From January 28 to February 25, 2020, a total of 285 patients with confirmed COVID-19 were treated in the Respiratory and Critical Care Unit of Dabie Mountain Regional Medical Center under the jurisdiction of the Shandong Medical Team. Among these patients, 113 (39.6%) were included in the present study. The research flow chart is shown in Fig. 1.
The comparison of baseline data is shown in Table 1. The age of the patients was 55.1 ± 14.2 years, and 52 (46%) patients were female. Among these patients, 39 (34.5%) suffered from comorbidities, including 26 (23.0%) with hypertension, 13 (11.5%) with diabetes, 7 (6.2%) with coronary heart disease, 6 (5.3%) with COPD, and 4 (3.5%) with cerebrovascular diseases. The maximum body temperature before admission was 38.5℃ (37.7–39.0), and the time from onset to hospitalization was 7.0 days (5.0–10.0). Forty-seven patients (41.6%) received IVIG. Compared with patients who did not receive IVIG, fewer patients who received IVIG therapy had coronary heart disease [0 (0) vs 7 (10.6%), P = 0.021]. In addition, patients who received IVIG therapy had a higher body temperature [38.9 (38.2–39.0) vs 38.0 (37.5–38.8), P = 0.002] before hospital admission, a higher white blood cell count [7.45 (4.73–9.42) vs 5.00 (3.68–6.79), P < 0.001], a lower lymphocyte count [0.79 (0.62–1.21) vs 1.24 (0.90–1.75), P < 0.001], and a higher glutamate aminotransferase level [29.7 (18.0–47) vs 21.0 (14.2–29.2), P = 0.008]. More patients in the IVIG group used glucocorticoids [39 (83.0%) vs 18 (27.3%), P < 0.001]. In contrast, there were no statistically significant differences between the groups of patients in age, sex, comorbidities, concurrent hypertension, diabetes, COPD, cerebrovascular disease, platelet count, ALT level, serum creatinine level, PT level and D-dimer level.
Table 1
Demographic data and clinical characteristics of patients in the IVIG and non-IVIG groups
Parameter
|
Total
n = 113
|
Non-IVIG
n = 66
|
IVIG
n = 47
|
P
|
Age
|
55.1 ± 14.2
|
55.3 ± 15.5
|
54.8 ± 12.4
|
0.865
|
Female
|
52 (46.0%)
|
32 (48.5%)
|
20 (42.6%)
|
0.533
|
Comorbidity
|
39 (34.5%)
|
23 (34.8%)
|
16 (34.0%)
|
0.929
|
Hypertension
|
26 (23.0%)
|
14 (21.2%)
|
12 (25.5%)
|
0.591
|
Diabetes
|
13 (11.5%)
|
6 (9.1%)
|
7 (14.9%)
|
0.341
|
Coronary heart disease
|
7 (6.2%)
|
7 (10.6%)
|
0 (0)
|
0.021
|
COPD
|
6 (5.3%)
|
5 (7.6%)
|
1 (2.1%)
|
0.203
|
Cerebrovascular disease
|
4 (3.5%)
|
4 (6.1%)
|
0 (0)
|
0.086
|
Onset time
|
7.0 (5.0–10.0)
|
7.0 (5.0-9.2)
|
7.0 (5.0–10.0)
|
0.268
|
Maximum body temperature
|
38.5 (37.8–39.0)
|
38.0 (37.5–38.8)
|
38.9 (38.2–39.0)
|
0.002
|
WBC
|
5.61 (4.09–8.04)
|
5.00 (3.68–6.79)
|
7.45 (4.73–9.42)
|
< 0.001
|
LYM
|
1.07 (0.72–1.51)
|
1.24 (0.90–1.75)
|
0.79 (0.62–1.21)
|
< 0.001
|
PLT
|
200.0 (153.0-256.0)
|
203.0 (149.8-252.2)
|
190.0 (159.0-257.0)
|
0.836
|
ALT
|
23.0 (16.5–37.2)
|
21.0 (14.2–29.2)
|
29.7 (18.0–47)
|
0.008
|
AST
|
21.0 (17.0–33.0)
|
20.6 (16.8–26.2)
|
22.0 (17.0–40.0)
|
0.287
|
Cr
|
78.1 ± 23.9
|
78.2 ± 24.3
|
78.8 ± 23.6
|
0.896
|
PT
|
44.6 ± 1.3
|
11.4 ± 1.2
|
11.9 ± 1.4
|
0.56
|
DD
|
192.0 (115.0-456.0)
|
182.5 (105.8-294.5)
|
216.0 (125.0-840.0)
|
0.249
|
GC
|
57 (50.4%)
|
18 (27.3%)
|
39 (83.0%)
|
< 0.001
|
Abbreviations: IVIG, intravenous immunoglobulin; COPD, chronic obstructive pulmonary disease; WBC, white blood cell; LYM, lymphocyte; PLT, platelet; ALT, alanine aminotransferase; AST, aspartate aminotransferase; Cr, serum creatinine; PT, prothrombin time; DD, D-dimer; GC, Glucocorticoid.
The outcome indicators are shown in Table 2. A total of 17 (15.0%) patients reached the composite end point, including 13 (11.5%) patients who died and 11 (9.7%) patients who received mechanical ventilation. Compared with the non-IVIG group, more patients in the IVIG group reached the composite end point [12 (25.5%) vs 5 (7.6%), P = 0.008]. Specifically, an increased percentage of patients in the IVIG group died [9 (19.1%) vs 4 (6.1%), P = 0.032] or received mechanical ventilation [10 (21.3%) VS 1 (1.5%), P < 0.001].
Table 2
The effect of IVIG therapy on the primary and secondary prognostic endpoints
Parameter
|
Total
n = 113
|
Non-IVIG
n = 66
|
IVIG
n = 47
|
P
|
P*
|
Composite end point
|
17 (15.0%)
|
5 (7.6%)
|
12 (25.5%)
|
0.008
|
0.167
|
Death
|
13 (11.5%)
|
4 (6.1%)
|
9 (19.1%)
|
0.032
|
-
|
Mechanical ventilation
|
11 (9.7%)
|
1 (1.5%)
|
10 (21.3%)
|
< 0.001
|
-
|
Length of hospital stay
|
20.0 (15.0–25.0)
|
16.0 (13.8–22.0)
|
23.0 (19.0–31.0)
|
< 0.001
|
0.041
|
* Corrected by age, sex, comorbidities, maximum body temperature, WBC, LYM, AST, PT, DD and use of glucocorticoids
The univariate analysis results are provided in Table 3. Several variables were statistically significant differences between patients who reached the prognostic endpoint and those who did not reach the prognostic endpoint; those variables were age [59.0 (52.0-73.5) vs 54.0 (45.2–62.0), P = 0.042], maximum body temperature [38.9 (38.2–39.4) vs 38.4 (37.6–39.0), P = 0.041], female [4 (23.5%) vs 48 (50.0%), P = 0.044], comorbidities [11 (64.7%) vs 28 (29.2%), P = 0.004], white blood cell count [8.43 (6.58–16.21) vs 5.28 (4.02–7.22), P = 0.001], lymphocyte count [36.0 (18.0-45.4) vs 20.6 (17.0–27.0), P = 0.029], AST level [36.0 (18.0-45.4) vs 20.6 (17.0–27.0), P = 0.029], PT (12.9 ± 1.6 vs 11.4 ± 1.2, P < 0.001), D-dimer level [851.0 (217.0-9954.5) vs 172.0 (107.9-285.5), P < 0.001], use of glucocorticoids [14 (82.4%) vs 43 (44.8%), P = 0.004], and use of IVIG [12 (70.6%) vs 35 (36.5%), P = 0.008]. After adjusting for the above confounding factors, there was no statistically significant difference in the rate of reaching the composite end point between the IVIG group and the non-IVIG group (OR = 2.605, 95%CI 0.67–10.10, P = 0.167). Multivariate logistic regression analysis showed that the factors related to reaching the prognostic endpoint included comorbidities (OR = 4.187, 95%CI 1.14–15.41, P = 0.031), white blood cell count (OR = 1.18, 95%CI 1.06–1.31, P = 0.003), and PT (OR = 2.15, 95%CI 1.30–3.54, P = 0.003).
Table 3
Univariate analysis of the patients who reached the composite end point and the patients who failed to reach the composite end point
Parameter
|
Patients who reached the composite end point
n = 96
|
Patients who failed to reach the composite end point
n = 17
|
P
|
Age
|
54.0 (45.2–62.0)
|
59.0 (52.0-73.5)
|
0.042
|
Female
|
48 (50.0%)
|
4 (23.5%)
|
0.044
|
Comorbidity
|
28 (29.2%)
|
11 (64.7%)
|
0.004
|
Hypertension
|
19 (19.8%)
|
7 (41.2%)
|
0.053
|
Diabetes
|
9 (9.4%)
|
4 (23.5%)
|
0.092
|
Coronary heart disease
|
4 (4.2%)
|
3 (17.6%)
|
0.034
|
COPD
|
4 (4.2%)
|
2 (11.8%)
|
0.198
|
Cerebrovascular disease
|
2 (2.1%)
|
2 (11.8%)
|
0.046
|
Time of onset
|
7.0 (5.0–10.0)
|
7.0 (6.5–10.0)
|
0.499
|
Body temperature
|
38.4 (37.6–39.0)
|
38.9 (38.2–39.4)
|
0.041
|
WBC
|
5.28 (4.02–7.22)
|
8.43 (6.58–16.21)
|
0.001
|
LYM
|
1.12 (0.78–1.54)
|
0.67 (0.55–1.03)
|
0.001
|
PLT
|
201.0 (159.2-258.5)
|
191.0 (124.0-213.5)
|
0.086
|
ALT
|
23.0 (15.0-34.7)
|
29.7 (21.5–74.0)
|
0.065
|
AST
|
20.6 (17.0–27.0)
|
36.0 (18.0-45.4)
|
0.029
|
Cr
|
76.6 ± 22.2
|
88.6 ± 30.5
|
0.056
|
PT
|
11.4 ± 1.2
|
12.9 ± 1.6
|
< 0.001
|
DD
|
172.0 (107.9-285.5)
|
851.0 (217.0-9954.5)
|
< 0.001
|
GC
|
43 (44.8%)
|
14 (82.4%)
|
0.004
|
IVIG
|
35 (36.5%)
|
12 (70.6%)
|
0.008
|
Abbreviations: IVIG, intravenous immunoglobulin; COPD, chronic obstructive pulmonary disease; WBC, white blood cell; LYM, lymphocyte; PLT, platelet; ALT, alanine aminotransferase; AST, aspartate aminotransferase; Cr, serum creatinine; PT, prothrombin time; DD, D-dimer; GC, Glucocorticoid.
Analysis of the secondary prognostic endpoints showed that the length of hospital stay was 20.0 days (15.0–25.0). Compared with the non-IVIG group, patients in the IVIG group had a longer hospital stay [23.0 days (19.0–31.0) vs 16.0 (13.8–22.0), P < 0.001]. After adjusting for confounding factors including age, sex, maximum body temperature, comorbidities, AST, hormones, WBC, D-dimer and PT, it was found that the patients in the IVIG group had a significantly longer hospital stay compared with that for the patients in the non-IVIG group (P = 0.041) (Table 2).