Infection & COVID: 15 papers
Peer-reviewed work on the endothelial glycocalyx, microvascular health and the ingredients in our formulas, newest first. Abstracts are indexed here and every paper links to the journal.
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Published paper
Association of COVID-19 with impaired endothelial glycocalyx, vascular function and myocardial deformation four months after infection
This case-control study compared 70 people four months after COVID-19 infection with 70 age- and sex-matched untreated hypertensive patients and 70 healthy controls, measuring glycocalyx thickness (sublingual perfused boundary region), endothelial and coronary function, arterial stiffness, cardiac strain, and blood markers. Post-COVID patients showed impaired glycocalyx, reduced flow-mediated dilatation and coronary flow reserve, and stiffer arteries — similar to hypertensive patients and worse than healthy controls — plus markedly higher oxidative stress and thrombomodulin. Right ventricular function was worse in the COVID group than in either comparison group, and residual cardiovascular symptoms tracked with these abnormalities.
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Published paper
Association between the lactate-albumin ratio and microcirculation changes in Pediatric Septic patients
This retrospective single-center study of 178 children with sepsis compared the lactate/albumin ratio (LAR) measured on PICU admission with sublingual video microscopy measures of the microcirculation taken at the same time. An elevated LAR (>0.5) was associated with reduced microvascular blood flow, lower small-capillary (4–6 µm) density, greater inflammation, more vasoactive support and higher mortality, but was not associated with glycocalyx thickness as measured by the perfused boundary region (PBR).
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Published paper
Endothelial Glycocalyx Integrity in Treatment-Naïve People Living with HIV before and One Year after Antiretroviral Treatment Initiation
This prospective observational study measured sublingual endothelial glycocalyx thickness (via the perfused boundary region, PBR) in 66 treatment-naive people living with HIV before and at 24 and 48 weeks after starting combination antiretroviral therapy. PBR fell progressively (indicating thicker, healthier glycocalyx) over the first year, with no significant difference between integrase inhibitor- and protease inhibitor-based regimens. Final values remained above previously reported healthy-control values, suggesting only partial recovery.
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Published paper
Relationship of the main indicators of systemic COVID-associated endotheliopathy with the morphofunctional state and hemodynamics of the retina and chorioid in the acute period of the disease
Russian researchers compared retinal and choroidal imaging (OCT) with sublingual microvascular glycocalyx measurements (GlycoCheck PBR) in 44 people convalescing from moderate or severe COVID-19 and 18 healthy volunteers. Patients showed thicker choroids and wider peripapillary retinal vessels in proportion to disease severity, and these ocular changes correlated with inflammatory/coagulation blood markers and with glycocalyx indices. The authors interpret this as indirect evidence linking post-COVID retinal microangiopathy to systemic endotheliopathy.
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Published paper
Endothelial glycocalyx improvement after six months and one-year of antiretroviral therapy in treatment naive patients with human immunodeficiency virus
This conference abstract reports on 54-58 newly diagnosed, treatment-naive HIV patients whose sublingual microvascular glycocalyx was measured with sidestream dark-field imaging (GlycoCheck) before and after starting antiretroviral therapy. Perfusion boundary region (PBR), an inverse marker of glycocalyx thickness, fell at 6 months and further at 12 months, indicating improved glycocalyx integrity, even though body weight and blood pressure rose over the same period.
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Published paper
Persistent capillary rarefication in long COVID syndrome
This prospective observational study used sublingual sidestream dark-field videomicroscopy with GlycoCheck software to compare microvascular structure and function in 27 long COVID patients, 15 healthy controls, and 16 historical critically ill COVID-19 patients. Long COVID patients showed a marked loss of the smallest capillaries and impaired capillary recruitment a median of ~18 months after infection, while glycocalyx thickness (PBR) was similar to healthy controls. The authors conclude that COVID-19 may leave persistent capillary rarefication, though the design cannot establish causality with symptoms.
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Published paper
Microvascular and proteomic signatures overlap in COVID-19 and bacterial sepsis: the MICROCODE study
This multi-center observational study compared sublingual microcirculation, glycocalyx dimensions (PBR by GlycoCheck) and 184 plasma proteins in 22 COVID-19 patients, 43 bacterial sepsis patients and 10 healthy controls. Microvascular and proteomic abnormalities were largely similar in the two diseases and tracked with illness severity rather than diagnosis. Two mutually opposed coregulated protein clusters were identified, and their ratio ("Microcode") predicted 28-day mortality/intubation in an independent COVID-19 cohort.
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Published paper
Vascular Endothelial Glycocalyx Damage in COVID-19
This narrative review, which includes a small structured literature search, argues that damage to the vascular endothelial glycocalyx is a common mechanism linking COVID-19 risk factors (hypertension, diabetes, obesity, smoking, cardiovascular disease) to severe outcomes such as ARDS, DIC, and microvascular thrombosis. The author proposes a new concept, 'systemic inflammation-reactive microvascular endotheliopathy' (SIRME), defined by inflammation, thrombogenic endothelial damage with increased permeability, and organ injury, with shed glycocalyx fragments or bilateral ground-glass lung shadows marking progression. Of six eligible clinical reports identified, all showed elevated circulating glycocalyx components in severe COVID-19.
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Published paper
Case Report: Endothelial Glycocalyx Damage in Critically ill Patients With SARS-CoV-2-Related Multisystem Inflammatory Syndrome (MIS-C)
This single-center case report describes two critically ill children with MIS-C in whom endothelial glycocalyx damage was documented using plasma syndecan-1 and sublingual video microscopy (GlycoCheck) alongside a marked systemic inflammatory response. Both children had abnormal perfused boundary region (PBR) values and reduced capillary density compared with a postoperative control child, and PBR normalized (1.68 and 1.54 microns) before transfer out of intensive care after immunoglobulin and methylprednisolone treatment plus supportive care. The authors argue that microcirculatory and glycocalyx involvement may partly explain shock, capillary leak, and prothrombotic features in MIS-C.
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Published paper
Apremilast improves endothelial glycocalyx and microvascular perfusion: a possible protective mechanism against COVID-19
In this randomized comparison, 90 patients with psoriasis received apremilast, etanercept, or cyclosporine for 4 months, with sublingual glycocalyx (perfused boundary region, GlycoCheck/SDF imaging), arterial stiffness, and echocardiographic measures assessed before and after treatment. Only apremilast was associated with a reduction in PBR (indicating thicker glycocalyx) and it produced greater improvements in microvascular perfusion, pulse wave velocity, central systolic blood pressure, and left ventricular strain than the comparators. The authors speculate that glycocalyx protection could relate to reported benefits of apremilast in COVID-19, but no COVID-19 outcomes were studied.
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Published paper
Visual and Biochemical Evidence of Glycocalyx Disruption in Human Dengue Infection, and Association With Plasma Leakage Severity
This prospective observational study in Vietnam re-analyzed stored sublingual sidestream dark-field videos with GlycoCheck software and measured plasma syndecan-1 and endocan in 75 patients with confirmed dengue and 12 outpatients with other febrile illness. Patients with the most severe grade of plasma leakage showed a thinner, more degraded glycocalyx (higher perfused boundary region) and much higher plasma levels of shed glycocalyx proteoglycans during the critical illness phase. There were no significant glycocalyx differences between mild outpatient dengue and other febrile illnesses.
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Published paper
Microvascular dysfunction in COVID-19: the MYSTIC study
This prospective, multi-center cross-sectional study used sublingual sidestream dark-field video microscopy (GlycoCheck) plus blood biomarkers to characterize microvascular and endothelial glycocalyx changes in 23 hospitalized COVID-19 patients versus 15 healthy controls. Patients showed marked loss of small capillaries, slower red blood cell velocity, and evidence of glycocalyx damage, most pronounced in those on mechanical ventilation. Higher perfused boundary region (thinner glycocalyx) and lower ADAMTS13 were associated with 60-day in-hospital mortality.
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Published paper
Tocilizumab improves oxidative stress and endothelial glycocalyx: A mechanism that may explain the effects of biological treatment on COVID-19
Eighty patients with rheumatoid arthritis were randomized to 3 months of the IL-6 receptor blocker tocilizumab or to intensified conventional DMARDs plus glucocorticoids, with 40 age- and sex-matched healthy subjects as a comparison group. Endothelial glycocalyx thickness (sublingual perfused boundary region, PBR), arterial stiffness, echocardiographic myocardial work/strain, and inflammatory and oxidative stress markers were measured before and after treatment. Tocilizumab was associated with reduced PBR (indicating thicker glycocalyx), lower arterial stiffness, greater falls in CRP and oxidative stress markers, and greater improvement in myocardial deformation and work than conventional treatment.
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Published paper
In Vivo Imaging of the Buccal Mucosa Shows Loss of the Endothelial Glycocalyx and Perivascular Hemorrhages in Pediatric Plasmodium falciparum Malaria
Researchers used incident dark-field video microscopy of the inner cheek (buccal mucosa) in Tanzanian children to measure the perfused boundary region (PBR), an inverse indicator of endothelial glycocalyx thickness, alongside plasma glycocalyx shedding markers. Children with severe malaria had a significantly increased PBR and higher circulating hyaluronic acid, heparan sulfate, sulfated glycosaminoglycans, syndecan-1 and glypican-1 than healthy controls, consistent with substantial glycocalyx loss. Imaging also revealed perivascular hemorrhages and sequestering late-stage parasites, and markers of vascular instability (low angiopoietin-1, high angiopoietin-2) tracked with these changes.
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Published paper
The impact of periodontal disease treatment on endothelium of sublingual microvessels
Thirty-five patients with severe chronic periodontitis had their sublingual microvessels assessed by sidestream/darkfield microscopy with GlycoCheck RI software before and after treatment. One group received only local anti-inflammatory therapy, the other also underwent periodontal surgery. Glycocalyx measures changed little early on, but six months after surgery the surgical group showed a reduced permeable glycocalyx thickness and increased red blood cell filling of the capillaries.
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