Background: In most countries, it is hard to effectively control coronavirus disease 2019 (COVID-19). This study conducted the most comprehensive evaluation of the effects of pharmacological (like vaccination, pharmacotherapy ) and non-pharmacological (like isolation, social distancing and mask-wearing) interventions taken singly or in combination for the first time globally.Methods: We estimate that across these 12 countries that are different but presentative, interventions prevented or delayed roughly millions of confirmed cases. This study constructs mathematical model, which interventions includes vaccination, pharmacotherapy, isolation, social distancing and mask-wearing , and analyses the effect of these interventions used alone and in combination.Findings: The basic reproduction number (R0) of each country mostly range from 3 to 5. In terms of the effect of single intervention, for countries such as China, South Korea, Thailand, US, South Africa and Algeria, it is preferred to recommend these countries to adopt isolation to prevent and control the second wave of COVID-19 outbreak, while for countries such as Russia, UK, Saudi Arabia, India and Brazil, wearing masks is the best choice. Especially pharmacotherapy can play a good role in Iran. When combinations with different interventions were taken, the situation was different. For US, Brazil and Algeria, the combination of “Vaccination & Isolation & Wearing mask” is recommended in these countries to prevent and control the development of COVID-19, and the combination of “Isolation & Social distancing & Wearing mask” is recommended in UK and China. For the rest, we suggest that Russia, Iran, Saudi Arabia, India, Thailand and South Africa take the intervention measures of “Vaccination & Medical treatment & Isolation & Wearing mask”, “Vaccination & Medical treatment”, “Vaccination & Social distancing & Wearing mask”, “Medical treatment & Social distancing & Wearing mask”, “Vaccination & Medical Treatment & Isolation”, “Vaccination & Medical Treatment & Wearing mask”, respectively to deal with the second wave of outbreaks that may come by the end of this year.Interpretation: Our model is operable and selective for the prevention and control of epidemic situations in various countries. These findings may help policy makers in the 180+ countries where COVID-19 has been reported around the world to identify the most effective and socioeconomically acceptable measures to prevent and control the second wave of COVID-19 epidemic, and inform if when these policies should be deployed, intensified or replaced.Funding: This study was partly supported by the Bill & Melinda Gates Foundation (INV-005834), the Science and Technology Program of Fujian Province (No: 2020Y0002), the Xiamen New Coronavirus Prevention and Control Emergency Tackling Special Topic Program (No: 3502Z2020YJ03), and the Open Research Fund of State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics (SKLVD2019KF005).Declaration of Interests: The authors declare no competing interests.