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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (13)

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NSP3 (1)

ORF1ab (1)

NSP2 (1)


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    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.

    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.

    Qualitatively distinct modes of Sputnik V vaccine-neutralization escape by SARS-CoV-2 Spike PROTEIN variants

    Authors: Satoshi Ikegame; Mohammed N. A. Siddiquey; Chuan-Tien Hung; Griffin Haas; Luca Brambilla; Kasopefoluwa Y. Oguntuyo; Shreyas Kowdle; Ariel Esteban Vilardo; Alexis Edelstein; Claudia Perandones; Jeremy P. Kamil; Benhur Lee

    doi:10.1101/2021.03.31.21254660 Date: 2021-04-02 Source: medRxiv

    The novel pandemic betacoronavirus, severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), has infected at least 120 million people since its identification as the cause of a December 2019 viral pneumonia MESHD outbreak in Wuhan, China. Despite the unprecedented pace of vaccine development, with six vaccines already in use worldwide, the emergence of SARS-CoV-2 variants of concern (VOC) across diverse geographic locales suggests herd immunity may fail to eliminate the virus. All three officially designated VOC carry Spike (S) polymorphisms thought to enable escape from neutralizing antibodies elicited during initial waves of the pandemic. Here, we characterize the biological consequences of the ensemble of S mutations present in VOC lineages B.1.1.7 (501Y.V1) and B.1.351 (501Y.V2). Using a replication-competent EGFP-reporter vesicular stomatitis virus MESHD ( VSV MESHD) system, rcVSV-CoV2-S, which encodes S from SARS coronavirus 2 in place of VSV MESHD-G, coupled with a clonal HEK-293T ACE2 HGNC TMPRSS2 cell line optimized for highly efficient S-mediated infection, we determined that 8 out of 12 (75%) of serum samples from 12 recipients of the Russian Sputnik V Ad26 / Ad5 vaccine showed dose response curve slopes indicative of failure to neutralize rcVSV-CoV2-S: B.1.351. The same set of sera efficiently neutralized S from B.1.1.7 and showed only moderately reduced activity against S carrying the E484K substitution alone. Taken together, our data suggest that control of emergent SARS-CoV-2 variants may benefit from updated vaccines.

    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.

    Circadian regulation of SARS-CoV-2 infection MESHD in lung epithelial cells

    Authors: Xiaodong Zhuang; Senko Tsukuda; Florian Wrensch; Peter AC Wing; Helene Borrmann; James M Harris; Sophie B Morgan; Laurent Mailly; Nazia Thakur; Carina Conceicao; Harshmeena Sanghani; Laura Heydmann; Charlotte Bach; Anna Ashton; Steven Walsh; Tiong Kit Tan; Lisa Schimanski; Kuan-Ying A Huang; Catherine Schuster; Koichi Watashi; Timothy SC Hinks; Aarti Jagannath; Sridhar R Vausdevan; Dalan Bailey; Thomas F Baumert; Jane A McKeating

    doi:10.1101/2021.03.20.436163 Date: 2021-03-21 Source: bioRxiv

    The COVID-19 pandemic MESHD, caused by SARS-CoV-2 coronavirus MESHD, is a global health issue with unprecedented challenges for public health. SARS-CoV-2 primarily infects cells of the respiratory tract, via binding human angiotensin-converting enzyme ( ACE2 HGNC), and infection can result in pneumonia MESHD and acute respiratory distress syndrome MESHD. Circadian rhythms coordinate an organisms response to its environment and recent studies report a role for the circadian clock to regulate host susceptibility to virus infection MESHD. Influenza A infection of arhythmic mice, lacking the circadian component BMAL1, results in higher viral replication and elevated inflammatory responses leading to more severe bronchitis MESHD, highlighting the impact of circadian pathways in respiratory function. We demonstrate circadian regulation of ACE2 in lung epithelial cells and show that silencing BMAL1 or treatment with the synthetic REV-ERB agonist SR9009 reduces ACE2 expression and inhibits SARS-CoV-2 entry MESHD and RNA replication. Treating infected cells with SR9009 limits viral replication and secretion of infectious particles, showing that post-entry steps in the viral life cycle are influenced by the circadian system. Our study suggests new approaches to understand and improve therapeutic targeting of COVID-19 MESHD.

    COVID-19 MESHD IN IRAQ, THE RURAL INITIATION (AL-MUTHANNA PROVINCE AS AN EXAMPLE)

    Authors: Hazim Talib Thwiny; Safa Ibrahim Jaber; Hekmat Kadhum Ateya; Ali Mosa Al-Yasari; Nawar Jasim Alsalih; Moyed A. AL- Saadawe; Emad Salih Jasim; Mohenned A Alsaadawi

    doi:10.1101/2021.03.16.21251969 Date: 2021-03-20 Source: medRxiv

    A sustained pneumonia MESHD outbreak associated with a novel coronavirus named acute respiratory coronavirus 2 syndrome MESHD (SARS-CoV-2) was identified in Wuhan, Hubei Province, China in December 2019 which was later called COVID-19 MESHD. The first confirmed case of COVID-19 MESHD was reported in Najaf/ Iraq on 24th February. This paper provided some information on COVID-19 MESHD infection in the Province of Al-Muthanna / South Iraq, which was then statistically analyzed and concluded. Confirmed cases of COVID-19 MESHD infections were reported by the Iraqi Ministry of Health in the Province of Al-Muthanna. The first foci started and the first dead infected individual was from Hilal which refers mainly to the role or rural places in starting and transmission of COVID-19 MESHD in Iraq. Many of the infections resulted in non-traveling persons because they were contaminated by contact (96%). Therefore, contact is perceived to be the best-recognized form of transmission. It was also reported that infections in Soweir District of Samawah City were the highest (45%) compared to other areas of the region. They should also be observed, however, that the steps to enforce and monitor the curfew are directly related to the direction of the City Centre because the more they drive away from the city centers, the less stringent the procedures. Infections were focused between the ages of 20 and 50 years old, as that is the expected result because these ranges are at the core of active age groups including social and sports events.

    Diagnostic accuracy and predictive value of clinical symptoms for the diagnosis of mild COVID 19

    Authors: Vasyl Ivanovich Popovych; Ivana Koshel; Yulia Haman; Vitaly Leschak; Ruslan Duplikhin

    doi:10.1101/2021.03.05.21252963 Date: 2021-03-08 Source: medRxiv

    Objective To assess the diagnostic accuracy of clinical symptoms and their predictive values in patients with suspected mild COVID 19 and to identify target groups for self isolation and outpatient treatment without additional testing in the primary health care system. Methods We conducted an open label prospective study in both male and female patients aged 18 to 72 years with suspected mild COVID 19 who were sequentially enrolled in the study. The clinical diagnosis was performed in accordance with the WHO recommendations based on the acute onset of such symptoms as olfactory dysfunction MESHD, hyperthermia MESHD, myalgia MESHD, nasal congestion, nasal discharge, cough, rhinolalia MESHD, sore throat, without pneumonia MESHD or hypoxia MESHD in persons in contact with a confirmed case of COVID 19. The physician assessed clinical symptoms using a 4-point scale. The patient self-assessed clinical symptoms using a ten point visual analogue scale (VAS). All enrolled patients underwent laboratory testing to confirm the diagnosis of COVID 19. Results Of the 120 patients underwent testing, the diagnosis of mild COVID 19 was confirmed in 96 patients and ruled out in 24 patients. When assessing symptoms by a physician according to the correlation analysis, hyperthermia MESHD, myalgia MESHD, nasal congestion and rhinolalia MESHD have a positive predictive value with a significance level of more than 0.6. When self-assessing symptoms by a patient, fever MESHD, myalgia MESHD and nasal congestion have a diagnostic accuracy with a significance level of more than 0.5. Nasal discharge, cough MESHD and sore throat have negative predictive values. Discussion The presence of these symptoms in patients with an acute onset of the disease can help to make a clinical diagnosis of coronavirus disease MESHD and identify target groups for self-isolation and outpatient treatment without additional testing. Highly suspect asymptomatic patients are not considered as those who have possible mild COVID 19 infection. Keywords: diagnostic accuracy, predictive values, COVID 19, symptom

    Horse Owner Compliance to Non-Pharmaceutical Interventions During the COVID-19 Pandemic MESHD

    Authors: Veronica Fowler; Loni Loftus

    id:10.20944/preprints202103.0211.v1 Date: 2021-03-08 Source: Preprints.org

    In December 2019, an unusual cluster of pneumonia MESHD cases were reported in Wuhan and promptly confirmed to be caused by a new virus known as severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) of which the disease it caused would be known as COVID-19 MESHD. In March 2020, in the absence of any vaccines, and in response to the global spread of SARS-CoV-2 the UK implemented non-pharmaceutical intervention (NPI) measures in the form of a national lockdown to decelerate the spread. Compliance with NPIs can have significant impact on reducing disease transmission however there are currently no studies measuring compliance within the horse ownership world which naturally brings groups of people together during everyday caregiving activities. This article describes the reported horse owner compliance during the COVID-19 pandemic MESHD from March 2020 to December 2020 as deduced from 1036 respondents which completed an anonymous online survey between December 30th, 2020 and January 11th, 2021. Where rules/guidance did exist, there was good compliance with 92.76% of respondents indicating that they were following them. The most common rule/guidance implemented was social distancing, which was also the most common rule/guidance to be breached. Riding with others whilst at the yard (hacking or in an arena) and meeting up with non-household members (family and friends) when off the yard were also common rules/guidelines breached. Respondents who kept their horses at either DIY livery, or on a private yard were most likely to breach rules/regulations whereas respondents who kept their horses at full livery were least likely to breach rules/regulations. The results indicate that compliance of horse owners with COVID-19 MESHD rules/guidance is high when rules/guidance exists. However, just under half of respondents indicated that there were no rules/guidelines on their yards indicating that there is room for an increased contribution from the horse owning community by encouraging more yards to impose control measures where they currently do not exist.

    Hope, Depression, Anxiety MESHD and Associated Factors Among Parents of Retinoblastoma MESHD Patients During the Pneumonia Epidemic in COVID-19 MESHD: A Cross-Sectional Study

    Authors: Changjuan Zeng; Wenting Cao; Ting Zhao; Li Li; Lili Hou

    doi:10.21203/rs.3.rs-296459/v1 Date: 2021-03-04 Source: ResearchSquare

    BackgroundThe 2019 coronavirus disease MESHD ( COVID-19 MESHD) is a global public health emergency. So far, only a limited number of studies have investigated the impact of the pneumonia MESHD pandemic in COVID-19 MESHD on the mental health of parents having children with cancer MESHD. This study investigated the hope, depression MESHD, anxiety MESHD, and relevant influencing factors among parents of retinoblastoma MESHD patients during the pneumonia epidemic in COVID-19 MESHD.MethodsA total of 317 parents having children with retinoblastoma MESHD admitted to the Ninth People’s Hospital affiliated with the Shanghai Jiao Tong University, School of Medicine, and Qilu Children’s Hospital of Shandong University were investigated by cross-sectional investigation and convenient sampling. The survey tools included a Demographic Questionnaire, Herth Hope Index (HHI), The Generalized Anxiety Disorder MESHD (GAD-7), and The Patient Health Questionnaires (PHQ)-2. ResultsThe hope level score of the parents of retinoblastoma MESHD patients was (35.36 ±4.42), which was at the medium level. The highest dimension of the hope score was to take positive action (12.07± 1.57), and the lowest dimension was to maintain a close relationship with others (11.50± 1.64). The incidence rates of anxiety MESHD and depression MESHD were 41.32% (131/317) and 29.97% (95/317), respectively. Hope level was negatively correlated with anxiety and depression MESHD. Monoculus or binoculus disease, sleep quality, health status, having anxiety/depression MESHD or not, had a statistically significant effect on the research subjects' hope level (p<0.05). Multiple linear regression analysis revealed that the course of the disease, education level, and depression MESHD were independent influencing factors (p<0.05), which could explain 22.60% of the variation in hope level.ConclusionDuring the COVID-19 MESHD outbreak, medical staff should formulate targeted intervention measures according to the different characteristics of eye disease MESHD, the course of the disease, the parents' educational level, health status, and emotional state so as to improve parents' hope level.

    Discharge from the Emergency Department and Early Hospital Revaluation in Patients with COVID-19 MESHD Pneumonia: an Observational Study

    Authors: Massimo Mattioli; Devis Benfaremo; Francesca Fulgenzi; Silvia Gennarini; Luciano Mucci; Margherita Lambertini; Francesca Padiglione; Ramona Brugnera; Barbara Gabrielli; Flavia Giorgino; Maria Capalbo; Edoardo Berselli; Gianluca Moroncini; Gabriele Frausini; Umberto Gnudi

    doi:10.21203/rs.3.rs-289317/v1 Date: 2021-03-01 Source: ResearchSquare

    Background Health National Systems world-wide are facing the severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) pandemic. We purpose an outpatient management for patients affected by SARS-CoV-2 related pneumonia at risk of progression, after discharge from Emergency Department (ED).Methods This was a single-center prospective observational study. We enrolled patients with confirmed SARS-CoV-2 pneumonia MESHD, without hypoxemic respiratory failure MESHD, and at least one of the following: age ≥ 65 or presence of one or more comorbidities or pneumonia MESHD involvement > 25% on high resolution computed tomography (HRCT). The ambulatorial visit was performed after at least 48 hours, then patients could be discharged, admitted for hospitalization, or deferred for a further visit. As a control, we evaluated a historical cohort of patients hospitalized with comparable clinical and radiological features.Results A total of 84 patients were enrolled (51 M, mean age 62.8 y). Two-thirds of patients had at least one comorbidity and 41.6% had a lung involvement > 25% at HRCT; the mean duration of symptoms was 8 ± 3 days and the mean PaO2/FiO2 ratio 357.5 ± 38.6. At the end of the follow-up period, 69 patients had been discharged and 15 hospitalized (mean stay 6 days). Older age and higher NEWS2 were significant predictors of hospitalization at the first follow-up visit. One hospitalized patient died of septic shock MESHD. In the control group, the mean hospital stay was 8 days.Conclusions Adopting a “discharge and early revaluation” strategy appear to be safe and feasible. This approach may help to optimize hospital resources during the SARS-CoV-2 pandemic.

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MeSH Disease
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SARS-CoV-2 Proteins


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