The Immunopathogenesis of a Cytokine Storm: The Key Mechanisms Underlying Severe COVID-19

Cytokine & Growth Factor Reviews, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

A cytokine storm is marked by excessive pro-inflammatory release, and has emerged as a key factor in severe COVID-19 cases - making it critical therapeutic target. However, its pathophysiology was poorly understood, which hindered effective treatment. SARS-CoV-2 initially disrupts angiotensin signalling, promoting inflammation through ACE-2 downregulation. Some patients' immune systems then fail to shift from innate adaptive immunity, suppressing interferon responses leading pyroptosis neutrophil activation. This amplifies tissue damage inflammation, creating loop. The result the disruption of Th1/Th2 Th17/Treg balances, lymphocyte exhaustion, extensive blood clotting. Cytokine treatments include glucocorticoids suppress system, monoclonal antibodies neutralize specific cytokines, JAK inhibitors block receptor signalling. most treatment options for mitigating infection remain vaccines preventive measure antiviral drugs early stages infection. article synthesizes insights into dysregulation COVID-19, offering framework better understand storms improve monitoring, biomarker discovery, strategies other conditions involving storms.

Язык: Английский

---

The neutrophil-lymphocyte ratio predicts all-cause and cardiovascular mortality among U.S. adults with rheumatoid arthritis: results from NHANES 1999-2020

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Ноя. 17, 2023

Background The neutrophil-to-lymphocyte ratio (NLR) is recognized as a biomarker for systemic inflammation and immune activation. However, its connection with the mortality risk in individuals rheumatoid arthritis (RA) not well understood. This study aimed to investigate association between NLR all-cause cardiovascular U.S. adults RA. Methods Data were gathered from National Health Nutrition Examination Survey (NHANES) cycles spanning 1999 March 2020. We included aged ≥20 years. was computed by dividing neutrophil count lymphocyte complete blood counts. maximally selected rank statistics method helped identify optimal cutoff value associated significant survival outcomes. Multivariable logistic regression models performed relationship of Restricted cubic spline (RCS) analyses utilized detect whether there linear or non-linear relationships mortality. Results In this study, 2002 RA included, 339 having higher (≥3.28) 1663 lower (<3.28). During median follow-up 84 months, 79 died. Participants had 2-fold increased (HR = 2.02, 95% CI: 1.53-2.66) 2.48, 1.34-4.57) versus NLR, after adjusting demographics, socioeconomic status, lifestyle factors. Kaplan-Meier analysis revealed that rate group significantly than group, terms both (both P<0.0001). RCS curve demonstrated positive Conclusion A independently predictive elevated long-term may serve an inexpensive, widely available prognostic marker

Язык: Английский

---

Coronavirus disease 2019 (COVID-19) pandemic and autoimmune rheumatic diseases: Outcomes and prospects

Rheumatology Science and Practice, Год журнала: 2024, Номер 62(1), С. 32 - 54

Опубликована: Фев. 29, 2024

The pandemic of coronavirus disease 2019 (COVID-19), etiologically related to the SARS-CoV-2 virus (severe acute respiratory syndrome coronavirus-2), has drawn attention new clinical and fundamental problems in immunopathology human diseases associated with virus-induced autoimmunity autoinflammation. provision that “the experience gained rheumatology process studying pathogenetic mechanisms pharmacotherapy immunoinflammatory rheumatic as most common severe forms autoimmune autoinflammatory pathology humans will be demand for deciphering nature pathological processes underlying COVID-19 developing approaches effective pharmacotherapy” was confirmed numerous studies conducted over next 3 years midst pandemic. main focus on a critical analysis data regarding role inflammation, which basis pathogenesis immune-mediated context COVID-19.

Язык: Английский

---

Neutrophil extracellular traps and their implications in airway inflammatory diseases

Frontiers in Medicine, Год журнала: 2024, Номер 10

Опубликована: Янв. 12, 2024

Neutrophil extracellular traps (NETs) are essential for immune defense and have been increasingly recognized their role in infection inflammation. In the context of airway inflammatory diseases, there is growing evidence suggesting involvement significance NETs. This review aims to provide an overview formation mechanisms components NETs impact on various including acute lung injury/ARDS, asthma, chronic obstructive pulmonary disease (COPD) cystic fibrosis. By understanding inflammation, we can gain valuable insights into underlying pathogenesis these diseases identify potential targets future therapeutic strategies that either target or modulate harmful effects. Further research warranted elucidate complex interactions between inflammation develop targeted therapies effectively mitigate detrimental effects while preserving beneficial functions host defense.

Язык: Английский

---

A Dual Pharmacological Strategy against COVID-19: The Therapeutic Potential of Metformin and Atorvastatin

Microorganisms, Год журнала: 2024, Номер 12(2), С. 383 - 383

Опубликована: Фев. 13, 2024

Metformin (MET) and atorvastatin (ATO) are promising treatments for COVID-19. This review explores the potential of MET ATO, commonly prescribed diabetes dyslipidemia, respectively, as versatile medicines against SARS-CoV-2. Due to their immunomodulatory antiviral capabilities, well cost-effectiveness ubiquitous availability, they highly suitable options treating virus. MET’s effect extends beyond managing blood sugar, impacting pathways that can potentially decrease severity fatality rates linked with It partially block mitochondrial complex I stimulate AMPK, which indicates it be used more widely in viral infections. however, impacts cholesterol metabolism, a crucial element replicative cycle, demonstrates anti-inflammatory characteristics could modulate intense immune reactions individuals Retrospective investigations clinical trials show decreased hospitalizations, severity, mortality patients receiving these medications. Nevertheless, journey from observing something applying therapeutic setting is intricate, inherent diversity data necessitates carefully executed, forward-looking trials. highlights requirement efficacious, easily obtainable, secure COVID-19 therapeutics identifies ATO this worldwide health emergency.

Язык: Английский

---

Ribociclib leverages phosphodiesterase 4 inhibition in the treatment of neutrophilic inflammation and acute respiratory distress syndrome

Journal of Advanced Research, Год журнала: 2024, Номер 62, С. 229 - 243

Опубликована: Март 27, 2024

Overwhelming neutrophil activation and oxidative stress significantly contribute to acute respiratory distress syndrome (ARDS) pathogenesis. However, the potential of repurposing ribociclib, a cyclin-dependent kinase 4 6 (CDK4/6) inhibitor used clinically in cancer treatment, for treating neutrophilic ARDS remains uncertain. This study illustrated ability underlying mechanism ribociclib inflammation.

Язык: Английский

---

The Role of Myeloid Cells in Thromboinflammatory Disease

Seminars in Thrombosis and Hemostasis, Год журнала: 2024, Номер unknown

Опубликована: Март 28, 2024

Abstract Inflammation contributes to the development of thrombosis, but mechanistic basis for this association remains poorly understood. Innate immune responses and coagulation pathways are activated in parallel following infection or injury, represent an important host defense mechanism limit pathogen spread bloodstream. However, dysregulated proinflammatory activity is implicated progression venous thromboembolism arterial thrombosis. In review, we focus on role myeloid cells propagating thromboinflammation acute inflammatory conditions, such as sepsis coronavirus disease 2019 (COVID-19), chronic obesity, atherosclerosis, bowel disease. Myeloid considered key drivers via upregulated tissue factor activity, formation neutrophil extracellular traps (NETs), contact pathway activation, aberrant factor–mediated protease-activated receptor (PAR) signaling. We discuss how strategies target intersection between cell–mediated inflammation activation blood exciting new approach combat immunothrombosis. Specifically, repurposed anti-inflammatory drugs, immunometabolic regulators, NETosis inhibitors present opportunities that have potential dampen immunothrombotic without interfering with hemostasis. Such therapies could far-reaching benefits patient care across many thromboinflammatory conditions.

Язык: Английский

---

Investigating the relationship between the immune response and the severity of COVID-19: a large-cohort retrospective study

Frontiers in Immunology, Год журнала: 2025, Номер 15

Опубликована: Янв. 8, 2025

The COVID-19 pandemic has left an indelible mark globally, presenting numerous challenges to public health. This crisis, while disruptive and impactful, provided a unique opportunity gather precious clinical data extensively. In this observational, case-control study, we utilized collected at the Azienda Sanitaria Universitaria Friuli Centrale, Italy, comprehensively characterize immuno-inflammatory features in patients. Specifically, employed multicolor flow cytometry, cytokine assays, inflammatory biomarkers elucidate interplay between infectious agent host's immune status. We characterized profiles within first 72 hours of hospital admission, stratified by age, disease severity, time elapsed since symptom onset. Our findings indicate that patients admitted shortly after onset exhibit distinct pattern compared those who arrive later, more active response heightened activity, but lower markers tissue damage. used univariate multivariate logistic regression models identify informative for outcome severity. Predictors incorporating significantly outperformed standard baselines, identifying up 59% with positive outcomes maintaining false omission rate as low 4%. Overall, our study sheds light on aspects observed prior vaccination, providing insights guiding management first-time infections novel virus.

Язык: Английский

---

Role of CXCL12/CXCR4 pathway and miRNA expression profiles on polymorphonuclear mobilization in COVID-19 patients

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Янв. 10, 2025

Introduction: Polymorphonuclear neutrophils (PMN) are actively recruited during COVID-19 and yet dysfunctions associated with its prognosis. The PMN receptor CXCR4 ligand SDF-1/CXCL12 known to play a role in the recruitment of PMN. primary objective was evaluate modulation this pathway patients after treatment dexamethasone (DXM). Secondary objectives were miRNA expression profiles. Material Methods We conducted prospective study comparing admitted emergency department from December 2022 April 2023 for SARS-CoV-2 infection control population. studied surface receptor, circulating levels SDF-1 miR levels. Patients treated (DXM) sampled again at H48. Results Forty-four infected 20 controls analyzed. significantly increased decreased by DXM + percentages significantly. on admission risk mechanical ventilation. Levels 15b-5p, 146a-5p, 155-5p 30d-5p patients. miR-hsa-122 found mortality variation need Conclusions Our suggests possible involvement SDF-1/CXCR4 axis physiopathogenesis COVID-19.

Язык: Английский

---

The Antiviral Efficacy and Safety of Azvudine in Hospitalized SARS‐CoV‐2 Infected Patients with Liver Diseases Based on a Multicenter, Retrospective Cohort Study

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Фев. 22, 2025

Abstract Despite azvudine being prioritized for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, its effectiveness and safety remain inadequately substantiated in hospitalized SARS‐CoV‐2 infected patients with liver diseases. A retrospective nine‐center cohort study along an independent validation is conducted to examine efficacy (Clinical Trial Registration Number: NCT06349655). The primary outcome all‐cause mortality secondary composite disease progression. Efficacy assessed via Kaplan–Meier analysis Cox regression, subgroup sensitivity analyses further validation. Among 32 864 patients, 1022 eligible recipients, controls are included through propensity score match. reveals that associated a lower risk progression (both p <0.0001). regression suggests recipients could have 39% than (95% confidence interval [CI]: 0.468–0.795, <0.001), but no notable significance (hazard ratio: 0.85, 95% CI: 0.686‐1.061, = 0.154). Subgroup has greater benefit both kidney diseases or without autoimmune Three cohorts confirm robustness findings. Safety observes few adverse events recipients. Within 15 days after administration, significant difference function indexes observed between two groups except time points. These findings demonstrate shows potential clinical improving diseases, acceptable effects.

Язык: Английский

---