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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (5)

NSP5 (2)

ProteinN (2)

ProteinS1 (2)

NSP3 (1)


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SARS-CoV-2 Proteins
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    Transcriptional Profiling of Leukocytes in Critically Ill COVID19 MESHD Patients: Implications for Interferon Response and Coagulation

    Authors: Sean E. Gill; Claudia C. dos Santos; David B. O’Gorman; David E. Carter; Eric K. Patterson; Marat Slessarev; Claudio Martin; Mark Daley; Michael R. Miller; Gediminas Cepinskas; Douglas D. Fraser

    doi:10.21203/rs.3.rs-63632/v2 Date: 2020-08-21 Source: ResearchSquare

    Background: COVID19 MESHD is caused by the SARS-CoV-2 virus MESHD and has been associated with severe inflammation MESHD leading to organ dysfunction and mortality. Our aim was to profile the transcriptome in leukocytes from critically ill patients positive for COVID19 MESHD compared to those negative for COVID19 MESHD to better understand the COVID19 MESHD associated host response. For these studies, all patients admitted to our tertiary care intensive care unit (ICU) suspected of being infected with SARS-CoV-2, using standardized hospital screening methodologies, had blood samples collected at the time of admission to the ICU. Transcriptome profiling of leukocytes via ribonucleic acid sequencing (RNAseq) was then performed and differentially expressed genes as well as significantly enriched gene sets were identified.Results: We enrolled seven COVID19 MESHD+ (PCR positive, 2 SARS-CoV-2 genes) and seven age- and sex-matched COVID19 MESHD- (PCR negative) control ICU patients. Cohorts were well-balanced with the exception that COVID19 MESHD- patients had significantly higher total white blood cell counts and circulating neutrophils and COVID19 MESHD+ patients were more likely to suffer bilateral pneumonia MESHD. The mortality rate for this cohort of COVID19 MESHD+ ICU patients was 29%. As indicated by both single-gene based and gene set (GSEA) approaches, the major disease-specific transcriptional responses of leukocytes in critically ill COVID19 MESHD+ ICU patients were: (i) a robust overrepresentation of interferon related gene expression; (ii) a marked decrease in the transcriptional level of genes contributing to general protein synthesis and bioenergy metabolism; and (iii) the dysregulated expression of genes associated with coagulation, platelet function, complement activation, and tumour necrosis factor MESHD/ interleukin 6 HGNC signalling.  Conclusions: Our findings demonstrate that critically ill COVID19 MESHD+ patients on day 1 of admission to the ICU display a unique leukocyte transcriptional profile that distinguishes them from COVID19 MESHD- patients, providing guidance for future targeted studies exploring novel prognostic and therapeutic aspects of COVID19 MESHD.

    Genome-wide bioinformatic analyses predict key host and viral factors in SARS-CoV-2 pathogenesis

    Authors: Mariana Ferrarini; Avantika Lal; Rita Rebollo; Andreas Gruber; Andrea Guarracino; Itziar Martinez Gonzalez; Taylor Floyd; Daniel Siqueira de Oliveira; Justin Shanklin; Ethan Beausoleil; Taneli Pusa; Brett Pickett; Vanessa Aguiar-Pulido

    doi:10.21203/rs.3.rs-63136/v1 Date: 2020-08-20 Source: ResearchSquare

    The novel betacoronavirus named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) caused a worldwide pandemic ( COVID-19 MESHD) after initially emerging in Wuhan, China. Here we applied a novel, comprehensive bioinformatic strategy to public RNA sequencing and viral genome sequencing data, to better understand how SARS-CoV-2 interacts with human cells. To our knowledge, this is the first meta-analysis to predict host factors that play a specific role in SARS-CoV-2 pathogenesis, distinct from other respiratory viruses. We identified differentially expressed genes, isoforms and transposable element families specifically altered in SARS-CoV-2 infected MESHD cells. Well-known immunoregulators including CSF2 HGNC, IL-32 HGNC, IL-6 HGNC and SERPINA3 HGNC were differentially expressed, while immunoregulatory transposable element families were overexpressed. We predicted conserved interactions between the SARS-CoV-2 genome and human RNA-binding proteins such as hnRNPA1 HGNC, PABPC1 HGNC and eIF4b HGNC, which may play important roles in the viral life cycle. We also detected four viral sequence variants in the spike, polymerase, and nonstructural proteins that correlate with severity of COVID-19 MESHD. The host factors we identified likely represent important mechanisms in the disease profile of this pathogen, and could be targeted by prophylactics and/or therapeutics against SARS-CoV-2.

    Lower respiratory tract myeloid cells harbor SARS-CoV-2 and display an inflammatory phenotype

    Authors: William Bain; Hernan F. Penaloza; Mark S. Ladinsky; Rick van der Geest; Mara Sullivan; Mark Ross; Georgios D Kitsios; Barbara Methe; Bryan J. McVerry; Alison Morris; Alan M. Watson; Simon C. Watkins; Claudette M. St. Croix; Donna B. Stolz; Pamela J. Bjorkman; Janet S. Lee

    doi:10.1101/2020.08.11.20171967 Date: 2020-08-14 Source: medRxiv

    SARS-CoV-2 pneumonia MESHD may induce an aberrant immune response with brisk recruitment of myeloid cells into the lower respiratory tract, which may contribute to morbidity and mortality. We describe endotracheal aspirate samples from seven patients with SARS-CoV-2 pneumonia MESHD requiring mechanical ventilation. We note SARS-CoV-2 virions within lower respiratory tract myeloid cells shown by electron tomography, immunofluorescence confocal imaging, and immuno-electron microscopy. Endotracheal aspirates are primarily composed of mononuclear and polymorphonuclear leukocytes. These myeloid cells that harbor virus are frequently positive for CD14 HGNC and/or CD16 HGNC and most display an inflammatory phenotype marked by expression of IL-6 HGNC and tissue factor HGNC mRNA transcript and protein expression.

    Natural Killer cell activation, reduced ACE2 HGNC, TMPRSS2 HGNC, cytokines G-CSF HGNC, M-CSF HGNC and SARS-CoV-2-S pseudovirus infectivity by MEK HGNC inhibitor treatment of human cells

    Authors: Lanlan Zhou; Kelsey Huntington; Shengliang Zhang; Lindsey Carlsen; Eui-Young So; Cassandra Parker; Ilyas Sahin; Howard Safran; Suchitra Kamle; Chang-Min Lee; Chun-Geun Lee; Jack A. Elias; Kerry S. Campbell; Mandar T. Naik; Walter J. Atwood; Emile Youssef; Jonathan A. Pachter; Arunasalam Navaraj; Attila A. Seyhan; Olin Liang; Wafik El-Deiry

    doi:10.1101/2020.08.02.230839 Date: 2020-08-03 Source: bioRxiv

    COVID-19 MESHD affects vulnerable populations including elderly individuals and patients with cancer MESHD. Natural Killer (NK) cells and innate-immune TRAIL HGNC suppress transformed and virally-infected cells. ACE2 HGNC, and TMPRSS2 HGNC protease promote SARS-CoV-2 infectivity MESHD, while inflammatory cytokines IL-6 HGNC, or G-CSF HGNC worsen COVID-19 MESHD severity. We show MEK HGNC inhibitors (MEKi) VS-6766, trametinib and selumetinib reduce ACE2 HGNC expression in human cells. Chloroquine or hydroxychloroquine increase cleaved active SP-domain of TMPRSS2 HGNC, and this is potentiated by MEKi. In some human cells, remdesivir increases ACE2 HGNC-promoter luciferase-reporter expression, ACE2 HGNC mRNA and protein, and ACE2 HGNC expression is attenuated by MEKi. We show elevated cytokines in COVID-19 MESHD- (+) patient plasma (N=9) versus control (N=11). TMPRSS2 HGNC, inflammatory cytokines G-CSF HGNC, M- CSF HGNC, IL-1a HGNC, IL-6 HGNC and MCP-1 HGNC are suppressed by MEKi alone or in combination with remdesivir. MEKi enhance NK cell (but not T-cell) killing of target-cells, without suppressing TRAIL HGNC-mediated cytotoxicity MESHD. We generated a pseudotyped SARS-CoV-2 virus with a lentiviral core but with the SARS-CoV-2 D614 or G614 SPIKE (S) protein PROTEIN on its envelope and used VSV-G lentivirus as a negative control. Our results show infection of human bronchial epithelial cells or lung cancer MESHD cells and that MEKi suppress infectivity of the SARS-CoV-2-S pseudovirus following infection MESHD. We show a drug class-effect with MEKi to promote immune responses involving NK cells, inhibit inflammatory cytokines and block host-factors for SARS-CoV-2 infection MESHD leading also to suppression of SARS-CoV-2-S pseudovirus infection MESHD of human cells in a model system. MEKi may attenuate coronavirus infection MESHD to allow immune responses and antiviral agents to control COVID-19 MESHD disease progression and severity.

    Use of a humanized anti- CD6 HGNC monoclonal antibody (itolizumab) in elderly patients with moderate COVID-19 MESHD

    Authors: Mayra Ramos-Suzarte; Yayquier Diaz; Yordanis Martin; Nestor Antonio Calderon; William Santiago; Orlando Vinet; Yulieski La O; Jorge Perez; Augusto Oyarzabal; Yoan Perez; Geidy Lorenzo; Meylan Cepeda; Danay Saavedra; Zayma Mazorra; Daymys Estevez; Patricia Lorenzo-Luaces; Carmen Valenzuela; Armando Caballero; Kalet leon; Tania Crombet; Carlos Jorge Hidalgo

    doi:10.1101/2020.07.24.20153833 Date: 2020-07-30 Source: medRxiv

    Abstract Introduction: The Severe Acute Respiratory Syndrome Coronavirus 2 MESHD (SARS-CoV-2) has caused a recent outbreak of Coronavirus Disease MESHD ( COVID-19 MESHD). In Cuba, the first case of COVID-19 MESHD was reported on March 11 HGNC. Elderly with multiple comorbidities are particularly susceptible to adverse clinical outcomes in the course of SARS CoV-2 infection MESHD. During the outbreak, a local transmission event took place in a nursing home in Villa Clara province, Cuba, in which nineteen elderly residents were positive for SARS-CoV-2. Methods: Based on the increased susceptibility to viral-induced cytokine release syndrome inducing respiratory MESHD and systemic complications in this population, the patients were included in an expanded access clinical trial to receive itolizumab, an anti- CD6 HGNC monoclonal antibody. Results: All the patients had underlying medical conditions. The product was well tolerated. After the first dose, the course of the disease was favorable and 18 out of 19 (94.7%) patients were discharged clinically recovered with negative RT-PCR at 13 days (median). One dose of itolizumab, circulating IL-6 HGNC decreased in the first 24-48 hours in patients with high baseline values, whereas in patients with low levels, this concentration remained over low values. To preliminary assess the effect of itolizumab, a control group was selected among the Cuban COVID-19 MESHD patients, which did not receive immunomodulatory therapy. Control subjects were well-matched regarding age, comorbidities and severity of the disease. Every three moderately ill patients treated with itolizumab, one admission in intensive care unit (ICU) was prevented. Discussion/Conclusion: Itolizumab was well tolerated. Its effect is associated with a reduction and controlling IL-6 HGNC serum levels. Moreover, treated patients had a favorable clinical outcome, considering their poor prognosis. This treatment is associated significantly with a decrease the risk to be admitted in ICU and reduced 10 times the risk of death MESHD. This study corroborates that the timely use of itolizumab, in combination with other antiviral and anticoagulant therapies, is associated with a reduction the COVID-19 MESHD disease worsening and mortality. The humanized antibody itolizumab emerges as a therapeutic alternative for patients with COVID-19 MESHD and suggests its possible use in patients with cytokine release syndrome from other pathologies.

    Genome-wide bioinformatic analyses predict key host and viral factors in SARS-CoV-2 pathogenesis

    Authors: Mariana G. Ferrarini; Avantika Lal; Rita Rebollo; Andreas Gruber; Andrea Guarracino; Itziar Martinez Gonzalez; Taylor Floyd; Daniel Siqueira de Oliveira; Justin Shanklin; Ethan Beausoleil; Taneli Pusa; Brett Pickett; Vanessa Aguiar-Pulido

    doi:10.1101/2020.07.28.225581 Date: 2020-07-29 Source: bioRxiv

    The novel betacoronavirus named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) caused a worldwide pandemic ( COVID-19 MESHD) after initially emerging in Wuhan, China. Here we applied a novel, comprehensive bioinformatic strategy to public RNA sequencing and viral genome sequencing data, to better understand how SARS-CoV-2 interacts with human cells. To our knowledge, this is the first meta-analysis to predict host factors that play a specific role in SARS-CoV-2 pathogenesis, distinct from other respiratory viruses. We identified differentially expressed genes, isoforms and transposable element families specifically altered in SARS-CoV-2 infected MESHD cells. Well-known immunoregulators including CSF2 HGNC, IL-32 HGNC, IL-6 HGNC and SERPINA3 HGNC were differentially expressed, while immunoregulatory transposable element families were overexpressed. We predicted conserved interactions between the SARS-CoV-2 genome and human RNA-binding proteins such as hnRNPA1 HGNC, PABPC1 HGNC and eIF4b HGNC, which may play important roles in the viral life cycle. We also detected four viral sequence variants in the spike, polymerase, and nonstructural proteins that correlate with severity of COVID-19 MESHD. The host factors we identified likely represent important mechanisms in the disease profile of this pathogen, and could be targeted by prophylactics and/or therapeutics against SARS-CoV-2.

    Point mutation bias in SARS-CoV-2 variants results in increased ability to stimulate inflammatory responses

    Authors: Masato Kosuge; Emi Furusawa-Nishii; Koyu Ito; Yoshiro Saito; Kouetsu Ogasawara

    doi:10.21203/rs.3.rs-48745/v1 Date: 2020-07-25 Source: ResearchSquare

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection MESHD induces severe pneumonia MESHD and is the cause of a worldwide pandemic. Coronaviruses, including SARS-CoV-2, have RNA proofreading enzymes in their genomes, resulting in fewer gene mutations than other RNA viruses. Nevertheless, variants of SARS-CoV-2 exist and may induce different symptoms; however, the factors and the impacts of these mutations are not well understood. We found that there is a bias to the mutations occurring in SARS-CoV-2 variants, with disproportionate mutation to uracil (U). These point mutations to U are mainly derived from cytosine (C), which is consistent with the substrate specificity of host RNA editing enzymes, APOBECs. We also found the point mutations which are consistent with other RNA editing enzymes, ADARs. For the C-to-U mutations, the context of the upstream uracil and downstream guanine from mutated position was found to be most prevalent. Further, the degree of increase of U in SARS-CoV-2 variants correlates with enhanced production of cytokines, such as TNF-a HGNC and IL-6 HGNC, in cell lines when compared with stimulation by the ssRNA sequence of the isolated virus in Wuhan. Therefore, RNA editing is a factor for mutation bias in SARS-CoV-2 variants, which affects host inflammatory cytokines production.

    Early initiation of Extracorporeal Blood Purification using the AN69ST (oXiris®) hemofilter as a treatment modality for COVID - 19 patients: a single-centre case series

    Authors: Petar Ugurov; Dijana Popevski; Tanja Gramosli; Dashurie Neziri; Dragica Vuckova; Emil Stoicovski; Lidija Veljanovska-Kiridjievska; Katerina Ignevska; Sanja Mehandziska; Elena Ambarkova; Rodney Alexander Rosalia; Zan Mitrev

    doi:10.21203/rs.3.rs-44717/v1 Date: 2020-07-17 Source: ResearchSquare

    Introduction: Our understanding of the COVID-19 MESHD disease has been steadily evolving since the original outbreak in December 2019. Advanced disease is characterised by a hyperinflammatory state, systemic coagulopathies MESHD and multiorgan involvement, in particular respiratory distress. We here describe our initial experience with treating of COVID-19 MESHD patients based on early initiation of extracorporeal blood purification, systemic heparinisation and respiratory support.Methods: 15 patients were included; 2 were females. We monitored real-time several biochemical, immunological and coagulation biomarkers associated with disease severity following admission to our dedicated COVID-19 MESHD intensive care unit. To guide personalised treatment, we monitored among others levels of IL-6 HGNC, IL-8 HGNC, TNF-α HGNC, C-Reactive Protein HGNC ( CRP HGNC), Neutrophil-to-Lymphocyte ratios, Thrombocyte counts, D-Dimers, Fibrinogen HGNC, and Activation Clotting time (ACT).Treatment consisted of individualised respiratory support supplemented with 1 - 4 cycles of 24-hour Extracorporeal Organ Support (ECOS) and Blood Purification using the AN69ST (oXiris®) hemofilter. We administered heparin (300 U/kg) to counter suspected hypercoagulability MESHD (= elevated Fibrinogen HGNC or D-dimers) states to maintain ACT ≥ 180 seconds.Results: N = 10 presented with severe to critical disease MESHD (= dyspnoea MESHD, hypoxia MESHD, respiratory rate > 30/min, peripheral oxygen saturation < 90%, or > 50% lung involvement on X-ray imaging). A single case was admitted with a critical condition (= respiratory failure MESHD). One patient died after 5 days of hospitalisation after developing Acute Respiratory Syndrome MESHD. 8 Patients have been discharged - average ICU length-of-stay was 9.9 ± 2.4 days. Clinical improvement was associated with normalisation (increase) of thrombocytes, white blood cells, stable levels of IL-6 HGNC (< 50 ng/mL) and a decrease of CRP HGNC and Fibrinogen HGNC. Conclusion: Means to monitor COVID-19 MESHD disease severity during hospitalisation are crucial to control disease progression and prevent hyperinflammation and irreversible multiorgan failure. We present here a real-time monitoring system accounting for biochemical, immunological, coagulation parameters and radiological imaging. The combination of systemic heparin anticoagulation regimens and blood purification may prevent hyperinflammation, thromboembolism MESHD during hospitalisation and thus support clinical recovery. 

    Immunophenotyping of Circulating Leukocytes Reveal Non-specific Activation of Innate and Adaptive Immune Systems in Multi-System Inflammatory Syndrome of Childhood Temporally Associated with SARS-Cov-2 Infection MESHD: Descriptive Cohort Study

    Authors: Michael J. Carter; Matthew Fish; Aislinn Jennings; Katie J. Doores; Paul Wellman; Jeffrey Seow; Sam Acors; Emma Timms; Julia Kenny; Stuart Neil; Michael H. Malim; Shane M. Tibby; Manu Shankar-Hari

    id:10.20944/preprints202007.0252.v1 Date: 2020-07-12 Source: Preprints.org

    We describe the innate and adaptive immune system trajectory in Multi-system inflammatory syndrome MESHD of childhood (MIS-C), at acute(within 72 hours of hospitalization), resolution (at clinical improvement) and convalescent phase. In our cohort, in the acute phase, 68% of the children were SARS-CoV-2 seropositive, with hypercytokinenemia (high interleukin(IL)-1beta HGNC, IL-6 HGNC, IL-8 HGNC, IL-10 HGNC, IL-17 HGNC, interferon gamma HGNC), procoagulant state, myocardial dysfunction MESHD, activated neutrophils and monocytes; differential T and B cell subset lymphopenia MESHD; activated chemokine receptor type-7 positive and gamma-delta T cell subsets; antigen presenting cells had reduced HLA-DR expression; and B-cell class-switch responses occurred with illness resolution. MIS-C is an immunopathogenic illness associated with SARS-CoV-2 infections MESHD in children.

    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.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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