020, and August 1, 2022, structural path modeling evaluated hypothesized directional pathways among HDI, CHI, vaccination and booster coverage, and COVID-19 mortality change. Variables were standardized and annualized, and before/after ratios captured mortality changes associated with vaccination rollout. Vaccination and booster coverage were measured at a harmonized late-2021 reference point to ensure cross-national comparability prior to outcome assessment.

The model demonstrated acceptable fit and statistically significant associations within the modeled pathways (p < 0.05). Higher HDI was associated with greater CHI, higher vaccination and booster coverage, and lower mortality change. Booster uptake showed an additional negative association with mortality change, consistent with an implementation pathway linking structural capacity and mortality outcomes.

Structural development and policy context were associated with implementation and mortality dynamics at the population level. The integrated global analytical framework suggests that observed mortality dynamics vary according to structural capacity. These findings provide context for global public health decision-making, emphasizing structural readiness alongside biomedical strategies and highlighting the role of health system capacity and governance in shaping differences in the real-world effectiveness of vaccination programs during large-scale infectious threats. Sustained booster uptake emerged as a key operational pathway linking structural capacity to mortality change across countries.