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Since the pandemic of COVID-19 began in January 2020, the world has witnessed drastic social-economic changes. To harness the virus spread, several studies have been done to study contributing factors that are pertinent to COVID-19 transmission risks. However, little has been done to investigate how human activities on the spatial network are correlated to the virus transmission and spread. This paper performs a statistical analysis to examine interrelationships between spatial network characteristics and cumulative cases of COVID-19 in US counties. Specifically, both county-level transportation profiles (e.g., the total number of commute workers, route miles of freight railroad) and road network characteristics of US counties are considered. Then, the lasso regression model is utilized to identify a sparse set of significant variables that are sensitive to the response variable of COVID-19 cases. Finally, the fixed-effect model is built to capture the relationship between the selected set of predictors and the response variable. This work helps identify and determine salient features from spatial network characteristics and transportation profiles, thereby improving the understanding of COVID-19 spread dynamics. These significant variables can also be utilized to develop simulation models for the prediction of real-time positions of virus spread and the optimization of intervention strategies.