Table 1. Demographics and clinical characteristics of subjects
Factors
|
Control group
(n= 273)
|
COVID-19
|
Total (n= 91)
|
Moderate group (n= 69)
|
Severe group (n= 22)
|
Age (years)
|
47.55 ± 15.33
|
47.53 ± 15.43
|
44.00 ± 14.32
|
58.59 ± 13.69†, ‡
|
Gender (male/female)
|
120/153
|
40/51
|
26/43
|
14/8‡
|
BMI (kg/m2)
|
23.58 ± 3.38
|
23.57 ± 3.49
|
23.18 ± 3.41
|
24.95 ± 3.49‡
|
HGB (g/L)
|
141.99 ± 13.60
|
138.23 ± 17.39
|
138.48 ± 16.61
|
137.45 ± 20.34
|
LEU*(*109/L)
|
1.73 ± 0.24
|
1.59 ± 0.32†
|
1.59 ± 0.32†
|
1.58 ± 0.32†
|
LYM%
|
35.92 ± 7.90
|
32.54 ± 10.46†
|
34.17 ± 9.72
|
27.43 ± 11.27†, ‡
|
eGFR* (ml/min*1.73m2)
|
4.70 ±0.15
|
4.66 ± 0.15†
|
4.68 ± 0.15
|
4.57 ± 0.13†, ‡
|
AST* (U/L)
|
3.06 ± 0.29
|
3.03 ± 0.39
|
2.96 ± 0.36
|
3.24 ± 0.41†, ‡
|
ALB/GLB
|
1.74 ± 0.24
|
1.35 ± 0.22†
|
1.38 ± 0.22†
|
1.24 ± 0.18 †, ‡
|
α-HBDH* (U/L)
|
4.91 ± 0.17
|
4.90 ± 0.23
|
4.84 ± 0.20†
|
5.06 ± 0.24†, ‡
|
LDH* (U/L)
|
5.14 ± 0.18
|
5.14 ± 0.25
|
5.08 ± 0.22†
|
5.32 ± 0.26†, ‡
|
FPG (mmol/L)
|
4.66 (4.39-5.05)
|
5.31
(4.890-6.18) †
|
5.06
(4.830-5.81) †
|
5.80
(5.340-7.36) †, ‡
|
PaO2/FiO2*
|
-
|
5.94± 0.53
|
6.19 ± 0.25
|
5.12 ± 0.36‡
|
Days from onset to admission
|
-
|
3.0 (1.0-6.0)
|
3.0 (1.00-6.0)
|
4.0 (1.750-6.0)
|
Days from admission to PCR negative)
|
-
|
9.0
(4.00-13.0)
|
8.0
(4.00-10.0)
|
11.50
(4.750-20.75) ‡
|
UA* (μmol/L)
|
|
|
|
|
Total
|
5.80 ± 0.24
|
5.65 ± 0.28†
|
5.66 ± 0.29†
|
5.62 ± 0.25†
|
Male
|
5.95 ± 0.18
|
5.78 ± 0.26†
|
5.86 ± 0.20†
|
5.61 ± 0.28†, ‡
|
Female
|
5.68 ± 0.21
|
5.55 ± 0.26†
|
5.53 ± 0.26†
|
5.63 ± 0.20
|
Creatinine* (μmol/L)
|
|
|
|
|
Total
|
4.14 ± 0.20
|
4.10 ± 0. 26
|
4.08 ± 0.27
|
4.16 ± 0.22
|
Male
|
4.31 ± 0.13
|
4.30 ± 0.21
|
4.32 ± 0.22
|
4.26 ± 0.19
|
Female
|
4.01 ± 0.14
|
3.94 ± 0.18
|
3.93 ± 0.19†
|
4.00 ± 0.15
|
UA/Cr ratio*
|
|
|
|
|
Total
|
1.65 ± 0.20
|
1.55 ± 0.27†
|
1.58 ± 0.24†
|
1.45 ± 0.32†
|
Male
|
1.64 ± 0.20
|
1.48 ± 0.28†
|
1.54 ± 0.23†
|
1.35 ± 0.34†, ‡
|
Female
|
1.67 ± 0.21
|
1.60 ± 0.24†
|
1.60 ± 0.25
|
1.63 ± 0.18
|
Note: Data were expressed as the mean ± standard deviation (SD) or median (P25–P75). Days (from onset to admission): the days from symptom appearance to hospitalization, days (from admission to PCR negative): the days from hospitalization to result of nucleic acid of SARS-CoV-2 negative.
a*: The data were transformed into Ln (a).
Compared with the control group: P<0.05 labeled as †;
Compared with the moderate group: P<0.05 labeled as ‡.
Abbreviations: BMI: body mass index, HGB: hemoglobin, LEU: leukocyte, LYM: lymphocyte, eGFR: estimated glomerular filtration rate, AST: aspartic transaminase, ALB: albumin, GLB: globulin, α-HBDH: α-hydroxybutyrate dehydrogenase, LDH: lactate dehydrogenase, FPG: fasting plasma glucose, UA: uric acid, Cr: creatinine.
Table 2. Association of UA*, UA/Cr ratio* with COVID-19 and gender
|
Model 1
|
Model 2
|
Model 3
|
β (95% CI)
|
β (95% CI)
|
β (95% CI)
|
UA*
|
COVID-19
|
-0.25† (-0. 20, -0.10)
|
-0.21† (-0.20, -0.06)
|
-0.15† (-0.17, -0.01)
|
Male
|
0.50† (0.22, 0.31)
|
0.53† (0.22, 0.33)
|
0.47† (0.19, 0.30)
|
COVID-19*Male
|
-
|
-0.06 (-0.15, 0.06)
|
-0.001 (-0.10, 0.10)
|
UA/Cr ratio*
|
COVID-19
|
-0.21† (-0.16, -0.06)
|
-0.13 (-0.13, 0.01)
|
-0.06 (-0.11, 0.05)
|
Male
|
-0.12† (-0.10, -0.01)
|
-0.07 (-0.09, 0.02)
|
-0.08 (-0.09, -0.02)
|
COVID-19*Male
|
-
|
-0.13 (-0.20, -0.01)
|
-0.11 (-0.18, 0.02)
|
Note: Model 1: Including COVID-19 and gender
Model 2: Including Model 1 and COVID-19*gender
Model 3 of UA*: Including Model 2 and LEU*†, LYM%†, eGFR*†, ALB/GLB, FPG†
Model 3 of UA/Cr ratio*: Including Model 2 and LEU*†, LYM%†, ALB/GLB, FPG
a*: The data were transformed into Ln (a).
†P <0.05
Table 3. Incidence rate ratio of COVID-19 patients
|
UA Group
|
Severe
COVID-19
|
Person-Days
|
Incidence Rate
|
Incidence Rate Ratio (95% CI)
|
Total
|
High-UA (n=45)
|
10 (22.2%)
|
323
|
0.031
|
0.84 (0.36, 1.98)
|
Low-UA (n=45)
|
11 (24.4%)
|
423
|
0.026
|
Male
|
High-UA (n=19)
|
3 (15.8%)
|
152
|
0.020
|
4.05 (1.11, 14.72)
|
Low-UA (n=20)
|
10 (55.0%)
|
123
|
0.081
|
Female
|
High-UA (n=25)
|
6 (24.0%)
|
257
|
0.023
|
0.26 (0.05, 1.29)
|
Low-UA (n=26)
|
2 (7.7%)
|
313
|
0.006
|
Notes: the cut-off point of total patients between high-UA and low-UA is 277μmol /L (Median)
the cut-off point of male patients between high-UA and low-UA is 334μmol /L (Median)
the cut-off point of female patients between high-UA and low-UA is 252μmol /L (Median)
Days referred to the time from admission to the severe period
One patient was not analyzed because he was severe type at admission.
Table 4. Multivariable-adjusted association of clinical characteristics with severe symptoms among 91 COVID-19 patients.
|
Model 1
|
Model 2
|
Characteristics
|
Univariable
|
Multivariable
|
Univariable
|
Multivariable
|
OR
|
95% CI
|
P
|
OR
|
95%CI
|
P
|
OR
|
95%CI
|
P
|
OR
|
95%CI
|
P
|
UA*
|
0.01
|
0.00, 0.30
|
0.01
|
0.15
|
0.002, 11.91
|
0.40
|
——
|
——
|
——
|
——
|
——
|
——
|
UA/Cr ratio*
|
——
|
——
|
——
|
——
|
——
|
——
|
0.07
|
0.004, 1.07
|
0.06
|
2.96
|
0.73, 119.40
|
0.57
|
Age (year)
|
1.07
|
1.02, 1.12
|
0.01
|
1.01
|
0.93, 1.09
|
0.84
|
1.07
|
1.02, 1.12
|
0.01
|
1.02
|
0.94, 1.11
|
0.60
|
BMI (Kg/m2)
|
1.05
|
0.86, 1.28
|
0.61
|
|
|
|
1.05
|
0.86, 1.28
|
0.61
|
|
|
|
LYM%
|
0.90
|
0.83, 0.98
|
0.01
|
0.94
|
0.84, 1.07
|
0.35
|
0.90
|
0.83, 0.98
|
0.01
|
0.96
|
0.86, 1.07
|
0.42
|
eGFR* (ml/min*1.73m2)
|
0.09
|
0.002, 5.38
|
0.25
|
|
|
|
—— —— ——
—— ——- ——
|
—— ——- ——
——- —— ——
|
Creatinine* (mmol/L)
|
0.18
|
0.01, 6.23
|
0.34
|
|
|
|
AST* (U/L)
|
4.75
|
0.71, 31.91
|
0.11
|
|
|
|
4.75
|
0.71, 31.91
|
0.11
|
|
|
|
ALB/GLB
|
0.001
|
0.00, 0.12
|
0.004
|
0.22
|
0.00, 9.59
|
0.22
|
0.001
|
0.00, 0.12
|
0.004
|
0.004
|
0.00, 1.99
|
0.08
|
α-HBDH*
|
93.45
|
3.33, 2625.68
|
0.01
|
113.35
|
0.00, 152226922
|
0.51
|
93.45
|
3.33, 2625.68
|
0.01
|
265.88
|
0.00, 651131887
|
0.46
|
LDH*
|
113.87
|
4.32, 3004.26
|
0.005
|
0.26
|
0.00, 127547.12
|
0.84
|
113.87
|
4.32, 3004.26
|
0.005
|
0.27
|
0.00, 196556.71
|
0.85
|
FPG (mmol/L)
|
1.09
|
0.84, 1.42
|
0.51
|
|
|
|
1.09
|
0.84, 1.42
|
0.51
|
|
|
|
Days from onset of COVID-19 to admission
|
1.07
|
0.91, 1.25
|
0.41
|
|
|
|
1.05
|
0.9, 1.25
|
0.41
|
|
|
|
Diabetes
|
3.45
|
0.50, 23.94
|
0.21
|
|
|
|
3.45
|
0.50, 23.94
|
0.21
|
|
|
|
Hypertension
|
1.45
|
0.240, 8.76
|
0.69
|
|
|
|
1.45
|
0.24, 8.76
|
0.69
|
|
|
|
Abbreviations: BMI: body mass index, HGB: hemoglobin, LEU: leukocyte, LYM: lymphocyte, eGFR: estimated glomerular filtration rate, AST: aspartic transaminase, ALB: albumin, GLB: globulin, α-HBDH: α-hydroxybutyrate dehydrogenase, LDH: lactate dehydrogenase, FPG: fasting plasma glucose, UA: uric acid, Cr: creatinine.
Notes: a*: The data were transformed into Ln (a).
“—” means the characteristic was not been calculated.
Model 1: Including UA*, eGFR*, Creatinine* and other variables.
Model 2: Including UA/Cr ratio* and other variables.
Table 5: Linear mixed effects models of changes in the levels of UA and UA/Cr ratio between severe and moderate symptoms and three time points by gender
Fixed Effects
|
UA
|
UA/Cr ratio
|
Male
|
Female
|
Male
|
Female
|
Effect Size
|
95% CI
|
Effect Size
|
95% CI
|
Effect Size
|
95% CI
|
Effect Size
|
95% CI
|
Moderate
|
Ref
|
Ref
|
Ref
|
Ref
|
Ref
|
Ref
|
Ref
|
Ref
|
Severe
|
-0.17
|
(-0.29, -0.05)
|
0.07
|
(-0.11, 0.24)
|
-0.19
|
(-0.35, -0.04)
|
0.02
|
(-0.15, 0.19)
|
Admission
|
Ref
|
Ref
|
Ref
|
Ref
|
Ref
|
Ref
|
Ref
|
Ref
|
Discharge
|
-0.05
|
(-0.12, 0.01)
|
-0.11
|
(-0.18, -0.04)
|
-0.06
|
(-0.14, 0.01)
|
-0.18
|
(-0.25, -0.12)
|
Follow-up
|
0.04
|
(-0.04, 0.13)
|
0.04
|
(-0.03, 0.11)
|
0.05
|
(-0.04, 0.14)
|
-0.03
|
(-0.10, 0.04)
|