Corpus overview


Overview

MeSH Disease

Human Phenotype

Transmission

Seroprevalence
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    Proposal of selective wedge instillation of pulmonary surfactant for COVID-19 pneumonia HP pneumonia MESHD based on computational fluid dynamics simulation

    Authors: Hiroko Kitaoka; Hisato Kobayashi; Takayuki Takimoto; Takashi Kijima

    doi:10.21203/rs.3.rs-75938/v1 Date: 2020-09-11 Source: ResearchSquare

    Background: The most important target cell of SARS-CoV-2 is Type II pneumocyte which produces and secretes pulmonary MESHD surfactant (PS) that prevents alveolar MESHD collapse. PS instillation therapy is dramatically effective for infant respiratory distress HP respiratory distress MESHD syndrome but has been clinically ineffective for ARDS. Nowadays, ARDS is regarded as non-cardiogenic pulmonary edema HP pulmonary edema MESHD with vascular hyper-permeability regardless of direct relation to PS dysfunction. However, there is a possibility that the ineffectiveness of PS instillation for ARDS is due to insufficient delivery MESHD. Then, we performed PS instillation simulation with realistic human airway models by the use of computational fluid dynamics, and investigated how instilled PS would move in the liquid layer covering the airway wall and reach to alveolar regions MESHD.Methods: Two types of 3D human airway model were prepared: One was from the trachea to lobular bronchi and the other was from a sub-segmental bronchus to respiratory bronchioles. Thickness of the liquid layer covering the airway was assigned as 14 % of the inner radius of the airway segment. Initially existing liquid layer was assumed to be replaced by instilled PS. Flow rate of instilled PS was assigned a constant value, which was determined by the total amount and instillation time in clinical use. The PS concentration of the liquid layer during instillation was computed by solving advective-diffusion equation.Results: The driving pressure from the trachea to respiratory bronchioles was calculated at 317 cmH2O, which is about 20 times of a standard value in conventional PS instillation method where the driving pressure is given by difference between inspiratory and end-expiratory pressures of a ventilator. It means that almost all PS would not reach alveolar MESHD regions but move to and fro within the airway according to the change of ventilator pressure. On the other hand, the driving pressure from sub-segmental bronchus was calculated at 273 cm H2O, that is clinically possible by wedge instillation under bronchoscopic observation. Conclusions: The simulation study has revealed that selective wedge instillation under bronchoscopic observation should be tried for COVID-19 pneumonia HP pneumonia MESHD even before ARDS. It will be also useful for preventing secondary lung fibrosis MESHD

    Single-cell analysis reveals the function of lung progenitor cells in COVID-19 patients

    Authors: Wei Zuo; Zixian Zhao; Yu Zhao; Yueqing Zhou; Xiaofan Wang; Ting Zhang

    doi:10.1101/2020.07.13.200188 Date: 2020-07-13 Source: bioRxiv

    The high mortality of severe 2019 novel coronavirus disease MESHD (COVID-19) cases is mainly caused by acute respiratory distress HP respiratory distress MESHD syndrome ( ARDS MESHD), which is characterized by increased permeability of the alveolar MESHD epithelial barriers, pulmonary edema HP pulmonary edema MESHD and consequently inflammatory tissue damage. Some but not all patients showed full functional recovery after the devastating lung damage, and so far there is little knowledge about the lung repair process1. Here by analyzing the bronchoalveolar lavage fluid (BALF) of COVID-19 patients through single cell RNA-sequencing (scRNA-Seq), we found that in severe (or critical) cases, there is remarkable expansion of TM4SF1+ and KRT5+ lung progenitor cells. The two distinct populations of progenitor cells could play crucial roles in alveolar MESHD cell regeneration and epithelial barrier re-establishment, respectively. In order to understand the function of KRT5+ progenitors in vivo, we transplanted a single KRT5+ cell-derived cell population into damaged mouse lung. Time-course single-cell transcriptomic analysis showed that the transplanted KRT5+ progenitors could long-term engrafted into host lung and differentiate into HOPX+ OCLN+ alveolar MESHD barrier cell which restored the epithelial barrier and efficiently prevented inflammatory cell infiltration. Similar barrier cells were also identified in some COVID-19 patients with massive leukocyte infiltration. Altogether this work uncovered the mechanism that how various lung progenitor cells work in concert to prevent and replenish alveoli loss MESHD post severe SARS-CoV-2 infection MESHD.

    The Molecular Basis of Gender TRANS Variations in Mortality Rates Associated with the Novel Coronavirus (COVID-19) Outbreak

    Authors: Ibrahim Y. Hachim; Mahmood Y. Hachim; Iman Mamdouh Talaat; Vanessa M. López-Ozuna; Narjes Saheb Sharif-Askari; Rabih Halwani; Qutayba Hamid

    id:10.20944/preprints202005.0364.v1 Date: 2020-05-23 Source: Preprints.org

    Since the outbreak of the novel coronavirus disease MESHD (COVID-19) at the end of 2019, the clinical presentation of the disease showed a great heterogeneity with a diverse impact between different subpopulations. Emerging evidence from different parts of the world showed significantly poor outcome among males TRANS compared to female TRANS patients. A better understanding of the molecular mechanisms behind this difference might be a fundamental step for a more effective and targeted response to the outbreak. For that reason, here we try to investigate the molecular basis of the gender TRANS variations in mortality rates related to COVID-19 infection MESHD. To achieve this, we used our in-house pipeline to process publicly available lung transcriptomic data from 141 females TRANS compared to 286 males TRANS. After excluding Y specific genes, our results showed a shortlist of 73 genes that are differentially expressed between the two groups. Our results showed downregulation of a group of genes that are involved in the regulation of hydrolase activity including (AGTR1, CHM MESHD, DDX3X, FGFR3, SFRP2, and NLRP2), which is also believed to be essential for lung immune response and antimicrobial activity in the lung tissues in males TRANS compared to females TRANS. In contrast, our results showed an upregulation of angiotensin II receptor type 1 (AGTR1), a member of the renin-angiotensin system (RAS) that plays a role in angiotensin-converting enzyme 2 (ACE2) activity modulation. Interestingly, recent reports and experimental animal models highlight an important role of this receptor in SARS-Coronavirus lung damage MESHD as well as pulmonary edema HP pulmonary edema MESHD, suggesting a possible role of its blockers like losartan and olmesartan as potential therapeutic options for COVID-19 infection MESHD. Finally, our results also showed a differential expression of different genes that are involved in the immune response including the NLRP2 and PTGDR2, further supporting the notion of the sex-based immunological differences. Taken together, our results provide an initial evidence of the molecular mechanisms that might be involved in the differential outcomes observed between both genders TRANS during the COVID-19 outbreak. This might be essential for the discovery of new targets and more precise therapeutic options to treat COVID-19 patients from different clinical and epidemiological characteristics with the aim of improving their outcome.

    COVID-19: In the Eye of the Cytokine Storm

    Authors: Roberto de la Rica; Marcio Borges; Marta Gonzalez-Freire

    id:10.20944/preprints202005.0157.v1 Date: 2020-05-09 Source: Preprints.org

    The dysregulated release of cytokines has been identified as one of the key factors behind poorer outcomes in COVID-19. This ‘cytokine storm ‘produces an excessive inflammatory and immune response, especially in the lungs, leading to acute respiratory distress HP respiratory distress MESHD (ARDS), pulmonary edema HP pulmonary edema MESHD and multi-organ failure MESHD. Alleviating this inflammatory state is crucial to improve prognosis. Pro-inflammatory factors play a central role in COVID-19 severity, especially in patients with comorbidities In these situations, an overactive, untreated immune response can be deadly, suggesting that mortality in COVID-19 cases is likely due to this virally driven hyperinflammation. Administering immunomodulators has not yielded conclusive improvements in other pathologies characterized by dysregulated inflammation MESHD such as sepsis HP sepsis MESHD, SARS-CoV-1 and MERS. The success of these drugs at reducing COVID-19-driven inflammation MESHD is still anecdotal and comes with serious risks. It is also imperative to screen the elderly TRANS for risk factors that predispose them to severe COVID-19. Immunosenescence and comorbidities should be taken into consideration. In this review, we summarize the latest data available about the role of the cytokine storm in COVID-19 disease severity as well as potential therapeutic approaches to ameliorate it. We also examine the role of inflammation MESHD in other diseases often comorbid with COVID-19, such as aging, sepsis HP sepsis MESHD, and pulmonary disorders MESHD. Finally, we identify gaps in our knowledge and suggest priorities for future research aimed at stratifying patients according to risk as well as personalizing therapies in the context of COVID19-driven hyperinflammation.

    Identification of pulmonary comorbid diseases network based repurposing effective drugs for COVID-19

    Authors: Jai Chand Patel; Rajkumar Tulswani; Pankaj Khurana; Yogendra Kumar Sharma; Lilly Ganju; Bhuvnesh Kumar; Ragumani Sugadev

    doi:10.21203/rs.3.rs-28148/v1 Date: 2020-05-08 Source: ResearchSquare

    The number of hospitalization of COVID-19 patients with one or more comorbid diseases is highly alarming. Despite the lack of large clinical data and incomplete understanding of virus pathology, identification of the COVID-19 associated diseases with clinical precision are highly limited. In this regard, our text mining of 6238 PubMed abstracts (as on 23 April 2020) successfully identified broad spectrum of COVID-19 comorbid diseases/disorders (54), and their prevalence SERO on the basis of the number of occurrence of disease terms in the abstracts. The disease ontology based semantic similarity network analysis revealed the six highly comorbid diseases of COVID-19 namely Viral Pneumonia HP, Pulmonary Fibrosis HP Pulmonary Fibrosis MESHD, Pulmonary Edema HP Pulmonary Edema MESHD, Acute Respiratory Distress Syndrome MESHD Respiratory Distress HP Syndrome ( ARDS MESHD), Chronic Obstructive Pulmonary Disease HP Chronic Obstructive Pulmonary Disease MESHD ( COPD MESHD) and Asthma HP. The disease gene bipartite network revealed 15 genes that were strongly associated with several viral pathways including the corona viruses may involve in the manifestation (mild to critical) of COVID-19. Our tripartite network- based repurposing of the approved drugs in the world market revealed six promising drugs namely resveratrol, dexamethasone, acetyl cysteine, Tretinoin, simvastatin and aspirin to treat comorbid symptoms of COVID-19 patients. Our animal studies in rats and literatures strongly supported that resveratrol is the most promising drug to possibly reduce several comorbid symptoms associated with COVID-19 including the severe hypoxemia HP hypoxemia MESHD induced vascular leakage. Overall, the anti-viral properties of resveratrol against corona virus could be readily exploited to effectively control the viral load at early stage of COVID-19 infection through nasal administration.

    COVID-19: Multiple Diseases Simulating Extreme High-Altitude Exposure? Oxygen Transport Physiology and Scarce Need of Ventilators; Andean Condor’s-Eye-View

    Authors: Gustavo R. Zubieta-Calleja; Natalia Zubieta-DeUrioste; Thuppil Venkatesh; Kusal Das; Jorge Soliz

    id:10.20944/preprints202005.0085.v1 Date: 2020-05-05 Source: Preprints.org

    The critical hypoxia MESHD in COVID-19 patients during this pandemic, has taken away many lives all around the globe. The mechanism has been poorly understood and initially, word got around that it was a SARS ( Severe Acute Respiratory Syndrome MESHD) pneumonia HP pneumonia MESHD. The atypical images in lung computerized axial tomography (CAT) scans were alarming. This immediately alerted everyone including poor countries to purchase lacking sophisticated ventilator equipment. However, in some countries, even 88% of the patients on ventilators lost their lives. New observations and pathological findings are gradually clarifying the disease. What seems evident is that it is not only one disease but several, with different responses in different countries and different altitudes. The critical hypoxia MESHD and «gasping» present in some patients are not totally understood. It was mentioned that it could be like a High-Altitude Pulmonary Edema HP (HAPE). Hereby, as high-altitude medicine and hypoxia MESHD physiology specialists, we compare the pathophysiology with that of high-altitude exposure in order to understand the mechanisms involved. Some differences in lung radiological images along with transmission TRANS and viral attack mechanisms are discussed. The oxygen transport triad used at high-altitude can be applied on this pathology in order to propose even the use of erythropoietin (EPO) early in the treatment. The immune system is the most important long-term survival tool, so we suggest a short-term strategy: the use of special Earth open-circuit astronaut-resembling suits with effective outside air filtering re-breathing mechanisms in order to return to work and daily activities, without contamination risk. Thereby, the curve can be flattened without quarantine and the economy could recover.

    Automatic Detection of Coronavirus Disease MESHD (COVID-19) in X-ray and CT Images: A Machine Learning-Based Approach

    Authors: Sara Hosseinzadeh Kassani; Peyman Hosseinzadeh Kassasni; Michal J. Wesolowski; Kevin A. Schneider; Ralph Deters

    id:2004.10641v1 Date: 2020-04-22 Source: arXiv

    The newly identified Coronavirus pneumonia MESHD pneumonia HP, subsequently termed COVID-19, is highly transmittable and pathogenic with no clinically approved antiviral drug or vaccine available for treatment. The most common symptoms of COVID-19 are dry cough HP, sore throat, and fever HP fever MESHD. Symptoms can progress to a severe form of pneumonia HP pneumonia MESHD with critical complications, including septic shock MESHD shock HP, pulmonary edema HP pulmonary edema MESHD, acute respiratory distress syndrome MESHD respiratory distress HP syndrome and multi-organ failure MESHD. While medical imaging is not currently recommended in Canada for primary diagnosis of COVID-19, computer-aided diagnosis systems could assist in the early detection of COVID-19 abnormalities and help to monitor the progression of the disease, potentially reduce mortality rates. In this study, we compare popular deep learning-based feature extraction frameworks for automatic COVID-19 classification. To obtain the most accurate feature, which is an essential component of learning, MobileNet, DenseNet, Xception, ResNet, InceptionV3, InceptionResNetV2, VGGNet, NASNet were chosen amongst a pool of deep convolutional neural networks. The extracted features were then fed into several machine learning classifiers to classify subjects as either a case of COVID-19 or a control. This approach avoided task-specific data pre-processing methods to support a better generalization ability for unseen data. The performance SERO of the proposed method was validated on a publicly available COVID-19 dataset of chest X-ray and CT images. The DenseNet121 feature extractor with Bagging tree classifier achieved the best performance SERO with 99% classification accuracy. The second-best learner was a hybrid of the a ResNet50 feature extractor trained by LightGBM with an accuracy of 98%.

    Early Oxygen Inhalation to Prevent SARS-CoV-2-Induced Acute Respiratory Distress Syndrome MESHD Respiratory Distress HP Syndrome

    Authors: Shu Yuan; Si-Cong Jiang; Zi-Lin Li

    id:10.20944/preprints202004.0360.v1 Date: 2020-04-20 Source: Preprints.org

    Acute respiratory distress HP syndrome ( ARDS MESHD) and the serious complications are the most frequent causes of death of SARS-CoV-2 infection MESHD. We bring out a hypothesis that early low-flow oxygen inhalation would maintain the hypoxic pulmonary vasoconstriction MESHD (an essential protection mechanism of the lung that optimize gas exchange) and accelerate the re-absorption of pulmonary edema HP pulmonary edema MESHD fluid. The optimal time for oxygen therapy was analyzed and four comments are proposed: (1) Finger SpO2 should be measured at home simultaneously with the first-time nucleic acid test. (2) If the patient's SpO2 was lower than the reference value by 2% or more, it is suggested to be hospitalized immediately for standard low-flow oxygen inhalation. (3) If it was not possible to be admitted to hospital immediately, the patient is recommended to take oxygen in the home. (4) The Patients with low SpO2 are advised to use prone position as much as possible.

    Supramolecular Organization Predicts Protein Nanoparticle Delivery to Neutrophils for Acute Lung Inflammation MESHD Diagnosis and Treatment

    Authors: Jacob W Myerson; Priyal N Patel; Nahal Habibi; Landis R Walsh; Yi-Wei Lee; David C Luther; Laura T Ferguson; Michael H Zaleski; Marco E Zamora; Oscar A. Marcos-Contreras; Patrick M Glassman; Ian Johnston; Elizabeth D Hood; Tea Shuvaeva; Jason V Gregory; Raisa Y Kiseleva; Jia Nong; Kathryn M Rubey; Colin F Greineder; Samir Mitragotri; George S Worthen; Vincent M Rotello; Joerg Lahann; Vladimir R Muzykantov; Jacob S Brenner

    doi:10.1101/2020.04.15.037564 Date: 2020-04-18 Source: bioRxiv

    Acute lung inflammation MESHD has severe morbidity, as seen in COVID-19 patients. Lung inflammation MESHD is accompanied or led by massive accumulation of neutrophils in pulmonary capillaries ("margination"). We sought to identify nanostructural properties that predispose nanoparticles to accumulate in pulmonary marginated neutrophils, and therefore to target severely inflamed lungs. We designed a library of nanoparticles and conducted an in vivo screen of biodistributions in naive mice and mice treated with lipopolysaccharides. We found that supramolecular organization of protein in nanoparticles predicts uptake in inflamed lungs. Specifically, nanoparticles with agglutinated protein (NAPs) efficiently home to pulmonary neutrophils, while protein nanoparticles with symmetric structure (e.g. viral capsids) are ignored by pulmonary neutrophils. We validated this finding by engineering protein-conjugated liposomes that recapitulate NAP targeting to neutrophils in inflamed lungs. We show that NAPs can diagnose acute lung injury MESHD in SPECT imaging and that NAP-like liposomes can mitigate neutrophil extravasation and pulmonary edema HP pulmonary edema MESHD arising in lung inflammation MESHD. Finally, we demonstrate that ischemic MESHD ex vivo human lungs selectively take up NAPs, illustrating translational potential. This work demonstrates that structure-dependent interactions with neutrophils can dramatically alter the biodistribution of nanoparticles, and NAPs have significant potential in detecting and treating respiratory conditions arising from injury or infections MESHD.

    Kinins and Cytokines in COVID-19: A Comprehensive Pathophysiological Approach

    Authors: Frank van de Veerdonk; Mihai G. Netea; Marcel van Deuren; Jos W.M. van der Meer; Quirijn de Mast; Roger J. Bruggemann; Hans van der Hoeven

    id:10.20944/preprints202004.0023.v1 Date: 2020-04-03 Source: Preprints.org

    Most striking observations in COVID-19 patients are the hints on pulmonary edema HP pulmonary edema MESHD (also seen on CT scans as ground glass opacities), dry cough MESHD cough HP, fluid restrictions to prevent more severe hypoxia MESHD, the huge PEEP that is needed while lungs are compliant, and the fact that anti-inflammatory therapies are not powerful enough to counter the severity of the disease. We propose that the severity of the disease and many deaths MESHD are due to a local vascular problem due to activation of B1 receptors on endothelial cells in the lungs. SARS-CoV-2 enters the cell via ACE2, a cell membrane bound molecule with enzymatic activity that next to its role in RAS is needed to inactivate des-Arg9 bradykinin, the potent ligand of the bradykinin receptor type 1 (B1). In contrast to bradykinin receptor 2 (B2), the B1 receptor on endothelial cells is upregulated by proinflammatory cytokines. Without ACE2 acting as a guardian to inactivate the ligands of B1, the lung environment is prone for local vascular leakage leading to angioedema HP angioedema MESHD. Angioedema HP Angioedema MESHD is likely a feature already early in disease, and might explain the typical CT scans and the feeling of people that they drown. In some patients, this is followed by a clinical worsening of disease around day 9 due to the formation antibodies SERO directed against the spike (S)-antigen of the corona-virus that binds to ACE2 that could contribute to disease by enhancement of local immune cell influx and proinflammatory cytokines leading to damage. In parallel, inflammation MESHD induces more B1 expression, and possibly via antibody SERO-dependent enhancement of viral infection MESHD leading to continued ACE2 dysfunction in the lung because of persistence of the virus. In this viewpoint we propose that a bradykinin-dependent local lung angioedema HP angioedema MESHD via B1 and B2 receptors is an important feature of COVID-19, resulting in a very high number of ICU admissions. We propose that blocking the B1 and B2 receptors might have an ameliorating effect on disease caused by COVID-19. This kinin-dependent pulmonary edema HP pulmonary edema MESHD is resistant to corticosteroids or adrenaline and should be targeted as long as the virus is present. In addition, this pathway might indirectly be responsive to anti-inflammatory agents or neutralizing strategies for the anti-S- antibody SERO induced effects, but by itself is likely to be insufficient MESHD to reverse all the pulmonary edema HP pulmonary edema MESHD. Moreover, we provide a suggestion of how to ventilate in the ICU in the context of this hypothesis.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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