Corpus overview


MeSH Disease

Human Phenotype


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    A Network Medicine Approach to Investigation and Population-based Validation of Disease MESHD Manifestations and Drug Repurposing for COVID-19

    Authors: Yadi Zhou; Yuan Hou; Jiayu Shen; Asha Kalianpur; Joe Zein; Daniel A. Culver; Samar Farha; Suzy Comhair; Claudio Fiocchi; Michaela U. Gack; Reena Mehra; Thaddeus S Stappenbeck; Timothy Chan; Charis Eng; Jae U. Jung; Lara Jehi; Serpil Erzurum; Feixiong Cheng

    doi:10.26434/chemrxiv.12579137.v1 Date: 2020-07-02 Source: ChemRxiv

    The global Coronavirus Disease MESHD 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2), has led to unprecedented social and economic consequences. The risk of morbidity and mortality due to COVID-19 increases dramatically in the presence of co-existing medical conditions while the underlying mechanisms remain unclear. Furthermore, there are no proven effective therapies for COVID-19. This study aims to identify SARS-CoV-2 pathogenesis, diseases MESHD manifestations, and COVID-19 therapies using network medicine methodologies along with clinical and multi-omics observations. We incorporate SARS-CoV-2 virus-host protein-protein interactions, transcriptomics, and proteomics into the human interactome. Network proximity measure revealed underlying pathogenesis for broad COVID-19-associated manifestations. Multi-modal analyses of single-cell RNA-sequencing data showed that co-expression of ACE2 and TMPRSS2 was elevated in absorptive enterocytes from the inflamed ileal tissues of Crohn's disease HP disease MESHD patients compared to uninflamed tissues, revealing shared pathobiology by COVID-19 and inflammatory bowel disease MESHD. Integrative analyses of metabolomics and transcriptomics (bulk and single-cell) data from asthma MESHD asthma HP patients indicated that COVID-19 shared intermediate inflammatory endophenotypes with asthma MESHD asthma HP (includingIRAK3 and ADRB2). To prioritize potential treatment, we combined network-based prediction and propensity score (PS) matching observational study of 18,118 patients from a COVID-19 registry. We identified that melatonin (odds ratio (OR) = 0.36, 95% confidence interval (CI) 0.22-0.59) was associated with 64% reduced likelihood of a positive laboratory test result for SARS-CoV-2. Using PS-matching user active comparator design, melatonin was associated with 54% reduced likelihood of SARS-CoV-2 positive test result compared to angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors (OR = 0.46, 95% CI 0.24-0.86).

    Ulcerative Colitis MESHD Ulcerative Colitis HP Developed in a COVID-19 Patient: A Case Report

    Authors: Muhammet Fatih Aydin; Hamit Tasdemir

    doi:10.21203/ Date: 2020-06-29 Source: ResearchSquare

    Background: COVID-19 pneumonia MESHD pneumonia HP is a widespread viral disease MESHD, which affects all the world and has been accepted as pandemic by the World Health Organization (WHO). Coronavirus can remain in the stool for certain time even after recovery from COVID-19 pneumonia MESHD pneumonia HP in some infected patients. Studies increasingly report involvement of other organs including gastrointestinal system in addition to respiratory symptoms in COVID-19. Ulcerative colitis MESHD Ulcerative colitis HP is an inflammatory bowel disease MESHD with unknown cause. Emerging data suggest that gastrointestinal system may also be influenced by COVID-19 based via the expression of ACE-2. However, data abour the association of COVID-19 and inflammatory bowel diseases MESHD including ulcerative colitis MESHD ulcerative colitis HP are lacking. Case Presentation: In this report, we present a case of ulcerative colitis MESHD ulcerative colitis HP diagnosed in a 50-year-old male TRANS patient who presented with the complaints of bloody diarrhea HP diarrhea MESHD and abdominal pain MESHD abdominal pain HP following the completion of the treatment of COVID-19 pneumonia MESHD pneumonia HP. Conclusion: Patients presenting with gastrointestnal complaints should also be evaluated for COVID-19.

    Does Biological Therapy Protect against Severe COVID-19?

    Authors: Ramon Mazzucchelli; Raquel Almodovar-Gonzalez; Natalia Crespi-Villarias; Elena Garcia-Zamora; Elia Perez-Fernandez; Javier Quiros-Donate; Monserrat Perez-Encinas; Patricia Sanmartin-Fenollera; Maria Velasco-Arribas; Pilar Lopez-Serrano; Jose lazaro Perez-Calle; Conrado Fernandez-Rodriguez; Jose Luis Lopez-Estebaranz; Pedro Zarco-Montejo

    doi:10.1101/2020.06.21.20136788 Date: 2020-06-24 Source: medRxiv

    Objective. To estimate COVID-19 infection MESHD incidence rate with severe affectation (requiring hospitalization) in patients with biological treatment due to rheumatoid arthritis MESHD rheumatoid arthritis HP (RA), psoriatic arthritis MESHD arthritis HP (PsA), spondyloarthritis (SpA), psoriasis MESHD (Ps), and inflammatory bowel disease MESHD (IBD) and compare it with incidence rate in the general population. Methods: Retrospective observational study based on information provided by two administrative databases. One of these two databases contains information on all patients seen in our hospital and diagnosed with COVID-19 infection MESHD between March 4th 2020 and April 26th 2020. The other database contains data from patients seen at Rheumatology, Dermatology and Digestive Departments in our hospital who are currently receiving biological therapy. We calculated the crude and age TRANS and sex adjusted incidence in both groups. To compare both groups we calculated the Incidence Rate Ratio. Results: There was a total of 2,182 patients with COVID-19 requiring hospitalization. Four patients out of a total of 797 patients receiving biological therapy had contracted COVID-19 and required hospital care. Crude incidence rate of COVID-19 requiring hospital care among the general population was 1.41%, and it was 0.50% among the group receiving biological therapy. Rates adjusted by age TRANS and sex in the biological group was 0.45% (CI95% 0.11-4.13). The IRR of the group receiving biological therapy compared to the general population was 0.39 (CI95% 0.14-1, p=0.049). Conclusion: Findings suggest that prior use of biological therapy does not associate with severe manifestations of COVID-19, and it is likely to have a protective effect against them when compared to the general population.

    Intestinal inflammation MESHD modulates the expression of ACE2 and TMPRSS2 and potentially overlaps with the pathogenesis of SARS-CoV-2 related disease MESHD

    Authors: Mayte Suárez-Fariñas; Minami Tokuyama; Gabrielle Wei; Ruiqi Huang; Alexandra Livanos; Divya Jha; Anais Levescot; Roman Kosoy; Haritz Irizar; Wenhui Wang; Ryan Ungaro; Antonio Di Narzo; Gustavo Martinez; Maria Suprun; Michael J Corley; Aleksandar Stojmirovic; Sander Houten; Mark Curran; Carrie Brodmerkel; Jacqueline Perrigoue; Joshua R Friedman; Ke Hao; Eric E Schadt; Jun Zhu; Huaibin M Ko; Judy Cho; Marla C Dubinsky; Bruce E Sands; Lishomwa Ndhlovu; Nadine Cerf-Bensusan; Andrew Kasarskis; Jean-Frederic Colombel; Noam Harpaz; Carmen Argmann; Saurabh Mehandru

    doi:10.1101/2020.05.21.109124 Date: 2020-05-23 Source: bioRxiv

    Immune dysregulation HP and cytokine release syndrome MESHD have emerged as pathological hallmarks of severe Coronavirus Disease MESHD 2019 (COVID-19), leading to the evaluation of cytokine antagonists as therapeutic agents. A number of immune-directed therapies being considered for COVID-19 patients are already in clinical use in chronic inflammatory conditions like inflammatory bowel disease MESHD (IBD). These considerations led us to systematically examine the intersections between COVID-19 and the GI tract during health and intestinal inflammation MESHD. We have observed that IBD medications, both biologic and non-biologic, do not significantly impact ACE2 and TMPRSS2 expression in the uninflamed intestines. Additionally, by comparing SARS CoV2-induced epithelial gene signatures with IBD-associated genes, we have identified a shared molecular subnetwork between COVID-19 and IBD. These data generate a novel appreciation of the confluence of COVID-19- and IBD-associated inflammation MESHD and provide mechanistic insights supporting further investigation of specific IBD drugs in the treatment of COVID-19.

    COVID-19 and Inflammatory Bowel Diseases MESHD: risk assessment, shared molecular pathways and therapeutic challenges

    Authors: Iolanda Valentina Popa; Mircea Diculescu; Catalina Mihai; Cristina Cijevschi-Prelipcean; Alexandru Burlacu

    doi:10.1101/2020.04.28.20082859 Date: 2020-05-01 Source: medRxiv

    Background. The novel coronavirus SARS-CoV-2 causing COVID-19 disease MESHD is yielding a global outbreak with serious threats to public health. In this paper, we aimed to review the current knowledge about COVID-19 infectious risk status in inflammatory bowel disease MESHD (IBD) patients requiring immunosuppressive medication. Also, we focused on several molecular insights that could explain why IBD patients appear to not have higher risks of infection TRANS risks of infection TRANS infection MESHD and worse outcome in COVID-19 than the general population, in attempt to provide scientific support for safer decisions in IBD patient care. Methods. PubMed electronic database was interogated for relevant articles involving data about common molecular pathways and shared treatment strategies between SARS-CoV-2, SARS-CoV-1, MERS-CoV and inflammatory bowel diseases MESHD. In addition, Neural Covidex, an artificial intelligence tool, was used to answer queries about pathogenic coronaviruses and possible IBD interactions using the COVID-19 Open Research Dataset (CORD-19). Discussions. Few molecular and therapeutic interactions between IBD and pathogenic coronaviruses were explored. First, we showed how the activity of soluble angiotensin-converting enzyme 2, CD209L alternate receptor and phosphorylated subunit of eukaryotic translation initiation factor 2 might exert protective impact in IBD in case of coronavirus infection MESHD. Second, IBD medication was discussed in the context of possible beneficial effects on COVID-19 pathogeny including "cytokine storm" prevention and treatment, immunomodulation, interferon signaling blocking, viral endocytosis inhibition. Conclusions. Using current understanding of SARS-CoV-2 as well as other pathogenic coronaviruses immunopathology, we showed why IBD patients should not be considered at an increased risk of infection TRANS risk of infection TRANS infection MESHD or more severe outcomes. Whether our findings are entirely applicable to the pathogenesis, disease susceptibility MESHD and treatment management of SARS-CoV-2 infection MESHD in IBD must be further explored.

    Reduced expression of COVID-19 host receptor, ACE2 is associated with small bowel inflammation MESHD, more severe disease MESHD, and response to anti-TNF therapy in Crohn's disease HP disease MESHD

    Authors: Alka A Potdar; Shishir Dube; Takeo Naito; Gregory Botwin; Talin Haritunians; Dalin Li; Shaohong Yang; Janine Bilsborough; Lee A Denson; Mark Daly; Stephan R Targan; Phillip Fleshner; Jonathan Braun; Subra Kugathasan; Thaddeus S Stappenbeck; Dermot P B McGovern

    doi:10.1101/2020.04.19.20070995 Date: 2020-04-23 Source: medRxiv

    Angiotensin-Converting Enzyme 2 (ACE2) has been identified as the host receptor for SARS-coronavirus 2 (SARS-CoV-2) which has infected millions world-wide and likely caused hundreds of thousands of deaths MESHD. Utilizing transcriptomic data from four cohorts taken from Crohn's disease HP disease MESHD (CD) and non- inflammatory bowel disease MESHD (IBD) subjects, we observed evidence of increased ACE2 mRNA in ileum with demographic features that have been associated with poor outcomes in COVID-19 including age TRANS and raised BMI. ACE2 was downregulated in CD compared to controls in independent cohorts. Within CD, ACE2 expression was reduced in inflamed ileal tissue and also remarkably, from uninvolved tissue in patients with a worse prognosis in both adult TRANS and pediatric cohorts. In active CD, small bowel ACE2 expression was restored by anti-TNF therapy particularly in anti-TNF responders. Collectively our data suggest that ACE2 downregulation is associated with inflammation MESHD and worse outcomes in CD.

    Questionnaire assessment helps the self-management of patients with inflammatory bowel disease MESHD during the outbreak of Coronavirus Disease MESHD 2019

    Authors: Meiping Yu; Zhenghao Ye; Yu Chen; Tingting Qin; Jiguang Kou; Dean Tian; Fang Xiao

    doi:10.1101/2020.03.25.20043364 Date: 2020-03-27 Source: medRxiv

    Background and Aims: The outbreak of Coronavirus Disease MESHD 2019 (COVID-19) may affect the disease MESHD status of patients with inflammatory bowel disease MESHD (IBD). This study aimed to assess the disease MESHD status of IBD patients in Hubei province by questionnaire online and guide to the self-management of IBD patients during this epidemic. Methods: A questionnaire was designed containing the Harvey-Bradshaw Index (HBI), the Partial Mayo Score (PMS), the short inflammatory bowel disease MESHD questionnaire (SIBDQ) and distributed to Hubei IBD patients online within one month of traffic control after the outbreak of COVID-19. This questionnaire also included some questions about patients' self-report disease MESHD conditions and their epidemiological history of COVID-19. Results: A total of 102 eligible questionnaires were included in the analysis. No patient reported infection MESHD infection with severe HP with severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) in our study. Our result showed that 69.64% of patients with ulcerative colitis MESHD ulcerative colitis HP (UC) and 80.44% of patients with Crohn's disease HP disease MESHD (CD) were in remission. There was not a statistically significant difference in the proportion of the active disease MESHD stage between the two types of disease MESHD (p=0.103). The majority of patients (85.29%) had a good health-related quality of life (HRQoL) (SIBDQ[≥]50). The reduction in physical exercise is a risk factor for worsening in conditions (OR=17.593, 95%CI 2.035 to 152.097, p=0.009). Conclusions: The outbreak of COVID-19 might not have a significant impact on most Hubei IBD patients within one month after the traffic control. The patient's disease MESHD condition could be assessed by our questionnaires. Doctors utilized the information and advised for IBD patients about self-management during the period of COVID-19.

    Exploring diseases MESHD/traits and blood SERO proteins causally related to expression of ACE2, the putative receptor of 2019-nCov: A Mendelian Randomization analysis

    Authors: Shitao Rao; Alexandria Lau; Hon-Cheong So

    doi:10.1101/2020.03.04.20031237 Date: 2020-03-08 Source: medRxiv

    COVID-19 has become a major public health problem globally. There is good evidence that ACE2 is a receptor for SARS-CoV-2, and high expression of ACE2 may increase susceptibility to infection MESHD. We aimed to explore risk factors affecting susceptibility to infection MESHD and prioritize drug repositioning candidates, based on Mendelian randomization (MR) studies on ACE2 lung expression. We conducted a phenome-wide MR study to prioritize diseases MESHD/traits and blood SERO proteins causally linked to ACE2 lung expression in GTEx. We also explored drug candidates whose targets overlapped with the top-ranked proteins in MR, as these drugs may alter ACE2 expression and may be clinically relevant. The most consistent finding was tentative evidence of an association between diabetes-related traits and increased ACE2 expression. Based on one of the largest GWAS on type 2 diabetes (T2DM) to date (N=898,130), T2DM was causally linked to raised ACE2 expression (p=2.91E-03;MR-IVW). Significant associations (at nominal level; p<0.05) with ACE2 expression was observed across multiple DM datasets and analytic methods, for type 1 and 2 diabetes and related traits including early start of insulin. Other diseases MESHD/traits having nominal significant associations with increased expression included inflammatory bowel disease MESHD, (ER+) breast and lung cancers, asthma MESHD asthma HP, smoking and elevated ALT. We also identified drugs that may target the top-ranked proteins in MR, such as fostamatinib and zinc. In conclusion, our analysis suggested that diabetes and related traits may increase ACE2 expression, which may influence susceptibility to infection MESHD (or more severe infection HP infection MESHD). However, none of these findings withstood rigorous multiple testing corrections (at FDR<0.05). Proteome-wide MR analyses might help uncover mechanisms underlying ACE2 expression and guide drug repositioning. Further studies are required to verify our findings.

    ACE2 expression by colonic epithelial cells is associated with viral infection MESHD, immunity and energy metabolism

    Authors: Jun Wang; Shanmeizi Zhao; Ming Liu; Zhiyao Zhao; Yiping Xu; Ping Wang; Meng Lin; Yanhui Xu; Bing Huang; Xiaoyu Zuo; Zhanghua Chen; Fan Bai; Jun Cui; Andrew M Lew; Jincun Zhao; Yan Zhang; Haibin Luo; Yuxia Zhang

    doi:10.1101/2020.02.05.20020545 Date: 2020-02-07 Source: medRxiv

    Respiratory disease MESHD caused by the 2019 novel coronavirus (2019-nCoV) pneumonia MESHD pneumonia HP first emerged in Wuhan, Hubei Province, China, in December 2019 and spread rapidly to other provinces and other countries. Angiotensin-converting enzyme 2 (ACE2) is the receptor for SARS-CoV and has been suggested to be also the receptor for 2019-nCoV. Paradoxically, ACE2 expression in the lung protects mice from SARS-CoV spike protein induced lung injury MESHD by attenuating the renin-angiotensin system. In the intestine, ACE2 also suppresses intestinal inflammation MESHD by maintaining amino acid homeostasis, antimicrobial peptide expression and ecology of the gut microbiome. Upon analysis of single cell-RNA sequencing data from control subjects and those with colitis MESHD colitis HP or inflammatory bowel disease MESHD (IBD), we found that ACE2 expression in the colonocytes was positively associated with genes regulating viral infection MESHD, innate and cellular immunity, but was negatively associated with viral transcription, protein translation, humoral immunity, phagocytosis and complement activation. In summary, we suggest that ACE2 may play dual roles in mediating the susceptibility and immunity of 2019-nCoV infection MESHD.

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MeSH Disease
Human Phenotype

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