Temporal change in Syndecan-1 as a therapeutic target and a biomarker for the severity classification of COVID-19

Abstract

Background Coronavirus disease 2019 (COVID-19) pneumonitis associated with severe respiratory failure is associated with high mortality. The pathogenesis of COVID-19 is associated with microembolism or microvascular endothelial injuries. Here, we report that syndecan-1 (SDC-1), a component of the endothelial glycocalyx, may be a biomarker of severity classification for COVID-19 related to endothelial injury. Methods and analysis We analyzed the data of COVID-19 patients for 1 year from February 2020 at Yokohama City University Hospital and Yokohama City University Medical Center Hospital. We selected COVID-19 patients who required admission care, including intensive care, and analyzed the classification of severe and critical COVID-19 retrospectively, using various clinical data and laboratory data with SDC-1 by ELISA. Results We analyzed clinical and laboratory data with SDC-1 in five severe COVID-19 and ten critical COVID-19 patients. In the two groups, their backgrounds were almost the same. In laboratory data, the LDH, CHE, and CRP levels showed significant differences in each group (P = 0.032, P < 0.0001, and P = 0.007, respectively) with no significant differences in coagulation-related factors (platelet, PT-INR, d-dimer, ISTH score; P = 0.200, 0.277, 0.655, and 0.36, respectively). For the clinical data, the SOFA score was significantly different from admission day to day 14 of admission (p < 0.0001). The SDC-1 levels of critical COVID-19 patients were significantly higher on admission day and all-time course compared with the levels of severe COVID-19 patients (P = 0.009 and P < 0.0001, respectively). Conclusions Temporal change of SDC-1 levels closely reflect the severity of COVID-19, therefore, SDC-1 may be a therapeutic target and a biomarker for the severity classification of Covid-19.

Mineralocorticoid receptor-antagonism prevents COVID-19-dependent glycocalyx damage

“…Of note, the level of eGC damage depends on the severity of the disease course: sera derived from patients with mild symptoms reduced the eGC by approximately 49%, whereas sera from patients with severe symptoms reduced the height of the eGC by > 60%. This underscores clinical observations showing correlations between disease severity and syndecan-1 levels [30,31].…”

Relationship Between Endothelial and Angiogenesis Biomarkers Envisage Mortality in a Prospective Cohort of COVID-19 Patients Requiring Respiratory Support

“…Elevation of the endothelial injury biomarkers, syndecan-1 and thrombomodulin (TM) in patients with sepsis is associated with intensive care unit (ICU) mortality ( 13 , 14 ). In COVID-19, reports of syndecan-1 increase are related to disease severity and have been suggested as an assessment of the clinical course of the patient ( 15 , 16 ). Soluble TM plasma elevation is also related to increased mortality in patients with COVID-19, as it marks direct endothelial cell damage ( 17 , 18 ).…”

Endothelial Glycocalyx Degradation in Critical Illness and Injury

“…Another study found that plasma heparanase activity and plasma heparan concentration were higher in COVID-19 patients compared to healthy controls, and that heparanase activity was significantly higher in ventilated ICU COVID patients vs. non-ICU COVID patients (62). Plasma syndecan-1 was significantly higher in COVID-19 patients classified as "critical" compared to those in the "severe" category; a difference that persisted for 14 days of ICU admission (63). A further study showed plasma HS concentrations were increased in COVID-19 patients compared to healthy controls (59,64) and were associated with the severity of disease (64).…”