Hypoalbuminemia – An Indicator of the Severity and Prognosis of COVID-19 Patients: A Multicentre Retrospective Analysis

Figures & data

Table 1 Differences in COVID-19 Patients Characteristics Between Hypoalbuminemia and Normal Albumin Group

Indicators	Total (n=482)	Albumin		P value
		Albumin≥35 (n=223,46.3%)	Albumin<35 (n=259,53.7%)
Age, median (IQR)	56(39–67)	44(34–63)	64(49–69)	<0.001
Sex
Male	243(50.4%)	97(43.5%)	146(56.4%)	0.0060
Female	239(49.6%)	126(56.5%)	113(43.6%)
Severity
Nonsevere	294(61.0%)	186(83.4%)	108(41.7%)	<0.001
Severe	188(39.0%)	37(16.6%)	151(58.3%)
Hospital stays, median (IQR) days	13(10–17)	13(10–16)	13(10–18)	0.3000
Comorbidities
Hypertension	122(25.3%)	49(22.1%)	73(28.1%)	0.1310
Diabetes	72(14.9%)	24(10.8%)	48(18.5%)	0.0190
Cardiovascular disease	37(7.7%)	13(5.9%)	24(9.2%)	0.1650
COPD	18(3.7%)	8(3.60%)	10(3.9%)	0.889
Malignancy	15(3.1%)	4(1.80%)	11(4.2%)	0.1260
Autoimmune diseases	15(3.1%)	7(3.17%)	8(3.1%)	0.9610
Signs and symptoms
Fever	424(88.0%)	182(81.6%)	242(93.4%)	<0.001
Rigor	58(12.0%)	22(9.9%)	36(13.9%)	0.1750
Cough	289(60.0%)	130(58.3%)	159(61.4%)	0.4890
Chest distress or pain	145(30.1)	69(30.9%)	76(29.3%)	0.7030
Dyspnea	82(17.0%)	26(11.7%)	56(21.6%)	0.0040
Fatigue	159(33.0%)	69(30.9%)	90(34.8%)	0.4110
Myalgia	193(40.0%)	57(25.6%)	136(52.5%)	<0.001
Nausea	28(5.8%)	9(4.1%)	19(7.3%)	0.1280
Vomiting	27(5.6%)	10(4.5%)	17(6.6%)	0.3340
Diarrhea	129(26.8%)	54(24.2%)	75(29.0%)	0.2410
Complications
ARDS	44(9.1%)	1(0.5%)	43(16.5%)	<0.001
Acute kidney injury	47(9.8%)	16(7.2%)	31(11.9%)	0.0820
Acute cardiac injury	7(1.5%)	3(1.4%)	4(1.5%)	1.0000
DIC	1(0.2%)	0(0%)	1(0.4%)	1.0000
Pulmonary CT presentation on admission
With signs of viral pneumonia	475(98.5%)	217(97.3%)	257(99.2%)	0.2560
No obvious abnormalities	7(1.5%)	6(3.7%)	2(0.8%)
Discharge status
Chest CT normal or fibrosis	49(10.2%)	40(18.0%)	9(3.5%)	<0.001
Chest CT improvement	330(68.8%)	167(75.2%)	163(62.7%)	<0.001
CRP normal	187(38.8%)	113(50.9%)	74(28.46%)	<0.001
Lymphocyte count normal	338(70.1%)	208(93.69%)	130(50%)	<0.001
Treatment after admission
Antiviral	472(97.9%)	215(96.85%)	257(98.85%)	0.1980
Antibiotic	436(90.5%)	194(87.39%)	242(93.08%)	0.0340
Corticosteroid	179(37.1%)	37(16.67%)	142(54.62%)	<0.001
Mechanical ventilation	66(13.7%)	26(11.71%)	40(15.38%)	0.2420
Clinical outcome
Discharged	418(86.7%)	221(99.10%)	197(76.15%)	<0.001
Died	64(13.3%)	2(0.9%)	62(23.85%)

Abbreviations: COVID-19, coronavirus disease 2019; IQR, interquartile range; COPD, chronic obstructive pulmonary disease; ARDS, acute respiratory distress syndrome; DIC, diffuse intravascular coagulation; CRP, C-reactive protein.

Table 2 Laboratory Findings in COVID-19 Patients Characteristics Between Hypoalbuminemia and Normal Albumin Group

Indicators	Total (n=482)	Albumin		P value
		≥35 (223,42.3%)	<35 (259,53.7%)
Albumin, g/L	34.15(30.6–38.0)	38.3(36.6–39.7)	30.8(28.5–32.9)
CRP, mg/L	16.1(3.5–51.3)	4.6(0.8–14.5)	42.3(0.5–9.1)	<0.001
>10	268/461(58.1%)	69/209(33.0%)	199/252(79.0%)	<0.001
WBC count, ×10^9 /L	5.2(3.9–6.9)	4.9(3.8–6.2)	5.6(4.0–7.6)	<0.001
<4	129/481(26.8%)	65/222(29.3%)	64/259(24.7%)	NA
4–10	314/481(65.3%)	156/222(70.3%)	158/259(61.0%)	NA
>10	38/481(7.9%)	1/222(0.5%)	37/259(14.3%)	<0.001
Platelet count, ×10^9 /L	202(149–265)	206(153.3–266.8)	194.5(140.7–258.3)	0.071
Lymphocyte count, ×10^9 /L	1.1(0.73–1.50)	1.37(1.03–1.78)	0.86(0.64–1.24)	<0.001
<1.0	202/481(42.0%)	48/222(21.6%)	154/259(59.4%)	<0.001
Eosinophil count, ×10^9 /L	0.02(0–0.07)	0.04(0.01–0.09)	0.01(0–0.06)	<0.001
<0.02	226/481(47.0%)	72/222(32.4%)	154/259(59.5%)	<0.001
Creatinine, μmol/L	68(57.0–83.7)	66.1(57.4–79.8)	70(56.3–86)	0.074
>133	15/479(3.1%)	3/222(1.4%)	12/257(4.7%)	0.069
ALT, U/L	21(15–35)	19(13.5–28)	24(17–42.3)	<0.001
>40	96/482(19.9%)	25/223(11.2%)	71/259(27.4%)	<0.001
AST, U/L	26(19–37)	22(17–28.5)	32(23–46)	<0.001
>40	98/482(20.3%)	17/223(7.6%)	81/259(31.3%)	<0.001
TBil, μmol/L	9.1(6.6–12.6)	8(6–10.4)	10.4(7.6–13.6)	<0.001
ALP, U/L	64(53–79)	62(52–75)	66(52.7–84)	0.013
γ-GT, U/L	26(16–48)	21(14–36.5)	30(19–62.3)	<0.001
LDH, U/L	244(193–331)	206(177–253)	307.5(235–437)	<0.001
>245	223/450(49.6%)	56/209(26.8%)	167/238(70.2%)	<0.001
CK, μmol/L	70(48–133)	50(3–81.5)	90(51.5–164)	<0.001
>185	42/262(16.0%)	11/120(9.2%)	31/142(21.8%)	0.005
PT, seconds	13.4(12.7–14.2)	13.3(12.8–14)	13.6(12.3–14.4)	0.156
≥16	24/458(5.2%)	2/210(1.0%)	22/248(8.9%)	<0.001
APTT, seconds	37.2(33.1–41.3)	38(34.4–41.7)	36.3(29.7–40.8)	0.006
D-dimer, μg/mL	0.58(0.31–1.33)	0.36(0.22–0.60)	0.95(0.49–2.2)	<0.001
≥0.5	244/446(54.7%)	66/204(32.4%)	178/242(73.6%)	<0.001
Hemoglobin, g/L	129(118–138)	129(120–140)	128(116–137)	0.105
Globulin, g/L	31(27.7–34.5)	29.2(26.3–32.1)	32.7(29.4–36.3)	<0.001

Abbreviations: COVID-19, coronavirus disease 2019; CRP, C-reactive protein; WBC, white blood cell; ALT, alanine aminotransferase; AST, aspartate aminotransferase; TBil, total bilirubin; ALP, alkaline phosphatase; γ-GT, γ-glutamyl transpeptidase; LDH, lactate dehydrogenase; CK, Creatine kinase; PT, Prothrombin time; APTT, activated partial thromboplastin time; NA, not available.

Table 3 Univariate and Multivariate Analysis of COVID-19 Patients with Hypoalbuminemia

Indicators	Univariate Analysis OR (95% CI)	P value	Multivariate Analysis OR (95% CI)	P value
Baseline characteristics
Age, years	1.053(1.04–1.067)	<0.001	1.044(1.025–1.062)	<0.001
Sex, male	1.622(1.131–2.327)	0.009	0.865(0.506–1.477)	0.595
Severity
Severe	5.761(3.807–8.716)	<0.001	2.654(1.528–4.607)	0.001
Diabetes	1.942(1.158–3.255)	0.012	0.907(0.44–1.871)	0.792
Signs and symptoms
Fever	3.207(1.765–5.827)	<0.001	1.908(0.886–4.111)	0.099
Anorexia	2.182(1.508–3.158)	<0.001	1.931(1.165–3.201)	0.011
Dyspnea	2.185(1.311–3.64)	0.003	0.955(0.458–1.991)	0.902
Laboratory findings
CRP, mg/L	1.050(1.039–1.061)	<0.001	1.038(1.024–1.052)	<0.001
WBC count, ×10^9 /L	1.204(1.111–1.296)	<0.001	1.005(0.897–1.16)	0.947
Lymphocyte count, ×10^9/L	0.144(0.092–0.224)	<0.001	0.551(0.303–1.001)	0.050
Eosinophil count, ×10^9/L	0.004(0–0.008)	<0.001	0.322(0.008–13.598)	0.553
Creatinine, μmol/L	1.003(0.998–1.008)	0.177	NA	NA
ALT, U/L	1.012(1.005–1.019)	0.001	1.014(0.997–1.031)	0.108
AST, U/L	1.044(1.029–1.058)	<0.001	0.984(0.953–1.016)	0.317
Total bilirubin, μmol/L	1.095(1.052–1.14)	<0.001	1.012(0.953–1.076)	0.695
ALP, U/L	1.011(1.005–1.018)	0.001	1.004(0.991–1.018)	0.514
γ-GT, U/L	1.008(1.003–1.013)	0.001	0.998(0.992–1.004)	0.599
LDH, U/L	1.01(1.007–1.012)	<0.001	1.001(0.998–1.005)	0.400
CK, μmol/L	1.003(1.002–1.005)	<0.001	0.999(0.997–1.001)	0.328
PT, seconds	1.003(0.977–1.029)	0.827	NA	NA
APTT, seconds	0.991(0.971–1.011)	0.352	NA	NA
D-dimer, μg/mL	1.098(1.042–1.158)	<0.001	0.972(0.907–1.042)	0.426
Hemoglobin, g/L	0.996(0.987–1.004)	0.298	NA	NA
Globulin, g/L	1.152(1.105–1.201)	<0.001	0.999(0.949–1.052)	0.963

Abbreviations: COVID-19, coronavirus disease 2019; OR, odds ratio; CI, confidence interval; CRP, C-reactive protein; WBC, white blood cell; ALT, alanine aminotransferase; AST, aspartate aminotransferase; TBil, total bilirubin; ALP, alkaline phosphatase; γ-GT, γ-glutamyl transpeptidase; LDH, lactate dehydrogenase; CK, Creatine kinase; PT, Prothrombin time; APTT, activated partial thromboplastin time; NA, not available.

Table 4 Univariate and Multivariate Analysis of COVID-19 Patients with Severity

Indicators	Univariate Analysis OR (95% CI)	P value	Multivariate Analysis OR (95% CI)	P value
Baseline characteristics
Age, years	1.034(1.021–1.046)	<0.001	1.011(0.995–1.027)	0.178
Signs and symptoms
Anorexia	1.497(1.037–2.163)	0.031	0.936(0.599–1.464)	0.773
Fever	3.213(1.621–6.369)	0.001	1.806(0.831–3.929)	0.136
Laboratory findings
Hypoalbuminemia	5.761(3.807–8.716)	<0.001	2.121(1.258–3.577)	0.005
WBC count, ×10^9 /L	1.258(1.164–1.359)	<0.001	1.17(1.037–1.32)	0.011
Eosinophil count, ×10^9 /L	0	<0.001	0.003(0–0.382)	0.019
Lymphocyte count, ×10^9 /L	0.171(0.109–0.267)	<0.001	0.432(0.248–0.755)	0.003
CRP, mg/L	1.019(1.014–1.024)	<0.001	0.999(0.992–1.006)	0.761
AST, U/L	1.021(1.012–1.031)	<0.001	0.992(0.98–1.004)	0.196
LDH, U/L	1.008(1.006–1.01)	<0.001	1.004(1.001–1.007)	0.009
D-dimer, μg/mL	1.129(1.072–1.19)	<0.001	1.017(0.969–1.067)	0.496

Abbreviations: COVID-19, coronavirus disease 2019; OR, odds ratio; CI, confidence interval; WBC, white blood cell; CRP, C-reactive protein; AST, aspartate aminotransferase; LDH, lactate dehydrogenase.

Table 5 Univariate and Multivariate Analysis of COVID-19 Patients with Abnormal Liver Biochemistries

Indicators	Univariate Analysis OR (95% CI)	P value	Multivariate Analysis OR (95% CI)	P value
Severity
Severe	2.266(1.558–3.297)	<0.001	1.46(0.901–2.364)	0.124
Complications
Diabetes	1.52(0.929–2.487)	0.095	1.183(0.666–2.102)	0.566
Signs and symptoms
Fever	4.838(2.239–10.455)	<0.001	3.075(1.349–7.011)	0.008
Anorexia	1.918(1.325–2.776)	0.001	1.732(1.126–2.663)	0.012
Dyspnea	2.568(1.577–4.183)	<0.001	1.719(0.976–3.03)	0.061
Laboratory findings
Albumin, g/L	2.760(1.884–4.045)	<0.001	1.434(0.861–2.389)	0.166
Globulin, g/L	1.085(1.046–1.127)	<0.001	1.026(0.981–1.073)	0.267
CRP, mg/L	1.013(1.009–1.018)	<0.001	1.006(0.999–1.012)	0.073
WBC count, ×10^9 /L	1.066(1.006–1.131)	0.031	0.964(0.883–1.053)	0.421
Lymphocyte count, ×10^9 /L	0.547(0.384–0.779)	0.001	1.199(0.747–1.925)	0.451
Eosinophil count, ×10^9 /L	0.006(0–0.185)	0.003	0.089(0.002–3.198)	0.185
ALT, U/L	1.02(1.012–1.028)	<0.001	1.014(1.001–1.028)	0.036
AST, U/L	1.03(1.019–1.041)	<0.001	1.002(0.982–1.022)	0.869
ALP, U/L	1.007(1.001–1.012)	0.017	0.997(0.987–1.006)	0.475
γ-GT, U/L	1.008(1.003–1.012)	<0.001	1.003(0.998–1.009)	0.211
LDH, U/L	1.002(1.001–1.003)	<0.001	0.999(0.998–1.001)	0.456
APTT, seconds	1.034(1.009–1.058)	0.007	1.04(1.012–1.07)	0.005

Abbreviations: COVID-19, coronavirus disease 2019; OR, odds ratio; CI, confidence interval; CRP, C-reactive protein; WBC, white blood cell; ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase; γ-GT, γ-glutamyl transpeptidase; LDH, lactate dehydrogenase; APTT, activated partial thromboplastin time.

Table 6 Univariate and Multivariate Analysis of COVID-19 Patients with Death

Indicators	Univariate Analysis OR (95% CI)	P value	Multivariate Analysis OR (95% CI)	P value
Sex, male	1.906 (1.105–3.289)	0.02	0.854 (0.225–3.232)	0.816
Age, years	1.098 (1.069–1.128)	<0.001	1.126 (1.056–1.2)	<0.001
Diabetes	2.938 (1.614–5.348)	<0.001	2.444 (0.634–9.42)	0.194
Fever	9.947 (1.353–73.143)	0.024	15.352 (0.641–367.512)	0.092
Dyspnea	4.516 (2.544–8.016)	<0.001	3.007 (0.835–10.82)	0.092
CRP, mg/L	1.025 (1.019–1.03)	<0.001	0.996 (0.983–1.009)	0.557
WBC count, ×10^9 /L	1.602 (1.431–1.794)	<0.001	1.373 (1.097–1.72)	0.006
Lymphocyte count, ×10^9 /L	0.024 (0.009–0.063)	<0.001	0.321 (0.056–1.827)	0.2
Eosinophil count, ×10^9 /L	0 (0–0)	<0.001	0 (0–0.004)	0.016
Albumin, g/L	34.777 (8.397–144.036)	<0.001	4.012 (0.317–50.806)	0.283
Globulin, g/L	1.175 (1.109–1.244)	<0.001	0.944 (0.817–1.089)	0.427
AST, U/L	1.024 (1.015–1.034)	<0.001	0.98 (0.952–1.009)	0.171
Creatinine, μmol/L	1.007 (1.002–1.013)	0.01	1.006 (0.997–1.016)	0.207
TBil, μmol/L	1.146 (1.095–1.199)	<0.001	1.028 (0.9101.161)	0.657
ALP, U/L	1.009 (1.003–1.015)	0.004	1 (0.98–1.02)	0.997
LDH, U/L	1.013 (1.01–1.015)	<0.001	1.011 (1.005–1.017)	0.001
CK, μmol/L	1.003 (1.002–1.005)	<0.001	1 (0.996–1.003)	0.953
APTT, seconds	1.054 (1.018–1.091)	0.003	1.14 (1.044–1.244)	0.003
D-dimer, μg/mL	1.2 (1.143–1.26)	<0.001	1.057 (0.978–1.142)	0.161

Abbreviations: COVID-19, coronavirus disease 2019; OR, odds ratio; CI, confidence interval; CRP, C-reactive protein; WBC, white blood cell; AST, aspartate aminotransferase; TBil, total bilirubin; ALP, alkaline phosphatase; LDH, lactate dehydrogenase; CK, Creatine kinase; APTT, activated partial thromboplastin time.

Table 7 Linear Regression Analysis of Hospital Stays for Patients with COVID-19

Indicators	Univariate Linear Regression		P	Multiple Linear Regression		P
	β	95% CI		β	95% CI
Age, years	−0.004	(−0.038, 0.03)	0.828	NA	NA	NA
Anorexia	0.751	(−0.325, 1.827)	0.171	NA	NA	NA
Fever	1.429	(−0.116, 2.973)	0.070	NA	NA	NA
Severe	2.647	(1.518, 3.777)	<0.001	1.84	(0.686, 2.995)	0.002
Hypoalbuminemia	2.672	(1.634, 3.71)	<0.001	1.479	(0.3, 2.658)	0.014
Lymphocytopenia	0.289	(−0.79, 1.367)	0.599	NA	NA	NA
CRP, mg/L	0.035	(0.021, 0.049)	<0.001	0.021	(0.005, 0.036)	0.010

Abbreviations: COVID-19, coronavirus disease; CI, confidence interval; CRP, C-reactive protein; NA, not available.

Table 8 Linear Regression Analysis of Days Between the Appearance of Hypoalbuminemia and Hospital Admission in Patients with COVID-19 and Hypoalbuminemia

Indicators	Univariate Linear Regression		P	Multiple Linear Regression		P
	β	95% CI		β	95% CI
Age, years	−0.039	(−0.066, −0.012)	0.005	−0.031	(−0.058, −0.004)	0.024
Dyspnea	−1.182	(−2.127, −0.237)	0.014	−0.716	(−1.659, 0.226)	0.136
C-reactive protein, mg/L	−0.014	(−0.02, −0.007)	0	−0.009	(−0.016, −0.001)	0.02
WBC count, ×10^9 /L	−0.17	(−0.27, −0.069)	0.001	−0.085	(−0.195, 0.026)	0.133

Abbreviations: COVID-19, coronavirus disease 2019; CI, confidence interval; CRP, C-reactive protein; WBC, white blood cell.

Figure 1 Changes in albumin and other laboratory tests before and after enteral nutrition therapy in 10 patients with COVID-2019 and hypoalbuminemia. Statistical analysis was achieved by the t-test. **P < 0.01, ***P < 0.001 and ****P< 0.0001.

Abbreviations: COVID-19, coronavirus disease 2019; WBC, White blood cell; CRP, C-reactive protein; LDH, Lactate dehydrogenase.