COVID-19 pandemic outbreak, caused by the SARS-CoV-2 virus, affected millions of people worldwide causing hundreds of thousands of related fatalities. It is crucial to understand why the virus transmission seems to spread more easily in some regions with respect to others. The residuals, with respect to the modeled COVID-19 per-day hospitalized patients in Intensive Care Unit, were linked to meteorological and air-pollutant variables in four major metropolitan areas in Italy. COVID-19 pandemic related infections are slow down by higher tropospheric Ozone concentrations (p < 0.01). We quantitatively assessed that higher levels of tropospheric Ozone, already proven effective against viruses and microbial contaminants, play a role in flagging COVID-19 pandemic transmission. Because the tropospheric ozone production is depending, among others, by air-quality and sunlight, this can explain why the virus is spreading differential.