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HGNC Genes

SARS-CoV-2 proteins

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SARS-CoV-2 Proteins
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    ESCAPE: An Open-Label Trial of Personalized Immunotherapy in Critically Ill COVID-19 MESHD Patients

    Authors: Eleni Karakike; George N Dalekos; Ioannis Koutsodimitropoulos; Maria Saridaki; Chryssa Pourzitaki; Georgios Papathanakos; Antigone Kotsaki; Stamatios Chalvatzis; Vasiliki Dimakopoulou; Nikolaos Vechlidis; Elisabeth Paramythiotou; Christina Avgoustou; Aikaterini Ioakeimidou; Elli Kouriannidi; Apostolos Komnos; Evangelia Neou; Nikoletta Rovina; Eleni Stefanatou; Haralampos Milionis; George Nikolaidis; Antonia Koutsoukou; Georgia Damoraki; George Dimopoulos; Vassileios Zoumpos; Jesper Eugen-Olsen; Karolina Akinosoglou; Nikolaos K Gatselis; Vasilios Koulouras; Eleni Gkeka; Nikolaos Markou; Mihai G Netea; Evangelos J Giamarellos-Bourboulis

    doi:10.1101/2021.01.20.21250182 Date: 2021-01-26 Source: medRxiv

    ABSTRACT Rationale Macrophage activation syndrome MESHD ( MAS MESHD) and complex immune dysregulation MESHD ( CID MESHD) often underlie acute respiratory distress MESHD (ARDS) in COVID-19 MESHD. Objective To investigate the outcome of personalized immunotherapy in critical COVID-19 MESHD. Methods In this open-label prospective trial, 102 patients with SOFA (sequential organ failure assessment) score [≥]2 or ARDS by SARS-CoV-2 were screened for MAS MESHD (ferritin more than 4420 ng/ml) and CID MESHD (ferritin [≤]4420 ng/ml and low expression of HLA-DR on CD14 HGNC-monocytes). Patients with MAS MESHD and CID MESHD with increased aminotransferases were assigned to intravenous anakinra; those with CID MESHD and normal aminotransferases to tocilizumab. The primary outcome was at least 25% decrease of SOFA score and/or 50% increase of respiratory ratio by day 8; 28-day mortality, change of SOFA score by day 28; serum biomarkers and cytokine production by mononuclear cells were secondary endpoints. Measurements and Main Results The primary study endpoint was met in 58.3% of anakinra-treated patients and in 33.3% of tocilizumab-treated patients (odds ratio 3.11; 95% CIs 1.29-7.73; P: 0.011). No differences were found in mortality and in SOFA score changes. By day 4, ferritin was decreased among anakinra-treated patients; interleukin (IL)-6 HGNC, soluble urokinase plasminogen activator receptor HGNC (suPAR) and the expression of HLA-DR were increased among tocilizumab-treated patients. Anakinra increased capacity of mononuclear cells to produce IL-6 HGNC. Survivors by day 28 who received anakinra were distributed to scales of the WHO clinical progression of lower severity. Greater incidence of secondary infections was found with tocilizumab treatment. Conclusions Biomarkers may guide favourable anakinra responses in critically ill MESHD patients with COVID-19 MESHD. Trial Registration: ClinicalTrials.gov, NCT04339712 Key-words: anakinra; tocilizumab; acute respiratory distress syndrome MESHD; COVID-19 MESHD; interleukin-6 HGNC; ferritin; HLA-DR; macrophage activation; monocytes Abstract Word count: 250

    Cytokine ranking via mutual information algorithm correlates cytokine profiles with disease severity in patients with COVID-19 MESHD

    Authors: Kelsey Huntington; Anna Louie; Chun Geun Lee; Jack A. Elias; Eric A. Ross; Wafik S. El-Deiry

    doi:10.1101/2020.11.24.20235721 Date: 2020-11-27 Source: medRxiv

    Although the range of immune responses to COVID-19 MESHD infection is variable, cytokine storm is observed in many affected individuals. Here we utilize a mutual information algorithm that classifies the information gain for COVID-19 MESHD Severity Score (CSS) prediction provided by cytokine expression levels and clinical variables. We found a small number of clinical and cytokine expression variables are predictive of presenting COVID-19 MESHD disease severity, raising questions about the mechanism of COVID-19 MESHD severe illness. Variables that were most predictive of CSS included clinical variables such as age, abnormal chest x-ray, and cytokines such as macrophage colony-stimulating factor ( M-CSF HGNC), interferon-inducible protein 10 ( IP-10 HGNC) and Interleukin-1 Receptor Antagonist HGNC ( IL-1RA HGNC). Our results suggest that SARS-CoV-2 infection MESHD causes a plethora of changes in cytokine profiles and that particularly in severely ill patients, these changes are consistent with the presence of Macrophage Activation Syndrome MESHD and could furthermore be used as a biomarker to predict disease severity.

    Monocyte-driven atypical cytokine storm and aberrant neutrophil activation as key mediators of COVID-19 MESHD disease severity

    Authors: Lore Vanderbeke; Pierre Van Mol; Yannick van Herck; Frederik De Smet; Stephanie Humblet-Baron; Kimberly Martinod; Asier Antoranz; Ingrid Arijs; Bram Boeckx; Francesca Bosisio; Michael Casaer; Dieter Dauwe; Walter De Wever; Christophe Dooms; Erwin Dreesen; Annelies Emmaneel; Jessica Filtjens; Mieke Gouwy; Jan Gunst; Greet Hermans; Sander Jansen; Katrien Lagrou; Adrian Liston; Natalie Lorent; Philippe Meersseman; Toine Mercier; Johan Neyts; Julie Odent; Dena Panovska; Pier Andree Penttila; Emily Pollet; Paul Proost; Junbin Qian; Katrien Quintelier; Jeroen Raes; Steffen Rex; Yvan Saeys; Jenny Sprooten; Sabine Tejpar; Dries Testelmans; Karin Thevissen; Tina Van Buyten; Jessica Vandenhaute; Sofie Van Gassen; Leydi Velasquez Pereira; Robin Vos; Birgit Weynand; Alexander Wilmer; Jonas Yserbyt; Abhishek Garg; Patrick Matthys; Carine Wouters; Diether Lambrechts; Els Wauters; Joost Wauters

    doi:10.21203/rs.3.rs-60579/v1 Date: 2020-08-16 Source: ResearchSquare

    Epidemiological and clinical reports have indicated that the host immune response to SARS-CoV-2, more so than viral factors, determines COVID-19 MESHD disease severity. To elucidate the immunopathology underlying COVID-19 MESHD severity, cytokine and multiplex immune profiling was performed in mild-moderate and critically-ill COVID-19 MESHD patients. Hypercytokinemia in COVID-19 MESHD differed from the IFN-γ HGNC-driven cytokine storm in macrophage activation syndrome MESHD, and was more pronounced in critical versus mild-moderate COVID-19 MESHD. Systems modelling of cytokine levels followed by deep-immune profiling showed that classical monocytes drive this hyper-inflammatory MESHD phenotype and that a reduction in T-lymphocytes correlates with disease severity, with CD8 HGNC+ cells being disproportionately affected. Expression of antigen presenting machinery was reduced in critical disease, while also neutrophils contributed to disease severity and local tissue damage by amplifying hypercytokinemia and neutrophil extracellular trap formation. We suggest a myeloid-driven immunopathology, in which hyperactivated neutrophils and an ineffective adaptive immune system act as mediators of COVID-19 MESHD disease severity.

    Be-careful! Behind the storm of severe COVID-19 MESHD, could be hidden macrophage activation syndrome. A case report with excellent outcome.

    Authors: Rafaela Silva Guimarães Gonçalves; André da Costa Victor; Ana Carolina Oliveira Cavalcanti Tavare; Angela Luzia Branco Pinto Duarte

    doi:10.21203/rs.3.rs-47499/v1 Date: 2020-07-22 Source: ResearchSquare

    In severe cases of COVID-19 MESHD, it is important to note that some laboratory signs may alert to the presence of underlying macrophage activation syndrome MESHD ( MAS MESHD), and we ratify that the classic signs of primary MAS MESHD are often not present. Here we show a case report of COVID-19 MESHD complicated by MAS MESHD treated with high doses of methylprednisolone and intravenous Immunoglobulin, with excellent clinical outcome, avoiding orotracheal intubation indeed. The interpretation of laboratory signs leads to early diagnosis and the introduction of effective therapy.

    Cytokine release syndrome is not usually caused by secondary hemophagocytic lymphohistiocytosis in a cohort of 19 critically ill COVID-19 MESHD patients

    Authors: Georg Lorenz; Philipp Moog; Quirin Bachmann; Paul La Rosee; Heike Schneider; Michaela Schlegl; Christoph Spinner; Uwe Heemann; Roland M Schmid; Hana Algül; Tobias Lahmer; Wolfgang Huber; Christoph Schmaderer

    doi:10.21203/rs.3.rs-31847/v1 Date: 2020-05-27 Source: ResearchSquare

    Background: Severe COVID-19 MESHD associated respiratory failure MESHD, poses the one challenge of our days. Assessment and treatment of COVID-19 MESHD associated hyperinflammation may be key to improve outcomes. It was speculated that in subgroups of patients secondary hemophagocytic lymphohistiocytosis MESHD (sHLH) or cytokine release syndrome (CRS) with features of macrophage activation syndrome MESHD might drive severe disease trajectories. If confirmed, profound immunosuppressive therapy would be a rationale treatment approach.Methods: Over a median observation period of 11 (IQR: 8; 16) days, 19 consecutive confirmed severe COVID-19 MESHD-patients admitted to our intensive-care-unit were tested for presence of sHLH by two independent experts. HScores and 2004-HLH diagnostic criteria were assessed. Patients were grouped according to short-term clinical courses: discharge from ICU versus ongoing ARDS or death MESHD at time of analysis.Results: The median HScore at admission was 157 (IQR: 98;180), without the key clinical triad of HLH, i.e. progressive cytopenia MESHD, persistent fever MESHD and organomegaly MESHD. Independent expert chart review revealed the absence of sHLH in all cases. No patient reached more than 3/6 of modified HLH 2004 criteria. Nevertheless, patients presented hyperinflammation with peripheral neutrophilic signatures (neutrophil/lymphocyte-ratio>3.5). The latter best paralleled their short-term clinical courses, with declining relative neutrophil numbers prior to extubation (4.4, [IQR: 2.5;6.3]; n=8) versus those with unfavourable courses (7.6, [IQR: 5.2;31], n=9).Conclusion: Our study rules out virus induced sHLH as the leading cause of most severe- COVID-19 MESHD trajectories. Instead, an associated innate neutrophilic hyperinflammatory response or virus-associated-CRS appears dominant in patients with an unfavourable clinical course. Therapeutic implications are discussed.

    Pathophysiology of SARS-CoV-2: targeting of endothelial cells renders a complex disease with thrombotic microangiopathy and aberrant immune response. The Mount Sinai COVID-19 MESHD autopsy experience

    Authors: Clare Bryce; Zachary Grimes; Elisabet Pujadas; Sadhna Ahuja; Mary Beth Beasley; Randy Albrecht; Tahyna Hernandez; Aryeh Stock; Zhen Zhao; Mohamed Al Rasheed; Joyce Chen; Li Li; Diane Wang; Adriana Corben; Kenneth Haines; William Westra; Melissa Umphlett; Ronald E Gordon; Jason Reidy; Bruce Petersen; Fadi Salem; MariaIsabel Fiel; Siraj M El Jamal; Nadejda M Tsankova; Jane Houldsworth; Zarmeen Mussa; Wen-Chun Liu; Brandon Veremis; Emilia Sordillo; Melissa Gitman; Michael Nowak; Rachel Brody; Noam Harpaz; Miriam Merad; Sacha Gnjatic; Ryan Donnelly; Patricia Seigler; Calvin Keys; Jennifer Cameron; Isaiah Moultrie; Kae-Lynn Washington; Jacquelyn Treatman; Robert Sebra; Jeffrey Jhang; Adolfo Firpo; John Lednicky; Alberto Paniz-Mondolfi; Carlos Cordon-Cardo; Mary Fowkes

    doi:10.1101/2020.05.18.20099960 Date: 2020-05-22 Source: medRxiv

    BACKGROUND Severe Acute Respiratory Syndrome Coronavirus-2 MESHD (SARS-CoV-2) and its associated clinical syndrome COVID-19 MESHD are causing overwhelming morbidity and mortality around the globe, disproportionately affecting New York City. A comprehensive, integrative autopsy series that advances the mechanistic discussion surrounding this disease process is still lacking. METHODS Autopsies were performed at the Mount Sinai Hospital on 67 COVID-19 MESHD positive patients and data from the clinical records were obtained from the Mount Sinai Data Warehouse. The experimental design included a comprehensive microscopic examination carried out by a team of expert pathologists, along with transmission electron microscopy, immunohistochemistry, RNA in situ hybridization, as well as immunology and serology assays. RESULTS Laboratory results of our COVID-19 MESHD cohort show elevated inflammatory markers, abnormal coagulation values, and elevated cytokines IL-6 HGNC, IL-8 HGNC and TNF HGNC. Autopsies revealed large pulmonary emboli MESHD in four cases. We report microthrombi in multiple organ systems including the brain, as well as conspicuous hemophagocytosis MESHD and a secondary hemophagocytic lymphohistiocytosis-like syndrome MESHD in many of our patients. We provide electron microscopic, immunofluorescent and immunohistochemical evidence of the presence of the virus and the ACE2 HGNC receptor in our samples. CONCLUSIONS We report a comprehensive autopsy series of 67 COVID-19 MESHD positive patients revealing that this disease, so far conceptualized as a primarily respiratory viral illness MESHD, also causes endothelial dysfunction, a hypercoagulable state, and an imbalance of both the innate and adaptive immune responses. Novel findings reported here include an endothelial phenotype of ACE2 HGNC in selected organs, which correlates with clotting abnormalities and thrombotic microangiopathy MESHD, addressing the prominent coagulopathy and neuropsychiatric symptoms MESHD. Another original observation is that of macrophage activation syndrome MESHD, with hemophagocytosis MESHD and a hemophagocytic lymphohistiocytosis-like disorder MESHD, underlying the microangiopathy MESHD and excessive cytokine release. We discuss the involvement of critical regulatory pathways.

    Management of rheumatic diseases in the times of COVID-19 pandemic MESHD COVID-19 pandemic MESHD- perspectives of rheumatology practitioners from India

    Authors: Latika Gupta; Durga Misra; Vishwesh Agarwal; Suma Balan; Vikas Agarwal

    doi:10.1101/2020.04.03.20048389 Date: 2020-04-07 Source: medRxiv

    Background. The Coronavirus disease MESHD 19 ( COVID-19 MESHD) pandemic has led to widespread concerns about the risk of infection in patients with rheumatic diseases MESHD ( RD MESHD) receiving disease modifying ant-rheumatic drugs (DMARDs) and other immunosuppressants (IS). Methods. A SurveyMonkey based electronic survey was conducted amongst members of the Indian Rheumatology Association to understand the need for changes in prevailing practices. Results. Of the 861 invitees, 221 responded. In the wake of the pandemic, 47.5% would reduce biological DMARDs (bDMARDs) while only 12.2% would reduce the use of conventional synthetic DMARDs. 64.2% were likely to defer change in IS, the reluctance being most with rituximab (58.3%) followed by cyclophosphamide (53.3%), anti- tumor MESHD tumor HGNC necrosis MESHD factor alpha agents (52.4%) and Janus kinase inhibitors (34.39%). Hydroxychloroquine was the preferred choice (81.9%) for the treatment of COVID-19 MESHD followed by protease inhibitors (22.1%) and intravenous immunoglobulin (8.1%). Chloroquine was less preferred (19%). More than two-thirds (70.5%) believed that COVID-19 MESHD might trigger macrophage activation syndrome MESHD. Social distancing (98.1%) and hand hygiene (74.6%) were recommended by majority. 62.8% would avoid touch for clinical examination whenever feasible. Conclusion. Most rheumatologists perceived the need to change treatment of RDs during the COVID-19 pandemic MESHD; reduce immunosuppression and defer the usage of rituximab and bDMARDs.

    Significance of hydrophobic and charged sequence similarities in sodium-bile acid cotransporter and vitamin D-binding protein HGNC macrophage activating factor

    Authors: Ibne Raihan Zunaid; Stefania Pacini; Marco Ruggiero

    doi:10.1101/2020.03.03.975524 Date: 2020-03-05 Source: bioRxiv

    Sodium-bile acid cotransporter, also denominated sodium-taurocholate cotransporting polypeptide HGNC ( NTCP HGNC) is an integral membrane protein with multiple hydrophobic transmembrane domains. The third extracellular domain of NTCP HGNC presents a stretch of nine aminoacids (KGIVISLVL) that is characterized by pronounced hydrophobicity and serves as receptor for a protein, preS1, showing the hydrophobic epta-peptide sequence NPLGFFP. Vitamin D-binding protein macrophage activating factor HGNC ( DBP HGNC DBP MESHD- MAF HGNC) is a multifunctional protein that is characterized by two hydrophobic regions able to bind fatty acids and vitamin D, respectively. Here we demonstrate that NTCP HGNC and DBP HGNC- MAF HGNC show significant sequence similarities as far as hydrophobic stretches of aminoacids are concerned. Alignment of the sequence of seven aminoacids preceding the 157-KGIVISLVL-165 stretch of NTCP HGNC shows four aminoacids that are identical to those of the corresponding sequence of DBP-MAF MESHD DBP-MAF HGNC MAF HGNC, and two that are conserved substitutions. In addition, in the sequence of DBP HGNC- MAF HGNC that is aligned with the sequence YKGIVISLVL of NTCP HGNC, there are two contiguous negatively charged aminoacids (ED) and, in the preceding epta-peptide sequence, there are three negatively charged aminoacids (D-ED), whereas in the corresponding sequence of NTCP HGNC there are only two (D--D) that are not contiguous. This concentration of negatively charged aminoacids may be involved in binding of protein inserts characterized by high density of positively charges residues. The alternating hydrophobic and electrostatic interactions described in this paper may help elucidating the biological roles of these proteins as far as protein-protein interactions are concerned.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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