Dexamethasone may improve severe COVID-19 via ameliorating endothelial injury and inflammation: A preliminary pilot study

Abstract

Dexamethasone provides benefits in patients with coronavirus disease 2019 (COVID-19), although data regarding immunological profiles and viral clearance are limited. This study aimed to evaluate for differences in biomarkers among patients with severe COVID-19 who did and did not receive dexamethasone. We measured plasma biomarkers of lung epithelial/endothelial injury and inflammation in 31 patients with severe COVID-19 and in 13 controls. Changes in biomarkers and clinical parameters were compared during the 7-day period among COVID-19 patients, and also according to dexamethasone use. Thirty-two patients with severe COVID-19 who received mechanical ventilation (n = 6), high-flow nasal cannula (n = 11), and supplemental oxygen (n = 15) were analyzed. Relative to controls, patients with severe COVID-19 had significantly higher concentrations of biomarkers related to glycocalyx shedding (endocan and syndecan-1), endothelial injury (von Willebrand factor), and inflammation (soluble receptor for advanced glycation end-products [sRAGE] and interleukin-6). The 7-day decreases in biomarkers of endothelial injury (angiopoietin-2 [Ang-2] and intercellular adhesion molecule-1 [ICAM-1]) and sRAGE, but not in the biomarker of lung epithelial injury (surfactant protein D), were correlated with decreases in C-reactive protein and radiologic score at day 7. Twenty patients (63%) received dexamethasone, and the dexamethasone and non-dexamethasone groups differed in terms of disease severity. However, dexamethasone was associated marginally with increased SpO2/FiO2 and significantly with decreases in C-reactive protein and radiologic score after adjusting for baseline imbalances. Furthermore, the dexamethasone group exhibited a significant decrease in the concentrations of Ang-2, ICAM-1, soluble form of the Tie2 receptor (a biomarker of glycocalyx shedding), and sRAGE. Both groups exhibited a clinically insignificant increase in the cycle threshold value. Severe COVID-19 may be characterized by more severe endothelial injury and inflammation, and less severe lung epithelial injury. There is a possibility that dexamethasone improved severe COVID-19 and related endothelial injury without delaying viral clearance.

Endothelial glycocalyx damage in patients with severe COVID-19 on mechanical ventilation – A prospective observational pilot study

“…Our patients received therapeutic dosing of LMWH. Heparin has been proved to protect EG and EC [35] in COVID-19 patients and our results support this concept, despite the fact that anticoagulation therapy with LMWH is not standard of care in severe COVID-19 patients [36]. Another factor affecting our results could be the corticosteroid therapy that was administered to all our COVID-19 patients.…”

Plasma Soluble CD14 Subtype Levels Are Associated With Clinical Outcomes in Critically Ill Subjects With Coronavirus Disease 2019

“…Enhanced understanding of pathogenic immune pathways has the potential to inform an improved approach to therapy. We found that sCD14-ST is independently associated with VFDs when adjusting for IL-6 and CRP, commonly measured inflammatory biomarkers ( 44 ). We hypothesize that the use of a therapeutic targeting the CD14 pathway may have benefit in addition currently used immunomodulatory medications.…”

An intra-cytoplasmic route for SARS-CoV-2 transmission unveiled by Helium-ion microscopy

“…This response can lead to a fatal multiorgan failure and subsequent death. Although therapeutic options are available, like corticosteroids 15 or cytokines adsorption 16 , they cannot always control this often fatal progression of the coronavirus disease (COVID19). Despite a large percentage of the population in several countries being vaccinated, the occurrence of new symptomatic infections in individuals who were effectively vaccinated (“breakthrough infections” in vaccine-responders) has raised the question as to the cause of immune escape and renewed disease progression by SARS-CoV-2 17 .…”