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The main goal of this study is to analyze the relation between commercial trade and pandemic severity in society, in order to support new hypotheses which can explain transmission dynamics of COVID-19, as well as promote policy responses to cope with future epidemics similar to COVID-19. This study considers the role of trade in the dynamics of pandemic diffusion, within and between countries, which has not been investigated yet in this emerging field of research. We focus on three large countries in Europe: Italy, France, and Spain. The analysis is performed at regional level (involving in total 52 European regions). Results suggest that the association between trade and pandemic severity seems to be supported by empirical evidence, making it possible to introduce new hypotheses for explaining transmission dynamics of COVID-19 within and between countries. In particular, international trade data is supposed to be used as a comprehensive indicator accounting for population density, economic dynamism, and human mobility. The statistical analyses, also in a multivariate context, strongly support this hypothesis and suggest that crisis management has to focus in the very first place on infections occurring outside the national boundaries, in order to cope with pandemic threat of new waves of COVID-19 and future similar epidemics/pandemics. • The interdisciplinary research is shown to be strategic in pandemic to propose new data analysis and perspectives. • Economic data about international trade are used to describe transmission dynamics of COVID-19. • Comparative analysis involving all the regions of Italy, Spain, and France are presented for the first time. [ABSTRACT FROM AUTHOR]