Corpus overview


MeSH Disease

Human Phenotype


    displaying 1 - 10 records in total 292
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    Dynamic changes in serum SERO IL-6, IL-8, and IL-10 are associated with the outcome of patients with severe COVID-19 in ICU

    Authors: Jia Li; Liu Rong; Ran Cui; Jiaqi Feng; Yuyang Jin; Yuetian Yu; Xiaoxiang Chen; Renying Xu

    doi:10.21203/ Date: 2020-09-25 Source: ResearchSquare

    Background: Biomarkers that would help prognosticate outcomes and guide treatment of patients with severe coronavirus disease MESHD 2019 (COVID-19) are currently required. We aimed to investigate whether the dynamic variation of cytokines was associated with the survival of patients admitted to an intensive care unit (ICU).Methods: A retrospective study was performed on 40 patients with COVID-19 admitted to an ICU in Wuhan, China. Demographic, clinical, and laboratory variables were collected, and serum SERO cytokines were kinetically assessed. A multivariable- adjusted generalized linear regression model was used to evaluate the differences in serum SERO cytokine levels between survivor and non-survivors.Results: Among the 40 patients included, a significant positive correlation was found between multiple cytokines. Serum SERO levels of IL-6, IL-10, and tumor MESHD necrosis MESHD factor alpha in non-survivors were consistently elevated compared to that of the survivors. Kinetic variations of IL-6, IL-8, and IL-10 were associated with a fatal outcome in severe patients with COVID-19, independent of sex, age TRANS, absolute lymphocyte count, direct bilirubin, hypertension HP hypertension MESHD, chronic obstructive pulmonary disease HP chronic obstructive pulmonary disease MESHD, and cancer MESHD.Conclusion: Dynamic changes in serum SERO IL-6, IL-8, and IL-10 levels were associated with survival in ICU and could serve as a predictive biomarker in patients with severe COVID-19 to determine therapeutic options.

    In silico identification and validation of inhibitors of the interaction between neuropilin receptor 1 and SARS-CoV-2 Spike MESHD protein

    Authors: Samantha Perez-Miller; Marcel Patek; Aubin Moutal; Carly R Cabel; Curtis A. Thorne; Samuel K Campos; Rajesh Khanna

    doi:10.1101/2020.09.22.308783 Date: 2020-09-23 Source: bioRxiv

    Neuropilin-1 (NRP-1) is a multifunctional transmembrane receptor for ligands that affect developmental axonal growth MESHD and angiogenesis. In addition to a role in cancer MESHD, NRP-1 is a reported entry point for several viruses, including severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), the causal agent of coronavirus disease MESHD 2019 (COVID-19). The furin cleavage product of SARS-CoV-2 Spike MESHD protein takes advantage of the vascular endothelial growth factor A (VEGF-A) binding site on NRP-1 which accommodates a polybasic stretch ending in a C-terminal arginine. This site has long been a focus of drug discovery efforts for cancer MESHD therapeutics. We recently showed that interruption of the VEGF-A/NRP-1 signaling pathway ameliorates neuropathic pain MESHD pain HP and hypothesize that interference of this pathway by SARS-CoV-2 spike protein interferes with pain HP pain MESHD signaling. Here, we report hits from a small molecule and natural product screen of nearly 0.5 million compounds targeting the VEGF-A binding site on NRP-1. We identified nine chemical series with lead- or drug-like physico-chemical properties. Using an ELISA SERO, we demonstrate that six compounds disrupt VEGF-A-NRP-1 binding more effectively than EG00229, a known NRP-1 inhibitor. Secondary validation in cells revealed that almost all tested compounds inhibited VEGF-A triggered VEGFR2 phosphorylation. Two compounds displayed robust inhibition of a recombinant vesicular stomatitis MESHD stomatitis HP virus protein that utilizes the SARS-CoV-2 Spike for entry and fusion. These compounds represent a first step in a renewed effort to develop small molecule inhibitors of the VEGF-A/NRP-1 signaling for the treatment of neuropathic pain MESHD pain HP and cancer MESHD with the added potential of inhibiting SARS-CoV-2 virus entry.

    Ruling In and Ruling Out COVID-19: Computing SARS-CoV-2 Infection Risk TRANS Infection Risk TRANS From Symptoms, Imaging and Test Data.

    Authors: Chistopher D'Ambrosia; Henrik Christensen; Eliah Aronoff-Spencer

    doi:10.1101/2020.09.18.20197582 Date: 2020-09-22 Source: medRxiv

    Background: Assigning meaningful probabilities of SARS CoV2 infection risk TRANS infection risk TRANS presents a diagnostic challenge across the continuum of care. Methods: We integrated patient symptom and test data using machine learning and Bayesian inference to quantify individual patient risk of SARS CoV 2 infection MESHD. We trained models with 100,000 simulated patient profiles based on thirteen symptoms, estimated local prevalence SERO, imaging, and molecular diagnostic performance SERO from published reports. We tested these models with consecutive patients who presented with a COVID 19 compatible illness at the University of California San Diego Medical Center over 14 days starting in March 2020. Results: We included 55 consecutive patients with fever HP fever MESHD (78%) or cough HP cough MESHD (77%) presenting for ambulatory (n=11) or hospital care (n=44). 51% (n=28) were female TRANS, 49% were age TRANS <60. Common comorbidities included diabetes MESHD (22%), hypertension HP hypertension MESHD (27%), cancer MESHD (16%) and cardiovascular disease MESHD (13%). 69% of these (n=38) were RT-PCR confirmed positive for SARS CoV2 infection, 11 had repeated negative nucleic acid testing and an alternate diagnosis. Bayesian inference network, distance metric learning, and ensemble models discriminated between patients with SARS CoV2 infection MESHD and alternate diagnoses with sensitivities SERO of 81.6 to 84.2%, specificities of 58.8 to 70.6%, and accuracies of 61.4 to 71.8%. After integrating imaging and laboratory test statistics with the predictions of the Bayesian inference network, changes in diagnostic uncertainty at each step in the simulated clinical evaluation process were highly sensitive to location, symptom, and diagnostic test choices. Conclusions: Decision support models that incorporate symptoms and available test results can help providers diagnose SARS CoV2 infection MESHD in real world settings.

    Immune checkpoint inhibitors use and effects on prognosis of COVID-19 infection MESHD: A systematic review and meta-analysis

    Authors: Wenwei Qian; Ying Ye; Lugen Zuo; Ting Song; Qing Xu; Yinghong Wang; Yun Tian

    doi:10.21203/ Date: 2020-09-22 Source: ResearchSquare

    Background: The influence of prior exposure to immune checkpoint inhibitors (ICIs) on the coronavirus disease MESHD 2019 (COVID-19) infection remains unknown. Methods: We searched the PubMed, Embase, and Web of Science databases from the inception of each database through August 8, 2020. We included studies that reported ICI use in cancer MESHD patients and their prognosis in the context of COVID-19. Raw data from the included studies were pooled to determine effect estimates. Chi-squared and I2 tests were used to calculate heterogeneity among the included studies.Results: Eighteen studies were included for the systematic review, and 8 of those were included in the meta-analysis. Patients with prior ICI treatment exhibited a higher rate of hospitalization (OR [odds ratio] 2.6, 95% CI 1.45-4.68, p=0.001; I2=0%) and severe disease (OR 1.98, 95% CI 1.14-3.43, p=0.015). However, the OR of mortality in ICI-exposed cases was similar to non-ICI exposed patients (OR 0.90, 95% CI 0.60-1.34, p= 0.60; I2=49%). No statistically significant difference in mortality was observed between patients exposed to ICI and other antitumor treatments.Conclusions: Although a higher rate of hospitalization and severe disease was observed, prior exposure to ICI did not significantly increase the rate of death in the context of COVID-19.

    SARS-CoV-2 antigen and antibody SERO prevalence SERO among UK staff working with cancer MESHD patients during the COVID-19 pandemic.

    Authors: David M Favara; Karen McAdam; Anthony Cooke; Alex Bordessa-Kelly; Ieva Budriunaite; Sophie Bossingham; Sally Houghton; Rainer Doffinger; Nicola Ainsworth; Pippa Corrie; Yimin Tong; Jin Zhong; Youhua Xie; Xinquan Wang; Zhenghong Yuan; Dongming Zhou; Rong Zhang; Qiang Ding; Kristen J Brennand; Katherine H Hullsiek; David R Boulware; SARAH M LOFGREN; Martirene A da Silva; Brian Custer; Manoel Barral-Netto; Moritz Kraemer; Rafael HM Pererira; Oliver G Pybus; Michael P Busch; Márcia C Castro; Christopher Dye; Vitor H Nascimento; Nuno R Faria; Ester C Sabino

    doi:10.1101/2020.09.18.20197590 Date: 2020-09-20 Source: medRxiv

    Background International guidelines for testing potentially immunosuppressed cancer MESHD patients receiving non-surgical anticancer therapies for SARS-CoV-2 (COVID-19) are currently lacking. The value of routinely testing staff treating cancer MESHD patients is not known. Methods: Patient-facing oncology department staff at work during the COVID-19 pandemic consented to have a nasopharyngeal swab SARS-CoV-2 antigen test by polymerase chain reaction (PCR) and blood SERO tests for SARS-CoV-2 antibody SERO using a laboratory Luminex-based assay and a rapid point-of-care (POC) assay on 2 occasions 28 days apart in June and July 2020. Results 434 participants were recruited: nurses (58.3%), doctors (21.2%), radiographers (10.4%) and administrators (10.1%). 82% were female TRANS; median age TRANS 40-years (range 19-66). 26.3% reported prior symptoms suggestive of SARS-CoV-2 infection MESHD and 1.4% tested PCR-positive prior to June 2020. All were PCR-negative at both study day 1 and 28. 18.4% were SARS-CoV-2 sero-positive on day 1 by Luminex, of whom 42.5% also tested positive by POC. 47.5% of Luminex sero-positives had antibodies SERO to both nucleocapsid (N) and surface (S) antigens. Nurses (21.3%) and doctors (17.4%) had higher prevalence SERO trends of Luminex sero-positivity compared with administrators (13.6%) and radiographers (8.9%) (p=0.2). 38% of sero-positive participants reported previous symptoms suggestive of SARS-CoV-2 infection MESHD, a 1.9-fold higher odds than sero-negative participants (p=0.01). 400 participants re-tested on day 28: 13.3% were Luminex sero-positive of whom 92.5% were previously positive and 7.5% newly positive. Nurses (16.5%) had the highest seroprevalence SERO trend amongst staff groups (p=0.07). 32.5% of day 1 sero-positives became sero-negative by day 28: the majority being previously reactive to the N-antigen only (p<0.0001). Conclusion The high prevalence SERO of SARS-CoV-2 IgG sero-positivity in oncology nurses, and the high decline of positivity over 4 weeks supports regular antigen and antibody testing SERO in this staff group for SARS-CoV-2 as part of routine patient care prior to availability of a vaccine.

    Clinical Thrombosis MESHD Rate was not Increased in a Cohort of Cancer MESHD Patients with COVID-19

    Authors: Phaedon D Zavras; Rafi Kabarriti; Vikas Mehta; Sanjay Goel; Henny H. Billett; Johanna I. Blase; Dora Bordoni; Jeanette Franzenburg; Ulf Geisen; Jonathan Josephs-Spaulding; Philipp Koehler; Axel Kuenstner; Elisa Rosati; Anna C. Aschenbrenner; Petra Bacher; Nathan Baran; Teide Boysen; Burkhard Brandt; Niklas Bruse; Jonathan Doerr; Andreas Draeger; Gunnar Elke; David Ellinghaus; Julia Fischer; Michael Forster; Andre Franke; Soeren Franzenburg; Norbert Frey; Anette Friedrichs; Janina Fuss; Andreas Glueck; Jacob Hamm; Finn Hinrichsen; 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:10.1101/2020.09.15.20195263 Date: 2020-09-18 Source: medRxiv

    Increased rates of thromboembolic MESHD events (TE) have been reported in patients with coronavirus disease MESHD (COVID-19), even without prior predisposition to thrombosis MESHD. D-dimer levels have been shown to positively correlate with disease severity and mortality, leading to adoption of new empiric anticoagulation protocols by many centers. We aimed to assess whether COVID-19 further increased the risk of TE events in a cancer MESHD population who tested positive for COVID-19 at Montefiore Medical Center, Bronx, NY. The electronic medical records of 218 cancer MESHD patients were retrospectively reviewed up to April 10th, 2020. Work-up of thrombosis MESHD was done by the primary team upon clinical or laboratory suspicion. All imaging studies' reports, within 20 days of COVID-19 positive test, were reviewed for presence of new arterial or venous thrombosis HP venous thrombosis MESHD. Mortality was assessed up to one month since positive COVID-19 test result. Twelve patients (5.5%) were found to have new arterial (N=6, 50%) or venous (N=6, 50%) thrombosis MESHD. Five patients (41.7%) had history of prior TE events. Incidence of deep venous thrombosis HP deep venous thrombosis MESHD and pulmonary embolism HP pulmonary embolism MESHD was 1.8% and 0.5%, respectively. Arterial events occurred in the brain (66.7%), aorta (16.7%) and coronary arteries (16.7%). Median time from COVID test was 8 days (IQR, 1.5 - 11.3). Five patients (41.7%) had received either prophylactic or therapeutic anticoagulation for a median 2 days (IQR, 1 - 5). Median peak D-dimer within 36 hours of the TE event was 9.8 mcg/mL (N=4 patients, IQR, 1.7 - 18.3). Mortality did not differ significantly between the patients with new TE events vs those without; mortality 41.7% vs 37.4%, respectively, p=0.77. Empiric anticoagulation did not improve mortality. Fifty percent of all TE events were arterial. The overall TE rate of 5.5% in the cancer MESHD population was not higher than the risk of general population. Our findings support the need for larger studies in the COVID-19+ cancer MESHD population.

     Seroprevalence of SARS-CoV-2 in an Asymptomatic TRANS US Population 

    Authors: Steven Rigatti, MD; Robert L. Stout, PhD.

    doi:10.21203/ Date: 2020-09-18 Source: ResearchSquare

    Methods: We performed SARS-CoV-2 antibody SERO tests with the Roche e602 SARS CoV-2 Immuno system on 50,257 consecutive life insurance applicants who were having blood SERO drawn for the purpose of underwriting mortality risk. Other variables included height, weight, and blood SERO pressure at the time of the blood SERO draw, a history of smoking and common ch ronic diseases ( MESHD hypertension HP pertension, MESHDhe art disease, MESHDdi abetes, MESHDand ca ncer). MESHDResults: The overall prevalence SERO of SARS-CoV-2 was 3.0%, and was fairly consistent across the age TRANS range and similar in males TRANS and females TRANS. Geographical distribution revealed a very high level of positivity in the state of New York compared to all other areas (17.1%). Using US Census state population data to adjust state specific rates of positivity, it is estimated that this level of seropositivity would correspond to 6.98 million (99% CI: 6.56-7.38 million) SA RS-CoV-2 infections i MESHDn the US, which is 3.8 times the cumulative number of cases in the US reported to the CDC as of June 1, 2020.Conclusions: The estimated number of total SA RS-CoV-2 infections b MESHDased on positive serology is substantially higher than the total number of cases reported to the CDC. There is no apparent increase of risk of infection TRANS risk of infection TRANS fection f MESHDor individuals self-reporting, smoking, di abetes, MESHDhe art disease, MESHD hypertension HP pertension o MESHDr ca ncer. MESHD

    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.

    Identification of potential biomarkers and inhibitors for SARS-CoV-2 infection MESHD

    Authors: Hanming Gu; Gongsheng Yuan; Giridhara R Babu; Manjunatha M Venkataswamy; Prameela Dinesh; Prakash B G Kumar; Daisy A John; Anita Desai; Ravi Vasanthapuram; Jonathan Flint; Eleazar Eskin; Chongyuan Luo; Shangxin Yang; Omai B Garner; Yi Yin; Joshua S Bloom; Leonid Kruglyak; Jason M Goldstein; Joel M Montgomery; Christina F Spiropoulou

    doi:10.1101/2020.09.15.20195487 Date: 2020-09-18 Source: medRxiv

    The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) has overwhelmed many health systems globally. Here, we aim to identify biological markers and associated biological processes of COVID-19 using a bioinformatics approach to elucidate their potential pathogenesis. The gene expression profile of the GSE152418 dataset was originally produced by using the high-throughput Illumina NovaSeq 6000. Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) and Gene Ontology (GO) enrichment analyses were applied to identify functional categories and biochemical pathways. KEGG and GO results suggested that biological pathways such as Cancer MESHD pathways and Insulin pathways were mostly affected in the development of COVID-19. Moreover, we identified several genes including EP300, CREBBP, and POLR2A were involved in the virus activities in COVID-19 patients. We further predicted that some inhibitors may have the potential to block the SARS-CoV-2 infection MESHD based on the L1000FWD analysis. Therefore, our study provides further insights into the underlying pathogenesis of COVID-19.

    Fixed single-cell RNA sequencing for understanding virus infection MESHD and host response

    Authors: Hoang Van Phan; Michiel van Gent; Nir Drayman; Anindita Basu; Michaela Gack; Savas Tay; Patricio O. Craig; Leandro A. Cossio; Liliana Dain; Fernanda Elias; Natalia B. Fernandez; Javier Gasulla; Natalia Gorojovsky; Gustavo E. Gudesblat; Maria G. Herrera; Lorena I. Ibañez; Tommy Idrovo; Matias Iglesias Rando; Laura Kamenetzky; Alejandro D Nadra; Diego G. Noseda; Carlos H. Pavan; Maria F. Pavan; Maria F. Pignataro; Ernesto Roman; Lucas A.M Ruberto; Natalia Rubinstein; Javier Santos; Francisco Velazquez; Alicia M. Zelada; Catherine M.K. Ho; Chelsea L Kennard; Daniel Knott; Stephanie Leung; Vanessa Lucas; Adam Mabbutt; Alexandra L Morrison; Didier Ngabo; Jemma Paterson; Elizabeth J Penn; Steve Pullan; Irene Taylor; Tom Tipton; Stephen Thomas; Julia A Tree; Carrie Turner; Nadina Wand; Nathan R Wiblin; Sue Charlton; Bassam Hallis; Geoffrey Pearson; Emma L Rayner; Andrew G Nicholson; Simon G Funnell; Mike J Dennis; Fergus V Gleeson; Sally Sharpe; Miles W Carroll

    doi:10.1101/2020.09.17.302232 Date: 2020-09-17 Source: bioRxiv

    Single-cell RNA sequencing studies requiring intracellular protein staining, rare-cell sorting, or pathogen inactivation are severely limited because current high-throughput methods are incompatible with paraformaldehyde treatment, a very common and simple tissue/cell fixation and preservation technique. Here we present FD-seq, a high-throughput method for droplet-based RNA sequencing of paraformaldehyde-fixed, stained and sorted single-cells. We used FD-seq to address two important questions in virology. First, by analyzing a rare population of cells supporting lytic reactivation of the human tumor MESHD virus KSHV, we identified TMEM119 as a host factor that mediates reactivation. Second, we studied the transcriptome of lung cells infected with the 2 coronavirus OC43, which causes the common cold and also serves as a safer model pathogen for SARS-CoV-2. We found that pro-inflammatory pathways are primarily upregulated in abortively-infected MESHD or uninfected bystander cells, which are exposed to the virus but fail to express high level of viral genes. FD-seq is suitable for characterizing rare cell populations of interest, for studying high-containment biological samples after inactivation, and for integrating intracellular phenotypic with transcriptomic information.

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MeSH Disease
Human Phenotype

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