This study was to explore the performance of immune function and compositions of hospitalization cost for patients with COVID-19 as well as the application of a grey relational mathematical model (GRMM). A total of 100 COVID-19 patients diagnosed by nucleic acid test and chest CT examination in our hospital were collected in this study. They were divided into 2 groups: non-severe group (mild and moderate patients, n = 57 cases), and severe group (severe and critical patients, n = 43 cases) based on the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7) published by the World Health Organization (WHO). The general clinical data, blood routine indexes, cellular immune and humoral immune function test indexes, and the composition of hospitalization costs of the two groups of patients were collected and analyzed. The results showed that the average age, proportion of males, smoking history, and the number and proportion of patients in the non-severe group were smaller than those in the severe group (P < 0.05); the severe group had significantly more shortness of breath patients than the non-severe group (P < 0.05). Compared with the non-severe group, the number of white blood cells (WBC), the number and proportion of neutrophils, and the count of neutrophils/lymphocytes in the severe group increased obviously (P < 0.05), and the number of lymphocytes and the proportion of monocytes decreased dramatically (P < 0.05); the number and proportion of CD3+, CD4+, CD8+, and CD19+ in the severe group were much lower in contrast to those in the non-severe group (P < 0.05), while the ratio of CD4+/CD8+ was greatly higher in contrast to that of non-severe patients (P < 0.05). Compared with the non-severe group, the bed fee, laboratory test fee, diagnosis fee, and medicine fee of the severe group were increased observably (P < 0.05). The changes in hospitalization cost of patients in the severe group was related to bed fees, laboratory fees, and expenses of proprietary Chinese medicines, while the hospitalization cost of patients in the severe group was related to bed fees, laboratory fees, and examination fees. The results revealed that elderly COVID-19 patients with basic diseases were prone to develop severe disease, immune cell depletion may be one of the reasons for the development of severe patients, and the medical insurance policy greatly reduced the hospitalization costs of COVID-19 patients.