Long Covid: where we stand and challenges ahead

Cell Death and Differentiation, Journal Year: 2022, Volume and Issue: unknown

Published: Sept. 7, 2022

Abstract Post-acute sequelae of SARS-CoV-2 (PASC), also known as Post-Covid Syndrome, and colloquially Long Covid, has been defined a constellation signs symptoms which persist for weeks or months after the initial infection. PASC affects wide range diverse organs systems, with manifestations involving lungs, brain, cardiovascular system other such kidney neuromuscular system. The pathogenesis is complex multifactorial. Evidence suggests that seeding persistence in different organs, reactivation, response to unrelated viruses EBV, autoimmunity, uncontrolled inflammation are major drivers PASC. relative importance pathogenetic pathways may differ tissue organ contexts. vaccination, addition protecting against disease, reduces breakthrough infection although its actual impact remains be defined. represents formidable challenge health care systems dissecting mechanisms pave way targeted preventive therapeutic approaches.

Language: Английский

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Combining L-Arginine with vitamin C improves long-COVID symptoms: The LINCOLN Survey

Pharmacological Research, Journal Year: 2022, Volume and Issue: 183, P. 106360 - 106360

Published: July 19, 2022

Language: Английский

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Glutathione: A Samsonian life-sustaining small molecule that protects against oxidative stress, ageing and damaging inflammation

Frontiers in Nutrition, Journal Year: 2022, Volume and Issue: 9

Published: Nov. 1, 2022

Many local and systemic diseases especially that are leading causes of death globally like chronic obstructive pulmonary disease, atherosclerosis with ischemic heart disease stroke, cancer severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing 19 (COVID-19), involve both, (1) oxidative stress excessive production reactive oxygen species (ROS) lower glutathione (GSH) levels, (2) inflammation. The GSH tripeptide (γ- L-glutamyl-L-cysteinyl-glycine), the most abundant water-soluble non-protein thiol in cell (1–10 mM) is fundamental for life by (a) sustaining adequate redox signaling needed to maintain physiologic levels control processes, (b) limiting tissue damage. activity facilitated activation Kelch-like ECH-associated protein 1 (Keap1)-Nuclear factor erythroid 2-related (Nrf2)-antioxidant response element (ARE) regulator pathway, releasing Nrf2 regulates expression genes controlling antioxidant, inflammatory immune system responses. exists thiol-reduced (>98% total GSH) disulfide-oxidized (GSSG) forms, concentrations GSSG their molar ratio indicators functionality cell. depletion may play a central role COVID-19 pathophysiology, host severity mortality. Therapies enhancing could become cornerstone reduce fatal outcomes increasing prevent subdue these diseases. value makes paramount research field biology medicine be key against inflammation SARS-CoV-2 infection disease. In this review, we emphasize on as risk (ischemic stroke), importance antioxidants (3) significance counteract persistent damaging inflammation, inflammaging early (premature) associated damage caused lack antioxidant defenses younger individuals, (4) new therapies include restoration.

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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SARS-CoV-2 S protein activates NLRP3 inflammasome and deregulates coagulation factors in endothelial and immune cells

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 15, 2024

Abstract Background Hyperinflammation, hypercoagulation and endothelial injury are major findings in acute post-COVID-19. The SARS-CoV-2 S protein has been detected as an isolated element human tissues reservoirs is the main product of mRNA COVID-19 vaccines. We investigated whether alone triggers pro-inflammatory pro-coagulant responses primary cultures two cell types deeply affected by SARS-CoV-2, such monocytes cells. Methods In umbilical vein cells (HUVEC) monocytes, components NF-κB NLRP3 inflammasome system, well coagulation regulators, were assessed qRT-PCR, Western blot, flow cytometry, or indirect immunofluorescence. Results activated NF-κB, promoted cytokines release, triggered priming activation system resulting mature IL-1β formation both types. This was paralleled enhanced production factors von Willebrand factor (vWF), VIII tissue factor, that mediated, at least part, IL-1β. Additionally, failed to enhance ADAMTS-13 levels counteract activity vWF multimers. Monocytes HUVEC barely expressed angiotensin-converting enzyme-2. Pharmacological approaches gene silencing showed TLR4 receptors mediated effects but not HUVEC. Conclusion behaves a stimulus Interfering with signaling pathways evoked may help preventing immune vascular complications driven viral element.

Language: Английский

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Impact of vaccination on the association of COVID-19 with cardiovascular diseases: An OpenSAFELY cohort study

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 11, 2024

Abstract Infection with SARS-CoV-2 is associated an increased risk of arterial and venous thrombotic events, but the implications vaccination for this are uncertain. With approval NHS England, we quantified associations between COVID-19 diagnosis cardiovascular diseases in different variant eras using linked electronic health records ~40% English population. We defined a ‘pre-vaccination’ cohort (18,210,937 people) wild-type/Alpha (January 2020-June 2021), ‘vaccinated’ ‘unvaccinated’ cohorts (13,572,399 3,161,485 people respectively) Delta era (June-December 2021). showed that incidence each thrombotic, other outcomes was substantially elevated during weeks 1-4 after COVID-19, compared before or without less markedly time periods beyond week 4. Hazard ratios were higher hospitalised than non-hospitalised pre-vaccination unvaccinated vaccinated cohort. reduces events infection. People who had being at least two years.

Language: Английский

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The potential role of ischaemia–reperfusion injury in chronic, relapsing diseases such as rheumatoid arthritis, Long COVID, and ME/CFS: evidence, mechanisms, and therapeutic implications

Biochemical Journal, Journal Year: 2022, Volume and Issue: 479(16), P. 1653 - 1708

Published: Aug. 31, 2022

Ischaemia-reperfusion (I-R) injury, initiated via bursts of reactive oxygen species produced during the reoxygenation phase following hypoxia, is well known in a variety acute circumstances. We argue here that I-R injury also underpins elements pathology chronic, inflammatory diseases, including rheumatoid arthritis, ME/CFS and, our chief focus and most proximally, Long COVID. Ischaemia may be fibrin amyloid microclot blockage capillaries, for instance as exercise started; reperfusion necessary corollary when it finishes. rehearse mechanistic evidence these occurrences here, terms their manifestation oxidative stress, hyperinflammation, mast cell activation, production marker metabolites related activities. Such microclot-based phenomena can explain both breathlessness/fatigue post-exertional malaise observed conditions, many other observables. The recognition processes implies, mechanistically, therapeutic benefit potentially to had from antioxidants, anti-inflammatories, iron chelators, suitable, safe fibrinolytics, and/or anti-clotting agents. review considerable existing consistent with this, biochemical mechanisms involved.

Language: Английский

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Organ and cell-specific biomarkers of Long-COVID identified with targeted proteomics and machine learning

Molecular Medicine, Journal Year: 2023, Volume and Issue: 29(1)

Published: Feb. 21, 2023

Survivors of acute COVID-19 often suffer prolonged, diffuse symptoms post-infection, referred to as "Long-COVID". A lack Long-COVID biomarkers and pathophysiological mechanisms limits effective diagnosis, treatment disease surveillance. We performed targeted proteomics machine learning analyses identify novel blood Long-COVID.A case-control study comparing the expression 2925 unique proteins in outpatients versus inpatients healthy control subjects. Targeted was accomplished with proximity extension assays, used most important for identifying patients. Organ system cell type patterns were identified Natural Language Processing (NLP) UniProt Knowledgebase.Machine analysis 119 relevant differentiating (Bonferonni corrected P < 0.01). Protein combinations narrowed down two optimal models, nine five each, both having excellent sensitivity specificity status (AUC = 1.00, F1 1.00). NLP highlighted organ involvement Long-COVID, well involved types, including leukocytes platelets, key components associated Long-COVID.Proteomic plasma from patients highly models proteins, respectively. The reflected widespread expression. Optimal protein individual hold potential accurate diagnosis therapeutics.

Language: Английский

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Vascular Alterations Following COVID-19 Infection: A Comprehensive Literature Review

Life, Journal Year: 2024, Volume and Issue: 14(5), P. 545 - 545

Published: April 24, 2024

SARS-CoV-2, the causative agent of ongoing COVID-19 pandemic, has revealed a broader impact beyond respiratory system, predominantly affecting vascular system with various adverse manifestations. The infection induces endothelial dysfunction and immune dysregulation, creating an inflammatory hypercoagulable state. It affects both microvasculature macrovasculature, leading to thromboembolic events, cardiovascular manifestations, impaired arterial stiffness, cerebrovascular complications, nephropathy, as well retinopathy-frequently observed in cases severe illness. Evidence suggests that SARS-CoV-2 may result persistent effects on identified long-term COVID-19. This is characterized by prolonged inflammation, endotheliopathy, increased risk complications. Various imaging modalities, histopathological studies, diagnostic tools such video capillaroscopy magnetic resonance have been employed visualize alterations. review aims comprehensively summarize evidence concerning short alterations following infection, investigating their patients' prognosis, providing overview preventive strategies mitigate associated

Language: Английский

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Neurovascular coupling impairment as a mechanism for cognitive deficits in COVID-19

Brain Communications, Journal Year: 2024, Volume and Issue: 6(2)

Published: Jan. 1, 2024

Abstract Components that comprise our brain parenchymal and cerebrovascular structures provide a homeostatic environment for proper neuronal function to ensure normal cognition. Cerebral insults (e.g. ischaemia, microbleeds infection) alter cellular physiologic processes within the neurovascular unit contribute cognitive dysfunction. COVID-19 has posed significant complications during acute convalescent stages in multiple organ systems, including brain. Cognitive impairment is prevalent complication patients, irrespective of severity SARS-CoV-2 infection. Moreover, overwhelming evidence from vitro, preclinical clinical studies reported SARS-CoV-2-induced pathologies components are associated with impairment. Neurovascular disruption alters coupling response, critical mechanism regulates cerebromicrovascular blood flow meet energetic demands locally active neurons. Normal processing achieved through response involves coordinated action cells (i.e. neurons glia) cell types endothelia, smooth muscle pericytes). However, current work on COVID-19-induced yet investigate as causal factor. Hence, this review, we aim describe SARS-CoV-2's effects how they can impact decline disease. Additionally, explore potential therapeutic interventions mitigate Given great both individuals public health, necessity effort fundamental scientific research application becomes imperative. This integrated endeavour crucial mitigating deficits induced by its subsequent burden especially vulnerable population.

Language: Английский

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