Corpus overview


MeSH Disease

Human Phenotype


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    Insights into the first wave of the COVID-19 pandemic in Bangladesh: Lessons learned from a high-risk country

    Authors: Md. Hasanul Banna Siam; Md Mahbub Hasan; Enayetur Raheem; Md. Hasinur rahaman Khan; Mahbubul H Siddiqee; Mohammad Sorowar Hossain

    doi:10.1101/2020.08.05.20168674 Date: 2020-08-06 Source: medRxiv

    Background South Asian countries including Bangladesh have been struggling to control the COVID-19 pandemic despite imposing months of lockdown and other public health measures (as of June 30, 2020). In-depth epidemiological information from these countries is lacking. From the perspective of Bangladesh, this study aims to understand the epidemiological features and gaps in public health preparedness. Method This study used publicly available data (8 March-30 June 2020) from the respective health departments of Bangladesh and Johns Hopkins University Coronavirus Resource Centre. Descriptive statistics was used to report the incidence, case fatality rates (CFR), and trend analysis. Spatial distribution maps were created using ArcGIS Desktop. Infection MESHD dynamics were analyzed via SIR models. Findings In 66 days of nationwide lockdown and other public health efforts, a total of 47,153 cases and 650 deaths MESHD were reported. However, the incidence was increased by around 50% within a week after relaxing the lockdown. Males TRANS were disproportionately affected in terms of infections MESHD (71%) and deaths MESHD (77%) than females TRANS. The CFR for males TRANS was higher than females TRANS (1.38% vs 1.01%). Over 50% of infected cases were reported among young adults TRANS (20-40-year age group TRANS). Geospatial analysis between 7 June 2020 and 20 June 2020 showed that the incidences increased 4 to 10-fold in 12 administrative districts while it decreased in the epicenter. As compared to the EU and USA, trends of the cumulative incidence were slower in South Asia with lower mortality. Conclusion Our findings on gaps in public health preparedness and epidemiological characteristics would contribute to facilitating better public health decisions for managing current and future pandemics like COVID-19 in the settings of developing countries.

    Repurposing drugs for treatment of SARS-CoV-2 infection MESHD: Computational design insights into mechanisms of action

    Authors: Shubhangi Kandwal; Darren Fayne

    doi:10.21203/ Date: 2020-08-06 Source: ResearchSquare

    The COVID-19 pandemic has negatively affected human life globally. It has led to economic crises and health emergencies MESHD across the world, spreading rapidly among the human population and has caused many deaths MESHD. Currently, there are no treatments available for COVID-19 so there is an urgent need to develop therapeutic interventions that could be used against the novel coronavirus infection MESHD. In this research, we used computational drug design technologies to repurpose existing drugs as inhibitors of SARS-CoV-2 viral proteins. The Broad Institute’s Drug Repurposing Hub consists of in-development/approved drugs and was computationally screened to identify potential hits which could inhibit protein targets encoded by the SARS-CoV-2 genome. By virtually screening the Broad collection, using rationally designed pharmacophore features, we identified molecules which may be repurposed against viral nucleocapsid and non-structural proteins. The pharmacophore features were generated after careful visualisation of the interactions between co-crystalised ligands and the protein binding site. The ChEMBL database was used to determine the compound’s level of inhibition of SARS-CoV-2 and correlate the predicted viral protein target with whole virus in vitro data. The results from this study may help to accelerate drug development against COVID-19 and the hit compounds should be progressed through further in vitro and in vivo studies on SARS-CoV-2.

    Safety of hot and cold site admissions within a high volume urology department in the United Kingdom at the peak of the COVID-19 pandemic

    Authors: Luke Stroman; Beth Russell; Pinky Kotecha; Anastasia Kantarzi; Luis Ribeiro; Bethany Jackson; Vugar Ismaylov; Adeoye Oluwakanyinsola Debo-Aina; Findlay MacAskill; Francesca Kum; Meghana Kulkarni; Raveen Sandher; Anna Walsh; Ella Doerge; Katherine Guest; Yamini Kailash; Nick Simson; Cassandra R McDonald; Elsie Mensah; Li June Tay; Ramandeep Chalokia; Sharon Clovis; Elizabeth Eversden; Jane Cossins; Jonah Rusere; Grace Zisengwe; Louisa Fleure; Leslie Cooper; Kathryn Chatterton; Amelia Barber; Catherine Roberts; Thomasia Azavedo; Jeffrey Ritualo; Harold Omana; Liza Mills; Lily Studd; Oussama El Hage; Rajesh Nair; Sachin Malde; Arun Sahai; Archana Fernando; Claire Taylor; Ben Challacombe; Ramesh Thurairaja; Rick Popert; Jonathon Olsburgh; Paul Cathcart; Christian Brown; Marios Hadjipavlou; Ella Di Benedetto; Matthew Bultitude; Jonathon Glass; Tet Yap; Rhana Zakri; Majed Shabbir; Susan Willis; Kay Thomas; Tim O'Brien; Muhammad Shamim Khan; Prokar Dasgupta

    doi:10.1101/2020.08.04.20154203 Date: 2020-08-06 Source: medRxiv

    Importance: Contracting COVID-19 peri-operatively has been associated with a mortality rate as high as 23%. Using hot and cold sites has led to a low rate of post-operative diagnosis of COVID-19 infection MESHD and allowed safe continuation of important emergency MESHD and cancer operations in our centre. Objective: The primary objective was to determine the safety of the continuation of surgical admissions and procedures during the height of the COVID-19 pandemic using hot and cold surgical sites. The secondary objective is to determine risk factors of contracting COVID-19 to help guide further prevention. Setting: A single surgical department at a tertiary care referral centre in London, United Kingdom. Participants: All consecutive patients admitted under the care of the urology team over a 3-month period from 1st March to 31st May 2020 over both hot acute admission sites and cold elective sites were included. Exposures: COVID-19 was prevalent in the community over the three months of the study at the height of the pandemic. The majority of elective surgery was carried out in a cold site requiring patients to have a negative COVID-19 swab 72 hours prior to admission and to self-isolate for 14 days pre-operatively, whilst all acute admissions were admitted to the hot site. Main outcomes and measures: COVID-19 was detected in 1.6% of post-operative patients. There was 1 (0.2%) post-operative mortality due to COVID-19. Results: A total of 611 patients, 451 (73.8%) male TRANS and 160 (26.2%) female TRANS, with a median age TRANS of 57 (interquartile range 44-70) were admitted under the surgical team. Of these, 101 (16.5%) were admitted on the cold site and 510 (83.5%) on the hot site. Surgical procedures were performed in 495 patients of which 8 (1.6%) contracted COVID-19 post-operatively with 1 (0.2%) post-operative mortality due to COVID-19. Overall, COVID-19 was detected in 20 (3.3%) patients with 2 (0.3%) deaths MESHD. On multivariate analysis, length of stay was associated with contracting COVID-19 in our cohort (OR 1.25, 95% CI 1.13-1.39). Conclusions and Relevance: Continuation of surgical procedures using hot and cold sites throughout the COVID-19 pandemic was safe practice, although the risk of COVID-19 remained and is underlined by a post-operative mortality. Reducing length of stay may be able to reduce contraction of COVID-19.

    Inflammasome activation in COVID-19 patients

    Authors: Tamara S Rodrigues; Keyla SG Sa; Adriene Y Ishimoto; Amanda Becerra; Samuel Oliveira; Leticia Almeida; Augusto V Goncalves; Debora B Perucello; Warrison A Andrade; Ricardo Castro; Flavio P Veras; Juliana E Toller-Kawahisa; Daniele C Nascimento; Mikhael HF de Lima; Camila MS Silva; Diego B Caetite; Ronaldo B Martins; Italo A Castro; Marjorie C Pontelli; Fabio C de Barros; Natalia B do Amaral; Marcela C Giannini; Leticia P Bonjorno; Maria Isabel F Lopes; Maira N Benatti; Rodrigo C Santana; Fernando C Vilar; Maria Auxiliadora-Martins; Rodrigo Luppino-Assad; Sergio CL de Almeida; Fabiola R de Oliveira; Sabrina S Batah; Li Siyuan; Maira N Benatti; Thiago M Cunha; Jose C Alves-Filho; Fernando Q Cunha; Larissa D Cunha; Fabiani G Frantz; Tiana Kohlsdorf; Alexandre T Fabro; Eurico Arruda; Rene DR de Oliveira; Paulo Louzada-Junior; Dario S Zamboni

    doi:10.1101/2020.08.05.20168872 Date: 2020-08-06 Source: medRxiv

    Severe cases of COVID-19 are characterized by a strong inflammatory process that may ultimately lead to organ failure and patient death MESHD. The NLRP3 inflammasome is a molecular platform that promotes inflammation MESHD via cleavage and activation of key inflammatory molecules including active caspase-1 (Casp1p20), IL-1{beta} and IL-18. Although the participation of the inflammasome in COVID-19 has been highly speculated, the inflammasome activation and participation in the outcome of the disease MESHD is unknown. Here we demonstrate that the NLRP3 inflammasome is activated in response to SARS-CoV-2 infection MESHD and it is active in COVID-19, influencing the clinical outcome of the disease MESHD. Studying moderate and severe COVID-19 patients, we found active NLRP3 inflammasome in PBMCs and tissues of post-mortem patients upon autopsy. Inflammasome-derived products such as Casp1p20 and IL-18 in the sera correlated with the markers of COVID-19 severity, including IL-6 and LDH. Moreover, higher levels of IL-18 and Casp1p20 are associated with disease MESHD severity and poor clinical outcome. Our results suggest that the inflammasome is key in the pathophysiology of the disease MESHD, indicating this platform as a marker of disease MESHD severity and a potential therapeutic target for COVID-19.

    Testing for SARS-CoV-2 in care home staff and residents in English care homes: A service evaluation

    Authors: Emma Smith; Clare F Aldus; Julii Brainard; Sharon Dunham; Paul R Hunter; Nicholas Steel; Paul Everden

    doi:10.1101/2020.08.04.20165928 Date: 2020-08-05 Source: medRxiv

    Background COVID-19 has especially affected care home residents. Aim To evaluate a nurse-led Enhanced Care Home Team (ECHT) enhanced SARS-CoV-2 testing strategy. Design and setting Service evaluation in care homes in Norfolk UK. Method Residents and staff received nose and throat swab tests (7 April to 29 June 2020). Resident test results were linked with symptoms on days 0-14 after test and mortality to 13 July 2020. Results Residents (n=518) in 44 homes and staff (n=340) in 10 care homes were tested. SARS-CoV-2 positivity was identified in 103 residents in 14 homes and 49 staff in seven homes. Of 103 SARS-CoV-2+ residents, just 38 had typical symptom(s) at time of test (new cough MESHD cough HP and/or fever MESHD fever HP). Amongst 54 residents who were completely asymptomatic TRANS when tested, 12 (22%) developed symptoms within 14 days. Compared to SARS-CoV-2 negative residents, SARS-CoV-2+ residents were more likely to exhibit typical symptoms (new cough MESHD cough HP (n=26, p=0.001); fever MESHD fever HP (n=24, p=<0.001)) or as generally-unwell (n=18, p=0.001). Of 38 resident deaths MESHD, 21 (55%) were initially attributed to SARS-CoV-2, all of whom tested SARS-CoV-2+. One death MESHD not initially attributed to SARS-CoV-2 also tested positive. Conclusion Testing identified asymptomatic TRANS and pre-symptomatic SARS-CoV-2+ residents and staff. Being generally-unwell was common amongst symptomatic residents and may indicate SARS-CoV-2 infection MESHD in older people in the absence of more typical symptoms. Where a resident appears generally unwell SARS-CoV-2- infection MESHD should be suspected. Protocols for testing involved integrated health and social care teams.

    Concurrent cavitary pulmonary tuberculosisand COVID-19 pneumonia MESHD pneumonia HP with in vitro immune cell anergy:a case report.

    Authors: Maria Musso; Francesco Di Gennaro; Gina Gualano; Silvia Mosti; Carlotta Cerva; Saeid Najafi Fard; Raffaella Libertone; Virginia Di Bari; Massimo Cristofaro; Roberto Tonnarini; Delia Goletti; Fabrizio Palmieri

    doi:10.21203/ Date: 2020-08-05 Source: ResearchSquare

    Tuberculosis MESHD (TB) is top infectious disease MESHD killer caused by a single organismresponsible for 1.5 million deaths MESHD in 2018. Both COVID 19 and the pandemic responseare risking to affect control measures for TB and continuity of essential services forpeople affected by this infection MESHD in western countries and even more in developingcountries. Knowledges about concomitant pulmonary TB and COVID-19 are extremelylimited. The double burden of these two diseases MESHD can have devastating effects. Herewe describe from both the clinical and the immunological point of view a case of apatient with in vitro immune cell anergy affected by bilateral cavitary pulmonary TB andsubsequent COVID-19-associated pneumonia MESHD pneumonia HP with a worst outcome. COVID-19 can bea precipitating factor in TB respiratory failure HP and, during ongoing SARS COV 2 pandemic, clinicians must be aware of this possible coinfection MESHD in differential diagnosisof patients with active TB and new or worsening chest imaging

    Reconciling epidemiological models with misclassified case-counts for SARS-CoV-2 with seroprevalence SERO surveys: A case study in Delhi, India

    Authors: Rupam Bhattacharyya; Ritwik Bhaduri; Ritoban Kundu; Maxwell Salvatore; Bhramar Mukherjee

    doi:10.1101/2020.07.31.20166249 Date: 2020-08-04 Source: medRxiv

    Underreporting of COVID-19 cases and deaths MESHD is a hindrance to correctly modeling and monitoring the pandemic. This is primarily due to limited testing, lack of reporting infrastructure and a large number of asymptomatic infections MESHD asymptomatic TRANS. In addition, diagnostic tests (RT-PCR tests for detecting current infection MESHD) and serological antibody tests SERO for IgG (to assess past infections MESHD) are imperfect. In particular, the diagnostic tests have a high false negative rate. Epidemiologic models with a latent compartment for unascertained infections MESHD like the Susceptible-Exposed-Infected-Removed (SEIR) models can provide predictions for unreported cases and deaths MESHD under certain assumptions. Typically, the number of unascertained cases is unobserved and thus we cannot validate these estimates for a real study except for simulation studies. Population-based seroprevalence SERO studies can provide a rough estimate of the total number of infections MESHD and help us check epidemiologic model projections. In this paper, we develop a method to account for high false negative rates in RT-PCR in an extension to the classic SEIR model. We apply this method to Delhi, the national capital region of India, with a population of 19.8 million and a COVID-19 hotspot of the country, obtaining estimates of underreporting factor for cases at 34-53 times and that for deaths MESHD at 8-13 times. Based on a recently released serological survey for Delhi with an estimated 22.86% seroprevalence SERO, we compute adjusted estimates of the true number of infections MESHD reported by the survey (after accounting for misclassification of the antibody test SERO results) which is largely consistent with the model outputs, yielding an underreporting factor for cases from 30-42. Together with the model and the serosurvey, this implies approximately 96-98% cases in Delhi remained unreported and whereas only 109,140 cases were reported on July 10, the true number of infections MESHD varied somewhere between 4.4-4.6 million across different estimates. While repeated serological monitoring is resource intensive, model-based adjustments, run with the most up to date data, can provide a viable option to keep track of the unreported cases and deaths MESHD and gauge the true extent of transmission TRANS of this insidious virus.

    Correlation between daily infections MESHD and fatality rate due to Covid-19 in Germany

    Authors: Dieter Mergel

    doi:10.1101/2020.08.03.20167304 Date: 2020-08-04 Source: medRxiv

    The daily Covid-19 fatality rate is modelled with a trend line based on nominal day-to-day reproduction rates and a cosine to take account of weekly fluctuations. The fatality trajectory represented by this trend line can be projected from the number of daily infections MESHD by assuming a time lapse between symptom onset TRANS and death MESHD between 17 and 19 days and a nominal time-dependent fatality rate. The time trajectory of this fatality rate suggests a change of the infection MESHD dynamics at April 3, with an increase from 2.5% to 6% within 20 days perhaps indicating spread of infection MESHD to more vulnerable people. Later in summer, the nominal fatality rate decreases down to 1% in mid-July raising the question whether Covid-19 is intrinsically less lethal in summer. Although the time trajectories of infections MESHD and fatality are pronouncedly different, the reproduction rates obtained therefrom are similar indicating that the infection MESHD dynamics may reasonably well be deduced from the potentially biased reported infection MESHD rate if it is biased consistently, i.e. the same way, over an extended period of time. The administrative measures to contain the pandemic seem not to have an immediate effect on the infection MESHD dynamics but well the ease of restrictions. An effect of mask wearing on decreasing lethality cannot be excluded.

    Clinical course and severity outcome indicators among COVID 19 hospitalized patients in relation to comorbidities distribution Mexican cohort

    Authors: Genny Carrillo; Nina Mendez Dominguez; Kassandra D Santos Zaldivar; Andrea Rochel Perez; Mario Azuela Morales; Osman Cuevas Koh; Alberto Alvarez Baeza

    doi:10.1101/2020.07.31.20165480 Date: 2020-08-04 Source: medRxiv

    Introduction: COVID-19 affected worldwide, causing to date, around 500,000 deaths MESHD. In Mexico, by April 29, the general case fatality was 6.52%, with 11.1% confirmed case TRANS mortality and hospital recovery rate around 72%. Once hospitalized, the odds for recovery and hospital death MESHD rates depend mainly on the patients' comorbidities and age TRANS. In Mexico, triage guidelines use algorithms and risk estimation tools for severity assessment and decision-making. The study's objective is to analyze the underlying conditions of patients hospitalized for COVID-19 in Mexico concerning four severity outcomes. Materials and Methods: Retrospective cohort based on registries of all laboratory-confirmed patients with the COVID-19 infection MESHD that required hospitalization in Mexico. Independent variables were comorbidities and clinical manifestations. Dependent variables were four possible severity outcomes: (a) pneumonia MESHD pneumonia HP, (b) mechanical ventilation (c) intensive care unit, and (d) death MESHD; all of them were coded as binary Results: We included 69,334 hospitalizations of laboratory-confirmed and hospitalized patients to June 30, 2020. Patients were 55.29 years, and 62.61% were male TRANS. Hospital mortality among patients aged TRANS<15 was 9.11%, 51.99% of those aged TRANS >65 died. Male TRANS gender TRANS and increasing age TRANS predicted every severity outcome. Diabetes and hypertension MESHD hypertension HP predicted every severity outcome significantly. Obesity MESHD Obesity HP did not predict mortality, but CKD, respiratory diseases MESHD, cardiopathies were significant predictors. Conclusion: Obesity MESHD Obesity HP increased the risk for pneumonia MESHD pneumonia HP, mechanical ventilation, and intensive care admittance, but it was not a predictor of in-hospital death MESHD. Patients with respiratory diseases MESHD were less prone to develop pneumonia MESHD pneumonia HP, to receive mechanical ventilation and intensive care unit assistance, but they were at higher risk of in-hospital death MESHD.

    Waves of COVID-19 pandemic. Detection and SIR simulations

    Authors: Igor Nesteruk

    doi:10.1101/2020.08.03.20167098 Date: 2020-08-04 Source: medRxiv

    Background. Unfortunately, the COVID-19 pandemic is still far from stabilizing. Of particular concern is the sharp increase in the number of diseases MESHD in June-July 2020. The causes and consequences of this sharp increase in the number of cases are still waiting for their researchers, but there is already an urgent need to assess the possible duration of the pandemic, the expected number of patients and deaths MESHD. The resumption of international passenger traffic needs the information for deciding which countries' citizens are welcome guests. Correct simulation of the infectious disease MESHD dynamics needs complicated mathematical models and many efforts for unknown parameters identification. Constant changes in the pandemic conditions (in particular, the peculiarities of quarantine and its violation, situations with testing and isolation of patients) cause various epidemic waves, lead to changes in the parameter values of the mathematical models. Objective. In this article, pandemic waves in Ukraine and in the world will be detected, calculated and discussed. The estimations for hidden periods, epidemic durations and final numbers of cases will be presented. The probabilities of meeting a person spreading the infection MESHD and reproduction numbers TRANS will be calculated for different countries and regions. Methods. We propose a simple method for the epidemic waves detection based on the differentiation of the smoothed number of cases. We use the known SIR (susceptible-infected-removed) model for the dynamics of the epidemic waves. The known exact solution of the SIR differential equations and statistical approach were modified and used. Results. The optimal values of the SIR model parameters were identified for four waves of pandemic dynamics in Ukraine and five waves in the world. The number of cases and the number of patients spreading the infection MESHD versus time were calculated. In particular, the pandemic probably began in August 2019. If current trends continue, the end of the pandemic should be expected no earlier than in March 2021 both in Ukraine and in the world, the global number of cases will exceed 20 million. The probabilities of meeting a person spreading the infection MESHD and reproduction numbers TRANS were calculated for different countries and regions. Conclusions. The SIR model and statistical approach to the parameter identification are helpful to make some reliable estimations of the epidemic waves. The number of persons spreading the infection MESHD versus time was calculated during all the epidemic waves. The obtained information will be useful to regulate the quarantine activities, to predict the medical and economic consequences of the pandemic and to decide which countries' citizens are welcome guests.

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MeSH Disease
Human Phenotype

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