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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (15)

ProteinN (6)

NSP5 (4)

ProteinS1 (3)

NSP3 (2)


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SARS-CoV-2 Proteins
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    Effect of SARS-CoV-2 proteins on vascular permeability

    Authors: Rossana Rauti; Meishar Shahoha; Yael Leichtmann-Bardoogo; Rami Nasser; Rina Tamir; Victoria Miller; Tal Babich; Kfir Shaked; Avner Ehrlich; Konstantinos Ioannidis; Yaakov Nahmias; Roded Sharan; Uri Ashery; Ben Meir Maoz

    doi:10.1101/2021.02.27.433186 Date: 2021-03-01 Source: bioRxiv

    SARS CoV 2 infection MESHD leads to severe disease associated with cytokine storm, vascular dysfunction MESHD, coagulation, and progressive lung damage MESHD. It affects several vital organs, seemingly through a pathological effect on endothelial cells. The SARS-CoV-2 genome encodes 29 proteins, whose contribution to the disease manifestations, and especially endothelial complications, is unknown. We cloned and expressed 26 of these proteins in human cells and characterized the endothelial response to overexpression of each, individually. Whereas most proteins induced significant changes in endothelial permeability, nsp2 HGNC, nsp HGNC5_c145a (catalytic dead mutant of nsp5 HGNC) and nsp7 also reduced CD31 HGNC, and increased von Willebrand MESHD factor expression and IL-6 HGNC, suggesting endothelial dysfunction. Using propagation-based analysis of a protein protein interaction (PPI) network, we predicted the endothelial proteins affected by the viral proteins that potentially mediate these effects. We further applied our PPI model to identify the role of each SARS CoV 2 protein in other tissues affected by COVID 19. Overall, this work identifies the SARS CoV 2 proteins that might be most detrimental in terms of endothelial dysfunction, thereby shedding light on vascular aspects of COVID 19.

    Some bacteria residing in the human body may contribute to the COVID-19 MESHD “cytokine storm”

    Authors: László Földvári-Nagy; Tamás Schnabel; Gabriella Dörnyei; Tamás Korcsmáros; Katalin Lenti

    doi:10.21203/rs.3.rs-276092/v1 Date: 2021-02-25 Source: ResearchSquare

    The COVID -19 pandemic has swept the globe. It is now evident that severe COVID-19 MESHD cases are associated with hyper-activation of the immune system, known as the “cytokine storm”. One of the central molecules involved in a cytokine storm is interleukin-6 HGNC (or IL-6 HGNC). At normal levels, IL-6 HGNC helps fight infection but when in excess, IL-6 HGNC can help trigger a cytokine storm. Some bacterial species are known to directly or indirectly affect IL-6 HGNC signaling and thus help contribute to the creation of cytokine storms. Researchers have hypothesized that these bacterial species could also contribute to the cytokine storm in COVID-19 MESHD. They propose a mechanism through which these bacterial species can contribute to the development of the COVID-19 MESHD cytokine storm. If their hypothesis is confirmed, it could mean that antibiotic treatment before or at an early stage of infection could reduce the chance of later developing a cytokine storm and help reduce the number of life-threatening cases of COVID-19 MESHD.

    Targeting of the NLRP3 HGNC Inflammasome for early COVID-19 MESHD

    Authors: Carlo Marchetti; Kara Mould; Isak W. Tengesdal; William J. Janssen; Charles A. Dinarello

    doi:10.1101/2021.02.24.432734 Date: 2021-02-24 Source: bioRxiv

    Following entry and replication of Severe Acute Respiratory Syndrome-coronavirus MESHD 2 (SARS-CoV-2) into ACE2 expressing cells, the infected cells undergo lysis releasing more virus but also cell contents. In the lung, constitutive cytokines such as IL-1 HGNC are released together with other cell contents. A cascade of inflammatory cytokines ensues, including chemokines and IL-1{beta}, triggering both local as well as systemic inflammation MESHD. This cascade of inflammatory cytokines in patients with COVID-19 MESHD is termed Cytokine Release Syndrome ( CRS MESHD), and is associated with poor outcomes and death MESHD. Many studies reveal that blocking IL-1{beta HGNC} activities in COVID-19 MESHD patients reduces disease severity and deaths MESHD. Here we report highly significant circulating levels of IL-1{beta HGNC}, IL-1 Receptor antagonist HGNC, IL-6 HGNC, TNF HGNC, IL-10 HGNC and soluble urokinase plasminogen activator receptor HGNC in COVID-19 MESHD patients with mild or no symptoms. We also report that in circulating myeloid cells from the same patients, there is increased expression of the NOD-, LRR- and pyrin domain-containing 3 ( NLRP3 HGNC) early in the infection. We observed increased NLRP3 HGNC gene expression in myeloid cells correlated with IL-1{beta HGNC} gene expression and also with elevated circulating IL-1{beta HGNC} levels. We conclude that early in SARS-CoV-2 infection MESHD, NLRP3 HGNC activation takes place and initiates the CRS. Thus, NLRP3 HGNC is a target to reduce the organ damage of inflammatory cytokines of the CRS.

    Endogenous control of inflammation MESHD characterizes pregnant women with asymptomatic or paucisymptomatic SARS-CoV-2 infection MESHD

    Authors: Sara De Biasi; Domenico Lo Tartaro; Lara Gibellini; Annamaria Paolini; Andrew Quong; Carlene Petes; Geneve Awong; Samuel Douglas; Dongxia Lin; Jordan Nieto; Rebecca Borella; Lucia Fidanza; Marco Mattioli; Chiara Leone; Marianna Meschiari; Erica Franceschini; Luca Cicchetti; Tommaso Trenti; Mario Sarti; Massimo Girardis; Giovanni Guaraldi; Cristina Mussini; Fabio Facchinetti; Andrea Cossarizza

    doi:10.21203/rs.3.rs-263619/v1 Date: 2021-02-21 Source: ResearchSquare

    In 14 pregnant women who had asymptomatic or paucisymptomatic SARS-CoV-2 infection MESHD, we performed a detailed 38-parameter analysis of peripheral blood mononuclear cells by mass cytometry, studied the expression of T-cell master regular genes, investigated cell proliferation and cytokine production, and measured plasma levels of 62 cytokines. No patient showed lymphopenia MESHD or gross alterations of white blood cells. Unsupervised analyses revealed that most immune parameters were similar in patients and uninfected controls, apart from an increase in low density neutrophils in SARS-CoV-2 positive women. Also, patients did not show altered plasma levels of interleukin-6 HGNC or other main inflammatory molecules, but displayed significant increases of anti-inflammatory cytokines such as IL-1RA HGNC, IL-10 HGNC and IL-19 HGNC, and decreased levels of IL-17 HGNC, PD-L1 HGNC and D-dimer. The endogenous control of inflammation MESHD, as evidenced by plasma levels of soluble molecules, could be a strategy used during pregnancy to avoid virus-induced damages and maintain a normal immune response.

    Chyawanprash for the prevention of COVID-19 MESHD infection among healthcare workers: A Randomized Controlled Trial

    Authors: Arun Gupta; Amit Madan; Babita Yadav; Richa Singhal; Pallavi Suresh Mundada; Yogesh Kumar Pandey; Riju Agarwal; Rakesh Rana; Arunabh Tripathi; Bhagwan Sahay Sharma; BCS Rao; Bharti Gupta; Narayanam Srikanth; Kartar Singh Dhiman

    doi:10.1101/2021.02.17.21251899 Date: 2021-02-19 Source: medRxiv

    Background: Coronavirus disease 2019 MESHD ( Covid19 MESHD) occurs after exposure to severe acute respiratory syndrome coronavirus 2 MESHD (SARSCoV2). For persons who are at high risk of exposure, the standard of care is personal protection from getting infected. Whether Ayurvedic rasayana drug like Chyawanprash can prevent symptomatic infection in frontline health care workers is unknown. Objective: To evaluate the effect of the combination of Chyawanprash and Standard Preventive Regimen compared to the use of Standard Preventive Regimen alone on the proportion of RT-PCR confirmed COVID 19 infections among frontline healthcare workers (HCWs). Methods: An open label randomized controlled trial was conducted in the HCWs between 25 to 60 years age currently working in an environment with chance of direct exposure to COVID 19 cases. The interventions to be compared in this trial were Standard Preventive Regimen as per institutional guidelines and based on their roles (Group I) and Ayurvedic Intervention viz., Chyawanprash 12 g twice for 30 days from day of randomization plus Standard Preventive Regimen (Group II). The incidence of RT PCR confirmed COVID19 MESHD cases in both groups, was the primary outcome measure. Evaluation of the safety of the study drug (by any statistically significant change in various biochemical and hematological parameters and occurrence of any adverse drug reactions); incidence of any other infective diseases (bacterial / viral / fungal / etc.) like upper respiratory tract illness during the study period and any change in the immunoglobulins like IgG, IgM and IgE and inflammatory markers like TNF alpha HGNC, IL6 HGNC and IL10 HGNC were the secondary outcome measures. Results: Out of 193 participants who completed the study, no participant in both groups was COVID 19 positive at the end of one month. In post intervention follow up, 4 subjects in Group I and 2 subjects in Group II were COVID 19 positive. No adverse drug reaction or any serious adverse event was reported during the study. No clinically significant change in the safety parameters was observed before and after the study. Statistically significant rise in Serum IgG level was seen in Group II but other inflammatory and immune markers did not show statistically significant difference. Conclusion: Chyawanprash was well tolerated by all the participants in the intervention group but to prove its adaptogenic effect and efficacy as an add-on to the standard care in preventing the occurrence of COVID 19, clinical trial for longer duration with larger sample size is needed. Trial registration: Clinical Trials Registry of India vide CTRI/2020/05/025275 dated 20/05/2020 Date of IEC approval: 19.5.2020 Keywords: Adaptogen, Ayurveda, Health personnel, Prophylaxis, Rasayana, SARS CoV 2

    Development and validation of a dynamic 48-hour in-hospital prognostic risk stratification for COVID-19 MESHD in a UK teaching hospital: a retrospective cohort study

    Authors: Martin Wiegand; Sarah L Cowan; Claire S Waddington; David J Halsall; Victoria L Keevil; Brian D M Tom; Vince Taylor; Effrossyni Gkrania-Klotsas; Jacobus Preller; Robert JB Goudie

    doi:10.1101/2021.02.15.21251150 Date: 2021-02-18 Source: medRxiv

    We propose a prognostic dynamic risk stratification for 48-hour in-hospital mortality in patients with COVID-19 MESHD, using demographics and routinely-collected observations and laboratory tests: age, Clinical Frailty Scale score, heart rate, respiratory rate, SpO2/FiO2 ratio, white cell count, acidosis MESHD (pH < 7.35) and Interleukin-6 HGNC. We train and validate the model using data from a UK teaching hospital, adopting a landmarking approach that accounts for competing risks and informative missingness. Internal validation of the model on the first wave of patients presenting between March 1 HGNC and September 12, 2020 achieves an AUROC of 0.90 (95% CI 0.87-0.93). Temporal validation on patients presenting between September 13, 2020 and January 1, 2021 gives an AUROC of 0.91 (95% CI 0.88-0.95). The resulting mortality stratification tool has the potential to provide physicians with an assessment of a patient's evolving prognosis throughout the course of active hospital treatment.

    Cytokine Signature and COVID-19 MESHD Prediction Models in the Two Waves of Pandemics.

    Authors: Serena Cabaro; Vittoria D'Esposito; Tiziana Di Matola; Silvia Sale; Michele Cennamo; Daniela Terracciano; Valentina Parisi; Francesco Oriente; Giuseppe Portella; Francesco Beguinot; Luigi Atripaldi; Mario Sansone; Pietro Formisano

    doi:10.21203/rs.3.rs-251338/v1 Date: 2021-02-17 Source: ResearchSquare

    In Europe, two waves of infections with SARS-CoV-2 ( COVID-19 MESHD) have been observed to date. Here, we have investigated whether common patterns of cytokines could be detected in individuals with mild and severe forms of COVID-19 MESHD in the two pandemic waves, and whether machine learning approach could be useful to identify the best predictors. An increasing trend of multiple cytokines was observed in patients with mild or severe/critical symptoms of COVID-19 MESHD, compared with healthy volunteers. Linear Discriminant Analysis (LDA) clearly recognized the three groups based on cytokine patterns. Classification and Regression Tree (CART) further indicated that IL-6 HGNC discriminated controls and COVID-19 MESHD patients, whilst IL-8 HGNC defined disease severity. During the second wave of pandemics, a less intense cytokine storm was observed. CART analysis revealed that IL-6 HGNC was the most robust predictor of infection and discriminated moderate COVID-19 MESHD patients from healthy controls, regardless of epidemic peak curve. Thus, serum cytokine patterns provide non-invasive biomarkers useful for COVID-19 MESHD diagnosis and prognosis. Further definition of individual cytokines may allow to envision novel therapeutic options and pave the way to set up innovative diagnostic tools.

    Identification of common key genes and pathways between Covid-19 MESHD and lung cancer MESHD by using protein-protein interaction network analysis

    Authors: Kang Soon Nana; Kalimuthu Karuppanan; Suresh Kumar

    doi:10.1101/2021.02.16.431364 Date: 2021-02-16 Source: bioRxiv

    COVID-19 MESHD is indeed an infection that is caused by a recently found coronavirus group, a type of virus proven to cause human respiratory diseases MESHD. The high mortality rate was observed in patients who had pre-existing health conditions like cancer MESHD. However, the molecular mechanism of SARS-CoV-2 infection MESHD SARS-CoV-2 infection MESHD in lung cancer patients was not discovered yet at the pathway level. This study was about determining the common key genes of COVID-19 MESHD and lung cancer MESHD through network analysis. The hub genes associated with COVID-19 MESHD and lung cancer MESHD were identified through Protein-Protein interaction analysis. The hub genes are ALB HGNC, CXCL8 HGNC, FGF2 HGNC, IL6 HGNC, INS, MMP2 HGNC, MMP9 HGNC, PTGS2 HGNC, STAT3 HGNC and VEGFA HGNC. Through gene enrichment, it is identified both COVID-19 MESHD and lung cancer MESHD have a common pathway in EGFR tyrosine kinase inhibitor resistance, IL-17 HGNC signalling pathway, AGE-RAGE signalling pathway in diabetic complications MESHD, HIF-1 HGNC signalling pathway and pathways in cancer MESHD.

    Dysregulation of the Leukocyte Signaling Landscape during Acute COVID-19 MESHD

    Authors: Isaiah Turnbull; Anja Fuchs; Kenneth Remy; Michael Kelly; Elfaridah Frazier; Sarbani Ghosh; Shin-wen Chang; Monty Mazer; Annie Hess; Jennifer Leonard; Mark Hoofnagle; Marco Colonna; Richard Hotchkiss

    doi:10.21203/rs.3.rs-244150/v1 Date: 2021-02-15 Source: ResearchSquare

    The global COVID-19 pandemic MESHD has claimed the lives of more than 450,000 US citizens. Dysregulation of the immune system underlies the pathogenesis of COVID-19 MESHD, with inflammation MESHD mediated local tissue injury to the lung in the setting of suppressed systemic immune function. To define the molecular mechanisms of immune dysfunction MESHD in COVID-19 MESHD we utilized a systems immunology approach centered on the circulating leukocyte phosphoproteome measured by mass cytometry. COVID-19 MESHD is associated with wholesale activation of a broad set of signaling pathways across myeloid and lymphoid cell populations. STAT3 HGNC phosphorylation predominated in both monocytes and T cells and was tightly correlated with circulating IL-6 HGNC levels. High levels of STAT3 HGNC phosphorylation was associated with decreased markers of myeloid cell maturation/activation and decreased ex-vivo T cell IFN-gamma HGNC production, demonstrating that during COVID-19 MESHD dysregulated cellular activation is associated with suppression of immune effector cell function. Collectively, these data reconcile the systemic inflammatory response and functional immunosuppression induced by COVID-19 MESHD and suggest STAT3 HGNC signaling may be the central pathophysiologic mechanism driving immune dysfunction in COVID-19 MESHD.

    Tocilizumab-induced unexpected increase of several inflammatory cytokines in critically ill COVID-19 MESHD patients

    Authors: Fanny Ponthieux; Nicolas Dauby; Evelyne Maillart; Jean-François Fils; Julie Smet; Marc Claus; Tatiana Besse-Hammer; David De Bels; Francis Corazza; Carole Nagant

    doi:10.21203/rs.3.rs-234733/v1 Date: 2021-02-11 Source: ResearchSquare

    Early evidence during the COVID-19 pandemic MESHD indicated high levels of IL-6 HGNC in patients with severe COVID-19 MESHD. This led to the off-label use of tocilizumab (TCZ) during the first wave of the pandemic.We aimed to monitor IL-6 HGNC and several inflammatory cytokines in critically ill COVID-19 MESHD patients receiving off-label TCZ. Fifteen critically ill SARS-CoV-2 PCR confirmed cases were enrolled and serum samples were collected during 8 days, before and following administration of a single dose of TCZ. In parallel, a control group consisting of 8 non-treated COVID-19 MESHD patients not receiving TCZ was established. Serum profile of 12 cytokines (IL-1β, -2, -4, -6, -8, -10, -12, -13, -17, -18, TNF-α HGNC and INF-γ) and of  IL-6R HGNC were assessed in these two groups. Although the increased IL-6 HGNC concentrations after TCZ infusion were expected, we observed an unexpected increase in IL-1β, -2, -4, -10, -12p70, -18 and IL-6R HGNC levels in the treated patients with maximal values reached 2 to 4 days after TCZ. In contrast, no change in cytokine levels was observed in the control group. There was no significant difference in cytokine levels between survivors (TCZ/S) or non-survivors (TCZ/D). This observation suggests that some inflammatory pathways escape IL-6R HGNC blockade leading to an increase in several pro-inflammatory cytokines. Our findings could highlight an anti-inflammatory role of IL-6 HGNC and may explain why TCZ has failed to improve survival in critically ill COVID-19 MESHD patients when given alone.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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