Sivelestat Inhibits Vascular Endothelial Injury Induced by Inflammatory Response and Improves the Prognosis of Hemorrhagic Fever with Renal Syndrome in Children: An Ambispective Cohort Study

Abstract

Wang Yi,1,2 Weikai Wang,3 Hua Zhang,2 Ying Wang,2 Yong Zhou,2 Zhangyan Guo,2 Jingmei Li,2 Le Ma,2 Dan Yao,2 Taining Zhang,3 Yanqiang Du,2 Li Liu1 1Department of Neonatology, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Pediatric Intensive Care Unit, the Affiliated Children’s Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 3Pediatric intensive care unit, Gansu Provincial Maternity and Child Health Hospital, Gansu Provincial Central Hospital, Lanzhou, Gansu, People’s Republic of ChinaCorrespondence: Li Liu, Department of Neonatology, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Yanta District, Xi’an, Shaanxi, 710003, People’s Republic of China, Email [email protected] Yanqiang Du, Department of pediatric intensive care unit, the Affiliated Children’s Hospital of Xi’an Jiaotong University, No. 69, Xiju Lane, Lianhu District, Xi’an, Shaanxi, 710003, People’s Republic of China, Email [email protected]: In Asia, Hanta virus (HTNV) results in severe hemorrhagic fever with renal syndrome (HFRS). The efficacy of sivelestat in treating children with HTNV-induced HFRS remains unclear.Methods: An ambispective cohort study was performed on children diagnosed with HFRS and hospitalized at the Children’s Hospital Affiliated to Xi’an Jiaotong University from August 2018 to 2023. Patients who received neutrophil elastin-inhibitor infusion between August 2019 and August 2023 were assigned to the sivelestat group, while patients who did not were assigned to the control group. The independent sample t test was used for inter-group analysis. The Chi-square test and Fisher’s exact probability test were used for categorical variables. Spearman correlation test was used to evaluate the correlation between two sets of continuous variables. Kaplan-Meier survival curve and Log -Rank test was used to evaluate the difference in cumulative probability of survival between the two groups.Results: No significant differences were observed between the two groups in gender, age, contact history, body mass index, HFRS severity, clinical indexes at admission. Compared to the control group, the sivelestat group exhibited a significant decrease in the interleukin-8 level at 48 h (28.5± 3 vs 34.5± 3.5) and 72 h (21.3± 4.5 vs 31.5± 5.6) (P< 0.05), as well as the ICAM-1 level at 48 h (553± 122 vs 784± 187) and 72 h (452± 130 vs 623± 85) (P< 0.05). The concentration of VCAM-1 in the sivelestat group exhibited a consistent downward trend. Moreover, the level of VCAM-1 was significantly lower than that in the control group at 24 h (1760± 289 vs 2180± 445), 48 h (1450± 441 vs 1890± 267), and 72 h (1149± 338 vs 1500± 396) (P< 0.05). Kaplan-Meier curve analysis revealed a statistically significant difference in the cumulative probability of survival between two groups (P = 0.041). In the secondary outcomes, the sivelestat group demonstrated a decrease in the utilization rate of mechanical ventilation and continuous renal replacement therapy (CRRT).Conclusion: Sivelestat may suppress neutrophil-mediated inflammatory response to reduce endothelial and organ damage, and improve clinical outcomes in children with severe hemorrhagic fever and renal syndrome.Keywords: Sivelestat, hemorrhagic fever with renal syndrome, vascular endothelial injury, inflammatory response, cohort study, children

Keywords

• sivelestat
• hemorrhagic fever with renal syndrome
• vascular endothelial injury
• inflammatory response
• cohort study
• children