J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website https://www.jocmr.org

Original Article

Volume 13, Number 5, May 2021, pages 258-267

Low Serum Albumin Predicts Severe Outcomes in COVID-19 Infection: A Single-Center Retrospective Case-Control Study

Figure 1. Flow diagram of eligible patient selection. RT-PCR: reverse transcriptase polymerase chain reaction; SARS-CoV-2: severe respiratory syndrome coronavirus 2.

**Table 1.** Study Definition
Study variables	Definitions
Coronavirus disease 2019 (COVID-19) patients	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detected on reverse transcriptase-polymerase chain reaction (RT-PCR) of nasopharyngeal swab
Hypoalbuminemia (low albumin)	Serum albumin less than 3.5 g/dL
Mild low albumin	Serum albumin 2.5 - 3.4 g/dL
Very low albumin	Serum albumin less than 2.5 g/dL
Composite outcome (at least one of the following complications	Death, acute encephalopathy, acute kidney injury, the requirement of new renal replacement therapy, acute hypercoagulability, acute circulatory failure, new-onset heart failure, acute cardiac injury, acute arrhythmia, ARDS, high flow oxygen support, intensive care unit (ICU) stay, mechanical ventilation.
Death	Death due to any cause within 21 days
Chronic kidney disease (CKD)	Glomerular filtration rate < 60 mL/min (CKD 3-5)
Smoking	Active smoker with > 100 cigarettes smoking in lifetime
Alcohol dependency	Men ≥ 15 drinks/week; female ≥ 8 drinks/week
Malignancy	Cancer patient getting active treatment or finished treatment within 6 months
Onset of symptoms	First day of onset of symptoms to presentation to hospital in days
Use of one of the following medicines	Tocilizumab, remdesivir, dexamethasone and/or convalescent plasma
Secondary infection (one of the following)	Procalcitonin level > 0.5; lactic acid > 2.0; positive blood; urine; body fluid; respiratory secretion culture
Quick sequential organ failure assessment (qSOFA)	Altered mental status, respiratory rate ≥ 22/min, systolic blood pressure ≤ 100 mm Hg
Acute kidney injury	Increase in serum creatinine by 0.3 mg/dL or more within 48 h or increase in serum creatinine to 1.5 times baseline or more within the last 7 days
New renal replacement therapy (RRT)	The requirement of new RRT within 21 days in patients who were not dialysis-dependent
Acute encephalopathy	Worsening of alertness and awareness compared to baseline, and/or change in mental status
Acute liver injury	Development of severe acute liver injury (aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 times normal) with encephalopathy and impaired synthetic function (INR of ≥ 1.5) in a patient without cirrhosis or preexisting liver disease
Acute hypercoagulability	D-dimer level > 0.5 ng/mL
Stroke	New focal neurological deficit and/or radiological evidence in computed tomography (CT) or magnetic resonance imaging (MRI)
Acute circulatory failure	Systolic blood pressure (SBP) less than 90 mm Hg and/or requiring pressure support
Acute cardiac injury	Increase in serum troponin value of > 0.015 in two occasions 6 h apart, and or ST-segment elevation or depression in electrocardiogram (EKG)
Arrhythmia	New-onset rhythm disorder proven on 12-lead EKG on two separate occasions
New-onset heart failure	New-onset systolic or diastolic heart failure on echocardiogram
Acute respiratory distress syndrome (ARDS)	The PaO₂/FiO₂ ≤ 300 mm Hg, on ventilator settings that include positive end-expiratory pressure (PEEP) or continuous positive airway pressure (CPAP) ≥ 5 cm H₂O.
High flow oxygen support	Requiring high flow oxygen of 15 L or more to maintain an oxygen saturation of 92% or more
New-onset oxygen dependency	Any amount of supplemental oxygen required to maintain an oxygen saturation of 92% and above on discharge
Physical debility	Discharge to a skilled nursing facility or rehabilitation center
Obesity	Body mass index (BMI) of 30.0 or higher

Table 1. Study Definition

Study variables

Definitions

Coronavirus disease 2019 (COVID-19) patients

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detected on reverse transcriptase-polymerase chain reaction (RT-PCR) of nasopharyngeal swab

Hypoalbuminemia (low albumin)

Serum albumin less than 3.5 g/dL

Mild low albumin

Serum albumin 2.5 - 3.4 g/dL

Very low albumin

Serum albumin less than 2.5 g/dL

Composite outcome (at least one of the following complications

Death, acute encephalopathy, acute kidney injury, the requirement of new renal replacement therapy, acute hypercoagulability, acute circulatory failure, new-onset heart failure, acute cardiac injury, acute arrhythmia, ARDS, high flow oxygen support, intensive care unit (ICU) stay, mechanical ventilation.

Death

Death due to any cause within 21 days

Chronic kidney disease (CKD)

Glomerular filtration rate < 60 mL/min (CKD 3-5)

Smoking

Active smoker with > 100 cigarettes smoking in lifetime

Alcohol dependency

Men ≥ 15 drinks/week; female ≥ 8 drinks/week

Malignancy

Cancer patient getting active treatment or finished treatment within 6 months

Onset of symptoms

First day of onset of symptoms to presentation to hospital in days

Use of one of the following medicines

Tocilizumab, remdesivir, dexamethasone and/or convalescent plasma

Secondary infection (one of the following)

Procalcitonin level > 0.5; lactic acid > 2.0; positive blood; urine; body fluid; respiratory secretion culture

Quick sequential organ failure assessment (qSOFA)

Altered mental status, respiratory rate ≥ 22/min, systolic blood pressure ≤ 100 mm Hg

Acute kidney injury

Increase in serum creatinine by 0.3 mg/dL or more within 48 h or increase in serum creatinine to 1.5 times baseline or more within the last 7 days

New renal replacement therapy (RRT)

The requirement of new RRT within 21 days in patients who were not dialysis-dependent

Acute encephalopathy

Worsening of alertness and awareness compared to baseline, and/or change in mental status

Acute liver injury

Development of severe acute liver injury (aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 times normal) with encephalopathy and impaired synthetic function (INR of ≥ 1.5) in a patient without cirrhosis or preexisting liver disease

Acute hypercoagulability

D-dimer level > 0.5 ng/mL

Stroke

New focal neurological deficit and/or radiological evidence in computed tomography (CT) or magnetic resonance imaging (MRI)

Acute circulatory failure

Systolic blood pressure (SBP) less than 90 mm Hg and/or requiring pressure support

Acute cardiac injury

Increase in serum troponin value of > 0.015 in two occasions 6 h apart, and or ST-segment elevation or depression in electrocardiogram (EKG)

Arrhythmia

New-onset rhythm disorder proven on 12-lead EKG on two separate occasions

New-onset heart failure

New-onset systolic or diastolic heart failure on echocardiogram

Acute respiratory distress syndrome (ARDS)

The PaO₂/FiO₂ ≤ 300 mm Hg, on ventilator settings that include positive end-expiratory pressure (PEEP) or continuous positive airway pressure (CPAP) ≥ 5 cm H₂O.

High flow oxygen support

Requiring high flow oxygen of 15 L or more to maintain an oxygen saturation of 92% or more

New-onset oxygen dependency

Any amount of supplemental oxygen required to maintain an oxygen saturation of 92% and above on discharge

Physical debility

Discharge to a skilled nursing facility or rehabilitation center

Obesity

Body mass index (BMI) of 30.0 or higher

**Table 2.** Abbreviations, Normal Ranges and Units
Abbreviations	Full forms	Normal ranges and units (where applicable)
AKI	Acute kidney injury
Albumin		3.5 - 5.0 g/dL
ALT	Alanine aminotransferase	12 - 78 U/L
AMS	Altered mental status
AST	Aspartate aminotransferase	15 - 37 U/L
CAD	Coronary artery disease
CHF	Congestive heart failure
CKD	Chronic kidney disease
COPD	Chronic obstructive pulmonary disease
COVID-19	Coronavirus disease 2019
CRP	C-reactive protein	< 3 mg/L
D-dimer		0.9 - 0.5 mg/dL
DM	Diabetes mellitus
ESR	Erythrocyte sedimentation rate	0 - 15 mm/h
ESRD on HD	End-stage renal disease on hemodialysis
Ferritin		26 - 388 ng/mL
HIV	Human immunodeficiency virus
HTN	Hypertension
IL-6	Interleukin-6	0 - 13 pg/mL
INR	International normalized ratio
Lactic acid		0.4 - 2 mmol/L
LDH	Lactate dehydrogenase	87 - 241 U/L
LO	Length of
Lymphocyte		0.9 - 2.9 × 10³/µL
Neutrophil		1.7 - 7 × 10³/µL
NL ratio	Neutrophil to lymphocyte ratio
Platelets		150 - 450 × 10³/µL
Procalcitonin		0.07 - 0.5 ng/mL
qSOFA	Quick sequential organ failure assessment
RT-PCR	Reverse transcriptase-polymerase chain reaction
SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2
SOB	Shortness of breath

Table 2. Abbreviations, Normal Ranges and Units

Abbreviations

Full forms

Normal ranges and units (where applicable)

AKI

Acute kidney injury

Albumin

3.5 - 5.0 g/dL

ALT

Alanine aminotransferase

12 - 78 U/L

AMS

Altered mental status

AST

Aspartate aminotransferase

15 - 37 U/L

CAD

Coronary artery disease

CHF

Congestive heart failure

CKD

Chronic kidney disease

COPD

Chronic obstructive pulmonary disease

COVID-19

Coronavirus disease 2019

CRP

C-reactive protein

< 3 mg/L

D-dimer

0.9 - 0.5 mg/dL

Diabetes mellitus

ESR

Erythrocyte sedimentation rate

0 - 15 mm/h

ESRD on HD

End-stage renal disease on hemodialysis

Ferritin

26 - 388 ng/mL

HIV

Human immunodeficiency virus

HTN

Hypertension

IL-6

Interleukin-6

0 - 13 pg/mL

INR

International normalized ratio

Lactic acid

0.4 - 2 mmol/L

LDH

Lactate dehydrogenase

87 - 241 U/L

Length of

Lymphocyte

0.9 - 2.9 × 10³/µL

Neutrophil

1.7 - 7 × 10³/µL

NL ratio

Neutrophil to lymphocyte ratio

Platelets

150 - 450 × 10³/µL

Procalcitonin

0.07 - 0.5 ng/mL

qSOFA

Quick sequential organ failure assessment

RT-PCR

Reverse transcriptase-polymerase chain reaction

SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2

SOB

Shortness of breath

**Table 3.** Baseline Characteristics of Normal and Low Serum Albumin Groups
	NSA vs. LSA group (primary group)	MLA vs. VLA group (subgroup)
*Significant P-values. NSA: normal serum albumin; LSA: low serum albumin; MLA: medium low albumin; VLA: very low albumin; m: mean; SD: standard deviation; n: number; CKD: chronic kidney disease; ESRD: end-stage renal disease; HD: hemodialysis; COPD: chronic obstructive pulmonary disease; CHF: congestive heart disease; CAD: coronary artery disease; HIV: human immunodeficiency virus; SOB: shortness of breath; AMS: altered mental status; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein; NL: neutrophil to lymphocyte; IL-6: interleukin-6; LDH: lactate dehydrogenase.
Age, m (SD)	56.76 (16.18)	55.67 (18.23)	0.68	55.91 (18.90)	54.68 (15.26)	0.59
Female, n (%)	18 (42.86)	150 (48.39)	0.50	109 (43.78)	41 (67.21)	0.001*
Race			0.48			0.01*
White, n (%)	10 (23.81)	73 (23.55)		49 (19.76)	23 (37.70)
African American, n (%)	24 (57.14)	152 (49.03)		126 (50.81)	26 (42.62)
Others, n (%)	8 (196.05)	85 (27.42)		73 (29.44)	12 (19.67)
Comorbid conditions
Diabetes mellitus, n (%)	20 (47.62)	111 (35.81)	0.13	95 (38.15)	16 (26.23)	0.08
Hypertension, n (%)	34 (80.95)	191 (61.61)	0.014*	155 (62.25)	36 (59.02)	0.64
CKD, n (%)	15 (35.71)	53 (17.10)	0.004*	41 (16.47)	12 (19.67)	0.55
ESRD on HD, n (%)	5 (11.90)	21 (6.77)	0.23	18 (7.23)	3 (4.92)	0.52
COPD, n (%)	4 (9.52)	31 (10)	0.92	25 (10.04)	6 (9.84)	0.96
Other lung diseases, n (%)	5 (11.90)	47 (15.21)	0.57	36 (14.52)	11 (18.03)	0.49
CHF, n (%)	7 (16.67)	37 (11.94)	0.38	29 (11.65)	8 (13.11)	0.75
CAD, n (%)	11 (26.19)	55(17.74)	0.18	45 (18.07)	10 (16.39)	0.75
HIV, n (%)	1 (2.38)	6 (1.94)	0.84	1 (0.40)	5 (8.20)	< 0.001*
Malignancy, n (%)	6 (14.29)	24 (7.74)	0.15	19 (7.63)	5 (8.20)	0.88
Smoking, n (%)	11 (26.19)	55 (18.52)	0.24	39 (16.53)	16 (26.23)	0.082
Alcohol dependency, n (%)	4 (9.52)	22 (7.10)	0.53	19 (7.63)	3 (4.92)	0.46
Obesity, n (%)	18 (42.86)	161 (51.94)	0.26	129 (51.81)	32 (52.46)	0.92
Cirrhosis, n (%)	1 (2.38)	5 (1.62)	0.72	4 (1.61)	1 (1.64)	0.98
Symptoms
Onset of symptoms (days), m (SD)	4.11 (3.6)	5.62 (4.97)	0.018*	5.52 (5.03)	5.98 (4.76)	0.51
Fever, n (%)	27 (64.29)	182 (58.90)	0.50	146 (58.63)	36 (59.02)	0.95
Cough, n (%)	31 (73.81)	194 (62.78)	0.16	150 (60.24)	44 (72.13)	0.085
SOB, n (%)	25 (59.52)	198 (64.08)	0.56	152 (61.04)	47 (77.05)	0.019*
Diarrhea, n (%)	6 (14.29)	33 (10.68)	0.48	21 (8.43)	13 (21.31)	0.004*
AMS, n (%)	6 (14.29)	35 (11.33)	0.57	31 (12.45)	4 (6.56)	0.192
Chest pain, n (%)	12 (28.57)	39 (12.66)	0.006*	30 (12.10)	9 (14.75)	0.57
Others, n (%)	12 (28.57)	74 (47.13)	0.026*	74 (47.13)	15 (24.59)	0.002*
Laboratory results
Albumin (g/dL), m (SD)	3.77 (0.28)	2.84 (0.41)	< 0.001*	3.01 (0.24)	2.15 (0.24)	< 0.001*
ESR (mm/h), m (SD)	24 (15.52)	57.90 (34.24)	< 0.001*	53.43 (34.40)	72.21 (29.30)	0.010*
CRP (mg/L), m (SD)	35.02 (43.28)	84.32 (60.49)	< 0.001*	81.33 (60.62)	101.21 (64.27)	0.043*
Neutrophil (× 10³/µL), m (SD)	3.65 (2.24)	5.99 (4.05)	< 0.001*	5.45 (3.18)	8.35 (6.87)	0.005*
Lymphocyte (× 10³/µL), m (SD)	1.38 (0.91)	1.14 (0.70)	0.21	1.21 (0.74)	0.89 (0.45)	< 0.001*
NL ratio, m (SD)	3.94 (3.68)	6.88 (6.74)	0.001*	6.28 (6.75)	8.87 (6.23)	0.011*
Platelets (× 10³/µL), m (SD)	220.90 (73.77)	233.51 (90.11)	0.83	217.86 (82.40)	245.48 (114.16)	0.07
Ferritin (ng/mL), m (SD)	571.83 (961.77)	925.69 (2,012.85)	0.14	744.46 (1,150.94)	1,650.90 (3,696.46)	0.073
IL-6 (pg/mL), m (SD)	92.87 (161.77)	244.18 (533.03)	0.032*	200 (433.68)	352.87 (601.61)	0.20
LDH (U/L), m (SD)	287.85 (148.17)	398.79 (377.32)	0.007*	367.92 (166.65)	515.76 (752.83)	0.16

Table 3. Baseline Characteristics of Normal and Low Serum Albumin Groups

NSA vs. LSA group (primary group)

MLA vs. VLA group (subgroup)

NSA (n = 42)

LSA (n = 310)

P-value

MLA (albumin 2.5 - 3.4, n = 249)

VLA (albumin < 2.5, n = 61)

P-value

*Significant P-values. NSA: normal serum albumin; LSA: low serum albumin; MLA: medium low albumin; VLA: very low albumin; m: mean; SD: standard deviation; n: number; CKD: chronic kidney disease; ESRD: end-stage renal disease; HD: hemodialysis; COPD: chronic obstructive pulmonary disease; CHF: congestive heart disease; CAD: coronary artery disease; HIV: human immunodeficiency virus; SOB: shortness of breath; AMS: altered mental status; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein; NL: neutrophil to lymphocyte; IL-6: interleukin-6; LDH: lactate dehydrogenase.

Age, m (SD)

56.76 (16.18)

55.67 (18.23)

0.68

55.91 (18.90)

54.68 (15.26)

0.59

Female, n (%)

18 (42.86)

150 (48.39)

0.50

109 (43.78)

41 (67.21)

0.001*

Race

0.48

0.01*

White, n (%)

10 (23.81)

73 (23.55)

49 (19.76)

23 (37.70)

African American, n (%)

24 (57.14)

152 (49.03)

126 (50.81)

26 (42.62)

Others, n (%)

8 (196.05)

85 (27.42)

73 (29.44)

12 (19.67)

Comorbid conditions

Diabetes mellitus, n (%)

20 (47.62)

111 (35.81)

0.13

95 (38.15)

16 (26.23)

0.08

Hypertension, n (%)

34 (80.95)

191 (61.61)

0.014*

155 (62.25)

36 (59.02)

0.64

CKD, n (%)

15 (35.71)

53 (17.10)

0.004*

41 (16.47)

12 (19.67)

0.55

ESRD on HD, n (%)

5 (11.90)

21 (6.77)

0.23

18 (7.23)

3 (4.92)

0.52

COPD, n (%)

4 (9.52)

31 (10)

0.92

25 (10.04)

6 (9.84)

0.96

Other lung diseases, n (%)

5 (11.90)

47 (15.21)

0.57

36 (14.52)

11 (18.03)

0.49

CHF, n (%)

7 (16.67)

37 (11.94)

0.38

29 (11.65)

8 (13.11)

0.75

CAD, n (%)

11 (26.19)

55(17.74)

0.18

45 (18.07)

10 (16.39)

0.75

HIV, n (%)

1 (2.38)

6 (1.94)

0.84

1 (0.40)

5 (8.20)

< 0.001*

Malignancy, n (%)

6 (14.29)

24 (7.74)

0.15

19 (7.63)

5 (8.20)

0.88

Smoking, n (%)

11 (26.19)

55 (18.52)

0.24

39 (16.53)

16 (26.23)

0.082

Alcohol dependency, n (%)

4 (9.52)

22 (7.10)

0.53

19 (7.63)

3 (4.92)

0.46

Obesity, n (%)

18 (42.86)

161 (51.94)

0.26

129 (51.81)

32 (52.46)

0.92

Cirrhosis, n (%)

1 (2.38)

5 (1.62)

0.72

4 (1.61)

1 (1.64)

0.98

Symptoms

Onset of symptoms (days), m (SD)

4.11 (3.6)

5.62 (4.97)

0.018*

5.52 (5.03)

5.98 (4.76)

0.51

Fever, n (%)

27 (64.29)

182 (58.90)

0.50

146 (58.63)

36 (59.02)

0.95

Cough, n (%)

31 (73.81)

194 (62.78)

0.16

150 (60.24)

44 (72.13)

0.085

SOB, n (%)

25 (59.52)

198 (64.08)

0.56

152 (61.04)

47 (77.05)

0.019*

Diarrhea, n (%)

6 (14.29)

33 (10.68)

0.48

21 (8.43)

13 (21.31)

0.004*

AMS, n (%)

6 (14.29)

35 (11.33)

0.57

31 (12.45)

4 (6.56)

0.192

Chest pain, n (%)

12 (28.57)

39 (12.66)

0.006*

30 (12.10)

9 (14.75)

0.57

Others, n (%)

12 (28.57)

74 (47.13)

0.026*

74 (47.13)

15 (24.59)

0.002*

Laboratory results

Albumin (g/dL), m (SD)

3.77 (0.28)

2.84 (0.41)

< 0.001*

3.01 (0.24)

2.15 (0.24)

< 0.001*

ESR (mm/h), m (SD)

24 (15.52)

57.90 (34.24)

< 0.001*

53.43 (34.40)

72.21 (29.30)

0.010*

CRP (mg/L), m (SD)

35.02 (43.28)

84.32 (60.49)

< 0.001*

81.33 (60.62)

101.21 (64.27)

0.043*

Neutrophil (× 10³/µL), m (SD)

3.65 (2.24)

5.99 (4.05)

< 0.001*

5.45 (3.18)

8.35 (6.87)

0.005*

Lymphocyte (× 10³/µL), m (SD)

1.38 (0.91)

1.14 (0.70)

0.21

1.21 (0.74)

0.89 (0.45)

< 0.001*

NL ratio, m (SD)

3.94 (3.68)

6.88 (6.74)

0.001*

6.28 (6.75)

8.87 (6.23)

0.011*

Platelets (× 10³/µL), m (SD)

220.90 (73.77)

233.51 (90.11)

0.83

217.86 (82.40)

245.48 (114.16)

0.07

Ferritin (ng/mL), m (SD)

571.83 (961.77)

925.69 (2,012.85)

0.14

744.46 (1,150.94)

1,650.90 (3,696.46)

0.073

IL-6 (pg/mL), m (SD)

92.87 (161.77)

244.18 (533.03)

0.032*

200 (433.68)

352.87 (601.61)

0.20

LDH (U/L), m (SD)

287.85 (148.17)

398.79 (377.32)

0.007*

367.92 (166.65)

515.76 (752.83)

0.16

**Table 4.** In-Hospital Complications and Duration of Stays in Normal and Low Serum Albumin Groups
	NSA vs. LSA group (primary group)	MLA vs. VLA group (subgroup)
*Significant P-values. NSA: normal serum albumin; LSA: low serum albumin; MLA: medium low albumin; VLA: very low albumin; m: mean; SD: standard deviation; n: number; qSOFA: quick sequential organ failure assessment; AKI: acute kidney injury; CVA: cerebrovascular accident; HD: hemodialysis; INR: international normalized ratio; AST: aspartate aminotransferase; ALT: alanine aminotransferase; ARDS: acute respiratory distress syndrome; LO: length of; ICU: intensive care unit.
Composite outcome, n (%)	17 (6.12)	261 (93.88)	< 0.001*	202 (81.12)	59 (96.72)	0.003*
Death, n (%)	1 (2.38)	43 (13.87)	0.035*	24 (9.64)	19 (31.15)	< 0.001*
Tocilizumab, n (%)	4 (9.52)	73 (23.62)	0.038*	51 (20.48)	22 (36.07)	0.010*
Remdesivir, n (%)	1 (2.38)	71 (22.98)	0.002*	54 (21.69)	17 (27.87)	0.30
Dexamethasone, n (%)	10 (23.81)	106 (34.30)	0.17	87 (34.94)	19 (31.67)	0.63
Convalescent plasma, n (%)	2 (4.76)	35 (11.33)	0.194	22 (8.84)	13 (21.31)	0.006*
qSOFA 2-3, n (%)	3 (7.14)	68 (21.94)	0.025*	50 (20.08)	18 (29.51)	0.11
Acute circulatory failure, n (%)	1 (2.38)	64 (20.65)	0.004*	43 (17.27)	21 (34.43)	0.003*
Secondary infection
Procalcitonin > 0.5 ng/mL, n (%)	3 (9.09)	96 (35.29)	0.002*	62 (28.57)	35 (63.64)	< 0.001*
Lactic acid > 2 mmol/L, n (%)	4 (15.38)	53 (20.08)	0.56	38 (17.92)	16 (30.77)	0.04*
Blood culture, n (%)	0 (0)	19 (7.12)	0.138	12 (5.53)	8 (16)	0.011*
Urine culture, n (%)	0 (0)	16 (9.25)	0.146	13 (8.97)	4 (14.29)	0.38
Body fluid culture, n (%)	1 (4.55)	6 (6.41)	0.97	5 (4.39)	1 (4.55)	0.97
Respiratory secretion culture, n (%)	7 (26.92)	47 (24.35)	0.77	38 (23.75)	9 (27.27)	0.66
AKI, n (%)	6 (14.28)	133 (43.36)	0.004*	95 (38.30)	38 (62.29)	0.002*
Requiring new HD, n (%)	1 (2.38)	17 (5.52)	0.38	5 (2.02)	12 (19.67)	< 0.001*
INR > 1.5	0 (0)	22 (8.83)	0.34	13 (6.63)	9 (16.98)	0.071
AST or ALT > 5 times normal	2 (4.76)	32 (10.49)	0.24	19 (7.79)	13 13 (21.31)	0.002*
Acute hypercoagulability			< 0.001*			< 0.001*
D-dimer > 1 mg/dL, n (%)	7 (21.21)	132 (50.96)		92 (44.66)	40 (75.47)
D-dimer 0.5 - 1 mg/dL, n (%)	3 (9.09)	62 (23.90)		55 (26.70)	7 (13.21)
Acute encephalopathy, n (%)	3 (7.14)	71 (22.90)	0.019*	48 (19.28)	23 (37.70)	0.002*
Cerebrovascular accident, n (%)	0 (0)	0 (0)	n/a	0 (0)	0 (0)	n/a
Acute cardiac injury, n (%)	3 (7.32)	89 (29.87)	0.002*	67 (28.03)	22 (37.29)	0.164
New-onset heart failure, n (%)	1 (2.44)	13 (4.22)	0.58	9 (3.63)	4 (6.67)	0.29
New-onset arrhythmia, n (%)	4. (9.76)	34 (10.97)	0.81	21 (8.43)	13 (21.31)	0.004*
ARDS, n (%)	1 (2.27)	60 (20.98)	0.008*	34 (15.04)	26 (43.33)	< 0.001*
Mechanical ventilation, n (%)	1 (2.38)	41 (13.27)	0.041*	23 (9.27)	18 (29.51)	< 0.001*
Requiring > 3 L O₂, n (%)	8 (19.05)	166 (53.55)	< 0.001*	117 (46.99)	49 (80.33)	< 0.001*
Requiring > 15 L high flow O₂, n (%)	4 (9.52)	88 (28.39)	0.009*	57 (22.89)	31 (50.82)	< 0.001*
New-onset oxygen dependency, n (%)	1 (2.38)	41 (13.80)	0.035*	27 (11.20)	14 (25)	0.007*
LO stay (days), m (SD)	4.16 (5.55)	9.32 (9.70)	< 0.001*	8.14 (8.53)	14.18 (12.40)	< 0.001*
LO ICU stay (days), m (SD)	0.24 (1.56)	1.96 (5.59)	< 0.001*	1.4 (4.9)	4.24 (7.44)	0.005*
LO mechanical vent (days), m (SD)	0.24 (1.56)	1.60 (4.96)	< 0.001*	1.13 (4.16)	3.59 (7.13)	0.01*
Physical debility (days), n (%)	3 (7.32)	75 (24.51)	0.013*	56 (22.67)	19 (32.20)	0.12
Discharged, n (%)	41 (97.62)	270 (87.10)	0.046*	221 (88.76)	49 (80.33)	0.078*
Readmission, n (%)	5 (11.90)	47 (15.16)	0.57	38 (15.26)	9 (14.75)	0.92

Table 4. In-Hospital Complications and Duration of Stays in Normal and Low Serum Albumin Groups

NSA vs. LSA group (primary group)

MLA vs. VLA group (subgroup)

NSA (n = 42)

LSA (n = 310)

P-value

MLA (albumin 2.5 - 3.4, n = 249)

VLA (albumin < 2.5, n = 61)

P-value

*Significant P-values. NSA: normal serum albumin; LSA: low serum albumin; MLA: medium low albumin; VLA: very low albumin; m: mean; SD: standard deviation; n: number; qSOFA: quick sequential organ failure assessment; AKI: acute kidney injury; CVA: cerebrovascular accident; HD: hemodialysis; INR: international normalized ratio; AST: aspartate aminotransferase; ALT: alanine aminotransferase; ARDS: acute respiratory distress syndrome; LO: length of; ICU: intensive care unit.

Composite outcome, n (%)

17 (6.12)

261 (93.88)

< 0.001*

202 (81.12)

59 (96.72)

0.003*

Death, n (%)

1 (2.38)

43 (13.87)

0.035*

24 (9.64)

19 (31.15)

< 0.001*

Tocilizumab, n (%)

4 (9.52)

73 (23.62)

0.038*

51 (20.48)

22 (36.07)

0.010*

Remdesivir, n (%)

1 (2.38)

71 (22.98)

0.002*

54 (21.69)

17 (27.87)

0.30

Dexamethasone, n (%)

10 (23.81)

106 (34.30)

0.17

87 (34.94)

19 (31.67)

0.63

Convalescent plasma, n (%)

2 (4.76)

35 (11.33)

0.194

22 (8.84)

13 (21.31)

0.006*

qSOFA 2-3, n (%)

3 (7.14)

68 (21.94)

0.025*

50 (20.08)

18 (29.51)

0.11

Acute circulatory failure, n (%)

1 (2.38)

64 (20.65)

0.004*

43 (17.27)

21 (34.43)

0.003*

Secondary infection

Procalcitonin > 0.5 ng/mL, n (%)

3 (9.09)

96 (35.29)

0.002*

62 (28.57)

35 (63.64)

< 0.001*

Lactic acid > 2 mmol/L, n (%)

4 (15.38)

53 (20.08)

0.56

38 (17.92)

16 (30.77)

0.04*

Blood culture, n (%)

0 (0)

19 (7.12)

0.138

12 (5.53)

8 (16)

0.011*

Urine culture, n (%)

0 (0)

16 (9.25)

0.146

13 (8.97)

4 (14.29)

0.38

Body fluid culture, n (%)

1 (4.55)

6 (6.41)

0.97

5 (4.39)

1 (4.55)

0.97

Respiratory secretion culture, n (%)

7 (26.92)

47 (24.35)

0.77

38 (23.75)

9 (27.27)

0.66

AKI, n (%)

6 (14.28)

133 (43.36)

0.004*

95 (38.30)

38 (62.29)

0.002*

Requiring new HD, n (%)

1 (2.38)

17 (5.52)

0.38

5 (2.02)

12 (19.67)

< 0.001*

INR > 1.5

0 (0)

22 (8.83)

0.34

13 (6.63)

9 (16.98)

0.071

AST or ALT > 5 times normal

2 (4.76)

32 (10.49)

0.24

19 (7.79)

13 13 (21.31)

0.002*

Acute hypercoagulability

< 0.001*

D-dimer > 1 mg/dL, n (%)

7 (21.21)

132 (50.96)

92 (44.66)

40 (75.47)

D-dimer 0.5 - 1 mg/dL, n (%)

3 (9.09)

62 (23.90)

55 (26.70)

7 (13.21)

Acute encephalopathy, n (%)

3 (7.14)

71 (22.90)

0.019*

48 (19.28)

23 (37.70)

0.002*

Cerebrovascular accident, n (%)

0 (0)

n/a

0 (0)

n/a

Acute cardiac injury, n (%)

3 (7.32)

89 (29.87)

0.002*

67 (28.03)

22 (37.29)

0.164

New-onset heart failure, n (%)

1 (2.44)

13 (4.22)

0.58

9 (3.63)

4 (6.67)

0.29

New-onset arrhythmia, n (%)

4. (9.76)

34 (10.97)

0.81

21 (8.43)

13 (21.31)

0.004*

ARDS, n (%)

1 (2.27)

60 (20.98)

0.008*

34 (15.04)

26 (43.33)

< 0.001*

Mechanical ventilation, n (%)

1 (2.38)

41 (13.27)

0.041*

23 (9.27)

18 (29.51)

< 0.001*

Requiring > 3 L O₂, n (%)

8 (19.05)

166 (53.55)

< 0.001*

117 (46.99)

49 (80.33)

< 0.001*

Requiring > 15 L high flow O₂, n (%)

4 (9.52)

88 (28.39)

0.009*

57 (22.89)

31 (50.82)

< 0.001*

New-onset oxygen dependency, n (%)

1 (2.38)

41 (13.80)

0.035*

27 (11.20)

14 (25)

0.007*

LO stay (days), m (SD)

4.16 (5.55)

9.32 (9.70)

< 0.001*

8.14 (8.53)

14.18 (12.40)

< 0.001*

LO ICU stay (days), m (SD)

0.24 (1.56)

1.96 (5.59)

< 0.001*

1.4 (4.9)

4.24 (7.44)

0.005*

LO mechanical vent (days), m (SD)

0.24 (1.56)

1.60 (4.96)

< 0.001*

1.13 (4.16)

3.59 (7.13)

0.01*

Physical debility (days), n (%)

3 (7.32)

75 (24.51)

0.013*

56 (22.67)

19 (32.20)

0.12

Discharged, n (%)

41 (97.62)

270 (87.10)

0.046*

221 (88.76)

49 (80.33)

0.078*

Readmission, n (%)

5 (11.90)

47 (15.16)

0.57

38 (15.26)

9 (14.75)

0.92

**Table 5.** Results From Logistic Regression Analyses - Odds of Composite Outcome Based on Albumin Level Category
	Univariate analysis	Multivariate analysis^a
*Significant P-values. ^aControlled for age; sex; race; diabetes mellitus; hypertension; chronic kidney disease; end-stage renal disease on hemodialysis; chronic obstructive pulmonary disease; other lung diseases; congestive heart failure; coronary artery disease; human immunodeficiency virus infection; malignancy; smoking; alcohol dependency; obesity; and cirrhosis. NSA: normal serum albumin; LSA: low serum albumin; MLA: medium low albumin; VLA: very low albumin; CI: confidence interval.
Main group (LSA vs. NSA)	7.83	3.94 - 15.58	< 0.001*	10.88	4.74 - 24.97	< 0.001*
Subgroup (VLA vs. MLA)	6.86	1.62 - 29.10	0.009*	7.94	1.70 - 37.14	0.009*

Table 5. Results From Logistic Regression Analyses - Odds of Composite Outcome Based on Albumin Level Category

Univariate analysis

Multivariate analysis^a

Odds ratio

95% CI

P-value

Odds ratio

95% CI

P-value

*Significant P-values. ^aControlled for age; sex; race; diabetes mellitus; hypertension; chronic kidney disease; end-stage renal disease on hemodialysis; chronic obstructive pulmonary disease; other lung diseases; congestive heart failure; coronary artery disease; human immunodeficiency virus infection; malignancy; smoking; alcohol dependency; obesity; and cirrhosis. NSA: normal serum albumin; LSA: low serum albumin; MLA: medium low albumin; VLA: very low albumin; CI: confidence interval.

Main group (LSA vs. NSA)

7.83

3.94 - 15.58

< 0.001*

10.88

4.74 - 24.97

< 0.001*

Subgroup (VLA vs. MLA)

6.86

1.62 - 29.10

0.009*

7.94

1.70 - 37.14

0.009*

**Table 6.** Results From MV Analysis in Normal and Low Albumin Groups
Outcome	Normal vs. low albumin group (primary group)	Medium low vs. very low albumin group (subgroup)
MV controlled for age; sex; race; diabetes mellitus (DM); hypertension (HTN); chronic kidney disease (CKD); end-stage renal disease (ESRD) on hemodialysis (HD); chronic obstructive pulmonary disease (COPD); other lung diseases; congestive heart failure (CHF); coronary artery disease (CAD); human immunodeficiency virus (HIV) infection; malignancy; smoking; alcohol dependency; obesity; and cirrhosis. *Significant P-values. MV: multivariate; CI: confidence interval.
Albumin level (lower ref to higher)	10.88	4.74 - 24.97	< 0.001*	7.94	1.70 - 37.14	0.009*
Age	1.00	0.98 - 1.02	0.56	0.99	0.91 - 1.02	0.81
Sex	0.77	0.41 - 1.47	0.44	1.5	0.71 - 3.18	0.27
Race
White	0.37	0.16 - 0.82	0.015*	1.77	0.59 - 5.32	0.30
Others	0.73	0.33 - 1.63	0.45	1.16	0.49 - 2.71	0.72
Smoking	1.93	0.81 - 4.5	0.13	0.52	0.20 - 1.33	0.17
DM	0.61	0.32 - 1.19	0.15	1.12	0.52 - 2.40	0.76
HTN	1.04	0.46 - 2.36	0.91	0.38	0.14 - 1.04	0.06
CKD	0.54	0.22 - 1.32	0.18	2.04	0.66 - 6.32	0.21
ESRD on HD	1.11	0.30 - 4.11	0.86	0.38	0.08 - 1.69	0.20
COPD	0.41	0.13 - 1.21	0.1	1.30	0.34 - 4.92	0.69
CHF	1.40	0.45 - 4.32	0.55	4.78	1.06 - 21.38	0.041*
CAD	0.67	0.26 - 1.72	0.40	0.75	0.26 - 2.16	0.60
HIV	1.46	0.14 - 14.93	0.74	1
Malignancy	11.34	2.05 - 62.64	0.005*	0.78	0.20 - 2.99	0.72
Alcohol dependency	1.58	0.40 - 6.19	0.50	3.35	0.62 - 17.86	0.15
Obesity	0.66	0.35 - 2.14	0.22	0.66	0.31 - 1.39	0.28
Other lung disease	0.87	0.35 - 2.14	0.77	0.31	0.12 - 0.78	0.014*
Cirrhosis	0.06	0.08 - 0.57	0.014*	1.45	0.09 - 22.22	0.78

Table 6. Results From MV Analysis in Normal and Low Albumin Groups

Outcome

Normal vs. low albumin group (primary group)

Medium low vs. very low albumin group (subgroup)

Odds ratio

95% CI

P-value

Odds ratio

95% CI

P-value

MV controlled for age; sex; race; diabetes mellitus (DM); hypertension (HTN); chronic kidney disease (CKD); end-stage renal disease (ESRD) on hemodialysis (HD); chronic obstructive pulmonary disease (COPD); other lung diseases; congestive heart failure (CHF); coronary artery disease (CAD); human immunodeficiency virus (HIV) infection; malignancy; smoking; alcohol dependency; obesity; and cirrhosis. *Significant P-values. MV: multivariate; CI: confidence interval.

Albumin level (lower ref to higher)

10.88

4.74 - 24.97

< 0.001*

7.94

1.70 - 37.14

0.009*

Age

1.00

0.98 - 1.02

0.56

0.99

0.91 - 1.02

0.81

Sex

0.77

0.41 - 1.47

0.44

1.5

0.71 - 3.18

0.27

Race

White

0.37

0.16 - 0.82

0.015*

1.77

0.59 - 5.32

0.30

Others

0.73

0.33 - 1.63

0.45

1.16

0.49 - 2.71

0.72

Smoking

1.93

0.81 - 4.5

0.13

0.52

0.20 - 1.33

0.17

0.61

0.32 - 1.19

0.15

1.12

0.52 - 2.40

0.76

HTN

1.04

0.46 - 2.36

0.91

0.38

0.14 - 1.04

0.06

CKD

0.54

0.22 - 1.32

0.18

2.04

0.66 - 6.32

0.21

ESRD on HD

1.11

0.30 - 4.11

0.86

0.38

0.08 - 1.69

0.20

COPD

0.41

0.13 - 1.21

0.1

1.30

0.34 - 4.92

0.69

CHF

1.40

0.45 - 4.32

0.55

4.78

1.06 - 21.38

0.041*

CAD

0.67

0.26 - 1.72

0.40

0.75

0.26 - 2.16

0.60

HIV

1.46

0.14 - 14.93

0.74

Malignancy

11.34

2.05 - 62.64

0.005*

0.78

0.20 - 2.99

0.72

Alcohol dependency

1.58

0.40 - 6.19

0.50

3.35

0.62 - 17.86

0.15

Obesity

0.66

0.35 - 2.14

0.22

0.66

0.31 - 1.39

0.28

Other lung disease

0.87

0.35 - 2.14

0.77

0.31

0.12 - 0.78

0.014*

Cirrhosis

0.06

0.08 - 0.57

0.014*

1.45

0.09 - 22.22

0.78