Corpus overview


MeSH Disease

Human Phenotype


    displaying 1 - 10 records in total 336
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    Functional genomic screens identify human host factors for SARS-CoV-2 and common cold coronaviruses

    Authors: Ruofan Wang; Camille R. Simoneau; Jessie Kulsuptrakul; Mehdi Bouhaddou; Katherine Travisano; Jennifer M. Hayashi; Jared Carlson-Stevermer; Jennifer Oki; Kevin Holden; Nevan J. Krogan; Melanie Ott; Andreas S Puschnik; I. A. Rodenhuis-Zybert; J. M. Smit; Qiang Wang; Xueqin Huang; Qingsong Xu; Mei Luo; Dongxia Luo; Chenyan Zhao; Jian-Bao Han; Yong-Tang Zheng; Peng Liang

    doi:10.1101/2020.09.24.312298 Date: 2020-09-24 Source: bioRxiv

    The Coronaviridae are a family of viruses that causes disease in humans ranging from mild respiratory infection MESHD to potentially lethal acute respiratory distress syndrome MESHD respiratory distress HP syndrome. Finding host factors that are common to multiple coronaviruses could facilitate the development of therapies to combat current and future coronavirus pandemics. Here, we conducted parallel genome-wide CRISPR screens in cells infected by SARS-CoV-2 as well as two seasonally circulating common cold coronaviruses, OC43 and 229E. This approach correctly identified the distinct viral entry factors ACE2 (for SARS-CoV-2), aminopeptidase N (for 229E) and glycosaminoglycans (for OC43). Additionally, we discovered phosphatidylinositol phosphate biosynthesis and cholesterol homeostasis as critical host pathways supporting infection by all three coronaviruses. By contrast, the lysosomal protein TMEM106B appeared unique to SARS-CoV-2 infection MESHD. Pharmacological inhibition of phosphatidylinositol phosphate biosynthesis and cholesterol homeostasis reduced replication of all three coronaviruses. These findings offer important insights for the understanding of the coronavirus life cycle as well as the potential development of host-directed therapies.

    Nature and dimensions of the cytokine storm and its attenuation by convalescent plasma SERO in severe COVID-19

    Authors: Purbita Bandopadhyay; Ranit D'Rozario; Abhishake Lahiri; Jafar Sarif; Yogiraj Ray; Shekhar Ranjan Paul; Rammohan Roy; Rajsekhar Maiti; Kausik Chaudhuri; Sougata Bagchi; Ayan Maiti; Md. Masoom Parwez; Biswanath Sharma Sarkar; Devlina Roy; Rahul Chakraborty; Janani Srinivasa Vasudevan; Sachin Sharma; Durba Biswas; Chikam Maiti; Bibhuti Saha; Prasun Bhattacharya; Rajesh Pandey; Shilpak Chatterjee; Sandip Paul; Dipyaman Ganguly; Sarah Dorothea Müller; Uwe Gerd Liebert; Naveed Ishaque; Lars Kaderali; Leif Erik Sander; Sven Laudi; Christian Drosten; Roland Eils; Christian Conrad; Ulf Landmesser; Irina Lehmann

    doi:10.1101/2020.09.21.20199109 Date: 2020-09-23 Source: medRxiv

    In a randomized control trial on convalescent plasma SERO therapy (CPT) in severe COVID-19, we characterized the nature, in terms of abundance of forty eight cytokines, and dimensions, in terms of their interrelationships, of the hyper-immune activation-associated cytokine storm in patients suffering from acute respiratory distress syndrome MESHD respiratory distress HP syndrome. We found plasma SERO MCP3 level to be a key correlate for mitigation of hypoxia MESHD, irrespective of therapeutic regimen. We also identified an anti-inflammatory role of CPT independent of its neutralizing antibody SERO content, and a linear regression analysis revealed that neutralizing antibodies SERO as well as the anti-inflammatory effect of CPT both contribute to marked immediate reductions in hypoxia MESHD, as compared to patients on standard therapy.

    Understanding Structural Malleability of the SARS-CoV-2 Proteins MESHD and their Relation to the Comorbidities

    Authors: Sagnik Sen; Ashmita Dey; Sanghamitra Bandyopadhyay; Ujjwal Maulik; Vladimir Uversky

    doi:10.21203/ Date: 2020-09-23 Source: ResearchSquare

    Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), a causative agent of the coronavirus disease MESHD (CoVID-19), is a part of the β-coronaviridae family. In comparison with two other members of this family TRANS of coronaviruses infecting humans ( SARS-CoV and Middle East Respiratory Syndrome MESHD ( MERS MESHD) CoV), SARS-CoV-2 showed the most severe effects on the entire Earth population causing world-wide CoVID-19 pandemic. SARS-CoV-2 contains five major protein classes, such as four structural proteins (Nucleocapsid (N), Membrane (M), Envelop (E), and Spike Glycoprotein (S)) and Replicase polyproteins (R), which are synthesized as two polyproteins (ORF1a and ORF1ab) that are subsequently processed into 12 nonstructural proteins by three viral proteases. All these proteins share high sequence similarity with their SARS-CoV MESHD counterparts. Due to the severity of the current situation, most of the SARS-CoV-2-related research is focused on finding therapeutic solutions and the analysis of comorbidities during infection MESHD. However, studies on the peculiarities of the amino acid sequences of viral protein classes and their structure space analysis throughout the evolutionary time-frame are limited. At the same time, due to their structural malleability, viral proteins can be directly or indirectly associated with the dysfunctionality of the host cell proteins, which may lead to comorbidities during the infection and at the post infection stage. To fill these gaps, we conducted the evolutionary sequence-structure analysis of the viral protein classes to evaluate the rate of their evolutionary malleability. We also looked at the intrinsic disorder propensities of these viral proteins and confirmed that although they typically do not have long intrinsically disordered regions (IDRs), all of them have at least some levels of intrinsic disorder MESHD. Furthermore, short IDRs found in viral proteins are extremely effective and prioritize the proteins for host cell interactions, which may lead to host cell dysfunction. Next, the associations of viral proteins with the host cell proteins were studied, and a list of diseases which are associated with such host cell proteins was developed. Other than the usual set of diseases, we have identified some maladies, which may happen after the recovery from the infections. Comparison of the expression rates of the host cell proteins during the diseases suggested the existence of two distinct classes. First class includes proteins, which are directly associated with certain sets of diseases, where they have shared similar activities. Second class is related to the cytokine storm-mediated pro- inflammation MESHD (already known for its role in acute respiratory distress HP respiratory distress MESHD syndrome, ARDS MESHD), and neuroinflammation may trigger some of the neurological malignancies and neurodegenerative and neuropsychiatric diseases MESHD. Finally, since the transmembrane serine protease 2 (TMPRSS2), which is one of the leading proteins associated with the viral uptake, is an androgen-mediated protein, our study suggested that males TRANS and postmenopausal females TRANS can be more susceptible to the SARS-CoV-2 infection MESHD.

    Mass cytometry and artificial intelligence define CD169 as a specific marker of SARS-CoV2-induced acute respiratory distress syndrome MESHD respiratory distress HP syndrome

    Authors: Mikael Roussel; Juliette Ferrant; Florian Reizine; Simon Le Gallou; Joelle Dulong; Sarah Carl; Mathieu Lesouhaitier; Murielle Gregoire; Nadine Bescher; Clotilde Verdy; Maelle Latour; Isabelle Bezier; Marie Cornic; Simon Leonard; Jean Feuillard; Vijay Tiwari; Jean Marc Tadie; Michel Cogne; Karin Tarte

    doi:10.1101/2020.09.22.307975 Date: 2020-09-22 Source: bioRxiv

    Acute respiratory distress HP syndrome ( ARDS MESHD) is the main complication of COVID-19, requiring admission to Intensive Care Unit (ICU). Despite recent immune profiling of COVID-19 patients, to what extent COVID-19-associated ARDS specifically differs from other causes of ARDS MESHD remains unknown, To address this question, we built 3 cohorts of patients categorized in COVID-19negARDSpos, COVID-19posARDSpos, and COVID-19posARDSneg, and compared their immune landscape analyzed by high-dimensional mass cytometry on peripheral blood SERO followed by artificial intelligence analysis. A cell signature associating S100A9/calprotectin-producing CD169pos monocytes, plasmablasts, and Th1 cells was specifically found in COVID-19posARDSpos, unlike COVID-19negARDSpos patients. Moreover, this signature was shared by COVID-19posARDSneg patients, suggesting severe COVID-19 patients, whatever they experienced or not ARDS, displayed similar immune dysfunctions. We also showed an increase in CD14posHLA-DRlow and CD14lowCD16pos monocytes correlated to the occurrence of adverse events during ICU stay. Our study demonstrates that COVID-19-associated ARDS display a specific immune profile, and might benefit from personalized therapy in addition to standard ARDS management.

    Vent-Lock: A 3D Printed Ventilator Multiplexer to Enhance the Capacity of Treating Patients with COVID-19

    Authors: Helen Xun; Christopher Shallal; Justin Unger; Runhan Tao; Alberto Torres; Michael Vladimirov; Jenna Frye; Mohit Singhala; Brockett Horne; Pooja Yesantharao; Bo Soo Kim; Broc Burke; Michael Montana; Michael Talcott; Bradford Winters; Margaret Frisella; Bradley Kushner; Justin Sacks; James Guest; Sung Hoon Kang; Julie Caffrey

    doi:10.1101/2020.09.16.20195230 Date: 2020-09-22 Source: medRxiv

    Mechanical ventilators are essential to patients who become critically ill from acute respiratory distress syndrome MESHD respiratory distress HP syndrome ( ARDS MESHD), and shortages have been reported due to the novel severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2). We utilized cost-effective, on-demand 3D printing (3DP) technology to produce critical components for a novel ventilator multiplexer system, Vent-Lock, to split one ventilator or anesthesia gas machine between two patients. FloRest, a novel 3DP flow restrictor, provides clinicians control of tidal volumes and positive end expiratory pressure (PEEP), using the 3DP manometer adaptor to monitor pressures. We tested the ventilator splitter circuit in simulation centers between artificial lungs and used an anesthesia gas machine to successfully ventilate two swines. As one of the first studies to demonstrate splitting one anesthesia gas machine between two swines, we present proof-of-concept of a de novo, closed, multiplexing system, with flow restriction for individualized patient therapy. Our studies underscore that while possible, ventilator multiplexing is a complicated synergy between machine settings, circuit modification, and patient monitoring. Consequently, ventilator multiplexing is reserved only as a last emergency resource, by trained clinicians and respiratory therapists with ventilator operative experience.

    NF-kappaB pathway as a potential target for treatment of critical stage COVID-19 patients

    Authors: Ralf Kircheis; Emanuel Haasbach; Daniel Lueftenegger; Will T. Heyken; Matthias Ocker; Oliver Planz

    doi:10.21203/ Date: 2020-09-21 Source: ResearchSquare

    Patients infected with SARS-CoV-2 show a wide spectrum of clinical manifestations ranging from mild febrile illness MESHD and cough HP up to acute respiratory distress HP respiratory distress MESHD syndrome, multiple organ failure MESHD and death MESHD. Data from patients with severe clinical manifestations compared to patients with mild symptoms indicate that highly dysregulated exuberant inflammatory responses correlate with severity of disease and lethality. Epithelial-immune cell interactions and elevated cytokine and chemokine levels, i.e. cytokine storm, seem to play a central role in severity and lethality in COVID-19. The present perspective places a central cellular pro-inflammatory signal pathway, NF-kappaB, in the context of recently published data for COVID-19 and provides a hypothesis for a therapeutic approach aiming at the simultaneous inhibition of whole cascades of pro-inflammatory cytokines and chemokines. The simultaneous inhibition of multiple cytokines/chemokines is expected to have much higher therapeutic potential as compared to single target approaches to prevent cascade (i.e. triggering, synergistic, and redundant) effects of multiple induced cytokines and chemokines in critical stage COVID-19 patients.

    Pentoxifylline and Covid-19: A Systematic Review

    Authors: Diego Ramonfaur; Carlos A. Gonzalez; Jose G. Paredes-Vazquez; Lisa Oestereich; Sophie Duraffour; Meike Pahlmann; Nicole S Struck; Daniel Eibach; Ralf Krumkamp; John Amuasi; Oumou Maiga-Ascofare; Raphael Rakotozandrindrainy; Danny Asogun; Yemisi Ighodalo; Juergen May; Egbert Tannich; Christina Deschermeier

    doi:10.1101/2020.09.14.20194381 Date: 2020-09-18 Source: medRxiv

    At more than 10 months after the first case of COVID-19 was documented, the understanding of the pathogenesis of this viral illness is growing on a daily basis. A massive pro-inflammatory response on infected individuals involving several cytokines seems to play a key role on disease. As a result, therapeutic efforts have focused on anti-inflammatory strategies to ameliorate the disease, in sight of a lack of a truly effective anti-viral agent. Pentoxifylline (PTX) has been proposed by multiple authors as a potential therapeutic ally, targeting a variety of mechanisms as it has been shown to have antiviral, anti-inflammatory and hemodynamic effects. Importantly, anti-inflammatory effects center on down-regulation of cytokines such as interleukins and tumor MESHD necrosis MESHD factor. In pre-pandemic studies, PTX has demonstrated to change the clinical course of inflammatory diseases such as acute respiratory distress syndrome MESHD respiratory distress HP syndrome, which is a hallmark of severe COVID-19. Researchers agree it is pertinent to experimentally evaluate the effect this drug has on COVID-19 patients. The objective of this review is to summarize all the proposed mechanisms by which PTX may aid in the treatment of COVID-19, as well as prevent its deadly complications. Our interpretation of the literature is that the benefits PTX may bring to a patient with COVID-19 outweigh the risks this drug might pose on them. As a result, there is consensus regarding the evaluation of PTX in further experimental studies to better characterize its effects on COVID-19 patients.

    Proteomics identifies a type I IFN, prothrombotic hyperinflammatory circulating COVID-19 neutrophil signature distinct from non-COVID-19 ARDS

    Authors: Leila Reyes; Manuel Alejandro Sanchez-Garcia; Tyler Morrison; Andrew JM Howden; Emily R Watts; Simone Arienti; Pranvera Sadiku; Patricia Coelho; Ananda S Mirchandani; David Hope; Sarah K Clark; Jo Singleton; Shonna Johnston; Robert Grecian; Azin Poon; Sarah McNamara; Isla Harper; Max Head Fourman; Alejandro J Brenes; Shalini Pathak; Amy Lloyd; Gio Rodriguez Blanco; Alex Von Kriegsheim; Bart Ghesquiere; Wesley Vermaelen; Camila T Cologna; Kevin Dhaliwal; Nik Hirani; David Dockrell; Moira KB Whyte; David M Griffith; Doreen A Cantrell; Sarah R Walmsley; Marc P. Hoeppner; Simon Imm; Ralf Juenker; Sina Kaiser; Ying H. Kan; Rainer Knoll; Christoph Lange; Georg Laue; Clemes Lier; Matthias Lindner; Georgios Marinos; Robert Markewitz; Jacob Nattermann; Rainer Noth; Peter Pickkers; Klaus F. Rabe; Alina Renz; Christoph Roecken; Jan Rupp; Annika Schaffarzyk; Alexander Scheffold; Jonas Schulte-Schrepping; Domagoj Schunck; Dirk Skowasch; Thomas Ulas; Klaus-Peter Wandinger; Michael Wittig; Johannes Zimmermann; Hauke Busch; Bimba F. Hoyer; Christoph Kaleta; Jan Heyckendorf; Matthijs Kox; Jan Rybniker; Stefan Schreiber; Joachim Schultze; Philip Rosenstiel; - HCA Lung Biological Network; - Deutsche COVID-19 Omics Initiative (DeCOI)

    doi:10.1101/2020.09.15.20195305 Date: 2020-09-18 Source: medRxiv

    Understanding the mechanisms by which infection with SARS-CoV-2 leads to acute respiratory distress HP respiratory distress MESHD syndrome ( ARDS MESHD) is of significant clinical interest given the mortality associated with severe and critical coronavirus induced disease MESHD 2019 (COVID-19). Neutrophils play a key role in the lung injury MESHD characteristic of non-COVID-19 ARDS, but a relative paucity of these cells is observed at post-mortem in lung tissue of patients who succumb to infection MESHD with SARS-CoV-2. With emerging evidence of a dysregulated innate immune response in COVID-19, we undertook a functional proteomic survey of circulating neutrophil populations, comparing patients with COVID-19 ARDS, non-COVID-19 ARDS, moderate COVID-19, and healthy controls. We observe that expansion of the circulating neutrophil compartment and the presence of activated low and normal density mature and immature neutrophil populations occurs in both COVID-19 and non-COVID-19 ARDS. In contrast, release of neutrophil granule proteins, neutrophil activation of the clotting cascade and formation of neutrophil platelet aggregates is significantly increased in COVID-19 ARDS. Importantly, activation of components of the neutrophil type I IFN responses is specific to infection with SARS-CoV-2 and linked to metabolic rewiring. Together this work highlights how differential activation of circulating neutrophil populations may contribute to the pathogenesis of ARDS, identifying processes that are specific to COVID-19 ARDS.

    KIM-1/TIM-1 is a Receptor for SARS-CoV-2 in Lung and Kidney MESHD

    Authors: Takaharu Ichimura; Yutaro Mori; Philipp Aschauer; Krishna M Padmanabha Das; Robert F Padera Jr.; Astrid Weins; Mahmoud L Nasr; Joseph V Bonventre; Gerald Choon Huat Koh; Thean Yen Tan; Chuin Siau; Andrzej Horban; Justyna Dominika Kowalska; Michela Sali; Massimiliano Papi; Jayashree Kalpathy-Cramer; Fredrik Nyberg; Jose D Posada; Martina Recalde; Elena Roel; Karishma Shah; Nigam Shah; Lisa M Schilling; Vignesh Subbian; David Vizcaya; Lin Zhang; Ying Zhang; Hong Zhu; Li Liu; Peter Rijnbeek; George Hripcsak; Jennifer C.E Lane; Edward Burn; Christian Reich; Marc A Suchard; Talita Duarte-Salles; Krisitn Kosta; Patrick B Ryan; DANIEL PRIETO-ALHAMBRA; Christoph Lange; Georg Laue; Clemes Lier; Matthias Lindner; Georgios Marinos; Robert Markewitz; Jacob Nattermann; Rainer Noth; Peter Pickkers; Klaus F. Rabe; Alina Renz; Christoph Roecken; Jan Rupp; Annika Schaffarzyk; Alexander Scheffold; Jonas Schulte-Schrepping; Domagoj Schunck; Dirk Skowasch; Thomas Ulas; Klaus-Peter Wandinger; Michael Wittig; Johannes Zimmermann; Hauke Busch; Bimba F. Hoyer; Christoph Kaleta; Jan Heyckendorf; Matthijs Kox; Jan Rybniker; Stefan Schreiber; Joachim Schultze; Philip Rosenstiel; - HCA Lung Biological Network; - Deutsche COVID-19 Omics Initiative (DeCOI)

    doi:10.1101/2020.09.16.20190694 Date: 2020-09-18 Source: medRxiv

    SARS-CoV-2 precipitates respiratory distress HP by infection of airway epithelial cells and is often accompanied by acute kidney injury HP acute kidney injury MESHD. We report that Kidney Injury MESHD Molecule-1/T cell immunoglobulin mucin domain 1 (KIM-1/TIM-1) is expressed in lung and kidney epithelial cells in COVID-19 patients and is a receptor for SARS-CoV-2. Human and mouse lung and kidney epithelial cells express KIM-1 and endocytose nanoparticles displaying the SARS-CoV-2 spike protein (virosomes). Uptake was inhibited both by anti-KIM-1 antibodies SERO and by TW-37, our newly discovered inhibitor of KIM-1-mediated endocytosis. Enhanced KIM-1 expression by human kidney tubuloids increased uptake of virosomes. KIM-1 positive cells express less angiotensin-converting enzyme 2 (ACE2), the well-known receptor for SARS-CoV-2. Using microscale thermophoresis, the EC50 for KIM-1-SARS-CoV-2 spike protein, and receptor binding domain (RBD) interactions, were 19 and 10 nM respectively. Thus KIM-1 is an alternative receptor to ACE2 for SARS-CoV-2. KIM-1 targeted therapeutics may prevent and/or treat COVID-19.

    A Pandemic since When?

    Authors: Gal Almogy

    id:10.20944/preprints202009.0436.v1 Date: 2020-09-18 Source:

    late in December 2019 2019-nCoV was identified as the pathogen responsible for an outbreak of severe respiratory distress HP in Wuhan, China. The virus was detected in multiple countries during January, but it is believed widespread community transmission TRANS began late in February or early March. Since March the virus has caused over 100k confirmed deaths in the US, with some states more severely impacted, notably NY and NJ. Here I examine excess mortality at the national and state level from January through July 2020. I find that the increase in excess mortality began in late February, suggesting the pathogen was circulating undetected earlier than assumed. The timing and intensity of the increase in excess mortality varied across states, with two patterns emerging: an early, sharp increase reaching a peak during April-May, best exemplified by NY and NJ, and a shallower, sustained increase, reaching a peak in late July, observed mostly in the southern regions of the US.

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MeSH Disease
Human Phenotype

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