Backqround: There is a raising concern of a higher infectious Omicron BA.2 variant and the latest BA.4, BA.5 variantmade it more dificult in the mitigation process against COVID-19 pandemic. Our study aimed to find optimal controlstrategies by transmission of dynamic model from novel invasion theory. Methods: Based on the public data sources from January 31 to May 31, 2022,in four cities (Nanjing, Shanghai, Shen-zhen and Suzhou) of China. We segmented the theoretical curves into five phases based on the concept of biologicalinvasion.Then, a spatial autocorrelation analysis was carried out by detecting the clustering of the studied areas. Afterthat, we choose a mathematical model of COVID-19 based on system dynamics methodology to simulate numerousintervention measures scenarios. Finally, we have used publicly available migration data to calculate spillover risk. Results: Epidemics in Shanghai and Shenzhen has gone through the entire invasion phases, whereas Nanjing andSuzhou were all ended in the establishment phase. The results indicated that Rt value and public health and sociameasures (PHSM)-ingex of the epidemics were a negative corre ation in all cities, except Shenzhen, The interventiorhas come into effect in diferent phases of invasion in all studied cities. Until the May 31, most of the spillover risk inShanghai remained above the spilover risk threshold (18.81-303 .84) and the actual number of the spillovers (0.94-7498) was also increasing a ong with the time. Shenzhen reported Omicron cases that was onlv above the spiloveirisk threshold (17.92) at the phase of outbreak, consistent with an actual partial spilover. ln Nanjing and Suzhou, theactual number of reported cases did not exceed the spillover alert value.
