Corpus overview


MeSH Disease


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    SARS-CoV-2 utilizes a multipronged strategy to suppress host protein synthesis MESHD

    Authors: Yaara Finkel; Avi Gluck; Roni Winkler; Aharon Nachshon; Orel Mizrahi; Yoav Lubelsky; Binyamin Zuckerman; Boris Slobodin; Yfat Yahalom-Ronen; Hadas Tamir; Igor Ulitsky; Tomer Israely; Nir Paran; Michal Schwartz; Noam Stern-Ginossar; Qing Ye; Tian-Shu Cao; Nan Wang; Lei Wang; Lei Cao; Huiyu Wang; Desheng Kong; Juan Ma; Chunxia Luo; Yanjing Zhang; Jianhui Nie; Yao Sun; Zhe Lv; Neil Shaw; Qianqian Li; Xiao-Feng Li; Junjie Hu

    doi:10.1101/2020.11.25.398578 Date: 2020-11-25 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease MESHD 19 ( COVID-19 MESHD) pandemic. Despite the urgent need, we still do not fully understand the molecular basis of SARS-CoV-2 pathogenesis and its ability to antagonize innate immune responses. Here, we use RNA-sequencing and ribosome profiling along SARS-CoV-2 infection MESHD and comprehensively define the mechanisms that are utilized by SARS-CoV-2 to shutoff cellular protein synthesis. We show SARS-CoV-2 infection MESHD leads to a global reduction in translation but that viral transcripts are not preferentially translated. Instead, we reveal that infection leads to accelerated degradation of cytosolic cellular mRNAs which facilitates viral takeover of the mRNA pool in infected cells. Moreover, we show that the translation of transcripts whose expression is induced in response to infection, including innate immune genes, is impaired, implying infection MESHD prevents newly transcribed cellular mRNAs from accessing the ribosomes. Overall, our results uncover the multipronged strategy employed by SARS-CoV-2 to commandeer the translation machinery and to suppress host defenses.

    A model of endemic coronavirus infections MESHD

    Authors: David S Huen; Stefan Bracke; Guillaume Duboc; Max Dupre la Tour; Paolo Frasca; Claire Mathieu; Lulla Opatowski; Laurent Viennot; John Buckley; Paul Oh; Aashish Contractor; Sherry L Grace; Virginia K Kan; H Clifford Lane; Thomas A Murray; Roger Paredes; Mahesh K.B. Parmar; Sarah Pett; Andrew N Phillips; Mark N Polizzotto; Cavan Reilly; Uriel Sandkovsky; Shweta Sharma; Mark Teitelbaum; B. Taylor Thompson; Barnaby E Young; James D Neaton; Jens D Lundgren; - TICO study group

    doi:10.1101/2020.11.08.20227975 Date: 2020-11-12 Source: medRxiv

    This work proposes that epidemiological features of both endemic coronaviruses and the recent highly pathogenic outbreak coronaviruses can be combined within an integrated framework. In this framework, mortality amongst those infected for the first time is mostly amongst the old but survivors acquire fatal infection immunity (FII). Subjects with FII can subsequently be infected and infect MESHD others without suffering significant mortality. Under these conditions, coronaviruses induce endemic infections that elicit FII in individuals during childhood when the risk of mortality is low and maintain it throughout their lifetime, thereby protecting the population against the worst effects of infection. A multi-compartment ODE model was constructed to explore the implications of this proposal on the evolution of a zoonosis sharing properties of both SARS-CoV-2 and endemic coronaviruses. The results show that mortality has two components, the first incurred during transition to endemicity and the other is exacted on a continuing basis. The relative contribution of each depends on the longevity of the FII state. In particular, a one-time vaccination of the older subpopulation is sufficient to reduce total mortality if FII is long-lived. The effect of a regular vaccination was also examined when FII was shorter lived. Herd immunity was not achieved. The validity of this proposal with regard to Covid-19 MESHD depends on whether reinfection with SARS-CoV-2 behaves in the manner expected of FII. If it does, then certain considerations apply to how Covid-19 MESHD is to be managed and how vaccine choice could influence that.

    Spatial Profiling of Lung SARS-CoV-2 and Influenza Virus Infection Dissects Virus-Specific Host Responses and Gene Signatures

    Authors: Arutha Kulasinghe; Chin Wee Tan; Anna Flavia Ribeiro dos Santos Miggiolaro; James Monkman; Dharmesh Bhuva; Jarbas da Silva Motta Junior; Caroline Busatta Vaz de Paula; Seigo Nagashima; Cristina Pellegrino Baena; Paulo Souza-Fonseca Guimaraes; Lucia Noronha; Timothy McCulloch; Gustavo Rodrigues Rossi; Caroline Cooper; Benjamin Tang; Kirsty Short; Melissa J Davis; Fernando Souza-Fonseca Guimaraes; Gabrielle T Belz; Ken O'Byrne

    doi:10.1101/2020.11.04.20225557 Date: 2020-11-06 Source: medRxiv

    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged in late 2019 has spread globally, causing a pandemic of respiratory illness designated coronavirus disease MESHD coronavirus disease 2019 MESHD ( COVID-19 MESHD). Robust blood SERO biomarkers that reflect tissue damage are urgently needed to better stratify and triage infected MESHD patients. Here, we use spatial transcriptomics to generate an in-depth picture of the pulmonary transcriptional landscape of COVID-19 MESHD (10 patients), pandemic H1N1 (pH1N1) influenza (5) and uninfected control patients (4). Host transcriptomics showed a significant upregulation of genes associated with inflammation MESHD, type I interferon production, coagulation MESHD and angiogenesis in the lungs of COVID-19 MESHD patients compared to non-infected controls. SARS-CoV-2 was non-uniformly distributed in lungs with few areas of high viral load and these were largely only associated with an increased type I interferon response. A very limited number of genes were differentially expressed between the lungs of influenza and COVID-19 MESHD patients. Specific interferon-associated genes (including IFI27) were identified as candidate novel biomarkers for COVID-19 MESHD differentiating this COVID-19 MESHD from influenza. Collectively, these data demonstrate that spatial transcriptomics is a powerful tool to identify novel gene signatures within tissues, offering new insights into the pathogenesis of SARS-COV-2 to aid in patient triage and treatment.

    Ivermectin reduces coronavirus infection MESHD in vivo: a mouse experimental model

    Authors: Ana Paula Arevalo; Romina Pagotto; Jorge Porfido; Hellen Daghero; Mercedes Segovia; Kanji Yamasaki; Belen Varela; Marcelo Hill; Jose Manuel Verdes; Maite Duhalde Vega; Mariela Bollati-Fogolin; Martina Crispo; Shazaad Ahmad; Ben Parker; Alex Horsley; Gayatri Amirthalingam; Kevin Brown; Mary E Ramsay; Shamez Ladhani; Paul Moss; Peter Inglesby; Henry Drysdale; Angel Wong; Jonathan Cockburn; Robert Mcmanus; John Parry; Frank Hester; Sam Harper; Ian J Douglas; Liam Smeeth; Stephen JW Evans; Krishnan Bhaskaran; Rosalind M Eggo; Ben Goldacre; Laurie Tomlinson

    doi:10.1101/2020.11.02.363242 Date: 2020-11-02 Source: bioRxiv

    SARS-CoV2 is a single strand RNA virus member of the type 2 coronavirus family, responsible for causing COVID-19 MESHD disease in humans. The objective of this study was to test the ivermectin drug in a murine model of coronavirus infection MESHD using a type 2 family RNA coronavirus similar to SARS-CoV2, the mouse hepatitis virus MESHD hepatitis virus HP (MHV). BALB/cJ female TRANS mice were infected with 6,000 PFU of MHV-A59 (Group Infected; n=20) and immediately treated with one single dose of 500 ug/kg of ivermectin (Group Infected + IVM; n=20), or were not infected MESHD and treated with PBS (Control group; n=16). Five days after infection/treatment, mice were euthanized to obtain different tissues to check general health status and infection levels. Overall results demonstrated that viral infection induces the typical MHV disease in infected MESHD animals, with livers showing severe hepatocellular necrosis HP hepatocellular necrosis MESHD surrounded by a severe lymphoplasmacytic inflammatory infiltration associated with a high hepatic viral load (52,158 AU), while ivermectin administration showed a better health status with lower viral load (23,192 AU; p<0.05) and few livers with histopathological damage (p<0.05), not showing statistical differences with control mice (P=NS). Furthermore, serum SERO transaminase levels (aspartate aminotransferase and alanine aminotransferase) were significantly lower in treated mice compared to infected animals. In conclusion, ivermectin seems to be effective to diminish MHV viral load and disease in mice, being a useful model for further understanding new therapies against coronavirus diseases MESHD.

    Experience of Clinical Screening for Elective Orthopedic Surgery in The Midst of The COVID-19 MESHD Pandemic: An Alternative Proposal.

    Authors: Edwarth Soler Peña; Sammy Nicolas Farah Amin; Valeria Patricia Bustos; Sofia Elizabeth Muñoz; Ernesto Martinez; Jairo Fernando Gomez; Carlos Álvarez Moreno

    doi:10.21203/ Date: 2020-10-13 Source: ResearchSquare

    Background:  The COVID-19 MESHD ( Coronavirus disease 2019 MESHD) pandemic is the largest global event of recent times, leaving millions infected MESHD and hundreds of thousands of dead worldwide. Colombia is no stranger to this situation, being subject to massive cancellations of medically necessary surgical procedures categorized as ¨non vital¨. The objective of this study is to show the results of a program of elective essential and non-essential low and medium complexity orthopedic surgeries performed during the mitigation phase of the COVID-19 MESHD pandemic with a pre-surgical clinical protocol, without serological or molecular testing, during April, 2020 in two institutions in Bogotá, Colombia. Methodology​ :​ A multicenter, observational, retrospective, descriptive study of a cohort of patients who underwent elective orthopedic surgery at two institutions in the city of Bogota, Colombia, during April 2020. We performed a preoperative clinical protocol without including serological or molecular tests, an epidemiological survey, describing the type of surgery, their score in the MeNTs (medically necessary time sensitive) scale, and the presence of suggestive symptoms of COVID-19 MESHD postoperatively. Results​ :​ A total of 179 patients underwent orthopedic surgery with an average age TRANS of 47 years (swilk= 0.021) (Shapiro-Wilk) ranging between 18 and 81 years, with a majority of females TRANS (61.5%). As for the surgeries, 86 (48%) were knee operations, 42 (23.5%) hand surgeries, 34 (19%) shoulder surgeries, and 17 (9.5%) foot and ankle surgeries. The average MeNTS of all patients was 44.6 points. During the two weeks after surgery, four patients were considered suspects for COVID-19 MESHD for presenting at least two symptoms associated with the disease representing an incidence of 2.3%. Two (1.1%) of these four patients consulted an emergency department where RT-PCR(reverse transcription polymerase chain reaction) type tests were performed, obtaining a negative result for SARSCov-2 MESHD (severe acute respiratory syndrome Coronavirus-2 MESHD). No patients died or were hospitalized for symptoms associated with COVID-19 MESHD. Conclusion​ :​ Through the implementation of a pre-surgical clinical protocol (physical examination, clinical survey inquiring about signs, symptoms and epidemiological contacts), a pre-surgical isolation and without the performance SERO of molecular or serological diagnostic tests, the present study showed good results in the performance SERO of low and medium complexity elective orthopedic surgery at an early stage of the COVID-19 MESHD pandemic. Level of evidence​ :​ IV. 

    Detection of SARS-CoV-2 nucleic acid in CSF by ultrahigh depth sequencing in a patient with COVID-19 MESHD and neurological dysfunction MESHD: a case report

    Authors: Pan Xiang; Xinmin Xu; Xin Lu; Lili Gao; Huizhu Wang; Zhenpeng Li; Haofeng Xiong; Ruihong Li; Yanwen Xiong; Lin Pu; Tian Qin; Fangfang Jin; Hongyu Ren; Chuansheng Li; Jing Yang; Ming Zhang; Jie Gong; Xiaoping Chen; Han Zheng; Jianbo Tan; Yao Sun; Fei Zhao; Xuexin Hou; Yufeng Liu; Hebing Guo; Jingjing Hao; Biao Kan; Haijian Zhou; Yajie Wang; Jingyuan Liu

    doi:10.21203/ Date: 2020-10-11 Source: ResearchSquare

    Background: SARS-Coronavirus-2 (SARS-CoV-2), the pathogen of coronavirus disease 2019 MESHD ( COVID-19 MESHD), not only infects MESHD the respiratory tract, but also other organs. About a third of the inpatients of COVID-19 MESHD have neurological symptoms and in vitro experiments revealed that SARS-CoV-2 could infect human neural progenitor cells and brain organoids. However, the traditional test often reports negative owing to the low number of virus in the cerebrospinal fluid. To date, timely diagnosis of central nervous system infection of SARS-CoV-2 MESHD remains a challenge.Case presentation: On day 14 of COVID-19 MESHD, seizures MESHD seizures HP, maxillofacial convulsions MESHD, intractable hiccups MESHD and significant increase in intracranial pressure HP developed in a 56-year-old man. The RT-PCR of SARS-CoV-2 was negative. SARS-CoV-2 nucleic acid were detected in cerebrospinal fluid (CSF) by ultrahigh depth sequencing. The patient was successfully treated after 14 days of mechanical ventilation and treatment of pneumonia MESHD pneumonia HP and neurological dysfunction MESHD.Conclusions: This case suggests SARS-CoV-2 can invade the central nervous system and relevant examinations with CSF including ultrahigh depth sequencing of SARS-CoV-2 are needed among COVID-19 MESHD patients with neurological dysfunction MESHD.

    The role of Coronavirus Disease MESHD ( COVID-19 MESHD) pandemic on anxiety MESHD anxiety HP and stress among the Palestinian general population: A cross sectional study

    Authors: Hamzeh Al Zabadi; Maryam Haj-Yahya; Noor Yaseen; Thair Alhroub

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

    BackgroundImplication of quarantine as a global response to COVID-19 MESHD may have created a dramatic psychological and emotional effect on people, which are yet to be studied and thoroughly understood. We aimed to assess the prevalence SERO and predictors of anxiety MESHD anxiety HP and stress severity among the Palestinian population.MethodsA cross-sectional web-based survey throughout the social media on internet was conducted. An anonymous online questionnaire and snowball recruiting technique were used to target the general public in Palestine during the lockdowns of COVID-19 MESHD pandemic. Data was collected between 6- 16 April 2020 which corresponded to almost the middle interval of the strict massive lockdown measures in Palestine started 22 March to 5 May 2020. Multivariate logistic regression models were developed for the outcome variables (stress and anxiety MESHD anxiety HP severity).ResultsAbout 2819 individuals completed the questionnaire. The mean (range) age TRANS was 29.47 (18-71) years. Anxiety MESHD Anxiety HP prevalence SERO was 25.15%, with 20.08% as mild/moderate anxiety HP anxiety MESHD. The prevalence SERO of stress was 38.77% with 22.21% had mild/moderate stress. The prevalence SERO of both anxiety HP anxiety MESHD and stress was 20.3% among participants. Males TRANS were less likely to have mild\moderate degree or sever\extremely sever degree of stress compared to females TRANS. Shortage of food supply, those having high-risk group family member TRANS, those who considered conversation with other people as source of information and those reporting higher fear of being infected MESHD were more likely to have higher degree of stress and/or anxiety MESHD anxiety HP compared to normal. Those with a monthly income of less than 2000 New Israeli Shekels  (<555 USD) were significantly more likely to have mild/moderate stress compared to normal and higher monthly incomes. Gaza residency also shows significant negative predictor of stress severity compared to West Bank and Jerusalem. ConclusionsThis study reported high rates of anxiety HP anxiety MESHD and stress among the Palestinian general population during COVID-19 MESHD pandemic and lockdowns. These findings highlight the importance of follow up of these findings for better management of the pandemic and a preferable handling of the socio-economical factors and their impacts on the psychological health of the population. 

    Computational Modeling Indicates A Decreased Affinity of SARS-CoV-2 to ACE2 by Steroids

    Authors: Alireza Mansouri; Rasoul Kowsar; Khaled Sadeghi; Akio Miyamoto

    doi:10.21203/ Date: 2020-09-30 Source: ResearchSquare

    The novel coronavirus disease MESHD ( COVID-19 MESHD) presently poses significant concerns around the world. Latest reports show that the degree of disease and mortality of COVID-19 MESHD infected MESHD patients may vary from gender TRANS to gender TRANS with a very high risk of death MESHD for seniors. It was hypothesized that sex steroid hormones estradiol (E2), progesterone (P4), testosterone (T), and dexamethasone (DEX) may change the interaction of coronavirus spike protein (CSP) with angiotensin converting enzyme-2 (ACE2). Data showed that E2 was more strongly to interact with the main protease of the coronavirus, while T had the lowest affinity for CSP. The binding energy of the CSP to ACE2 was increased in the presence of steroids; the greatest increase was observed by DEX and E2. The binding free energy of the CSP to ACE2 was the highest in the presence of E2 and DEX. Together, the interaction between CSP and ACE2 can be disrupted by E2 and to a greater extent by DEX, in part explaining the lower incidence of COVID-19 MESHD infection in women than men. The potential use of E2 and DEX to reduce coronavirus attachment MESHD to ACE2 in the early phase of the coronavirus invasion needs to be clinically investigated.

    Structural insights into decreased affinity of SARS-CoV-2 to ACE2 by steroids

    Authors: Alireza Mansouri; Rasoul Kowsar; Khaled Sadeghi; Akio Miyamoto

    doi:10.21203/ Date: 2020-09-24 Source: ResearchSquare

    The novel coronavirus disease MESHD ( COVID-19 MESHD) presently poses significant concerns around the world. Latest reports show that the degree of disease and mortality of COVID-19 MESHD infected MESHD patients may vary from gender TRANS to gender TRANS with a very high risk of death MESHD for seniors. Clearly, different levels of sex steroid hormones are found in both men and women. It was hypothesized that sex steroid hormones estradiol (E2), progesterone (P4), and testosterone (T) may change the interaction of coronavirus spike protein with angiotensin converting enzyme-2 (ACE2, which is the major SARS-CoV-2 cell entry receptor.) in the presence or absence of dexamethasone (DEX, the potential anti-inflammatory agents). Data showed that E2 was more strongly to interact with the main protease of the coronavirus, while T had the lowest affinity for coronavirus spike protein than E2 and P4. The binding energy of the spike protein to ACE2 was increased in the presence of five molecules of each steroid; the greatest increase was observed by DEX and E2. The binding free energy of the spike protein to ACE2 was the highest in the presence of both E2 and DEX molecules. Together, the interaction between spike protein and ACE2 can be disrupted by female TRANS sex steroid hormone E2 and to a greater extent by E2 and anti-inflammatory DEX, in part explaining the lower incidence of COVID-19 MESHD infection in women than men. The potential use of E2 and DEX to reduce coronavirus attachment MESHD to ACE2 in the early phase of the coronavirus invasion needs to be clinically investigated.

    Immunobiochemical Aspects in the Pathogenesis, Diagnosis, and Management of Novel Coronavirus (SARS-Cov-2) Infection

    Authors: Venkata Bharat Kumar Pinnelli; Mangala N. Sirsikar; W. Vishnu Vandana; Shrabani Mohanty; Wilma Delphine Silvia CR; Ranjan Kumar Mohapatra; Sabitha Vadakedath; Venkataramana Kandi

    id:202009.0565/v1 Date: 2020-09-24 Source:

    Background: A new coronavirus (SARS-CoV-2) that emerged from Wuhan, Hubei Province, China, has spread throughout the world and is declared a pandemic by the World Health Organization (WHO). A lot remains to be understood of SARS-CoV-2 and the disease ( COVID-19 MESHD). SARS-CoV-2 has until recently been identified as responsible for both asymptomatic TRANS and serious life-threatening infections. The unavailability of specific therapeutic agents is a major hurdle in the treatment and management of COVID-19 MESHD patients. The present review attempts to evaluate the immunobiochemical aspects of the pathogenesis, diagnosis, and management of SARS-CoV-2 infection MESHD. Main Body: This review is a comprehensive evaluation of the data collected through various sources, including Google Scholar, PubMed, and Scopus. The articles were searched and selected using key words such as “Coronavirus disease ( COVID-19 MESHD)”, “Diagnosis of COVID-19 MESHD”, Pathogenesis of Covid-19 MESHD”, “management of COVID-19 MESHD”, “Immunology of COVID-19 MESHD”, and “Complications of COVID-19 MESHD”. The study noted that the novel Coronavirus infection MESHD could result in an exaggerated immune response, causing a cytokine storm and damaging several organs of the body. The infected MESHD patients develop several complications, including immunological, hematological, and biochemical alterations. Consequently, COVID-19 MESHD patients may develop cardiovascular, liver, renal, and neurological complications MESHD, among others. Conclusion: An increased understanding of the immunobiochemical aspects of the disease may contribute to better management of SARS-CoV-2-infected MESHD persons, as evidenced from the available literature. A holistic approach to the management of COVID-19 MESHD patients taking into consideration the effect of COVID-19 MESHD infection on various organs of the body assumes increased significance in patient management.

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MeSH Disease

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