Corpus overview


MeSH Disease

Human Phenotype


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    Nonstructural protein 1 of SARS-CoV-2 is a potent pathogenicity factor redirecting host protein synthesis machinery toward viral RNA.

    Authors: Shuai Yuan; Lei Peng; Jonathan J. Park; Yingxia Hu; Swapnil C. Devarkar; Matthew B. Dong; Shenping Wu; Sidi Chen; Ivan Lomakin; Yong Xiong

    doi:10.1101/2020.08.09.243451 Date: 2020-08-10 Source: bioRxiv

    The COVID-19 pandemic affects millions of people worldwide with a rising death MESHD toll. The causative agent, severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2), uses its nonstructural protein 1 (Nsp1) to redirect host translation machinery to the viral RNA by binding to the ribosome and suppressing cellular, but not viral, protein synthesis through yet unknown mechanisms. We show here that among all viral proteins, Nsp1 has the largest impact on host viability in the cells of human lung origin. Differential expression analysis of mRNA-seq data revealed that Nsp1 broadly alters the transcriptome in human cells. The changes include repression of major gene clusters in ribosomal RNA processing, translation, mitochondria function, cell cycle and antigen presentation; and induction of factors in transcriptional regulation. We further gained a mechanistic understanding of the Nsp1 function by determining the cryo-EM structure of the Nsp1-40S ribosomal subunit complex, which shows that Nsp1 inhibits translation by plugging the mRNA entry channel of the 40S. We also determined the cryo-EM structure of the 48S preinitiation complex (PIC) formed by Nsp1, 40S, and the cricket paralysis MESHD paralysis HP virus (CrPV) internal ribosome entry site (IRES) RNA, which shows that this 48S PIC is nonfunctional due to the incorrect position of the 3 region of the mRNA. Results presented here elucidate the mechanism of host translation inhibition by SARS-CoV-2, provide insight into viral protein synthesis, and furnish a comprehensive understanding of the impacts from one of the most potent pathogenicity factors of SARS-CoV-2. HighlightsORF screen identified Nsp1 as a major cellular pathogenicity factor of SARS-CoV-2 Nsp1 broadly alters the gene expression programs in human cells Nsp1 inhibits translation by blocking mRNA entry channel Nsp1 prevents physiological conformation of the 48S PIC

    Deciphering the state of immune silence in fatal COVID-19 patients

    Authors: Ido Amit; Pierre Bost; Francesco De Sanctis; Stefania Canè; Ugel Stefano; Katia Donadello; Monica Castellucci; Eyal David; Alessandra Fiore; Cristina Anselmi; Roza Barouni; Rosalinda Trovato; Simone Caligola; Alessia Lamolinara; Manuela Iezzi; Federica Facciotti; Anna Mazzariol; Davide Gibellini; Pasquale De Nardo; Evelina Tacconelli; Leonardo Gottin; Enrico Polati; Benno Schwikowski; Vincenzo Bronte

    doi:10.21203/ Date: 2020-08-10 Source: ResearchSquare

    Since the beginning of the SARS-CoV-2 pandemic, COVID-19 has appeared as a unique disease MESHD with unconventional tissue and systemic immune features. While COVID-19 severe forms share clinical and laboratory aspects with various pathologies such as hemophagocytic lymphohistiocyto-sis, sepsis MESHD sepsis HP or cytokine release syndrome MESHD, their exact nature remains unknown. This is severely imped-ing the ability to treat patients facing severe stages of the disease MESHD. To this aim, we performed an in-depth, single-cell RNA-seq analysis of more than 150.000 immune cells isolated from matched blood SERO samples and broncho-alveolar lavage fluids of COVID-19 patients and healthy controls, and integrated it with clinical, immunological and functional ex vivo data. We unveiled an immune sig-nature of disease MESHD severity that correlated with the accumulation of naïve lymphoid cells in the lung and an expansion and activation of myeloid cells in the periphery. Moreover, we demonstrated that myeloid-driven immune suppression is a hallmark of COVID-19 evolution and arginase 1 expression is significantly associated with monocyte immune regulatory features. Noteworthy, we found mon-ocyte and neutrophil immune suppression loss associated with fatal clinical outcome in severe pa-tients. Additionally, our analysis discovered that the strongest association of the patients clinical outcome and immune phenotype is the lung T cell response. We found that patients with a robust CXCR6+ effector memory T cell response have better outcomes. This result is line with the rs11385942 COVID-19 risk allel, which is in proximity to the CXCR6 gene and suggest effector memory T cell are a primary feature in COVID-19 patients. By systemically quantifying the viral landscape in the lung of severe patients, we indeed identified Herpes-Simplex MESHD-Virus 1 (HSV-1) as a potential opportunistic virus in COVID-19 patients. Lastly, we observed an unexpectedly high SARS-CoV-2 viral load in an immuno-compromised patient, allowing us to study the SARS-CoV-2 in-vivo life cycle. The development of myeloid dysfunctions and the impairment of lymphoid arm establish a condition of immune paralysis MESHD paralysis HP that supports secondary bacteria and virus infection MESHD and can progress to “immune silence” in patients facing death MESHD.

    Lung Mechanics in Type L CoVID-19 Pneumonia MESHD Pneumonia HP: A Pseudo-Normal ARDS.

    Authors: Lorenzo Viola; Emanuele Russo; Marco Benni; Emiliano Gamberini; Alessandro Circelli; Luca Bissoni; Domenico Pietro Santonastaso; Giovanni Scognamiglio; Giuliano Bolondi; Luca Mezzatesta; Vanni Agnoletti

    doi:10.21203/ Date: 2020-06-19 Source: ResearchSquare

    Since its outbreak, in January, 2020, it has been clear that CoVID-19 pneumonia MESHD pneumonia HP is atypical. Despite a full concordance to Berlin criteria for Acute Respiratory Distress HP Syndrome MESHD (ARDS), respiratory system mechanics is preserved [1]. Mechanical ventilation and muscular paralysis MESHD paralysis HP are recommended in worsening respiratory insufficiency MESHD respiratory insufficiency HP [2]; in a substantial number of cases, prone positioning significantly improves oxygenation.

    Impact of Governmental interventions on epidemic progression and workplace activity during the COVID-19 outbreak

    Authors: Sumit Kumar Ram; Didier Sornette

    doi:10.1101/2020.06.05.20122903 Date: 2020-06-07 Source: medRxiv

    In the first quarter of 2020, the COVID-19 pandemic brought the world to a state of paralysis MESHD paralysis HP. During this period, humanity has seen by far the largest organized travel TRANS restrictions and unprecedented efforts and global coordination to contain the spread of the SARS-CoV-2 virus. Using large scale human mobility and fine grained epidemic incidence data, we develop a framework to understand and quantify the effectiveness of the interventions implemented by various countries to control epidemic growth. Our analysis reveals the importance of timing and implementation of strategic policy in controlling the epidemic. Through our analysis, we also unearth significant spatial diffusion of the epidemic before and during the lock-down measures in several countries, casting doubt on the effectiveness or on the implementation quality of the proposed Governmental policies.

    T-cell hyperactivation and paralysis MESHD paralysis HP in severe COVID-19 infection MESHD revealed by single-cell analysis

    Authors: Bahire Kalfaoglu; José Almeida-Santos; Chanidapa Adele Tye; Yorifumi Satou; Masahiro Ono

    doi:10.1101/2020.05.26.115923 Date: 2020-05-26 Source: bioRxiv

    Severe COVID-19 patients can show respiratory failure HP, T-cell reduction, and cytokine release syndrome MESHD (CRS), which can be fatal in both young and aged TRANS patients and is a major concern of the pandemic. However, the pathogenetic mechanisms of CRS in COVID-19 are poorly understood. Here we show single cell-level mechanisms for T-cell dysregulation in severe SARS-CoV-2 infection MESHD, and thereby demonstrate the mechanisms underlying T-cell hyperactivation and paralysis MESHD paralysis HP in severe COVID-19 patients. By in silico sorting CD4+ T-cells from a single cell RNA-seq dataset, we found that CD4+ T-cells were highly activated and showed unique differentiation pathways in the lung of severe COVID-19 patients. Notably, those T-cells in severe COVID-19 patients highly expressed immunoregulatory receptors and CD25, whilst repressing the expression of the transcription factor FOXP3 and interestingly, both the differentiation of regulatory T-cells (Tregs) and Th17 was inhibited. Meanwhile, highly activated CD4+ T-cells express PD-1 alongside macrophages that express PD-1 ligands in severe patients, suggesting that PD-1-mediated immunoregulation was partially operating. Furthermore, we show that CD25+ hyperactivated T-cells differentiate into multiple helper T-cell lineages, showing multifaceted effector T-cells with Th1 and Th2 characteristics. Lastly, we show that CD4+ T-cells, particularly CD25-expressing hyperactivated T-cells, produce the protease Furin, which facilitates the viral entry of SARS-CoV-2. Collectively, CD4+ T-cells from severe COVID-19 patients are hyperactivated and FOXP3-mediated negative feedback mechanisms are impaired in the lung, while activated CD4+ T-cells continue to promote further viral infection MESHD through the production of Furin. Therefore, our study proposes a new model of T-cell hyperactivation and paralysis MESHD paralysis HP that drives pulmonary damage, systemic CRS and organ failure in severe COVID-19 patients.

    Hyperpyrexia leading to death MESHD in a patient with severe COVID-19 disease MESHD

    Authors: Tanu Singhal; Sourabh Phadtare; Sunil Pai; Amit Raodeo

    doi:10.1101/2020.05.18.20097220 Date: 2020-05-20 Source: medRxiv

    We describe here clinical course of a 42 year old male TRANS with severe COVID-19 disease MESHD treated at a private hospital in Mumbai India. This patient with very high inflammatory markers at admission was treated with supportive care, mechanical ventilation, anticoagulation, hydroxychloroquine, corticosteroids, tocilizumab, intravenous insulin, antibiotics, sedation and paralysis MESHD paralysis HP. There was sustained improvement in his respiratory status and decline in ventilator settings with decline and normalization of CRP, D dimer and PCT. However high fever MESHD fever HP persisted that did not respond to paracetamol and NSAIDS. On day 8 of admission his axillary temperature touched 107F followed by rapid clinical deterioration MESHD and death MESHD within the next 12 hours, Blood SERO cultures were consistently sterile.

    B Cells Over-Activation by Viral Proteins <70 kDa Causes Th2 Immune Suppression in COVID-19 Sepsis MESHD Sepsis HP

    Authors: Javier Martín

    id:10.20944/preprints202005.0244.v1 Date: 2020-05-14 Source:

    COVID-19 sepsis MESHD sepsis HP immune response remains unclear. Here we propose a new perspective in host response against pathogenic proteins that may lead to a vaccine design by polymerization of antigens of <70 kDa. In COVID-19, initial Th1 response kills infected cells releasing viral proteins. SARS-CoV-2 viral structural proteins are Spike (140 kDa), Nucleocapsid (50 kDa), Membrane (25 kDa) and Envelope (10 kDa). B cell receptor cannot capture antigens >70 kDa. The Spike protein (140 kDa) cannot be captured by B cells and triggers inflammatory Th1 response via the macrophages. Only proteins with a size <70 kDa can activate B cell receptor and trigger Th2 adaptative humoral response. Moreover, M-25 kDa and E-12 kDa glycoproteins can activate IgM-BCR like oligovalent or monovalent antigens. The sustained infected cells lysis overfeeds high levels of viral proteins <70 kDa, increases B cells activation and, in the shift from Th1 to Th2 immune response, triggers the cytokine storm. The continuous BCR activation increases IL-10 releasing and may lead to immune paralysis MESHD paralysis HP.

    Clinical characteristics of 106 patients with neurological diseases MESHD and co-morbid coronavirus disease MESHD 2019: a retrospective study

    Authors: Rong Yin; Zhiqi Yang; Yaxuan Wei; Yuanming Li; Hui Chen; Zhao Liu; Bo Zhao; Dandan Ma; Meiling Dan; Yingjie Zhang; Xuan Liu; Huiceng Leng; Dawei Xiang

    doi:10.1101/2020.04.29.20085415 Date: 2020-05-05 Source: medRxiv

    Objectives:To describe the clinical characteristics of patients with coronavirus disease MESHD 2019 (COVID-19) with co-morbid neurological symptoms. Design:Retrospective case series. Setting:Huoshenshan Hospital in Wuhan, China. Participants:From 4 February to 14 April 2020, 106 patients with neurological diseases MESHD were enrolled from all patients in the hospital with confirmed COVID-19 and divided into a severe group and a nonsevere group according to their COVID-19 diagnosis. Main outcome measures:Clinical characteristics, laboratory results, imaging findings, and treatment methods were all retrieved through an electronic medical records system and recorded in spreadsheets. Results:The mean (standard deviation, SD) age TRANS of patients was 72.7 (11.8) years, and 64 patients were male TRANS (60.4%). Among patients with co-morbid neurological diseases MESHD, 81 had a previous cerebral infarction MESHD (76.4%), 20 had dementia MESHD dementia HP (18.9%), 10 had acute cerebral infarction MESHD (9.4%), 5 had sequelae of cerebral haemorrhage (4.7%), 4 had intracranial mass lesions (3.8%), 3 had epilepsy MESHD (2.8%), 2 had Parkinsons disease MESHD (1.9%), and 1 had myelopathy HP (0.9%). Fever MESHD Fever HP (n = 62, 58.5%) was the most common symptom. The most common neurological symptoms were myalgia MESHD myalgia HP (n = 26, 24.5%), followed by extremity paralysis MESHD paralysis HP (n = 20, 18.9%), impaired consciousness (n = 17, 16%), and positive focal neurological signs (n = 42, 39.6%). Eight patients (7.5%) died. There were more patients with altered mental status in the severe group than in the non-severe group (6 [10.2%] vs. 0, P = 0.033). The inflammatory response in the severe group was more significant than that in the non-severe group. There were more patients taking anticoagulant drugs (25 [42.4%] vs. 4 [8.5%], P < 0.001) and sedative drugs (22 [37.3%] vs. 9 [19.1%], P = 0.041) in the severe group than in the non-severe group. Amid all 93 patients with cerebrovascular diseases MESHD, only 32 (34.4%) were taking aspirin, 13 (14%) taking clopidogrel, and 33 (35.5%) taking statins. Conclusions:Patients with COVID-19 with co-morbid neurological diseases MESHD had an advanced age TRANS, a high rate of severe illness, and a high mortality rate. Among the neurological symptoms, altered mental status was more common in patients with severe COVID-19 with co-morbid neurological diseases MESHD.

    Early Guillain-Barré syndrome MESHD in COronaVIrus Disease MESHD 2019 (COVID-19): a case report from an Italian COVID-Hospital

    Authors: Donatella Ottaviani; Federica Boso; Enzo Tranquillini; Ilaria Gapeni; Giovanni Pedrotti; Susanna Cozzio; Giovanni M. Guarrera; Bruno Giometto

    doi:10.21203/ Date: 2020-04-24 Source: ResearchSquare

    Guillain Barré syndrome MESHD (GBS) is an acute polyradiculoneuropathy MESHD associated with dysimmune processes, often related to a previous infectious exposure. During Italian Severe Acute Respiratory Syndrome MESHD Coronavirus-2 outbreak, a woman presented with a rapidly progressive flaccid paralysis MESHD paralysis HP with unilateral facial neuropathy after a few days of mild respiratory symptoms. Coronavirus was detected by nasopharyngeal swab, but there was no evidence of its presence in her cerebrospinal fluid, which confirmed the typical albumin-cytological dissociation of GBS, along with consistent neurophysiological data. Despite immunoglobulin infusions and intensive supportive care, her clinical picture worsened simultaneously both from respiratory and neurological point of view, as if reflecting different aspects of the same systemic inflammatory response. Similar early complications have already been observed in patients with para-infectious GBS related to Zika virus, but pathological mechanisms have yet to be established.

    Acute myelitis MESHD myelitis HP after SARS-CoV-2 infection MESHD: a case report.

    Authors: Kang Zhao; Jucun Huang; Dan Dai; Yuwei Feng; Liming Liu; Shuke Nie

    doi:10.1101/2020.03.16.20035105 Date: 2020-03-18 Source: medRxiv

    We report a case of acute myelitis MESHD myelitis HP in a patient infected with severe acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2). A 66-year-old man with coronavirus disease MESHD 2019 was admitted with acute flaccid paralysis MESHD paralysis HP of the bilateral lower limbs and urinary and bowel incontinence HP. All serum SERO microbiological test results were negative, except for SARS-CoV-2 nucleic acid testing. Clinical findings indicated post-infectious acute myelitis MESHD myelitis HP. He received treatment containing ganciclovir, lopinavir/ritonavir, moxifloxacin, dexamethasone, human immunoglobulin, and mecobalamin. With a diagnosis of post-infectious acute myelitis MESHD myelitis HP and comprehensive treatment, paralysis MESHD paralysis HP of the bilateral lower extremities ameliorated. After two negative novel coronavirus RNA nasopharyngeal swab tests, he was discharged and transferred to a designated hospital for isolation and rehabilitation therapy.

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MeSH Disease
Human Phenotype

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