Corpus overview


Overview

MeSH Disease

Human Phenotype

Transmission

Seroprevalence
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    SARS-CoV-2 Viral Load is Associated with Increased Disease MESHD Severity and Mortality

    Authors: Jesse M Fajnzylber; James Regan; Kendyll Coxen; Heather Corry; Colline Wong; Alexandra Rosenthal; Daniel Worrall; Francoise Giguel; Alicja Piechocka-Trocha; Caroline Atyeo; Stephanie Fischinger; Andrew Chan; Keith T Flaherty; Kathryn Hall; Michael Dougan; Edward T Ryan; Elizabeth Gillespie; Rida Chishti; Yijia Li; Nikolaus Jilg; Dusan Hanidziar; Rebecca M Baron; Lindsey Baden; Athe M Tsibris; Katrina A Armstrong; Daniel R Kuritzkes; Galit Alter; Bruce D Walker; Xu Yu; Jonathan Li; - Massachusetts Consortium for Pathogen Readiness

    doi:10.1101/2020.07.15.20131789 Date: 2020-07-17 Source: medRxiv

    The relationship between SARS-CoV-2 viral load and risk of disease progression MESHD remains largely undefined in coronavirus disease MESHD 2019 (COVID-19). We quantified SARS-CoV-2 viral load from participants with a diverse range of COVID-19 severity, including those requiring hospitalization, outpatients with mild disease MESHD, and individuals with resolved infection MESHD. SARS-CoV-2 plasma SERO RNA was detected in 27% of hospitalized participants and 13% of outpatients diagnosed with COVID-19. Amongst the participants hospitalized with COVID-19, higher prevalence SERO of detectable SARS-CoV-2 plasma SERO viral load was associated with worse respiratory disease MESHD severity, lower absolute lymphocyte counts, and increased markers of inflammation MESHD, including C-reactive protein and IL-6. SARS-CoV-2 viral loads, especially plasma SERO viremia MESHD viremia HP, were associated with increased risk of mortality. SARS-CoV-2 viral load may aid in the risk stratification of patients with COVID-19 and its role in disease MESHD pathogenesis should be further explored.

    SARS-CoV-2 Viral Load is Associated with Increased Disease MESHD Severity and Mortality

    Authors: Jesse Fajnzylber; James Regan; Kendyll Coxen; Heather Corry; Colline Wong; Alexandra Rosenthal; Daniel Worrall; Francoise Giguel; Alicja Piechocka-Trocha; Caroline Atyeo; Stephanie Fischinger; Andrew Chan; Keith Flaherty; Kathryn Hall; Michael Dougan; Edward Ryan; Elizabeth Gillespie; Rida Chishti; Yijia Li; Nikolaus Jilg; Dusan Hanidziar; Rebecca Baron; Lindsey Baden; Athe Tsibris; Katrina Armstrong; Galit Alter; Daniel Kuritzkes; Bruce Walker; Xu Yu; Jonathan Li

    doi:10.21203/rs.3.rs-43878/v1 Date: 2020-07-15 Source: ResearchSquare

    The relationship between SARS-CoV-2 viral load and risk of disease progression MESHD remains largely undefined in coronavirus disease MESHD 2019 (COVID-19). We quantified SARS-CoV-2 viral load from participants with a diverse range of COVID-19 severity, including those requiring hospitalization, outpatients with mild disease MESHD, and individuals with resolved infection MESHD. SARS-CoV-2 plasma SERO RNA was detected in 27% of hospitalized participants and 13% of outpatients diagnosed with COVID-19. Amongst the participants hospitalized with COVID-19, higher prevalence SERO of detectable SARS-CoV-2 plasma SERO viral load was associated with worse respiratory disease MESHD severity, lower absolute lymphocyte counts, and increased markers of inflammation MESHD, including C-reactive protein and IL-6. SARS-CoV-2 viral loads, especially plasma SERO viremia MESHD viremia HP, were associated with increased risk of mortality. SARS-CoV-2 viral load may aid in the risk stratification of patients with COVID-19 and its role in disease MESHD pathogenesis should be further explored.

    The antibody SERO response to the glycan α-Gal correlates with COVID-19 disease MESHD symptoms

    Authors: Jose Miguel Urra; Elisa Ferreras-Colino; Marinela Contreras; Carmen M Cabrera; Isabel G Fernandez de Mera; Margarita Villar; Christian Gortazar; Jose de la Fuente

    doi:10.1101/2020.07.14.201954 Date: 2020-07-14 Source: bioRxiv

    The coronavirus disease MESHD 19 (COVID-19) pandemic caused by severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) has affected millions of people worldwide. The characterization of the immunological mechanisms involved in disease MESHD symptomatology and protective response is important to advance in disease MESHD control and prevention. Humans evolved by losing the capacity to synthesize the glycan Gal1-3Gal{beta}1-(3)4GlcNAc-R (-Gal), which resulted in the development of a protective response against pathogenic viruses and other microorganisms containing this modification on membrane proteins mediated by anti--Gal IgM/IgG antibodies SERO produced in response to bacterial microbiota. In addition to anti--Gal antibody SERO-mediated pathogen opsonization, this glycan induces various immune mechanisms that have shown protection in animal models against infectious diseases MESHD without inflammatory responses. In this study, we hypothesized that the immune response to -Gal may contribute to the control of COVID-19. To address this hypothesis, we characterized the antibody SERO response to -Gal in patients at different stages of COVID-19 and in comparison with healthy control individuals. The results showed that while the inflammatory response and the anti-SARS-CoV-2 (Spike) IgG antibody SERO titers increased, reduction in anti--Gal IgE, IgM and IgG antibody SERO titers and alteration of anti--Gal antibody SERO isotype composition correlated with COVID-19 severity. The results suggested that the inhibition of the -Gal-induced immune response may translate into more aggressive viremia MESHD viremia HP and severe disease MESHD inflammatory symptoms. These results support the proposal of developing interventions such as probiotics based on commensal bacteria with -Gal epitopes to modify the microbiota and increase the -Gal-induced protective immune response and reduce the severity of COVID-19.

    A drug repurposing screen identifies hepatitis C MESHD hepatitis HP antivirals as inhibitors of the SARS-CoV-2 main protease.

    Authors: Jeremy D Baker; Rikki L Uhrich; Gerald C Kraemer; Jason E Love; Brian C Kraemer

    doi:10.1101/2020.07.10.197889 Date: 2020-07-10 Source: bioRxiv

    The SARS coronavirus type 2 (SARS-CoV-2) emerged in late 2019 as a zoonotic virus highly transmissible between humans that has caused the COVID-19 pandemic 1,2. This pandemic has the potential to disrupt healthcare globally and has already caused high levels of mortality, especially amongst the elderly TRANS. The overall case fatality rate for COVID-19 is estimated to be [~]2.3% overall 3 and 32.3% in hospitalized patients age TRANS 70-79 years 4. Therapeutic options for treating the underlying viremia MESHD viremia HP in COVID-19 are presently limited by a lack of effective SARS-CoV-2 antiviral drugs, although steroidal anti-inflammatory treatment can be helpful. A variety of potential antiviral targets for SARS-CoV-2 have been considered including the spike protein and replicase. Based upon previous successful antiviral drug development for HIV-1 and hepatitis C MESHD hepatitis HP, the SARS-CoV-2 main protease (Mpro) appears an attractive target for drug development. Here we show the existing pharmacopeia contains many drugs with potential for therapeutic repurposing as selective and potent inhibitors of SARS-CoV-2 Mpro. We screened a collection of [~]6,070 drugs with a previous history of use in humans for compounds that inhibit the activity of Mpro in vitro. In our primary screen we found [~]50 compounds with activity against Mpro (overall hit rate <0.75%). Subsequent dose validation studies demonstrated 8 dose responsive hits with an IC50 [≤] 50 M. Hits from our screen are enriched with hepatitis C MESHD hepatitis HP NS3/4A protease targeting drugs including Boceprevir (IC50=0.95 M), Ciluprevir (20.77M). Narlaprevir (IC50=1.10M), and Telaprevir (15.25M). These results demonstrate that some existing approved drugs can inhibit SARS-CoV-2 Mpro and that screen saturation of all approved drugs is both feasible and warranted. Taken together this work suggests previous large-scale commercial drug development initiatives targeting hepatitis C MESHD hepatitis HP NS3/4A viral protease should be revisited because some previous lead compounds may be more potent against SARS-CoV-2 Mpro than Boceprevir and suitable for rapid repurposing.

    Early postmortem mapping of SARS-CoV-2 RNA in patients with COVID-19 and correlation to tissue damage

    Authors: Stefanie Deinhardt-Emmer; Daniel Wittschieber; Juliane Sanft; Sandra Kleemann; Stefan Elschner; Karoline Frieda Haupt; Vanessa Vau; Clio Häring; Jürgen Rödel; Andreas Henke; Christina Ehrhardt; Michael Bauer; Mike Philipp; Nikolaus Gaßler; Sandor Nietzsche; Bettina Löffler; Gita Mall

    doi:10.1101/2020.07.01.182550 Date: 2020-07-02 Source: bioRxiv

    Clinical observations indicate that COVID-19 is a systemic disease MESHD. An investigation of the viral distribution within the human body in correlation to tissue damage can help understanding the pathophysiology of SARS-CoV-2 infection MESHD.We present a detailed mapping of viral RNA in 61 tissues and organs of 11 deceased patients with the diagnosis COVID-19. The autopsies were performed within the (very) early postmortem interval (mean: 5.6 hours) to avoid bias due to viral RNA and tissue degradation. Viral loads, blood SERO levels of cytokines, prothrombotic factors as well as macro- and micro-morphology were correlated.Very high (> 104 copies/ml) viral loads were detected in the lungs of most patients and then correlated to severe tissue damage. Intact viral particles could be verified in the lung tissue by transmission TRANS electron microscopy. Viral loads in the lymph nodes were associated with a loss of follicular architecture. Viral RNA was detected throughout further extra-pulmonary tissues and organs without visible tissue damage. Inflammatory cytokines as well as the prothrombotic factors were elevated in all patients.In conclusion, the dissemination of SARS-CoV-2-RNA throughout the body supports the hypothesis of a maladaptive host response with viremia MESHD viremia HP and multi-organ dysfunction.View Full Text

    Convalescent Plasma SERO Therapy for Covid-19: State of the Art

    Authors: Daniele Focosi; Julian Tang; Arthur Anderson; Marco Tuccori

    id:10.20944/preprints202004.0097.v7 Date: 2020-07-01 Source: Preprints.org

    Convalescent blood SERO product therapy has been introduced since early 1900s to treat emerging infectious disease MESHD based on the evidence that polyclonal neutralizing antibodies SERO can reduce duration of viremia MESHD viremia HP. Recent large outbreaks of viral diseases MESHD for whom effective antivirals or vaccines are still lacking has revamped the interest in convalescent plasma SERO as life-saving treatments. This review summarizes historical settings of application, and surveys current technologies for collection, manufacturing, pathogen inactivation, and banking, with a focus on COVID-19.

    Transplacental transmission TRANS of SARS-CoV-2 infection MESHD

    Authors: Alexandre Vivanti; Chistelle Vauloup-Fellous; Sophie Prevot; Veronique Zupan; Cecile Suffee; Jeremy Do Cao; Alexandra Benachi; Daniele De Luca

    doi:10.21203/rs.3.rs-28884/v1 Date: 2020-05-14 Source: ResearchSquare

    SARS-CoV-2 outbreak has spread and became the first pandemics of the century. SARS-CoV-2 infection MESHD is transmitted through droplets; other transmission TRANS routes have been hypothesized but never confirmed. So far, it has been unclear whether and how SARS-CoV-2 can be vertically transmitted from the mother to the fetus. We demonstrated for the first time the transplacental transmission TRANS of SARS-CoV-2 in a neonate born to mother infected in the last trimester. The transmission TRANS has been confirmed by a comprehensive virological study: SARS-CoV-2 transmission TRANS caused neonatal viremia MESHD viremia HP placental inflammation MESHD which has been demonstrated by histological examination and immunohistochemistry. The neonate presented with neurological manifestation, consistent with those described in adult TRANS patients. 

    Single-Cell RNA-seq Identifies Cell Subsets in Human Placenta That Highly Expresses Factors to Drive Pathogenesis of SARS-CoV-2

    Authors: Nancy Ashray; Anshul Bhide; Priyanka Chakarborty; Stacy Colaco; Anuradha Mishra; Karisma Chhabria; Mohit Kumar Jolly; Deepak Modi

    id:10.20944/preprints202005.0195.v1 Date: 2020-05-11 Source: Preprints.org

    Infection MESHD Infection by the Severe HP by the Severe Acute Respiratory Syndrome MESHD-Coronavirus-2 (SARS-CoV-2) results in the novel coronavirus disease MESHD COVID-19, which has posed a serious threat globally. Infection MESHD of SARS-CoV-2 during pregnancy is associated with complications like preterm labor and premature rupture of membranes HP rupture MESHD of membranes; a proportion of neonates born to the infected mothers are also positive for the virus. During pregnancy, the placental barrier protects the fetus from pathogens and ensures healthy development. However, whether or not SARS-CoV-2 can infect the placenta is unknown. Herein, utilizing single-cell RNA-seq data, we report that the SARS-CoV-2 binding receptor ACE2 and the S protein priming protease TMPRSS2 are co-expressed by a subset of syncytiotrophoblasts (STB) in the first trimester and extra villous trophoblasts (EVT) in the second trimester human placenta. The ACE2- and TMPRSS2-positive (ACE2+TMPRSS2+) placental subsets express mRNA for proteins involved in viral budding and replication. These cells also express mRNA for proteins that interact with SARS-CoV-2 structural and non-structural proteins in the host cells. We also discovered unique signatures of genes in ACE2+TMPRSS2+ STBs and EVTs. The ACE2+TMPRSS2+ STBs are highly differentiated cells and express genes involved mitochondrial metabolism and glucose transport. The second trimester ACE2+TMPRSS2+ EVTs are enriched for markers of endovascular trophoblasts. Further, both these subtypes abundantly expressed genes in Toll like receptor pathway, the second trimester EVTs (but not first trimester STBs) are also enriched for component of the JAK-STAT pathway that drive inflammation MESHD. To conclude, herein we uncovered the cellular targets for SARS-CoV-2 entry and show that these cells can potentially drive viremia MESHD viremia HP in the developing human placenta. Our results provide a basic framework towards understanding the paraphernalia involved in SARS-CoV-2 infections MESHD in pregnancy.

    Disruption of the CCL5/RANTES-CCR5 Pathway Restores Immune Homeostasis and Reduces Plasma SERO Viral Load in Critical COVID-19

    Authors: Bruce K Patterson; Harish Seethamraju; Kush Dhody; Michael J Corley; Kazemm Kazempour; Jay P Lalezari; Alina PS Pang; Christopher Sugai; Edgar B Francisco; Amruta Pise; Hallison Rodrigues; Matthew Ryou; Helen L Wu; Gabriela M Webb; Byung S Park; Scott Kelly; Nadar Pourhassan; Alena Lelic; Lama Kdouh; Monica Herrera; Eric Hall; Enver Aklin; Lishomwa Ndhlovu; Jonah B Sacha

    doi:10.1101/2020.05.02.20084673 Date: 2020-05-05 Source: medRxiv

    Severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease MESHD 2019 (COVID-19), is now pandemic with nearly three million cases reported to date. Although the majority of COVID-19 patients experience only mild or moderate symptoms, a subset will progress to severe disease MESHD with pneumonia MESHD pneumonia HP and acute respiratory distress HP syndrome MESHD (ARDS) requiring mechanical ventilation. Emerging results indicate a dysregulated immune response characterized by runaway inflammation MESHD, including cytokine release syndrome MESHD (CRS), as the major driver of pathology in severe COVID-19. With no treatments currently approved for COVID-19, therapeutics to prevent or treat the excessive inflammation MESHD in severe disease MESHD caused by SARS-CoV-2 infection MESHD are urgently needed. Here, in 10 terminally-ill, critical COVID-19 patients we report profound elevation of plasma SERO IL-6 and CCL5 (RANTES), decreased CD8+ T cell levels, and SARS-CoV-2 plasma SERO viremia MESHD viremia HP. Following compassionate care treatment with the CCR5 blocking antibody SERO leronlimab, we observed complete CCR5 receptor occupancy on macrophage and T cells, rapid reduction of plasma SERO IL-6, restoration of the CD4/CD8 ratio, and a significant decrease in SARS-CoV-2 plasma SERO viremia MESHD viremia HP. Consistent with reduction of plasma SERO IL-6, single-cell RNA-sequencing revealed declines in transcriptomic myeloid cell clusters expressing IL-6 and interferon-related genes. These results demonstrate a novel approach to resolving unchecked inflammation MESHD, restoring immunologic deficiencies, and reducing SARS-CoV-2 plasma SERO viral load via disruption of the CCL5-CCR5 axis, and support randomized clinical trials to assess clinical efficacy of leronlimab-mediated inhibition of CCR5 for COVID-19.

    Disruption of the CCL5/RANTES-CCR5 Pathway Restores Immune Homeostasis and Reduces Plasma SERO Viral Load in Critical COVID-19

    Authors: Bruce Pattterson; Harish Seetthamraju; Kush Dhody; Michael Corley; Kazem Kazempour; Jay Lalezari; Alina Pang; Christopher Sugai; Edgar Francisco; Amruta Pise; Hallison Rodrigues; Matthew Ryou; Helen Wu; Gabriela Webb; Byung Park; Scott Kelly; Nader Pourhassan; Alena Lelic; Lama Kdouh; Monica Herrera; Eric Hall; Enver Aklin; Lishomwa Ndhlovu; Jonah Sacha

    doi:10.21203/rs.3.rs-26517/v1 Date: 2020-05-02 Source: ResearchSquare

    Severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease MESHD 2019 (COVID-19), is now pandemic with nearly three million cases reported to date1. Although the majority of COVID-19 patients experience only mild or moderate symptoms, a subset will progress to severe disease MESHD with pneumonia MESHD pneumonia HP and acute respiratory distress HP syndrome MESHD (ARDS) requiring mechanical ventilation2. Emerging results indicate a dysregulated immune response characterized by runaway inflammation MESHD, including cytokine release syndrome MESHD (CRS), as the major driver of pathology in severe COVID-193,4. With no treatments currently approved for COVID-19, therapeutics to prevent or treat the excessive inflammation MESHD in severe disease MESHD caused by SARS-CoV-2 infection MESHD are urgently needed. Here, in 10 terminally-ill, critical COVID-19 patients we report profound elevation of plasma SERO IL-6 and CCL5 (RANTES), decreased CD8+ T cell levels, and SARS-CoV-2 plasma SERO viremia MESHD viremia HP. Following compassionate care treatment with the CCR5 blocking antibody SERO leronlimab, we observed complete CCR5 receptor occupancy on macrophage and T cells, rapid reduction of plasma SERO IL-6, restoration of the CD4/CD8 ratio, and a significant decrease in SARS-CoV-2 plasma SERO viremia MESHD viremia HP. Consistent with reduction of plasma SERO IL-6, single-cell RNA-sequencing revealed declines in transcriptomic myeloid cell clusters expressing IL-6 and interferon-related genes. These results demonstrate a novel approach to resolving unchecked inflammation MESHD, restoring immunologic deficiencies, and reducing SARS-CoV-2 plasma SERO viral load via disruption of the CCL5-CCR5 axis, and support randomized clinical trials to assess clinical efficacy of leronlimab-mediated inhibition of CCR5 for COVID-19.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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