Endothelial dysfunction in COVID-19: an overview of evidence, biomarkers, mechanisms and potential therapies

Acta Pharmacologica Sinica, Journal Year: 2022, Volume and Issue: 44(4), P. 695 - 709

Published: Oct. 17, 2022

Language: Английский

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Rethinking next-generation vaccines for coronaviruses, influenzaviruses, and other respiratory viruses

Cell Host & Microbe, Journal Year: 2023, Volume and Issue: 31(1), P. 146 - 157

Published: Jan. 1, 2023

Language: Английский

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COVID-19 and cellular senescence

Nature reviews. Immunology, Journal Year: 2022, Volume and Issue: 23(4), P. 251 - 263

Published: Oct. 5, 2022

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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SARS-CoV-2 infection induces DNA damage, through CHK1 degradation and impaired 53BP1 recruitment, and cellular senescence

Nature Cell Biology, Journal Year: 2023, Volume and Issue: 25(4), P. 550 - 564

Published: March 9, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the RNA virus responsible for disease 2019 (COVID-19) pandemic. Although SARS-CoV-2 was reported to alter several cellular pathways, its impact on DNA integrity and mechanisms involved remain unknown. Here we show that causes damage elicits an altered response. Mechanistically, proteins ORF6 NSP13 cause degradation of response kinase CHK1 through proteasome autophagy, respectively. loss leads deoxynucleoside triphosphate (dNTP) shortage, causing impaired S-phase progression, damage, pro-inflammatory pathways activation senescence. Supplementation deoxynucleosides reduces that. Furthermore, N-protein impairs 53BP1 focal recruitment by interfering with damage-induced long non-coding RNAs, thus reducing repair. Key observations are recapitulated in SARS-CoV-2-infected mice patients COVID-19. We propose SARS-CoV-2, boosting ribonucleoside levels promote replication at expense dNTPs hijacking RNAs' biology, threatens genome activation, induction inflammation

Language: Английский

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Damage to endothelial barriers and its contribution to long COVID

Angiogenesis, Journal Year: 2023, Volume and Issue: 27(1), P. 5 - 22

Published: April 27, 2023

Language: Английский

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Cellular senescence: Neither irreversible nor reversible

The Journal of Experimental Medicine, Journal Year: 2024, Volume and Issue: 221(4)

Published: Feb. 22, 2024

Cellular senescence is a critical stress response program implicated in embryonic development, wound healing, aging, and immunity, it backs up apoptosis as an ultimate cell-cycle exit mechanism. In analogy to replicative exhaustion of telomere-eroded cells, premature types senescence—referring oncogene-, therapy-, or virus-induced senescence—are widely considered irreversible growth arrest states well. We discuss here that entry into full-featured not necessarily permanent endpoint, but dependent on essential maintenance components, potentially transient. Unlike binary state switch, we view with its extensive epigenomic reorganization, profound cytomorphological remodeling, distinctive metabolic rewiring rather journey toward condition variable strength depth. Senescence-underlying maintenance-essential molecular mechanisms may allow reentry if continuously provided. Importantly, senescent cells resumed proliferation fundamentally differ from those never entered senescence, hence would reflect reversion dynamic progression post-senescent comes distinct functional clinically relevant ramifications.

Language: Английский

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Phase I/II clinical trial of efficacy and safety of EGCG oxygen nebulization inhalation in the treatment of COVID-19 pneumonia patients with cancer

BMC Cancer, Journal Year: 2024, Volume and Issue: 24(1)

Published: April 17, 2024

Abstract Background The antiviral drug Nirmatrelvir was found to be a key in controlling the progression of pneumonia during infectious phase COVID-19. However, there are very few options for effective treatment cancer patients who have viral pneumonia. Glucocorticoids is one means control pneumonia, but many adverse events. EGCG natural low toxic compound with anti-inflammatory function. Thus, this study designed investigate safety and efficacy epigallocatechin-3-gallate (EGCG) aerosol COVID-19 populations. Methods as prospective, single-arm, open-label I/II trial at Shandong Cancer Hospital Institute, between January 5, 2023 March 31,2023 on radiographic signs after confirmed novel coronavirus infection. These were treated nebulization 10 ml three times daily least seven days. concentrations increased from 1760-8817umol/L 4 levels dose escalation following standard Phase I design 3–6 per level. Any grade event caused by considered dose-limiting toxicity (DLT). maximum tolerated (MTD) defined highest less than one-third experiencing limiting (DLT) due EGCG. primary end points CT findings, former graded Common Terminology Criteria Adverse Events (CTCAE) v. 5.0. secondary point laboratory parameters before treatment. Result A total 60 high risk factors severe (factors such old age, smoking combined complications)were included I-II study. 54 final analysis pathologically tumor burden completed whole course patient bucking level 1760 umol/L no acute associated has been reported second or third gradients. At 8817umol/L, Grade 1 events nausea stomach discomfort occurred two patients, which resolved spontaneously within hour. After week treatment, showed that incidence non-progression 82% (32/39), improvement rate 56.4% (22/39). There significant difference inflammation-related (white blood cell count, lymphocyte IL-6, ferritin, C-reactive protein lactate dehydrogenase) Conclusion Aerosol inhalation well tolerated, preliminary investigation population suggests may COVID-19-induced can promote moderate prevent them developing into Trial registration ClinicalTrials.gov Identifier: NCT05758571. Date registration: 8 February 2023.

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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Attributable Mortality of Ventilator-associated Pneumonia Among Patients with COVID-19

American Journal of Respiratory and Critical Care Medicine, Journal Year: 2022, Volume and Issue: 206(2), P. 161 - 169

Published: May 10, 2022

Rationale: Patients with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are at higher risk of ventilator-associated pneumonia (VAP) and may have an increased attributable mortality (increased or decreased death if VAP occurs in patient) fraction (proportion deaths that to exposure) VAP-related compared subjects without disease (COVID-19). Objectives: Estimation the among patients COVID-19. Methods: Using REA-REZO surveillance network, three groups adult medical ICU were computed: control group (patients admitted between 2016 2019; prepandemic patients), pandemic COVID-19 (PandeCOV+), non-COVID-19 (PandeCOV-) during 2020. The primary outcome was estimation related these patients. multistate modeling causal inference, outcomes also evaluated. Measurements Main Results: A total 64,816 included group, 7,442 PandeCOV- 1,687 PandeCOV+ group. incidence 14.2 (95% confidence interval [CI], 13.9 14.6), 18.3 CI, 17.3 19.4), 31.9 29.8 34.2) per 1,000 ventilation-days each respectively. Attributable 90 days 3.15% (95%, 2.04% 3.43%), 2.91% -0.21% 5.02%), 8.13% 3.54% 12.24%), 1.22% 0.83 1.63), 1.42% -0.11% 2.61%), 9.17% 12.24%) for control, PandeCOV-, groups, Except developing VAP, shared similar characteristics lower (hazard ratio, 0.62; 95% 0.52 0.74) than Conclusions: VAP-attributable COVID-19, more 9% overall VAP.

Language: Английский

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