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ObjectiveTo investigate macro-scale estimators of the variations in COVID-19 cases and deaths among countries.DesignEpidemiological study.SettingCountry-based data from publicly available online databases of international organisations.ParticipantsThe study involved 170 countries/territories, each of which had complete COVID-19 and tuberculosis data, as well as specific health-related estimators (obesity, hypertension, diabetes and hypercholesterolaemia).Primary and secondary outcome measuresThe worldwide heterogeneity of the total number of COVID-19 cases and deaths per million on 31 December 2020 was analysed by 17 macro-scale estimators around the health-related, socioeconomic, climatic and political factors. In 139 of 170 nations, the best subsets regression was used to investigate all potential models of COVID-19 variations among countries. A multiple linear regression analysis was conducted to explore the predictive capacity of these variables. The same analysis was applied to the number of deaths per hundred thousand due to tuberculosis, a quite different infectious disease, to validate and control the differences with the proposed models for COVID-19.ResultsIn the model for the COVID-19 cases (R2=0.45), obesity (β=0.460), hypertension (β=0.214), sunshine (β=−0.157) and transparency (β=0.147); whereas in the model for COVID-19 deaths (R2=0.41), obesity (β=0.279), hypertension (β=0.285), alcohol consumption (β=0.173) and urbanisation (β=0.204) were significant factors (p<0.05). Unlike COVID-19, the tuberculosis model contained significant indicators like obesity, undernourishment, air pollution, age, schooling, democracy and Gini Inequality Index.ConclusionsThis study recommends the new predictors explaining the global variability of COVID-19. Thus, it might assist policymakers in developing health policies and social strategies to deal with COVID-19.Trial registration numberClinicalTrials.gov Registry (NCT04486508).