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BackgroundIn 2021, new variants of the SARS-CoV-2 virus appeared with increased transmissibility and virulence as compared with the original wild variant. The first variants of concern (VoCs), Alpha (B1.1.7) and Gamma (P.1), first appeared in the United Kingdom and Brazil, respectively. The Delta (B.1.617.2) variant, seen in India in October 2020, dominated COVID-19 infections across all regions through the second half of 2021. ObjectiveThis research explores the degree to which SARS-CoV-2 VoCs generate waves of fluctuations in case-fatality rates (CFRs) across countries in several regions, increase the risk of mortality to persons with certain comorbidities, and decrease the risk of mortality as the percentage of fully vaccinated populations increases. MethodsThis analysis introduces a measure of the temporal dynamics of COVID-19 infections in the form of a proxy CFR (pCFR), which can be compared among countries. It uses economic and demographic data reported by the World Bank and International Monetary Fund, plus publicly available epidemiological and medical statistics reported to the relevant national and international public health authorities. From these ecological data, pandemic average and daily COVID-19 CFRs and their correlations with potential cofactors were computed for 2021, a year dominated by the spread of World Health Organization–designated VoCs. The study does not investigate disease pathology; rather, it compares the daily case rates and pCFRs to reveal underlying contributing factors that vary from country to country and region to region. ResultsThe in-depth global regression analysis of cofactors found that the strongest single correlation with COVID-19 fatality was 0.36 (SD 0.02) with P |