Oxidative Stress and Hyper-Inflammation as Major Drivers of Severe COVID-19 and Long COVID: Implications for the Benefit of High-Dose Intravenous Vitamin C

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: April 29, 2022

Oxidative stress is a pivotal point in the pathophysiology of COVID-19 and presumably also Long-COVID. Inflammation oxidative are mutually reinforcing each other, thus contributing to systemic hyperinflammatory state coagulopathy which cardinal pathological mechanisms severe stages. patients, like other critically ill patients e.g. with pneumonia, very often show deficiency antioxidant vitamin C. So far, it has not been investigated how long this lasts or whether COVID symptoms suffer from deficiencies. A C deficit serious consequences because one most effective antioxidants, but co-factor many enzymatic processes that affect immune nervous system, blood circulation energy metabolism. Because its anti-oxidative, anti-inflammatory, endothelial-restoring, immunomodulatory effects supportive intravenous (iv) use supraphysiological doses so far 12 controlled observational studies altogether 1578 inpatients COVID-19. In these an improved oxygenation, decrease inflammatory markers faster recovery were observed. addition, early treatment iv high dose seems reduce risks courses disease such as pneumonia mortality. Persistent inflammation, thrombosis dysregulated response (auto-immune phenomena and/or persistent viral load) seem be major contributors inflammation involved development progression fatigue neuro-psychiatric various diseases by disrupting tissue (e.g. autoantibodies), flow thrombosis) neurotransmitter metabolism excitotoxicity). oncological diseases, infections autoimmune associated fatigue, cognitive disorders, pain depression similar Long-COVID, was shown significantly relieve symptoms. Supportive acute might therefore risk

Language: Английский

---

The Role of Cytokines and Chemokines in Severe Acute Respiratory Syndrome Coronavirus 2 Infections

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: April 7, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in countless infections and caused millions of deaths since its emergence 2019. Coronavirus disease 2019 (COVID-19)-associated mortality is by uncontrolled inflammation, aberrant immune response, cytokine storm, an imbalanced hyperactive system. The storm further results multiple organ failure lung immunopathology. Therefore, any potential treatments should focus on the direct elimination viral particles, prevention strategies, mitigation (hyperactive) This review focuses secretions innate adaptive responses against COVID-19, including interleukins, interferons, tumor necrosis factor-alpha, other chemokines. In addition to focus, we discuss immunotherapeutic approaches based relevant pathophysiological features, systemic response SARS-CoV-2, data from recent clinical trials experiments COVID-19-associated storm. Prompt use these cytokines as diagnostic markers aggressive management can help determine morbidity mortality. prophylaxis rapid appear significantly improve outcomes. For reasons, this study aims provide advanced information facilitate innovative strategies survive COVID-19 pandemic.

Language: Английский

---

The roles of critical pro‐inflammatory cytokines in the drive of cytokine storm during SARS‐CoV‐2 infection

Journal of Medical Virology, Journal Year: 2023, Volume and Issue: 95(4)

Published: April 1, 2023

Abstract In patients with severe COVID‐19, acute respiratory distress syndrome (ARDS), multiple organ dysfunction (MODS), and even mortality can result from cytokine storm, which is a hyperinflammatory medical condition caused by the excessive uncontrolled release of pro‐inflammatory cytokines. High levels numerous crucial cytokines, such as interleukin‐1 (IL‐1), IL‐2, IL‐6, tumor necrosis factor‐α, interferon (IFN)‐γ, IFN‐induced protein 10 kDa, granulocyte‐macrophage colony‐stimulating factor, monocyte chemoattractant protein‐1, IL‐10 so on, have been found in COVID‐19. They participate cascade amplification pathways responses through complex inflammatory networks. Here, we review involvements these critical cytokines SARS‐CoV‐2 infection discuss their potential roles triggering or regulating help to understand pathogenesis So far, there rarely effective therapeutic strategy for storm besides using glucocorticoids, proved fatal side effects. Clarifying key involved network will develop an ideal intervention, neutralizing antibody certain inhibitor some signal pathways.

Language: Английский

---

Advances and Challenges in Sepsis Management: Modern Tools and Future Directions

Cells, Journal Year: 2024, Volume and Issue: 13(5), P. 439 - 439

Published: March 2, 2024

Sepsis, a critical condition marked by systemic inflammation, profoundly impacts both innate and adaptive immunity, often resulting in lymphopenia. This immune alteration can spare regulatory T cells (Tregs) but significantly affects other lymphocyte subsets, leading to diminished effector functions, altered cytokine profiles, metabolic changes. The complexity of sepsis stems not only from its pathophysiology also the heterogeneity patient responses, posing significant challenges developing universally effective therapies. review emphasizes importance phenotyping enhance patient-specific diagnostic therapeutic strategies. Phenotyping cells, which categorizes patients based on clinical immunological characteristics, is pivotal for tailoring treatment approaches. Flow cytometry emerges as crucial tool this endeavor, offering rapid, low cost detailed analysis cell populations their functional states. Indeed, technology facilitates understanding dysfunctions contributes identification novel biomarkers. Our underscores potential integrating flow with omics data, machine learning observations refine management, highlighting shift towards personalized medicine care. approach could lead more precise interventions, improving outcomes heterogeneously affected population.

Language: Английский

---

Historical perspective of tumor glycolysis: A century with Otto Warburg

Seminars in Cancer Biology, Journal Year: 2022, Volume and Issue: 86, P. 325 - 333

Published: July 7, 2022

Language: Английский

---

COVID‐19 immunopathology: From acute diseases to chronic sequelae

Journal of Medical Virology, Journal Year: 2022, Volume and Issue: 95(1)

Published: Sept. 3, 2022

The clinical manifestation of coronavirus disease 2019 (COVID-19) mainly targets the lung as a primary affected organ, which is also critical site immune cell activation by severe acute respiratory syndrome 2 (SARS-CoV-2). However, recent reports suggest involvement extrapulmonary tissues in COVID-19 pathology. interplay both innate and adaptive responses key to management. As result, robust response provides first line defense, concomitantly, immunity neutralizes infection builds memory for long-term protection. dysregulated immunity, adaptive, can skew towards immunopathology chronic cases. Here we have summarized some findings that provide insight into caused SARS-CoV-2, post-acute Finally, further discuss immunomodulatory drugs preclinical trials dampening COVID-19.

Language: Английский

---

Human lungs show limited permissiveness for SARS-CoV-2 due to scarce ACE2 levels but virus-induced expansion of inflammatory macrophages

European Respiratory Journal, Journal Year: 2022, Volume and Issue: 60(6), P. 2102725 - 2102725

Published: June 21, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilises the angiotensin-converting enzyme (ACE2) transmembrane peptidase as cellular entry receptor. However, whether SARS-CoV-2 in alveolar compartment is strictly ACE2-dependent and to what extent virus-induced tissue damage and/or direct immune activation determines early pathogenesis still elusive.Spectral microscopy, single-cell/-nucleus RNA sequencing or ACE2 "gain-of-function" experiments were applied infected human lung explants adult stem cell derived organoids correlate related host factors with tropism, propagation, virulence compared SARS-CoV, influenza Middle East (MERS-CoV). Coronavirus disease 2019 (COVID-19) autopsy material was used validate ex vivo results.We provide evidence that expression must be considered scarce, thereby limiting propagation alveolus. Instead, lungs COVID-19 samples showed macrophages frequently positive for SARS-CoV-2. Single-cell/-nucleus transcriptomics further revealed nonproductive virus uptake a inflammatory anti-viral activation, especially "inflammatory macrophages", comparable those induced by SARS-CoV MERS-CoV, but different from NL63 infection.Collectively, our findings indicate severe injury probably results macrophage-triggered rather than viral of compartment.

Language: Английский

---

Moonlighting chromatin: when DNA escapes nuclear control

Cell Death and Differentiation, Journal Year: 2023, Volume and Issue: 30(4), P. 861 - 875

Published: Feb. 8, 2023

Abstract Extracellular chromatin, for example in the form of neutrophil extracellular traps (NETs), is an important element that propels pathological progression a plethora diseases. DNA drives interferon system, serves as autoantigen, and forms scaffold proteins innate immune system. An insufficient clearance extruded chromatin after release from nucleus into milieu can perform secret task moonlighting immune-inflammatory occlusive disorders. Here, we discuss (I) cellular events involved NET formation, (II) devastating consequence dysregulated (III) imbalance between formation clearance. We include role occlusion vessels ducts, lung disease, autoimmune diseases, chronic oral disorders, cancer, adhesions, traumatic spinal cord injury. To develop effective therapies, it utmost importance to target pathways cause decondensation during exaggerated aggregation. Alternatively, therapies support are conceivable.

Language: Английский

---

Neutrophil metabolomics in severe COVID-19 reveal GAPDH as a suppressor of neutrophil extracellular trap formation

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: May 5, 2023

Severe COVID-19 is characterized by an increase in the number and changes function of innate immune cells including neutrophils. However, it not known how metabolome patients with COVID-19. To address these questions, we analyzed neutrophils from severe or mild healthy controls. We identified widespread dysregulation neutrophil metabolism disease progression amino acid, redox, central carbon metabolism. Metabolic were consistent reduced activity glycolytic enzyme GAPDH. Inhibition GAPDH blocked glycolysis promoted pentose phosphate pathway but blunted respiratory burst. was sufficient to cause extracellular trap (NET) formation which required elastase activity. inhibition increased pH, blocking this prevented cell death NET formation. These findings indicate that have aberrant can contribute their dysfunction. Our work also shows formation, a pathogenic feature many inflammatory diseases, actively suppressed cell-intrinsic mechanism controlled

Language: Английский

---

Deciphering the Relationship between SARS-CoV-2 and Cancer

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(9), P. 7803 - 7803

Published: April 25, 2023

Some viruses are known to be associated with the onset of specific cancers. These microorganisms, oncogenic or oncoviruses, can convert normal cells into cancer by modulating central metabolic pathways hampering genomic integrity mechanisms, consequently inhibiting apoptotic machinery and/or enhancing cell proliferation. Seven promote tumorigenesis in humans: human papillomavirus (HPV), hepatitis B and C (HBV, HCV), Epstein-Barr virus (EBV), T-cell leukemia 1 (HTLV-1), Kaposi sarcoma-associated herpesvirus (KSHV), Merkel polyomavirus (MCPyV). Recent research indicates that SARS-CoV-2 infection COVID-19 progression may predispose recovered patients accelerate development. This hypothesis is based on growing evidence regarding ability modulate pathways, promoting chronic low-grade inflammation causing tissue damage. Herein, we summarize main relationships date between cancer, providing a summary proposed biochemical mechanisms behind cellular transformation. Mechanistically, DNA (such as HPV, HBV, EBV, MCPyV) encode their oncogenes. In contrast, RNA (like HCV, HTLV-1) oncogenes trigger host through cis-/-trans activation leading different types cancer. As for SARS-CoV-2, its role an seems occur inhibition oncosuppressors controlling autophagy infected cells. However, these effects could significant particular scenarios like those linked severe long COVID. On other hand, looking at SARS-CoV-2─cancer relationship from opposite perspective, oncolytic anti-tumor immune response were triggered some cases. summary, our work aims recall comprehensive attention scientific community elucidate and, more general, β-coronavirus susceptibility prevention supporting therapeutic approaches.

Language: Английский

---