Since its emergence, COVID-19 has placed severe strain on societies worldwide, with deaths occurring more frequently among older adults and people with chronic health conditions. Marked international differences in infection outcomes and case fatality rates (CFRs) have prompted investigation into the role of demographic and social conditions in shaping COVID-19 mortality. This study assessed how population age structure, disparities in human development, healthcare resources, and pandemic response measures contribute to cross-national and regional variation in COVID-19 CFRs. A cross-sectional analysis was performed using publicly available secondary data compiled from multiple global databases. Countries were grouped by region to examine differences in COVID-19 CFRs and to evaluate the extent to which selected sociodemographic characteristics and mitigation indicators explained observed regional patterns. COVID-19 CFRs differed considerably across world regions, alongside pronounced variation in the examined indicators. The highest average CFR was observed in South America (1.97% ± 0.74), whereas Oceania exhibited the lowest (0.26% ± 0.11). African regions consistently showed the weakest performance in terms of vaccination coverage, pandemic readiness, and related measures. Regression analysis identified population median age, vaccination coverage, and the Inequality-Adjusted Human Development Index (IHDI) as significant determinants of COVID-19 fatality rates. Higher median age and greater developmental inequality were associated with increased CFRs, while higher vaccination uptake was linked to reduced mortality. Differences in COVID-19 fatality rates across regions are closely tied to demographic composition, social inequality, and the effectiveness of pandemic control strategies. Countries with older populations, greater inequality in human development, and limited vaccination coverage experience disproportionately higher COVID-19 mortality.
