Participants
From January 29, 2020 to to February 29, 2020, 72 adult patients were hospitalized. After excluding five death cases, three were transferred to other hospitals, two with not controlled fever, one with severe hepatic dysfunction and two with severe renal dysfunction, a total of 59 patients were included in this study. There were 20 patients accepted rIL–2 treatment. Twenty patients were chosen and paired with the rIL–2 group from the 39 patients of non-rIL–2 group (Figure 1). The clinical data of patient demographic information and history of comorbidities were collected on admission. Symptoms, signs and laboratory data were collected before and after rIL–2 treatment in rIL–2 group and at the same time point in non-rIL–2 group. The in-hospital medications and interventions were obtained during the hospitalization. The length of hospital stay were collected at the time of patients discharged from hospital.
Baseline Characteristics of the participants and between groups
As shown in Table 1, the median age of all patients was 56 years ( 48, 64), ranging from 23 years to 88 years, among whom 54.24% were male. Comorbidities such as hypertension (28.81%), diabetes (15.25%), coronary heart disease (6.78%) and cerebrovascular disease (10.17%) were common. The symptoms before rIL–2 intervention of fatigue (49.15%) and cough (77.97%) were observed in most patients. There were 69.49% patients with fever on admission. After treatment no patient included in the study had fever. All patients’ white blood cell counted in a median of 5.90(4.2,7.2)×109/L, neutrophil in a median of 3.98(2.8,5.1)×109/L and lymphocyte in a median of 0.980(0.8,1.4)×109/L. High serum IL–6 level with a median of 6.420 (1.5,16.2) pg/mL and high CRP with a median of 27.220 (4.7,48.2) mg/L were demonstrated. During hospitalization, 53 (89.83%) patients accepted antiviral drugs therapy, 44 (74.58%) patients accepted antibiotics drugs therapy, 5 (10.17%) patients accepted systemic corticosteroids therapy and 56 (94.92%) patients accepted traditional Chinese medicine therapy. The above clinical characteristics in both groups before and after matching did not have significant difference.
Comparison of laboratory results in rIL–2 group patients before and after rIL–2 treatment
An obvious rising of lymphocyte count was detected after rIL–2 plus regular treatment, which was 1.935 (1.6, 3.0)×109/L compared to 1.110 (0.9, 1.4)×109/L before rIL–2 treatment in rIL–2 group (p<0.01). The CRP showed a significant decreasing after rIL–2 plus regular treatment, which lowered from 21.740 (0.5, 65.1) mg/L to 3.965 (1.5, 5.7) mg/L (p<0.05). The WBC count were 6.215 (5.4, 7.2)×109/L and 6.935 (5.2, 8.3)×109/L before and after rIL–2 treatment in rIL–2 group, respectively. The difference was not significant (p>0.05). The neutrophils count was 3.075 (2.2, 4.3)×109/L in rIL–2 group after rIL–2 treatment, that was similar with 3.830 (2.8, 4.9)×109/L before rIL–2 treatment (p>0.05). The IL–6 were 7.765 (1.6, 21.7) pg/mL before rIL–2 treatment. After rIL- 2 treatment, the IL–6 decreased to 3.730 (1.5, 7.7) pg/mL. But the decreasing did not get significant difference (p>0.05). There were no obvious difference in hemoglobin (Hb) levels, platelet (PLT) count, alanine aminotransferase (ALT) levels, aspartate aminotransferase (AST) levels, blood urea nitrogen (BUN) levels and serum creatinine (Scr) levels before and after rIL–2 treatment (130.5 [123.0, 148.8] g/L vs 128.0 [120.3, 138.8] g/L, 165.5 [132.5, 243.0] ×109/L vs 215.5 [117.8, 254.5] ×109/L, 43.0 [30.0, 59.5] U/L vs 52.0 [24.8, 67.8] U/L, 29.5 [21.0, 36.8] U/L vs 28.0 [19.0, 31.0] U/L, 4.845 [3.5, 7.4] mmol/L vs 4.305 [3.6, 5.1] mmol/L, 69.500 [58.7, 78.7] μmol/L vs 65.550 [54.3, 73.8]μmol/L, repectively. All p>0.05) (Table 2).
Comparison of laboratory results in non-rIL–2 group patients before and after rIL–2 treatment
There were a clearly visible increasing in lymphocyte count from 0.875 (0.7, 1.3)×109/L to 1.275 (1.0, 1.6)×109/L (p<0.01) and a decreasing in CRP level from 29.930 (7.6, 47.8) mg/L to 4.585 (2.8, 12.1) mg/L (p<0.05) in non rIL–2 group with regular treatment. No obvious effect was demonstrated on change in WBC count (5.070 [4.0, 7.3]×109/L vs 6.075 [4.6, 7.7]×109/L, p>0.05), neutrophils count (3.755 [2.5, 6.2]×109/L, 3.925 [2.8, 5.8]×109/L, p>0.05) and serum IL–6 levels (6.070 [1.5, 15.9] pg/mL, 2.445 [1.5, 8.0] pg/mL, p>0.05). In addition, regular treatment had no effect on Hb levels, PLT count, ALT levels, AST levels, BUN levels and Scr levels (123.500 [110.8, 139.8]g/L vs 131.000 [102.0, 137.8]g/L, 195.500 [156.5, 270.5]×109/L vs 217.000 [177.8, 342.8]×109/L, 25.500 [20.3, 52.3] U/L vs 31.500 [20.0, 49.8]U/L, 34.000 [24.5, 44.5] U/L vs 25.500 [18.3, 33.8]U/L, 4.480 [3.2, 5.5] mmol/L vs 4.405 [3.3, 5.9] mmol/L, 61.150 [52.0, 74.8] μmol/L vs 60.600 [53.8, 68.5]μmol/L, repectively. All p>0.05) (Table 2).
Comparison of laboratory results in rIL–2 group and non-rIL–2 group patients after rIL–2 treatment
Compared to non-IL–2 group, rIL–2 group had a significant higher level of lymphocytes, which was 1.935 (1.6, 3.0)×109/L in rIL–2 group vs 1.275 (1.0, 1.6)×109/L in non-rIL–2 group (p<0.01). The level of CRP did not show a significant difference between the two groups (3.965 [1.5, 5.7] mg/L in rIL–2 group vs 4.585 [2.8, 12.1] mg/L in non-rIL–2 group, p>0.05). There were no difference in WBC count, neutrophils count and IL–6 levels between the two groups (6.935 [5.2, 8.3]×109/L vs 6.075 [4.6, 7.7]×109/L, p>0.05; 3.075 [2.2,4.3]×109/L vs 3.925 [2.8, 5.8]×109/L, p>0.05; 3.730 [1.5, 7.7] pg/mL vs 2.445 [1.5, 8.0] pg/mL, p>0.05, respectively). The length of hospital stay between the two groups made no difference (34.00 [20.09,47.91] days vs 32.70 [17.07,48.33] days, p>0.05) (Table 2).
Drug associated adverse effects of rIL–2 treatment
After regular treatment such as antiviral drugs, antibiotics, corticosteroids and traditional Chinese medicine, all participants were in normal temperature. In rIL–2 treatment group, 4 (20%) cases of fever associated with rIL–2 were reported with the temperature lowered than 38.5℃ for less than 4 days. The patients complained muscle soreness accompanied with fever. No patients with new fever onset was reported in non-rIL–2 group. The difference was significant (p<0.05). However, rIL–2 treatments did not make obvious change in Hb, PLT count, ALT, AST, BUN and Scr levels (p>0.05) (Table 2).