Mechanisms of long COVID and the path toward therapeutics

Cell, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

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Numerical analysis of an advanced infrared-based graphene metasurface surface plasmon resonance sensor for COVID-19 detection

Diamond and Related Materials, Journal Year: 2024, Volume and Issue: unknown, P. 111601 - 111601

Published: Sept. 1, 2024

Language: Английский

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Mechanisms of endothelial activation, hypercoagulation and thrombosis in COVID-19: a link with diabetes mellitus

Cardiovascular Diabetology, Journal Year: 2024, Volume and Issue: 23(1)

Published: Feb. 20, 2024

Abstract Early since the onset of COVID-19 pandemic, medical and scientific community were aware extra respiratory actions SARS-CoV-2 infection. Endothelitis, hypercoagulation, hypofibrinolysis identified in patients as subsequent responses endothelial dysfunction. Activation barrier may increase severity disease contribute to long-COVID syndrome post-COVID sequelae. Besides, it cause alterations primary, secondary, tertiary hemostasis. Importantly, these have been highly decisive evolution infected also diagnosed with diabetes mellitus (DM), who showed previous In this review, we provide an overview potential triggers activation related under diabetic milieu. Several mechanisms are induced by both viral particle itself immune-defensive response (i.e., NF-κB/NLRP3 inflammasome pathway, vasoactive peptides, cytokine storm, NETosis, complement system). Alterations coagulation mediators such factor VIII, fibrin, tissue factor, von Willebrand factor: ADAMST-13 ratio, kallikrein-kinin or plasminogen-plasmin systems reported. Moreover, imbalance thrombotic thrombolytic (tPA, PAI-I, fibrinogen) factors favors hypercoagulation hypofibrinolysis. context DM, can be exacerbated leading higher loss However, a series therapeutic strategies targeting activated endothelium specific antibodies inhibitors against thrombin, key cytokines, X, system, system might represent new opportunities address hypercoagulable state present DM. Antidiabetics ameliorate dysfunction, inflammation, platelet aggregation. By improving microvascular pathology subjects, associated comorbidities risk mortality could reduced.

Language: Английский

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Comparative Analysis of Virology and Pathogenesis of SARS-CoV-2 and HIV Infections: Implications for Public Health and Treatment Strategies

Infection and Drug Resistance, Journal Year: 2025, Volume and Issue: Volume 18, P. 269 - 283

Published: Jan. 1, 2025

Introduction: Coronavirus Disease 19 (COVID-19), caused by the Severe Acute Respiratory Syndrome 2 (SARS-CoV -2), and Human Immunodeficiency Virus (HIV) are significant 21st-century pandemics with distinct virological clinical characteristics.COVID-19 primarily presents as an acute respiratory illness, while HIV leads to chronic immune suppression.Understanding their differences can enhance public health strategies treatment approaches.Purpose: This narrative review compares virology, transmission, responses, outcomes of SARS-CoV-2 inform interventions.Methods: A was conducted, synthesizing data from peer-reviewed literature expert commentary 2010 2024.Databases such PubMed, Cochrane Library, Google Scholar were searched for relevant studies.Results: spreads through airborne droplets contaminated surfaces, transmits direct contact infected bodily fluids.The response involves both innate adaptive systems, potentially leading a cytokine storm in severe cases.In contrast, evades system integrating into host cells, resulting infection progressive deterioration.Treatment focuses on symptom management prevention, antiviral medications vaccines playing crucial roles.Conversely, relies antiretroviral therapy (ART) suppress viral replication maintain function. Conclusion:The highlights nature versus progression HIV.Tailored prevention essential effective disease management.Recommendations: Public should address unique transmission routes viruses.Further research vaccine development therapeutic interventions is critical improving management.

Language: Английский

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SARS-CoV-2 spike protein induces lung endothelial cell dysfunction and thrombo-inflammation depending on the C3a/C3a receptor signalling

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: July 14, 2023

The spike protein of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can interact with endothelial cells. However, no studies demonstrated the direct effect subunit 1 (S1) in inducing lung vascular damage and potential mechanisms contributing to injury. Here, we found that S1 injection mice transgenic for human angiotensin converting enzyme (ACE2) induced early loss thromboresistance at 3 days, as revealed by thrombomodulin von Willebrand factor (vWF) increase. In parallel, epithelial C3 deposits enhanced C3a receptor (C3aR) expression were observed. These changes preceded diffuse alveolar fibrin(ogen)/platelets aggregates 7 well inflammatory cell recruitment fibrosis. Treatment C3aR antagonist (C3aRa) inhibited accumulation C3a/C3aR activation, limiting thrombo-inflammation Our study demonstrates triggers dysfunction activates complement system, instrumental thrombo-inflammatory By extension, our data indicate C3aRa a valuable therapeutic strategy limit S1-dependent pathology.

Language: Английский

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Exploring the Pathophysiology of Long COVID: The Central Role of Low-Grade Inflammation and Multisystem Involvement

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(12), P. 6389 - 6389

Published: June 9, 2024

Long COVID (LC), also referred to as Post COVID-19 Condition, Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), and other terms, represents a complex multisystem disease persisting after the acute phase COVID-19. Characterized by myriad symptoms across different organ systems, LC presents significant diagnostic management challenges. Central disorder is role low-grade inflammation, non-classical inflammatory response that contributes chronicity diversity observed. This review explores pathophysiological underpinnings LC, emphasizing importance inflammation core component. By delineating pathogenetic relationships clinical manifestations this article highlights necessity for an integrated approach employs both personalized medicine standardized protocols aimed at mitigating long-term consequences. The insights gained not only enhance our understanding but inform development therapeutic strategies could be applicable chronic conditions with similar features.

Language: Английский

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Sialylated Glycan Bindings from SARS-CoV-2 Spike Protein to Blood and Endothelial Cells Govern the Severe Morbidities of COVID-19

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(23), P. 17039 - 17039

Published: Dec. 1, 2023

Consistent with well-established biochemical properties of coronaviruses, sialylated glycan attachments between SARS-CoV-2 spike protein (SP) and host cells are key to the virus’s pathology. SP attaches aggregates red blood (RBCs), as shown in many pre-clinical clinical studies, causing pulmonary extrapulmonary microthrombi hypoxia severe COVID-19 patients. heavily surfaces platelets (which, like RBCs, have no ACE2) endothelial (having minimal compound this vascular damage. Notably, experimentally induced RBC aggregation vivo causes same morbidities for COVID-19, including microvascular occlusion, clots, myocarditis. Key risk factors morbidity, older age, diabetes obesity, all characterized by markedly increased propensity clumping. For mammalian species, degree susceptibility correlates aggregability p = 0.033. five human betacoronaviruses, two common cold strains express an enzyme that releases attachments, while deadly SARS, MERS do not, although viral loads infections similar. These insights also explain previously puzzling efficacy certain generics against may support development future therapeutic strategies long COVID

Language: Английский

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Endothelial Growth Media Components Alters SARS-CoV-2 Spike-Directed Growth Kinetics

Journal of Virological Methods, Journal Year: 2025, Volume and Issue: unknown, P. 115111 - 115111

Published: Jan. 1, 2025

Language: Английский

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SARS-CoV-2 S-protein expression drives syncytia formation in endothelial cells

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 28, 2025

SARS-CoV-2 is a viral infection, best studied in the context of epithelial cell infection. Epithelial cells, when infected with express S-protein, which causes host cells to fuse together into large multi-nucleated known as syncytia. Because infections also frequently present cardiovascular phenotypes, we sought understand if S-protein expression would result syncytia formation endothelial cells. was sufficient induce an average 10% all forming 6 nuclei per after 72 h expression. Formation associated gaps between suggesting potential for compromise barrier function. Inhibition myosin light chain kinase (MLCK), but not Rho-associated protein kinase, inhibited syncytia, role MLCK formation. Further supporting cellular contractility formation, observed reduction occurrence grown on substrates reduced stiffness. are exposed physiological forces due blood flow, examined effects cyclic biaxial stretch and fluid shear stress. While did affect stress were more resistant Finally, that suitable infection replication, Our studies indicate addition should be considered target driver COVID-19-associated pathology.

Language: Английский

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Effects of COVID-19 Infection on Endothelial Vascular Function

Viruses, Journal Year: 2025, Volume and Issue: 17(3), P. 305 - 305

Published: Feb. 23, 2025

Most studies analyzing data from patients who experienced at least one episode of acute COVID-19 infection have attributed the cascade immediate and late complications to disruption inflammatory system neutrophil activity in particular. Among various functions neutrophils is release pro-inflammatory mediators, including interleukin-6 (IL-6). Oxidative stress induced by mediators secreted leads vascular endothelial dysfunction. Neutrophil counts neutrophil-to-lymphocyte ratio (NLR) are directly associated with patient survival, higher values correlating increased mortality. To assess dysfunction secondary infection, we conducted a retrospective study involving two cohorts, each comprising 99 participants: group history another without. The aimed demonstrate presence moderate using flow-mediated dilatation (FMD) brachial artery evaluate its correlation key markers (erythrocyte sedimentation rate—ESR, fibrinogen, NLR, IL-6). FMD were significantly reduced (p < 0.0001) post-COVID-19 compared those without prior infection. ESR 0.0001), fibrinogen C-reactive protein (CRP) leukocyte count granulocyte inversely correlated values. patients, all analyzed parameters demonstrated statistically significant impact on FMD, showing strongest effect, accounting for nearly 63% dependency. ANOVA testing confirmed an inverse association between NLR quartiles as well IL-6 levels FMD. In conclusion, this highlights assessed demonstrates correlations values, levels, ratio.

Language: Английский

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