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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (42)

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NSP5 (9)

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    COLI-NET: Fully Automated COVID-19 MESHD Lung and Infection Pneumonia Lesion MESHD Detection and Segmentation from Chest CT Images

    Authors: Isaac Shiri; Hossein Arabi; Yazdan Salimi; Amir Hossein Sanaat; Azadeh Akhavanalaf; Ghasem Hajianfar; Dariush Askari; Shakiba Moradi; Zahra Mansouri; Masoumeh Pakbin; Saleh Sandoughdaran; Hamid Abdollahi; Amir Reza Radmard; Kiara Rezaei-Kalantari; Mostafa Ghelich Oghli; Habib Zaidi

    doi:10.1101/2021.04.08.21255163 Date: 2021-04-13 Source: medRxiv

    Background We present a deep learning ( DL MESHD)-based automated whole lung and COVID-19 MESHD pneumonia infectious lesions MESHD (COLI-Net) detection and segmentation from chest CT images. Methods We prepared 2358 ( 347259, 2D slices) and 180 (17341, 2D slices) volumetric CT images along with their corresponding manual segmentation of lungs and lesions, respectively, in the framework of a multi-center/multi-scanner study. All images were cropped, resized and the intensity values clipped and normalized. A residual network (ResNet) with non-square Dice loss function built upon TensorFlow was employed. The accuracy of lung and COVID-19 MESHD lesions segmentation was evaluated on an external RT-PCR positive COVID-19 MESHD dataset (7333, 2D slices) collected at five different centers. To evaluate the segmentation performance, we calculated different quantitative metrics, including radiomic features. Results The mean Dice coefficients were 0.98&0.011 (95% CI, 0.98-0.99) and 0.91&0.038 (95% CI, 0.90-0.91) for lung and lesions segmentation, respectively. The mean relative Hounsfield unit differences were 0.03&0.84% (95% CI, -0.12-0.18) and -0.18&3.4% (95% CI, -0.8 - 0.44) for the lung and lesions, respectively. The relative volume difference for lung and lesions were 0.38&1.2% (95% CI, 0.16-0.59) and 0.81&6.6% (95% CI, -0.39-2), respectively. Most radiomic features had a mean relative error less than 5% with the highest mean relative error achieved for the lung for the Range first-order feature (-6.95%) and least axis length shape feature (8.68%) for lesions. Conclusion We set out to develop an automated deep learning-guided three-dimensional whole lung and infected regions segmentation in COVID-19 MESHD patients in order to develop fast, consistent, robust and human error immune framework for lung and pneumonia lesion MESHD detection and quantification. Keywords: X-ray CT, COVID-19 MESHD, pneumonia MESHD, deep learning MESHD, segmentation.

    ADAM17 inhibition prevents neutrophilia MESHD and lung injury MESHD in a mouse model of Covid-19 MESHD

    Authors: Nathaniel L. Lartey; Salvador Valle-Reyes; Hilda Vargas-Robles; Karina E. Jiménez-Camacho; Idaira M. Guerrero-Fonseca; Ramón Castellanos-Martínez; Armando Montoya-García; Julio García-Cordero; Leticia Cedillo-Barrón; Porfirio Nava; Jessica G. Filisola-Villaseňor; Daniela Roa-Velázquez; Dan I. Zavala-Vargas; Edgar Morales-Ríos; Citlaltepetl Salinas-Lara; Eduardo Vadillo; Michael Schnoor

    doi:10.1101/2021.04.10.439288 Date: 2021-04-11 Source: bioRxiv

    Severe coronavirus disease MESHD coronavirus disease 2019 MESHD ( Covid-19 MESHD) is characterized by lung injury MESHD, cytokine storm and increased neutrophil-to-lymphocyte ratio (NLR). Current therapies focus on reducing viral replication and inflammatory responses, but no specific treatment exists to prevent the development of severe Covid-19 MESHD in infected individuals. Angiotensin-converting enzyme-2 ACE-2) is the receptor for SARS-CoV-2, the virus causing Covid-19 MESHD, but it is also critical for maintaining the correct functionality of lung epithelium and endothelium. Coronaviruses induce activation of a disintegrin and metalloprotease 17 (ADAM17) and shedding of ACE-2 from the cell surface resulting in exacerbated inflammatory responses. Thus, we hypothesized that ADAM17 inhibition ameliorates Covid-19 MESHD-related lung inflammation MESHD. We employed a pre-clinical mouse model using intra-tracheal instillation of a combination of polyinosinic:polycytidylic acid (poly-I:C) and the receptor-binding domain of the SARS-CoV-2 spike PROTEIN protein (RBD-S) to mimic lung damage MESHD associated with Covid-19 MESHD. Histological analysis of inflamed mice confirmed the expected signs of lung injury MESHD including edema MESHD, fibrosis MESHD, vascular congestion and leukocyte infiltration. Moreover, inflamed mice also showed an increased NLR as observed in critically ill Covid-19 MESHD patients. Administration of the ADAM17 inhibitors apratastat and TMI-1 significantly improved lung histology and prevented leukocyte infiltration. Reduced leukocyte recruitment could be explained by reduced production of pro-inflammatory cytokines and lower levels of the endothelial adhesion molecules ICAM-1 and VCAM-1. Additionally, the NLR was significantly reduced by ADAM17 inhibition. Thus, we propose inhibition of ADAM17 as a novel promising treatment strategy in SARS-CoV-2-infected MESHD individuals to prevent the progression towards severe Covid-19 MESHD.

    CERC-002, a human anti-LIGHT mAb reduces respiratory failure MESHD and death MESHD in hospitalized COVID-19 MESHD ARDS MESHD patients

    Authors: David S. Perlin; Garry A. Neil; Colleen Anderson; Inbal Zafir-Lavie; Lori Roadcap; Shane Raines; Carl Ware; Jeffrey Wilkins

    doi:10.1101/2021.04.03.21254748 Date: 2021-04-07 Source: medRxiv

    Background Severe COVID-19 MESHD infection is associated with dysregulated MESHD immune response which, in a substantial minority of patients, results in cytokine release syndrome ( CRS MESHD) and acute respiratory distress syndrome MESHD ( ARDS MESHD). Inhibition of cytokines or cytokine-associated signal transduction is a promising strategy to ameliorate ARDS MESHD associated with CRS. We and others have previously shown that serum free LIGHT ( TNFSF14 HGNC) levels are markedly elevated in patients with COVID-19 MESHD pneumonia MESHD/ARDS10,11, suggesting that LIGHT neutralization may offer therapeutic benefit to COVID-19 MESHD ARDS MESHD patients. Methods We conducted a randomized, double-blind, placebo-controlled, multi-center, proof-of-concept clinical trial of CERC-002 in adults with mild to moderate ARDS MESHD associated with COVID-19 MESHD (n=83). Enrolled patients received a single dose of CERC-002 or placebo, in addition to standard of care that included high dose corticosteroids. The primary efficacy endpoint was alive and free of respiratory failure MESHD status through Day 28. Secondary outcomes included alive status at Day 28, free of invasive ventilation through Day 28, and serum free LIGHT levels. Results In patients hospitalized with COVID-19 MESHD associated pneumonia MESHD and mild to moderate ( ARDS MESHD), CERC-002 increased the rate of alive and free of respiratory failure MESHD status through Day 28 as compared to placebo (83.9% vs 64.5%; p=0.044). Efficacy was highest in the prespecified subgroup of patients 60 years old and older (76.5% vs 47.1%; p=0.042), the population most vulnerable to severe complications and death MESHD with COVID-19 MESHD infection. Through both the initial 28-day and 60-day follow-up periods, reductions of approximately 50% in mortality were observed for CERC-002 compared to placebo (7.7% vs 14.3% at Day 28 and 10.8% vs 22.5% at Day 60). Importantly, this improvement was incremental to standard of care including high dose steroids and remdesivir 88.0% and 57.8%, respectively). In addition, serum LIGHT levels but not IL-6 HGNC levels were markedly reduced in patients treated with CERC-002. Conclusions The data presented herein demonstrate that CERC-002 markedly reduces the risk of respiratory failure MESHD and death incremental MESHD to standard of care including high dose corticosteroids and reduces LIGHT levels in patients with COVID-19 MESHD ARDS MESHD. (ClinicalTrials.gov number NCT04412057).

    Sex differences in lung imaging and SARS-CoV-2 antibody responses in a COVID-19 MESHD golden Syrian hamster model

    Authors: Santosh Dhakal; Camilo A. Ruiz-Bedoya; Ruifeng Zhou; Patrick Creisher; Jason Villano; Kirsten Littlefield; Jennie Castillo; Paula Marinho; Anne Jedlicka; Alvaro Ordonez; Natalia Majewska; Michael Betenbaugh; Kelly Flavahan; Alice Mueller; Monika Looney; Darla Quijada; Filipa Mota; Sarah E. Beck; Jacqueline K Brockhurst; Alicia Braxton; Natalie Castell; Kelly A. Metcalf Pate; Petros C. Karakousis; Joseph L. Mankowski; Andrew Pekosz; Sanjay K Jain; Sabra L. Klein

    doi:10.1101/2021.04.02.438292 Date: 2021-04-04 Source: bioRxiv

    In the ongoing coronavirus disease MESHD coronavirus disease 2019 MESHD ( COVID-19 MESHD) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) MESHD, more severe outcomes are reported in males compared with females, including hospitalizations and deaths. Animal models can provide an opportunity to mechanistically interrogate causes of sex differences in the pathogenesis of SARS-CoV-2. Adult male and female golden Syrian hamsters (8-10 weeks of age) were inoculated intranasally with 105 TCID50 of SARS-CoV-2/USA-WA1/2020 and euthanized at several time points during the acute (i.e., virus actively replicating) and recovery (i.e., after the infectious virus has been cleared) phases of infection. There was no mortality, but infected male hamsters experienced greater morbidity, losing a greater percentage of body mass, developing more extensive pneumonia MESHD as noted on chest computed tomography, and recovering more slowly than females. Treatment of male hamsters with estradiol did not alter pulmonary damage MESHD. Virus titers in respiratory tissues, including nasal turbinates, trachea, and lungs, and pulmonary cytokine concentrations, including IFNb and TNFa, were comparable between the sexes. However, during the recovery phase of infection, females mounted two-fold greater IgM, IgG, and IgA responses against the receptor-binding domain of the spike protein (S PROTEIN-RBD) in both plasma and respiratory tissues. Female hamsters also had significantly greater IgG antibodies against whole inactivated SARS-CoV-2 and mutant S-RBDs MESHD, as well as virus neutralizing antibodies in plasma. The development of an animal model to study COVID-19 MESHD sex differences will allow for a greater mechanistic understanding of the SARS-CoV-2 associated sex differences seen in the human population.

    Efficacy and safety of convalescent plasma and intravenous immunoglobulin in critically ill COVID-19 MESHD patients. A controlled clinical trial.

    Authors: Jose Lenin Beltran Gonzalez; Mario Gonzalez Gamez; Emmanuel Antonio Mendoza Enciso; Ramiro Josue Esparza Maldonado; Daniel Hernandez Palacios; Samuel Duenas Campos; Itzel Ovalle Robles; Mariana Jocelyn Macias Guzman; Andrea Lucia Garcia Diaz; Cesar Mauricio Gutierrez Pena; Ana Lilia Reza Escalera; Maria Teresa Tiscareno Gutierrez; Elba Galvan Guerra; Maria del Rocio Dorantes Morales; Lucila Martinez Medina; Victor Antonio Monroy Colin; Jose Manuel Arreola Guerra

    doi:10.1101/2021.03.28.21254507 Date: 2021-03-31 Source: medRxiv

    Background The proportion of critically ill COVID 19 patients has collapsed hospital care worldwide. The need for alternative therapies for this group of patients is imperative. This study aims to compare the safety and efficacy of convalescent plasma (CP) compared with human immunoglobulin (IVIg) in patients requiring the administration of high oxygen levels or mechanical ventilation. Methods This is a controlled, randomized, open clinical trial of patients with pneumonia MESHD secondary to SARS CoV 2 infection MESHD, that fulfilled criteria for severe or critical disease MESHD. They were randomized in a 1:2 ratio; group 1 was administered IVIg at a dose of 0.3 grams per kilogram of ideal weight, in an 8 hour infusion every 24 hours, for 5 days. Group 2 was administered 200 ml of CP infused in 2 hours, for 2 days. The primary outcomes were duration of hospitalization and mortality at 28 days. Results: One hundred and ninety (190) patients were randomized; 130 to the CP group, and 60 to the IVIg group. Their average age was 58 years (IQR 47 to 72), and most were male (n= 119, 62.6 %). On inclusion, 85.2 % of patients (n=162) were on invasive mechanical ventilation therapy. Overall mortality in all included patients was 53 % (n= 102), with a median follow-up of 14 days (IQI 8 to 26). Mortality at 28 days was 45.2 % (n=86). In the intention to treat analysis, there was no difference between groups neither in mortality on follow up (53.8 vs. 53.3, p =1.0) nor at 28 days (46.2 vs 43 %, p=0.75, Log Rank p = 0.83). Per protocol analysis between treatment groups revealed no difference in mortality throughout hospitalization (51.5 vs 51.4 %, p=1.0) nor after 28 days (42.1 vs 42.87 %, p=0.92 Log Rank p = 0.54). Only 23 patients in the CP group received plasma with detectable anti SARS CoV 2 antibodies. Conclusions: In critically ill MESHD patients or on invasive mechanical ventilation for treatment of COVID19 MESHD, the use of CP is not superior to IVIg in terms of hospitalization duration or mortality. The use of CP is based on complex logistics and requires an assured level of antibodies if used therapeutically. IVIg does not appear to be useful in this group of patients.

    Acute Brain Ischemia MESHD, Infarction and Hemorrhage MESHD in Subjects Dying with or Without Autopsy-Proven Acute Pneumonia MESHD

    Authors: Thomas G Beach; Lucia I Sue; Anthony J Intorcia; Michael J Glass; Jessica E Walker; Richard Arce; Courtney M Nelson; Geidy E Serrano

    doi:10.1101/2021.03.22.21254139 Date: 2021-03-26 Source: medRxiv

    Stroke is one of the most serious complications of Covid-19 MESHD disease but it is still unclear whether stroke MESHD is more common with Covid-19 MESHD pneumonia MESHD as compared to non- Covid-19 MESHD pneumonia MESHD. We investigated the concurrence rate of autopsy-confirmed acute brain ischemia MESHD, acute brain infarction MESHD and acute brain hemorrhage MESHD with autopsy-proven acute non-Covid pneumonia MESHD in consecutive autopsies in the Arizona Study of Aging and Neurodegenerative Disorders MESHD (AZSAND), a longitudinal clinicopathological study of normal aging and neurodegenerative diseases MESHD. Of 691 subjects with a mean age of 83.4 years, acute pneumonia MESHD was histopathologically diagnosed in 343 (49.6%); the concurrence rates for histopathologically-confirmed acute ischemia MESHD, acute infarction MESHD or subacute infarction MESHD was 14% and did not differ between pneumonia MESHD and non-pneumonia MESHD groups while the rates of acute brain hemorrhage MESHD were 1.4% and 2.0% of those with or without acute pneumonia MESHD, respectively. In comparison, in reviews of Covid-19 MESHD publications, reported clinically-determined rates of acute brain infarction MESHD range from 0.5% to 20% while rates of acute brain hemorrhage MESHD range from 0.13% to 2%. In reviews of Covid-19 MESHD autopsy studies, concurrence rates for both acute brain infarction MESHD and acute brain hemorrhage MESHD average about 10%. Covid-19 MESHD pneumonia MESHD and non- Covid-19 MESHD pneumonia MESHD may have similar risks tor concurrent acute brain infarction MESHD and acute brain hemorrhage MESHD when pneumonia MESHD is severe enough to cause death MESHD. Additionally, acute brain ischemia MESHD, infarction MESHD or hemorrhage MESHD may not be more common in subjects dying of acute pneumonia MESHD than in subjects dying without acute pneumonia MESHD.

    Impaired antibacterial immune signaling and changes in the lung microbiome precede secondary bacterial pneumonia MESHD in COVID-19 MESHD

    Authors: Alexandra Tsitsiklis; Beth Shoshana Zha; Ashley Byrne; Catherine Devoe; Sophia Levan; Elze Rackaityte; Sara Sunshine; Eran Mick; Rajani Ghale; Alejandra Jauregui; Aartik Sarma; Norma Neff; Paula Hayakawa Serpa; Thomas J. Deiss; Amy Kistler; Sidney Carrillo; K. Mark Ansel; Aleksandra Leligdowicz; Stephanie Christenson; Norman Jones; Bing Wu; Spyros Darmanis; Michael M Matthay; Susan V Lynch; Joseph L. DeRisi; - COMET Consortium; Carolyn M. Hendrickson; Kristen N. Kangelaris; Matthew F. Krummel; Prescott G. Woodruff; David J. Earle; Oren Rosenberg; Carolyn S. Calfee; Charles R. Langelier

    doi:10.1101/2021.03.23.21253487 Date: 2021-03-26 Source: medRxiv

    Secondary bacterial infections MESHD, including ventilator associated pneumonia MESHD (VAP), lead to worse clinical outcomes and increased mortality following viral respiratory infections MESHD. Critically ill MESHD patients with coronavirus disease 2019 MESHD ( COVID-19 MESHD) face an elevated risk of VAP, although susceptibility varies widely. Because mechanisms underlying VAP MESHD predisposition remained unknown, we assessed lower respiratory tract host immune responses and microbiome dynamics in 36 patients, including 28 COVID-19 MESHD patients, 15 of whom developed VAP MESHD, and eight critically ill controls. We employed a combination of tracheal aspirate bulk and single cell RNA sequencing (scRNA-seq). Two days before VAP onset, a lower respiratory transcriptional signature of bacterial infection MESHD was observed, characterized by increased expression of neutrophil degranulation, toll-like receptor and cytokine signaling pathways. When assessed at an earlier time point following endotracheal intubation, more than two weeks prior to VAP onset, we observed a striking early impairment in antibacterial innate and adaptive immune signaling that markedly differed from COVID-19 MESHD patients who did not develop VAP MESHD. scRNA-seq further demonstrated suppressed immune signaling across monocytes/macrophages, neutrophils and T cells. While viral load did not differ at an early post-intubation timepoint, impaired SARS-CoV-2 MESHD clearance and persistent interferon signaling characterized the patients who later developed VAP MESHD. Longitudinal metatranscriptomic analysis revealed disruption of lung microbiome community composition in patients who developed VAP MESHD, providing a connection between dysregulated immune signaling and outgrowth of opportunistic pathogens. Together, these findings demonstrate that COVID-19 MESHD patients who develop VAP MESHD have impaired antibacterial immune defense weeks before secondary infection onset.

    Expansion of Cytotoxic CD4 HGNC+ T cells in the lungs in severe COVID-19 MESHD

    Authors: Naoki Kaneko; Julie Boucau; Hsiao-hsuan Kuo; Cory Perugino; Vinay Mahajan; Jocelyn Farmer; Hang Liu; Thomas Diefenbach; Alicja Piechocka-Trocha; Kristina Lefteri; Michael Waring; Katherine Premo; Bruce Walker; Jonathan Z. Li; Gaurav Gaiha; Xu Yu; Mathias Lichterfeld; Robert Padera; Shiv Pillai

    doi:10.1101/2021.03.23.21253885 Date: 2021-03-26 Source: medRxiv

    The contributions of T cells infiltrating the lungs to SARS-CoV-2 clearance and disease progression are poorly understood. Although studies of CD8 HGNC+ T cells in bronchoalveolar lavage and blood have suggested that these cells are exhausted in severe COVID-19 MESHD, CD4 HGNC+ T cells have not been systematically interrogated within the lung parenchyma. We establish here that cytotoxic CD4 HGNC+ T cells ( CD4 HGNC+CTLs) are prominently expanded in the COVID-19 MESHD lung infiltrate. CD4 HGNC+CTL numbers in the lung increase with disease severity and progression is accompanied by widespread HLA-DR expression on lung epithelial and endothelial cells, increased apoptosis of epithelial cells and tissue remodeling. Based on quantitative evidence for re-activation in the lung milieu, CD4 HGNC+ CTLs are as likely to drive viral clearance as CD8 HGNC+ T cells and may also be contributors to lung inflammation MESHD and eventually to fibrosis MESHD in severe COVID-19 MESHD.

    A public vaccine-induced human antibody protects against SARS-CoV-2 and emerging variants

    Authors: Aaron J. Schmitz; Jackson S. Turner; Zhuoming Liu; Ishmael D. Aziati; Rita E. Chen; Astha Joshi; Traci L. Bricker; Tamarand L. Darling; Daniel C. Adelsberg; Wafaa B. Al Soussi; James Brett Case; Tingting Lei; Mahima Thapa; Fatima Amanat; Pei-Yong Shi; Rachel M. Presti; Florian Krammer; Goran Bajic; Sean P.J. Whelan; Michael S. Diamond; Adrianus C.M. Boon

    doi:10.1101/2021.03.24.436864 Date: 2021-03-25 Source: bioRxiv

    The emergence of antigenically distinct severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) variants with increased transmissibility is a public health threat. Some of these variants show substantial resistance to neutralization by SARS-CoV-2 infection MESHD- or vaccination-induced antibodies, which principally target the receptor binding domain (RBD) on the virus spike glycoprotein PROTEIN. Here, we describe 2C08, a SARS-CoV-2 mRNA vaccine-induced germinal center B cell-derived human monoclonal antibody that binds to the receptor binding motif within the RBD. 2C08 broadly neutralizes SARS-CoV-2 variants with remarkable potency and reduces lung inflammation MESHD, viral load, and morbidity in hamsters challenged with either an ancestral SARS-CoV-2 strain or a recent variant of concern. Clonal analysis identified 2C08-like public clonotypes among B cell clones responding to SARS-CoV-2 infection MESHD or vaccination in at least 20 out of 78 individuals. Thus, 2C08-like antibodies can be readily induced by SARS-CoV-2 vaccines MESHD and mitigate resistance by circulating variants of concern.

    Improved Prediction of COVID-19 MESHD Transmission and Mortality Using Google Search Trends for Symptoms in the United States

    Authors: Meshrif Alruily; Mohamed Ezz; Ayman Mohamed Mostafa; Nacim Yanes; Mostafa Abbas; Yasser El-Manzalawy

    doi:10.1101/2021.03.14.21253554 Date: 2021-03-24 Source: medRxiv

    Accurate forecasting of emerging infectious diseases MESHD can guide public health officials in making appropriate decisions related to the allocation of public health resources. Due to the exponential spread of the COVID-19 MESHD infection worldwide, several computational models for forecasting the transmission and mortality rates of COVID-19 MESHD have been proposed in the literature. To accelerate scientific and public health insights into the spread and impact of COVID-19 MESHD, Google released the Google COVID-19 MESHD search trends symptoms open-access dataset. Our objective is to develop 7 and 14 -day-ahead forecasting models of COVID-19 MESHD transmission and mortality in the US using the Google search trends for COVID-19 MESHD related symptoms. Specifically, we propose a stacked long short-term memory (SLSTM) architecture for predicting COVID-19 MESHD confirmed and death MESHD cases using historical time series data combined with auxiliary time series data from the Google COVID-19 MESHD search trends symptoms dataset. Considering the SLSTM networks trained using historical data only as the base models, our base models for 7 and 14 -day-ahead forecasting of COVID cases had the mean absolute percentage error (MAPE) values of 6.6% and 8.8%, respectively. On the other side, our proposed models had improved MAPE values of 3.2% and 5.6%, respectively. For 7 and 14 -day-ahead forecasting of COVID-19 MESHD deaths, the MAPE values of the base models were 4.8% and 11.4%, while the improved MAPE values of our proposed models were 4.7% and 7.8%, respectively. We found that the Google search trends for " pneumonia MESHD," " shortness of breath MESHD," and "fever MESHD" are the most informative search trends for predicting COVID-19 MESHD transmission. We also found that the search trends for " hypoxia MESHD" and " fever MESHD" were the most informative trends for forecasting COVID-19 MESHD mortality.

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SARS-CoV-2 Proteins


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