Understanding COVID-19-associated coagulopathy

Nature reviews. Immunology, Journal Year: 2022, Volume and Issue: 22(10), P. 639 - 649

Published: Aug. 5, 2022

Language: Английский

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SARS-CoV-2 crosses the blood–brain barrier accompanied with basement membrane disruption without tight junctions alteration

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Sept. 6, 2021

Abstract SARS-CoV-2 has been reported to show a capacity for invading the brains of humans and model animals. However, it remains unclear whether how crosses blood–brain barrier (BBB). Herein, RNA was occasionally detected in vascular wall perivascular space, as well brain microvascular endothelial cells (BMECs) infected K18-hACE2 transgenic mice. Moreover, permeability vessel increased. Furthermore, disintegrity BBB discovered hamsters by administration Evans blue. Interestingly, expression claudin5, ZO-1, occludin ultrastructure tight junctions (TJs) showed unchanged, whereas, basement membrane disrupted Using an vitro that comprises primary BMECs with astrocytes, found infect cross through BMECs. Consistent vivo experiments, MMP9 increased collagen IV decreased while markers TJs were not altered SARS-CoV-2-infected Besides, inflammatory responses including vasculitis, glial activation, upregulated factors occurred after infection. Overall, our results provide evidence supporting can transcellular pathway accompanied without obvious alteration TJs.

Language: Английский

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SARS-CoV-2-Specific Immune Response and the Pathogenesis of COVID-19

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(3), P. 1716 - 1716

Published: Feb. 2, 2022

The review aims to consolidate research findings on the molecular mechanisms and virulence pathogenicity characteristics of coronavirus disease (COVID-19) causative agent, severe acute respiratory syndrome 2 (SARS-CoV-2), their relevance four typical stages in development viral infection. These are invasion; primary blockade antiviral innate immunity; engagement virus’s protection against factors adaptive acute, long-term complications COVID-19. invasion stage entails recognition spike protein (S) SARS-CoV-2 target cell receptors, namely, main receptor (angiotensin-converting enzyme 2, ACE2), its coreceptors, potential alternative receptors. presence a diverse repertoire receptors allows infect various types cells, including those not expressing ACE2. During second stage, majority polyfunctional structural, non-structural, extra proteins synthesizes infected cells involved blockage immunity. A high degree redundancy systemic action characterizing these pathogenic overcome at initial invasion. third includes passive active virus from immunity, overcoming barrier function focus inflammation, generalization body. fourth is associated with deployment variants SARS-CoV-2’s ability induce autoimmune autoinflammatory pathways tissue both immunosuppressive hyperergic inflammation critical this

Language: Английский

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SARS-CoV-2 drives NLRP3 inflammasome activation in human microglia through spike protein

Molecular Psychiatry, Journal Year: 2022, Volume and Issue: 28(7), P. 2878 - 2893

Published: Nov. 1, 2022

Coronavirus disease-2019 (COVID-19) is primarily a respiratory disease, however, an increasing number of reports indicate that SARS-CoV-2 infection can also cause severe neurological manifestations, including precipitating cases probable Parkinson's disease. As microglial NLRP3 inflammasome activation major driver neurodegeneration, here we interrogated whether promote activation. Using transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) as COVID-19 pre-clinical model, established the presence virus in brain together with and upregulation comparison to uninfected mice. Next, utilising model monocyte-derived microglia, identified isolates bind enter microglia absence viral replication. This interaction directly induced robust activation, even another priming signal. Mechanistically, demonstrated purified spike glycoprotein activated LPS-primed ACE2-dependent manner. Spike protein could prime through NF-κB signalling, allowing for either ATP, nigericin or α-synuclein. Notably, protein-mediated was significantly enhanced α-synuclein fibrils entirely ablated by NLRP3-inhibition. Finally, demonstrate infected hACE2 treated orally post-infection inhibitory drug MCC950, have reduced increased survival untreated These results support possible mechanism innate immune SARS-CoV-2, which explain vulnerability developing symptoms akin disease individuals, potential therapeutic avenue intervention.

Language: Английский

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Long-Term Effects of COVID-19

Mayo Clinic Proceedings, Journal Year: 2022, Volume and Issue: 97(3), P. 579 - 599

Published: Jan. 12, 2022

Language: Английский

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COVID-19 and cognitive impairment: neuroinvasive and blood‒brain barrier dysfunction

Journal of Neuroinflammation, Journal Year: 2022, Volume and Issue: 19(1)

Published: Sept. 7, 2022

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a global pandemic. Although COVID-19 was initially described as disease, there is growing evidence that SARS-CoV-2 able invade the brains of patients and cause cognitive impairment. It been reported may have invasive effects on variety cranial nerves, including olfactory, trigeminal, optic, vagus spread other brain regions via infected nerve endings, retrograde transport, transsynaptic transmission. In addition, blood-brain barrier (BBB), composed neurovascular units (NVUs) lining microvasculature, acts physical between cells circulating immune system regulate transfer substances blood parenchyma. Therefore, BBB be an important structure for direct indirect interaction with circulation. this review, we assessed potential involvement neuroinvasion under infection, impact disorder infection

Language: Английский

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Role of SARS-CoV-2 Spike-Protein-Induced Activation of Microglia and Mast Cells in the Pathogenesis of Neuro-COVID

Cells, Journal Year: 2023, Volume and Issue: 12(5), P. 688 - 688

Published: Feb. 22, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes disease 2019 (COVID-19). About 45% of COVID-19 patients experience several symptoms a few months after the initial infection and develop post-acute sequelae SARS-CoV-2 (PASC), referred to as “Long-COVID,” characterized by persistent physical mental fatigue. However, exact pathogenetic mechanisms affecting brain are still not well-understood. There is increasing evidence neurovascular inflammation in brain. precise role neuroinflammatory response that contributes severity long COVID pathogenesis clearly understood. Here, we review reports spike protein can cause blood–brain barrier (BBB) dysfunction damage neurons either directly, or via activation mast cells microglia release various molecules. Moreover, provide recent novel flavanol eriodictyol particularly suited for development an effective treatment alone together with oleuropein sulforaphane (ViralProtek®), all which have potent anti-viral anti-inflammatory actions.

Language: Английский

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Long COVID, the Brain, Nerves, and Cognitive Function

Neurology International, Journal Year: 2023, Volume and Issue: 15(3), P. 821 - 841

Published: July 6, 2023

SARS-CoV-2, a single-stranded RNA coronavirus, causes an illness known as coronavirus disease 2019 (COVID-19). Long-term complications are increasing issue in patients who have been infected with COVID-19 and may be result of viral-associated systemic central nervous system inflammation or arise from virus-induced hypercoagulable state. incite changes brain function wide range lingering symptoms. Patients often experience fatigue note fog, sensorimotor symptoms, sleep disturbances. Prolonged neurological neuropsychiatric symptoms prevalent can interfere substantially everyday life, leading to massive public health concern. The mechanistic pathways by which SARS-CoV-2 infection sequelae important subject ongoing research. Inflammation- induced blood-brain barrier permeability viral neuro-invasion direct nerve damage involved. Though the mechanisms uncertain, resulting documented numerous patient reports studies. This review examines constellation spectrum seen long COVID incorporates information on prevalence these contributing factors, typical course. Although treatment options generally lacking, potential therapeutic approaches for alleviating improving quality life explored.

Language: Английский

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Pathophysiological, immunological, and inflammatory features of long COVID

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 28, 2024

The COVID-19 pandemic continues to cause severe global disruption, resulting in significant excess mortality, overwhelming healthcare systems, and imposing substantial social economic burdens on nations. While most of the attention therapeutic efforts have concentrated acute phase disease, a notable proportion survivors experience persistent symptoms post-infection clearance. This diverse set symptoms, loosely categorized as long COVID, presents potential additional public health crisis. It is estimated that 1 5 exhibit clinical manifestations consistent with COVID. Despite this prevalence, mechanisms pathophysiology COVID remain poorly understood. Alarmingly, evidence suggests cases within condition develop debilitating or disabling symptoms. Hence, urgent priority should be given further studies equip systems for its management. review provides an overview available information emerging condition, focusing affected individuals’ epidemiology, pathophysiological mechanisms, immunological inflammatory profiles.

Language: Английский

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The choroid plexus and its role in the pathogenesis of neurological infections

Fluids and Barriers of the CNS, Journal Year: 2022, Volume and Issue: 19(1)

Published: Sept. 10, 2022

The choroid plexus is situated at an anatomically and functionally important interface within the ventricles of brain, forming blood-cerebrospinal fluid barrier that separates periphery from central nervous system. In contrast to blood-brain barrier, its epithelial have received considerably less attention. As main producer cerebrospinal fluid, secretory functions cells aid in maintenance CNS homeostasis are capable relaying inflammatory signals brain. acts as immunological niche where several types peripheral immune can be found stroma including dendritic cells, macrophages, T cells. Including epithelia these perform immunosurveillance, detecting pathogens changes cytokine milieu. such, their activation leads release homing molecules induce chemotaxis circulating driving response plexus. Research into properties shown how inflammation alter structural junctions promote increased bidirectional transmigration pathogens. goal this review highlight our foundational knowledge discuss recent research has shifted understanding towards viewing a highly dynamic contributor pathogenesis neurological infections. With emergence high-profile diseases, ZIKA SARS-CoV-2, provides pertinent update on cellular diseases. Historically, pharmacological interventions disorders proven difficult develop, however, greater focus role would provide for novel targets routes therapeutics.

Language: Английский

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