Immune-Based Prediction of COVID-19 Severity and Chronicity Decoded Using Machine Learning

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

Published: June 28, 2021

Expression of CCR5 and its cognate ligands have been implicated in COVID-19 pathogenesis, consequently therapeutics directed against are being investigated. Here, we explored the role across immunologic spectrum COVID-19. We used a bioinformatics approach to predict model phases COVID so that effective treatment strategies can be devised monitored. investigated 224 individuals including healthy controls patients spanning disease continuum. assessed plasma isolated peripheral blood mononuclear cells (PBMCs) from 29 controls, 26 Mild-Moderate individuals, 48 Severe 121 with post-acute sequelae (PASC) symptoms. Immune subset profiling 14-plex cytokine panel were run on all each group. B-cells significantly elevated compared control (P<0.001) as was CD14+, CD16+, CCR5+ monocytic (P<0.001). CD4 CD8 positive T-cells expressing PD-1 well T-regulatory lower than (P<0.001 P=0.01 respectively). CCL5/RANTES, IL-2, IL-4, CCL3, IL-6, IL-10, IFN-γ, VEGF (all P<0.001). Conversely GM-CSF CCL4 levels (P=0.01). Data further analyzed classes balanced using SMOTE. With working dataset, constructed 3 random forest classifiers: multi-class predictor, group binary classifier PASC classifier. Models also for feature importance identify relevant cytokines generate score. Multi-class models generated score specific defined S1 = (IFN-γ + IL-2)/CCL4-MIP-1β. Second, S2 (IL-6+sCD40L/1000 VEGF/10 10*IL-10)/(IL-2 IL-8). characterized by excessive inflammation dysregulated T cell activation, recruitment, counteracting activities. While profile able induce activation effector pro-inflammatory properties capacity generating an immune response eliminate virus but without proper recruitment signals attract activated cells.

Language: Английский

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COVID-19 and the Vasculature: Current Aspects and Long-Term Consequences

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: Feb. 15, 2022

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was first identified in December 2019 as a novel respiratory pathogen and is the causative agent of Corona Virus disease (COVID-19). Early on during this pandemic, it became apparent that SARS-CoV-2 not only restricted to infecting tract, but virus also found other tissues, including vasculature. Individuals with underlying pre-existing co-morbidities like diabetes hypertension have been more prone develop severe illness fatal outcomes COVID-19. In addition, critical clinical observations made COVID-19 patients include hypercoagulation, cardiomyopathy, heart arrythmia, endothelial dysfunction, which are indicative for an involvement vasculature pathology. Hence, review summarizes impact infection details how promotes (chronic) vascular inflammation. We provide general overview SARS-CoV-2, its entry determinant Angiotensin-Converting Enzyme II (ACE2) detection extrapulmonary tissue. Further, we describe relation between cardiovascular diseases (CVD) their Clinical findings changes reviewed detail recent evidence from vitro studies susceptibility cells discussed. conclude current notions contribution events long term consequences COVID-19, known “Long-COVID-syndrome”. Altogether, our provides detailed perspectives influence

Language: Английский

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Bacterial lipopolysaccharide-induced endothelial activation and dysfunction: a new predictive and therapeutic paradigm for sepsis

European journal of medical research, Journal Year: 2023, Volume and Issue: 28(1)

Published: Sept. 12, 2023

Abstract Background Lipopolysaccharide, a highly potent endotoxin responsible for severe sepsis, is the major constituent of outer membrane gram-negative bacteria. Endothelial cells participate in both innate and adaptive immune responses as first cell types to detect lipopolysaccharide or other foreign debris bloodstream. are able recognize presence LPS recruit specific adaptor proteins domains TLR4, thereby initiating an intracellular signaling cascade. However, binding endothelial induces activation even damage, manifested by expression proinflammatory cytokines adhesion molecules that lead sepsis. Main findings involved local systemic inflammation, activating immunity. Translocation into circulation causes endotoxemia. dysfunction, including exaggerated coagulopathy vascular leakage, may play central role dysregulated host response pathogenesis By discussing many strategies used treat this review attempts provide overview how ever more complex syndrome sepsis potential development novel therapeutics. Conclusions To reduce patient morbidity mortality, preservation function would be management Graphical

Language: Английский

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A high-risk gut microbiota configuration associates with fatal hyperinflammatory immune and metabolic responses to SARS-CoV-2

Gut Microbes, Journal Year: 2022, Volume and Issue: 14(1)

Published: May 15, 2022

Protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and associated clinical sequelae requires well-coordinated metabolic immune responses that limit viral spread promote recovery of damaged systems. However, the role gut microbiota in regulating these has not been thoroughly investigated. In order to identify mechanisms underpinning interactions with host systems influence disease 2019 (COVID-19) outcomes, we performed a multi-omics analysis on hospitalized COVID-19 patients compared those most outcome (i.e. death, n = 41) non-fatal (n 89), or mild/moderate 42), recovered. A distinct subset 8 cytokines (e.g. TSLP) 140 metabolites quinolinate) sera identified fatal infection. addition, elevated levels multiple pathobionts lower protective anti-inflammatory microbes were observed fecal microbiome poorest outcomes. Weighted gene correlation network (WGCNA) modules severity-associated tryptophan metabolism, coagulation-linked fibrinopeptides, bile acids pathobionts, such as Enterococcus. contrast, less outcomes are clusters Bifidobacterium Ruminococcus, short chain fatty (SCFAs) IL-17A. Our study uncovered mechanistic link processes SARS-CoV-2 These features may be useful at risk individuals, but also highlight for modifying hyperinflammatory other infectious agents.

Language: Английский

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The Vascular Endothelium and Coagulation: Homeostasis, Disease, and Treatment, with a Focus on the Von Willebrand Factor and Factors VIII and V

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(15), P. 8283 - 8283

Published: July 27, 2022

The vascular endothelium has several important functions, including hemostasis. homeostasis of hemostasis is based on a fine balance between procoagulant and anticoagulant proteins fibrinolytic antifibrinolytic ones. Coagulopathies are characterized by mutation-induced alteration the function certain coagulation factors or disturbed mechanisms responsible for regulating coagulation. Homeostatic therapies consist in replacement nonreplacement treatments administration agents. Rebalancing products reestablish inhibiting natural pathways. These agents include monoclonal antibodies, such as concizumab marstacimab, which target tissue factor pathway inhibitor; interfering RNA therapies, fitusiran, targets antithrombin III; protease inhibitors, serpinPC, active protein C. In cases thrombophilia (deficiency C, S, V Leiden), treatment may direct oral anticoagulants, therapy (plasma recombinant ADAMTS13) congenital deficiency ADAMTS13, immunomodulators (prednisone) if autoimmune. Monoclonal-antibody-based anti-vWF immunotherapy (caplacizumab) used context severe thrombophilia, regardless cause disorder. disseminated intravascular coagulation, choice consists antifibrinolytics, all-trans-retinoic acid, soluble human thrombomodulin.

Language: Английский

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Endotheliopathy in Acute COVID-19 and Long COVID

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(9), P. 8237 - 8237

Published: May 4, 2023

The pulmonary endothelium is a highly regulated organ that performs wide range of functions under physiological and pathological conditions. Since endothelial dysfunction has been demonstrated to play direct role in sepsis acute respiratory distress syndrome, its COVID-19 also extensively investigated. Indeed, apart from the COVID-19-associated coagulopathy biomarkers, new biomarkers were recognised early during pandemic, including markers cell activation or injury. We systematically searched literature up 10 March 2023 for studies examining association between long severity outcomes biomarkers.

Language: Английский

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Neutrophils and the Systemic Inflammatory Response Syndrome (SIRS)

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(17), P. 13469 - 13469

Published: Aug. 30, 2023

We are not entirely able to understand, assess, and modulate the functioning of immune system in clinical situations that lead a systemic inflammatory response. In search for diagnostic treatment strategies (which still far from perfect), it became very important study pathogenesis participation endogenous inflammation mediators. This attempts more precisely establish role neutrophils individual phenomena occurring during an anti-inflammatory reaction, taking into account their cidal, immunoregulatory, reparative abilities. Pro- anticoagulatory properties endothelium response syndrome (SIRS) emphasised, along with resulting implications (the application immunotherapy using mesenchymal stem/stromal cells (MSCs) or IL-6 antagonists sepsis COVID-19 treatment, among others). Special attention is paid reactive oxygen species (ROS), produced by activated “respiratory burst” course SIRS; protective pathogenic these mediators highlighted. Moreover, clinically useful biomarkers SIRS (neutrophil extracellular traps, cell-free DNA, DAMP, TREMs, NGAL, miRNA, selected cytokines, ROS, recognised markers endothelial damage group adhesins means immunohistochemical techniques) related presented, diagnosing forecasting sepsis, burn disease, emphasised. Finally, examples immunomodulation antioxidative thermal injury therapy presented.

Language: Английский

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Peptides in Chronic Wound Healing: Fighting Infections and Facilitating Diabetic Wound Management

Journal of Drug Delivery Science and Technology, Journal Year: 2025, Volume and Issue: unknown, P. 106599 - 106599

Published: Jan. 1, 2025

Language: Английский

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Immunologic and inflammatory consequences of SARS-CoV-2 infection and its implications in renal disease

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Feb. 12, 2025

The emergence of the COVID-19 pandemic made it critical to understand immune and inflammatory responses SARS-CoV-2 virus. It became increasingly recognized that response was a key mediator illness severity its mechanisms needed be better understood. Early infection both tissue cells, such as macrophages, leading pyroptosis-mediated inflammasome production in an organ system for systemic oxygenation likely plays central role morbidity wrought by SARS-CoV-2. Delayed transcription Type I III interferons may lead early disinhibition viral replication. Cytokines interleukin-1 (IL-1), IL-6, IL-12, tumor necrosis factor α (TNFα), some which produced through involving nuclear kappa B (NF-κB), contribute hyperinflammatory state patients with severe COVID-19. Lymphopenia, more apparent among natural killer (NK) CD8+ T-cells, B-cells, can disease reflect direct cytopathic effects or end-organ sequestration. Direct activation endothelial cells mechanism systems are impacted. In this context, endovascular neutrophil extracellular trap (NET) formation microthrombi development seen lungs other organs throughout body, heart, gut, brain. kidney most impacted extrapulmonary owing high concentration ACE2 exposure kidney, acute tubular injury, myofibroblast activation, collapsing glomerulopathy select populations account COVID-19-related AKI CKD development. COVID-19-associated nephropathy (COVAN), particular, mediated IL-6 signal transducer activator 3 (STAT3) signaling, suggesting connection between chronic disease. Chronic manifestations also include conditions like Multisystem Inflammatory Syndrome Children (MIS-C) Adults (MIS-A) post-acute sequelae (PASC), spectrum clinical presentations persistent dysregulation. lessons learned those undergoing continued study have broad implications understanding infections’ immunologic consequences beyond coronaviruses.

Language: Английский

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Syndecan-1, an indicator of endothelial glycocalyx degradation, predicts outcome of patients admitted to an ICU with COVID-19

Molecular Medicine, Journal Year: 2021, Volume and Issue: 27(1)

Published: Dec. 1, 2021

Abstract Background We investigated the feasibility of two biomarkers endothelial damage (Syndecan-1 and thrombomodulin) in coronavirus disease 2019 (COVID-19), their association with inflammation, coagulopathy, mortality. Methods The records 49 COVID-19 patients who were admitted to an intensive care unit (ICU) Wuhan, China between February April 2020 examined. Demographic, clinical, laboratory data, outcomes compared survivors non-survivors patients, high low serum Syndecan-1 levels. dynamics levels also analyzed. Results significantly higher non-survivor group survivor (median 1031.4 versus 504.0 ng/mL, P = 0.002), thrombomodulin not different these groups 4534.0 3780.0 0.070). Kaplan–Meier survival analysis showed that had worse overall (log-rank test: 0.023). Patients thrombomodulin, interleukin-6, tumor necrosis factor-α. Data on indicated much greater variations than survivors. Conclusions develop more serious inflammatory reactions, have increased has potential for use as a marker progression or severity COVID-19. Protecting glycocalyx from destruction is treatment

Language: Английский

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