Corpus overview


MeSH Disease

Human Phenotype


    displaying 1 - 5 records in total 5
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    Dose-dependent response to infection MESHD with SARS-CoV-2 in the ferret model: evidence of protection to re-challenge

    Authors: Kathryn A Ryan; Kevin R Bewley; Susan A Fotheringham; Phillip Brown; Yper Hall; Anthony C Marriott; Julia A Tree; Lauren Allen; Marilyn J Aram; Emily Brunt; Karen R Buttigieg; Breeze E Cavell; Daniel P Carter; Rebecca Cobb; Naomi S Coombes; Kerry J Godwin; Karen E Gooch; Jade Gouriet; Rachel Halkerston; Debbie J Harris; Holly E Humphries; Laura Hunter; Catherine M K Ho; Chelsea L Kennard; Stephanie Leung; Didier Ngabo; Karen L Osman; Jemma Paterson; Elizabeth J Penn; Steven T Pullen; Emma Rayner; Gillian S Slack; Kimberley Steeds; Irene Taylor; Tom Tipton; Stephen Thomas; Nadina I Wand; Robert J Watson; Nathan R Wiblin; Sue Charlton; Bassam Hallis; Julian A Hiscox; Simon Funnell; Mike J Dennis; Catherine J Whittaker; Michael G Catton; Julian Druce; Francisco J Salguero; Miles W Carroll

    doi:10.1101/2020.05.29.123810 Date: 2020-06-01 Source: bioRxiv

    In December 2019 an outbreak of coronavirus disease MESHD (COVID-19) emerged in Wuhan, China. The causative agent was subsequently identified and named severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) which rapidly spread worldwide causing a pandemic. Currently there are no licensed vaccines or therapeutics available against SARS-CoV-2 but numerous candidate vaccines are in development and repurposed drugs are being tested in the clinic. There is a vital need for authentic COVID-19 animal models to further our understanding of pathogenesis and viral spread in addition to pre-clinical evaluation of candidate interventions. Here we report a dose titration study of SARS-CoV-2 to determine the most suitable infectious dose to use in the ferret model. We show that a high (5x106 pfu) and medium (5x104 pfu) dose of SARS-CoV-2 induces consistent upper respiratory tract (URT) viral RNA shedding in both groups of six challenged animals, whilst a low dose (5x102 pfu) resulted in only one of six displaying signs of URT viral RNA replication. The URT shedding lasted up to 21 days in the high dose animals with intermittent positive signal from day 14. Sequential culls revealed distinct pathological signs of mild multifocal bronchopneumonia MESHD in approximately 5-15% of the lung, observed on day 3 in high and medium dosed animals, with presence of mild broncho-interstitial pneumonia MESHD pneumonia HP on day 7 onwards. No obvious elevated temperature or signs of coughing MESHD coughing HP or dyspnoea were observed although animals did present with a consistent post-viral fatigue MESHD fatigue HP lasting from day 9-14 in the medium and high dose groups. After virus shedding ceased, re-challenged ferrets were shown to be fully protected from acute lung pathology. The endpoints of URT viral RNA replication in addition to distinct lung pathology and post viral fatigue MESHD fatigue HP were observed most consistently in the high dose group. This ferret model of SARS-CoV-2 infection MESHD presents a mild clinical disease MESHD (as displayed by 80% of patients infected with SARS-CoV-2). In addition, intermittent viral shedding on days 14-21 parallel observations reported in a minority of clinical cases.

    A pattern categorization of CT findings to predict outcome of COVID-19 pneumonia MESHD pneumonia HP

    Authors: Chao Jin; Yan Wang; Carol C. Wu; Huifang Zhao; Ting Liang; Zhe Liu; Zhijie Jian; Runqing Li; Zekun Wang; Fen Li; Jie Zhou; Shubo Cai; Yang Liu; Hao Li; Zhongyi Li; Yukun Liang; Heping Zhou; Xibin Wang; Zhuanqin Ren; Jian Yang

    doi:10.1101/2020.05.19.20107409 Date: 2020-05-25 Source: medRxiv

    Purpose As global healthcare system is overwhelmed by novel coronavirus disease MESHD (COVID-19), early identification of risks of adverse outcomes becomes the key to optimize management and improve survival. This study aimed to provide a CT-based pattern categorization to predict outcome of COVID-19 pneumonia MESHD pneumonia HP. Methods 165 patients with COVID-19 (91 men, 4-89 years) underwent chest CT were retrospectively enrolled. CT findings were categorized as Pattern0 (negative), Pattern1 ( bronchopneumonia MESHD), Pattern2 (organizing pneumonia MESHD pneumonia HP), Pattern3 (progressive organizing pneumonia MESHD pneumonia HP) and Pattern4 (diffuse alveolar damage). Clinical findings were compared across different categories. Time-dependent progression of CT patterns and correlations with clinical outcomes, i.e. discharge or adverse outcome (admission to ICU, requiring mechanical ventilation, or death MESHD), with pulmonary sequelae (complete absorption or residuals) on CT after discharge were analyzed. Results Of 94 patients with outcome, 81(86.2%) were discharged, 3(3.2%) were admitted to ICU, 4(4.3%) required mechanical ventilation, 6(6.4%) died. 31(38.3%) had complete absorption at median day 37 after symptom-onset TRANS. Significant differences between pattern-categories were found in age TRANS, disease MESHD-severity, comorbidity and laboratory results (all P<0.05). Remarkable evolution was observed in Pattern0-2 and Pattern3-4 within 3 and 2 weeks after symptom-onset TRANS, respectively; most of patterns remained thereafter. After controlling for age TRANS, CT pattern significantly correlated with adverse outcomes (Pattern4 vs. Pattern0-3 [reference]; hazard-ratio[95%CI], 18.90[1.91-186.60], P=0.012). CT pattern (Pattern3-4 vs. Pattern0-2 [reference]; 0.26[0.08-0.88], P=0.030) and C-reactive protein (>10 vs. [≤]10mg/L [reference]; 0.31[0.13-0.72], P=0.006) were risk-factors associated with pulmonary residuals. Conclusion CT pattern categorization allied with clinical characteristics within 2 weeks after symptom-onset TRANS would facilitate early prognostic stratification in COVID-19 pneumonia MESHD pneumonia HP.

    Curbing the AI-induced enthusiasm in diagnosing COVID-19 on chest X-Rays: the present and the near-future

    Authors: Alexandru Burlacu; Radu Crisan-Dabija; Iolanda Valentina Popa; Bogdan Artene; Vasile Birzu; Mihai Pricop; Cristina Plesoianu; Daniele Generali

    doi:10.1101/2020.04.28.20082776 Date: 2020-05-01 Source: medRxiv

    In the current context of COVID-19 pandemic, a rapid and accessible screening tool based on image processing of chest X-rays (CXRs) using machine learning (ML) approaches would be much needed. Initially, we intended to create and validate an ML software solution able to discriminate on the basis of the CXR between SARS-CoV-2-induced bronchopneumonia MESHD and other bronchopneumonia MESHD etiologies. A systematic search of PubMed, Scopus and arXiv databases using the following search terms ["artificial intelligence" OR "deep learning" OR "neural networks"], AND ["COVID-19" OR "SARS-CoV-2"] AND ["chest X-ray" OR "CXR" OR "X-ray"] found 14 recent studies. Most of them declared to be able to confidently identify COVID-19 based on CXRs using deep neural networks. Firstly, weaknesses of artificial intelligence (AI) solutions were analyzed, tackling the issues with datasets (from both medical and technical points of view) and the vulnerability of used algorithms. Then, arguments were provided for why our study design is stronger and more realistic than the previously quoted papers, balancing the possible false expectations with facts. The authors consider that the potential of AI use in COVID-19 diagnosis on CXR is real. However, scientific community should be careful in interpreting statements, results and conclusions regarding AI use in imaging. It is therefore necessary to adopt standards for research and publication of data, because it seems that in the recent months scientific reality suffered manipulations and distortions. Also, a call for responsible approaches to the imaging methods in COVID-19 is raised. It seems mandatory to follow some rigorous approaches in order to provide with adequate results in daily routine. In addition, the authors intended to raise public awareness about the quality of AI protocols and algorithms and to encourage public sharing of as many CXR images with common quality standards.

    STAT2 signaling as double-edged sword restricting viral dissemination but driving severe pneumonia MESHD pneumonia HP in SARS-CoV-2 infected hamsters

    Authors: Robbert Boudewijns; Hendrik Jan Thibaut; Suzanne J.F. Kaptein; Rong Li; Valentijn Vergote; Laura Seldeslachts; Carolien De Keyzer; Lindsey Bervoets; Sapna Sharma; Johan Van Weyenbergh; Laurens Liesenborghs; Ji Ma; Sander Jansen; Dominique Van Looveren; Thomas Vercruysse; Dirk Jochmans; Xinyu Wang; Erik Martens; Kenny Roose; Dorien De Vlieger; Bert Schepens; Tina Van Buyten; Sofie Jacobs; Yanan Liu; Joan Martí-Carreras; Bert Vanmechelen; Tony Wawina-Bokalanga; Leen Delang; Joana Rocha-Pereira; Lotte Coelmont; Winston Chiu; Pieter Leyssen; Elisabeth Heylen; Dominique Schols; Lanjiao Wang; Lila Close; Jelle Matthijnssens; Marc Van Ranst; Veerle Compernolle; Georg Schramm; Koen Van Laere; Xavier Saelens; Nico Callewaert; Ghislain Opdenakker; Piet Maes; Birgit Weynand; Christopher Cawthorne; Greetje Vande Velde; Zhongde Wang; Johan Neyts; Kai Dallmeier

    doi:10.1101/2020.04.23.056838 Date: 2020-04-24 Source: bioRxiv

    Introductory paragraphSince the emergence of SARS-CoV-2 causing COVID-19, the world is being shaken to its core with numerous hospitalizations and hundreds of thousands of deaths MESHD. In search for key targets of effective therapeutics, robust animal models mimicking COVID-19 in humans are urgently needed. Here, we show that productive SARS-CoV-2 infection MESHD in the lungs of mice is limited and restricted by early type I interferon responses. In contrast, we show that Syrian hamsters are highly permissive to SARS- CoV-2 and develop bronchopneumonia MESHD and a strong inflammatory response in the lungs with neutrophil infiltration and edema MESHD edema HP. Moreover, we identify an exuberant innate immune response as a key player in pathogenesis, in which STAT2 signaling plays a dual role, driving severe lung injury MESHD on the one hand, yet restricting systemic virus dissemination on the other. Finally, we assess SARS-CoV- 2-induced lung pathology in hamsters by micro-CT alike used in clinical practice. Our results reveal the importance of STAT2-dependent interferon responses in the pathogenesis and virus control during SARS-CoV-2 infection MESHD and may help rationalizing new strategies for the treatment of COVID-19 patients.

    Pathological Study of the 2019 Novel Coronavirus Disease MESHD (COVID-19) through Post-Mortem Core Biopsies

    Authors: Sufang Tian; Yong Xiong; Huan Liu; Li Niu; Jianchun Guo; Meiyan Liao; Shu-Yuan Xiao

    id:10.20944/preprints202003.0311.v1 Date: 2020-03-20 Source:

    Data on pathologic changes of the 2019 novel coronavirus disease MESHD (COVID-19) are scarce. To gain knowledge about the pathology that may contribute to disease progression MESHD and fatality, we performed post-mortem needle core biopsies of lung, liver, and heart in four patients who died of COVID-19 pneumonia MESHD pneumonia HP. The patients’ ages TRANS ranged from 59 to 81, including 3 males TRANS and 1 female TRANS. Each patient had at least one underlying disease MESHD, including immunocompromised status (chronic lymphocytic leukemia MESHD leukemia HP and renal transplantation) or other conditions ( cirrhosis HP, hypertension MESHD hypertension HP, and diabetes). Time from disease MESHD onset to death MESHD ranged from 15 to 52 days. All patients had elevated white blood SERO cell counts, with significant rise toward the end, and all had lymphocytopenia except for the patient with leukemia MESHD leukemia HP. Histologically, the main findings are in the lungs, including injury to the alveolar epithelial cells, hyaline membrane formation, and hyperplasia MESHD of type II pneumocytes, all components of diffuse alveolar damage. Consolidation by fibroblastic proliferation with extracellular matrix and fibrin forming clusters in airspaces is evident. In one patient, the consolidation consists of abundant intra-alveolar neutrophilic infiltration, consistent with superimposed bacterial bronchopneumonia MESHD. The liver exhibits mild lobular infiltration by small lymphocytes, and centrilobular sinusoidal dilation. Patchy necrosis MESHD is also seen. The heart shows only focal mild fibrosis MESHD and mild myocardial hypertrophy MESHD, changes likely related to the underlying conditions. In conclusion, the post-mortem examinations show advanced diffuse alveolar damage, as well as superimposed bacterial pneumonia MESHD pneumonia HP in some patients. Changes in the liver and heart are likely secondary or related to the underlying diseases MESHD.

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MeSH Disease
Human Phenotype

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