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SARS-CoV-2 proteins

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    A Meta-analysis of Comorbidities in COVID-19 MESHD: Which Diseases increase the Susceptibility of SARS-CoV-2 Infection MESHD?

    Authors: Srinivasan Ramachandran; Manoj Kumar Singh; Ahmed Mobeen; Amit Chandra; Sweta Joshi

    id:10.20944/preprints202009.0486.v1 Date: 2020-09-21 Source: Preprints.org

    Background: Comorbidities have been frequently reported in COVID-19 MESHD patients, which often lead to more severe outcomes. The underlying molecular mechanisms behind these clinical observations have not yet been explained. Herein, we investigated the disease-specific gene expression signatures that may induce susceptibility to SARS-CoV-2 infection MESHD. Methods: We studied 30 frequently occurring acute, chronic, or infectious diseases of recent times that have shown comorbidity in one or another respiratory disease MESHD(s) caused by pathogenic human infecting coronaviruses, especially SARS-CoV-2. We retrieved array-based gene expression data for each disease and control from relevant datasets. Subsequently, all the datasets were quantile normalized, and log-2 transformed data was used for analysis. Results The expression of ACE2 HGNC receptor and host proteases, namely FURIN HGNC and TMPRSS2 HGNC that are essential for cellular entry of SARS-CoV-2, was upregulated in all six studied subtypes of leukemia MESHD (hereafter, referred as leukemia MESHD). The expression of ACE2 HGNC was also increased in psoriasis MESHD, lung cancer MESHD, Non-alcoholic fatty liver disease MESHD ( NAFLD MESHD), breast cancer MESHD, and pulmonary arterial hypertension MESHD patients. The expression of FURIN HGNC was higher in psoriasis MESHD, NAFLD MESHD, lung cancer MESHD, and in type II diabetic liver MESHD, whereas it was lowered in breast cancer MESHD. Similarly, the expression of TMPRSS2 HGNC was increased during lung cancer MESHD and type II diabetes MESHD; it was decreased during psoriasis MESHD, NAFLD MESHD, lung cancer MESHD, breast cancer MESHD, and cervical cancer MESHD.Furthermore, a heightened expression of genes that are involved in immune response was observed in leukemia MESHD patients, as shown by the higher expression of IFNA2 HGNC, IFNA8 HGNC, IFNA10 HGNC, IFNA14 HGNC, IFNA16 HGNC, IFNA21 HGNC, IFNB1 HGNC, CXCL10 HGNC, and IL6 HGNC. The expression of JAK1 HGNC, STAT1 HGNC, IL6 HGNC, and CXCL10 HGNC was higher in NAFLD MESHD. Besides, JAK1 HGNC and STAT1 HGNC were upregulated in type II diabetic muscles MESHD. In addition, most of the upregulated genes in COVID-19 MESHD patients showed a similar trend in leukemia MESHD, NAFLD MESHD, and psoriasis MESHD. Furthermore, SARS-CoV-2, SARS-CoV MESHD and MERS CoV, were found to commonly alter two genes, namely, CARBONIC ANHYDRASE 11 and CLUSTERIN.Conclusions: The genes that may confer susceptibility to SARS-CoV-2 infection MESHD are mostly upregulated in leukemia MESHD patients; hence, leukemia MESHD patients are relatively more susceptible to develop COVID-19 MESHD, followed by other chronic disorders MESHD, such as, NAFLD MESHD, type II diabetes MESHD, psoriasis MESHD, and hypertension MESHD. This study identifies key genes that are altered in the studied diseases types, which may aid in the infection of SARS-CoV-2 MESHD and underlie COVID-19 MESHD associated comorbidities.

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

    Phase II randomized controlled trial to evaluate the efficacy and safety of HeberFERON versus Heberon alpha R in symptomatic or asymptomatic patients infected with the SARS-CoV-2 (Study ESPERANZA/HOPE).

    Authors: Bello-Rivero Iraldo; Francisco Hernandez-Bernal; Hugo Nodarse-Cuni; Yaquelin Duncan-Roberts; Claudia Martínez Suarez; Ivan Campa-Legrá; Idelsis Esquivel-Moynelo; Verena Muzio-Gonzalez; Gerardo Guillen-Nieto

    doi:10.21203/rs.3.rs-28958/v2 Date: 2020-05-14 Source: ResearchSquare

    Background: As the outbreak of COVID-19 MESHD has accelerated, an urgent need for finding strategies to combat the virus is growing. Results from in vitro studies suggest that a combination of IFN type I and Type II MESHD may be effective against SARS-CoV MESHD. The aim of this study is to investigate the efficacy of treatment with a recombinant IFN alpha 2b HGNC and gamma, provided with standard protocol (Kaletra (lopinavir-ritonavir 200/50 mg; 200/100 mg every 12 hour for 30 days; Chloroquine (250 mg) every 12 hours for 10 days) for COVID-19 MESHD patients, compared to standard protocol ( IFN alpha 2b HGNC/Kaletra/Chloroquine) for COVID-19 MESHD hospitalized patients, positive diagnosed for SARS-Cov-2. Methods: Hospitalized adult patients with qPCR confirmed SARS-Cov-2 will be enrolled in this open-labeled, single center, prospective, randomized and controlled clinical trial. One hundred and twenty eligible patients with confirmed SARS-CoV-2 positivity by qPCR amplification in oropharyngeal/nasopharyngeal swab samples will be enrolled at “Luis Diaz Soto” Hospital, Havana, Cuba. The primary outcomes are the time to 2019-nCoV RNA negativity in patients and the time until progression to severe COVID-19 MESHD. Discussion: This will be the first randomized controlled trial of a potential treatment for SARC-Cov-2 using the combinations of IFNs. Trial registration: The study is sponsored by Center for Genetic and Biotechnology and Ministry of Health of Cuba and was duly registered April 2020 at http://registroclinico.sld.cu/en/trials/RPCEC00000307-En. Enrolment for this study began in April 11, 2020, and has enrolled one hundred patients as of May-26-2020.

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SARS-CoV-2 Proteins


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