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

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Neutrophil activation and neutrophil extracellular traps (NETs) in COVID‐19 ARDS and immunothrombosis

European Journal of Immunology, Journal Year: 2022, Volume and Issue: 53(1)

Published: Oct. 14, 2022

Acute respiratory distress syndrome (ARDS) is an acute inflammatory condition with a dramatic increase in incidence since the beginning of coronavirus disease 19 (COVID-19) pandemic. Neutrophils play vital role immunopathology severe 2 (SARS-CoV-2) infection by triggering formation neutrophil extracellular traps (NETs), producing cytokines including interleukin-8 (CXCL8), and mediating recruitment other immune cells to regulate processes such as chronic inflammation, which can lead ARDS. CXCL8 involved recruitment, activation, degranulation neutrophils, therefore contributes inflammation amplification severity disease. Furthermore, activation neutrophils also supports prothrombotic phenotype, may explain development immunothrombosis observed COVID-19 This review aims describe hyperinflammatory ARDS due SARS-CoV-2 infection. In addition, we address critical polymorphonuclear cytokines, potential targeting treating population.

Language: Английский

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Platelets in the NETworks interweaving inflammation and thrombosis

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

Published: Aug. 1, 2022

Platelets are well characterized for their indispensable role in primary hemostasis to control hemorrhage. Research over the past years has provided a substantial body of evidence demonstrating that platelets also participate host innate immunity. The surface expression pattern recognition receptors, such as TLR2 and TLR4, provides with ability sense bacterial products environment. Platelet α-granules contain microbicidal proteins, chemokines growth factors, which upon release may directly engage pathogens and/or contribute inflammatory signaling. Additionally, platelet interactions neutrophils enhance neutrophil activation often crucial induce sufficient immune response. In particular, can activate form extracellular traps (NETs). This specific effector function is by expelling chromatin fibres decorated histones antimicrobial proteins into space where they serve trap kill pathogens. Until now, mechanisms signaling pathways between inducing NET formation still not fully characterized. NETs were detected thrombotic lesions several disease backgrounds, pointing towards an interface neutrophils, thrombosis, known immunothrombosis. negatively charged DNA within procoagulant surface, particular NET-derived platelets. light current COVID-19 pandemic, topic immunothrombosis become more relevant than ever, majority patients display thrombi lung capillaries other vascular beds. Furthermore, be found tissues associated increased mortality. Here, virus infiltration lead cytokine storm potently activates leads massive formation. resulting presumably coagulation further contributing subsequent emergence microthrombi pulmonary capillaries. this review, we will discuss interplay potential alliance influence course diseases. A better understanding underlying molecular identification treatment targets utmost importance increase patients' survival improve clinical outcome.

Language: Английский

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Role of SARS-CoV-2-induced cytokine storm in multi-organ failure: Molecular pathways and potential therapeutic options

International Immunopharmacology, Journal Year: 2022, Volume and Issue: 113, P. 109428 - 109428

Published: Nov. 7, 2022

Language: Английский

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Pathophysiological mechanisms of thrombosis in acute and long COVID-19

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

Published: Nov. 16, 2022

COVID-19 patients have a high incidence of thrombosis, and thromboembolic complications are associated with severe mortality. disease is hyper-inflammatory response (cytokine storm) mediated by the immune system. However, role inflammatory in thrombosis remains incompletely understood. In this review, we investigate crosstalk between inflammation context COVID-19, focusing on contributions to pathogenesis propose combined use anti-inflammatory anticoagulant therapeutics. Under conditions, interactions neutrophils platelets, platelet activation, monocyte tissue factor expression, microparticle release, phosphatidylserine (PS) externalization as well complement activation collectively involved immune-thrombosis. Inflammation results apoptosis blood cells, leading release PS cells microparticles, which significantly enhances catalytic efficiency tenase prothrombinase complexes, promotes thrombin-mediated fibrin generation local clot formation. Given risk importance antithrombotic therapies has been generally recognized, but certain deficiencies treatment gaps remain. Antiplatelet drugs not combination treatments, thus fail dampen procoagulant activity. Current treatments also do an optimal time for anticoagulation. The efficacy depends therapy initiation. best early possible after diagnosis, ideally stage disease. We elaborate mechanisms long COVID complications, including persistent inflammation, endothelial injury dysfunction, coagulation abnormalities. above-mentioned contents provide therapeutic strategies further improve patient outcomes.

Language: Английский

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The role of cell death in SARS-CoV-2 infection

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Sept. 20, 2023

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), showing high infectiousness, resulted in an ongoing pandemic termed disease 2019 (COVID-19). COVID-19 cases often experience distress syndrome, which has caused millions of deaths. Apart from triggering inflammatory and immune responses, many viral infections can cause programmed cell death infected cells. Cell mechanisms have a vital role maintaining suitable environment to achieve normal functionality. Nonetheless, these processes are dysregulated, potentially contributing pathogenesis. Over the past decades, multiple pathways becoming better understood. Growing evidence suggests that induction by may significantly contributes infection pathogenicity. However, interaction SARS-CoV-2 with death, together its associated mechanisms, is yet be elucidated. In this review, we summarize existing concerning molecular modulation as well viral-host interactions, shed new light on antiviral therapy against SARS-CoV-2.

Language: Английский

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Innate and Adaptive Immunity during SARS-CoV-2 Infection: Biomolecular Cellular Markers and Mechanisms

Vaccines, Journal Year: 2023, Volume and Issue: 11(2), P. 408 - 408

Published: Feb. 10, 2023

The coronavirus 2019 (COVID-19) pandemic was caused by a positive sense single-stranded RNA (ssRNA) severe acute respiratory syndrome 2 (SARS-CoV-2). However, other human coronaviruses (hCoVs) exist. Historical pandemics include smallpox and influenza, with efficacious therapeutics utilized to reduce overall disease burden through effectively targeting competent host immune system response. is composed of primary/secondary lymphoid structures initially eight types cell types, many subtypes, traversing membranes utilizing signaling cascades that contribute towards clearance pathogenic proteins. Other proteins discussed cluster differentiation (CD) markers, major histocompatibility complexes (MHC), pleiotropic interleukins (IL), chemokines (CXC). historical concepts immunity are the innate adaptive systems. represented T cells, B antibodies. macrophages, neutrophils, dendritic complement system. viruses can affect regulate cycle progression for example, in cancers papillomavirus (HPV: cervical carcinoma), Epstein-Barr virus (EBV: lymphoma), Hepatitis C (HB/HC: hepatocellular carcinoma) Leukemia Virus-1 (T leukemia). Bacterial infections also increase risk developing cancer (e.g.,

Language: Английский

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Pathogenesis and Mechanisms of SARS-CoV-2 Infection in the Intestine, Liver, and Pancreas

Cells, Journal Year: 2023, Volume and Issue: 12(2), P. 262 - 262

Published: Jan. 9, 2023

The novel coronavirus, SARS-CoV-2, rapidly spread worldwide, causing an ongoing global pandemic. While the respiratory system is most common site of infection, a significant number reported cases indicate gastrointestinal (GI) involvement. GI symptoms include anorexia, abdominal pain, nausea, vomiting, and diarrhea. Although mechanisms pathogenesis are still being examined, viral components isolated from stool samples infected patients suggest potential fecal–oral transmission route. In addition, RNA has been detected in blood patients, making hematologic dissemination virus proposed route for Angiotensin-converting enzyme 2 (ACE2) receptors serve as cellular entry mechanism virus, these particularly abundant throughout tract, intestine, liver, pancreas extrapulmonary sites infection reservoirs developing mutations new variants that contribute to uncontrolled disease resistance treatments. This dysregulation immune play role profound inflammatory coagulative cascades increased severity risk death several COVID-19 patients. article reviews various gastrointestinal, pancreatic injury.

Language: Английский

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Microvascular Thrombosis as a Critical Factor in Severe COVID-19

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2492 - 2492

Published: Jan. 27, 2023

Platelet-endothelial interactions have a critical role in microcirculatory function, which maintains tissue homeostasis. The subtle equilibrium between platelets and the vessel wall is disturbed by coronavirus disease 2019 (COVID-19), affects all three components of Virchow's triad (endothelial injury, stasis hypercoagulable state). Endotheliitis, vasculitis, glycocalyx degradation, alterations blood flow viscosity, neutrophil extracellular trap formation microparticle shedding are only few pathomechanisms contributing to endothelial damage microthrombosis resulting capillary plugging ischemia. In following opinion paper, we discuss major pathological processes leading microvascular activation thrombosis as possible adverse factor driving deterioration patient course severe COVID-19.

Language: Английский

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The Effects of Curcumin on Inflammasome: Latest Update

Molecules, Journal Year: 2023, Volume and Issue: 28(2), P. 742 - 742

Published: Jan. 11, 2023

Curcumin, a traditional Chinese medicine extracted from natural plant rhizomes, has become candidate drug for the treatment of different diseases due to its anti-inflammatory, anticancer, antioxidant, and antibacterial activities. Curcumin is generally beneficial improve human health with anti-inflammatory antioxidative properties as well antitumor immunoregulatory properties. Inflammasomes are NLR family, pyrin domain-containing 3 (NLRP3) proteins that activated in response variety stress signals promote proteolytic conversion pro-interleukin-1β pro-interleukin-18 into active forms, which central mediators inflammatory response; inflammasomes can also induce pyroptosis, type cell death. The NLRP3 protein involved pathologies, including neurological autoimmune disorders, lung diseases, atherosclerosis, myocardial infarction, many others. Different functional foods may have preventive therapeutic effects wide range pathologies inflammasome activated. In this review, we focused on curcumin evidenced potential such neurodegenerative respiratory arthritis by acting inflammasome.

Language: Английский

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