Corpus overview


MeSH Disease

Human Phenotype


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    Molecular Basis of Kidney Defects in COVID-19 Patients

    Authors: Smartya Pulai; Madhurima Basu; Chinmay Saha; Nitai P. Bhattacharyya; Arpita Ray Chaudhury; Sujoy Ghosh

    id:10.20944/preprints202007.0452.v1 Date: 2020-07-20 Source:

    Background: Kidney damage is considered to be one of the risk factors for severity and mortality among COVID-19 patients. However, molecular nature of such observations remains unknown. Hypothesis: Altered gene expressions due to infection MESHD infection and in chronic HP and in chronic kidney disease MESHD could explain severity in COVID-19 with kidney defects. Methods: We collected gene expression data from publicly available resources Gene Expression Omnibus CKD, Enrichr for deregulated genes in SARS-CoV infected cells in vitro, DisGeNET and others and carried out enrichment analysis using Enrichr. Result: Number of common genes altered in chronic kidney disease HP kidney disease MESHD (CKD) and SARS-CoV infected cells was 2834. Enrichment analysis revealed that biological processes related viral life cycle and growth, cytokines, immunity, interferon, inflammation MESHD, apoptosis, autophagy, oxidative stress and others were significantly enriched with common deregulated genes. Similarly, significantly enriched pathways related to viral and bacterial infections MESHD, immunity and inflammation MESHD, cell cycle, ubiquitin mediated proteolysis, signaling pathways like Relaxin signaling pathway, mTOR signaling pathway, IL-17 signaling pathway, NF-kappa B signaling pathway were enriched with the common deregulated genes. These processes and pathways are known to be related to kidney damage. DisGeNET terms enriched include and related to Dengue MESHD fever MESHD fever HP, chronic Hepatitis MESHD chronic Hepatitis HP, measles MESHD, retroviridae infections MESHD, respiratory syncytial virus Infections MESHD and many others. Kidney dysfunction related terms ischemia MESHD of kidney, renal fibrosis HP fibrosis MESHD and diabetic nephropathy MESHD nephropathy HP. Conclusion: Common deregulated genes in SARS-CoV infected cells and chronic kidney disease HP kidney disease MESHD, as well as their enrichment with molecular processes and pathways relevant for viral pathogenesis and renal dysfunctions, could explain the severity of COVID-19 with kidney disease MESHD. This observation not only provides molecular relation of severity in COVID-19 with renal dysfunctions but might also help in the management and treatment targets for these cases.

    IL-33 expression in response to SARS-CoV-2 correlates with seropositivity in COVID-19 convalescent individuals

    Authors: Michal A Stanczak; David E Sanin; Petya Apostolova; Gabriele Nerz; Dimitrios Lampaki; Maike Hofmann; Daniel Steinmann; Robert Thimme; Gerhard Mittler; Cornelius F Waller; Edward J Pearce; Erika L Pearce

    doi:10.1101/2020.07.09.20148056 Date: 2020-07-10 Source: medRxiv

    Our understanding of severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) is still developing. We investigated seroprevalence SERO and immune responses in subjects professionally exposed to SARS-CoV-2 and their family members TRANS (155 individuals; ages TRANS 5-79 years). Seropositivity for SARS-CoV-2 spike glycoprotein aligned with PCR results that confirmed previous infection MESHD. Anti-spike IgG titers remained high 60 days post- infection MESHD and did not associate with symptoms, but spike-specific IgM did associate with malaise and fever MESHD fever HP. We found limited household transmission TRANS, with children TRANS of infected individuals seldomly seropositive, highlighting professional exposure as the dominant route of infection MESHD in our cohort. We analyzed PBMCs from a subset of seropositive and seronegative adults TRANS. TLR7 agonist- activation revealed an increased population of IL-6+TNF-IL-1{beta}+ monocytes, while SARS-CoV-2 peptide stimulation elicited IL-33, IL-6, IFNa2, and IL-23 expression in seropositive individuals. IL-33 correlated with CD4+ T cell activation in PBMCs from convalescent subjects, and was likely due to T cell-mediated effects on IL-33- producing cells. IL-33 is associated with pulmonary infection MESHD infection and chronic HP and chronic diseases MESHD like asthma MESHD asthma HP and COPD, but its role in COVID-19 is unknown. Analysis of published scRNAseq data of bronchoalveolar lavage fluid (BALF) from patients with mild to severe COVID-19 revealed a population of IL-33-producing cells that increases with disease MESHD. Together these findings show that IL-33 production is linked to SARS-CoV- 2 infection MESHD and warrant further investigation of IL-33 in COVID-19 pathogenesis and immunity.

    Profiling pre-symptomatic and asymptomatic TRANS cases with confirmed TRANS SARS-CoV-2 infection MESHD in Mexico City

    Authors: Omar Yaxmehen Bello-Chavolla; Neftali Eduardo Antonio-Villa; Arsenio Vargas-Vázquez; Carlos A. Fermín-Martínez; Alejandro Márquez-Salinas; Jessica Paola Bahena-López

    doi:10.1101/2020.07.02.20145516 Date: 2020-07-04 Source: medRxiv

    BACKGROUND: Asymptomatic TRANS SARS-CoV-2 infections MESHD are potential sources for transmission TRANS. OBJECTIVES: Here, we aimed to profile pre-symptomatic/ asymptomatic TRANS SARS-CoV-2 infections MESHD in Mexico City, its associated comorbidities and outcomes. METHODS: Prospective observational study of SARS-CoV-2 cases assessed by contact tracing TRANS within the National Epidemiological Surveillance System in Mexico City. We classified subjects as cases with and without respiratory and non-respiratory symptoms (RS, NRS, respectively) assessed for SARS-CoV-2 using real time RT-PCR from nasopharyngeal swabs to evaluate clinical characteristics as well as features associated with severe COVID-19. RESULTS: Amongst 80735 cases with confirmed TRANS SARS-CoV-2 infection MESHD as of July 23th, 2020, we identified 9659 cases without RS (12.0%), 5605 had only NRS (6.9%) and 4054 who were initially asymptomatic TRANS (5.1%). Compared to asymptomatic TRANS cases, those with NRS and those with RS+NRS had higher rates of severe COVID-19 outcomes including hospitalization, ICU admission, and intubation (p<0.001). Mortality was higher for cases with RS+NRS (HR 7.58, 95%CI 4.56-12.58) or NRS (HR 3.13, 95%CI 1.80-5.45) compared to asymptomatic TRANS cases, adjusted for age TRANS, sex and comorbidities. Predictors for mortality in asymptomatic TRANS SARS-Co-V-2 infections MESHD infections, chronic HP, chronic kidney disease MESHD, previous exposure with suspected infection MESHD cases and older age TRANS were predictors for lethality. CONCLUSIONS: Definition of pre-symptomatic/ asymptomatic TRANS cases has relevant implications for SARS-CoV-2 infection MESHD outcomes. Older age TRANS and comorbidity impact on the probability of developing severe complications for cases who were asymptomatic TRANS or had only NRS at evaluation and were sent for domiciliary treatment. Extending testing for detection of asymptomatic TRANS cases must be considered in Mexico to better understand the impact of the pandemic.

    SARS-CoV-2 Spike protein binds to bacterial lipopolysaccharide and boosts proinflammatory activity

    Authors: Ganna Petruk; Manoj Puthia; Jitka Petrlova; Ann-Charlotte Strömdahl; Sven Kjellström; Artur Schmidtchen

    doi:10.1101/2020.06.29.175844 Date: 2020-06-29 Source: bioRxiv

    ABSTRACTThere is a well-known and established link between high lipopolysaccharide (LPS) levels in blood SERO and the metabolic syndrome MESHD (MS). MS is a risk factor for developing severe COVID-19 and acute respiratory distress HP syndrome MESHD (ARDS). Here we define an interaction between SARS-CoV-2 Spike (S) protein and LPS and its link to aggravated inflammation MESHD in vitro and in vivo. Electrophoresis under native conditions demonstrated that SARS-CoV-2 S protein binds to Escherichia coli LPS, forming high molecular weight aggregates. Microscale thermophoresis analysis further defined the interaction, having a KD of ~47 nM, similar to the observed affinity between LPS and the human receptor CD14. Moreover, S protein, when combined with low levels of LPS, boosted nuclear factor-kappa B (NF-κB) and cytokine responses in monocytic THP-1 cells and human blood SERO, respectively. In an experimental model of localized inflammation MESHD, employing NF-κB reporter mice and in vivo bioimaging, S protein in conjunction with LPS significantly increased the inflammatory response HP when compared with S protein and LPS alone. Apart from providing information on LPS as a ligand for S protein, our results are of relevance for studies on comorbidities involving bacterial endotoxins, such as the MS, or co-existing acute and chronic infections HP infections MESHD in COVID-19 patients.Competing Interest StatementA.S is a founder and shareholder of in2cure AB, a company developing therapies based on host defense peptides. A patent application related to the present work, with A.S. and G.P. listed as inventors, has been filed.AbbreviationsARDSacute respiratory distress HP syndromeCOVID-19coronavirus disease MESHD 2019MSmetabolic syndromeLBPLPS-binding proteinLPSlipopolysaccharideNF-κBnuclear factor-kappa BSARS-CoV-2 Spike proteinS proteinTLR4Toll-like receptor 4View Full Text

    Chronic treatment with hydroxychloroquine and SARS-CoV-2 infection MESHD.

    Authors: Antonio Ferreira; Antonio Oliveira-e-Silva; Paulo Bettencourt

    doi:10.1101/2020.06.26.20056507 Date: 2020-06-29 Source: medRxiv

    Background: Hydroxychloroquine sulphate (HCQ) is being scrutinized for repositioning in the treatment and prevention of SARS-Cov-2 infection MESHD. This antimalarial drug is also chronically used to treat patients with autoimmune diseases MESHD. Methods: By analyzing the Portuguese anonymized data on private and public based medical prescriptions we have identified all cases chronically receiving HCQ for the management of diseases MESHD such as systemic lupus erythematosus MESHD systemic lupus erythematosus HP, rheumatoid arthritis MESHD rheumatoid arthritis HP, and other autoimmune diseases MESHD. Additionally, we have detected all laboratory confirmed cases TRANS of SARS-CoV-2 infection and all laboratory MESHD confirmed negative cases in the Portuguese population (mandatorily registered in a centrally managed database). Cross linking the two sets of data has allowed us to compare the proportion of HCQ chronic treatment (at least 2 grams per month) in laboratory confirmed cases TRANS of SARS-CoV-2 infection with laboratory MESHD confirmed negative cases. Results: Out of 26,815 SARS-CoV-2 positive patients, 77 (0.29%) were chronically treated with HCQ, while 1,215 (0.36%) out of 333,489 negative patients were receiving it chronically (P=0.04). After adjustment for age TRANS, sex, and chronic treatment with corticosteroids and/or immunosuppressants, the odds ratio of SARS-CoV-2 infection MESHD infection for chronic HP for chronic treatment with HCQ has been 0.51 (0.37-0.70). Conclusions: Our data suggest that chronic treatment with HCQ confer protection against SARS-CoV-2 infection MESHD.

    Interactions of SARS-CoV-2 infection MESHD infection with chronic HP with chronic obesity MESHD obesity HP inflammation MESHD: a complex network phenomenon

    Authors: Giovani Marino Favero; Luis Paulo Gomes Mascarenhas; Meirielly Furmann; Juliana Berton; Pedro Jeferson Miranda

    doi:10.1101/2020.06.12.148577 Date: 2020-06-12 Source: bioRxiv

    Obesity MESHD Obesity HP is one of the biggest public health problems in the world, and its pathophysiological characteristics include chronic inflammation MESHD with an increase in various circulating inflammatory markers, such as acute inflammatory cytokines. Complications in the respiratory tract are related to bodily problems, which lead to a restriction of lung function due to reduced volume, inducing an increase in respiratory work. SARS-CoV-2 has a high potential for contamination by respiratory secretions and, therefore, obesity MESHD obesity HP is one of the main risk factors for complications due to the association established between obesity MESHD obesity HP, chronic inflammation MESHD and respiratory infection MESHD. The objective was to analyze the complex relationships between obesity MESHD obesity HP and COVID-19 in a meta-analysis study using complex network modeling and the theoretical knockouts technique. Here, we identify and justify through a mathematical analysis the relationships between all the immunological agents added to the proposed immunological networks, considered as a simple evident interaction, relationship, influence, response, activation, based on our quantifiers. They performed the knockouts of all 52 vertices in the COVID-19 network and obesity MESHD obesity HP - regardless of the environment, which would result in nonsense - and the COVID-19 infection MESHD network without considering obesity MESHD obesity HP. The stationary flow vector (flow profile), for some knockouts of immunological interest in COVID-19 infections MESHD, was chosen IFN, IL-6, IL-10, IL-17 and TNF. This initial study pointed out the importance of chronic inflammation MESHD in the obese individual as an important factor in potentiating the disease MESHD caused by covid-19 and, in particular, the importance on IL-17.

    Comorbidity and its impact on 1,590 patients with COVID-19 in China: A Nationwide Analysis

    Authors: Wei-jie Guan; Wen-hua Liang; Yi Zhao; Heng-rui Liang; Zi-sheng Chen; Yi-min Li; Xiao-qing Liu; Ru-chong Chen; Chun-li Tang; Tao Wang; Chun-quan Ou; Li Li; Ping-yan Chen; Ling Sang; Wei Wang; Jian-fu Li; Cai-chen Li; Li-min Ou; Bo Cheng; Shan Xiong; Zheng-yi Ni; Yu Hu; Jie Xiang; Lei Liu; Hong Shan; Chun-liang Lei; Yi-xiang Peng; Li Wei; Yong Liu; Ya-hua Hu; Peng Peng; Jian-ming Wang; Ji-yang Liu; Zhong Chen; Gang Li; Zhi-jian Zheng; Shao-qin Qiu; Jie Luo; Chang-jiang Ye; Shao-yong Zhu; Lin-ling Cheng; Feng Ye; Shi-yue Li; Jin-ping Zheng; Nuo-fu Zhang; Nan-shan Zhong; Jian-xing He

    doi:10.1101/2020.02.25.20027664 Date: 2020-02-27 Source: medRxiv

    Objective: To evaluate the spectrum of comorbidities and its impact on the clinical outcome in patients with coronavirus disease MESHD 2019 (COVID-19). Design: Retrospective case studies Setting: 575 hospitals in 31 province/autonomous regions/provincial municipalities across China Participants: 1,590 laboratory-confirmed hospitalized patients. Data were collected from November 21st, 2019 to January 31st, 2020. Main outcomes and measures: Epidemiological and clinical variables (in particular, comorbidities) were extracted from medical charts. The disease MESHD severity was categorized based on the American Thoracic Society guidelines for community-acquired pneumonia MESHD pneumonia HP. The primary endpoint was the composite endpoints, which consisted of the admission to intensive care unit (ICU), or invasive ventilation, or death MESHD. The risk of reaching to the composite endpoints was compared among patients with COVID-19 according to the presence and number of comorbidities. Results: Of the 1,590 cases, the mean age TRANS was 48.9 years. 686 patients (42.7%) were females TRANS. 647 (40.7%) patients were managed inside Hubei province, and 1,334 (83.9%) patients had a contact history of Wuhan city. Severe cases accounted for 16.0% of the study population. 131 (8.2%) patients reached to the composite endpoints. 399 (25.1%) reported having at least one comorbidity. 269 (16.9%), 59 (3.7%), 30 (1.9%), 130 (8.2%), 28 (1.8%), 24 (1.5%), 21 (1.3%), 18 (1.1%) and 3 (0.2%) patients reported having hypertension MESHD hypertension HP, cardiovascular diseases MESHD, cerebrovascular diseases MESHD, diabetes, hepatitis B MESHD hepatitis HP infections MESHD infections, chronic HP, chronic obstructive pulmonary disease MESHD obstructive pulmonary disease, chronic HP kidney diseases MESHD, malignancy and immunodeficiency HP, respectively. 130 (8.2%) patients reported having two or more comorbidities. Patients with two or more comorbidities had significantly escalated risks of reaching to the composite endpoint compared with those who had a single comorbidity, and even more so as compared with those without (all P<0.05). After adjusting for age TRANS and smoking status, patients with COPD (HR 2.681, 95%CI 1.424-5.048), diabetes (HR 1.59, 95%CI 1.03-2.45), hypertension MESHD hypertension HP (HR 1.58, 95%CI 1.07-2.32) and malignancy (HR 3.50, 95%CI 1.60-7.64) were more likely to reach to the composite endpoints than those without. As compared with patients without comorbidity, the HR (95%CI) was 1.79 (95%CI 1.16-2.77) among patients with at least one comorbidity and 2.59 (95%CI 1.61-4.17) among patients with two or more comorbidities. Conclusion: Comorbidities are present in around one fourth of patients with COVID-19 in China, and predispose to poorer clinical outcomes.

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MeSH Disease
Human Phenotype

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