Severe/critical COVID-19 early warning system based on machine learning algorithms using novel imaging scores

Table 1 Demographics and clinical features of patients

Variable		Classification	Overall (n = 153)	Common (n = 48)	Severe/critical (n = 105)	P value
Basic information and vital signs	Age, median (IQR)		69 (66, 74)	69.0 (66.0, 74.0)	69.0 (66.0, 76.0)	0.79
Comorbidity	Sex, n (%)	Male	78 (50.980)	19 (39.583)	59 (56.190)	0.057
		Female	75 (49.020)	29 (60.417)	46 (43.810)
	Heart rate, median (IQR)		90 (79, 102)	87.0 (79.0, 98.0)	91.0 (79.0, 104.0)	0.329
	Temperature, median (IQR)		36.7 (36.3, 37.1)	36.7 (36.4, 37.0)	36.7 (36.3, 37.2)	0.576
	Body mass index, mean (SD)		20.290 (9.929)	20.789 (7.825)	20.041 (10.819)	0.715
	Respiratory rate, median (IQR)		21 (20, 24)	20.0 (20.0, 22.0)	22.0 (20.0, 25.0)	P < 0.001
	Blood oxygen saturation, median (IQR)		94 (90, 97)	98.0 (96.0, 99.0)	92.0 (85.0, 95.0)	P < 0.001
	Coronary heart disease, n (%)	No	126 (82.353)	38 (79.167)	88 (83.810)	0.485
		Yes	27 (17.647)	10 (20.833)	17 (16.190)
	Pulmonary disease, n (%)	No	124 (81.046)	37 (77.083)	87 (82.857)	0.398
		Yes	29 (18.954)	11 (22.917)	18 (17.143)
	Diabetes, n (%)	No	99 (64.706)	30 (62.500)	69 (65.714)	0.699
		Yes	54 (35.294)	18 (37.500)	36 (34.286)
Laboratory tests	Platelet, mean (SD)		225.125 (86.792)	215.563 (73.367)	229.538 (91.997)	0.359
	Neutrophil, mean (SD)		5.469 (3.729)	3.821 (1.999)	6.230 (4.080)	P < 0.001
	Lymphocyte, mean (SD)		0.929 (0.418)	1.028 (0.373)	0.883 (0.429)	0.047
	Hemoglobin, mean (SD)		125.151 (17.785)	117.958 (16.285)	128.471 (17.464)	P < 0.001
	Alanine aminotransferase, median (IQR)		24 (15, 40)	16.0 (11.0, 24.0)	27.0 (19.0, 44.0)	P < 0.001
	Aspartate aminotransferase, median (IQR)		29 (21, 42)	21.0 (17.0, 27.0)	36.0 (26.0, 49.0)	P < 0.001
	Albumin, median (IQR)		32.6 (30.1, 35.5)	35.1 (31.5, 38.2)	31.9 (29.6, 34.4)	P < 0.001
	Total bilirubin, median (IQR)		10.0 (7.4, 14.2)	9.5 (6.9, 12.5)	10.7 (8.2, 14.6)	0.066
	Direct bilirubin, median (IQR)		4.4 (3.3, 6.2)	3.7 (3.1, 5.1)	4.9 (3.6, 7.0)	0.005
	Lactate dehydrogenase, median (IQR)		294 (239, 398)	251.0 (224.0, 284.0)	341.0 (266.0, 464.0)	P < 0.001
	Urea, median (IQR)		4.8 (3.6, 6.6)	4.0 (3.2, 5.0)	5.2 (4.0, 7.8)	0.002
	Creatinine, median (IQR)		72 (59, 88)	68.0 (59.0, 80.0)	75.0 (59.0, 91.0)	0.115
	Prothrombin time, median (IQR)		14.2 (13.6, 14.9)	14.1 (13.5, 14.5)	14.3 (13.8, 15.1)	0.019
	Activated partial thromboplastin time, median (IQR)		40.0 (36.0, 44.5)	38.9 (35.6, 42.9)	40.6 (36.3, 45.4)	0.035
	Fibrinogen, mean (SD)		5.208 (1.495)	4.640 (1.236)	5.468 (1.531)	0.001
	D-Dimer, mean (SD)		3.394 (5.451)	1.827 (3.304)	4.125 (6.065)	0.003
	C-Response Protein, mean (SD)		61.199 (66.732)	24.943 (30.023)	77.583 (72.082)	P < 0.001
	calcitoninogen, mean (SD)		0.483 (3.484)	0.047 (0.053)	0.678 (4.177)	0.305
	Ferritin, mean (SD)		956.507 (874.540)	486.000 (328.994)	1170.374 (957.550)	P < 0.001
Cytokines	IL-1, mean (SD)		3.639 (5.076)	2.853 (1.351)	3.996 (6.019)	0.213
	IL-2R, mean (SD)		895.375 (630.955)	621.844 (321.241)	1019.707 (694.756)	P < 0.001
	IL-6, mean (SD)		48.628 (88.255)	13.359 (15.597)	64.691 (101.986)	P < 0.001
	IL-10, mean (SD)		6.464 (8.108)	3.907 (5.734)	7.626 (8.738)	0.003
	IL-8, mean (SD)		22.083 (22.814)	13.900 (15.389)	25.802 (24.600)	0.004
	TNF, mean (SD)		10.424 (8.969)	9.158 (13.597)	11.000 (5.649)	0.256
Scores	IL6/IL10, mean (SD)		9.051 (15.654)	3.848 (3.570)	11.417 (18.241)	P < 0.001
	CURB65, median (IQR)		1 (1, 2)	1.0 (1.0, 1.0)	1.0 (1.0, 2.0)	0.035
	qSOFA, median (IQR)		1 (0, 1)	0.0 (0.0, 1.0)	1.0 (0.0, 1.0)	P < 0.001

Table 2 Characteristics of computed tomography scans

	Computed tomography scoring item	Overall (n = 110)	Common (n = 41)	Severe/Critical (n = 69)	P value
Right upper area	Crazy-paving pattern score, median (IQR)	0.000 (0.000, 0.000)	0.000 (0.000, 0.000)	0.000 (0.000, 0.000)	0.1
	Consolidation score, median (IQR)	0.000 (0.000, 0.000)	0.000 (0.000, 0.000)	0.000 (0.000, 1.000)	0.027
	GGO, median (IQR)	1.000 (1.000, 2.000)	1.000 (1.000, 1.000)	2.000 (1.000, 3.000)	0.003
	Overall lung involment score, median (IQR)	1.000 (1.000, 3.000)	1.000 (1.000, 1.000)	2.000 (1.000, 3.000)	0.006
Left upper area	Crazy-paving pattern score, median (IQR)	0.000 (0.000, 0.000)	0.000 (0.000, 0.000)	0.000 (0.000, 0.000)	0.071
	Consolidation score, median (IQR)	0.000 (0.000, 0.000)	0.000 (0.000, 0.000)	0.000 (0.000, 1.000)	0.019
	GGO, median (IQR)	1.000 (1.000, 2.000)	1.000 (0.000, 1.000)	2.000 (1.000, 2.000)	P < 0.001
	Overall lung involment score, median (IQR)	1.000 (1.000, 2.000)	1.000 (1.000, 1.000)	2.000 (1.000, 3.000)	P < 0.001
Right medium area	Crazy-paving pattern score, median (IQR)	0.000 (0.000, 0.000)	0.000 (0.000, 0.000)	0.000 (0.000, 1.000)	0.085
	Consolidation score, median (IQR)	0.000 (0.000, 1.000)	0.000 (0.000, 0.000)	0.000 (0.000, 1.000)	0.007
	GGO, median (IQR)	2.000 (1.000, 3.000)	1.000 (1.000, 2.000)	2.000 (1.000, 3.000)	0.002
	Overall lung involment score, median (IQR)	2.000 (1.000, 3.000)	1.000 (1.000, 2.000)	2.000 (2.000, 3.000)	P < 0.001
Left medium area	Crazy-paving pattern score, median (IQR)	0.000 (0.000, 0.000)	0.000 (0.000, 0.000)	0.000 (0.000, 1.000)	0.279
	Consolidation score, median (IQR)	0.000 (0.000, 1.000)	0.000 (0.000, 0.000)	0.000 (0.000, 2.000)	0.006
	GGO, median (IQR)	2.000 (1.000, 3.000)	1.000 (1.000, 1.000)	2.000 (1.000, 3.000)	0.001
	Overall lung involment score, median (IQR)	2.000 (1.000, 3.000)	1.000 (1.000, 2.000)	2.000 (1.000, 3.000)	P < 0.001
Right lower area	Crazy-paving pattern score, median (IQR)	0.000 (0.000, 1.000)	0.000 (0.000, 0.000)	0.000 (0.000, 1.000)	0.122
	Consolidation score, median (IQR)	0.000 (0.000, 1.000)	0.000 (0.000, 0.000)	0.000 (0.000, 2.000)	0.002
	GGO, median (IQR)	1.000 (1.000, 3.000)	1.000 (1.000, 2.000)	2.000 (1.000, 3.000)	0.004
	Overall lung involment score, median (IQR)	2.000 (1.000, 3.000)	1.000 (1.000, 2.000)	2.000 (1.000, 3.000)	P < 0.001
Left lower area	Crazy-paving pattern score, median (IQR)	0.000 (0.000, 0.000)	0.000 (0.000, 0.000)	0.000 (0.000, 0.000)	0.357
	Consolidation score, median (IQR)	0.000 (0.000, 1.000)	0.000 (0.000, 0.000)	0.000 (0.000, 1.000)	0.007
	GGO, median (IQR)	1.000 (1.000, 3.000)	1.000 (1.000, 1.000)	2.000 (1.000, 3.000)	P < 0.001
	Overall lung involment score, median (IQR)	2.000 (1.000, 3.000)	1.000 (1.000, 1.000)	2.000 (1.000, 3.000)	P < 0.001

IQR: Interquartile range.

Table 3 Comparison prediction performances of different models

	Model	AUC (95%CI)	Accuracy	Sensitivity	Specificity	PPV	NPV	F1
Mean	XGBoost	0.841 (0.690-0.987)	0.745	0.768	0.88	0.92	0.572	0.823
SD	XGBoost	0.044 (0.066-0.018)	0.052	0.122	0.16	0.098	0.169	0.033
Mean	RandomForest	0.843 (0.709-0.974)	0.731	0.698	0.975	0.988	0.554	0.809
SD	RandomForest	0.081 (0.139-0.025)	0.105	0.145	0.05	0.025	0.147	0.097
Mean	logistic	0.892 (NaN-NaN)	0.828	0.88	0.848	0.932	0.666	0.896
SD	logistic	0.069 (NaN-NaN)	0.079	0.119	0.189	0.087	0.177	0.066
Mean	LightGBM	0.813 (0.690-0.937)	0.324	0.671	0.956	NaN	0.324	NaN
SD	LightGBM	0.067 (0.098-0.038)	0.071	0.092	0.058	NaN	0.071	NaN
Mean	MLP	0.617 (0.397-0.829)	0.655	0.634	0.764	NaN	0.503	NaN
SD	MLP	0.219 (0.228-0.212)	0.162	0.326	0.172	NaN	0.099	NaN

AUC: Area under the curve; PPV: Pulse pressure variation; NPV: Nucleopolyhedroviruses.