This study has two goals. The first is to explain the geo-environmental determinants of the accelerated diffusion of COVID-19 in Italy that is generating a high level of deaths. The second is to suggest a strategy to cope with future epidemic threats having accelerated viral infectivity in society. Using data on N = 55 Italian province capitals, and data of infected individuals at as of April 7th, 2020, results reveal that the accelerate and vast diffusion of COVID-19 in North Italy has a high association with air pollution of cities measured with days exceeding the limits set for PM10 (particulate matter 10 μm or less in diameter) or ozone in previous years. In particular, hinterland cities with average higher number of days exceeding the limits set for PM10 (and a low intensity of wind speed) have a very high number of infected people on 7th April 2020 (arithmetic mean about 2200 infected, with average polluted days greater than 80), than coastal cities also having days of exceeding the limits set for PM10 or ozone but with high intensity of wind speed (arithmetic mean about 944.70 infected individuals, with about 60 average polluted days); moreover, cities having more than 100 days of air pollution (exceeding the limits set for PM10), they have a very high average number of infected people (about 3350 infected individuals, 7th April 2020), whereas cities having less than 100 days of air pollution, they have a lower average number of infected individuals (about 1014). The findings here also suggest that to minimize the impact of future epidemics similar to COVID-19, the max number of days per year in which Italian provincial capitals can exceed the limits set for PM10 or for ozone, considering their meteorological conditions, is about 48 days. Moreover, results here reveal that the explanatory variable of air pollution in cities under study seems to be a more important predictor in the initial phase of diffusion (on 17th March 2020, b1 = 1.27, p < 0.001) than interpersonal contacts (b2 = 0.31, p < 0.05). In the second phase of maturity of the transmission dynamics of COVID-19, air pollution reduces intensity (on 7th April 2020 with b′1 = 0.81, p < 0.001) also because of indirect effect of lockdown, whereas coefficient of transmission by interpersonal contacts has stability (b′2 = 0.31, p < 0.01). This result reveals that accelerated transmissions dynamics of COVID-19 is due to mainly to the mechanism of “air pollution-to-human transmission” rather than “human-to-human transmission”. Overall, then, transmission dynamics of viral infectivity, such as COVID-19, is due to systemic causes: general factors that are the same for all regions (e.g., biological characteristics of virus, incubation period, etc.) and specific factors which are different for each region (e.g., complex interaction between air pollution, meteorological conditions and biological characteristics of viral infectivity) and health level of individuals (habits, immune system, age, sex, etc.). Lessons learned for COVID-19 in the case study of Italy suggest that a proactive strategy to cope with future epidemics is to also apply especially an environmental and sustainable policy based on reduction of levels of air pollution mainly in hinterland and polluting cities- having low wind speed, high percentage of moisture and fog days-that seem to have an environment that may damage immune system of people and foster a fast transmission dynamics of viral infectivity in society. Hence, in the presence of polluting industrialization in regions that can trigger the mechanism of air pollution-to-human transmission dynamics of viral infectivity, this study must conclude that a comprehensive strategy to prevent future epidemics similar to COVID-19 has to be also designed in environmental and socioeconomic terms, that is also based on sustainability science and environmental science, and not only in terms of biology, healthcare and health sector.