Objective: To explore the epidemic spread and prevention strategy of COVID-19 by Omicron variant in a single office building. Methods: Retrospective data were collected for the period from March 19, 2022 to March 28, 2022. During this period, the infection rate, epidemic survey, transmission chain, population vaccination and Ct value of infected cases, as well as other data of 458 persons at risk in the single office building were collected. The response measures and outcomes were recorded, and the characteristics of this round of epidemic transmission were analyzed, and the prevention and control strategies were summarized. Results: The epidemic situation in a single office building lasted for 10 days from March 19 to March 28. Forty-two out of the 458 persons in the office building were infected, with an infection rate of 9.17%. After the large-scale single room isolation measure was put in place for key populations on March 21, the infection rate showed a significant downward trend, reversing the previous upward trend. The real-time reproduction number (Rt) value changed dynamically with time (from 10.8 to 2.2) and reached a value of lower than 1 on the third day of isolation. For patients with Ct value above 30, the positive conversion rate of close contacts was about 6.0%. For patients with Ct value between 20-30, the positive conversion rate of close contacts is higher, about 25.6%. Among patients with Ct value below 20, the conversion rate of close contacts was as high as 62.5%. Compared with CT value >30 and their corresponding close contacts as the reference group, the infection risk of close contacts of infected persons with CT value of 20-30 increased significantly (OR=5.37, 95% CI: 1.88-15.33). The infection risk of close contacts of infected persons with CT value <20 increased further (OR=25.95, 95% CI: 9.11-73.94). Conclusions: The transmission power of the variant of SARS-coV-2is closely related to the level of nucleic acid Ct value of the disseminator. For those with low Ct value, priority should be given to transport treatment, and their close contacts should be isolated. Fine management according to the Ct value of the infected person may play a great role in blocking the high-risk transmission chain of the disease and may be of great significance to avoid the outbreak of the virus in the community.