Syndecan-1, an indicator of endothelial glycocalyx degradation, predicts outcome of patients admitted to an ICU with COVID-19

Dong Zhang,Qiuju Cui,Yanli Yang,Kedi Wen,Meng Xiao,Surita Aodeng,Yingchun Xu,Jie Ma,Yongzhe Li,Jing Xie,Yu Chen,Liubing Li

doi:10.1186/s10020-021-00412-1

Abstract

BackgroundWe investigated the feasibility of two biomarkers of endothelial damage (Syndecan-1 and thrombomodulin) in coronavirus disease 2019 (COVID-19), and their association with inflammation, coagulopathy, and mortality.MethodsThe records of 49 COVID-19 patients who were admitted to an intensive care unit (ICU) in Wuhan, China between February and April 2020 were examined. Demographic, clinical, and laboratory data, and outcomes were compared between survivors and non-survivors COVID-19 patients, and between patients with high and low serum Syndecan-1 levels. The dynamics of serum Syndecan-1 levels were also analyzed.ResultsThe levels of Syndecan-1 were significantly higher in non-survivor group compared with survivor group (median 1031.4 versus 504.0 ng/mL, P = 0.002), and the levels of thrombomodulin were not significantly different between these two groups (median 4534.0 versus 3780.0 ng/mL, P = 0.070). Kaplan–Meier survival analysis showed that the group with high Syndecan-1 levels had worse overall survival (log-rank test: P = 0.023). Patients with high Syndecan-1 levels also had significantly higher levels of thrombomodulin, interleukin-6, and tumor necrosis factor-α. Data on the dynamics of Syndecan-1 levels indicated much greater variations in non-survivors than survivors.ConclusionsCOVID-19 patients with high levels of Syndecan-1 develop more serious endothelial damage and inflammatory reactions, and have increased mortality. Syndecan-1 has potential for use as a marker for progression or severity of COVID-19. Protecting the glycocalyx from destruction is a potential treatment for COVID-19.

Highlights

Coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a critical problem in many countries
Baseline characteristics of COVID‐19 patients We retrospectively examined the records of 49 patients with COVID-19 who were admitted to our intensive care unit (ICU) within a 3-month period (Table 1)
Comparison of laboratory characteristics between survivors and non‐survivors COVID‐19 patients The levels of Syndecan-1 were significantly higher in non-survivor group compared with survivor group, and the levels of thrombomodulin were not significantly different between these two groups

Summary

Introduction

Coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a critical problem in many countries. An elevated level of Ang-II increases the production of superoxide anion, thereby increasing oxidative stress, dysfunction, and damage of endothelial cells (Han et al 2018; Boegehold et al 2015). The binding of SARS-CoV-2 to ACE2 may lead to Ang-II-induced endothelial injury, and which has been observed in lung, kidney and other organs at autopsies in COVID-19 patients (Ackermann et al 2020; Su et al 2020). Recent studies reported the levels of Syndecan-1 and thrombomodulin in COVID-19 patients (Karampoor 2021; Juneja et al 2021; Suzuki et al 2021; Bouck et al 2021; Fraser 2020a; Goshua et al 2020). There are controversies regarding the association between these biomarkers and endothelial damage status in COVID-19 patients. We investigated the feasibility of two biomarkers of endothelial damage (Syndecan-1 and thrombomodulin) in coronavirus disease 2019 (COVID-19), and their association with inflammation, coagulopathy, and mortality

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