Objective This study aimed to evaluate the factors associated with death in patients with coronavirus disease 2019 by clarifying the clinical characteristics and immune responses. Methods The clinical characteristics and laboratory findings, including cytokine and lymphocyte subsets, were obtained from the electronic medical records of patients in Wuhan Tongji Hospital. Results This study included 836 patients with confirmed COVID-19. In total, 699 (83.6%) were cured and discharged, and 137 (16.4%) died. Our analysis revealed that age >= 65 years, male sex, malignancy, chronic obstructive pulmonary disease, dyspnea, dizziness, respiratory rate > 20 bpm, heart rate > 100 bpm, systolic blood pressure < 90 mmHg, neutrophils > 6.3x109/L, lymphopenia, thrombocytopenia, D-dimer >= 0.5 mg/L, lactate dehydrogenase > 250 U/L, aspartate aminotransferase > 40 U/L, total bilirubin > 26 mu mol/L, albumin < 35 g/L, blood urea nitrogen > 9.5 mmol/L, estimated glomerular filtration rate < 90 ml/min/1.73, elevated cardiac troponin I, N-terminal pro-brain natriuretic peptide >= 900 pg/ml, C-reactive protein >= 25 mg/L, procalcitonin >= 0.05 ng/ml and ferritin > 400 mu g/L were associated with death in patients with COVID-19. The multivariate logistic regression analysis revealed that an estimated glomerular filtration rate < 90 ml/min/1.73, elevated cardiac troponin I, C-reactive protein >= 25 mg/L and procalcitonin >= 0.05 ng/ml were predictive of mortality. Regarding immune responses, IL-2R, IL-6, IL-8, IL-10, and TNF alpha were remarkably higher in the deceased group at admission, and the levels of IL-2R, IL-6, IL-8, IL-10, and TNF alpha in the deceased group showed a rapid increase; the dynamics of these cytokines were highly consistent with disease deterioration. Lymphocyte subset analysis revealed that the deceased patients showed significant decreases in lymphocyte counts, especially helper T cells, suppressor T cells and NK cells. Conclusions This study identified that an estimated glomerular filtration rate < 90 ml/min/1.73, elevated cardiac troponin I, C-reactive protein >= 25 mg/L and procalcitonin >= 0.05 ng/ml were predictors of mortality in COVID-19 patients. Elevated cytokine levels and a continued increasing trend, including in IL-2R, IL-6, IL-8, IL-10 and TNF alpha, and a decrease in lymphocyte subsets, especially helper T cells, suppressor T cells and NK cells, were associated with a poor prognosis.