Association between serum endothelial glycocalyx biomarkers and prognosis in paediatric sepsis

Abstract

Objective

To investigate endothelial glycocalyx (eGCX) serum degradation products in children with sepsis and evaluate their association with clinical outcomes.

Methods

This retrospective observational study enrolled children diagnosed with sepsis and age- and sex-matched healthy controls. Sepsis severity was classified as mild or severe according to organ dysfunction and hypoperfusion. Severe cases were further grouped by shock presence, and shock cases were stratified based on 28-day survival. Clinical data were collected at admission, and blood samples were analysed for inflammatory markers (C-reactive protein, interleukin-6, procalcitonin [PCT]) and eGCX biomarkers (syndecan-1 [SDC-1], heparan sulfate [HS], hyaluronic acid [HA]).

Results

A total of 85 children with sepsis and 19 healthy controls were included. Serum SDC-1, HS and HA levels were significantly higher in patients with sepsis than in controls. Patients with severe sepsis showed elevated SDC-1, HS and HA levels compared with mild cases, and HA was further increased in those with shock. In the septic shock cohort, non-survivors had higher SDC-1, HS and HA levels than survivors. Moreover, SDC-1, HS and HA positively correlated with inflammatory markers and disease severity. Receiver operating characteristic analyses demonstrated that HA, SDC-1 and HS effectively distinguished severe from mild sepsis. Multivariate analysis identified SDC-1, HA and PCT as independent predictors of severe sepsis. In septic shock, SDC-1 ≥ 89.47 ng/mL predicted significantly lower 28-day survival (P = 0.004).

Conclusion

Serum eGCX levels are elevated in paediatric sepsis and correlate with inflammation and disease severity, indicating that eGCX biomarkers reflect the extent of endothelial injury and disease progression in paediatric sepsis.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12879-026-12688-x.

Introduction

Sepsis is a life-threatening systemic inflammatory response to infection characterised by abnormal immune responses and multiple organ dysfunction [1]. This condition is the leading cause of death among critically ill children admitted to paediatric intensive care units around the world [2]. Globally, the mortality rate of paediatric sepsis is around 25% [3], posing a serious threat to the life and safety of children. Septic shock, the most severe complication of sepsis, is defined as patients with acute circulatory failure and persistent hypotension even after adequate volume resuscitation [4]. In recent decades, with advances in diagnostic and treatment technology, the mortality rate of children with septic shock in developed countries has decreased, but the case fatality rate of sepsis in developing countries remains higher than that in developed countries [3]. However, there is currently no effective targeted therapy to substantially improve outcomes, highlighting the urgent need for a deeper understanding and innovative treatment strategies for paediatric sepsis.

The endothelial glycocalyx (eGCX) is a carbohydrate-rich layer lining the luminal surface of vascular endothelial cells and is composed of transmembrane proteoglycans such as syndecans, which connect to the intracellular cytoskeleton, and glypicans, which are anchored to the plasma membrane via a glycosylphosphatidylinositol linkage [5]. Composed primarily of core proteoglycans and glycosaminoglycan chains, most notably heparan sulfate (HS) and hyaluronic acid (HA), the eGCX plays a crucial role in maintaining vascular homeostasis by regulating permeability, vasomotor tone, coagulation and inflammatory responses [6, 7]. When the glycocalyx is damaged, its components, including syndecan-1 (SDC-1), HS and HA, are shed into the circulation, serving as useful biomarkers of endothelial injury [8, 9]. Although eGCX degradation is well documented in adult sepsis [10, 11], paediatric evidence remains limited. Most data come from children undergoing cardiac surgery or trauma, with few studies reporting elevated eGCX markers in paediatric sepsis linked to disease severity [12–14]. Recently, Sallee et al. [15] found higher HS and SDC-1 in children with sepsis-associated paediatric acute respiratory distress syndrome, highlighting their potential role in reflecting endothelial dysfunction and severity [16]. However, the broader clinical significance and outcome associations of these markers in paediatric sepsis remain unclear.

Therefore, this study was conducted to better characterise glycocalyx alterations in paediatric sepsis and to explore their clinical relevance. Specifically, we aimed to compare the serum levels of SDC-1, HS and HA among children with shock, sepsis without shock and healthy controls and to examine their correlations with inflammatory indicators and clinical outcomes. Clarifying these relationships may enhance our understanding of endothelial dysfunction in paediatric sepsis and support the development of early risk stratification tools based on vascular biomarkers.

Materials and methods

Study participants

This retrospective observational study enrolled patients aged between 1 month and 18 years who were diagnosed with sepsis or septic shock and admitted to the Department of Paediatrics at the First Affiliated Hospital of Xinxiang Medical University between March 2022 and December 2023. All cases were reevaluated and confirmed using the newly established Phoenix sepsis criteria [16] to ensure diagnostic accuracy. The sepsis group was further classified as mild or severe based on organ dysfunction (e.g. hypoxaemia, thrombocytopenia, coagulopathy, hyperbilirubinaemia) or evidence of tissue hypoperfusion, such as elevated lactate levels, prolonged capillary refill time or mottled skin [17]. The severe group was divided into shock and non-shock subgroups based on the presence of shock, whereas the shock group was further stratified into survival and death subgroups according to 28-day outcomes. Additionally, 19 age- and sex-matched healthy children were included as controls. The exclusion criteria were as follows: (1) incomplete clinical data; (2) presence of autoimmune diseases, inherited metabolic disorders, haematologic disorders, diabetes, chronic kidney failure or malignancies; and (3) lack of informed consent from the patient’s family.

This study was reviewed and approved by the Ethics Committee of the First Affiliated Hospital of Xinxiang Medical University (approval number: EC-024-602). The healthy control group was selected from the remaining serum samples obtained by the physical examination department. All participants’ family members were informed of the study details and provided signed consent forms in accordance with medical ethics requirements.

Data collection

Demographic data, including age, sex and weight, were collected for all patients. Organ failure scores, including the pediatric sequential organ failure assessment (pSOFA) and the paediatric critical illness score (PCIS), were recorded based on the worst values within the first 48 h after diagnosis. The pSOFA evaluates the severity of organ dysfunction in sepsis across six systems [18], whereas the PCIS assesses the severity of critical illness in children based on key physiological parameters [19]. Clinical outcomes were evaluated by 28-day mortality to assess patient prognosis.

Blood samples were collected into EDTA-Na₂/K₂ tubes within 24 h of admission, ensuring no haemolysis. Tubes were stored at room temperature or at 2–8 °C overnight. Serum was then separated and centrifuged again at approximately 1,000 × g for 20 min to remove any residual cells or debris, and the supernatant was collected for immediate assay. If immediate measurement was not possible, the supernatant was stored at − 80 °C, avoiding repeated freeze–thaw cycles. Standardised protocols were followed, and samples were processed promptly to minimise analytical errors and ensure accurate biomarker measurements.

Complete blood count, lactate levels, liver function (alanine aminotransferase, aspartate aminotransferase, bilirubin, blood ammonia), renal function (creatinine, blood urea nitrogen) and coagulation tests (prothrombin time, activated partial thromboplastin time [aPTT], fibrinogen) were analysed. Inflammatory markers included C-reactive protein (CRP), interleukin (IL)-6, procalcitonin (PCT), serum amyloid A (SAA) and high mobility group box 1 (HMGB1). Levels of SDC-1 (#EP0231), HS (#EH4010), HA (#EU2556) and HMGB1 (#EH0884) were determined using enzyme-linked immunosorbent assay kits (Feen Biotechnology Co., Ltd., Wuhan, China) according to the manufacturer’s instructions.

Statistical analysis

Relevant data were statistically analysed using SPSS 27.0 software (IBM, Armonk, NY, USA). As most variables deviated from a normal distribution, data were expressed as the median (M) with the interquartile range (Q1, Q3). Group comparisons were performed using the Mann–Whitney U test for non-parametric data, whereas the chi-squared test was applied to contingency table analyses. Spearman’s rank correlation was also conducted to assess associations between variables. Receiver operating characteristic (ROC) curve analysis was used to evaluate the association of eGCX degradation biomarkers with severe sepsis in paediatric patients. Logistic regression was applied to assess the association between potential risk factors selected based on univariate analyses and clinical relevance and the development of severe sepsis (dependent variable), and a multivariate model was constructed to evaluate their combined effect. Kaplan–Meier survival analysis, along with the log-rank test, was performed to compare outcomes between groups stratified by SDC-1 levels. GraphPad Prism 8.0 software was used to generate graphical representations. A two-sided P-value < 0.05 was considered statistically significant.

Results

Clinical and demographic characteristics of the study population

A total of 96 paediatric patients were screened for enrolment between March 2022 and December 2023. After diagnostic evaluation and follow-up, 11 were excluded due to autoimmune diseases (n = 3), inherited metabolic disorders (n = 1), diabetes mellitus (n = 1), acute-on-chronic renal failure (n = 1) or incomplete clinical data (n = 5). The final analysis included 85 confirmed cases of paediatric sepsis.

Nineteen age- and sex-matched healthy children (10 boys and 9 girls; median age 6 years) served as controls. Among the sepsis cohort, 54 were boys (63.53%) and 31 were girls (36.47%), with a median age of 5.12 (2.04, 9.75) years. No significant differences were observed between the sepsis and control groups in sex, age, weight or other baseline characteristics (P > 0.05).

The sepsis group was further classified into a mild group (n = 39) and a severe group (n = 46), the latter including 26 with septic shock and 20 without shock. All patients were followed for 28 days after dignosis, and 19 children in the shock group survived during follow-up. Compared with the mild group, the severe group exhibited significantly higher levels of HMGB1, PCT, IL-6, CRP, lactate, blood ammonia, D-dimer and aPTT and lower albumin levels (P < 0.05). The two groups did not differ significantly in height, weight, age, temperature, white blood cell count, SAA, fibrinogen or platelet count (P > 0.05). Detailed data are presented in Supplementary Table 1.

Comparison and clinical correlations of endothelial glycocalyx biomarkers in paediatric sepsis

Serum concentrations of SDC-1, HS and HA were significantly elevated in children with sepsis (n = 85) compared with healthy controls (n = 19) (Fig. 1A). Within the sepsis cohort, the severe group (n = 46) showed markedly higher levels of SDC-1 (82.34 [73.83–90.33] vs. 59.53 [55.86–66.18] ng/mL), HS (4,725.64 [4,180.29–6,588.34] vs. 3,509.55 [2,799.28–4,204.26] ng/mL) and HA (32.62 [17.59–57.12] vs. 6.55 [4.32–13.44] ng/mL) than the mild group (n = 39) (all P < 0.05) (Fig. 1B). When comparing the shock (n = 26) and non-shock (n = 20) subgroups within the severe group, only HA was significantly elevated in the shock subgroup (P < 0.05), whereas SDC-1 and HS showed no statistical differences (Fig. 1C).

Fig. 1.

Serum levels of glycocalyx degradation markers across different groups. Note: (A) Comparison of syndecan-1 (SDC-1), heparan sulfate (HS), and hyaluronic acid (HA) between healthy controls (red) and sepsis patients (blue). (B) Comparison of SDC-1, HS, and HA between mild sepsis (red) and severe sepsis (blue) groups. (C) Comparison of SDC-1, HS, and HA between non-shock (red) and shock (blue) subgroups in severe sepsis. Data are shown as median with interquartile range (IQR) as bar graphs, without individual data points. Statistical significance was assessed using the Mann–Whitney U test. ***P < 0.001; ****P < 0.0001; NS, not significant

In the septic shock cohort, 19 children survived and 7 died during the 28-day follow-up. Compared with the survivors, the non-survivors had significantly higher levels of SDC-1, HS, HA, HMGB1, IL-6 and blood ammonia, along with higher pSOFA and lower PCIS scores (all P < 0.05). The duration of hospitalisation was longer in the survival group (Table 1).

Table 1.

Comparison of glycocalyx biomarkers and clinical indicators between survival and death group in children with shock

Variable	Survival group (n = 19)	Death group (n = 7)	P
Clinical Characteristics
Age (years)	5.00 (2.17, 9.50)	7.00 (1.54, 9.00)	0.7593
Weight (kg)	20.00 (14.00, 40.00)	23.00 (12.65, 29.50)	0.6907
Height (cm)	113.00 (85.00, 143.00)	125.00 (80.00, 140.00)	0.9512
Length of stay (day)	20.00 (12.50, 30.50)	6.00 (5.00, 15.00)	0.0309
Temperature (℃)	38.80 (37.85, 39.00)	39.30 (38.75, 40.00)	0.0675
eGCX indicators
SDC-1 (ng/mL)	79.35 (69.35, 88.77)	107.07 (94.69, 112.10)	< 0.0001
HA (ng/mL)	4670.83 (4126.58, 5762.24)	8504.09 (7696.25, 9043.58)	0.0001
HS (ng/mL)	22.22 (15.92, 53.67)	70.61 (56.70, 570.12)	0.0005
Inflammatory indicators
PCT (ng/mL)	5.29 (1.31, 17.87)	13.72 (7.77, 85.05)	0.1224
SAA (mg/L)	213.20 (86.45, 401.36)	312.50 (246.85, 389.50)	0.2513
IL-6 (pg/mL)	48.44 (17.56, 196.50)	1081.00 (226.50, 3581.00)	0.0201
CRP (mg/L)	32.49 (9.43, 123.20)	34.40 (14.50, 122.79)	0.9285
HMGB1 (ng/mL)	905.17 (739.58, 1352.71)	2376.81 (2009.52, 2547.00)	0.0002
Other indicators
Lactate (mmol/L)	4.10 (2.80, 6.10)	6.70 (5.35, 7.00)	0.0687
Ammonia (µmol/L)	43.50 (30.25, 67.50)	81.00 (54.35, 111.75)	0.0178
pSOFA score	7.00 (6.00, 9.50)	11.00 (8.00, 11.50)	0.0245
PCIS score	66.00 (64.00, 70.00)	64.00 (60.00, 67.00)	0.0339
Glasgow score	9.00 (7.00, 11.50)	6.00 (5.50, 8.50)	0.0772
Organs involved (a)	3.00 (2.00, 4.00)	4.00 (3.50, 4.50)	0.3624

Note: Data are presented as median (interquartile range) and compared using the Mann–Whitney U test. SDC-1: Syndecan-1; HA: Hyaluronan; HS: Heparan sulfate; PCT: Procalcitonin; SAA: Serum amyloid A; IL-6: Interleukin-6; CRP: C-reactive protein; HMGB1: High mobility group box 1; pSOFA: pediatric sequential organ failure assessment; PCIS: paediatric critical illness score

To further investigate the clinical relevance of eGCX biomarkers, Spearman correlation analyses were conducted between eGCX components (SDC-1, HS, and HA) and indicators of disease severity, including lactate, blood ammonia, inflammatory markers, and critical illness scores. The results showed that SDC-1 was significantly positively correlated with blood ammonia, IL-6, SAA, PCT, and HMGB1, but not with CRP or lactate. In addition, HS was positively correlated with blood ammonia, IL-6, PCT, HMGB1, and the pSOFA score, whereas HA showed significant positive correlations with all biochemical and inflammatory markers (all P < 0.05) (Table 2).

Table 2.

Correlation analysis of glycocalyx degradation biomarkers syndecan-1, heparan sulfate, and hyaluronan with clinical indicators

Variable	SDC-1 (ng/mL)	HS (ng/mL)	HA (ng/mL)
Lactate	0.184	0.043	0.409*
Blood ammonia	0.317*	0.294*	0.348*
CRP	0.112	0.054	0.249*
IL-6	0.377*	0.309*	0.366*
SAA	0.227*	0.100	0.329*
PCT	0.344*	0.409*	0.367*
HMGB1	0.717*	0.673*	0.545*
pSOFA score	0.040	0.356*	0.243
PCIS score	-0.133	-0.043	-0.268

Note: Data are presented as Spearman correlation coefficients; * indicates P < 0.05. SDC-1, syndecan-1; HS, heparan sulfate; HA, hyaluronan; CRP, C-reactive protein; IL-6, interleukin-6; SAA, serum amyloid A; PCT, procalcitonin; pSOFA, pediatric sequential organ failure assessment; PCIS, paediatric critical illness score

Diagnostic accuracy of endothelial glycocalyx biomarkers in children with severe sepsis

The sepsis cohort was classified as mild or severe based on organ dysfunction or tissue hypoperfusion. Receiver operating characteristic curve analyses were conducted to evaluate the ability of eGCX biomarkers to distinguish severe from mild sepsis. Hyaluronic acid showed the highest diagnostic performance, with an area under the curve (AUC) of 0.858 (95% CI: 0.77–0.93; P < 0.001); at a cutoff of > 13.14 ng/mL, its sensitivity and specificity were 86% and 74%, respectively. Moreover, SDC-1 had an AUC of 0.852 (95% CI: 0.76–0.93), with a cutoff of 73.29 ng/mL, yielding 76% sensitivity and 94% specificity, and HS exhibited an AUC of 0.816 (95% CI: 0.72–0.90), with a cutoff of 4,116.63 ng/mL, sensitivity of 82% and specificity of 71% (Fig. 2).

Fig. 2.

Receiver operating characteristic curves for glycocalyx degradation markers. Note: ROC analysis of syndecan-1, heparan sulfate, and hyaluronic acid for distinguishing severe sepsis, showing AUC values and corresponding performance metrics

Factors associated with severe sepsis in children: univariate and multivariate logistic regression analysis

A univariate logistic regression analysis was performed with the development of severe sepsis as the outcome variable. The results showed a significant positive correlation with HA, HS, SDC-1, HMGB1, IL-6, CRP, PCT, D-dimer, lactate, GCS score, blood ammonia and albumin (P < 0.05).

To ensure a comprehensive selection of variables and avoid overfitting or omitting important factors, independent variables were screened based on group comparisons, univariate logistic regression and clinical relevance. Multivariate logistic regression, conducted using stepwise selection with severe sepsis as the dependent variable, identified SDC-1, HA and PCT levels as factors independently associated with severe sepsis (P < 0.05).

Association of endothelial glycocalyx biomarkers with 28-day mortality in paediatric septic shock

To evaluate the association of eGCX biomarkers with 28-day all-cause mortality in children with septic shock, ROC and Kaplan–Meier survival analyses were performed. The ROC analysis results showed that SDC-1 had the highest discriminative ability, with an AUC of 0.932 (95% CI: 0.836–1.000) and an optimal cutoff of 89.47 ng/mL (sensitivity 100%, specificity 79%). Heparan sulfate exhibited an AUC of 0.932 (95% CI: 0.823–1.000) with a cutoff of 7,812.08 ng/mL (sensitivity 71.4%, specificity 100%), whereas HA had an AUC of 0.797 (95% CI: 0.613–0.981) with a cutoff of 44.23 ng/mL (sensitivity 100%, specificity 48%) (Fig. 3). Kaplan–Meier analysis based on the SDC-1 cutoff demonstrated that children with SDC-1 ≥ 89.47 ng/mL had significantly lower 28-day survival than those with lower levels (P = 0.004) (Fig. 4).

Fig. 3.

Receiver operating characteristic curve for 28-day mortality in children with septic shock. Note: ROC analysis of syndecan-1, heparan sulfate, and hyaluronan levels in relation to 28-day mortality among paediatric patients with septic shock

Fig. 4.

Kaplan–Meier survival estimates for patients with shock based on syndecan-1 levels. Note: Kaplan-Meier survival curves comparing 28-day survival in patients with high vs. low syndecan-1 levels (cut-off: 89.47 ng/mL), with a significant survival difference (P = 0.004)

Discussion

In recent years, although the incidence of childhood sepsis has decreased considerably, it remains a rapidly progressing condition characterised by its complexity and the involvement of multiple organs and systems [16, 20]. Children are particularly vulnerable to sepsis due to their immature immune systems [21], and the condition can lead to severe outcomes, including death or long-term disability. More than 3 million children continue to die from sepsis every year, affecting the public health safety of children [16]. In the early stages of sepsis, the vascular endothelium is particularly affected, exhibiting prothrombotic, inflammatory and fibrinolytic changes. During the progression of sepsis, enzymes such as a disintegrin and metalloproteinase 15 and heparanase cleave glycoproteins (e.g. CD44) and glycosaminoglycans (e.g. HS), respectively, leading to degradation of the eGCX. After eGCX damage, the endothelial layer becomes thinner and more fragmented, with its degradation products released into the bloodstream. This phenomenon has been observed in both animal models of sepsis and in patients experiencing sepsis, trauma or shock [22–25]. Currently, the assessment of the eGCX in clinical studies relies on two primary methods, both providing indirect information. One approach measures eGCX degradation products in plasma/serum and urine, such as SDC-1, HA, HS and chondroitin sulfate. The other uses video microscopy to evaluate the eGCX in microcirculatory vessels [26]. In the present study, the first method was employed to extract markers from serum samples, enabling an assessment of endothelial cell damage and further exploring whether serum levels of glycocalyx components correlate with the severity of sepsis in children.

The present study found that the serum levels of SDC-1, HS and HA were significantly increased in children with sepsis, which is consistent with previous sepsis-related studies [27–29]. For example, Anand et al. [27] evaluated glycocalyx levels in healthy individuals and patients with sepsis and found that markers of glycocalyx damage, SDC-1 and HS, were significantly elevated in the latter compared with the former. Higher levels of SDC-1 were found in children with sepsis in a single-centre observational study [30]. In the present study, SDC-1, HS and HA levels were higher in children with severe sepsis than in those with mild sepsis, with HA showing the highest sensitivity, consistent with previous reports. Nelson et al. [28] found that HS and HA levels were elevated in patients with shock and were further increased in non-survivors. Similarly, SDC-1, HS and HA levels were significantly higher in the shock death group than in survivors. Correlation analysis identified SDC-1 and HA as independent risk factors for severe sepsis [31]. Receiver operating characteristic analysis showed that HA, HS and SDC-1 had high sensitivity and specificity for distinguishing children with severe sepsis and shock. These findings indicate that the extent of eGCX shedding closely reflects disease severity.

The present study found that the glycocalyx markers of sepsis, HA, HS and SDC-1 were positively associated with PCT, and in a recent comparative analysis of CRP and PCT as biomarkers for prognosis evaluation of paediatric sepsis, PCT proved to be a valuable biomarker for assessing the severity and management of sepsis in children [29]. Moreover, SDC-1, HA and HS levels were found to be more strongly associated with sepsis severity in children with shock than PCT. Glycocalyx degradation is driven by inflammatory mechanisms, where enzymes such as metalloproteinases, heparanase and hyaluronidase, activated by reactive oxygen species and pro-inflammatory cytokines, directly damage endothelial cells [32]. Heparan sulfate cleavage may also enhance Angiopoietin-2 expression, supporting the notion that cytokines may contribute to the pathophysiology driving glycocalyx degradation and endothelial damage [33]. Henrich et al. [34] reported that pro-inflammatory cytokines, including elevated tumour necrosis factor-alpha (TNF-α) in sepsis, increase vascular permeability and impair tissue perfusion. Consistently, the present study found positive correlations between glycocalyx degradation products and pro-inflammatory markers (IL-6, CRP, PCT), suggesting that cytokines amplify glycocalyx damage and endothelial dysfunction. The nuclear protein HMGB1, released during cellular stress or injury, acts as a pro-inflammatory mediator by promoting TNF-α and IL-1β production, further exacerbating glycocalyx and endothelial injury and impairing microcirculation [35]. Elevated HMGB1 levels in this cohort were associated with greater sepsis severity, supporting its role in linking pro-inflammatory cytokines to glycocalyx degradation and endothelial damage, consistent with previous observations [35].

Cytokine responses to infection in shock are closely linked to severe endothelial dysfunction, highlighting impaired microcirculation in vital organs as a central mechanism in sepsis and shock [36]. In the present study, elevated lactate levels in patients with severe sepsis suggested microcirculatory disturbances. A prospective cohort study using sublingual video microscopy in hospitalised children with sepsis found that prolonged capillary refill time was associated with increased glycocalyx degradation (2.21 vs. 2.08 μm; odds ratio: 2.65, 95% CI: 1.09–6.34; P = 0.02) [37]. Early lactate elevation has also been strongly linked to higher Paediatric Risk of Mortality III scores [38], and a lactate threshold of 2.2 mmol/L was associated with increased mortality risk (hazard ratio: 3.61, 95% CI: 1.24–10.54; P = 0.0189) [39]. In the present study, elevated lactate correlated positively with severe sepsis, reinforcing these associations. Glycocalyx degradation is further associated with albumin and D-dimer alterations. Hypoalbuminemia has been linked to disrupted microcirculation, increased vascular permeability and enhanced glycocalyx shedding in children with sepsis [40]. Glycocalyx maintains vascular osmotic pressure and prevents protein leakage, whereas HS binds antithrombin and enhances inhibition of thrombin and coagulation factors [41]. Its shedding can thus promote microthrombosis and capillary leakage. In the present study, children with severe sepsis exhibited lower albumin and higher D-dimer levels than those with mild sepsis, indirectly indicating that glycocalyx loss contributed to these changes.

This study has several limitations. First, it was conducted at a single centre with a relatively small sample of children with sepsis, which may limit the generalisability of the findings. Larger multi-centre studies are needed to confirm and extend these results. Second, data were collected at a single time point and do not capture dynamic changes in the condition. Additionally, factors such as cost and available facilities may affect the feasibility of incorporating these biomarker tests into routine clinical care. Despite these limitations, the study provides important insights into the associations between serum markers and sepsis severity in children, supporting further exploration in larger, longitudinal cohorts.

Conclusion

Elevated serum levels of SDC-1, HS and HA, along with their correlation with inflammatory markers and disease severity, indicate that eGCX biomarkers are closely linked to paediatric sepsis. Changes in these markers reflect the extent of glycocalyx injury and endothelial dysfunction, highlighting their potential role in assessing disease severity and guiding clinical management.

Supplementary Information

Below is the link to the electronic supplementary material.

Abbreviations

aPTT

activated partial thromboplastin time

AUC

Area under the curve

CD44

Cluster of differentiation 44

CI

Confidence interval

CRP

C-reactive protein

EDTA

Ethylenediaminetetraacetic acid

eGCX

endothelial glycocalyx

ELISA

Enzyme-linked immunosorbent assay

GCS

Glasgow Coma Scale

HA

Hyaluronic acid

HMGB1

High mobility group box 1

HS

Heparan sulfate

IL-6

Interleukin-6

PCIS

Paediatric critical illness score

PCT

Procalcitonin

ROC

Receiver operating characteristic

SAA

Serum amyloid A

SDC-1

Syndecan-1

pSOFA

Pediatric sequential organ failure assessment

Author contributions

Conception and design of the work: Liu L; Data collection: Ren RJ, Xu YP, Wang TJ, Zhan XW; Supervision: Liu L; Analysis and interpretation of the data: Ma HK, Wang ZY, Li SJ; Statistical analysis: Liu L, Li SJ; Drafting the manuscript: Liu L; Critical revision of the manuscript: all authors; Approval of the final manuscript: all authors.

Funding

Study on the protective mechanism of blood purification on endothelial polysaccharide coating in children with severe sepsis by removing inflammatory mediators (No. QN-2022-A17).

Data availability

All data generated or analyzed during this study are included in the article.

Declarations

Ethics approval and consent to participate

This study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of The First Affiliated Hospital of Xinxiang Medical University (Approval number: EC-024-602). All study participants’ family members were informed of the study details and signed consent forms.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.