Western countries are experiencing surges in
COVID-19 cases and deaths due to increasing public transportation during holiday seasons. This study aimed to explore whether mainland China will face an epidemic rebound during the Spring Festival holiday, when millions of Chinese people travel across the country, and investigate which
nucleic acid testing (
NAT) strategy is optimal to contain the epidemic. A microsimulation model was used to simulate SARS-CoV-2 transmission among railway travelers and evaluated the effects of various
NAT strategies. An extended susceptible-exposed-infectious-recovered (SEIR) model was built to forecast local transmission during the Spring Festival period under different scenarios of testing strategies. The total number of
infections, testing burden, and medical expenditure were calculated to devise an optimal strategy during the Spring Festival travel rush. Assuming the daily incidence of 20 per 10 million persons, our model simulated that there would be 97 active
infections on the day of travel among 10 million railway passengers without
NAT and symptom screening. Pre-travel testing could reduce the number of active
infections. Compared with no
NAT, testing passengers from risk tier 2-4 regions 3 days before travelling could significantly reduce the risk of transmission, and it is more economical and efficient than testing for all passengers.