Predictive accuracy of 4C Mortality Score and Acute Physiology and Chronic Health Evaluation scores for mortality in COVID-19 patients admitted to intensive care unit

Table 1 Calculation of 4C Mortality Score

Variable	4C Mortality Score
Age (years)
< 50	-
50-59	+2
60-69	+4
70-79	+6
≥ 80	+7
Sex at birth
Female	-
Male	+1
1Number of comorbidities
0	0
1	+1
≥ 2	+2
Respiratory rate (breaths/minute)
< 20	-
20-29	+1
≥ 30	+2
Peripheral oxygen saturation on room air (%)
≥ 92	-
< 92	+2
Glasgow coma scale score
15	-
< 15	+2
Urea (mmol/L)
< 7	-
7-14	+1
> 14	+3
C reactive protein (mg/L)
< 50	-
50-99	+1
≥ 100	+2

¹Comorbidities were defined by using Charlson comorbidity index.

Table 2 Baseline characteristics of all patients stratified by hospital outcome, n (%)

	All patients, n = 140	Alive, n = 121	Died, n = 19	P value
Age, years (mean ± SD)	55.6 ± 16.8	53.3 ± 16.6	70.1 ± 9.6	< 0.001
Sex				0.03
Male	87 (62.1)	71 (81.6)	16 (18.4)
Female	53 (37.9)	50 (94.3)	3 (5.7)
No of comorbidities				0.03
0	62 (44.3)	59 (95.2)	3 (4.8)
1	41 (29.3)	33 (80.5)	8 (19.5)
≥ 2	37 (26.4)	29 (78.4)	8 (21.6)
Process measures
Prone positioning				0.57
No	58 (41.4)	49 (85.5)	9 (15.5)
Yes	82 (58.6)	72 (87.8)	10 (12.2)
Mechanical ventilation				0.009
No	89 (63.6)	82 (92.1)	7 (7.9)
Yes	51 (36.4)	39 (76.5)	12 (23.5)
NIV + HFNP				0.15
No	50 (35.7)	46 (92.0)	4 (8.0)
Yes	90 (64.3)	75 (83.3)	15 (16.7)
Vasopressors				0.03
No	97 (69.3)	88 (90.7)	9 (9.3)
Yes	43 (30.7)	33 (76.7)	10 (23.3)
CRRT				0.69
No	138 (98.6)	120 (87.0)	18 (13.0)
Yes	2 (1.4)	1 (50.0)	1 (50.0)
COVID specific treatment
Antiviral agents				0.57
No	58 (41.4)	49 (84.5)	9 (15.5)
Yes	82 (58.6)	72 (87.8)	10 (12.2)
Monoclonal antibodies				0.16
No	109 (77.9)	91 (83.5)	18 (16.5)
Tocilizumab	30 (21.4)	29 (96.7)	1 (3.3)
Sotrovimab	1 (0.7)	1 (100)	0 (0)
Baricitinib				0.53
No	97 (69.3)	85 (87.6)	12 (12.4)
yes	43 (30.7)	36 (83.7)	7 (16.3)
Length of stay, days
ICU, median and [IQR]	5.9 [3.2-12.8]	5 [2.8-11.2]	13 [9.8-18.3]	0.004
Hospital, median and [IQR]	13.2 [7.7-22.6]	11.9 [7.3-21.9]	18.4 [14.1-22.3]	0.09

NIV: Non-invasive ventilation; HFNP: O₂ via high flow nasal prongs; CRRT: Continuous renal replacement therapy; ICU: Intensive care unit.

Table 3 Physiological and laboratory parameters of all patients stratified by hospital outcome

	All patients, n = 140	Alive, n = 121	Died, n = 19	P value
At hospital admission
Respiratory rate (breath/minute)	28.8 ± 9.8	29.4 ± 10.2	25.4 ± 6.1	0.10
Peripheral oxygen saturation on room air (%)	92.6 ± 7.3	92.2 ± 7.7	94.8 ± 2.7	0.14
Glasgow coma scale score	14.7 ± 1.1	14.7 ± 1.2	14.6 ± 0.8	0.55
Urea (mmol/L)	6.8 ± 5.0	6.4 ± 4.5	8.9 ± 7.4	0.048
C reactive protein (mg/L) [IQR]	75 [41-121]	74 [40-125]	89 [42-107]	0.81
At ICU admission
Respiratory rate (breath/minute)	28.1 ± 9.5	28.2 ± 9.5	26.9 ± 9.3	0.56
Peripheral oxygen saturation on room air (%)	93.4 ± 3.9	93.5 ± 4.1	93.2 ± 2.8	0.75
Glasgow coma scale score	12.9 ± 4.3	12.9 ± 4.4	13.3 ± 3.8	0.72
Urea (mmol/L)	7.2 ± 4.4	6.8 ± 4.1	9.6 ± 5.4	0.01
C reactive protein (mg/L) [IQR]	75 [33-125]	64 [31-124]	100 [71-134]	0.09

mean ± SD. ICU: Intensive care unit.

Table 4 Predictive scores of all patients stratified by hospital outcome

	All patients, n = 140	Alive, n = 121	Died, n = 19	P value
Mortality prediction scores
4C Mortality Score at hospital admission	7.6 ± 4.2	7.2 ± 4.2	10.6 ± 2.7	< 0.001
4C Mortality Score at ICU admission	8.4 ± 4.2	7.8 ± 4.1	12.1 ± 2.6	< 0.0001
APACHE II	12.9 ± 5.4	12.3 ± 5.3	16.9 ± 4.5	0.0004
APACHE III	50.7 ± 18.0	48.1 ± 16.7	67.2 ± 17.5	< 0.0001

mean ± SD. ICU: Intensive care unit; APACHE: Acute Physiology and Chronic Health Evaluation.

Table 5 Predictive accuracy of 4C mortality and Acute Physiology and Chronic Health Evaluation scores

	AUROC	95%CI
4C Mortality Score at hospital admission	0.75	0.65-0.84
4C Mortality Score at ICU admission	0.80	0.71-0.88
APACHE II	0.75	0.65-0.85
APACHE III	0.79	0.69-0.90

APACHE: Acute Physiology and Chronic Health Evaluation; AUROC: Area under receiver operating characteristic curve; CI: Confidence interval.

Table 6 Optimal cut-off value for the four predictive scores

	Cut-off value	Sensitivity	Specificity	AUROC	95%CI for cut-off value
Hospital 4C mortality	9	0.74	0.72	0.73	7.2-10.8
ICU 4C mortality	10	0.84	0.72	0.78	8.9-11.1
APACHE II	14	0.68	0.67	0.68	11.8-16.2
APACHE III	56	0.79	0.73	0.76	52.0-60.0

APACHE: Acute Physiology and Chronic Health Evaluation; AUROC: Area under receiver operating characteristic curve; CI: Confidence interval.

Table 7 Comparison of mortality rates across intensive care unit 4C score risk groups, n (%)

Risk groups	Total, n = 140	Alive, n = 121	Died, n = 19
Low (0-3)	15	15	0
Intermediate (4-8)	59	58	1 (1.7)
High (9-15)	57	41	16 (28.1)
Very high (16-21)	9	7	2 (22.2)

Table 8 Comparison with previous studies

Ref.	Study design	Sample size	Mortality%	4C Mortality Score calculated at	Comparison	AUROC1	95%CI
Knight et al[2], United Kingdom	Multicenter prospective observational	22361	30.9	Hospital admission	Derivation and validation	0.77	0.76-0.77
Covino et al[12], Italy	Single centre retrospective	210	20	Hospital admission	COVID-GRAM, qCSI, NEWS	0.79	0.73-0.85
Wellbelove et al[10], United Kingdom	Exploratory analysis	53	11	Hospital admission	CURB-65, CRB-65, qSOFA, NEWS	0.83	0.71-0.95
Kuroda et al[11], Japan	Multicenter retrospective	693	34.4	Hospital admission	RISE-UP, A-DROP, REMS	0.84	0.80-0.88
Jones et al[13], Canada	Multicenter retrospective	959	23	Hospital admission	4C score in wave1, 2 and 3	0.77	0.74-0.80
Lombardi et al[3], France	Multicenter retrospective	14343	35.3	Hospital admission	32 scores	0.78	0.77-0.79
Vicka et al[6], Lithuania	Single centre retrospective	249	41.4	Hospital admission	APACHE II, SOFA, SAPS	0.75	0.69-0.81
Mohammad et al[8], Saudi Arabia	Multicenter retrospective	506	6.1	Hospital admission	External validation	0.90	0.85-0.95
Durie et al[5], Australia	Multicenter prospective observational	1492	13.2	ICU admission	APACHE II	0.79	0.68-0.90
Altreby et al[4], Saudi Arabia	Single centre retrospective	1493	37.9	ICU admission	External validation	0.81	0.79-0.83
Ocho et al[9], Japan	Multicenter retrospective	206	10.1	Hospital admission	A-DROP, CURB-65, SOFA	0.84	0.76-0.92
Our study	Single centre retrospective	140	13.6	Hospital admission, ICU admission	APACHE II, APACHE III	0.75, 0.80	0.65-0.84, 0.71-0.88

¹Indicates AUROC for 4C score.

²Indicates 149 of 461 patients with complete data.

APACHE: Acute Physiology and Chronic Health Evaluation; SOFA: Sequential Organ Failure Assessment; qSOFA: Quick SOFA; SAPS: Simplified Acute Physiology Score; CRB-65: Confusion, Respiratory rate, Blood pressure, 65 years of age and older; A-DROP: Age, Dehydration, Respiratory failure, Orientation failure, low blood Pressure; NEWS: National Early Warning Score; REMS: Rapid Emergency Medicine Score; RISE UP: Risk Stratification in the Emergency Department in Acutely ill Older Patients; qCSI: Quick COVID-19 Severity Index.