Objective To analyze the characteristics of traditional Chinese medicine (TCM) syndromes of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant in a shelter hospital in Shanghai. Methods A total of 621 patients infected with SARS-CoV-2 omicron variant from Apr. 4 to May 24, 2022 in a shelter hospital in Shanghai were enrolled. The data of the patients, including the general information and common clinical syndromes (such as fever, headache, stuffy nose, runny nose, cough, and sputum), were collected on admission by TCM syndrome electronic scale, and core syndrome characteristics were analyzed base on the proportion of each symptom. The syndromes were divided according to the symptom score of patients, and the differences of disease course among the syndromes were compared. Results The proportion of patients aged 30 to 49 years old was the highest among 621 patients infected with omicron variant (49.76%, 309/621). The most prominent symptoms were cough and expectoration, accounting for 62.32% (387/621) and 68.12% (423/621), respectively. The more common symptoms included sore throat, stuffy nose, runny nose, fatigue, muscle pain, and headache. White sputum was mostly seen in the expectoration and clear mucus was mostly seen in runny nose. According to the clinical symptoms, the core syndrome characteristic of patients infected with omicron variant was cold epidemic constraint in the lung featuring dampness and toxins. The main syndrome was plague invading the defensive exterior, accounting for 40.10% (249/621). The second and third ones were heat toxin attacking the lung syndrome (29.95%, 186/621) and dampness obstructing (17.55%, 109/621), while the least common syndrome was deficiency of qi and yin (7.73%, 48/621). The course of qi and yin deficiency was longer than the other 3 syndromes (P<0.05). Conclusion The core TCM syndrome characteristic of patients infected with SARS-CoV-2 omicron variant is cold epidemic constraint in the lung featuring dampness and toxins. The main syndrome is plague invading the defensive exterior. The pattern tends to convert into qi and yin deficiency along the long course.