COVID-19 and Long COVID: Disruption of the Neurovascular Unit, Blood-Brain Barrier, and Tight Junctions

The Neuroscientist, Год журнала: 2023, Номер 30(4), С. 421 - 439

Опубликована: Сен. 11, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of disease 2019 (COVID-19), could affect brain structure and function. SARS-CoV-2 can enter through different routes, including olfactory, trigeminal, vagus nerves, blood immunocytes. may also from peripheral a disrupted blood-brain barrier (BBB). The neurovascular unit in brain, composed neurons, astrocytes, endothelial cells, pericytes, protects parenchyma by regulating entry substances blood. astrocytes highly express angiotensin converting enzyme (ACE2), indicating that BBB be disturbed lead to derangements tight junction adherens proteins. This leads increased permeability, leakage components, movement immune cells into parenchyma. cross microvascular an ACE2 receptor–associated pathway. exact mechanism dysregulation COVID-19/neuro-COVID is not clearly known, nor development long COVID. Various biomarkers indicate severity neurologic complications COVID-19 help objectively diagnose those developing review highlights importance disruption, as well some potentially useful COVID-19, COVID/neuro-COVID.

Язык: Английский

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Neutrophil degranulation, endothelial and metabolic dysfunction in unvaccinated long COVID patients

European Journal of Clinical Investigation, Год журнала: 2024, Номер 54(4)

Опубликована: Янв. 16, 2024

Abstract Background Long COVID symptoms are widely diffused and have a poorly understood pathophysiology, with possible involvement of inflammatory cytokines. Materials Methods A prospective follow‐up study involved 385 unvaccinated patients, started 1 month after SARS‐CoV‐2 infection continued for up to 12 months. We compared circulating biomarkers neutrophil degranulation, endothelial metabolic dysfunction in subjects long asymptomatic post‐COVID controls. Results The highest occurrence (71%) was 3 months from the infection, decreasing 62.3% 29.4% at 6 months, respectively. Compared controls, patients had increased levels neutrophilic degranulation indices MMP‐8 MPO, L‐selectin P‐selectin. Among dysfunction, leptin were higher than Conclusion In may persist year acute dysfunction. clinical implications specific require further attention, especially individuals fatigue COVID‐linked cognitive dysfunctions.

Язык: Английский

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Enhanced complement activation and MAC formation accelerates severe COVID-19

Cellular and Molecular Life Sciences, Год журнала: 2024, Номер 81(1)

Опубликована: Сен. 16, 2024

Emerging evidence indicates that activation of complement system leading to the formation membrane attack complex (MAC) plays a detrimental role in COVID-19. However, their pathogenic roles have never been experimentally investigated before. We used three knock out mice strains (1. C3

Язык: Английский

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Endothelial activation and damage as a common pathological substrate in different pathologies and cell therapy complications

Frontiers in Medicine, Год журнала: 2023, Номер 10

Опубликована: Ноя. 14, 2023

The endothelium is a biologically active interface with multiple functions, some of them common throughout the vascular tree, and others that depend on its anatomical location. Endothelial cells are continually exposed to cellular humoral factors, all those elements (biological, chemical, or hemodynamic) circulate in blood at certain time. It can adapt different stimuli but this capability may be lost if strong enough and/or persistent If loses adaptability it become dysfunctional, becoming potential real danger host. dysfunction present clinical conditions, such as chronic kidney disease, obesity, major depression, pregnancy-related complications, septic syndromes, COVID-19, thrombotic microangiopathies, among other pathologies, also association cell therapies, hematopoietic stem transplantation treatment chimeric antigen receptor T cells. In these diverse evidence suggests presence severity endothelial correlate associated disease. More importantly, has diagnostic prognostic value for development critical complications that, although differ according underlying have background common. Our multidisciplinary team women devoted many years exploring role mentioned diseases conditions. research group characterized mechanisms proposed biomarkers damage. A better knowledge would provide therapeutic strategies either prevent treat dysfunction.

Язык: Английский

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Soluble Proteoglycans and Proteoglycan Fragments as Biomarkers of Pathological Extracellular Matrix Remodeling

Proteoglycan Research, Год журнала: 2024, Номер 2(4)

Опубликована: Окт. 1, 2024

Proteoglycans and their proteolytic fragments diffuse into biological fluids such as plasma, serum, urine, or synovial fluid, where they can be detected by antibodies mass-spectrometry. Neopeptides generated the proteolysis of proteoglycans are recognized specific neoepitope act a proxy for activity certain proteases. Proteoglycan proteoglycan potentially used prognostic, diagnostic, theragnostic biomarkers several diseases characterized dysregulated extracellular matrix remodeling osteoarthritis, rheumatoid arthritis, atherosclerosis, thoracic aortic aneurysms, central nervous system disorders, viral infections, cancer. Here, we review main mechanisms accounting presence soluble in fluids, potential application biomarkers, highlight challenges opportunities ahead clinical translation.

Язык: Английский

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Angiogenic markers as prognostic tools in patients with COVID-19: CRACoV-HHS study

Kardiologia Polska, Год журнала: 2025, Номер unknown

Опубликована: Янв. 15, 2025

Язык: Английский

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VEGF-A in COVID-19: a systematic review and meta-analytical approach to its prognostic value

Clinical and Experimental Medicine, Год журнала: 2025, Номер 25(1)

Опубликована: Март 12, 2025

Abstract Numerous studies have reported vascular endothelial growth factor A (VEGF-A) has a significant impact on the pathophysiology of COVID-19. The objective this systematic review and meta-analysis is to determine prognostic value increased levels VEGF-A in individuals with literature search was conducted across multiple electronic databases, including PubMed, Web Science, Cochrane Library, Scopus, EMBASE, Google Scholar, up January 2024. Studies examining serum or plasma COVID-19 patients were incorporated, specific attention given contrasting severe/critical cases against moderate cases. Standardized mean differences (SMD) 95% confidence intervals (CIs) calculated using random-effects model overall effect sizes. Meta-regressions subgroup analyses performed explore potential sources heterogeneity. synthesized data from 11 involving total 1119 patients. Elevated significantly associated disease severity, pooled SMD 0.525 (95% CI 0.239–0.058; P = 0.028). Research indicated that nature relationship differs among various age groups, there minor discrepancies techniques employed obtain measurements. Furthermore, meta-regression analysis correlation between assay technique body mass index (BMI). This provides compelling evidence for potency Understanding intricate interplay holds promise development targeted therapeutic strategies indicators management

Язык: Английский

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MixOmics Integration of Biological Datasets Identifies Highly Correlated Variables of COVID-19 Severity

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(10), С. 4743 - 4743

Опубликована: Май 15, 2025

Despite several years passing since the COVID-19 pandemic was declared, challenges remain in understanding factors that can predict severity of disease and complications SARS-CoV-2 infection. While many large-scale multi-omic datasets have been published, integration these has potential to substantially increase biological insight gained, allowing a more complex comprehension pathogenesis. Such may improve our ability progression, detect severe cases rapidly develop effective therapeutics. In this study, we applied an innovative machine learning algorithm delineate COVID based on paired samples proteomic transcriptomic data from small cohort patients testing positive for infection with differential severity. Targeted plasma proteomics onco-immune targeted panel were performed sequential 23 severe, 21 moderate 10 mild patients. We DIABLO, new integrative method, identify multi-omics biomarker panels discriminate between multiple phenotypic groups, such as varied As is known among sample group, train models using outcome variable calculate features are important predictors disease. highly correlated key variables discriminant analysis methods. This approach highlights power patients, offering better molecular mechanisms driving opportunity prediction trajectories

Язык: Английский

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Systematic Review of Individual Patient Data COVID-19 Infection and Vaccination–Associated Thrombotic Microangiopathy

Kidney International Reports, Год журнала: 2024, Номер 9(11), С. 3134 - 3144

Опубликована: Авг. 8, 2024

IntroductionSporadic cases of atypical hemolytic uremic syndrome (aHUS) have been described in the literature association with COVID-19 infection and vaccination adults pediatric patients. The exact mechanisms underlying COVID-19–associated thrombotic microangiopathies (TMAs) remain incompletely understood. Herein, we present a detailed meta-analysis clinical characteristics, outcomes, management strategies aHUS thrombocytopenic purpura (TTP).MethodsThis study was performed following Preferred Reporting Items for Systematic Reviews Meta-analyses updated guidelines. PubMed utilized searching case reports series. Adverse outcome at last follow-up defined as estimated glomerular filtration rate < 30 ml/min per 1.73 m2 (patients aHUS), no remission therapy, or patient death. Data were analyzed using Wilcoxon rank Chi-square tests.ResultsOur analysis cohort included 118 studies reporting on 170 These 84 86 TTP resulting from (n = 92) 78). Significantly more reported after 65) than immunization 19), compared to TTP, where reverse true 27 n 59, respectively; P 0.001). In patients stage 3 acute kidney injury (AKI), requirement replacement therapy (KRT) seen three-fourths median 15. severe (P 0.04) predicted nonremission death follow-up. Administration i.v., rituximab caplacizumab protective 0.03 0.06, respectively). Immune (iTTP) often HUS mRNA vaccines (81% vs. 58%; 0.06).ConclusionCOVID-19 are potential trigger onset relapse especially who not maintenance complement inhibitors immunosuppression.

Язык: Английский

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COVID‐19 vaccine adverse events: Evaluating the pathophysiology with an emphasis on sulfur metabolism and endotheliopathy

European Journal of Clinical Investigation, Год журнала: 2024, Номер 54(10)

Опубликована: Авг. 8, 2024

Abstract In this narrative review, we assess the pathophysiology of severe adverse events that presented after vaccination with DNA and mRNA vaccines against COVID‐19. The focus is on perspective an undersulfated degraded glycocalyx, considering its impact immunomodulation, inflammatory responses, coagulation oxidative stress. paper explores various factors lead to glutathione inorganic sulfate depletion their subsequent effect glycocalyx sulfation other metabolites, including hormones. Components COVID‐19 vaccines, such as material, spike protein antigen lipid nanoparticles, are involved in possible cytotoxic effects. common thread connecting these endotheliopathy or degradation, caused by depleted levels, shear stress from circulating aggregation formation coronas; leading imbalanced immune responses chronic release pro‐inflammatory cytokines, ultimately resulting systemic response syndrome. By understanding underlying events, better treatment options can be explored.

Язык: Английский

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