During the Omicron Pandemic Wave, the Severe Systemic Inflammatory Status of COVID-19 Indicated a Higher Risk of In-Hospital Mortality and Mediated the Clinical Efficacy of Corticosteroids

Figures & data

Table 1 Difference of General Characteristics Between Surviving Cases and In-Hospital Mortality Cases

Characteristics	Total	Death = 0	Death = 1	P
N	684	588	96
Sex (Female)	291 (42.5%)	260 (44.2%)	31 (32.3%)	0.028
Age	69.50±15.86	67.95±15.90	78.98±11.82	<0.001
Severity of COVID-19				<0.001
Mild	56 (8.2%)	54 (9.2%)	2 (2.1%)
Moderate	401 (58.6%)	376 (63.9%)	25 (26.0%)
Severe	82 (12.0%)	64 (10.9%)	18 (18.8%)
Critical	128 (18.7%)	78 (13.3%)	50 (52.1%)
Missing	17 (2.5%)	16 (2.7%)	1 (1.0%)
Comorbidity
Hypertension	329 (48.1%)	272 (46.3%)	57 (59.4%)	0.017
DM	183 (26.8%)	151 (25.7%)	32 (33.3%)	0.12
CVD	148 (21.6%)	120 (20.4%)	28 (29.2%)	0.053
Cancer	89 (13.0%)	77 (13.1%)	12 (12.5%)	0.87
Arrhythmia	67 (9.8%)	53 (9.0%)	14 (14.6%)	0.089
Heart failure	19 (2.8%)	12 (2.0%)	7 (7.3%)	0.004
Cerebrovascular disease	85 (12.4%)	60 (10.2%)	25 (26.0%)	<0.001
COPD	57 (8.3%)	47 (8.0%)	10 (10.4%)	0.43
CHB	56 (8.2%)	52 (8.8%)	4 (4.2%)	0.12
Liver cirrhosis	60 (8.8%)	54 (9.2%)	6 (6.3%)	0.35
Renal dysfunction	145 (21.2%)	102 (17.3%)	43 (44.8%)	<0.001
Laboratory test
WBC	5.76 (3.99, 7.91)	5.44 (3.85, 7.58)	8.17 (5.91, 11.44)	<0.001
NEU	4.05 (2.54, 6.49)	3.67 (2.38, 5.80)	7.05 (4.99, 10.18)	<0.001
LYM	0.90 (0.59, 1.27)	0.93 (0.62, 1.33)	0.65 (0.42, 0.98)	<0.001
MONO	0.4 (0.29, 0.57)	0.39 (0.25, 0.60)	0.40 (0.29, 0.57)	0.64
PLT	172 (123, 225)	173 (124, 220)	163 (110.5, 240)	0.78
CRP	33.70 (8.80, 71.84)	27.25 (7.40, 65.20)	72.35 (52.27, 104.66)	<0.001
Procalcitonin	0.08 (0.04, 0.26)	0.06 (0.04, 0.17)	0.38 (0.15, 1.25)	<0.001
Albumin	32.6 (28.0, 35.9)	33.25 (28.9, 36.45)	28.0 (25.6, 31.6)	<0.001
Globulin	31.8 (26.9, 37.4)	31.3 (26.6, 36.8)	34.3 (28.8, 41.4)	<0.001
AST	29 (20, 48)	27 (20, 44)	48 (30, 72)	<0.001
ALT	24 (16, 37)	23 (16, 36)	25 (19, 44)	0.051
eGFR	84.2 (65.1, 96.0)	86.6 (70.1, 96.8)	65.45 (42.5, 86.2)	<0.001
Creatinine	70 (57, 91)	68 (57, 86)	83 (63, 134)	<0.001
Urea	5.61 (4.07, 8.45)	5.28 (3.96, 7.24)	9.17 (6.36, 14.26)	<0.001
Fibrinogen	3.81 (3.01, 4.66)	3.76 (2.99, 4.59)	4.17 (3.16, 4.87)	0.080
D-Dimer	364.5 (177.0, 1019.5)	322 (157, 813)	1630 (499, 4192)	<0.001
PT	12.2 (11.45, 13.5)	12.1 (11.3, 13.4)	13.0 (11.8, 14.0)	<0.001
PTINR	1.10 (1.04, 1.21)	1.09 (1.03, 1.20)	1.16 (1.05, 1.26)	<0.001
Systemic inflammatory indicators
NLR	4.51 (2.28, 9.57)	3.84 (2.12, 7.78)	10.87 (6.62, 18.69)	<0.001
CLR	36.05 (8.72, 101.08)	28.31 (6.73, 83.37)	108.84 (63.49, 218.80)	<0.001
CAR	1.27 (0.38, 2.62)	0.96 (0.27, 2.30)	2.61 (1.68, 3.62)	<0.001
Hospital stay (days)	11 (7, 15)	11 (7, 15)	7 (5, 13)	<0.001
Oxygen support
Inhalation oxygen with facemask	147 (21.5%)	107 (18.2%)	40 (41.7%)	<0.001
Optiflow	81 (11.8%)	46 (7.8%)	35 (36.5%)	<0.001
Non-invasive ventilation	28 (4.1%)	11 (1.9%)	17 (17.7%)	<0.001
Invasive ventilation	147 (21.5%)	107 (18.2%)	40 (41.7%)	<0.001
Antibiotic treatment	207 (30.3%)	156 (26.5%)	51 (53.1%)	<0.001
Anticoagulation treatment	149 (21.8%)	122 (20.7%)	27 (28.1%)	0.10
Vitaminotherapy	139 (20.3%)	101 (17.2%)	38 (39.6%)	<0.001

Abbreviations: DM, diabetes mellitus; CVD, cardiovascular disease; WBC, white blood cell; NEU, neutrophil; LYM, lymphocyte; CRP, C-reactive protein; PLT, platelet; AST, aspartate aminotransferase; ALT, alanine aminotransferase; eGFR, estimated glomerular filtration rate; PT, prothrombin time; PTINR, prothrombin time international normalized ratio; NLR, ratio of neutrophil and lymphocyte; CLR, ratio of CRP and lymphocyte; CAR, ratio of CRP and albumin.

Figure 1 The flow chart of subject inclusion in the study.

Figure 2 The comparison of systemic inflammatory indicators between surviving cases and fatal cases.

Figure 3 The performance of systemic inflammatory indicators in diagnosis of in-hospital mortality among COVID-19 patients.

Table 2 The Association Between Systemic Inflammatory Indicators and In-Hospital Mortality Among COVID-19 Patients Under Multivariate Analysis

Systemic Inflammatory Indicators	OR (95% CI)	P
NLR	3.81 (1.89, 7.69)	<0.0001
CLR	3.76 (1.89, 7.50)	<0.0001
CAR	5.10 (2.58, 10.07)	<0.0001

Abbreviations: NLR, ratio of neutrophil and lymphocyte; CLR, ratio of CRP and lymphocyte; CAR, ratio of CRP and albumin.

Table 3 The Clinical Efficacy of Corticosteroid Use on In-Hospital Mortality with Stratification of Systemic Inflammatory Indicators Under Multivariate Analysis

	Corticosteroid use beyond 72 hours		Corticosteroid use within 72 hours
	OR (95% CI)	P	OR (95% CI)	P
All patients	1.22 (0.57, 2.64)	0.601	2.88 (1.51, 5.53)	0.001
Age
<65 yrs	4.69 (0.49, 44.75)	0.179	1.59 (0.23, 10.79)	0.637
≥65 yrs	1.03 (0.45, 2.33)	0.949	2.52 (1.26, 5.02)	0.009
Number of comorbidities
≤1	0.73 (0.13, 4.02)	0.721	2.04 (0.45, 9.15)	0.352
≤3	0.77 (0.22, 2.77)	0.692	2.24 (0.93, 5.39)	0.072
>3	2.76 (0.61, 12.52)	0.187	6.24 (1.62, 23.98)	0.008
Severity of COVID-19
Mild/Moderate	1.02 (0.29, 3.62)	0.969	5.54 (1.85, 16.56)	0.002
Severe/Critical	1.38 (0.49, 3.86)	0.539	2.03 (0.92, 4.52)	0.081
Systemic inflammatory indicators
NLR<6.131	1.22 (0.22, 6.79)	0.817	3.55 (0.85, 14.97)	0.083
NLR≥6.131	0.92 (0.38, 2.28)	0.864	2.11 (0.98, 4.53)	0.055
CLR<45.455	0.21 (0.01, 3.68)	0.286	0.64 (0.09, 4.65)	0.657
CLR≥45.455	1.19 (0.53, 2.71)	0.673	2.94 (1.39, 6.22)	0.005
CAR<1.436	0.49 (0.05, 4.57)	0.533	1.13 (0.18, 7.01)	0.896
CAR≥1.436	0.93 (0.40, 2.20)	0.873	2.31 (1.05, 5.05)	0.036

Abbreviations: NLR, ratio of neutrophil and lymphocyte; CLR, ratio of CRP and lymphocyte; CAR, ratio of CRP and albumin.

Figure 4 The Kaplan-Meier plot of patient survival in three groups, based on the use of corticosteroid.