Corpus overview


MeSH Disease

Human Phenotype


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    IFN signaling and neutrophil degranulation transcriptional signatures are induced during SARS-CoV-2 infection MESHD

    Authors: Bruce A. Rosa; Mushtaq Ahmed; Dhiraj K. Singh; Jose Alberto Choreno-Parra; Journey Cole; Luis Armando Jimenez-Alvarez; Tatiana Sofia Rodriguez-Reyna; Bindu Singh; Olga Golzalez; Ricardo Carrion; Larry S. Schlesinger; John Martin; Joaquin Zuniga; Makedonka Mitreva; Shabaana A Khader; Deepak Kaushal

    doi:10.1101/2020.08.06.239798 Date: 2020-08-06 Source: bioRxiv

    The novel virus SARS-CoV-2 has infected more than 14 million people worldwide resulting in the Coronavirus disease MESHD 2019 (COVID-19). Limited information on the underlying immune mechanisms that drive disease MESHD or protection during COVID-19 severely hamper development of therapeutics and vaccines. Thus, the establishment of relevant animal models that mimic the pathobiology of the disease is urgent. Rhesus macaques infected with SARS-CoV-2 exhibit disease pathobiology similar to human COVID-19, thus serving as a relevant animal model. In the current study, we have characterized the transcriptional signatures induced in the lungs of juvenile and old rhesus macaques following SARS-CoV-2 infection MESHD. We show that genes associated with Interferon (IFN) signaling, neutrophil degranulation and innate immune pathways are significantly induced in macaque infected lungs MESHD, while pathways associated with collagen formation are downregulated. In COVID-19, increasing age TRANS is a significant risk factor for poor prognosis and increased mortality. We demonstrate that Type I IFN and Notch signaling pathways are significantly upregulated in lungs of juvenile infected MESHD macaques when compared with old infected macaques. These results are corroborated with increased peripheral neutrophil counts and neutrophil lymphocyte ratio in older individuals with COVID-19 disease. In contrast, pathways involving VEGF are downregulated in lungs of old infected macaques. Using samples from humans with SARS-CoV-2 infection MESHD and COVID-19, we validate a subset of our findings. Finally, neutrophil degranulation, innate immune system and IFN gamma signaling pathways are upregulated in both tuberculosis MESHD and COVID-19, two pulmonary diseases MESHD where neutrophils are associated with increased severity. Together, our transcriptomic studies have delineated disease pathways to improve our understanding of the immunopathogenesis of COVID-19 to facilitate the design of new therapeutics for COVID-19.

    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 coronavirus 2 MESHD (SARS-CoV-2) spared children TRANS from severe disease. However, after the initial wave of infections, clusters of a novel hyperinflammatory disease MESHD have been reported in regions with ongoing SARS-CoV-2 MESHD 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 MESHD and autoimmunity HP that indicate enhanced antigen presentation and Fc-mediated responses. Finally, to assess the role for autoimmunity HP secondary to infection, we profiled the auto-antigen reactivity of MIS-C plasma SERO, which revealed both known disease-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 resolution tracking with normalization of inflammatory markers.

    Risk and protective factors of SARS-CoV-2 infection MESHD - Meta-regression of data from worldwide nations

    Authors: Hisato Takagi; Toshiki Kuno; Yujiro Yokoyama; Hiroki Ueyama; Takuya Matsushiro; Yosuke Hari; Tomo Ando

    doi:10.1101/2020.06.06.20124016 Date: 2020-06-07 Source: medRxiv

    Although it has been reported that coexistent chronic diseases MESHD are strongly associated with COVID-19 severity, investigations of predictors for SARS-CoV-2 infection MESHD itself have been seldom performed. To screen potential risk and protective factors for SARS-CoV-2 infection MESHD, meta-regression of data from worldwide nations were herein conducted. We extracted total confirmed COVID-19 cases in worldwide 180 nations (May 31, 2020), nation total population, population ages TRANS 0-14/65 and above, GDP/GNI per capita, PPP, life expectancy at birth, medical-doctor and nursing/midwifery-personnel density, hypertension HP hypertension MESHD/ obesity HP obesity MESHD/ diabetes MESHD prevalence SERO, annual PM2.5 concentrations, daily ultraviolet radiation, population using safely-managed drinking-water/sanitation services and hand-washing facility with soap/water, inbound tourism, and bachelor's MESHD or equivalent (ISCED 6). Restricted maximum-likelihood meta-regression in the random-effects model was performed using Comprehensive Meta-Analysis version 3. To adjust for other covariates, we conducted the hierarchical multivariate models. A slope (coefficient) of the meta-regression line for the COVID-19 prevalence SERO was significantly negative for population ages TRANS 0-14 (-0.0636; P = .0021) and positive for obesity HP obesity MESHD prevalence SERO (0.0411; P = .0099) and annual PM2.5 concentrations in urban areas (0.0158; P = .0454), which would indicate that the COVID-19 prevalence SERO decreases significantly as children TRANS increase and that the COVID-19 prevalence SERO increases significantly as the obese MESHD and PM2.5 increase. In conclusion, children TRANS (negatively) and obesity HP obesity MESHD/PM2.5 (positively) may be independently associated with SARS-CoV-2 infection MESHD.

    Epidemiological and clinical characteristics of COVID-19 patients in Nanjing

    Authors: Wei Chen; Chunmei Hu; Lili Huang; Min Cai; Yongchen Zhang; Hongxia Wei; Yun Chi; Zhiliang Hu; Yi Zeng; Yishan Zheng; Ying Liu; Cong Cheng; Hongmei Zhang; Weixiao Wang; Xia Zhang; Yongxiang Yi

    doi:10.21203/ Date: 2020-03-18 Source: ResearchSquare

    Background: Since December 2019, the outbreak of COVID-19 has spread quickly and thumped many countries and regions. The epidemic of central China was under the spotlight and attracted much more attentions. However, there are few reports describing COVID-19 patients in the regions outside of Wuhan, which are undergoing the change from sporadic imported cases to community-acquired transmission TRANS.Methods: The electronic medical records of 74 laboratory-confirmed patients of COVID-19 were retrospectively reviewed and analyzed. Their epidemiological, demographic, clinical and radiological characteristics were systematically summarized. The difference between severe patients and non-severe patients were also analyzed statistically.Results: The 74 COVID-19 patients were composed of 4 (5.4%) mild patients, 56 (75.7%) common patients, 13 (17.6%) severe patients and 1 (1.4%) critical patient. 43 were male TRANS, and 31 were female TRANS, with the average age TRANS 48.1±17.5. No significant difference of susceptibility was observed between genders TRANS, and almost people with all age TRANS were susceptible to SARS-CoV-2 infection MESHD. Before Jan 26, only imported sporadic cases were observed. However, from that day onward, family cluster infection MESHD cases increased dramatically, up to 70.3% (52/74), which were mainly from 15 family. The incubation period TRANS spanned from 0 to 19 days, with the median 5, and 81.4% had symptom onset TRANS within 7 days. At admission, 31.1% of patients had underlying diseases MESHD and the most common underlying diseases were hypertension HP hypertension MESHD (13.5%) and diabetes MESHD (5.4%). The most common symptoms were fever HP fever MESHD (90.5%), cough HP (75.7%), fatigue HP fatigue MESHD (36.5%) and chest distress (32.4%). 36.5% and 16.2% of patients had leukopenia HP leukopenia MESHD and lymphocytopenia MESHD. 43.2% of patients had increased C reactive protein (CRP), and 40.5% had higher erythrocyte sedimentation rate (ESR) and 21.6% had higher calcitonin. 74.3% of patients had obvious lesions in both lung lobes MESHD and 56.8% of lesions manifested as ground glass opacity. Compared with non-severe group, the severe/critical group were significantly older and had more underlying diseases. After treatment, all patients improved and were discharged. No medical professional infection MESHD and death case were reported.Conclusion: The epidemic of COVID-19 in Nanjing were mainly caused by family cluster infection MESHD. The entire prevalence SERO and illness were much milder than those of Wuhan. The disease of COVID-19 could be controlled and cured.  

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MeSH Disease
Human Phenotype

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