Clinical diagnosis of severe COVID-19: A derivation and validation of a prediction rule

Table 1 Patient demographics and clinical characteristics in the training and internal validation sets

	Training sets			Internal testing sets
	Mild, n = 224 (62.0%)	Severe, n = 38 (10.5%)	P value	Mild, n = 90 (25.8%)	Severe, n = 9 (2.5%)	P value
Age (yr)	48.5 (36.0-59.0)	64 (57.5-66.0)		43.0 (34.0-54.8)	64.0 (62.0-69.0)
≥ 60 yr	54 (24.1)	26 (68.4)	0.000	14 (15.6)	8 (88.9)	0.000
Sex			0.002			0.159
Male	106 (47.3)	29 (76.3)		38 (42.2)	6 (66.7)
Female	118 (52.7)	9 (23.7)		52 (57.8)	3 (33.3)
BMI > 24	57 (25.4)	11 (28.9)	0.000	22 (24.4)	4 (44.4)	0.024
BMI > 27	21 (9.4)	14 (36.8)		5 (5.6)	2 (22.2)
Onset to hospitalization (> 5 d)	62 (27.7)	25 (65.8)	0.000	34 (37.8)	5 (55.6)	0.000
Symptoms
Fever > 37.3°C	172 (76.8)	29 (76.3)	0.000	78 (86.7)	7 (77.8)	0.005
Fever > 39°C	8 (3.6)	7 (18.4)		1 (1.1)	2 (22.2)
Charlson index > 0	72 (32.2)	33 (86.8)	0.000	39 (43.3)	8 (88.9)	0.000
P/F	13 (5.8)	16 (42.1)	0.000	3 (3.3)	3 (33.3)	0.006
NLR > 2	80 (35.7)	15 (39.5)	0.000	39 (16.7)	3 (33.3)	0.009
NLR > 4	24 (10.7)	17 (44.7)		7 (7.8)	4 (44.4)
Score ≥ 7	31 (13.8)	35 (92.1)	0.000	13 (13.1)	9 (100)	0.000

BMI: Body mass index; P/F: PaO₂/FiO₂; NLR: Neutrophil/lymphocyte ratio.

Table 2 Demographic clinical characteristics of external validation sets

	Mild, n = 110 (%)	Severe, n = 16	P value
Age (yr)	49.0 (35.0-57.8)	70.0 (64.0-78.0)
> 60	27 (24.6)	12 (75.0)	0.000
Sex			0.007
Male	51 (46.4)	13 (81.3)
Female	59 (53.6)	3 (18.7)
BMI > 24	30 (27.3)	8 (50.0)	0.021
> 27	15 (13.6)	4 (25.0)
Onset to hospitalization (> 5 d)	37 (33.6)	15 (94.0)	0.000
Symptoms
Fever > 37.3°C	87 (79.1)	12 (75.0)	0.025
Fever > 39°C	4 (3.6)	3 (18.8)
Charlson index > 0	54 (49.1)	15 (93.8)	0.000
P/F	1 (0.9)	6 (37.5)	0.000
NLR > 2	44 (40.0)	2 (12.5)	0.000
NLR > 4	6 (5.5)	14 (87.5)
Score ≥ 7	23 (20.9)	15 (93.8)	0.000

BMI: Body mass index; P/F: PaO₂/FiO₂; NLR: Neutrophil/lymphocyte ratio.

Table 3 Risk factors of severe patients with coronavirus disease 2019

Variable	Univariate analysis		Multivariate analysis
	OR	P value	OR	P value
Age ≥ 60 yr	6.821 (3.224-14.431)	0.000	-	-
Sex	3.587 (1.624-7.924)	0.002	-	-
BMI	2.701 (1.727-4.224)	0.000	3.939 (1.409-11.015)	0.009
Illness onset at admission	5.025 (2.418-10.441)	0.000	7.107 (1.449-34.849)	0.016
Smoker	4.060 (1.912-8.621)	0.000	-	-
Dry cough	3.395 (1.604-7.184)		-	-
Productive sputum	2.612 (1.284-5.312)	0.008	-	-
Fever	4.615 (1.948-10.935)	0.001	6.794(1.401-32.951)	0.017
Shortness of breath	3.312 (1.161-9.448)	0.025	-	-
Fatigue	3.450 (1.661-7.164)	0.001	-	-
Charlson index	2.371 (1.813-3.100)	0.000	2.917 (1.279-6.654)	0.011
PaO2/FiO2	11.804 (5.028-27.714)	0.000	17.570 (1.117-276.832)	0.041
Platelet count	0.423 (0.180-0.992)	0.048	-	-
NLR	3.766 (2.271-6.245)	0.000	3.574 (1.048-12.191)	0.042
D-Dimer	4.385 (2.102-9.148)	0.000	-	-
ESR	11.023 (2.583-47.048)	0.001	-	-
hs-CRP	4.314 (2.359-7.887)	0.000	-	-
AST	6.332 (2.753-14.563)	0.000	-	-
Cr	16.258 (3.994-66.188)	0.000	-	-
IL-6	2.346 (1.224-4.494)	0.010	-	-
PCT	3.961 (1.062-14.772)	0.040	-	-
ROX	0.237 (0.111-0.505)	0.000	-	-

BMI: Body mass index; NLR: Neutrophil/lymphocyte ratio; ESR: Erythrocyte sedimentation rate; CRP: C-reactive protein; AST: Aspartate aminotransferase; IL: Interleukin; PCT: Procalcitonin.

Table 4 The proposed score rules for clinical diagnosis of severe coronavirus disease 2019

Variables	Description	Score
BMI	≥ 24	1
	≥ 27	2
Time from onset to admission	≥ 5 d	2
Fever	≥ 37.3 °C	2
	≥ 39 °C	4
Charlson index		1
P/F score	< 300	6
NLR	≥ 2	1
	≥ 4	2

BMI: Body mass index; P/F: PaO₂/FiO₂; NLR: Neutrophil/lymphocyte ratio.

Table 5 Comparison of predictive performance between the proposed method and CURB-65

	Proposed model	CURB-65
Internal validation
AUROC	0.941 (0.901-0.981)	0.704 (0.564-0.863)
Precision	0.270 (0.234-0.307)	1.000
Sensitivity	0.930 (0.896-0.964)	0.156 (0.085-0.228)
Specificity	0.622 (0.602-0.641)	1.000
External validation
AUROC	0.936 (0.886-0.987)	0.654 (0.518-0.791)
Precision	0.413 (0.261-0.565)	0.481 (0.254-0.708)
Sensitivity	0.927 (0.873-0.980)	0.292 (0.186-0.399)
Specificity	0.804 (0.728-0.880)	0.954 (0.925-0.983)

AUROC: Area under the receiver operating curve.