Objective:To evaluate the role of interleukin-6 (IL-6) and CD4 + T-lymphocytopenia in assessing the severity and prognosis of coronavirus disease 2019 (COVID-19). Methods:A prospective observational study was conducted. Forty-five patients with COVID-19 admitted to Henan Provincial People's Hospital from January 13 to March 13, 2020 were enrolled and divided into normal group (13 cases), severe group (20 cases), critically severe group (12 cases) according to the severity of the disease. A total of 15 healthy subjects receiving physical examinations during the same period were collected as the healthy control group. Clinical data were collected to compare the clinical characteristics, general test results, IL-6 and CD4 + T-lymphocytopenia levels of patients in different disease severity groups and healthy control group. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of each indicator for the severity of COVID-19. Multivariate Cox regression analysis was used to analyze the risk factors affecting the prognosis of COVID-19 patients, and Kaplan-Meier survival curve analysis was performed. Results:The age of the critically severe group was significantly higher than that of the severe and normal groups (years old: 66.91±17.01 vs. 59.35±18.07, 40.23±12.61, both P < 0.05), and the negative conversion time of the 2019 novel coronavirus (2019-nCoV) was significantly longer than that of the severe and normal groups (days: 19.00±10.66 vs. 18.00±7.18, 9.31±3.49, both P < 0.05). With the increase of the severity of disease, white blood cell count (WBC), C-reactive protein (CRP), calcitonin (PCT), total bilirubin (TBil), troponin I (TnI), IL-6, D-dimer and other indicators were significantly increased, while lymphocyte count (LYM), platelet count (PLT), CD4 +, CD8 +, oxygenation index (PaO 2/FiO 2) were significantly decreased (all P < 0.01). ROC curve showed that PaO 2/FiO 2, IL-6 and CD4 + had certain predictive value for disease severity of COVID-19, the area under the ROC curve (AUC) of them were 0.903, 0.871, 0.689, and the 95% confidence interval (95% CI) were 0.806-0.949, 0.769-0.974, 0.542-0.853; the best cut-off values were 196.00 mmHg (1 mmHg = 0.133 kPa), 6.02 ng/L, 355 cells/μL, respectively; the sensitivity were 73.3%, 99.3%, 73.3%, and the specificity were 96.6%, 62.1%, 65.5%, respectively. Multivariate Cox regression analysis showed that age, PaO 2/FiO 2, high IL-6 and low CD4 + (IL-6≥6.02 ng/L and CD4 + < 355 cells/μL) were independent risk factors affecting the prognosis of COVID-19 [hazard ratio ( HR) was 1.077, 0.053 and 3.490, respectively, all P < 0.05]. Kaplan-Meier survival analysis showed that when both high IL-6 and low CD4 + (IL-6≥6.02 ng/L and CD4 + < 355 cells/μL) were present, the mean time of adverse prognosis was (20.53±5.71) days; when increased IL-6 and decreased CD4 + were inconsistent, the mean time of adverse prognosis was (53.21±3.16) days. Conclusions:The levels of IL-6 and CD4 + T-lymphocytopenia are closely related to the severity of COVID-19 disease. When IL-6 ≥ 6.02 ng/L and CD4 + < 355 cells/μL occur simultaneously, the prognosis is poor.