scholarly journals Endothelium Infection and Dysregulation by SARS-CoV-2: Evidence and Caveats in COVID-19

Viruses ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 29
Author(s):  
Isabelle Bernard ◽  
Daniel Limonta ◽  
Lara K. Mahal ◽  
Tom C. Hobman
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Human Lung ◽  
Neurological Diseases ◽  
Severe Disease ◽  
Respiratory Illness ◽  
Global Public Health ◽  
Angiotensin Converting Enzyme 2 ◽  
The Relationship ◽  
Cardiac Microvascular Endothelial Cells

The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by the acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) poses a persistent threat to global public health. Although primarily a respiratory illness, extrapulmonary manifestations of COVID-19 include gastrointestinal, cardiovascular, renal and neurological diseases. Recent studies suggest that dysfunction of the endothelium during COVID-19 may exacerbate these deleterious events by inciting inflammatory and microvascular thrombotic processes. Although controversial, there is evidence that SARS-CoV-2 may infect endothelial cells by binding to the angiotensin-converting enzyme 2 (ACE2) cellular receptor using the viral Spike protein. In this review, we explore current insights into the relationship between SARS-CoV-2 infection, endothelial dysfunction due to ACE2 downregulation, and deleterious pulmonary and extra-pulmonary immunothrombotic complications in severe COVID-19. We also discuss preclinical and clinical development of therapeutic agents targeting SARS-CoV-2-mediated endothelial dysfunction. Finally, we present evidence of SARS-CoV-2 replication in primary human lung and cardiac microvascular endothelial cells. Accordingly, in striving to understand the parameters that lead to severe disease in COVID-19 patients, it is important to consider how direct infection of endothelial cells by SARS-CoV-2 may contribute to this process.

scholarly journals Pathophysiological Association of Endothelial Dysfunction with Fatal Outcome in COVID-19

2021 ◽  
Vol 22 (10) ◽  
pp. 5131
Author(s):  
Tatsuya Maruhashi ◽  
Yukihito Higashi
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Severe Disease ◽  
Fatal Outcome ◽  
Major Complication ◽  
High Morbidity ◽  
Angiotensin Converting Enzyme 2 ◽  
Disease Outcomes ◽  
Thrombotic Complications ◽  
Hypoxic Respiratory Failure

The outbreak of coronavirus disease 2019 (COVID-19) caused by the betacoronavirus SARS-CoV-2 is now a worldwide challenge for healthcare systems. Although the leading cause of mortality in patients with COVID-19 is hypoxic respiratory failure due to viral pneumonia and acute respiratory distress syndrome, accumulating evidence has shown that the risk of thromboembolism is substantially high in patients with severe COVID-19 and that a thromboembolic event is another major complication contributing to the high morbidity and mortality in patients with COVID-19. Endothelial dysfunction is emerging as one of the main contributors to the pathogenesis of thromboembolic events in COVID-19. Endothelial dysfunction is usually referred to as reduced nitric oxide bioavailability. However, failures of the endothelium to control coagulation, inflammation, or permeability are also instances of endothelial dysfunction. Recent studies have indicated the possibility that SARS-CoV-2 can directly infect endothelial cells via the angiotensin-converting enzyme 2 pathway and that endothelial dysfunction caused by direct virus infection of endothelial cells may contribute to thrombotic complications and severe disease outcomes in patients with COVID-19. In this review, we summarize the current understanding of relationships between SARS-CoV-2 infection, endothelial dysfunction, and pulmonary and extrapulmonary complications in patients with COVID-19.

scholarly journals SARS-CoV-2 Omicron variant replication in human respiratory tract ex vivo

2021 ◽  
Author(s):  
Michael C. W. Chan ◽  
Kenrie PY Hui ◽  
John Ho ◽  
Man-chun Cheung ◽  
Ka-chun Ng ◽  
...  
Keyword(s):  
Human Lung ◽  
Ex Vivo ◽  
Natural Infection ◽  
Severe Disease ◽  
Lung Parenchyma ◽  
Global Public Health ◽  
Wild Type ◽  
Human Respiratory Tract ◽  
Human Bronchus ◽  
Cellular Tropism

Abstract Emergence of SARS-CoV-2 variants of concern (VOC) with progressively increased transmissibility between humans is a threat to global public health. Omicron variant also evades immunity from natural infection or vaccines1. It is unclear whether its exceptional transmissibility is due to immune evasion or inherent virological properties.We compared the replication competence and cellular tropism of the wild type (WT) virus, D614G, Alpha, Beta, Delta and Omicron variants in ex vivo explant cultures of human bronchus and lung. Dependence on TMPRSS2 for infection was also evaluated. We show that Omicron replicated faster than all other SARS-CoV-2 in the bronchus but less efficiently in the lung parenchyma. All VOCs had similar cellular tropism as the WT. Delta was more dependent on serine protease than other VOCs tested.Our findings demonstrate that Omicron is inherently able to replicate faster than other variants known to date and this likely contributes to its inherently higher transmissibility, irrespective of its ability to evade antibody immunity. The lower replication competence of Omicron in human lung may be compatible with reduced severity but the determinants of severe disease are multifactorial. These findings provide important biological clues to the transmissibility and pathogenesis of SARS-CoV-2 VOCs.

Plasma Level of IL-1β in Disseminated Intravascular Goagulation

1991 ◽  
Vol 65 (04) ◽  
pp. 364-368 ◽  
Author(s):  
Hideo Wada ◽  
Shigehisa Tamaki ◽  
Motoaki Tanigawa ◽  
Mikio Takagi ◽  
Yoshitaka Mori ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tumor Necrosis Factor ◽  
Plasma Level ◽  
Organ Failure ◽  
Tumor Necrosis ◽  
Mononuclear Cells ◽  
Solid Cancer ◽  
Normal Individuals ◽  
The Relationship ◽  
Necrosis Factor

SummaryThe plasma level of interleukin-1β (IL-1β) was determined in normal individuals, patients with disseminated intravascular coagulation (DIC), patients in the pre-DIC period (within 7 days before the onset of DIC), and non-DIC patients to examine the relationship between DIC and the plasma ILlp level. The plasma IL-1β level was 0-0.085 ng/ml in normal individuals, with little difference being seen according to related age. It was significantly higher in the DIC group (0.19 ± 0.19 ng/ml) than in the pre-DIC group (0.05 ± 0.08 ng/ml) or the non-DIC group (0.09 ± 0.01 ng/ml). The plasma IL-1β level was not markedly elevated in leukemia patients, even in the DIC group, but it was significantly increased in the DIC group of solid cancer patients and was generally elevated in patients with sepsis. It was markedly elevated to 0.39 ± 0.26 ng/ml in patients with organ failure. When mononuclear cells were incubated with lipopolysaccharide, it was found that IL-1β, tumor necrosis factor, and tissue factor (TF) were released into the medium, and there was an increase of TF release from endothelial cells incubated with this medium. These results suggest that the increase in IL-Iβ reflected the activation of monocytes and may be an important factor in DIC and its associated organ failure.

The Effects of P75NTR on Learning Memory Mediated by Hippocampal Apoptosis and Synaptic Plasticity

2020 ◽  
Vol 26 ◽  
Author(s):  
Jun-Jie Tang ◽  
Shuang Feng ◽  
Xing-Dong Chen ◽  
Hua Huang ◽  
Min Mao ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Learning And Memory ◽  
Neurological Diseases ◽  
Neurotrophin Receptor ◽  
P75 Neurotrophin Receptor ◽  
Negative Effects ◽  
Apoptotic Effect ◽  
New Ideas ◽  
The Relationship

: Neurological diseases bring great mental and physical torture to the patients, and have long-term and sustained negative effects on families and society. The attention to neurological diseases is increasing, and the improvement of the material level is accompanied by an increase in the demand for mental level. The p75 neurotrophin receptor (p75NTR) is a low-affinity neurotrophin receptor and involved in diverse and pleiotropic effects in the developmental and adult central nervous system (CNS). Since neurological diseases are usually accompanied by the regression of memory, the pathogenesis of p75NTR also activates and inhibits other signaling pathways, which has a serious impact on the learning and memory of patients. The results of studies shown that p75NTR is associated with LTP/LTD-induced synaptic enhancement and inhibition, suggest that p75NTR may be involved in the progression of synaptic plasticity. And its pro-apoptotic effect is associated with activation of proBDNF and inhibition of proNGF, and TrkA/p75NTR imbalance leads to pro-survival or pro-apoptotic phenomena. It can be inferred that p75NTR mediates apoptosis in the hippocampus and amygdale, which may affect learning and memory behavior. This article mainly discusses the relationship between p75NTR and learning memory and associated mechanisms, which may provide some new ideas for the treatment of neurological diseases.

Endothelial Dysfunction and Inflammatory Markers of Vascular Disease

2020 ◽  
Vol 19 (3) ◽  
pp. 243-249 ◽  
Author(s):  
Sevket Balta
Keyword(s):  
Endothelial Dysfunction ◽  
Vascular Disease ◽  
Inflammatory Markers ◽  
Vascular Diseases ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Non Invasive ◽  
Von Willebrand ◽  
The Relationship ◽  
Willebrand Factor

: Vascular diseases are the main reason for morbidity and mortality worldwide. As we know, the earlier phase of vascular diseases is endothelial dysfunction in humans, the endothelial tissues play an important role in inflammation, coagulation, and angiogenesis, via organizing ligand-receptor associations and the various mediators’ secretion. We can use many inflammatory non-invasive tests (flowmediated dilatation, epicedial fat thickness, carotid-intima media thickness, arterial stiffness and anklebrachial index) for assessing the endothelial function. In addition, many biomarkers (ischemia modified albumin, pentraxin-3, E-selectin, angiopoietin, endothelial cell specific molecule 1, asymmetrical dimethylarginine, von Willebrand factor, endothelial microparticles and endothelial progenitor cells) can be used to evaluate endothelial dysfunction. We have focused on the relationship between endothelial dysfunction and inflammatory markers of vascular disease in this review.

Can Mandated BCG Vaccine Promote herd Immunity against Novel Coronavirus? A Potential Solution at Hand to Tackle Covid-19 Pandemic

2020 ◽  
Vol 16 (1) ◽  
pp. 6-11
Author(s):  
Ashok Arasu ◽  
Pavithra Balakrishnan ◽  
Thirunavukkarasu Velusamy ◽  
Thiagarajan Ramesh
Keyword(s):  
Protective Factor ◽  
Herd Immunity ◽  
Bcg Vaccine ◽  
Intestinal Cells ◽  
Global Public Health ◽  
Wuhan City ◽  
Live Attenuated Vaccine ◽  
Angiotensin Converting Enzyme 2 ◽  
Lung Epithelial ◽  
Novel Coronavirus

The 2019 novel coronavirus (2019-nCoV) infection is an emerging pandemic that poses a severe threat to global public health. This pandemic started from the Wuhan City of Hubei Province in China, and is speculated to have originated from bats and spread among humans with an unknown intermediate transmitter. The virus binds to angiotensin-converting enzyme 2 (ACE2), which is abundantly expressed on various human cells, including lung epithelial and intestinal cells, thereby entering into these cells and causing infection. It is transmitted to other humans through airborne droplets from infected patients. Presently there are no specific treatments or vaccines that are available to curtail the spread of this disease. There are few indirect reports that explain the potential importance of the mandated BCG vaccine as a protective factor against COVID-19. There is a speculation that a live attenuated vaccine (BCG vaccine) can be beneficial against COVID-19 to develop the initial immune response, and can also spread in the community, thereby boosting herd immunity to fight against COVID-19. This review summarizes the conclusions of various reports on the BCG vaccine, and is an attempt to establish BCG-vaccination mediated herd immunity as an effective instant intermediate approach in curbing COVID-19 spread in highly populous countries.

scholarly journals Generation of a Novel In Vitro Model to Study Endothelial Dysfunction from Atherothrombotic Specimens

2021 ◽  
Author(s):  
Susan Gallogly ◽  
Takeshi Fujisawa ◽  
John D. Hung ◽  
Mairi Brittan ◽  
Elizabeth M. Skinner ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
In Vitro Model ◽  
Umbilical Vein ◽  
Coronary Syndrome ◽  
Coronary Endothelial Cells ◽  
Vitro Model ◽  
Umbilical Vein Endothelial Cells

Abstract Purpose Endothelial dysfunction is central to the pathogenesis of acute coronary syndrome. The study of diseased endothelium is very challenging due to inherent difficulties in isolating endothelial cells from the coronary vascular bed. We sought to isolate and characterise coronary endothelial cells from patients undergoing thrombectomy for myocardial infarction to develop a patient-specific in vitro model of endothelial dysfunction. Methods In a prospective cohort study, 49 patients underwent percutaneous coronary intervention with thrombus aspiration. Specimens were cultured, and coronary endothelial outgrowth (CEO) cells were isolated. CEO cells, endothelial cells isolated from peripheral blood, explanted coronary arteries, and umbilical veins were phenotyped and assessed functionally in vitro and in vivo. Results CEO cells were obtained from 27/37 (73%) atherothrombotic specimens and gave rise to cells with cobblestone morphology expressing CD146 (94 ± 6%), CD31 (87 ± 14%), and von Willebrand factor (100 ± 1%). Proliferation of CEO cells was impaired compared to both coronary artery and umbilical vein endothelial cells (population doubling time, 2.5 ± 1.0 versus 1.6 ± 0.3 and 1.2 ± 0.3 days, respectively). Cell migration was also reduced compared to umbilical vein endothelial cells (29 ± 20% versus 85±19%). Importantly, unlike control endothelial cells, dysfunctional CEO cells did not incorporate into new vessels or promote angiogenesis in vivo. Conclusions CEO cells can be reliably isolated and cultured from thrombectomy specimens in patients with acute coronary syndrome. Compared to controls, patient-derived coronary endothelial cells had impaired capacity to proliferate, migrate, and contribute to angiogenesis. CEO cells could be used to identify novel therapeutic targets to enhance endothelial function and prevent acute coronary syndromes.

scholarly journals Symptom cluster is associated with prolonged return-to-play in symptomatic athletes with acute respiratory illness (including COVID-19): a cross-sectional study—AWARE study I

2021 ◽  
pp. bjsports-2020-103782
Author(s):  
Martin Schwellnus ◽  
Nicola Sewry ◽  
Carolette Snyders ◽  
Kelly Kaulback ◽  
Paola Silvia Wood ◽  
...  
Keyword(s):  
Online Survey ◽  
Severe Disease ◽  
Univariate Analysis ◽  
Respiratory Illness ◽  
Symptom Cluster ◽  
Return To Play ◽  
Whole Body ◽  
Multiple Model ◽  
Acute Respiratory Illness ◽  
Cross Sectional

BackgroundThere are no data relating symptoms of an acute respiratory illness (ARI) in general, and COVID-19 specifically, to return to play (RTP).ObjectiveTo determine if ARI symptoms are associated with more prolonged RTP, and if days to RTP and symptoms (number, type, duration and severity) differ in athletes with COVID-19 versus athletes with other ARI.DesignCross-sectional descriptive study.SettingOnline survey.ParticipantsAthletes with confirmed/suspected COVID-19 (ARICOV) (n=45) and athletes with other ARI (ARIOTH) (n=39).MethodsParticipants recorded days to RTP and completed an online survey detailing ARI symptoms (number, type, severity and duration) in three categories: ‘nose and throat’, ‘chest and neck’ and ‘whole body’. We report the association between symptoms and RTP (% chance over 40 days) and compare the days to RTP and symptoms (number, type, duration and severity) in ARICOV versus ARIOTH subgroups.ResultsThe symptom cluster associated with more prolonged RTP (lower chance over 40 days; %) (univariate analysis) was ‘excessive fatigue’ (75%; p<0.0001), ‘chills’ (65%; p=0.004), ‘fever’ (64%; p=0.004), ‘headache’ (56%; p=0.006), ‘altered/loss sense of smell’ (51%; p=0.009), ‘Chest pain/pressure’ (48%; p=0.033), ‘difficulty in breathing’ (48%; p=0.022) and ‘loss of appetite’ (47%; p=0.022). ‘Excessive fatigue’ remained associated with prolonged RTP (p=0.0002) in a multiple model. Compared with ARIOTH, the ARICOV subgroup had more severe disease (greater number, more severe symptoms) and more days to RTP (p=0.0043).ConclusionSymptom clusters may be used by sport and exercise physicians to assist decision making for RTP in athletes with ARI (including COVID-19).

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