Direct activation of the alternative complement pathway by SARS-CoV-2 spike proteins is blocked by factor D inhibition

Blood, Год журнала: 2020, Номер 136(18), С. 2080 - 2089

Опубликована: Сен. 2, 2020

Язык: Английский

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COVID-19, immunothrombosis and venous thromboembolism: biological mechanisms

Thorax, Год журнала: 2021, Номер 76(4), С. 412 - 420

Опубликована: Янв. 6, 2021

Thrombotic events that frequently occur in COVID-19 are predominantly venous thromboemboli (VTE) and associated with increasing disease severity worse clinical outcomes. Distinctive microvascular abnormalities include endothelial inflammation, disruption of intercellular junctions microthrombi formation. A distinct COVID-19-associated coagulopathy along increased cytokines activation platelets, endothelium complement COVID-19, which is more frequent worsening severity. This proinflammatory milieu may result immunothrombosis, a host defence mechanism can become dysregulated, leading to excess formation immunologically mediated thrombi affect the microvasculature. The haemostatic immune systems intricately linked, multifactorial processes likely contribute VTE immunothrombosis COVID-19. state-of-the-art review will explore pathobiological mechanisms focusing on: coagulopathy, pathology, dysfunction haemostasis, system thrombosis, genetic associations additional thrombotic mechanisms. An understanding complex interplay between these necessary for developing assessing how new treatments

Язык: Английский

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Endothelial dysfunction and altered endothelial biomarkers in patients with post-COVID-19 syndrome and chronic fatigue syndrome (ME/CFS)

Journal of Translational Medicine, Год журнала: 2022, Номер 20(1)

Опубликована: Март 22, 2022

Abstract Background Fatigue, exertion intolerance and post-exertional malaise are among the most frequent symptoms of Post-COVID Syndrome (PCS), with a subset patients fulfilling criteria for Myalgic Encephalomyelitis/Chronic Fatigue (ME/CFS). As SARS-CoV-2 infects endothelial cells, causing endotheliitis damaging endothelium, we investigated dysfunction (ED) biomarkers in PCS. Methods We studied function 30 PCS persistent fatigue as well 15 age- sex matched seronegative healthy controls (HCs). 14 fulfilled diagnostic ME/CFS. The other were considered to have Peripheral was assessed by reactive hyperaemia index (RHI) using peripheral arterial tonometry (PAT) HCs. In larger cohort HCs, including post-COVID reconvalescents (PCHCs), Endothelin-1 (ET-1), Angiopoietin-2 (Ang-2), Endocan (ESM-1), IL-8, Angiotensin-Converting Enzyme (ACE) ACE2 analysed biomarkers. Results Five ME/CFS five 16 showed ED defined diminished RHI (< 1.67), but none HCs exhibited this finding. A paradoxical positive correlation age, blood pressure BMI found not patients. ET-1 concentration significantly elevated both compared PCHCs. serum Ang-2 lower PCHCs Conclusion display evidence shown altered Different associations clinical parameters varying biomarker profiles may suggest distinct pathomechanisms patient subgroups.

Язык: Английский

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Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): a Systemic Infection

Clinical Microbiology Reviews, Год журнала: 2021, Номер 34(2)

Опубликована: Янв. 12, 2021

To date, seven identified coronaviruses (CoVs) have been found to infect humans; of these, three highly pathogenic variants emerged in the 21st century. The newest member this group, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first detected at end 2019 Hubei province, China. Since then, novel has spread worldwide, causing a pandemic; disease caused by virus is called (COVID-19). clinical presentation ranges from asymptomatic mild tract infections and influenza-like illness with accompanying lung injury, multiorgan failure, death. Although lungs are believed be site which SARS-CoV-2 replicates, infected patients often report other symptoms, suggesting involvement gastrointestinal tract, heart, cardiovascular system, kidneys, organs; therefore, following question arises: COVID-19 or systemic disease? This review aims summarize existing data on replication different tissues both ex vivo models.

Язык: Английский

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Hypoxia: A key feature of COVID-19 launching activation of HIF-1 and cytokine storm

Journal of Inflammation, Год журнала: 2020, Номер 17(1)

Опубликована: Окт. 29, 2020

Abstract COVID-19, disease caused by the new coronavirus, SARS-CoV-2, appeared in end of 2019 and was rapidly spread most countries. This respiratory virus has different symptoms from moderate to severe, results lung pneumonia following acute distress syndrome (ARDS) patient’s death severe cases. ARDS is a form injury that high inflammatory response innate immunity cells. Hypoxia common feature sites with having various impacts on this condition induction some factors such as hypoxia inducible factor-1α (HIF-1α). HIF-1α regulates important cellular processes including cell proliferation, metabolism angiogenesis. Furthermore, factor activated during immune responses plays roles inflammation site inducing pro-inflammatory cytokines production through So, study possible effect COVID-19 pathogenesis emphasizes its role been discussed.

Язык: Английский

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Silent hypoxia in COVID-19: pathomechanism and possible management strategy

Molecular Biology Reports, Год журнала: 2021, Номер 48(4), С. 3863 - 3869

Опубликована: Апрель 1, 2021

Язык: Английский

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ICU Admission Levels of Endothelial Biomarkers as Predictors of Mortality in Critically Ill COVID-19 Patients

Cells, Год журнала: 2021, Номер 10(1), С. 186 - 186

Опубликована: Янв. 19, 2021

Endotheliopathy is suggested to be an important feature of COVID-19 in hospitalized patients. To determine whether endotheliopathy involved COVID-19-associated mortality, markers endothelial damage were assessed critically ill patients upon intensive care unit (ICU) admission. Thirty-eight included this observational study, 10 whom died the ICU. Endothelial biomarkers, including soluble (s)E-selectin, sP-selectin, angiopoietin 1 and 2 (Ang-1 Ang-2, respectively), intercellular adhesion molecule (sICAM-1), vascular growth factor (VEGF), (VE)-cadherin, von Willebrand (vWf), measured ICU The cohort was subsequently divided into survivors non-survivors; Kaplan–Meier analysis used explore associations between biomarkers survival, while receiver operating characteristic (ROC) curves generated their potential prognostic value. sE-selectin, sICAM-1 significantly elevated non-survivors compared survivors, also associated with a higher mortality probability analysis. values from ROC greater than 0.85. Hence, we conclude that our cohort, had levels specific survivors. Elevated these admission could possibly predict COVID-19.

Язык: Английский

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Endothelial Dysfunction Driven by Hypoxia—The Influence of Oxygen Deficiency on NO Bioavailability

Biomolecules, Год журнала: 2021, Номер 11(7), С. 982 - 982

Опубликована: Июль 3, 2021

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. The initial stage CVDs is characterized by endothelial dysfunction, defined as limited bioavailability nitric oxide (NO). Thus, any factors that interfere with synthesis or metabolism NO in cells involved CVD pathogenesis. It well established hypoxia both triggering factor accompanying cardiovascular disease, and diminished tissue oxygen levels have been reported to influence bioavailability. In cells, produced synthase (eNOS) from L-Arg, tetrahydrobiopterin (BH4) an essential cofactor. Here, we discuss mechanisms which affects bioavailability, including regulation eNOS expression activity. What particularly important fact contributes depletion cofactor BH4 deficiency substrate thus elicits uncoupling—a state enzyme produces superoxide instead NO. uncoupling resulting oxidative stress major driver dysfunction atherogenesis. Moreover, induces impairment mitochondrial respiration cell activation; thus, inflammation, along hypoxic response, contribute development dysfunction.

Язык: Английский

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Severe COVID-19: A multifaceted viral vasculopathy syndrome

Annals of Diagnostic Pathology, Год журнала: 2020, Номер 50, С. 151645 - 151645

Опубликована: Окт. 13, 2020

Язык: Английский

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Temporal omics analysis in Syrian hamsters unravel cellular effector responses to moderate COVID-19

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Авг. 11, 2021

In COVID-19, immune responses are key in determining disease severity. However, cellular mechanisms at the onset of inflammatory lung injury SARS-CoV-2 infection, particularly involving endothelial cells, remain ill-defined. Using Syrian hamsters as a model for moderate we conduct detailed longitudinal analysis systemic and pulmonary responses, corroborate it with datasets from COVID-19 patients. Monocyte-derived macrophages lungs exert earliest strongest transcriptional response to including induction pro-inflammatory genes, while epithelial cells show weak alterations. Without evidence productive react, depending on cell subtypes, by strong early expression anti-viral, pro-inflammatory, T recruiting genes. Recruitment cytotoxic well emergence IgM antibodies precede viral clearance day 5 post infection. Investigating infected thus identifies type-specific effector functions, providing insights into pathomechanisms informing therapeutic strategies.

Язык: Английский

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