Corpus overview


MeSH Disease

Human Phenotype


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    IFN signaling and neutrophil degranulation transcriptional signatures are induced during SARS-CoV-2 infection MESHD

    Authors: Bruce A. Rosa; Mushtaq Ahmed; Dhiraj K. Singh; Jose Alberto Choreno-Parra; Journey Cole; Luis Armando Jimenez-Alvarez; Tatiana Sofia Rodriguez-Reyna; Bindu Singh; Olga Golzalez; Ricardo Carrion; Larry S. Schlesinger; John Martin; Joaquin Zuniga; Makedonka Mitreva; Shabaana A Khader; Deepak Kaushal

    doi:10.1101/2020.08.06.239798 Date: 2020-08-06 Source: bioRxiv

    The novel virus SARS-CoV-2 has infected more than 14 million people worldwide resulting in the Coronavirus disease MESHD 2019 (COVID-19). Limited information on the underlying immune mechanisms that drive disease MESHD or protection during COVID-19 severely hamper development of therapeutics and vaccines. Thus, the establishment of relevant animal models that mimic the pathobiology of the disease is urgent. Rhesus macaques infected with SARS-CoV-2 exhibit disease pathobiology similar to human COVID-19, thus serving as a relevant animal model. In the current study, we have characterized the transcriptional signatures induced in the lungs of juvenile and old rhesus macaques following SARS-CoV-2 infection MESHD. We show that genes associated with Interferon (IFN) signaling, neutrophil degranulation and innate immune pathways are significantly induced in macaque infected lungs MESHD, while pathways associated with collagen formation are downregulated. In COVID-19, increasing age TRANS is a significant risk factor for poor prognosis and increased mortality. We demonstrate that Type I IFN and Notch signaling pathways are significantly upregulated in lungs of juvenile infected MESHD macaques when compared with old infected macaques. These results are corroborated with increased peripheral neutrophil counts and neutrophil lymphocyte ratio in older individuals with COVID-19 disease. In contrast, pathways involving VEGF are downregulated in lungs of old infected macaques. Using samples from humans with SARS-CoV-2 infection MESHD and COVID-19, we validate a subset of our findings. Finally, neutrophil degranulation, innate immune system and IFN gamma signaling pathways are upregulated in both tuberculosis MESHD and COVID-19, two pulmonary diseases MESHD where neutrophils are associated with increased severity. Together, our transcriptomic studies have delineated disease pathways to improve our understanding of the immunopathogenesis of COVID-19 to facilitate the design of new therapeutics for COVID-19.

    Serial co-expression analysis of host factors from SARS-CoV viruses MESHD highly converges with former high-throughput screenings and proposes key regulators and co-option of cellular pathways

    Authors: Antonio J. Perez-Pulido; Gualberto Asencio-Cortes; Ana M Brokate-Llanos; Gloria Brea-Calvo; Rosario Rodriguez-Grinolo; Andres Garzon; Manuel J Munoz

    doi:10.1101/2020.07.28.225078 Date: 2020-07-28 Source: bioRxiv

    The current genomics era is bringing an unprecedented growth in the amount of gene expression data, only comparable to the exponential growth of sequences in databases during the last decades. This data now allows the design of secondary analyses that take advantage of this information to create new knowledge through specific computational approaches. One of these feasible analyses is the evaluation of the expression level for a gene through a series of different conditions or cell types. Based on this idea, we have developed ASACO, Automatic and Serial Analysis of CO-expression, which performs expression profiles for a given gene along hundreds of normalized and heterogeneous transcriptomics experiments and discover other genes that show either a similar or an inverse behavior. It might help to discover co-regulated genes, and even common transcriptional regulators in any biological model, including human diseases MESHD or microbial infections. The present SARS-CoV-2 pandemic is an opportunity to test this novel approach due to the wealth of data that is being generated, which could be used for validating results. In addition, new cell mechanisms identified could become new therapeutic targets. Thus, we have identified 35 host factors in the literature putatively involved in the infectious cycle of SARS-CoV and/or SARS-CoV-2 and searched for genes tightly co-expressed with them. We have found around 1900 co-expressed genes whose assigned functions are strongly related to viral cycles. Moreover, this set of genes heavily overlap with those identified by former laboratory high-throughput screenings (with p-value near 0). Some of these genes aim to cellular structures such as the stress granules, which could be essential for the virus replication and thereby could constitute potential targets in the current fight against the virus. Additionally, our results reveal a series of common transcription regulators, involved in immune and inflammatory responses, that might be key virus targets to induce the coordinated expression of SARS-CoV-2 host factors. All of this proves that ASACO can discover gene co-regulation networks with potential for proposing new genes, pathways and regulators participating in particular biological systems. HighlightsO_LIASACO identifies regulatory associations of genes using public transcriptomics data. C_LIO_LIASACO highlights new cell functions likely involved in the infection of coronavirus. C_LIO_LIComparison with high-throughput screenings validates candidates proposed by ASACO. C_LIO_LIGenes co-expressed with hosts genes used by SARS-CoV-2 are related to stress granules. C_LIO_LIZNF91 and TRIM14 might be putative targets to interfere with the viral infection. C_LI

    Mapping Systemic Inflammation MESHD and Antibody SERO Responses in Multisystem Inflammatory Syndrome MESHD in Children TRANS (MIS-C)

    Authors: Conor Gruber; Roosheel Patel; Rebecca Trachman; Lauren Lepow; Fatima Amanat; Florian Krammer; Karen M. Wilson; Kenan Onel; Daniel Geanon; Kevin Tuballes; Manishkumar Patel; Konstantinos Mouskas; Nicole Simons; Vanessa Barcessat; Diane Del Valle; Samantha Udondem; Gurpawan Kang; Sandeep Gangadharan; George Ofori-Amanfo; Adeeb Rahman; Seunghee Kim-Schulze; Alexander Charney; Sacha Gnjatic; Bruce Gelb; Miriam Merad; Dusan Bogunovic

    doi:10.1101/2020.07.04.20142752 Date: 2020-07-06 Source: medRxiv

    Initially, the global outbreak of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) spared children TRANS from severe disease. However, after the initial wave of infections, clusters of a novel hyperinflammatory disease MESHD have been reported in regions with ongoing SARS-CoV-2 MESHD epidemics. While the characteristic clinical features are becoming clear, the pathophysiology remains unknown. Herein, we report on the immune profiles of eight Multisystem Inflammatory Syndrome MESHD in Children TRANS (MIS-C) cases. We document that all MIS-C patients had evidence of prior SARS-CoV-2 exposure, mounting an antibody SERO response with normal isotype-switching and neutralization capability. We further profiled the secreted immune response by high-dimensional cytokine assays, which identified elevated signatures of inflammation MESHD (IL-18 and IL-6), lymphocytic and myeloid chemotaxis and activation (CCL3, CCL4, and CDCP1) and mucosal immune dysregulation HP (IL-17A, CCL20, CCL28). Mass cytometry immunophenotyping of peripheral blood SERO revealed reductions of mDC1 and non-classical monocytes, as well as both NK- and T- lymphocytes, suggesting extravasation to affected tissues. Markers of activated myeloid function were also evident, including upregulation of ICAM1 and FcR1 in neutrophil and non-classical monocytes, well-documented markers in autoinflammation MESHD and autoimmunity HP that indicate enhanced antigen presentation and Fc-mediated responses. Finally, to assess the role for autoimmunity HP secondary to infection, we profiled the auto-antigen reactivity of MIS-C plasma SERO, which revealed both known disease-associated autoantibodies (anti-La) and novel candidates that recognize endothelial, gastrointestinal and immune-cell antigens. All patients were treated with anti- IL6R antibody SERO or IVIG, which led to rapid disease resolution tracking with normalization of inflammatory markers.

    In silico multi-epitope vaccine against covid19 showing effective interaction with HLA-B*15:03

    Authors: Muniba Faiza; Tariq Abdullah; Jose Franklin Calderon-Tantalean; Manish Ravindranath Upadhyay; Abdelrahman H. Abdelmoneim; Fareeha Akram; Bhupender Singh Thakur; Ibrahim Abdulaziz; Chimaobi James Ononamadu; Dina Abdelazim Ghoraba; Saba Munawar; MD Fakhrul Islam Faruque; Collins Kigen; Abhishek Sharma; Ashwani Kumar; Aqsa Khalid; Ali Gharip; Ankit Gupta; Manne Manikumar; Uma Chaudhary

    doi:10.1101/2020.06.10.143545 Date: 2020-06-14 Source: bioRxiv

    The recent outbreak of severe acute respiratory syndrome MESHD (SARS) coronavirus (CoV)-2 (SARS-CoV-2) causing coronavirus disease MESHD (covid19) has posed a great threat to human health. Previous outbreaks of SARS-CoV MESHD and Middle East respiratory Syndrome CoV MESHD (MERS-CoV) from the same CoV family had posed similar threat to human health and economic growth. To date, not even a single drug specific to any of these CoVs has been developed nor any anti-viral vaccine is available for the treatment of diseases MESHD caused by CoVs. Subunits present in spike glycoproteins of SARS-CoV MESHD and SARS-CoV-2 are involved in binding to human ACE2 Receptor which is the primary method of viral invasion. As it has been observed in the previous studies that there are very minor differences in the spike glycoproteins of SARS-CoV MESHD and SARS-CoV-2. SARS-CoV-2 has an additional furin cleavage site that makes it different from SARS-CoV MESHD (Walls et al., 2020). In this study, we have analyzed spike glycoproteins of SARS-CoV-2 and SARS-CoV MESHD phylogenetically and subjected them to selection pressure analysis. Selection pressure analysis has revealed some important sites in SARS-CoV-2 and SARS-CoV spike glycoproteins MESHD that might be involved in their pathogenicity. Further, we have developed a potential multi-epitope vaccine candidate against SARS-CoV-2 by analyzing its interactions with HLA-B*15:03 subtype. This vaccine consists of multiple T-helper (TH) cells, B-cells, and Cytotoxic T-cells (CTL) epitopes joined by linkers and an adjuvant to increase its immunogenicity. Conservation of selected epitopes in SARS, MERS, and human hosts, suggests that the designed vaccine could provide cross-protection. The vaccine is designed in silico by following a reverse vaccinology method acknowledging its antigenicity, immunogenicity, toxicity MESHD, and allergenicity. The vaccine candidate that we have designed as a result of this work shows promising result indicating its potential capability of simulating an immune response.

    Global research trend in the treatment of the new Coronavirus diseases (COVID-19) : bibliometric analysis.

    Authors: Maxime Descartes Mbogning Fonkou; Abdourahamane YACOUBA

    doi:10.1101/2020.06.13.20122762 Date: 2020-06-14 Source: medRxiv

    The Coronavirus 2019 (COVID-19) pandemic has caused worldwide concern and has become a major medical problem. Vaccines and therapeutics are important interventions for the management of this outbreak. This study aims to used bibliometric methods to identify research trends in the domain of therapeutics and vaccines to cure patients with COVID-19 since the beginning of the pandemic. The Web of Science Core Collection database was retrieved for articles on therapeutic approaches to coronavirus disease MESHD management published between January 1, 2020 and May 20, 2020. Identified and analyzed the data included title, corresponding author, language, publication time, publication type, research focus. A total of 1569 articles on coronavirus therapeutic means from 84 countries were published in 620 journals. We note the remarkable progressive increase in the number of publications related to research on therapies and vaccines for COVID-19. The United States provided the largest number of articles (405), followed by China (364). Journal of Medical Virology published most of them (n=40). 1005 (64.05%) were articles, 286 (18.23%) were letters, 230 (14.66%) were reviews. The terms "COVID- 19" or " SARS-CoV-2" MESHD or "Coronavirus" or "hydroxychloroquine" or "chloroquine" or "2019-nCOV" or "ACE2" or "treatment" or "remdesivir" or " pneumonia HP pneumonia MESHD" were most frequently used, as shown in the density visualization map. A network analysis based on keyword co-occurrence revealed five distinct types of studies: clinical, biological, epidemiological, pandemic management, and therapeutics (vaccines and treatments). COVID-19 is a major disease that has had an impact on international public health at the global level. Several avenues for treatment and vaccines have been explored. Most of them focus on older drugs used to treat other diseases MESHD that have been effective for other types of coronaviruses. There is a discrepancy in the results obtained from the studies of the drugs included in this study. Randomized clinical trials are needed to evaluate older drugs and develop new treatment options.

    Risk and protective factors of SARS-CoV-2 infection MESHD - Meta-regression of data from worldwide nations

    Authors: Hisato Takagi; Toshiki Kuno; Yujiro Yokoyama; Hiroki Ueyama; Takuya Matsushiro; Yosuke Hari; Tomo Ando

    doi:10.1101/2020.06.06.20124016 Date: 2020-06-07 Source: medRxiv

    Although it has been reported that coexistent chronic diseases MESHD are strongly associated with COVID-19 severity, investigations of predictors for SARS-CoV-2 infection MESHD itself have been seldom performed. To screen potential risk and protective factors for SARS-CoV-2 infection MESHD, meta-regression of data from worldwide nations were herein conducted. We extracted total confirmed COVID-19 cases in worldwide 180 nations (May 31, 2020), nation total population, population ages TRANS 0-14/65 and above, GDP/GNI per capita, PPP, life expectancy at birth, medical-doctor and nursing/midwifery-personnel density, hypertension HP hypertension MESHD/ obesity HP obesity MESHD/ diabetes MESHD prevalence SERO, annual PM2.5 concentrations, daily ultraviolet radiation, population using safely-managed drinking-water/sanitation services and hand-washing facility with soap/water, inbound tourism, and bachelor's MESHD or equivalent (ISCED 6). Restricted maximum-likelihood meta-regression in the random-effects model was performed using Comprehensive Meta-Analysis version 3. To adjust for other covariates, we conducted the hierarchical multivariate models. A slope (coefficient) of the meta-regression line for the COVID-19 prevalence SERO was significantly negative for population ages TRANS 0-14 (-0.0636; P = .0021) and positive for obesity HP obesity MESHD prevalence SERO (0.0411; P = .0099) and annual PM2.5 concentrations in urban areas (0.0158; P = .0454), which would indicate that the COVID-19 prevalence SERO decreases significantly as children TRANS increase and that the COVID-19 prevalence SERO increases significantly as the obese MESHD and PM2.5 increase. In conclusion, children TRANS (negatively) and obesity HP obesity MESHD/PM2.5 (positively) may be independently associated with SARS-CoV-2 infection MESHD.

    Finding disease modules for cancer MESHD and COVID-19 in gene co-expression networks with the Core&Peel method

    Authors: Marta Lucchetta; Marco Pellegrini

    doi:10.1101/2020.05.27.118414 Date: 2020-05-27 Source: bioRxiv

    Diseases imply dysregulation of cells functions at several levels. The study of differentially expressed genes in case-control cohorts of patients is often the first step in understanding the details of the cells dysregulation. A further level of analysis is introduced by noticing that genes are organized in functional modules (often called pathways), thus their action and their dysregulation may be better understood by the identification of the modules most affected by the disease ( aka disease MESHD modules, or active subnetworks). We describe how an algorithm based on the Core&Peel method developed originally for detecting protein complexes in PPI networks, can be adapted to detect disease modules in co-expression networks of genes. We first validate Core&Peel for the easier general task of functional module detection by comparison with 42 methods participating in the Disease Module Identification DREAM challenge of 2019. Next, we use four specific disease test cases ( colorectal cancer MESHD cancer, prostate HP prostate cancer MESHD, asthma HP asthma MESHD and rheumatoid arthritis HP rheumatoid arthritis MESHD), four state-of-the-art algorithms (ModuleDiscoverer, Degas, KeyPathwayMiner and ClustEx), and several pathway databases to validate the proposed algorithm. Core&Peel is the only method able to find significant associations of the predicted disease module with known validated relevant pathways for all four diseases. Moreover for the two cancer MESHD data sets, Core&Peel detects further nine relevant pathways enriched in the predicted disease module, not discovered by the other methods used in the comparative analysis. Finally we apply Core&Peel, along with other methods, to explore the transcriptional response of human cells to SARS-CoV-2 infection MESHD, at a modular level, aiming at finding supporting evidence for drug repositioning efforts.

    A First Review to Explore the Association of Air Pollution (PM and NO2) on Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2 MESHD)

    Authors: Chiara Copat; Antonio Cristaldi; Maria Fiore; Alfina Grasso; Pietro Zuccarello; Gea Oliveri Conti; Salvatore Santo Signorelli; Margherita Ferrante

    id:10.20944/preprints202005.0299.v1 Date: 2020-05-18 Source:

    A new coronavirus (SARS-CoV-2) have determined a pneumonia HP pneumonia MESHD outbreak in China (Wuhan and Hubei) on December 2019. While pharmaceutical and non-pharmaceutical intervention strategies are strengthened worldwide, the scientific community has been studying the risk factors associated with SARS-Cov-2, to enrich epidemiological information. For a long time, before the industrialized era, air pollution has been a real and big health concern and it is today a very serious environmental risk for many diseases MESHD and anticipated deaths in the world. It has long been known that air pollutants increasing the invasiveness of pathogens for humans by acting as a carrier TRANS and making people more sensitive to pathogens through a negative influence on the immune system. Based on scientific evidences, the hypothesis that air pollution, resulting from a combination of factors such as meteorological data, level of industrialization as well as regional topography, can acts both as an infection MESHD carrier TRANS as a harmful factor of the health outcomes of COVID-19 disease has been raised recently. This hypothesis is turning in scientific evidence, thanks to the numerous studies that have been launched all over the world. With this review, we want to provide a first unique view of all the first epidemiological studies relating the association between air pollution and SARS-CoV-2. Major findings are consistent, highlighting the important contribution of air pollution on the COVID-19 spread and with a less extent also PM10.

    Displacement ventilation: available ventilation strategy for makeshift hospitals and public buildings to contain Covid-19and other airborne diseases MESHD

    Authors: Rajesh Kumar Bhagat; Paul Linden

    doi:10.1101/2020.04.22.20075648 Date: 2020-04-28 Source: medRxiv

    The SARS-CoV-2 virus has so far infected more than2.4 million people around the world, and its impact is being felt by all. Patients with airborne diseases MESHD such as Covid-19 should ideally be treated in negative pressure isolation rooms. However, due to the overwhelming demand for hospital beds, patients treated in general wards, hospital corridors, and makeshift hospitals. Adequate building ventilationin hospitals and public spaces is a crucial factor to contain the disease [1,2], to exit the current lockdown situation, and reduce the chance of subsequent waves of outbreaks. Lu et al. [3] reported an air-conditioner induced Covid-19 outbreak, by an asymptomatic TRANS patient, in a restaurant in Guangzhou, China, which exposes our vulnerability to future outbreaks linked to ventilation in public spaces. We demonstrate that displacement ventilation(either mechanical or naturalventilation), where air intakes are at low level and extracts are at high level, is a viable alternative to negative pressure isolation rooms, which are often not available on site in hospital wards and makeshift hospitals. Displacement ventilation produces negative pressure at the occupant level, which draws fresh air from outdoor, and positive pressure near the ceiling, which expels the hot and contaminated air out. We acknowledge that, in both developed and developing countries, many modern large structures lack the openings required for natural ventilation. This lack of openings can be supplemented by installing extract fans. We provide guidelines for such mechanically assisted-naturally ventilated makeshift hospitals, and public spaces such as supermarkets and essential public buildings

    Ontological and Bioinformatic Analysis of Anti-Coronavirus Drugs and Their Implication for Drug Repurposing against COVID-19

    Authors: Yingtong Liu; Wallace K.B. Chan; Zhigang Wang; Junguk Hur; Jiangan Xie; Hong Yu; Yongqun He

    id:10.20944/preprints202003.0413.v1 Date: 2020-03-29 Source:

    Coronavirus-infected diseases MESHD have posed great threats to human health. In past years, highly infectious coronavirus-induced diseases MESHD, including COVID-19, SARS, and MERS, have resulted in world-wide severe infections HP. Our literature annotations identified 110 chemical drugs and 26 antibodies SERO effective against at least one human coronavirus infection MESHD in vitro or in vivo. Many of these drugs inhibit viral entry to cells and viral replication inside cells or modulate host immune responses. Many antimicrobial drugs, including antimalarial (e.g., chloroquine and mefloquine) and antifungal (e.g., terconazole and rapamycin) drugs as well as antibiotics (e.g., teicoplanin and azithromycin) were associated with anti-coronavirus activity. A few drugs, including remdesivir, chloroquine, favipiravir, and tocilizumab, have already been reported to be effective against SARS-CoV-2 infection MESHD in vitro or in vivo. After mapping our identified drugs to three ontologies ChEBI, NDF-RT, and DrON, many features such as roles and mechanisms of action (MoAs) of these drugs were identified and categorized. For example, out of 57 drugs with MoA annotations in NDF-RT, 47 have MoAs of different types of inhibitors and antagonists. A total of 29 anticoronaviral drugs are anticancer drugs with the antineoplastic role. Two clustering analyses, one based on ChEBI-based semantic similarity, the other based on drug chemical similarity, were performed to cluster 110 drugs to new categories. Moreover, differences in physicochemical properties among the drugs were found between those inhibiting viral entry and viral replication. A total of 163 host genes were identified as the known targets of 68 anti-coronavirus drugs, resulting in a network of 428 interactions among these drugs and targets. Chlorpromazine, dasatinib, and anisomycin are the hubs of the drug-target network with the highest number of connected target proteins. Many enriched pathways such as calcium signaling and neuroactive ligand-receptor interaction pathways were identified. These findings may be used to facilitate drug repurposing against COVID-19.

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MeSH Disease
Human Phenotype

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