The investigated characteristics of the subjects are described in Table 1. Demographics, clinical characteristics, and evaluated laboratory tests between the treatment and control group did not exhibit significant differences except for between: (1) serum creatinine (mg/dl), which was higher in the control group (1.0 [0.8 - 1.1] in the treatment group vs. 1.2 [1.0 - 1.4] in the control group; P = 0.001), (2) white blood cell (WBC) count (1000/mm3), which was also higher in the control group (5.05 [4.20 - 7.00] in the treatment group vs. 6.60 [5.00 – 10.90] in the control group; P = 0.026), and (3) the overall duration of hospitalisation (days) was longer in the treatment group (9 [7 – 13] in the treatment group vs. 7 [6 – 9] in the control group; P = 0.014).
Table 1. Evaluated characteristics of patients with severe COVID-19 infection
|
Total
|
IVIg Group
|
Control Group
|
P-value$
|
|
Age (years)*
|
|
56 (46 ,62)
|
55.5 (45 ,60)
|
56 (47 ,66)
|
0.375
|
Sex n (%)
|
Male
|
41 (69.5)
|
21 (70)
|
20 (68.9)
|
0.931
|
Female
|
18 (30.5)
|
9 (30)
|
9 (31)
|
HTN n (%)
|
|
13 (22)
|
7 (23.3)
|
6 (20.6)
|
0.807
|
DM n (%)
|
|
16 (27.1)
|
6 (20)
|
10 (34.4)
|
0.211
|
Chronic lung disease n (%)
|
2 (3.3)
|
2 (6.6)
|
0 (0)
|
0.157
|
HR/min
|
95 (89 ,105)
|
92.5 (89 ,100)
|
96 (90 ,108)
|
0.280
|
Systolic BP (mmHg)
|
120 (115 ,130)
|
120 (120 ,130)
|
120 (110 ,130)
|
0.428
|
Diastolic BP (mmHg)
|
80 (70 ,80)
|
80 (70 ,80)
|
80 (70 ,80)
|
0.542
|
RR /min
|
19 (18 ,22)
|
19.5 (18 ,22)
|
19 (18 ,21)
|
0.927
|
BT (°C)
|
37.1 (36.7 ,37.7)
|
37.05 (36.5 ,37.8)
|
37.1 (36.9 ,37.6)
|
0.772
|
O2 saturation (%)
|
88 (85 ,89)
|
88 (85 ,89)
|
88 (85 ,89)
|
0.436
|
WBC (1000/mm3)
|
5.6 (4.6 ,8.7)
|
5.0 (4.2 ,7)
|
6.6 (5 ,10.9)
|
0.026
|
Neutrophil (%)
|
78 (70 ,83)
|
74 (70 ,80)
|
80 (74 ,87)
|
0.114
|
Lymphocyte (%)
|
18 (11 ,22)
|
19 (14 ,25)
|
16 (9 ,20)
|
0.085
|
Hb (g/dl)
|
13.9 (12.4 ,15)
|
13.7 (12.2 ,15)
|
14 (13.1 ,15.1)
|
0.309
|
Plt (1000/mm3)
|
190 (137,226)
|
186 (133 ,220)
|
191 (160 ,234)
|
0.457
|
LDH (U/L)
|
591 (444 ,742)
|
545.5 (473 ,705)
|
611 (421 ,800)
|
0.677
|
BUN (mg/dl)
|
34 (27 ,58)
|
30.5 (27 ,46)
|
50 (27 ,68)
|
0.082
|
Creatinine (mg/dl)
|
1.1 (1 ,1.3)
|
1 (0.8 ,1.1)
|
1.2 (1 ,1.4)
|
0.001
|
K (mEq/L)
|
4.1 (3.9 ,4.4)
|
4 (3.9 ,4.5)
|
4.1 (3.9 ,4.3)
|
0.813
|
Na (mEq/L)
|
138 (136 ,140)
|
138 (137 ,140)
|
138 (135 ,143)
|
0.728
|
ESR
|
29 (20 ,46)
|
28 (23 ,50)
|
31 (20 ,41)
|
0.808
|
AST (U/L)
|
31 (21 ,42)
|
34.5 (21 ,53)
|
29 (18 ,40)
|
0.271
|
ALT (U/L)
|
35 (27 ,45)
|
34 (27 ,42)
|
38 (24 ,47)
|
0.596
|
BS (mg/dl)
|
120 (106 ,174)
|
118 (105 ,141)
|
131 (109 ,229)
|
0.295
|
pH
|
7.3 (7.3 ,7.4)
|
7.4 (7.3 ,7.4)
|
7.3 (7.3 ,7.4)
|
0.210
|
PaO2 (mmHg)
|
45 (38 ,49)
|
45 (40 ,49)
|
45 (37 ,50)
|
0.767
|
PCO2 (mmHg)
|
39 (36 ,45)
|
38 (35 ,42)
|
39 (38 ,47)
|
0.084
|
HCO3 (mEq/L)
|
24 (21 ,26)
|
24 (23 ,26)
|
24 (21 ,26)
|
0.522
|
Duration of stay in ICU (days)
|
3 (2 ,6)
|
4 (3 ,6)
|
3 (2 ,4)
|
0.101
|
Duration of hospitalization (days)
|
8 (6 ,11)
|
9 (7 ,13)
|
7 (6 ,9)
|
0.014
|
* Data are presented using median (and IQR), except for the following categories (reported as frequency and percentage): sex, HTN, DM, chronic lung disease. $ Comparison between IVIg and control groups.
IVIg, Intravenous immunoglobulin; HR, Heart rate; BP, Blood pressure; RR, Respiratory rate; BT, Body temperature; WBC, White blood cells; Hb, Hemoglobin; Plt, Platelet; LDH, Lactate dehydrogenase; BUN, Blood urea nitrogen; K, Serum potassium; Na, Serum sodium; ESR, Erythrocyte sedimentation rate; AST, Enzymes aspartate transaminase; ALT, alanine aminotransferase; ALP, Alkaline phosphatase; FBS, Fasting blood sugar; BS, Blood sugar; PaO2, Partial pressure of oxygen, PCO2, Partial pressure of carbon dioxide; HCO3, Bicarbonate; ICU, Intensive care unit.
The in-hospital mortality rate was significantly lower in the treatment group (6 [20.0%] in the treatment group vs 14 [48.3%] in the control group; P = 0.025; Table 2, Figure 1). Univariate regression analysis identified several variables potentially related to the mortality of patients (Table 2). By adjusting these variables, multivariate regression analysis demonstrated that the administration of IVIg had a statistically significant impact on in-hospital mortality and was thus an independent determinant of mortality (aOR = 0.003 [0.001 - 0.815]; P = 0.042). Moreover, increasing age, lower diastolic blood pressure, and increasing serum lactate dehydrogenase (LDH) were other determinants of elevated mortality in patients with severe COVID-19 infection (Table 3).
Table 2. The relationship between study variables and mortality of patients with severe COVID-19
|
Mortality
|
Unadjusted OR (95% CI)
|
P-value
|
|
|
No
|
Yes
|
|
|
|
Groups
|
Treatment
|
15 (38.4)
|
14 (70)
|
0.27 (0.08, 0.85)
|
0.025
|
|
|
Control
|
24 (61.5)
|
6 (30)
|
Ref
|
|
|
Age (years)
|
|
54 (44, 60)
|
60 (53.5, 70)
|
1.05 (1.01, 1.10)
|
0.014
|
Gender n (%)
|
Male
|
27 (70)
|
14 (70)
|
0.96 (0.30, 3.12)
|
0.951
|
Female
|
12 (30)
|
6 (30)
|
Ref
|
|
HTN n (%)
|
8 (23.3)
|
5 (25)
|
1.29 (0.36, 4.63)
|
0.694
|
DM n (%)
|
11 (20)
|
5 (25)
|
0.85 (0.25, 2.90)
|
0.793
|
Chronic lung disease n (%)
|
1 (6.6)
|
1 (5)
|
2.00 (0.12, 33.76)
|
0.630
|
HR/min
|
95 (90, 100)
|
95 (89, 108)
|
1.02 (0.96, 1.08)
|
0.543
|
Systolic BP (mmHg)
|
120 (120, 130)
|
120 (110, 130)
|
0.97 (0.93, 1.01)
|
0.173
|
Diastolic BP (mmHg)
|
80 (70, 80)
|
70 (70, 80)
|
0.95 (0.88, 1.01)
|
0.120
|
RR /min
|
19 (18, 22)
|
20 (18, 22)
|
0.98 (0.93, 1.04)
|
0.545
|
BT (C°)
|
37.1 (36.7, 37.7)
|
37.1 (36.75, 37.65)
|
1.26 (0.63, 2.52)
|
0.518
|
O2 saturation (%)
|
89 (87, 89)
|
85 (80, 88)
|
0.84 (0.74, 0.97)
|
0.015
|
WBC (1000/mm3)
|
5.1 (4.6, 7.4)
|
7.2 (5.1, 11.2)
|
1.00 (1.00, 1.00)
|
0.743
|
Hb (g/dl)
|
13.9 (12.6, 15)
|
13.5 (12.05, 15.25)
|
0.95 (0.80, 1.13)
|
0.566
|
Plt (1000/mm3)
|
210 (135, 247)
|
172.5 (139.5, 193)
|
1.00 (1.00, 1.00)
|
0.090
|
LDH (U/L)
|
520 (400, 687)
|
761 (560.5, 1021)
|
1.00 (1.00, 1.00)
|
0.003
|
BUN (mg/dl)
|
29 (25, 39)
|
64 (50, 129.5)
|
1.06 (1.02, 1.09)
|
0.001
|
Creatinine (mg/dl)
|
1 (1, 1.2)
|
1.2 (1.1, 1.55)
|
3.63 (0.95, 13.87)
|
0.059
|
K (mEq/L)
|
4 (3.7, 4.4)
|
4.2 (4.1, 4.3)
|
0.95 (0.80, 1.14)
|
0.616
|
Na (mEq/L)
|
138 (137, 139)
|
138 (135, 143.5)
|
1.04 (0.95, 1.14)
|
0.344
|
ESR
|
28 (20, 41)
|
40 (26, 49.5)
|
1.01 (0.99, 1.03)
|
0.424
|
AST (U/L)
|
31 (21, 39)
|
29.5 (15.5, 52.5)
|
1.00 (0.97, 1.02)
|
0.735
|
ALT (U/L)
|
34.5 (25, 41)
|
38.5 (29.5, 48)
|
1.01 (0.99, 1.02)
|
0.306
|
BS (mg/dl)
|
119 (105, 174)
|
126 (109.5, 184)
|
1.00 (0.99, 1.01)
|
0.845
|
PaO2 (mmHg)
|
46 (40, 50)
|
39.5 (34, 49)
|
0.92 (0.85, 0.99)
|
0.035
|
PCO2 (mmHg)
|
40 (35, 46)
|
38 (36, 39.5)
|
0.99 (0.91, 1.08)
|
0.798
|
HCO3 (mEq/L)
|
24 (22, 25)
|
24.5 (19.5, 26.5)
|
1.00 (0.89, 1.13)
|
0.946
|
pH
|
7.3 (7.3, 7.4)
|
7.3 (7.2, 7.4)
|
0.04 (0.00, 8.87)
|
0.243
|
|
|
|
|
|
|
|
|
* Data are presented using median (and IQR) except for the following categories (reported as frequency and percentage): sex, HTN, DM, chronic lung disease, treatment group, control group. Variables with P-value less than 0.2 were selected to enter multivariable regression analysis. IVIg, Intravenous immunoglobulin; HR, Heart rate; BP, Blood pressure; RR, Respiratory rate; BT, Body temperature; WBC, White blood cells; Hb, Hemoglobin; Plt, Platelet; LDH, Lactate dehydrogenase; BUN, Blood urea nitrogen; K, Serum potassium; Na, Serum sodium; ESR, Erythrocyte sedimentation rate; AST, Enzymes aspartate transaminase; ALT, Aka alanine aminotransferase, ALP, Alkaline phosphatase; FBS, Fasting blood sugar; BS, Blood sugar; PaO2, Partial pressure of oxygen, PCO2, Partial pressure of carbon dioxide; HCO3, Bicarbonate; ICU, Intensive care unit.
Table 3. Multivariable regression analysis result for prediction of mortality of patients with severe COVID-19
|
Adjusted OR (95% CI)
|
P-value
|
IVIg (Treatment Group)
|
0.003 (0.001, 0.815)
|
0.042
|
|
Age
|
1.485 (1.011, 2.181)
|
0.044
|
Systolic BP
|
1.078 (0.924, 1.258)
|
0.336
|
Diastolic BP
|
0.543 (0.303, 0.972)
|
0.040
|
O2 saturation
|
0.841 (0.621, 1.138)
|
0.262
|
PLT
|
1.000 (0.999, 1.000)
|
0.132
|
LDH
|
1.023 (1.000 ,1.046)
|
0.048
|
BUN
|
1.136 (0.990 ,1.304)
|
0.069
|
Creatinine
|
0.018 (0.001 ,6.085)
|
0.177
|
PaO2
|
0.834 (0.593 ,1.173)
|
0.298
|
|
IVIg, Intravenous immunoglobulin; BP, Blood pressure; LDH, Lactate dehydrogenase; BUN, Blood urea nitrogen; PaO2, Partial pressure of oxygen.