Abnormal Indexes of Liver and Kidney Injury Markers Predict Severity in COVID-19 Patients

Figures & data

Table 1 Baseline Characteristics Between Three Group Patients

Characteristics	Mild Group (235)	Severe Group (31)		P value
		Pre-Severe Group (31)	After-Severe Group (31)
Age (years)	43.86±15.71	57.42±14.28		<0.001
Sex (female, n%)	121(51.49%)	13(41.9%)		0.317
Smoking	22 (9.4%)	5 (16.1%)		0.241
Signs and symptoms
Fever	108(46.35%)	27(87.10%)	28(90.32%)	<0.001
Cough	166(70.64%)	23(74.19%)	12(38.71%)	0.014
Dyspnea	44(18.72%)	13(41.92%)	15(48.39%)	<0.001
Diarrhea	35(14.89%)	1(3.23%)	2(6.46%)	0.113
Anorexia	17(7.23%)	10(32.26%)	6(19.35%)	0.002
Headache	23(9.79%)	4(12.90%)	4(12.90%)	0.290
Temperature (°C)
≤37.2	102(43.40%)	7(22.58%)	5(16.13%)	0.002
37.2–38	57(24.26%)	6(19.35%)	11(35.48%)	0.299
38.1–39	46(19.15%)	16(51.61%)	12(38.71%)	<0.001
≥39.1	5(2.13%)	2(6.46%)	3(9.68%)	0.047
Comorbidities
Diabetes	22 (9.36%)	3 (9.68%)		1.000
Hypertension	35 (14.89%)	10 (32.26%)		0.015
Cerebral infarction	8 (3.40%)	1 (3.23%)		1.000
Heart disease	8 (3.40%)	3 (9.68%)		0.242
Liver disease	15 (6.38%)	3 (9.68%)		0.760
Chronic obstructive Pulmonary disease	4 (1.70%)	1 (3.23%)		1.000
Tumor	2 (0.85%)	0 (0.00%)		1.000
Laboratory indexes
WBC(×10^9/L)	5.07(3.86–6.49)	4.31(2.79–4.70)	9.07(6.16–11.73)	<0.001
NEUT(×10^9/L)	3.15(2.37–4.09)	2.76(1.80–3.17)	8.22(73.70–92.10)	<0.001
NEUT %	64.85(59.45–72.43)	68.20(64.00–73.70)	90.30(73.70–92.10)	<0.001
LYM(×10^9/L)	1.27(0.92–1.73)	0.80(0.69–0.97)	0.57(0.47–0.80)	<0.001
LYM%	25.40(18.50–30.00)	22.10(17.40–28.00)	6.20(4.80–19.70)	<0.001

Note: Statistically significant differences are emboldened.

Abbreviations: WBC, white blood cell; NEUT, neutrophil; LYM, lymphocyte.

Table 2 Comparison of Liver and Kidney Indexes Between Different Conditions of COVID-19 Patients

Liver and Kidney Indexes	Mild Group (235)	Severe Group (31)		P1 value (Mild vs Pre-Severe)	P2 value (Mild vs After-Severe)	P3 value (Pre-Severe vs After-Severe)
		Pre-Severe Group (31)	After-Severe Group (31)
TB(μmol/L)	10.87(8.12–15.65)	9.99(6.90–16.45)	13.91(8.61–17.10)	0.342	0.220	0.147
ALB (g/L)	38.72(35.83–42.30)	37.30(35.33–39.52)	32.88(29.50–36.50)	0.073	0.000	0.002
ALT(U/L)	19.85(14.16–29.90)	21.71(16.29–25.80)	24.00(16.20–57.24)	0.685	0.029	0.145
AST(U/L)	22.79(17.99–30.62)	30.70(26.28–43.50)	30.00(18.87–55.32)	0.000	0.032	0.617
LDH(U/L)	167.65(140.15–207.83)	197.40(179.00–280.00)	295.40(207.55–393.18)	0.000	0.000	0.003
BUN (mmol/L)	4.16(3.23–5.30)	4.40(3.45–5.08)	6.23(5.19–8.60)	0.632	0.000	0.000
Cr(μmol/L)	53.37(41.50–67.92)	56.48(50.00–74.00)	49.60(41.60–61.00)	0.108	0.724	0.125
PT (time)	11.70(11.10–12.50)	12.20(11.80–12.70)	12.10(10.88–12.90)	0.031	0.368	0.659
APTT (time)	33.10(30.60–35.80)	33.30(29.90–38.30)	30.85(25.88–34.50)	0.529	0.010	0.038
DD (mmol/L)	0.26(0.14–0.55)	0.31(0.14–0.56)	0.52(0.27–1.84)	0.765	0.001	0.037

Note: Statistically significant differences are emboldened.

Abbreviations: TB, total bilirubin; ALB, albumin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; LDH, lactic dehydrogenase; BUN, blood urea nitrogen; Cr, creatinine; PT, prothrombin time; APTT, activated partial thromboplastin time; DD, D-Dimer.

Table 3 Detailed Comparison of Liver and Kidney Indexes Between Mild Group and Severe Group

Laboratory Indexes	References	Mild Group (235)	After-Severe Group (31)	X^2	P-value
ALT(U/L)	0–42	19.85(14.16–29.90)	24.00(16.20–57.24)	24.719	<0.001
≤42		196 (83.4%)	19 (61.3%)
42–150		36 (15.3%)	9 (29.0%)
>150		1 (0.4%)	3 (9.7%)
AST(U/L)	0–37	22.79(17.99–30.62)	30.00(18.87–55.32)	35.087	<0.001
≤37		198 (84.3%)	17 (57.8%)
37–120		34 (14.5%)	10 (32.3%)
>120		1 (0.4%)	4 (12.9%)
TB(μmol/L)	3.4–20.5	10.87(8.12–15.65)	13.91(8.61–17.10)	2.685	0.762
≤20.5		211 (89.8%)	25 (80.6%)
20.5–31.5		16 (6.8%)	5 (16.1%)
>31.5		7 (3.0%)	1 (3.2%)
ALB (g/L)	35–55	38.72(35.83–42.30)	32.88(29.50–36.50)	72.550	<0.001
<35		41 (17.4%)	20 (64.5%)
35–55		182 (77.4)	11 (35.5%)
≥55		0	0
LDH(U/L)	135–225	167.65(140.15–207.83)	295.40(207.55–393.18)	52.246	<0.001
≤225		190 (80.9%)	8 (25.8%)
>225		43 (18.3%)	22 (71.0%)
BUN (mmol/L)	2.86–8.2	4.16(3.23–5.30)	6.23(5.19–8.60)	2.813	<0.001
≤8.2		214 (91.1%)	20 (64.5%)
>8.2		9 (3.8)	11 (35.5%)
Cr(μmol/L)	21.5–104	53.37(41.50–67.92)	49.60(41.60–61.00)	0.641	0.681
≤104		226 (96.2%)	29 (93.5%)
>104		7 (3.0%)	2 (6.5%)

Note: Statistically significant differences are emboldened.

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; TB, total bilirubin; ALB, albumin; LDH, lactic dehydrogenase; BUN, blood urea nitrogen; Cr, creatinine.

Table 4 Comparison of Clinical Laboratory Indexes Between Patients with and without Liver Injury

Clinical Laboratory Indexes	Patients without Liver Injury (228)	Patients with Liver Injury (38)	P value
WBC(×10^9/L)	5.11(3.86–6.85)	6.25(4.52–8.91)	0.021
NEUT(×10^9/L)	3.19(2.37–4.39)	3.91(2.81–7.85)	0.020
NEUT%	63.97(56.86–72.85)	66.42(61.00–89.40)	0.024
LYM (×10^9/L)	1.20(0.84–1.70)	1.02(0.57–1.50)	0.051
LYM%	26.26(18.90–32.51)	23.83(6.20–28.88)	0.012
PT (time)	11.80(11.10–12.70)	11.40(10.98–12.50)	0.483
APTT (time)	32.60(30.20–35.70)	33.55(27.45–35.45)	0.826
DD (mmol/L)	0.26(0.14–0.56)	0.39(0.24–0.74)	0.015
TB(μmol/L)	10.92(8.01–16.20)	11.75(8.64–17.10)	0.419
ALB(g/L)	38.45(35.48–42.38)	36.53(32.49–39.15)	0.015
ALT(U/L)	19.29(13.57–26.40)	53.66(28.79–97.23)	<0.001
AST(U/L)	22.38(17.45–28.40)	42.75(24.84–55.34)	<0.001
LDH(U/L)	171.30(141.00–210.50)	206.85(170.63–308.20)	0.001
BUN (mmol/L)	4.20(3.24–5.39)	5.20(4.57–6.55)	0.001
Cr(μmol/L)	53.68(41.48–67.15)	49.40(41.60–67.55)	0.956

Note: Statistically significant differences are emboldened.

Abbreviations: WBC, white blood cell; NEUT, neutrophil; LYM, lymphocyte; PT, prothrombin time; APTT, activated partial thromboplastin time; DD, D-Dimer; TB, total bilirubin; ALB, albumin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; LDH, lactic dehydrogenase; BUN, blood urea nitrogen; Cr, creatinine.

Table 5 Comparison of Clinical Laboratory Indicators Between Patients with and without Renal Injury

Clinical Laboratory Indexes	Patients without Renal Injury (248)	Patients with Renal Injury (18)	P value
WBC(×10^9/L)	5.06(3.77–6.84)	5.12(4.18–8.72)	0.268
NEU(×10^9/L)	3.17(2.32–4.39)	3.19(2.78–6.72)	0.240
NEUT%	65.11(58.80–73.08)	71.59(60.75–82.79)	0.263
LYM (×10^9/L)	1.12(0.80–1.62)	0.92(0.61–1.56)	0.367
LYM%	25.80(18.52–30.73)	19.95(11.00–30.76)	0.286
PT (time)	11.90(11.10–12.60)	12.25(11.38–13.60)	0.093
APTT (time)	32.70(30.10–35.70)	33.55(31.15–38.08)	0.270
DD (mmol/L)	0.27(0.15–0.56)	0.49(0.17–1.45)	0.049
TB(μmol/L)	11.29(8.15–16.43)	10.66(6.38–17.17)	0.400
ALB(g/L)	38.31(35.36–41.60)	36.12(29.08–42.00)	0.136
ALT(U/L)	20.13(14.55–29.12)	27.18(15.08–45.43)	0.184
AST(U/L)	23.60(18.84–33.17)	28.00(21.50–41.84)	0.092
LDH(U/L)	180.10(142.63–220.70)	224.35(180.43–314.25)	0.004
BUN (mmol/L)	4.29(3.37–5.34)	7.37(4.10–8.95)	0.001
Cr(μmol/L)	54.24(43.15–66.85)	62.46(37.58–120.11)	0.435

Note: Statistically significant differences are emboldened.

Abbreviations: WBC, white blood cell; NEUT, neutrophil; LYM, lymphocyte; PT, prothrombin time; APTT, activated partial thromboplastin time; DD, D-Dimer; TB, total bilirubin; ALB, albumin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; LDH, lactic dehydrogenase; BUN, blood urea nitrogen; Cr, creatinine.

Table 6 Binary Logistic Regression Analysis of Laboratory Indexes to Predict the Mild and After-Severe Patients

Laboratory Indexes	Regression Coefficient	Standard Deviation	OR	95% CI	P value
ALB(g/L)	−0.205	0.059	0.815	0.725–0.915	0.001
ALT(U/L)	0.009	0.004	1.009	1.002–1.016	0.013
BUN (mmol/L)	0.281	0.104	1.325	1.081–1.624	0.007
LDH(U/L)	0.005	0.002	1.005	1.001–1.008	0.006

Note: Statistically significant differences are emboldened.

Abbreviations: ALB, albumin; ALT, alanine aminotransferase; BUN, blood urea nitrogen; LDH, lactic dehydrogenase; OR, odds ratio; CI, confidence intervals.

Table 7 The ROC Analysis of Liver and Kidney Indexes to Predict the Mild and Severe Patients

Indexes	AUC (95% CI)	Critical Value	Sensitivity	Specificity	Jordan Index	P value
ALT(U/L)	0.619(0.506~0.733)	46.56	0.387	0.884	0.271	0.031
AST(U/L)	0.618(0.492~0.741)	37.43	0.452	0.854	0.306	0.032
LDH(U/L)	0.869(0.808~0.930)	189.2	0.900	0.665	0.565	<0.001
BUN (mmol/L)	0.800(0.717~0.883)	4.89	0.871	0.682	0.553	<0.001
Combined indexes	0.914(0.868–0.959)	0.023	0.867	0.830	0.697	<0.001

Note: Statistically significant differences are emboldened.

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; LDH, lactic dehydrogenase; BUN, blood urea nitrogen; ROC, receiver operating characteristic; AUC, area under curve.

Figure 1 The ROC analysis of liver and kidney indexes to predict the mild and severe patients.

Figure 2 The possible mechanism of hepatocyte injury in COVID-19 patients: SARS-CoV-2 enters hepatocytes through human angiotensin converting enzyme 2(ACE2) and TMPRSS2, leading to denaturation and necrosis of hepatocytes and subsequent accumulation of bile acids. The pathogenic T cells are rapidly activated to produce proinflammatory factors such as granulocyte-macrophage colony stimulating factor (GM-CS F), interleukin (IL)-6, which induces inflammatory “storms “. And drugs may also cause drug-induced liver damage.

Figure 3 The possible mechanism of kidney injury in COVID-19 patients: SARS-CoV-2 enters kidney cells through human angiotensin converting enzyme 2(ACE2), resulting in degeneration and necrosis of kidney cells. Immune injury, sepsis-related kidney injury, hypovolemic renal hypoperfusion and drug-related kidney injury are all possible mechanisms of kidney injury.