Prognostic Value of Neutrophil-to-Lymphocyte Ratio in Predicting Death Risk in Patients with Severe Hand, Foot and Mouth Disease

Figures & data

Table 1 Clinicodemographic Characteristics of Patients with Severe HFMD

Characteristics	Survived (n=567)	Died (n=97)	P
Male/Female	359/208	59/38	0.639
Age, yr			0.006
≤3	439 (77.4)	87 (76.8)
>3–6	128 (22.6)	10 (20.2)
Rash	567 (100.0)	97 (100.0)	–
Fever	566 (99.8)	97 (100.0)	–
Duration of fever >3 d	448 (79.2)	72 (74.2)	0.276
Temperature (°C)			<0.001
37.3 to ≤38	60 (10.6)	0 (0)
38–39	218 (38.4)	19 (19.6)
39–40	289 (51.0)	78 (80.4)
Hypersomnia	458 (96.6)	91 (93.8)	0.190
Hyperarousal	294 (62.0)	91 (93.8)	<0.001
Limb shaking	392 (82.7)	83 (85.6)	0.492
Convulsion	99 (20.9)	18 (18.6)	0.605
Vomiting	350 (61.7)	64 (66.0)	0.425
Pathologic reflexes	562 (99.1)	97 (100.0)	–
Dyspnea	36 (6.30)	97 (100.0)	–
Circulatory disturbance	40 (7.05)	97 (100.0)	–
PCT (>0.20 ng/mL)	243 (42.9)	49 (50.5)	0.160
NLR, median (range)	1.92 (0.20, 19.35)	3.43 (0.62, 13.85)	<0.001
NLR, mean±SD	2.69 ± 2.44	4.17 ± 2.81	–
NLR (≤3 yr, n=526)	2.43 ±2.20	3.91 ±2.73	<0.001
NLR (3–6 yr, n=138)	3.63 ±2.94	6.46 ±2.63	<0.001
NLR>2.01	271 (47.8)	75 (77.3)	<0.001
Fasting blood glucose level > 8.3 mmol/L	78 (13.8)	86 (88.7)	<0.001
EV71-positivity	366 (64.6)	84 (86.6)	<0.001
Death^#	0 (0)	97 (14.6)	–

Notes: Values are n or n (%), unless otherwise noted. ^#Causes of death were acute pulmonary oedema, brainstem encephalitis and circulatory failure.

Abbreviations: HFMD, hand, foot, and mouth disease; EV71, enterovirus 71; WBC, white blood cell; NLR, neutrophil/lymphocyte ratio.

Figure 1 ROC curve and interactive dot diagram for calculating optimal cutoff value of NLR in in predicting mortality generated for 664 patients with critical HFMD.

Table 2 Analysis of Potential Risk Factors for Severe HFMD

Risk Factors	Unadjusted OR	Adjusted^#
Gender	1.112 (0.714–1.730)	1.131 (0.615–2.079)
Age	0.394 (0.199–0.781)**	0.557 (0.234–1.323)
High fever (> 39.0°C)	3.949 (2.330–6.694)***	3.342 (1.736–6.432)***
EV71-positivity	3.549 (1.930–6.524)***	3.200 (1.529–6.698)**
Fasting glucose > 8.3 mmol/L	49.014 (25.042–95.935)***	37.343 (18.616–74.909)***
NLR > 2.01	3.724 (2.252–6.157)***	2.142 (1.125–4.079) *

Notes: Values are OR (95% CI). ^#In multivariate logistic regression model (n = 664), we controlled for age, gender, High fever (> 39.0°C), EV71-seropositivity, fasting glucose and NLR > 2.01. *P < 0.05, **P < 0.01, ***P < 0.001

Abbreviations: EV71, enterovirus 71; NLR, neutrophil/lymphocyte ratio.

Table 3 Clinicodemographic Characteristics of Patients with Critical HFMD Who Died or Survived During the Study Period

Relevant Factors	Survived (n=40)	Died (n=97)	P
Male/female	27/13	59/38	0.462
Age, yr			0.027
≤3	30 (75.0)	87 (89.7)
>3	10 (25.0)	10 (10.3)
Rash	40 (100.0)	97 (100.0)	–
Fever	40 (100.0)	97 (100.0)	–
Duration of fever >3 d	34 (85.0)	72 (74.2)	0.171
Peak temperature (>39 °C)	30 (75.0)	78 (80.4)	0.481
Hypersomnia	40 (100.0)	91 (93.8)	–
Hyperarousal	39 (97.5)	91 (93.8)	0.290
Limb shaking	35 (87.5)	83 (85.6)	0.766
Convulsion	21 (53.8)	40 (41.2)	0.228
Vomiting	33 (82.5)	64 (66.0)	0.053
Pathologic reflexes	39 (97.5)	97 (100.0)	–
Dyspnoea	36 (90.0)	97 (100.0)	–
Circulatory disturbance	40 (100.0)	97 (100.0)	–
PCT (>0.20ng/mL)	27 (67.5)	49 (50.5)	0.07
NLR, median (range)	1.87 (0.25–14.08)	3.43 (0.62–13.85)	0.001
NLR, mean±SD	2.77 ± 2.70	4.17 ± 2.81	–
NLR (≤3 yr, n=117)	2.54 ± 2.08 (n=30)	3.91 ± 2.73 (n=87)	0.014
NLR (3–6 yr, n=20)	3.48 ± 4.11 (n=10)	6.46 ± 2.63 (n=10)	0.07
NLR > 2.50	13 (32.5)	66 (68.0)	<0.001
Fasting blood glucose level >8.3 mmol/L	14 (35.0)	86 (88.7)	<0.001
EV71-positivity	27 (67.5)	84 (86.6)	0.01

Note: Values shown are n or n (%), unless otherwise noted.

Abbreviations: HFMD, hand, foot, and mouth disease; EV71, enterovirus 71; WBC, white blood cell; NLR, neutrophil/lymphocyte ratio.

Figure 2 ROC curve and interactive dot diagram for calculating optimal cutoff value of NLR in predicting mortality generated for 137 patients with critical HFMD.

Table 4 Analysis of Risk Factors for Mortality Associated with Severe HFMD

Risk Factors	Unadjusted	Adjusted^#
Gender	0.345 (0.131–0.909)*	0.587 (0.212–1.630)
Age	1.338 (0.615–2.910)	0.671 (0.170–2.650)
EV71-positivity	3.111 (1.287–7.520)*	3.441 (1.132–10.462)*
NLR > 2.50	4.422 (2.012–9.717)***	4.166 (1.570–11.051)*
Fasting glucose > 8.3 mmol/L	14.519 (5.883–35.832)***	14.173 (4.920–40.827)***

Notes: Values are OR (95% CI). ^#In multivariate logistic regression model (n = 137), we controlled for age, gender, EV71-seropositivity, fasting glucose and NLR > 2.50. *P < 0.05, ***P < 0.001.

Abbreviation: NLR, neutrophil/lymphocyte ratio.