Corpus overview


Overview

MeSH Disease

Human Phenotype

Transmission

Seroprevalence
    displaying 251 - 260 records in total 339
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    Clinical course and risk factors for mortality of COVID-19 patients with pre-existing cirrhosis HP cirrhosis MESHD: A multicenter cohort study

    Authors: Xiaolong Qi; Yanna Liu; Jonathan A. Fallowfield; Jitao Wang; Jianwen Wang; Xinyu Li; Jindong Shi; Hongqiu Pan; Shengqiang Zou; Hongguang Zhang; Zhenhuai Chen; Fujian Li; Yan Luo; Mei Mei; Huiling Liu; Zhengyan Wang; Jinlin Li; Hua Yang; Huihua Xiang; Xiaodan Li; Tao Liu; Ming-Hua Zheng; Chuan Liu; Yifei Huang; Dan Xu; Xiaoguo Li; Ning Kang; Qing He; Ye Gu; Guo Zhang; Chuxiao Shao; Dengxiang Liu; Lin Zhang; Xun Li; Norifumi Kawada; Zicheng Jiang; Fengmei Wang; Bin Xiong; Tetsuo Takehara; Don C. Rockey; COVID-Cirrhosis-CHESS Group

    doi:10.1101/2020.04.24.20072611 Date: 2020-04-28 Source: medRxiv

    Background: Patients with pre-existing cirrhosis HP cirrhosis MESHD are considered at increased risk of severe coronavirus disease MESHD 2019 (COVID-19) but the clinical course in these patients has not yet been reported. This study aimed to provide a detailed report of the clinical characteristics and outcomes among COVID-19 patients with pre-existing cirrhosis HP cirrhosis MESHD. Methods: In this retrospective, multicenter cohort study, we consecutively included all adult TRANS inpatients with laboratory-confirmed COVID-19 and pre-existing cirrhosis HP cirrhosis MESHD that had been discharged or had died by 24 March 2020 from 16 designated hospitals in China. Demographic, clinical, laboratory and radiographic findings on admission, treatment, complications during hospitalization and clinical outcomes were collected and compared between survivors and non-survivors. Findings: Twenty-one patients were included in this study, of whom 16 were cured and 5 died in hospital. Seventeen patients had compensated cirrhosis HP cirrhosis MESHD and hepatitis HP hepatitis MESHD B virus infection was the most common etiology. Lymphocyte and platelet counts were lower, and direct bilirubin levels were higher in patients who died than those who survived (p= 0.040, 0.032, and 0.006, respectively). Acute respiratory distress HP respiratory distress MESHD syndrome and secondary infection MESHD were both the most frequently observed complications. Only one patient developed acute on chronic liver failure MESHD. Of the 5 non-survivors, all patients developed acute respiratory distress syndrome MESHD respiratory distress HP syndrome and 2 patients progressed to multiple organ dysfunction syndrome MESHD. Interpretation: Lower lymphocyte and platelet counts, and higher direct bilirubin level might represent poor prognostic indicators in SARS-CoV-2-infected MESHD patients with pre-existing cirrhosis HP cirrhosis MESHD.

    Characterization of clinical progression of COVID-19 patients in Shenzhen, China

    Authors: Qifang Bi; Chengcheng Hong; Juan Meng; Zhenke Wu; Pengzheng Zhou; Chenfei Ye; Binbin Sun; Lauren M Kucirka; Andrew S Azman; Tong Wang; Jiancong Chen; Zhaoqin Wang; Lei Liu; Justin Lessler; Jessie K Edwards; Ting Ma; Guoliang Zhang

    doi:10.1101/2020.04.22.20076190 Date: 2020-04-27 Source: medRxiv

    Background: Understanding clinical progression of COVID-19 is a key public health priority that informs resource allocation during an emergency. We characterized clinical progression of COVID-19 and determined important predictors for faster clinical progression to key clinical events and longer use of medical resources. Methods and Findings: The study is a single-center, observational study with prospectively collected data from all 420 patients diagnosed with COVID-19 and hospitalized in Shenzhen between January 11th and March 10th, 2020 regardless of clinical severity. Using competing risk regressions according to the methods of Fine and Gray, we found that males TRANS had faster clinical progression than females TRANS in the older age group TRANS and the difference could not be explained by difference in baseline conditions or smoking history. We estimated the proportion of cases in each severity stage over 80 days following symptom onset TRANS using a nonparametric method built upon estimated cumulative incidence of key clinical events. Based on random survival forest models, we stratified cases into risk sets with very different clinical trajectories. Those who progressed to the severe stage (22%,93/420), developed acute respiratory distress syndrome MESHD respiratory distress HP syndrome (9%,39/420), and were admitted to the intensive care unit (5%,19/420) progressed on average 9.5 days (95%CI 8.7,10.3), 11.0 days (95%CI 9.7,12.3), and 10.5 days (95%CI 8.2,13.3), respectively, after symptom onset TRANS. We estimated that patients who were admitted to ICUs remained there for an average of 34.4 days (95%CI 24.1,43.2). The median length of hospital stay was 21.3 days (95%CI, 20.5,22.2) for cases who did not progress to the severe stage, but increased to 52.1 days (95%CI, 43.3,59.5) for those who required critical care. Conclusions: Our analyses provide insights into clinical progression of cases starting early in the course of infection MESHD. Patient characteristics near symptom onset TRANS both with and without lab parameters have tremendous potential for predicting clinical progression and informing strategic response.

    Lack of association between genetic variants at ACE2 and TMPRSS2 genes involved in SARS-CoV-2 infection MESHD and human quantitative phenotypes

    Authors: Esteban Lopera; Adriaan van der Graaf; Pauline Lanting; Marije van der Geest; - Lifelines Cohort Study; Jingyuan Fu; Morris Swertz; Lude Franke; Cisca Wijmenga; Patrick Deelen; Alexandra Zhernakova; Serena Sanna

    doi:10.1101/2020.04.22.20074963 Date: 2020-04-25 Source: medRxiv

    Coronavirus disease 2019 (COVID-19) shows a wide variation in expression and severity of symptoms, from very mild or no symptomes, to flu-like symptoms, and in more severe cases, to pneumonia HP pneumonia MESHD, acute respiratory distress syndrome MESHD respiratory distress HP syndrome and even death. Large differences in outcome have also been observed between males TRANS and females TRANS. The causes for this variability are likely to be multifactorial, and to include genetics. The SARS-CoV-2 virus responsible for the infection uses the human receptor angiotensin converting enzyme 2 (ACE2) for cell invasion, and the serine protease TMPRSS2 for S protein priming. Genetic variation in these two genes may thus modulate an individual's genetic predisposition to infection MESHD and virus clearance. While genetic data on COVID-19 patients is being gathered, we carried out a phenome-wide association scan (PheWAS) to investigate the role of these genes in other human phenotypes in the general population. We examined 178 quantitative phenotypes including cytokines and cardio-metabolic biomarkers, as well as 58 medications in 36,339 volunteers from the Lifelines population biobank, in relation to 1,273 genetic variants located in or near ACE2 and TMPRSS2. While none reached our threshold for significance, we observed a suggestive association of polymorphisms within the ACE2 gene with (1) the use of ARBs combination therapies (p=5.7x10-4), an association that is significantly stronger in females TRANS (pdiff=0.01), and (2) with the use of non-steroid anti-inflammatory and antirheumatic products (p=5.5x10-4). While these associations need to be confirmed in larger sample sizes, they suggest that these variants play a role in diseases such as hypertension HP hypertension MESHD and chronic inflammation MESHD that are often observed in the more severe COVID-19 cases. Further investigation of these genetic variants in the context of COVID-19 is thus promising for better understanding of disease variability. Full results are available at https://covid19research.nl.

    Accelerated hyaluronan concentration as the primary driver of morbidity and mortality in high-risk COVID-19 patients: with therapeutic introduction of an oral hyaluronan inhibitor in the prevention of "Induced Hyaluronan Storm" Syndrome

    Authors: Michael A Mong; Jacob A Awkal; Paul E Marik

    doi:10.1101/2020.04.19.20071647 Date: 2020-04-24 Source: medRxiv

    Background To date, more than 161,000 people have died from the coronavirus disease MESHD 2019 (COVID-19) yet the fundamental drivers of the morbidity and mortality remain uncertain. Clinicians worldwide appear to be at a loss to know how to prevent and treat the severe respiratory distress HP in these patients effectively. Consequently, the fundamental mechanisms leading to death in high-risk patients with COVID-19 need to be discovered and addressed with urgency. Despite a marked drop in frequency, the post-mortem autopsy remains an essential part of both discovering the cause of death MESHD in a particular individual, but also in advancing the science and treatment of disease, especially in the case of novel pathogens such as SARS-CoV-2[2]. The goal of an autopsy is to discover the cause of death MESHD (COD) using a macro/microscopic investigation. Traditionally, the intact organs are carefully removed, inspected, and weighed. Because lung weight is often affected by the cause of death MESHD and the last breath occurs very near if not at the moments of death MESHD, the evaluation of the lungs is one of the starting points of any COD investigation[3]. Method A comprehensive search was performed to systematically review all reported autopsy findings in COVID-19 patients in order to better understand the underlying disease mechanisms resulting in death MESHD. We then compared these findings with the results of a targeted literature review of hyaluronan in relationship to acute respiratory distress HP respiratory distress MESHD syndrome ( ARDS MESHD). Results In total, data from 181 autopsies were identified. From this group, 6 autopsies of COVID-19 patients were selected for a detailed review and statistical analysis. The average lung weight of those who were determined to have died as a result of SARS-CoV-2 was 2196g-approximately 2.5x normal lung weight. Hyaline membranes were consistently identified on histologic sections. A review of the literature reveals that hyaluronan has been associated with the pathophysiology of ARDS since 1967. However, its key role in driving the morbidity and mortality of the condition has heretofore not been fully recognized. Conclusions We propose that the induced hyaluronan storm syndrome or IHS, is the model that best addresses the heretofore perplexing respiratory failure HP respiratory failure MESHD that is the proximal cause of death MESHD in a minority, but ever rising number, of patients. In addition to treating and preventing IHS in currently infected individuals now; an aggressive research effort should be undertaken to discover why the majority of individuals who are exposed to the virus are either minimally or asymptomatic TRANS, while a minority of high-risk individuals rapidly progress to respiratory failure HP respiratory failure MESHD and death MESHD. Keywords Systematic review; COVID-19; SARS-CoV-2; Hyaline Membrane; Hyaluronan; Acute Respiratory Distress Syndrome MESHD Respiratory Distress HP Syndrome; ARDS MESHD; Autopsy; IHS; Induced Hyaluronan Storm Syndrome; COD MESHD; Cause of Death MESHD

    Clinical and Imaging Findings in COVID-19 Patients Complicated by Pulmonary Embolism HP Pulmonary Embolism MESHD

    Authors: Ting Li; Gregory Kicska; Paul E Kinahan; Chengcheng Zhu; Murat Alp Oztek; Wei Wu

    doi:10.1101/2020.04.20.20064105 Date: 2020-04-24 Source: medRxiv

    Objective: To describe clinical, and imaging findings including the evolution pattern in COVID-19 pneumonia HP pneumonia MESHD complicated by pulmonary embolism HP pulmonary embolism MESHD ( PE MESHD). Methods: Eleven of 1453 patients with a probable diagnosis of COVID-19 pneumonia HP pneumonia MESHD were retrospectively selected for the presence of PE MESHD. Clinical and laboratory data were recorded. All cross-sectional CT imaging was qualitatively scored for the first 28 days after onset of symptoms TRANS. Results: Of 24 patients underwent CTA- PE MESHD, 11 were confirmed with PE MESHD. All 11 patients developed acute respiratory distress syndrome MESHD respiratory distress HP syndrome ( ARDS MESHD). We observed an evolution pattern of predominant findings with ground-glass opacities (GGO) to GGO with crazy paving in 3 patients, then to consolidation with linear densities, or to reticulation in 9 patients. Lung cysts or traction bronchiectasis HP could be seen from day 5 to 9 after symptoms and reticulation, subpleural curvilinear lines were more common from day 20. The pulmonary opacities HP were predominantly peripheral in distribution with relative sparing of nondependent lungs. The severity of lung involvement was high with an average score of 9.7 in the first phase, 18 in the second phase plateauing in the next two phases, with a slight decrease to 16.9 in the late phase. The pulmonary emboli MESHD were most common in segmental and subsegmental pulmonary arteries. Conclusion: The incidence of PE MESHD among suspected patients in COVID-19 was high. Our study suggests PE MESHD may occur with increased frequency in the ARDS MESHD subgroup. The evolution of radiographic abnormalities showed a general pattern, but are also unique with more extensive lung injury MESHD and specific imaging features.

    The anti- HIV Drug Nelfinavir Mesylate MESHD (Viracept) is a Potent Inhibitor of Cell Fusion Caused by the SARS-CoV-2 Spike MESHD (S) Glycoprotein Warranting further Evaluation as an Antiviral against COVID-19 infections

    Authors: Farhana Musarrat; Vladimir Chouljenko; Rafiq Nabi; Achyut Dahai; Seetharama Jois; Konstantin Kousoulas

    doi:10.1101/2020.04.24.060376 Date: 2020-04-24 Source: bioRxiv

    Coronaviruses belong to a group of enveloped, positive-single stranded RNA viruses that are known to cause severe respiratory distress HP respiratory distress MESHD in animals and humans. The current SARS coronavirus-2 (SARS CoV-2) pandemic has caused more than 2,000, 000 infections globally MESHD and nearly 200,000 deaths. Coronaviruses enter susceptible cells via fusion of the viral envelope with the plasma SERO membrane and/or via fusion of the viral envelope with endosomal membranes after endocytosis of the virus into endosomes. Previous results with SARS and MERS CoV have shown that the Spike (S) glycoprotein is a major determinant of virus infectivity and immunogenicity. Herein, we show that expression of SARS CoV-2 S (S-n) glycoprotein after transient transfection of African green monkey kidney (Vero) cells caused extensive cell fusion in comparison to limited cell fusion caused by the SARS S (S-o) glycoprotein. S-n expression was detected intracellularly and on transfected Vero cell surfaces and caused the formation of very large multinucleated cells (syncytia) by 48 hours post transfection. These results are in agreement with published pathology observations of extensive syncytial formation in lung tissues of COVID-19 patients. This differential S-n versus S-o-mediated cell fusion suggests that SARS-CoV-2 is able to spread from cell-to-cell much more efficiently than SARS effectively avoiding extracellular spaces and neutralizing antibodies SERO. A systematic screening of several drugs for ability to inhibit S-n and S-o cell fusion revealed that the FDA approved HIV-protease inhibitor, nelfinavir mesylate (Viracept) drastically inhibited S-n and S-o-mediated cell fusion in a dose-dependent manner. Complete inhibition of cell fusion was observed at a 10 micromolar concentration. Computational modeling and in silico docking experiments suggested the possibility that nelfinavir may bind inside the S trimer structure, proximal to the S2 amino terminus directly inhibiting S-n and S-o-mediated membrane fusion. Also, it is possible that nelfinavir mesylate acts on cellular processes to inhibit S proteolytic processing. These results warrant further investigations of the potential of nelfinavir mesylate as an antiviral drug, especially at early times after SARS-CoV-2 symptoms appear.

    Central Disequilibrium Could be an Early Sign and Symptom of Rapidly Progressive SARS-CoV-2 related Respiratory Failure HP

    Authors: Ali Zreik; Ali Ammar; Charles. Hunley; Mario Madruga; Rumi Khan

    id:10.20944/preprints202004.0446.v1 Date: 2020-04-24 Source: Preprints.org

    We describe a 90-year-old male TRANS presenting with disequilibrium, loss of balance and difficulty walking HP for three days prior to initial presentation. Interestingly, he denied cough HP, fever HP fever MESHD or dyspnea HP dyspnea MESHD prior to arrival. Over the course of 48 hours, the patient developed acute respiratory distress syndrome MESHD respiratory distress HP syndrome ( ARDS MESHD) requiring intubation, diagnosed with COVID-19 infection MESHD and was treated in the intensive care unit where he died. Since the initial cases in Wuhan China in Dec 2019, the medical and epidemiological communities have learned much about the presenting features, symptomatology, epidemiology, transmission TRANS and common physical, laboratory and radiological findings of this disease. Although common symptoms are already established, it is very important to learn and record atypical symptoms or presentations of this highly contagious disease. By doing so, we will be able to recognize earlier atypical symptoms and prevent the environmental exposure to Health care workers and future patients as well. We report that Central disequilibrium may be such as initial presenting sign and symptom of impending respiratory failure HP respiratory failure MESHD from SARS-CoV-2 virus. These atypical findings such as presyncope HP may precede common respiratory complications of SARS-CoV-2.

    Atherosclerosis HP Atherosclerosis MESHD as Pathogenetic Substrate for Sars-Cov2 ‘‘Cytokine Storm’’

    Authors: Mattia Vinciguerra; Silvia Romiti; Ernesto Greco

    id:10.20944/preprints202004.0430.v1 Date: 2020-04-24 Source: Preprints.org

    Sars-CoV-2 outbreak represents a public health emergency, affecting different regions of the world. Lung is the organ more damaged due to the high presence of Sars-CoV-2 binding receptor ACE2 on epithelial alveolar MESHD cells. Severity of infection MESHD vary from absence of symptomatology to be more severe, characterized by acute respiratory distress syndrome MESHD respiratory distress HP syndrome ( ARDS MESHD), multiorgan failure MESHD and sepsis HP sepsis MESHD requiring treatment in Intensive Care Unit (ICU).It is not still clear why in a small percentage of patients immune system is not able to efficiently suppress viral replication. It has been documented as predictive factors for severity and susceptibility affections of cardiovascular system such as heart failure MESHD ( HF MESHD), coronary heart disease MESHD ( CHD MESHD) and risk factors for atherosclerotic MESHD progression, hypertension HP hypertension MESHD and diabetes MESHD among others. Atherosclerotic MESHD progression, as chronic inflammation process MESHD, is characterized by immune system dysregulation leading to pro-inflammatory pattern, including (Interleukin 6) IL-6, Tumor Necrosis MESHD Factor α (TNF-α) and IL-1β raise. Reviewing immune system and inflammation MESHD profiles in atherosclerosis HP atherosclerosis MESHD and laboratory results report in severe Sars-CoV-2 infection we have supposed a pathogenetic correlation. Atherosclerosis HP Atherosclerosis MESHD may be a pathogenetic ideal substrate to high viral replication ability leading to adverse outcomes, how reported in patients with cardiovascular factors. Moreover, level of atherosclerotic MESHD progression may impact on a different degree of severe infection HP infection MESHD and in a vicious circle feeding itself Sars-CoV-2 may exacerbate atherosclerotic MESHD progression due to excessive and aberrant plasmatic concentration of cytokines.

    Identification of Drugs Blocking SARS-CoV-2 Infection MESHD using Human Pluripotent Stem Cell-derived Colonic MESHD Organoids

    Authors: Xiaohua Duan; Yuling Han; Liuliu Yang; Benjamin E. Nilsson-Payant; Pengfei Wang; Tuo Zhang; Jenny Xiang; Dong Xu; Xing Wang; Skyler Uhl; Yaoxing Huang; Huanhuan Joyce Chen; Hui Wang; Benjamin tenOever; Robert E. Schwartz; David. D. Ho; Todd Evans; Fong Cheng Pan; Shuibing Chen

    doi:10.21203/rs.3.rs-24782/v1 Date: 2020-04-23 Source: ResearchSquare

    The current COVID-19 pandemic is caused by SARS-coronavirus MESHD 2 (SARS-CoV-2). There are currently no therapeutic options for mitigating this disease due to lack of a vaccine and limited knowledge of SARS-CoV-2 biology. As a result, there is an urgent need to create new disease models to study SARS-CoV-2 biology and to screen for therapeutics using human disease-relevant tissues. COVID-19 patients typically present with respiratory symptoms including cough HP, dyspnea HP dyspnea MESHD, and respiratory distress HP, but nearly 25% of patients have gastrointestinal indications including anorexia HP anorexia MESHD, diarrhea HP diarrhea MESHD, vomiting HP vomiting MESHD, and abdominal pain HP abdominal pain MESHD. Moreover, these symptoms are associated with worse COVID-19 outcomes1. Here, we report using human pluripotent stem cell-derived colonic MESHD organoids (hPSC-COs) to explore the permissiveness of colonic cell types to SARS-CoV-2 infection MESHD. Single cell RNA-seq and immunostaining showed that the putative viral entry receptor ACE2 is expressed in multiple hESC-derived colonic cell types, but highly enriched in enterocytes. Multiple cell types in the COs can be infected by a SARS-CoV-2 pseudo- entry virus, which was further validated in vivo using a humanized mouse model. We used hPSC-derived COs in a high throughput platform to screen 1280 FDA-approved drugs against viral infection MESHD. Mycophenolic acid and quinacrine dihydrochloride were found to block the infection of SARS-CoV-2 pseudo-entry virus in COs both in vitro and in vivo, and confirmed to block infection of SARS-CoV-2 MESHD virus. This study established both in vitro and in vivo organoid models to investigate infection of SARS-CoV-2 disease MESHD-relevant human colonic cell types and identified drugs that blocks SARS-CoV-2 infection MESHD, suitable for rapid clinical testing.

    Think Different with RNA Therapy: Can Antisense Oligonucleotides Be Used to Inhibit Replication and Transcription of SARS-Cov-2?

    Authors: Eric Barrey; Veronica Burzio; Sophie Dhorne-Pollet; Jean-François Eléouët; Bernard Delmas

    id:10.20944/preprints202004.0412.v1 Date: 2020-04-23 Source: Preprints.org

    The severity of the global COVID-19 pandemic, with a high transmission TRANS rate, 2.6-4.7% lethality and a huge economic impact, poses an urgent need for efficient medical treatments and vaccines. Currently, there are only non-specific treatments to assist the patients in acute respiratory distress HP during the inflammatory step following the preliminary infection by SARS-CoV-2. Clinical trials of drug repurposing were quickly launched at the international level. Specific treatments such as the transfusion of plasma SERO from patients who have recovered into infected MESHD patients or the use of specific inhibitors of the viral RNA-polymerase complex are promising strategies to block infection MESHD. To complete the therapeutic arsenal, we believe that the opportunity of targeting the SARS-CoV-2 genome by RNA therapy should be deeply investigated. In the present paper, we propose to design specific antisense oligonucleotides targeting transcripts encoding viral proteins associated to replication and transcription of SARS-CoV-2, aiming to block infection MESHD. We designed antisense oligonucleotides targeting the genomic 5’ untranslated region (5’-UTR), open reading frames 1a and 1b (ORF1a and ORF1b) governing expression of the replicase/transcriptase complex, and the gene N encoding the nucleoprotein that is genome-associated. To maximize the probability of efficiency, we predicted the antisense oligonucleotides by using two design methods: i) conventional antisense oligonucleotides with 100% phosphorothioate modifications (ASO); ii) antisense locked nucleic acids GapmeR. After binding the viral RNA target, the hetero-duplexes antisense oligonucleotide-RNA are cleaved by RNAse H1. Nine potent ASO candidates were found and we selected five of them targeting ORF1a (3), ORF1b (1) and N (1). Nine GapmeR candidates were predicted with excellent properties and we retained four of them targeting 5’-UTR (1), ORF1a (3), ORF1b (1) and N (1). The most potent GapmeR candidate targets the 5’-UTR, a key genomic domain with multiple functions in the viral cycle. By this open publication, we are pleased to share these in silico results with the scientific community in hopes of stimulating innovation in translational research in order to fight the unprecedented COVID-19 pandemic. These antisense oligonucleotide candidates should be now experimentally evaluated.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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