The average age of the cohort was 46.3 ± 16.4 years, and approximately 52.8% of them were male. Table 1 compared the baseline demographic, clinical, and biochemical characteristics of included patients by tertiles of the ALB. Compared with subjects in the highest tertile of the ALB, those in the lowest tertile were older, and more likely to have pulmonary disease, whereas participants with chronic liver disease was major in middle tertile of the ALB. Moreover, compared with the lowest tertile group, patients had a significantly higher lymphocyte and hemoglobin, and lower PT and D-dimer in the highest tertile group.
Table 1
Baseline Characteristics of participants according to the tertiles of ALB (n = 199). Values are mean ± SD/median (Q1-Q3) or n (%).
Characteristic
|
ALB (g/L)
|
P-value
|
P-value*
|
|
T1 (26.8–37.8)
|
T2 (38.0-42.3)
|
T3 (42.4–49.8)
|
|
|
No. Of participants
|
66
|
66
|
67
|
|
|
Age, years
|
53.61 ± 16.55
|
45.89 ± 15.02
|
39.49 ± 14.67
|
< 0.001
|
< 0.001
|
Sex
|
|
|
|
0.269
|
-
|
Male
|
31 (46.97%)
|
40 (60.61%)
|
34 (50.75%)
|
|
|
Female
|
35 (53.03%)
|
26 (39.39%)
|
33 (49.25%)
|
|
|
BMI, kg/m2
|
23.68 ± 3.44
|
23.54 ± 3.14
|
23.97 ± 3.70
|
0.776
|
0.768
|
Current smoking
|
|
|
|
0.104
|
-
|
No
|
61 (92.42%)
|
65 (98.49%)
|
60 (89.55%)
|
|
|
Yes
|
5 (7.58%)
|
1 (1.52%)
|
7 (10.45%)
|
|
|
Comorbidities
|
|
|
|
|
|
Hypertension
|
|
|
|
0.180
|
-
|
No
|
53 (80.30%)
|
54 (81.82%)
|
61 (91.05%)
|
|
|
Yes
|
13 (19.70%)
|
12 (18.18%)
|
6 (8.96%)
|
|
|
Diabetes
|
|
|
|
0.213
|
-
|
No
|
58 (87.88%)
|
62 (93.94%)
|
64 (95.52%)
|
|
|
Yes
|
8 (12.12%)
|
4 (6.06%)
|
3 (4.48%)
|
|
|
Cardiovascular disease
|
|
|
|
0.869
|
0.822
|
No
|
63 (95.46%)
|
63 (95.46%)
|
65 (97.02%)
|
|
|
Yes
|
3 (4.55%)
|
3 (4.55%)
|
2 (2.99%)
|
|
|
Chronic kidney disease
|
|
|
|
0.770
|
0.848
|
No
|
64 (96.97%)
|
65 (98.49%)
|
66 (98.51%)
|
|
|
Yes
|
2 (3.03%)
|
1 (1.52%)
|
1 (1.49%)
|
|
|
Pulmonary disease
|
|
|
|
0.008
|
-
|
No
|
58 (87.88%)
|
63 (95.46%)
|
67 (100.00%)
|
|
|
Yes
|
8 (12.12%)
|
3 (4.55%)
|
0 (0.00%)
|
|
|
Tumor
|
|
|
|
0.608
|
0.735
|
No
|
64 (96.97%)
|
64 (96.97%)
|
63 (94.03%)
|
|
|
Yes
|
2 (3.03%)
|
2 (3.03%)
|
4 (5.97%)
|
|
|
Chornic liver disease
|
|
|
|
0.002
|
-
|
No
|
65 (98.49%)
|
57 (86.36%)
|
66 (98.51%)
|
|
|
Yes
|
1 (1.52%)
|
9 (13.64%)
|
1 (1.49%)
|
|
|
Symptoms
|
|
|
|
|
|
Cough
|
|
|
|
0.292
|
-
|
No
|
27 (40.91%)
|
21 (31.82%)
|
30 (44.78%)
|
|
|
Yes
|
39 (59.09%)
|
45 (68.18%)
|
37 (55.22%)
|
|
|
Fever
|
|
|
|
0.077
|
-
|
No
|
14 (21.21%)
|
11 (16.67%)
|
22 (32.84%)
|
|
|
Yes
|
52 (78.79%)
|
55 (83.33%)
|
45 (67.16%)
|
|
|
Chest distress
|
|
|
|
0.052
|
-
|
No
|
56 (84.85%)
|
64 (96.97%)
|
61 (91.05%)
|
|
|
Yes
|
10 (15.15%)
|
2 (3.03%)
|
6 (8.96%)
|
|
|
Dyspnea
|
|
|
|
0.131
|
0.218
|
No
|
64 (96.97%)
|
66 (100.00%)
|
67 (100.00%)
|
|
|
Yes
|
2 (3.03%)
|
0 (0.00%)
|
0 (0.00%)
|
|
|
Fatigue
|
|
|
|
0.068
|
-
|
No
|
41 (62.12%)
|
50 (75.76%)
|
53 (79.10%)
|
|
|
Yes
|
25 (37.88%)
|
16 (24.24%)
|
14 (20.90%)
|
|
|
Expectoration
|
|
|
|
0.197
|
-
|
No
|
42 (63.64%)
|
40 (60.61%)
|
50 (74.63%)
|
|
|
Yes
|
24 (36.36%)
|
26 (39.39%)
|
17 (25.37%)
|
|
|
Headache
|
|
|
|
0.282
|
-
|
No
|
60 (90.91%)
|
60 (90.91%)
|
65 (97.02%)
|
|
|
Yes
|
6 (9.09%)
|
6 (9.09%)
|
2 (2.99%)
|
|
|
Diarrhea
|
|
|
|
0.194
|
-
|
No
|
57 (86.36%)
|
62 (93.94%)
|
63 (94.03%)
|
|
|
Yes
|
9 (13.64%)
|
4 (6.06%)
|
4 (5.97%)
|
|
|
Dizzy
|
|
|
|
0.916
|
-
|
No
|
61 (92.42%)
|
62 (93.94%)
|
63 (94.03%)
|
|
|
Yes
|
5 (7.58%)
|
4 (6.06%)
|
4 (5.97%)
|
|
|
Chills
|
|
|
|
0.819
|
-
|
No
|
60 (90.91%)
|
59 (89.39%)
|
62 (92.54%)
|
|
|
Yes
|
6 (9.09%)
|
7 (10.61%)
|
5 (7.46%)
|
|
|
Laboratory findings
|
|
|
|
|
|
Leukocytes, 10^9/L
|
5.16 ± 1.96
|
5.65 ± 2.95
|
5.49 ± 2.10
|
0.489
|
0.607
|
Neutrophil, 10^9/L
|
3.16 (2.05–4.39)
|
3.29 (2.43–4.16)
|
3.26 (2.22–4.51)
|
0.723
|
0.950
|
Lymphocyte, 10^9/L
|
1.24 ± 0.58
|
1.38 ± 0.66
|
1.58 ± 0.78
|
0.013
|
0.051
|
Platelets, 10^9/L
|
195.15 ± 66.61
|
207.70 ± 85.77
|
207.93 ± 56.73
|
0.494
|
0.335
|
Hemoglobin, g/L
|
129.77 ± 15.76
|
137.88 ± 18.14
|
143.18 ± 17.79
|
< 0.001
|
< 0.001
|
TBIL, µmol/L
|
12.45 (8.70-17.85)
|
12.45 (8.07–16.68)
|
13.00 (7.40–20.60)
|
0.203
|
0.625
|
ALT, U/L
|
22.50 (16.00–30.00)
|
27.50 (19.25–37.18)
|
22.70 (17.50–34.60)
|
0.090
|
0.136
|
AST, U/L
|
25.40 (21.00–32.00)
|
25.00 (21.00–33.00)
|
23.90 (19.00-30.15)
|
0.257
|
0.476
|
LDH, U/L
|
209.50 (164.00-347.75)
|
257.70 (174.75-406.75)
|
217.00 (168.00-436.00)
|
0.711
|
0.591
|
Creatinine, µmol/L
|
68.91 ± 19.73
|
66.93 ± 16.29
|
70.01 ± 17.44
|
0.605
|
0.716
|
BUN, mmol/L
|
3.95 ± 1.67
|
3.93 ± 1.53
|
4.07 ± 1.62
|
0.876
|
0.779
|
CK, U/L
|
70.00 (45.50-140.50)
|
70.30 (42.50-103.75)
|
60.00 (44.00-100.30)
|
0.444
|
0.577
|
CK-MB, U/L
|
9.70 (3.00–14.00)
|
7.35 (1.18-15.00)
|
6.00 (0.81–12.23)
|
0.274
|
0.125
|
PT, sec
|
12.07 ± 0.99
|
12.01 ± 1.01
|
11.61 ± 1.06
|
0.039
|
0.040
|
APTT, sec
|
31.43 ± 5.30
|
30.26 ± 4.30
|
30.87 ± 6.20
|
0.502
|
0.517
|
Fibrinogen, g/L
|
3.77 ± 0.97
|
3.56 ± 0.99
|
3.58 ± 0.92
|
0.426
|
0.289
|
D-dimer, mg/L
|
0.28 (0.18–0.49)
|
0.19 (0.02–0.32)
|
0.23 (0.02–0.34)
|
< 0.001
|
< 0.001
|
Adverse outcomes
|
|
|
|
0.197
|
-
|
No
|
55 (83.33%)
|
60 (90.91%)
|
62 (92.54%)
|
|
|
Yes
|
11 (16.67%)
|
6 (9.09%)
|
5 (7.46%)
|
|
|
ARDS
|
|
|
|
0.152
|
-
|
No
|
59 (89.39%)
|
64 (96.97%)
|
64 (95.52%)
|
|
|
Yes
|
7 (10.61%)
|
2 (3.03%)
|
3 (4.48%)
|
|
|
Respiratory failure
|
|
|
|
0.335
|
-
|
No
|
60 (90.91%)
|
62 (93.94%)
|
65 (97.02%)
|
|
|
Yes
|
6 (9.09%)
|
4 (6.06%)
|
2 (2.99%)
|
|
|
Shock
|
|
|
|
0.360
|
0.549
|
No
|
64 (96.97%)
|
66 (100.00%)
|
64 (96.97%)
|
|
|
Yes
|
2 (3.03%)
|
0 (0.00%)
|
2 (3.03%)
|
|
|
MOF
|
|
|
|
0.372
|
1.000
|
No
|
66 (100.00%)
|
66 (100.00%)
|
66 (98.51%)
|
|
|
Yes
|
0 (0.00%)
|
0 (0.00%)
|
1 (1.49%)
|
|
|
ICU admission
|
|
|
|
0.585
|
-
|
No
|
60 (90.91%)
|
63 (95.46%)
|
62 (92.54%)
|
|
|
Yes
|
6 (9.09%)
|
3 (4.55%)
|
5 (7.46%)
|
|
|
In-hospital mortality
|
|
|
|
0.363
|
0.663
|
No
|
65 (98.48%)
|
66 (100.00%)
|
67 (100.00%)
|
|
|
Yes
|
1 (1.52%)
|
0 (0.00%)
|
0 (0.00%)
|
|
|
*Continuous variable was obtained by Kruskal-Wallis rank sum test. If the count variable had a theoretical number < 10, the probability was calculated accurately using Fisher,s exact test |
BMI Body mass index, TBIL Total bilirubin, ALT alanine transaminase, AST aspartate transaminase, LDH Lactic dehydrogenase, BUN Blood urea nitrogen, CK Creatine kinase, CK-MB Creatine kinase isoenzyme-MB, PT prothrombin time, APTT activated partial thromboplastin time, ALB Albumin, ARDS Acute respiratory distresssyndrome, MOF Multiple organ failure, ICU Intensive Care Unit. |
Table 2 showed the univariate logistic regression models between baseline variables and adverse outcomes. The results of univariate analysis showed that Age (OR = 1.063, 95% CI, 1.033–1.094, P = 0.00003), Hypertension (OR = 4.878, 95% CI, 1.867–12.740, P = 0.00122), Cardiovascular disease (OR = 9.611, 95% CI, 2.213–41.737, P = 0.00252), Pulmonary disease (OR = 5.397, 95% CI, 1.440–20.224, P = 0.01238), Tumor (OR = 5.432, 95% CI, 1.203–24.532, P = 0.02782), Fatigue (OR = 3.023, 95% CI, 1.226–7.454, P = 0.01630), Leukocytes (OR = 1.191, 95% CI, 1.013–1.400, P = 0.03481), Neutrophil (OR = 1.134, 95% CI, 1.003–1.282, P = 0.04522), AST (OR = 1.053, 95% CI, 1.017–1.090, P = 0.00343), LDH (OR = 1.002, 95% CI, 1.000–1.005, P = 0.02875), Creatinine (OR = 1.030, 95% CI, 1.006–1.054, P = 0.01512), BUN (OR = 1.449, 95% CI, 1.155–1.818, P = 0.00135), CK (OR = 1.007, 95% CI, 1.002–1.012, P = 0.00876), Fibrinogen (OR = 1.830, 95% CI, 1.153–2.903, P = 0.01031) and D-dimer (OR = 3.240, 95% CI, 1.465–7.169, P = 0.00371) were positively correlated with the risk of adverse outcomes. The ALB (OR = 0.850, 95% CI, 0.776–0.931, P = 0.00045) was negatively correlated with the risk of adverse outcomes.
Table 2
The results of univariate analysis (n = 199). Values are mean ± SD or n (%)
Adverse outcomes
|
Statistics
|
Odds ratio (95% CIs), P-value
|
Age, years
|
46.3 ± 16.4
|
1.063 (1.033, 1.094) 0.00003
|
Sex
|
|
|
Male
|
105 (52.8%)
|
1.000
|
Female
|
94 (47.2%)
|
0.379 (0.142, 1.014) 0.05333
|
BMI, kg/m2
|
23.7 ± 3.4
|
1.054 (0.905, 1.228) 0.49623
|
Current smoking
|
|
|
No
|
186 (93.5%)
|
1.000
|
Yes
|
13 (6.5%)
|
1.509 (0.312, 7.301) 0.60892
|
Hypertension
|
|
|
No
|
168 (84.4%)
|
1.000
|
Yes
|
31 (15.6%)
|
4.878 (1.867, 12.740) 0.00122
|
Diabetes
|
|
|
No
|
184 (92.5%)
|
1.000
|
Yes
|
15 (7.5%)
|
2.171 (0.562, 8.386) 0.26085
|
Cardiovascular disease
|
|
|
No
|
191 (96.0%)
|
1.000
|
Yes
|
8 (4.0%)
|
9.611 (2.213, 41.737) 0.00252
|
Chronic kidney disease
|
|
|
No
|
195 (98.0%)
|
1.000
|
Yes
|
4 (2.0%)
|
2.762 (0.275, 27.771) 0.38829
|
Pulmonary disease
|
|
|
No
|
188 (94.5%)
|
1.000
|
Yes
|
11 (5.5%)
|
5.397 (1.440, 20.224) 0.01238
|
Tumor
|
|
|
No
|
191 (96.0%)
|
1.000
|
Yes
|
8 (4.0%)
|
5.432 (1.203, 24.532) 0.02782
|
Chornic liver disease
|
|
|
No
|
188 (94.5%)
|
1.000
|
Yes
|
11 (5.5%)
|
0.795 (0.097, 6.525) 0.83105
|
Cough
|
|
|
No
|
78 (39.2%)
|
1.000
|
Yes
|
121 (60.8%)
|
1.145 (0.457, 2.871) 0.77304
|
Fever
|
|
|
No
|
47 (23.6%)
|
1.000
|
Yes
|
152 (76.4%)
|
0.804 (0.295, 2.188) 0.66917
|
Chest distress
|
|
|
No
|
181 (91.0%)
|
1.000
|
Yes
|
18 (9.0%)
|
1.006 (0.215, 4.702) 0.99368
|
Dyspnea
|
|
|
No
|
197 (99.0%)
|
1.000
|
Yes
|
2 (1.0%)
|
8.381 (0.505, 139.005) 0.13790
|
Fatigue
|
|
|
No
|
144 (72.4%)
|
1.000
|
Yes
|
55 (27.6%)
|
3.023 (1.226, 7.454) 0.01630
|
Expectoration
|
|
|
No
|
132 (66.3%)
|
1.000
|
Yes
|
67 (33.7%)
|
1.754 (0.716, 4.300) 0.21909
|
Headache
|
|
|
No
|
185 (93.0%)
|
1.000
|
Yes
|
14 (7.0%)
|
1.375 (0.287, 6.591) 0.69044
|
Diarrhea
|
|
|
No
|
182 (91.5%)
|
1.000
|
Yes
|
17 (8.5%)
|
1.080 (0.230, 5.072) 0.92231
|
Dizzy
|
|
|
No
|
186 (93.5%)
|
1.000
|
Yes
|
13 (6.5%)
|
0.655 (0.081, 5.293) 0.69126
|
Chills
|
|
|
No
|
181 (91.0%)
|
1.000
|
Yes
|
18 (9.0%)
|
0.448 (0.057, 3.543) 0.44675
|
Leukocytes, 10^9/L
|
5.4 ± 2.4
|
1.191 (1.013, 1.400) 0.03481
|
Neutrophil, 10^9/L
|
3.7 ± 2.7
|
1.134 (1.003, 1.282) 0.04522
|
Lymphocyte, 10^9/L
|
1.4 ± 0.7
|
0.441 (0.194, 1.001) 0.05035
|
Platelets, 10^9/L
|
203.6 ± 70.6
|
0.995 (0.988, 1.003) 0.21206
|
Hemoglobin, g/L
|
137.0 ± 18.0
|
0.980 (0.958, 1.003) 0.09441
|
TBIL, µmol/L
|
14.3 ± 8.2
|
1.017 (0.966, 1.070) 0.52417
|
ALT, U/L
|
28.9 ± 17.3
|
1.005 (0.981, 1.029) 0.70716
|
AST, U/L
|
27.1 ± 10.8
|
1.053 (1.017, 1.090) 0.00343
|
LDH, U/L
|
295.7 ± 170.9
|
1.002 (1.000, 1.005) 0.02875
|
Creatinine, µmol/L
|
68.6 ± 17.8
|
1.030 (1.006, 1.054) 0.01512
|
BUN, mmol/L
|
4.0 ± 1.6
|
1.449 (1.155, 1.818) 0.00135
|
CK, U/L
|
89.2 ± 69.1
|
1.007 (1.002, 1.012) 0.00876
|
CK-MB, U/L
|
8.8 ± 7.7
|
1.011 (0.956, 1.070) 0.70019
|
PT, sec
|
11.9 ± 1.0
|
0.819 (0.510, 1.316) 0.40989
|
APTT, sec
|
30.9 ± 5.3
|
0.928 (0.840, 1.026) 0.14283
|
Fibrinogen, g/L
|
3.6 ± 1.0
|
1.830 (1.153, 2.903) 0.01031
|
D-dimer, mg/L
|
0.3 ± 0.4
|
3.240 (1.465, 7.169) 0.00371
|
ALB, g/L
|
40.2 ± 5.1
|
0.850 (0.776, 0.931) 0.00045
|
Univariate linear regression models were used to evaluate the associations between ALB and adverse outcomes. Meanwhile, we showed the non-adjusted and adjusted models in Table 3. In the crude model, ALB correlated with adverse outcomes (OR = 0.85, 95% CI, 0.78–0.93, P = 0.0004). In the minimally adjusted model (adjusted age, sex, BMI, current smoking), the values also had a significant correlation (OR = 0.88, 95% CI, 0.78–0.99, P = 0.0294). After adjusting other covariates, we still identified the significance in the fully adjusted model (OR = 0.70, 95% CI, 0.56–0.88, P = 0.0020). For the purpose of sensitivity analysis, we also handled ALB as a categorical variable (tertiles) and found the same trend (p for the trend was 0.0303).
Table 3
Relationship between ALB and adverse outcomes in different models
Exposure
|
Crude model
|
Minimally adjusted model
|
Fully adjusted model
|
ALB, g/L
|
0.85 (0.78, 0.93) 0.0004
|
0.88 (0.78, 0.99) 0.0294
|
0.70 (0.56, 0.88) 0.0020
|
ALB (g/L, tertiles)
|
|
|
|
T1
|
Ref
|
Ref
|
Ref
|
T2
|
0.50 (0.17, 1.44) 0.1999
|
0.47 (0.12, 1.91) 0.2921
|
0.14 (0.02, 1.07) 0.0579
|
T3
|
0.40 (0.13, 1.23) 0.1112
|
0.66 (0.16, 2.66) 0.5538
|
0.07 (0.00, 0.86) 0.0377
|
P for trend
|
0.0961
|
0.5074
|
0.0303
|
Crude model: we did not adjust other covariants |
Minimally adjusted model: we adjusted Age; Sex; BMI; Current smoking |
Fully adjusted model: we adjusted Age; Sex; BMI; Current smoking; Hypertension; Cardiovascular disease; Pulmonary disease; Tumor; Chornic liver disease; D-dimer; Creatinine; CK; Leukocytes; Neutrophil; LDH; BUN; Fibrinogen |
CI: confidence interval; Ref: reference |
In the present study, we analysed the non-linear relationship between ALB and adverse outcomes because ALB is a continuous variable (Fig. 1). We found that the relationship between ALB and adverse outcomes was non-linear (after adjusting Age, sex, BMI, current smoking, hypertension, cardiovascular disease, pulmonary disease, tumor, chornic liver disease, D-dimer, creatinine, CK, leukocytes, neutrophil, LDH, BUN and Fibrinogen). By using a two-piecewise linear regression model, we calculated that the inflection point was 32.6. On the right of the inflection point, the odds ratio, 95%CI and P value were 0.908, 0.686 to 1.203 and 0.5032, respectively. However, we also observed a negative relationship between ALB and adverse outcomes on the left side of the inflection point (OR = 0.204, 95% CI, 0.061–0.681, P = 0.0097) (Table 4).
Table 4
The results of the two-piecewise linear regression model
ALB (g/L)
|
Odds ratio (95% CIs)
|
P-value
|
≤ 32.6
|
0.204 (0.061, 0.681)
|
0.0097
|
> 32.6
|
0.908 (0.686, 1.203)
|
0.5032
|
Adjusted: Age; Sex; BMI; Current smoking; Hypertension; Cardiovascular disease; Pulmonary disease; Tumor; Chornic liver disease; D-dimer; Creatinine; CK; Leukocytes; Neutrophil; LDH; BUN; Fibrinogen |
The results of subgroup analysis revealed that interaction effect of age was significant (P for interaction = 0.0113), while the test for interactions were not significant differences for sex, BMI, hypertension, diabetes, pulmonary disease and chornic liver disease (P values for interactions were larger than 0.05) (Cardiovascular disease, Chronic kidney disease and Tumor were not included in subgroup analysis becasuse the sample size in the subgroup was less than 10). (Fig. 2)