Glycocalyx as Possible Limiting Factor in COVID-19

Wadowski, Patricia P.; Jilma, Bernd; Kopp, Christoph W.; Ertl, Sebastian; Gremmel, Thomas; Koppensteiner, Renate

doi:10.3389/fimmu.2021.607306

Cited by 31 publications

(44 citation statements)

References 79 publications

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“…Through both histology and electron microscopy, it was demonstrated that accumulation of viral inclusions and inflammatory cells occurred within the vascular endothelium of the lungs, heart, kidneys, and small bowel. In autopsy and surgical tissues, severe endothelial cell damage with disrupted cell membranes, intracellular virus, diffuse lymphocytic endotheliitis, and apoptotic bodies were found 109,131 . Johnson et al have shown through COVID‐19 autopsies that the lung alveoli were filled with fluid, eukaryotic material, and dead tissue.…”

Section: Pathogenesis Of Covid‐19mentioning

confidence: 99%

“…However, these positive findings seem to be limited to a predefined risk group of patients 80 . Controversy still remains regarding the use of high‐dose corticosteroids in viremia 80,142,146,280 and it has been reported that the use of steroids had adverse effects on GL integrity and En permeability 131 …”

Section: Therapeutic Approaches For Protecting the Glycocalyxmentioning

confidence: 99%

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Pathogenesis of COVID‐19 described through the lens of an undersulfated and degraded epithelial and endothelial glycocalyx

et al. 2021

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The glycocalyx surrounds every eukaryotic cell and is a complex mesh of proteins and carbohydrates. It consists of proteoglycans with glycosaminoglycan side chains, which are highly sulfated under normal physiological conditions. The degree of sulfation and the position of the sulfate groups mainly determine biological function. The intact highly sulfated glycocalyx of the epithelium may repel severe acute respiratory syndrome‐related coronavirus 2 (SARS‐CoV‐2) through electrostatic forces. However, if the glycocalyx is undersulfated and 3‐O‐sulfotransferase 3B (3OST‐3B) is overexpressed, as is the case during chronic inflammatory conditions, SARS‐CoV‐2 entry may be facilitated by the glycocalyx. The degree of sulfation and position of the sulfate groups will also affect functions such as immune modulation, the inflammatory response, vascular permeability and tone, coagulation, mediation of sheer stress, and protection against oxidative stress. The rate‐limiting factor to sulfation is the availability of inorganic sulfate. Various genetic and epigenetic factors will affect sulfur metabolism and inorganic sulfate availability, such as various dietary factors, and exposure to drugs, environmental toxins, and biotoxins, which will deplete inorganic sulfate. The role that undersulfation plays in the various comorbid conditions that predispose to coronavirus disease 2019 (COVID‐19), is also considered. The undersulfated glycocalyx may not only increase susceptibility to SARS‐CoV‐2 infection, but would also result in a hyperinflammatory response, vascular permeability, and shedding of the glycocalyx components, giving rise to a procoagulant and antifibrinolytic state and eventual multiple organ failure. These symptoms relate to a diagnosis of systemic septic shock seen in almost all COVID‐19 deaths. The focus of prevention and treatment protocols proposed is the preservation of epithelial and endothelial glycocalyx integrity.

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Section: Pathogenesis Of Covid‐19mentioning

confidence: 99%

Section: Therapeutic Approaches For Protecting the Glycocalyxmentioning

confidence: 99%

Pathogenesis of COVID‐19 described through the lens of an undersulfated and degraded epithelial and endothelial glycocalyx

et al. 2021

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“…However, in general, one has to be very careful when selecting an appropriate drug delivery carrier for the repurposing applications. Here, we focused on the development of an injectable anti-COVID formulation in order to facilitate fast delivery into the blood, wherein the damaged endothelial glycocalyx in COVID-19 patients [27][28][29][30][31][32] would preferably enable an enhanced uptake of the NIC drug out of the injected formulation.…”

Section: Introductionmentioning

confidence: 99%

“…It is worth mentioning here that BSA-based nano-biomaterials have been well-studied in the drug delivery field owing to their specificity of being able to get into an infected site. [40] In addition, albumin can easily be taken up by the virus-infected cells since a cytokine storm follows glycocalyx damage in elderly and severely affected COVID-19 patients [28][29][30][31]. In this context, we believed that BSA-coated Zein-NIC NPs would be highly preferred as an ideal injectable formulation for treating COVID-19 patients.…”

Section: Introductionmentioning

confidence: 99%

Bovine Serum Albumin-Coated Niclosamide-Zein Nanoparticles as Potential Injectable Medicine against COVID-19

Choi

Piao

2021

Materials

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(1) Background: COVID-19 has affected millions of people worldwide, but countries with high experimental anti-SARS-CoV-2 vaccination rates among the general population respectively show progress in achieving general herd immunity in the population (a combination of natural and vaccine-induced acquired immunity), resulting in a significant reduction in both newly detected infections and mortality rates. However, the longevity of the vaccines’ ability to provide protection against the ongoing pandemic is still unclear. Therefore, it is of utmost importance to have new medications to fight against the pandemic at the earliest point possible. Recently, it has been found that repurposing already existing drugs could, in fact, be an ideal strategy to formulate effective medication for COVID-19. Though there are many FDA-approved drugs, it has been found that niclosamide (NIC), an anthelmintic drug, has significantly high potential against the SARS-CoV-2 virus. (2) Methods: Here we deployed a simple self-assembling technique through which Zein nanoparticles were successfully used to encapsulate NIC, which was then coated with bovine serum albumin (BSA) in order to improve the drugs’ stability, injectablity, and selectivity towards the virus-infected cells. (3) Results: The particle size for the BSA-stabilized Zein-NIC nanohybrid was found to be less than 200 nm, with excellent colloidal stability and sustained drug release properties. In addition, the nanohybrid showed enhanced drug release behavior under serum conditions, indicating that such a hybrid drug delivery system could be highly beneficial for treating COVID-19 patients suffering from high endothelial glycocalyx damage followed by a cytokine storm related to the severe inflammations.

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“…Notably, treatment with soluble heparan sulfate or even heparin (a commonly used anticoagulant and vasodilator that is similar in structure to heparan sulfate [ 44 ]) potently blocked spike protein binding and viral infection ( 41 ). This finding is particularly interesting because degradation of heparan sulfate in the glycocalyx has previously been identified as an important contributor to ARDS and sepsis ( 45 ), two common and severe outcomes of COVID-19, and suggests that heparan sulfate could be a target for pharmaceutical inhibition of cell entry by SARS-CoV-2 ( 46 – 50 ). Together, this evidence suggests that heparan sulfate can serve as an important adhesion molecule for SARS-CoV-2 cell entry.…”

Section: Coronavirus Structure and Pathogenesismentioning

confidence: 88%

Pathogenesis, Symptomatology, and Transmission of SARS-CoV-2 through Analysis of Viral Genomics and Structure

et al. 2021

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Glycocalyx as Possible Limiting Factor in COVID-19

Cited by 31 publications

References 79 publications

Pathogenesis of COVID‐19 described through the lens of an undersulfated and degraded epithelial and endothelial glycocalyx

Pathogenesis of COVID‐19 described through the lens of an undersulfated and degraded epithelial and endothelial glycocalyx

Bovine Serum Albumin-Coated Niclosamide-Zein Nanoparticles as Potential Injectable Medicine against COVID-19

Pathogenesis, Symptomatology, and Transmission of SARS-CoV-2 through Analysis of Viral Genomics and Structure

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