The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that caused the Coronavirus Disease 2019 (COVID-19), generating high numbers of COVID-19 related infected individuals and deaths, is still circulating in 2021 with new variants of the coronavirus, such that the state of emergency remains in manifold countries. Currently, there is still a lack of a full understanding of the factors determining the COVID-19 diffusion that clarify the causes of the variability of infections across different provinces and regions within countries. The main goal of this study is to explain new and main determinants underlying the diffusion of COVID-19 in society. This study focuses on international trade because this factor, in a globalized world, can synthetize different drivers of virus spread, such as mobility patterns, economic potentialities, and social interactions of an investigated areas. A case study research is performed on 107 provinces of Italy, one of the first countries to experience a rapid increase in confirmed cases and deaths. Statistical analyses from March 2020 to February 2021 suggest that total import and export of provinces has a high association with confirmed cases over time (average
r
> 0.78,
p
-value <.001). Overall, then, this study suggests total import and export as complex indicator of COVID-19 transmission dynamics that outclasses other common parameters used to justify the COVID-19 spread, given by economic, demographic, environmental, and climate factors. In addition, this study proposes, for the first time, a time-dependent correlation analysis between trade data and COVID-19 infection cases to explain the relation between confirmed cases and social interactions that are a main source of the diffusion of SARS-CoV-2 and subsequent negative impact in society. These novel findings have main theoretical and practical implications directed to include a new parameter in modelling of the diffusion of COVID-19 pandemic to support effective policy responses of crisis management directed to constrain the impact of COVID-19 pandemic and similar infectious diseases in society.