How is the dynamics of Coronavirus Disease 2019 (COVID-19) in 2020 with non-pharmaceutical measures of control and 2021 with vaccinations as health policy? The present study confronts this question here by developing a comparative analysis of the effects of COVID-19 pandemic between April–September 2020 (with strong control measures) and April–September 2021 (with vaccinations) in Italy, which was one of first European countries to experience in 2020 high numbers of COVID-19 related infected individuals and deaths and in 2021 has a high share of people fully vaccinated against COVID-19 (>85% of population aged over 12 years in January 2022). Results suggest that over the period under study, the arithmetic mean of confirmed cases, hospitalizations of people and admissions to Intensive Care Units (ICUs) in 2020 and 2021 is significantly equal ( p-value<0.01), except fatality rate. In December 2021–January 2022, results suggest lower hospitalizations, admissions to ICUs, and fatality rate than 2020, though confirmed cases and mortality is higher in 2021 vs. 2020. These findings reveal that COVID-19 pandemic is driven by seasonality and environmental factors that reduce the negative effects in summer period, regardless control measures and/or vaccination campaign. These findings here can be of benefit to design health policy responses of crisis management for pandemic diseases considering the growth of COVID-19 associated with reduced temperatures and low solar radiation in winter months and the important role in planning strategies of prevention and control that should be set up during summer months and fully implemented during low-solar-irradiation periods (autumn and winter).