Corpus overview


Overview

MeSH Disease

Human Phenotype

Transmission

Seroprevalence
    displaying 1 - 10 records in total 17
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    Sustained Cellular Immune Dysregulation HP in Individuals Recovering from SARS-CoV-2 Infection MESHD

    Authors: Jacob K Files; Sushma Boppana; Mildred D Perez; Sanghita Sarkar; Kelsey E Lowman; Kai Qin; Sarah Sterrett; Eric Carlin; Anju Bansal; Steffanie Sabbaj; Dustin M Long; Olaf Kutsch; James Kobie; Paul A Goepfert; Nathan Erdmann

    doi:10.1101/2020.07.30.20165175 Date: 2020-08-01 Source: medRxiv

    SARS-CoV-2 causes a wide spectrum of clinical manifestations and significant mortality. Studies investigating underlying immune characteristics are needed to understand disease MESHD pathogenesis and inform vaccine design. In this study, we examined immune cell subsets in hospitalized and non-hospitalized individuals. In hospitalized patients, many adaptive and innate immune cells were decreased in frequency compared to healthy and convalescent individuals, with the exception of B lymphocytes which increased. Our findings show increased frequencies of T-cell activation markers (CD69, Ox40, HLA-DR and CD154) in hospitalized patients, with other T-cell activation/exhaustion markers (CD25, PD-L1 and TIGIT) remaining elevated in hospitalized and non-hospitalized individuals. B cells had a similar pattern of activation/exhaustion, with increased frequency of CD69 and CD95 during hospitalization, followed by an increase in PD1 frequencies in non-hospitalized individuals. Interestingly, many of these changes were found to increase over time in non-hospitalized longitudinal samples, suggesting a prolonged period of immune dysregulation HP following SARS-CoV-2 infection MESHD. Changes in T-cell activation/exhaustion in non-hospitalized patients were found to positively correlate with age TRANS. Severely infected individuals had increased expression of activation and exhaustion markers. These data suggest a prolonged period of immune dysregulation HP following SARS-CoV-2 infection MESHD highlighting the need for additional studies investigating immune dysregulation HP in convalescent individuals.

    Cell type-specific immune dysregulation HP in severely ill COVID-19 patients

    Authors: Changfu Yao; Stephanie A Bora; Tanyalak Parimon; Tanzira Zaman; Oren A Friedman; Joseph A Palatinus; Nirmala S Surapaneni; Yuri P Matusov; Giuliana Cerro Chiang; Alexander G Kassar; Nayan Patel; Chelsi ER Green; Adam W Aziz; Harshpreet Suri; Jo Suda; Andres A Lopez; Gislaine A Martins; Barry R Stripp; Sina A Gharib; Helen S Goodridge; Peter Chen

    doi:10.1101/2020.07.23.20161182 Date: 2020-07-24 Source: medRxiv

    Coronavirus disease MESHD 2019 (COVID-19) has quickly become the most serious pandemic since the 1918 flu pandemic. In extreme situations, patients develop a dysregulated inflammatory lung injury MESHD called acute respiratory distress HP syndrome MESHD (ARDS) that causes progressive respiratory failure HP requiring mechanical ventilatory support. Recent studies have demonstrated immunologic dysfunction in severely ill COVID-19 patients. To further delineate the dysregulated immune response driving more severe clinical course from SARS-CoV-2 infection MESHD, we used single-cell RNA sequencing (scRNAseq) to analyze the transcriptome of peripheral blood SERO mononuclear cells (PBMC) from hospitalized COVID-19 patients having mild disease MESHD (n = 5), developing ARDS (n = 6), and recovering from ARDS (n = 6). Our data demonstrated an overwhelming inflammatory response with select immunodeficiencies HP within various immune populations in ARDS patients. Specifically, their monocytes had defects in antigen presentation and deficiencies in interferon responsiveness that contrasted the higher interferon signals in lymphocytes. Furthermore, cytotoxic activity was suppressed in both NK and CD8 lymphocytes whereas B cell activation was deficient, which is consistent with the delayed viral clearance in severely ill COVID-19 patients. Finally, we identified altered signaling pathways in the severe group that suggests immunosenescence and immunometabolic changes could be contributing to the dysfunctional immune response. Our study demonstrates that COVID-19 patients with ARDS have an immunologically distinct response when compared to those with a more innocuous disease MESHD course and show a state of immune imbalance in which deficiencies in both the innate and adaptive immune response may be contributing to a more severe disease MESHD course in COVID-19.

    COVID-19 and Children TRANS With Down Syndrome MESHD: is There Any Real Reason to Worry? Case Report

    Authors: Ahmad Kantar; Angelo Mazza; Ezio Bonanomi; Marta Odoni; Manuela Seminara; Ilaria Dalla Verde; Camillo Lovati; Stefania Bolognini; Lorenzo D’Antiga

    doi:10.21203/rs.3.rs-44432/v1 Date: 2020-07-16 Source: ResearchSquare

    Background: Down syndrome MESHD (DS) is characterised by a series of immune dysregulations HP, of which interferon hyperreactivity is a key one as it is responsible for surging antiviral responses and probable initiation of an amplified cytokine storm. This biological condition is attributed to immune regulators encoded in chromosome 21. Moreover, DS is characterised by the coexistence of cardiovascular and respiratory anomalies as well as obesity MESHD obesity HP, which constitutes a risk factor for SARS-CoV-2 respiratory disease MESHD (COVID-19).Case presentation: Of the total number of children 55 admitted to paediatric wards in Bergamo in the period between February to May 2020 for COVID-19 infection MESHD, we present 2 children TRANS with DS and confirmed COVID-19 diagnosis that had a severe course. In addition, both cases had one or more comorbidities, being cardiovascular anomalies, obesity MESHD obesity HP, and/or OSA.Conclusions: Our observations indicate the need to consider children TRANS with DS a population at a risk of severe COVID-19.

    Tobacco, but not nicotine and flavor-less electronic cigarettes, induces ACE2 and immune dysregulation HP

    Authors: Abby C. Lee; Jaideep Chakladar; Wei Tse Li; Chengyu Chen; Eric Y. Chang; Jessica Wang-Rodriguez; Weg M. Ongkeko

    doi:10.1101/2020.07.13.198630 Date: 2020-07-13 Source: bioRxiv

    COVID-19, caused by the virus SARS-CoV-2, has infected millions worldwide. This pandemic overlaps with the ongoing epidemics of cigarette smoking and electronic cigarette (e-cig) vaping, with over 1 billion smokers and vapers worldwide. However, there is scarce data relating COVID-19 risks and outcome with cigarette or e-cig use. In this study, we mined 3 independent RNA expression datasets from smokers and vapers to understand the potential relationship between vaping/smoking and the dysregulation of key genes and pathways related to COVID-19. We found that smoking, but not vaping, upregulates ACE2, the cellular receptor that SARS-CoV-2 requires for infection MESHD. Both smoking and use of nicotine and flavor-containing e-cig led to upregulations of pro-inflammatory cytokine production and expression of genes related to inflammasomes. Vaping flavor-less and nicotine-less e-cig, however, did not lead to significant cytokine dysregulation and inflammasome activation. Release of inflammasome products, such as IL-1B, and cytokine storms are hallmarks of COVID-19 infection MESHD, especially in severe cases. Therefore, our findings demonstrated that smoking or vaping, specifically use of flavored or nicotine-containing e-cigs, may critically exacerbate COVID-19-related inflammation MESHD or increase susceptibility to the disease MESHD. Further scientific and public health investigations should be undertaken to address these concerning links between COVID-19 and e-cig/smoking.

    Mapping Systemic Inflammation MESHD and Antibody SERO Responses in Multisystem Inflammatory Syndrome MESHD in Children TRANS (MIS-C)

    Authors: Conor Gruber; Roosheel Patel; Rebecca Trachman; Lauren Lepow; Fatima Amanat; Florian Krammer; Karen M. Wilson; Kenan Onel; Daniel Geanon; Kevin Tuballes; Manishkumar Patel; Konstantinos Mouskas; Nicole Simons; Vanessa Barcessat; Diane Del Valle; Samantha Udondem; Gurpawan Kang; Sandeep Gangadharan; George Ofori-Amanfo; Adeeb Rahman; Seunghee Kim-Schulze; Alexander Charney; Sacha Gnjatic; Bruce Gelb; Miriam Merad; Dusan Bogunovic

    doi:10.1101/2020.07.04.20142752 Date: 2020-07-06 Source: medRxiv

    Initially, the global outbreak of COVID-19 caused by severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) spared children TRANS from severe disease MESHD. However, after the initial wave of infections MESHD, clusters of a novel hyperinflammatory disease MESHD have been reported in regions with ongoing SARS-CoV-2 epidemics. While the characteristic clinical features are becoming clear, the pathophysiology remains unknown. Herein, we report on the immune profiles of eight Multisystem Inflammatory Syndrome MESHD in Children TRANS (MIS-C) cases. We document that all MIS-C patients had evidence of prior SARS-CoV-2 exposure, mounting an antibody SERO response with normal isotype-switching and neutralization capability. We further profiled the secreted immune response by high-dimensional cytokine assays, which identified elevated signatures of inflammation MESHD (IL-18 and IL-6), lymphocytic and myeloid chemotaxis and activation (CCL3, CCL4, and CDCP1) and mucosal immune dysregulation HP (IL-17A, CCL20, CCL28). Mass cytometry immunophenotyping of peripheral blood SERO revealed reductions of mDC1 and non-classical monocytes, as well as both NK- and T- lymphocytes, suggesting extravasation to affected tissues. Markers of activated myeloid function were also evident, including upregulation of ICAM1 and FcR1 in neutrophil and non-classical monocytes, well-documented markers in autoinflammation and autoimmunity HP that indicate enhanced antigen presentation and Fc-mediated responses. Finally, to assess the role for autoimmunity HP secondary to infection MESHD, we profiled the auto-antigen reactivity of MIS-C plasma SERO, which revealed both known disease MESHD-associated autoantibodies (anti-La) and novel candidates that recognize endothelial, gastrointestinal and immune-cell antigens. All patients were treated with anti- IL6R antibody SERO or IVIG, which led to rapid disease MESHD resolution tracking with normalization of inflammatory markers.

    Baricitinib restrains the immune dysregulation HP in COVID-19 patients

    Authors: Vincenzo Bronte; Stefano Ugel; Elisa Tinazzi; Antonio Vella; Francesco De Sanctis; Stefania Canè; Veronica Batani; Rosalinda Trovato; Alessandra Fiore; Varvara Petrova; Francesca Hofer; Roza Maria Barouni; Chiara Musiu; Simone Caligola; Laura Pinton; Lorena Torroni; Enrico Polati; Katia Donadello; Simonetta Friso; Francesca Pizzolo; Manuela Iezzi; Federica Facciotti; Pier Giuseppe Pelicci; Daniela Righetti; Paolo Bazzoni; Marielisa Rampudda; Andrea Comel; Walter Mosaner; Caludio Lunardi; Oliviero Olivieri

    doi:10.1101/2020.06.26.20135319 Date: 2020-06-29 Source: medRxiv

    Severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing pandemic coronavirus disease MESHD 2019 (COVID-19). The majority of patients with COVID-19 have a good prognosis, but variable percentages in different countries develop pneumonia MESHD pneumonia HP associated with lymphocytopenia and severe inflammatory response due to uncontrolled release of cytokines. These immune mediators are transcriptionally regulated by JAK-STAT molecular pathways, which can be disabled by small molecules. Here, we provide evidences on the efficacy of baricitinib, a JAK1/JAK2 inhibitor, in correcting the immune abnormalities observed in patients hospitalized with COVID-19. Indeed, we demonstrate a significant reduction in serum SERO levels of interleukin (IL)-6, IL-1{beta} and tumor necrosis MESHD factor (TNF), a rapid recovery in circulating T and B cell frequencies and an increased antibody SERO production against SARS-CoV-2 spike protein in baricitinib-treated patients. Moreover, treated patients underwent a rapid reduction in oxygen flow need and progressive increase in the P/F. Our work provides the basis on developing effective treatments against COVID-19 pathogenesis using on-target therapy.

    Dissecting the common and compartment-specific features of COVID-19 severity in the lung and periphery with single-cell resolution

    Authors: Kalon J. Overholt; Jonathan R. Krog; Bryan D. Bryson

    doi:10.1101/2020.06.15.147470 Date: 2020-06-15 Source: bioRxiv

    As the global COVID-19 pandemic continues to escalate, no effective treatment has yet been developed for the severe respiratory complications of this disease MESHD. This may be due in large part to the unclear immunopathological basis for the development of immune dysregulation HP and acute respiratory distress HP syndrome MESHD (ARDS) in severe and critical patients. Specifically, it remains unknown whether the immunological features of the disease MESHD that have been identified so far are compartment-specific responses or general features of COVID-19. Additionally, readily detectable biological markers correlated with strata of disease MESHD severity that could be used to triage patients and inform treatment options have not yet been identified. Here, we leveraged publicly available single-cell RNA sequencing data to elucidate the common and compartment-specific immunological features of clinically severe COVID-19. We identified a number of transcriptional programs that are altered across the spectrum of disease MESHD severity, few of which are common between the lung and peripheral immune environments. In the lung, comparing severe and moderate patients revealed severity-specific responses of enhanced interferon, A20/I{kappa}B, IL-2, and IL-6 pathway signatures along with broad signaling activity of IFNG, SPP1, CCL3, CCL8, and IL18 across cell types. These signatures contrasted with features unique to ARDS observed in the blood SERO compartment, which included depletion of interferon and A20/I{kappa}B signatures and a lack of IL-6 response. The cell surface marker S1PR1 was strongly upregulated in patients diagnosed with ARDS compared to non-ARDS patients in {gamma}{delta} T cells of the blood SERO compartment, and we nominate S1PR1 as a potential marker for immunophenotyping ARDS in COVID-19 patients using flow cytometry. HIGHLIGHTSO_LICOVID-19 disease MESHD severity is associated with a number of compositional shifts in the cellular makeup of the blood SERO and lung environments. C_LIO_LITranscriptional data suggest differentially expressed cell surface proteins as markers for COVID-19 immunophenotyping from BALF and PBMC samples. C_LIO_LISeverity-specific features COVID-19 manifest at the pathway level, suggesting distinct changes to epithelia and differences between local and systemic immune dynamics. C_LIO_LIImmune-epithelial cellular communication analysis identifies ligands implicated in transcriptional regulation of proto-oncogenes in the lung epithelia of severe COVID-19 patients. C_LIO_LINetwork analysis suggests broadly-acting dysregulatory ligands in the pulmonary microenvironment as candidate therapeutic targets for the treatment of severe COVID-19. C_LI

    Single-Cell Analysis Reveals Macrophage-Driven T Cell Dysfunction in Severe COVID-19 Patients

    Authors: Xiaoqing Liu; Airu Zhu; Jiangping He; Zhao Chen; Longqi Liu; Yuanda Xu; Feng Ye; Huijian Feng; Lin Luo; Baomei Cai; Yuanbang Mai; Lihui Lin; Zhekun Zhang; Sibei Chen; Junjie Shi; Lilan Wen; Yuanjie Wei; Jianfen Zhuo; Yingying Zhao; Fang Li; Xiaoyu Wei; Dingbin Chen; Xinmei Zhang; Na Zhong; Yaling Huang; He Liu; Jinyong Wang; Xun Xu; Jie Wang; Ruchong Chen; Xinwen Chen; Nanshan Zhong; Jinxian Zhao; Yimin Li; Jincun Zhao; Jiekai Chen

    doi:10.1101/2020.05.23.20100024 Date: 2020-05-26 Source: medRxiv

    The vastly spreading COVID-19 pneumonia MESHD pneumonia HP is caused by SARS-CoV-2. Lymphopenia MESHD Lymphopenia HP and cytokine levels are tightly associated with disease MESHD severity. However, virus-induced immune dysregulation HP at cellular and molecular levels remains largely undefined. Here, the leukocytes in the pleural effusion MESHD pleural effusion HP, sputum, and peripheral blood SERO biopsies from severe and mild patients were analyzed at single-cell resolution. Drastic T cell hyperactivation accompanying elevated T cell exhaustion was observed, predominantly in pleural effusion MESHD pleural effusion HP. The mechanistic investigation identified a group of CD14+ monocytes and macrophages highly expressing CD163 and MRC1 in the biopsies from severe patients, suggesting M2 macrophage polarization. These M2-like cells exhibited up-regulated IL10, CCL18, APOE, CSF1 (M-CSF), and CCL2 signaling pathways. Further, SARS-CoV-2-specific T cells were observed in pleural effusion MESHD pleural effusion HP earlier than in peripheral blood SERO. Together, our results suggest that severe SARS-CoV-2 infection MESHD causes immune dysregulation HP by inducing M2 polarization and subsequent T cell exhaustion. This study improves our understanding of COVID-19 pathogenesis.

    A systems approach to inflammation MESHD identifies therapeutic targets in SARS-CoV-2 infection MESHD

    Authors: Frank L. van de Veerdonk; Nico A.F. Janssen; Inge Grondman; Aline H. de Nooijer; Valerie A.C.M. Koeken; Vasiliki Matzaraki; Collins K. Boahen; Vinod Kumar; Matthijs Kox; Hans J.P.M. Koenen; Ruben L. Smeets; Irma Joosten; Roger J.M. Brüggemann; Ilse J.E. Kouijzer; Hans G. van der Hoeven; Jeroen A. Schouten; Tim Frenzel; Monique Reijers; Wouter Hoefsloot; Anton S.M. Dofferhoff; Angèle P.M. Kerckhoffs; Marc J.T. Blaauw; Karin Veerman; Coen Maas; Arjan H. Schoneveld; Imo E. Hoefer; Lennie P.G. Derde; Loek Willems; Erik Toonen; Marcel van Deuren; Jos W.M. van der Meer; Reinout van Crevel; Evangelos J. Giamarellos-Bourboulis; Leo A.B. Joosten; Michel M. van den Heuvel; Jacobien Hoogerwerf; Quirijn de Mast; Peter Pickkers; Mihai G. Netea

    doi:10.1101/2020.05.23.20110916 Date: 2020-05-24 Source: medRxiv

    Background Infection MESHD with SARS-CoV-2 manifests itself as a mild respiratory tract infection MESHD respiratory tract infection HP in the majority of individuals, which progresses to a severe pneumonia MESHD pneumonia HP and acute respiratory distress HP syndrome MESHD (ARDS) in 10-15% of patients. Inflammation MESHD plays a crucial role in the pathogenesis of ARDS, with immune dysregulation HP in severe COVID-19 leading to a hyperinflammatory response. A comprehensive understanding of the inflammatory process in COVID-19 is lacking. Methods In this prospective, multicenter observational study, patients with PCR-proven or clinically presumed COVID-19 admitted to the intensive care unit (ICU) or clinical wards were included. Demographic and clinical data were obtained and plasma SERO was serially collected. Concentrations of IL-6, TNF-, complement components C3a, C3c and the terminal complement complex (TCC) were determined in plasma SERO by ELISA SERO. Additionally, 269 circulating biomarkers were assessed using targeted proteomics. Results were compared between ICU and non ICU patients. Findings A total of 119 (38 ICU and 91 non ICU) patients were included. IL-6 plasma SERO concentrations were elevated in COVID-19 (ICU vs. non ICU, median 174.5 pg/ml [IQR 94.5-376.3 vs. 40.0 pg/ml [16.5-81.0]), whereas TNF- concentrations were relatively low and not different between ICU and non ICU patients (median 24.0 pg/ml [IQR 16.5-33.5] and 21.5 pg/ml [IQR 16.0-33.5], respectively). C3a and terminal complement complex (TCC) concentrations were significantly higher in ICU vs. non ICU patients (median 556.0 ng/ml [IQR 333.3-712.5]) vs. 266.5 ng/ml [IQR 191.5-384.0 for C3a and 4506 mAU/ml [IQR 3661-6595 vs. 3582 mAU/ml [IQR 2947-4300] for TCC) on the first day of blood SERO sampling. Targeted proteomics demonstrated that IL-6 (logFC 2.2), several chemokines and hepatocyte growth factor (logFC 1.4) were significantly upregulated in ICU vs. non ICU patients. In contrast, stem cell factor was significantly downregulated (logFC -1.3) in ICU vs. non ICU patients, as were DPP4 (logFC -0.4) and protein C inhibitor (log FC -1.0), the latter two factors also being involved in the regulation of the kinin-kallikrein pathway. Unsupervised clustering pointed towards a homogeneous pathogenetic mechanism in the majority of patients infected with SARS-CoV-2, with patient clustering mainly based on disease MESHD severity. Interpretation We identified important pathways involved in dysregulation of inflammation MESHD in patients with severe COVID-19, including the IL-6, complement system and kinin-kallikrein pathways. Our findings may aid the development of new approaches to host-directed therapy.

    Intestinal inflammation MESHD modulates the expression of ACE2 and TMPRSS2 and potentially overlaps with the pathogenesis of SARS-CoV-2 related disease MESHD

    Authors: Mayte Suárez-Fariñas; Minami Tokuyama; Gabrielle Wei; Ruiqi Huang; Alexandra Livanos; Divya Jha; Anais Levescot; Roman Kosoy; Haritz Irizar; Wenhui Wang; Ryan Ungaro; Antonio Di Narzo; Gustavo Martinez; Maria Suprun; Michael J Corley; Aleksandar Stojmirovic; Sander Houten; Mark Curran; Carrie Brodmerkel; Jacqueline Perrigoue; Joshua R Friedman; Ke Hao; Eric E Schadt; Jun Zhu; Huaibin M Ko; Judy Cho; Marla C Dubinsky; Bruce E Sands; Lishomwa Ndhlovu; Nadine Cerf-Bensusan; Andrew Kasarskis; Jean-Frederic Colombel; Noam Harpaz; Carmen Argmann; Saurabh Mehandru

    doi:10.1101/2020.05.21.109124 Date: 2020-05-23 Source: bioRxiv

    Immune dysregulation HP and cytokine release syndrome MESHD have emerged as pathological hallmarks of severe Coronavirus Disease MESHD 2019 (COVID-19), leading to the evaluation of cytokine antagonists as therapeutic agents. A number of immune-directed therapies being considered for COVID-19 patients are already in clinical use in chronic inflammatory conditions like inflammatory bowel disease MESHD (IBD). These considerations led us to systematically examine the intersections between COVID-19 and the GI tract during health and intestinal inflammation MESHD. We have observed that IBD medications, both biologic and non-biologic, do not significantly impact ACE2 and TMPRSS2 expression in the uninflamed intestines. Additionally, by comparing SARS CoV2-induced epithelial gene signatures with IBD-associated genes, we have identified a shared molecular subnetwork between COVID-19 and IBD. These data generate a novel appreciation of the confluence of COVID-19- and IBD-associated inflammation MESHD and provide mechanistic insights supporting further investigation of specific IBD drugs in the treatment of COVID-19.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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