Parallels in Sepsis and COVID-19 Conditions: Implications for Managing Severe COVID-19

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Feb. 3, 2021

Sepsis is a life-threatening systemic illness attributed to dysregulated host response infection. global burden killing ~11 million persons annually. In December 2019, novel pneumonia condition termed coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome 2 (SARS-CoV-2), emerged and has resulted in more than 1,535,982 deaths globally as of 8th 2020. These two conditions share many pathophysiological clinical features. Notably, both sepsis COVID-19 patients experience consumptive thrombocytopenia, haemolytic anaemia, vascular microthrombosis, multi-organ dysfunction syndrome, coagulopathy, septic shock, failure, fever, leukopenia, hypotension, leukocytosis, high cytokine production predisposition opportunistic infections. Considering the parallels immunopathogenesis manifestations COVID-19, it highly likely that care, which well-established history most health systems, could inform on management. view this, present perspective compares pathophysiology non-SARS-CoV-2 induced sepsis, lessons from can be applicable

Language: Английский

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Trained Immunity and Reactivity of Macrophages and Endothelial Cells

Arteriosclerosis Thrombosis and Vascular Biology, Journal Year: 2020, Volume and Issue: 41(3), P. 1032 - 1046

Published: Dec. 31, 2020

Innate immune cells can develop exacerbated immunologic response and long-term inflammatory phenotype following brief exposure to endogenous or exogenous insults, which leads an altered towards a second challenge after the return nonactivated state. This phenomenon is known as trained immunity (TI). TI not only important for host defense vaccine but also chronic inflammations such cardiovascular metabolic diseases atherosclerosis. occur in innate monocytes/macrophages, natural killer cells, endothelial (ECs), nonimmune fibroblast. In this review, we analyze significance of ECs, are considered addition macrophages. be induced by variety stimuli, including lipopolysaccharides, BCG (bacillus Calmette-Guerin), oxLDL (oxidized low-density lipoprotein), defined risk factors diseases. Furthermore, ECs functional inflammation effectiveness transition inflammation. Rewiring cellular metabolism takes place during induction TI, increased glycolysis, glutaminolysis, accumulation tricarboxylic acid cycle metabolites acetyl-coenzyme A production, well mevalonate synthesis. Subsequently, epigenetic remodeling, resulting changes chromatin architecture that enables gene transcription enhanced proinflammatory response. However, pathways separated ensure memory stays when undergoes resolution. Additionally, reactive oxygen species play context-dependent roles TI. Therefore, plays significant EC macrophage pathology further characterization macrophages would provide novel insights into disease pathogenesis new therapeutic targets. Graphic Abstract: graphic abstract available article.

Language: Английский

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Heparan Sulfate Proteoglycans in Viral Infection and Treatment: A Special Focus on SARS-CoV-2

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(12), P. 6574 - 6574

Published: June 18, 2021

Heparan sulfate proteoglycans (HSPGs) encompass a group of glycoproteins composed unbranched negatively charged heparan (HS) chains covalently attached to core protein. The complex HSPG biosynthetic machinery generates an extraordinary structural variety HS that enable them bind plethora ligands, including growth factors, morphogens, cytokines, chemokines, enzymes, matrix proteins, and bacterial viral pathogens. These interactions translate into key regulatory activity HSPGs on wide range cellular processes such as receptor activation signaling, cytoskeleton assembly, extracellular remodeling, endocytosis, cell-cell crosstalk, others. Due their ubiquitous expression within tissues large functional repertoire, are involved in many physiopathological processes; thus, they have emerged valuable targets for the therapy human diseases. Among functions, assist viruses invading host cells at various steps life cycle. Viruses utilize attachment cell, internalization, intracellular trafficking, egress, spread. Recently, involvement pathogenesis SARS-CoV-2 infection has been established. Here, we summarize current knowledge molecular mechanisms underlying HSPG/SARS-CoV-2 interaction downstream effects, provide overview HSPG-based therapeutic strategies could be used combat fearsome virus.

Language: Английский

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Role of leukotriene pathway and montelukast in pulmonary and extrapulmonary manifestations of Covid-19: The enigmatic entity

European Journal of Pharmacology, Journal Year: 2021, Volume and Issue: 904, P. 174196 - 174196

Published: May 15, 2021

Language: Английский

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A Machine-Generated View of the Role of Blood Glucose Levels in the Severity of COVID-19

Frontiers in Public Health, Journal Year: 2021, Volume and Issue: 9

Published: July 28, 2021

SARS-CoV-2 started spreading toward the end of 2019 causing COVID-19, a disease that reached pandemic proportions among human population within months. The reasons for spectrum differences in severity across population, and particular why affects more severely aging those with specific preconditions are unclear. We developed machine learning models to mine 240,000 scientific articles openly accessible CORD-19 database, constructed knowledge graphs synthesize extracted information navigate collective an attempt search potential common underlying reason severity. machine-driven framework we repeatedly pointed elevated blood glucose as key facilitator progression COVID-19. Indeed, when systematically retraced steps infection, found evidence linking each major step life-cycle virus, disease, presentation symptoms. Specifically, elevations provide ideal conditions virus evade weaken first level immune defense system lungs, gain access deep alveolar cells, bind ACE2 receptor enter pulmonary accelerate replication cells increasing cell death inducing inflammatory response, which overwhelms already weakened innate trigger avalanche systemic infections, inflammation damage, cytokine storm thrombotic events. tested feasibility hypothesis by manually reviewing literature referenced machine-generated synthesis, reconstructing atomistically at surface airways, performing quantitative computational modeling effects levels on infection process. conclude elevation can facilitate through multiple mechanisms explain much seen population. study provides diagnostic considerations, new areas research treatments, cautions treatment strategies critical care induce levels.

Language: Английский

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Endothelial Dysfunction in COVID-19: Potential Mechanisms and Possible Therapeutic Options

Life, Journal Year: 2022, Volume and Issue: 12(10), P. 1605 - 1605

Published: Oct. 14, 2022

SARS-CoV-2, a novel coronavirus found in Wuhan (China) at the end of 2019, is etiological agent current pandemic that heterogeneous disease, named disease 2019 (COVID-19). SARS-CoV-2 affects primarily lungs, but it can induce multi-organ involvement such as acute myocardial injury, myocarditis, thromboembolic eventsandrenal failure. Hypertension, chronic kidney diabetes mellitus and obesity increase risk severe complications COVID-19. There no certain explanation for this systemic COVID-19 involvement, could be related to endothelial dysfunction, due direct (endothelial cells are infected by virus) indirect damage (systemic inflammation) factors. Angiotensin-converting enzyme 2 (ACE2), expressed human endothelium, has fundamental role respiratory syndrome (SARS-CoV-2) infection. In fact, ACE2 used receptor leading downregulation these receptors on cells; once inside, virus reduces integrity tissue, with exposure prothrombotic molecules, platelet adhesion, activation coagulation cascades and, consequently, vascular damage. Systemic microangiopathy thromboembolism lead failure an elevated death. Considering crucial immunological response developing form COVID-19, review, we will attempt clarify underlying pathophysiological mechanisms.

Language: Английский

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Role of SARS-CoV-2 -induced cytokines and growth factors in coagulopathy and thromboembolism

Cytokine & Growth Factor Reviews, Journal Year: 2021, Volume and Issue: 63, P. 58 - 68

Published: Oct. 25, 2021

Language: Английский

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The Role of Endothelium in COVID-19

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(21), P. 11920 - 11920

Published: Nov. 3, 2021

The 2019 novel coronavirus, known as severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) or coronavirus disease (COVID-19), is causing a global pandemic. virus primarily affects the upper and lower tracts raises risk of variety non-pulmonary consequences, most possibly fatal which are cardiovascular problems. Data show that almost one-third patients with moderate form COVID-19 had preexisting comorbidities such diabetes mellitus, obesity, hypertension, heart failure, coronary artery disease. SARS-CoV2 causes hyper inflammation, hypoxia, apoptosis, renin-angiotensin system imbalance in cell types, endothelial cells. Profound dysfunction associated can be cause impaired organ perfusion may generate myocardial injury, renal procoagulant state resulting thromboembolic events. We discuss recent results on involvement pathogenesis cardiometabolic diseases this review. also provide insights treatments reduce severity viral infection.

Language: Английский

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The effects of novel coronavirus (SARS-CoV-2) infection on cardiovascular diseases and cardiopulmonary injuries

Stem Cell Research, Journal Year: 2021, Volume and Issue: 51, P. 102168 - 102168

Published: Jan. 14, 2021

COVID-19 caused by a novel coronavirus named SARS-CoV-2, can elites severe acute respiratory syndrome, lung injury, cardiac and even death became worldwide pandemic. SARS-CoV-2 infection may result in injury via several mechanisms, including the expression of angiotensin-converting enzyme 2 (ACE2) receptor leading to cytokine storm, elicit an exaggerated host immune response. This response contributes multi-organ dysfunction. As emerging infectious disease, there are limited data on effects this patients with underlying cardiovascular comorbidities. In review, we summarize early-stage clinical experiences COVID-19, particular focus diseases cardiopulmonary injuries, explores potential available evidence regarding association between complications.

Language: Английский

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Possible Link between SARS-CoV-2 Infection and Parkinson’s Disease: The Role of Toll-Like Receptor 4

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(13), P. 7135 - 7135

Published: July 1, 2021

Parkinson’s disease (PD) is the most common neurodegenerative motor disorder characterized by selective degeneration of dopaminergic neurons in substantia nigra pars compacta (SNpc) midbrain, depletion dopamine (DA), and impaired nigrostriatal pathway. The pathological hallmark PD includes aggregation accumulation α-synuclein (α-SYN). Although precise mechanisms underlying pathogenesis are still unknown, activation toll-like receptors (TLRs), mainly TLR4 subsequent neuroinflammatory immune response, seem to play a significant role. Mounting evidence suggests that viral infection can concur with precipitation or parkinsonism. recently identified coronavirus named severe acute respiratory syndrome 2 (SARS-CoV-2) causative agent ongoing pandemic 2019 (COVID-19), responsible for 160 million cases led death more than three individuals worldwide. Studies have reported many patients COVID-19 display several neurological manifestations, including cerebrovascular diseases, conscious disturbance, typical non-motor symptoms accompanying PD. In this review, neurotropic potential SARS-CoV-2 its possible involvement discussed. Specifically, signaling pathway mediating virus entry, as well massive inflammatory response explored. binding spike (S) protein interaction between α-SYN contributing factors neuronal also considered.

Language: Английский

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