Persistent Endothelial Dysfunction in Post-Acute COVID-19 Syndrome: A Case-Control Study

Biomedicines, Journal Year: 2021, Volume and Issue: 9(8), P. 957 - 957

Published: Aug. 4, 2021

Background: Endothelial dysfunction has a key role in the pathogenesis of coronavirus disease 2019 (COVID-19) and its disabling complications. We designed case-control study to assess alterations endothelium-dependent flow-mediated dilation (FMD) among convalescent COVID-19 patients. Methods: patients referred Pulmonary Rehabilitation Unit within 2 months from swab test negativization were consecutively evaluated for inclusion compared controls matched age, gender, cardiovascular risk factors. Results: A total 133 (81.2% males, mean age 61.6 years) (80.5% 60.4 included. significantly lower FMD was documented as (3.2% ± 2.6 vs. 6.4% 4.1 p < 0.001), confirmed when stratifying population according major clinical variables. Among cases, females exhibited higher values males (6.1% 2.9 2.5% 1.9, 0.001). Thus, no significant difference observed between cases subgroup analysis on 5.3% 3.4, = 0.362). patients, showed direct correlation with arterial oxygen tension (rho 0.247, 0.004), forced expiratory volume 1 s 0.436, vital capacity 0.406, diffusing carbon monoxide 0.280, 0.008). Overall, after adjusting confounders, recent independent predictor (β −0.427, Conclusions: Post-acute syndrome is associated persistent sex-biased endothelial dysfunction, directly correlated severity pulmonary impairment.

Language: Английский

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Cytokine storm and histopathological findings in 60 cases of COVID-19-related death: from viral load research to immunohistochemical quantification of major players IL-1β, IL-6, IL-15 and TNF-α

Forensic Science Medicine and Pathology, Journal Year: 2021, Volume and Issue: 18(1), P. 4 - 19

Published: Aug. 31, 2021

This study involves the histological analysis of samples taken during autopsies in cases COVID-19 related death to evaluate inflammatory cytokine response and tissue localization virus various organs. In all selected cases, SARS-CoV-2 RT-PCR on swabs collected from upper (nasopharynx oropharynx) and/or lower respiratory (trachea primary bronchi) tracts were positive. Tissue was detected using antibodies against nucleoprotein spike protein. Overall, we tested hypothesis that overexpression proinflammatory cytokines plays an important role development COVID-19-associated pneumonia by estimating expression multiple (IL-1β, IL-6, IL-10, IL-15, TNF-α, MCP-1), cells (CD4, CD8, CD20, CD45), fibrinogen. Immunohistochemical staining showed endothelial expressed IL-1β lung obtained group (p < 0.001). Similarly, alveolar capillary strong diffuse immunoreactivity for IL-6 IL-15 TNF-α a higher than control CD8 + T where more numerous Current evidence suggests storm is major cause acute distress syndrome (ARDS) organ failure consistently linked with fatal outcomes.

Language: Английский

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Intestinal barrier dysfunction as a key driver of severe COVID-19

World Journal of Virology, Journal Year: 2023, Volume and Issue: 12(2), P. 68 - 90

Published: March 21, 2023

The intestinal lumen harbors a diverse consortium of microorganisms that participate in reciprocal crosstalk with immune cells and epithelial endothelial cells, forming multi-layered barrier enables the efficient absorption nutrients without an excessive influx pathogens. Despite being lung-centered disease, severe coronavirus disease 2019 (COVID-19) affects multiple systems, including gastrointestinal tract pertinent gut function. Severe acute respiratory syndrome 2 (SARS-CoV-2) can inflict either direct cytopathic injury to or indirect immune-mediated damage. Alternatively, SARS-CoV-2 undermines structural integrity by modifying expression tight junction proteins. In addition, induces profound alterations microflora at phylogenetic metabolomic levels (dysbiosis) are accompanied disruption local responses. ensuing dysregulation gut-lung axis impairs ability system elicit robust timely responses restrict viral infection. vasculature is vulnerable SARS-CoV-2-induced injury, which simultaneously triggers activation innate coagulation condition referred as "immunothrombosis" drives thrombotic complications. Finally, increased permeability allows aberrant dissemination bacteria, fungi, endotoxin into systemic circulation contributes, certain degree, over-exuberant hyper-inflammation dictate form COVID-19. this review, we aim elucidate SARS-CoV-2-mediated effects on homeostasis their implications progression disease.

Language: Английский

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

Cells, Journal Year: 2022, Volume and Issue: 11(12), P. 1972 - 1972

Published: June 19, 2022

COVID-19 is a highly infectious respiratory disease caused by new coronavirus known as SARS-CoV-2. characterized progressive failure resulting from diffuse alveolar damage, inflammatory infiltrates, endotheliitis, and pulmonary systemic coagulopathy forming obstructive microthrombi with multi-organ dysfunction, indicating that endothelial cells (ECs) play central role in the pathogenesis of COVID-19. The glycocalyx defined complex gel-like layer glycosylated lipid–protein mixtures, which surrounds all living acts buffer between cell extracellular matrix. (EGL) plays an important vascular homeostasis via regulating permeability, adhesion, mechanosensing for hemodynamic shear stresses, antithrombotic anti-inflammatory functions. Here, we review findings described EGL damage ARDS, coagulopathy, multisystem associated Mechanistically, mediators, reactive oxygen species (ROS), matrix metalloproteases (MMPs), fragments, viral proteins may contribute to In addition, potential therapeutic strategies targeting treatment severe are summarized discussed.

Language: Английский

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COVID-19 associated pediatric vasculitis: A systematic review and detailed analysis of the pathogenesis

Seminars in Arthritis and Rheumatism, Journal Year: 2022, Volume and Issue: 55, P. 152047 - 152047

Published: June 10, 2022

Language: Английский

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Outcomes of Hospitalized Patients With COVID-19 With Acute Kidney Injury and Acute Cardiac Injury

Frontiers in Cardiovascular Medicine, Journal Year: 2022, Volume and Issue: 8

Published: Feb. 15, 2022

This study investigated the incidence, disease course, risk factors, and mortality in COVID-19 patients who developed both acute kidney injury (AKI) cardiac (ACI), compared to those with AKI only, ACI no (NI).This retrospective consisted of hospitalized at Montefiore Health System Bronx, New York between March 11, 2020 January 29, 2021. Demographics, comorbidities, vitals, laboratory tests were collected during hospitalization. Predictive models used predict AKI, ACI, AKI-ACI onset. Longitudinal analyzed time-lock discharge alive or death.Of 5,896 patients, 44, 19, 9, 28% had NI, AKI-ACI, respectively. Most presented very early (within a day two) hospitalization contrast (p < 0.05). Patients combined significantly older, more often men higher levels cardiac, kidney, liver, inflammatory, immunological markers NI groups. The adjusted hospital-mortality odds ratios 17.1 [95% CI = 13.6-21.7, p 0.001], 7.2 5.4-9.6, 4.7 3.7-6.1, 0.001] for respectively, relative NI. A predictive model onset using top predictors yielded 97% accuracy. data predicted up 5 days prior outcome, an area-under-the-curve, ranging from 0.68 0.89.COVID-19 markedly worse outcomes only Common variables accurately AKI-ACI. ability identify could lead earlier intervention improvement clinical outcomes.

Language: Английский

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Retinal vessels modifications in acute and post-COVID-19

Scientific Reports, Journal Year: 2021, Volume and Issue: 11(1)

Published: Sept. 29, 2021

Coronavirus disease 2019 (COVID-19) is an infectious caused by SARS-CoV-2 primarily affecting the respiratory system which can damage vessels walls virtually in any body district. Changes retinal are a good marker for systemic vascular alterations. This study investigated during acute phase of COVID-19 and after patients recovery. Fifty-nine eyes from 32 80 53 unexposed subjects were included. Mean arteries diameter (MAD) mean veins (MVD) assessed through semi-automatic analysis on fundus color photos at baseline 6 months later to virus. At MAD MVD significantly higher compared (p < 0.0001). Both decreased follow-up (from 97.5 ± 10.9 92.2 11.4 µm, p 0.0001 133.1 19.3 124.6 16.1 0.0001, respectively). Despite this reduction remained severe subjects. Transient dilation could serve biomarker inflammation while long-lasting alterations seen likely reflect irreversible structural should be further their possible effects tissues perfusion function.

Language: Английский

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Cardiovascular signatures of COVID-19 predict mortality and identify barrier stabilizing therapies

EBioMedicine, Journal Year: 2022, Volume and Issue: 78, P. 103982 - 103982

Published: April 1, 2022

Endothelial cell (EC) activation, endotheliitis, vascular permeability, and thrombosis have been observed in patients with severe coronavirus disease 2019 (COVID-19), indicating that the vasculature is affected during acute stages of SARS-CoV-2 infection. It remains unknown whether circulating markers are sufficient to predict clinical outcomes, unique COVID-19, if permeability can be therapeutically targeted.Prospectively evaluating prevalence inflammatory, cardiac, EC activation as well developing a microRNA atlas 241 unvaccinated suspected infection allowed for prognostic value assessment using Random Forest model machine learning approach. Subsequent ex vivo experiments assessed responses patient plasma were used uncover modulated gene regulatory networks from which rational therapeutic design was inferred.Multiple inflammatory biomarkers associated mortality COVID-19 severity-matched SARS-CoV-2-negative patients, while dysregulation specific microRNAs at presentation poor COVID-19-related outcomes revealed disease-relevant pathways. Integrating datasets approach further enhanced risk prediction in-hospital mortality. Exposure ECs resulted severity-specific expression barrier dysfunction, ameliorated angiopoietin-1 mimetic or recombinant Slit2-N.Integration multi-omics data identified stabilizing therapies should explored treatment endothelial dysfunction other diseases where has central role pathogenesis.This work directly supported by grant funding Ted Rogers Center Heart Research, Toronto, Ontario, Canada Peter Munk Cardiac Center, Canada.

Language: Английский

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S Protein, ACE2 and Host Cell Proteases in SARS-CoV-2 Cell Entry and Infectivity; Is Soluble ACE2 a Two Blade Sword? A Narrative Review

Vaccines, Journal Year: 2023, Volume and Issue: 11(2), P. 204 - 204

Published: Jan. 17, 2023

Since the spread of deadly virus SARS-CoV-2 in late 2019, researchers have restlessly sought to unravel how enters host cells. Some proteins on each side interaction between and cells are involved as major contributors this process: (1) nano-machine spike protein behalf virus, (2) angiotensin converting enzyme II, mono-carboxypeptidase key component renin system cell, (3) some proteases exploited by SARS-CoV-2. In review, complex process entrance into with contribution well sequential conformational changes tending increase probability complexification latter receptor cells, discussed. Moreover, release catalytic ectodomain II its soluble form extracellular space positive or negative impact infectivity considered.

Language: Английский

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Double Trouble—COVID-19 and the Widespread Use of Corticosteroids: Are We Staring at an Osteonecrosis Epidemic?

Indian Journal of Orthopaedics, Journal Year: 2021, Volume and Issue: 56(2), P. 226 - 236

Published: Oct. 26, 2021

A combination of immune-mediated vascular damage and routine use systemic corticosteroid (CS) therapy in COVID-19 may significantly increase the risk burden osteonecrosis (ON) after COVID-19. This narrative review explores pathogenesis, factors, possible preventive early treatment measures for ON For this review, an extensive literature search was performed using PubMed, Medline, Science Direct databases from January 2000 to August 2021 relevant articles on etiopathogenesis, epidemiology, clinical manifestations, severe acute respiratory syndrome coronavirus (SARS-CoV) infection steroid-induced (SION). Pathogenesis COVID-19, utility corticosteroids pathogenesis SION vis-a-vis SARS-CoV infection, associated diagnosis following CS were discussed. Preliminary data similar trends SARS 2003 epidemic indicate that "angiocentric" SARS-CoV-2 with high-dose patients. Risk stratification based intake during can help identify subjects at moderate high-risk where follow-up plans be initiated.

Language: Английский

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