Objective:To analyze the epidemic characteristics and clinical key indicators of the patients infected with SARS-CoV-2 of the local Omicron variant epidemic, to understand the clinical characteristics of mild and severe patients, and to provide a scientific basis for the effective treatment and prevention of severe disease.Methods:From January 2020 to March 2022, the clinical and laboratory data of COVID-19 patients admitted to the Fifth People's Hospital of Wuxi were retrospective analyzed, including virus gene subtypes, demographic information, clinical classification, main clinical symptoms, and key indicators of clinical testing, and the changes of clinical characteristics of the patients infected with SARS-CoV-2.Results:A total of 150 patients with SARS-CoV-2 infection were admitted, 78, 52 and 20 in 2020, 2021 and 2022, including 10, 1 and 1 severe patient, and the main infected virus strains were L, Delta, and Omicron variants. The relapse rate of patients infected with the Omicron variant was as high as 15.0% (3/20), the incidence of diarrhea decreased to 10.0% (2/20), the incidence of severe disease decreased to 5.0% (1/20), and the number of hospitalization days of mild patients increased compared with 2020 (days: 20.43±1.78 vs. 15.84±1.12); respiratory symptoms were reduced, and the proportion of pulmonary lesions decreased to 10.5%; the virus titer of severely ill patients with SARS-CoV-2 Omicron variant infection (day 3) was higher than that of L-type strain (Ct value: 23.92±1.16 vs. 28.19±1.54). The acute plasma cytokines interleukin (IL-6, IL-10) and tumor necrosis factor-α (TNF-α) were significantly lower in patients with severe Omicron variant new coronavirus infection than those with mild disease [IL-6 (ng/L): 3.92±0.24 vs. 6.02±0.41, IL-10 (ng/L): 0.58±0.01 vs. 4.43±0.32, TNF-α (ng/L): 1.73±0.02 vs. 6.91±1.25, all P < 0.05], while γ-interferon (IFN-γ) and IL-17A were significantly higher than patients with mild disease [IFN-γ (ng/L): 23.07±0.17 vs. 13.52±2.34, IL-17A (ng/L): 35.58±0.08 vs. 26.39±1.37, both P < 0.05]. Compared with previous epidemics (2020 and 2021), the proportion of CD4/CD8 ratio, lymphocyte count, eosinophil and serum creatinine decreased in patients with mild Omicron infection in 2022 (36.8% vs. 22.1%, 9.8%; 36.8% vs. 23.5%, 7.8%; 42.1% vs. 41.2%, 15.7%; 42.1% vs. 19.1%, 9.8%), the proportion of patients with elevated monocyte count and procalcitonin was large (42.1% vs. 50.0%, 23.5%; 21.1% vs. 5.9%, 0). Conclusion:The incidences of severe disease in patients with SARS-CoV-2 Omicron variant infection was significantly lower than that of previous epidemics, and the occurrence of severe diseases was still related to the underlying diseases.