Endothelial glycocalyx degradation in multisystem inflammatory syndrome in children related to COVID-19

Abstract

Multisystem inflammatory syndrome in children (MIS-C) represents a rare but severe complication of severe acute respiratory syndrome coronavirus 2 infection affecting children that can lead to myocardial injury and shock. Vascular endothelial dysfunction has been suggested to be a common complicating factor in patients with coronavirus disease 2019 (COVID-19). This study aims to characterize endothelial glycocalyx degradation in children admitted with MIS-C. We collected blood and urine samples and measured proinflammatory cytokines, myocardial injury markers, and endothelial glycocalyx markers in 17 children admitted with MIS-C, ten of which presented with inflammatory shock requiring intensive care admission and hemodynamic support with vasopressors. All MIS-C patients presented signs of glycocalyx deterioration with elevated levels of syndecan-1 in blood and both heparan sulfate and chondroitin sulfate in the urine. The degree of glycocalyx shedding correlated with tumor necrosis factor-α concentration. Five healthy age-matched children served as controls. Patients with MIS-C presented severe alteration of the endothelial glycocalyx that was associated with disease severity. Future studies should clarify if glycocalyx biomarkers could effectively be predictive indicators for the development of complications in adult patients with severe COVID-19 and children with MIS-C. Key messages Children admitted with MIS-C presented signs of endothelial glycocalyx injury with elevated syndecan-1 and heparan sulfate level. Syndecan-1 levels were associated with MIS-C severity and correlated TNF-α concentration. Syndecan-1 and heparan sulfate may represent potential biomarkers for patients with severe COVID-19 or MIS-C.

Antibody response in children with multisystem inflammatory syndrome related to COVID-19 (MIS-C) compared to children with uncomplicated COVID-19

“…A prolonged presence of SARS-CoV-2 in the intestinal tract induce the release of zonulin, an important regulator of the intestinal permeability through modulation of intercellular tight junctions, into the bloodstream ( 29 ). Other soluble marker of barrier dysfunction, such as the measure of syndecan 1 (SD1) in MIS-C children has already been assessed in a sub-group of our MIS-C children ( 37 ). These results have shown that MIS-C children present signs of endothelial glycocalyx lesions with an association between the degree of damage of glycocalyx and the severity of MIS-C.…”

Myeloperoxidase inhibition may protect against endothelial glycocalyx shedding induced by COVID-19 plasma

“…Thus, hypertension may confound the increased in soluble EG degradation observed. Nonetheless, elevated sydencan-1 levels have been observed in younger populations with severe COVID-19 (31). Lastly, we could not compare differences in MPO activities in in vitro soluble EG shedding between acute and convalescent phases, owing to technical issues.…”

Vascular Endothelial Glycocalyx Damage and Potential Targeted Therapy in COVID-19

“…In a recent clinical study, the endothelial glycocalyx degradation was observed in all MIS-C subjects, with elevated levels of syndecan-1 in blood and increased HS and CS in the urine. Moreover, the degree of the glycocalyx deterioration was highly corrected with disease severity [ 95 ]. More importantly, children have a unique endothelial surface layer that differs from adults, but studies evaluating glycocalyx damage in pediatric diseases are relatively few [ 96 ].…”