Corpus overview


MeSH Disease

Frailty (21)

Disease (7)

Death (7)

Delirium (5)

Infections (5)

Human Phenotype


    displaying 1 - 10 records in total 21
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    Clinical Characteristics and Severity of COVID-19 Disease MESHD in Patients from Boston Area Hospitals

    Authors: Hesamaddin Torabi Dashti; David Bates; Julie M Fiskio; Elise C Roche; Samia Mora; Olga Demler

    doi:10.1101/2020.07.27.20163071 Date: 2020-08-04 Source: medRxiv

    We summarize key demographic, clinical, and medical characteristics of patients with respect to the severity of COVID-19 disease MESHD using Electronic Health Records Data of 4,140 SARS-CoV-2 positive subjects from several large Boston Area Hospitals. We found that prior use of antihypertensive medications as well as lipid lowering and other cardiovascular drugs (such as direct oral anticoagulants and antiplatelets) all track with increased severity of COVID-19 and should be further investigated with appropriate adjustment for confounders such as age TRANS and frailty MESHD. The three most common prior comorbidities are hyperlipidemia MESHD hyperlipidemia HP, hypertension MESHD hypertension HP, and prior pneumonia MESHD pneumonia HP, all associated with increased severity.

    TMPRSS2, a SARS-CoV-2 Internalization Protease is Downregulated in Head and Neck Cancer Patients.

    Authors: Andrea Sacconi; Sara Donzelli; Claudio Pulito; Stefano Ferrero; Aldo Morrone; Marta Rigoni; Fulvia Pimpinelli; Fabrizio Ensoli; Giuseppe Sanguineti; Raul Pellini; Nishant Agrawal; Evgeny Izumchenko; Gennaro Ciliberto; Aldo Giannì; Paola Muti; Sabrina Strano; Giovanni Blandino

    doi:10.21203/ Date: 2020-07-21 Source: ResearchSquare

    Background: SARS-coronavirus-2 enters host cells through binding of the Spike protein to ACE2 receptor and subsequent S priming by the TMPRSS2 protease. We aim to assess differences in both ACE2 and TMPRSS2 expression in normal tissues from oral cavity, pharynx, larynx and lung tissues as well as neoplastic tissues from the same areas.Methods: The study has been conducted using the TCGA and the Regina Elena Institute databases and validated by experimental model in HNSCC cells. We also included data from one COVID19 patient who went under surgery for HNSCC.Results: TMPRSS2 expression in HNSCC was significantly reduced compared to the normal tissues. It was more evident in women than in men, in TP53 mutated versus wild TP53 tumors, in HPV negative patients compared to HPV positive counterparts. Functionally, we modeled the multivariate effect of TP53, HPV, and other inherent variables on TMPRSS2. All variables had a statistically significant independent effect on TMPRSS2. In particular, in tumor tissues, HPV negative, TP53 mutated status and elevated TP53-dependent Myc-target genes were associated with low TMPRSS2 expression. The further analysis of both TCGA and our institutional HNSCC datasets identified a signature anti-correlated to TMPRSS2. As proof-of-principle we also validated the anti-correlation between microRNAs and TMPRSS2 expression in a SARS-CoV-2 positive HNSCC patient tissues Finally, we did not find TMPRSS2 promoter methylation.Conclusions: Collectively, these findings suggest that tumoral tissues, herein exemplified by HNSCC and lung cancers might be more resistant to SARS-CoV-2 infection MESHD due to reduced expression of TMPRSS2. These observations may help to better assess the frailty MESHD of SARS-CoV-2 positive cancer patients.

    Atypical Presentations of COVID-19 in Care Home Residents presenting to Secondary Care: A UK Single Centre Study

    Authors: Mark James Rawle; Deborah Lee Bertfield; Simon Edward Brill

    doi:10.1101/2020.07.07.20148148 Date: 2020-07-08 Source: medRxiv

    Background: The United Kingdom (UK) care home population has experienced high mortality during the COVID-19 pandemic. Atypical presentations of COVID-19 are being reported in older adults TRANS and may pose difficulties for early isolation and treatment, particularly in institutional care settings. We aimed to characterise the presenting symptoms and associated mortality of COVID-19 in older adults TRANS, with a focus on care home residents and older adults TRANS living in the community. Methods: This was a retrospective cohort study of consecutive inpatients over 80 years old hospitalised with PCR confirmed COVID-19 between 10th March 2020 and 8th April 2020. Symptoms at presentation, including those associated with frailty MESHD, were analysed. Differences between community dwelling and care home residents, and associations with mortality, were assessed using between-group comparisons and logistic regression. Results: Care home residents were less likely to experience cough MESHD cough HP (46.9% vs 72.9%, p=0.002) but more likely to present with delirium MESHD delirium HP (51.6% vs 31.4%, p=0.018), particularly hypoactive delirium MESHD delirium HP (40.6% vs 24.3%, p=0.043). Mortality was more likely in the very frail (OR 1.25, 95% CI 1.00, 1.58, p=0.049) and those presenting with anorexia MESHD anorexia HP (OR 3.20, 95% CI 1.21, 10.09, p=0.028). There were no differences in either mortality or length of stay between those admitted from care homes and community dwelling older adults TRANS. Conclusion: COVID-19 in those over 80 does not always present with typical symptoms, particularly in those admitted from institutional care. These individuals have a reduced incidence of cough MESHD cough HP and increased hypoactive delirium MESHD delirium HP. Individuals presenting atypically, especially with anorexia MESHD anorexia HP, have higher mortality.

    Prediction Regions for Poisson and Over-Dispersed Poisson Regression Models with Applications to Forecasting Number of Deaths MESHD during the COVID-19 Pandemic

    Authors: T. KIm; B. Lieberman; G. Luta; E. Pena

    id:2007.02105v2 Date: 2020-07-04 Source: arXiv

    Motivated by the current Coronavirus Disease MESHD (COVID-19) pandemic, which is due to the SARS-CoV-2 virus, and the important problem of forecasting daily deaths MESHD and cumulative deaths MESHD, this paper examines the construction of prediction regions or intervals under the Poisson regression model and for an over-dispersed Poisson regression model. For the Poisson regression model, several prediction regions are developed and their performance SERO are compared through simulation studies. The methods are applied to the problem of forecasting daily and cumulative deaths MESHD in the United States (US) due to COVID-19. To examine their performance SERO relative to what actually happened, daily deaths MESHD data until May 15th were used to forecast cumulative deaths MESHD by June 1st. It was observed that there is over-dispersion in the observed data relative to the Poisson regression model. An over-dispersed Poisson regression model is therefore proposed. This new model builds on frailty MESHD ideas in Survival Analysis and over-dispersion is quantified through an additional parameter. The Poisson regression model is a hidden model in this over-dispersed Poisson regression model and obtains as a limiting case when the over-dispersion parameter increases to infinity. A prediction region for the cumulative number of US deaths MESHD due to COVID-19 by July 16th, given the data until July 2nd, is presented. Finally, the paper discusses limitations of proposed procedures and mentions open research problems, as well as the dangers and pitfalls when forecasting on a long horizon, with focus on this pandemic where events, both foreseen and unforeseen, could have huge impacts on point predictions and prediction regions.

    Effectiveness of a group functional power training program for frail older adults TRANS implemented through neighbourhood senior centres – a randomised controlled study

    Authors: Nien Xiang Tou; Shiou-Liang Wee; Wei Ting Seah; Daniella Hui Min Ng; Benedict Wei Jun Pang; Lay Khoon Lau; Tze Pin Ng

    doi:10.21203/ Date: 2020-07-01 Source: ResearchSquare

    Background Several trials have demonstrated the efficacy of resistance training to reduce frailty MESHD and improve function of older adults TRANS. To narrow the research-practice gap, we designed and evaluated the implementation of a community-delivered group-based functional power training (FPT) program for frail older adults TRANS within their neighbourhoods.Methods Two-arm, multicentre assessor-blind stratified randomised controlled trial at four local senior activity centres. Older adults TRANS (n = 61) with low handgrip strength (HGS) were randomised to intervention (IG) or control (CG) group. The IG underwent the FPT program (power and balance exercises using simple equipments) delivered by a community provider. The 12-week program comprised 2 × 60 mins sessions/wk. CG continued usual activities at the centres. Functional performance SERO (SPPB and TUG), HGS, knee extensor strength (KES), and frailty MESHD status were assessed at baseline and 3-month. Program implementation was evaluated using RE-AIM framework.Results The program was halted due to Coronavirus Disease MESHD 2019 related suspension of senior centre activities. Results are reported from four centres (n = 61), which completed the program. IG showed significant improvement of moderate effect sizes in frailty MESHD status (0.36 points, 95CI [0.09, 0.64], p = 0.011) and SPPB (0.51 points, 95CI [0.13, 0.89], p = 0.010). IG improvement in TUG (0.57 s, 95CI [-0.07, 1.20], p = 0.080) did not achieve significance and there were no effects for HGS and KES. Only SPPB showed greater improvement in IG than CG (p = 0.047). The community program exhibited good reach, effectiveness, adoption, and implementation.Conclusions FPT is superior to regular activities at local senior centres in improving physical function and can be successfully implemented for frail older adults TRANS in their neighbourhoods.Trial registration:, NCT04438876. Registered 19 June 2020 – Retrospectively registered,

    Prognostic factors in patients admitted to an urban teaching hospital with COVID-19 infection MESHD

    Authors: Donogh Maguire; Marylynne Woods; Conor Richards; Ross Dolan; Jesse Wilson Veitch; Wei MJ Sim; Olivia EH Kemmett; David C Milton; Sophie LW Randall; Ly D Bui; Nicola Goldmann; Allan Cameron; Barry Laird; Dinesh Talwar; Ian Godber; Alan Davidson; Donald C McMillan

    doi:10.21203/ Date: 2020-06-29 Source: ResearchSquare

    BackgroundSevere COVID-19 infection MESHD results in a systemic inflammatory response (SIRS). This SIRS response shares similarities to the changes observed during the peri-operative period that are recognised to be associated with the development of multiple organ failure MESHD. MethodsElectronic patient records for patients who were admitted to an urban teaching hospital during the initial 7-week period of the COVID-19 pandemic in Glasgow, U.K. (17th March 2020 - 1st May 2020) were examined for routine clinical, laboratory and clinical outcome data. Age TRANS, sex, BMI and documented evidence of COVID-19 infection MESHD at time of discharge or death MESHD certification were considered minimal criteria for inclusion.ResultsOf the 224 patients who fulfilled the criteria for inclusion, 52 (23%) had died at 30-days following admission. COVID-19 related respiratory failure HP (75%) and multiorgan failure (12%) were the commonest causes of death MESHD recorded. Age TRANS>70 years (p<0.001), past medical history of cognitive impairment HP (p<0.001), previous delirium MESHD delirium HP (p<0.001), clinical frailty MESHD score>3 (p<0.001), hypertension MESHD hypertension HP (p<0.05), heart failure MESHD (p<0.01), national early warning score (NEWS) >4 (p<0.01), positive CXR (p<0.01), and subsequent positive COVID-19 swab (p<0.001) were associated with 30-day mortality. CRP>80 mg/L (p<0.05), albumin <35g/L (p<0.05), peri-operative Glasgow Prognostic Score (poGPS) (p<0.05), lymphocytes <1.5 109/l (p<0.05), neutrophil lymphocyte ratio (p<0.001), haematocrit (<0.40 L/L ( male TRANS) / <0.37 L/L ( female TRANS)) (p<0.01), urea>7.5 mmol/L (p<0.001), creatinine >130 mmol/L (p<0.05) and elevated urea: albumin ratio (<0.001) were also associated with 30-day mortality.On analysis, age TRANS >70 years (O.R. 3.9, 95% C.I. 1.4 – 8.2, p<0.001), past medical history of heart failure MESHD (O.R. 3.3, 95% C.I. 1.2 – 19.3, p<0.05), NEWS >4 (O.R. 2.4, 95% C.I. 1.1 – 4.4, p<0.05), positive initial CXR (O.R. 0.4, 95% C.I. 0.2-0.9, p<0.05) and poGPS (O.R. 2.3, 95% C.I. 1.1 – 4.4, p<0.05) remained independently associated with 30-day mortality. Among those patients who tested PCR COVID-19 positive (n=122), age TRANS >70 years (O.R. 4.7, 95% C.I. 2.0 - 11.3, p<0.001), past medical history of heart failure MESHD (O.R. 4.4, 95% C.I. 1.2 – 20.5, p<0.05) and poGPS (O.R. 2.4, 95% C.I. 1.1- 5.1, p<0.05) remained independently associated with 30-days mortality.ConclusionAge > 70 years and severe systemic inflammation MESHD as measured by the peri-operative Glasgow Prognostic Score are independently associated with 30-day mortality among patients admitted to hospital with COVID-19 infection MESHD.

    Intradialytic exercise in the treatment of social frailty MESHD during the COVID-19 pandemic: A single-center prospective study

    Authors: Koki Abe; Yoshinosuke Shimamura; Takuto Maeda; Yoshikazu Kato; Yasuyoshi Yoshimura; Tomomi Tanaka; Hideki Takizawa

    doi:10.21203/ Date: 2020-06-23 Source: ResearchSquare

    Background: Social frailty—the lack of a connection to society and infrequent social activities—has been reported to be associated with future declines in physical function in elderly TRANS individuals. This study aimed to evaluate both the association of social frailty MESHD with the physical function and the efficacy of intradialytic exercise as a therapy for social frailty MESHD among hemodialysis patients.Methods: A total of 16 hemodialysis patients in the hemodialysis department of a single medical center were enrolled in this single-center prospective single-arm interventional study. Patients received five questions which asked about going out infrequently, lack of visiting friends TRANS, feeling unhelpful to friends TRANS or family, living alone, and lack of talking with someone. Those to whom two or more of the above were applicable were categorized as socially frail. All patients were placed into exercise therapy to be performed during their thrice-weekly hemodialysis visits. Participants’ physical function (walking speed), muscle strength (grip strength), muscle mass (appendicular skeletal muscle mass index), and social frailty MESHD were evaluated at baseline and after three months of therapy.Results: Four (25%) of the 16 participants (median age TRANS 71.5 years, 8 women) were categorized as being socially frail. In comparison to the non-socially frail group (non-SF), the socially frail group (SF) had a significantly lower walking speed (0.70 ± 0.12 m/s vs 1.15 ± 0.26 m/s, p= 0.005) and significantly worse performance SERO on the Short Physical Performance SERO Battery. Three months of intradialytic exercise therapy significantly improved their walking speed, from 1.04 ± 0.30 m/s to 1.16 ± 0.29 m/s (p= 0.003). Intradialytic exercise therapy significantly improved walking speed in both the SF group and the non-SF group. The 2019 coronavirus disease MESHD pandemic occurred in the middle of the intervention period of this study, and although it was not statistically significant, the number of socially frail individuals among our participants increased to seven (43.8%, p= 0.248).Conclusions: Social frailty MESHD was associated with reduced physical function among hemodialysis patients. Intradialytic exercise therapy improved physical function regardless of the presence of social frailty MESHD.Trial registration: UMIN-CTR, UMIN-CTR000038313. Registered November 1, 2019,

    Delirium MESHD Delirium HP is a presenting symptom of COVID-19 in frail, older adults TRANS: a cohort study of 322 hospitalised and 535 community-based older adults TRANS

    Authors: Maria Beatrice Zazzara; Rose S. Penfold; Amy L. Roberts; Karla Lee; Hannah Dooley; Carole H. Sudre; Carly Welch; Ruth C. E. Bowyer; Alessia Visconti; Massimo Mangino; Maxim B. Freydin; Julia S. El-Sayed Moustafa; Kerrin Small; Benjamin Murray; Marc Modat; Jonathan Wolf; Sebastien Ourselin; Finbarr C. Martin; Claire J. Steves; Mary Ni Lochlainn

    doi:10.1101/2020.06.15.20131722 Date: 2020-06-17 Source: medRxiv

    Background: Frailty MESHD, increased vulnerability to physiological stressors, is associated with adverse outcomes. COVID-19 exhibits a more severe disease MESHD course in older, co-morbid adults TRANS. Awareness of atypical presentations is critical to facilitate early identification. Objective: To assess how frailty MESHD affects presenting COVID-19 symptoms in older adults TRANS. Design: Observational cohort study of hospitalised older patients and self-report data for community-based older adults TRANS. Setting: Admissions to St Thomas' Hospital, London with laboratory-confirmed COVID-19. Community-based data for 535 older adults TRANS using the COVID Symptom Study mobile application. Subjects: Hospital cohort: patients aged TRANS 65 and over (n=322); unscheduled hospital admission between March 1st, 2020 - May 5th, 2020; COVID-19 confirmed by RT-PCR of nasopharyngeal swab. Community-based cohort: participants aged TRANS 65 and over enrolled in the COVID Symptom Study (n=535); reported test-positive for COVID-19 from March 24th (application launch)- May 8th, 2020. Methods: Multivariate logistic regression analysis performed on age TRANS-matched samples from hospital and community-based cohorts to ascertain association of frailty MESHD with symptoms of confirmed COVID-19. Results: Hospital cohort: significantly higher prevalence SERO of delirium MESHD delirium HP in the frail sample, with no difference in fever MESHD fever HP or cough MESHD cough HP. Community-based cohort: significantly higher prevalence SERO of probable delirium MESHD delirium HP in frailer, older adults TRANS, and fatigue MESHD fatigue HP and shortness of breath. Conclusions: This is the first study demonstrating higher prevalence SERO of delirium MESHD delirium HP as a COVID-19 symptom in older adults TRANS with frailty MESHD compared to other older adults TRANS. This emphasises need for systematic frailty MESHD assessment and screening for delirium MESHD delirium HP in acutely ill older patients in hospital and community settings. Clinicians should suspect COVID-19 in frail adults TRANS with delirium MESHD delirium HP.

    TMPRSS2, a SARS-CoV-2 internalization protease is downregulated in head and neck cancer patients.

    Authors: Andrea Sacconi; Sara Donzelli; Claudio Pulito; Stefano Ferrero; Aldo Morrone; Marta Rigoni; Fulvia Pimipinelli; Fabrizio Ensoli; Giuseppe Sanguineti; Raul Pellini; Nishant Agrawal; Evgeny Izumchenko; Gennaro Ciliberto; Aldo Gianni; Paola Muti; Sabrina Strano; Giovanni Blandino

    doi:10.1101/2020.06.16.154211 Date: 2020-06-16 Source: bioRxiv

    ObjectivesTwo of the main target tissues of SARS-coronavirus 2 are the oral cavity pharynx-larynx epithelium, the main virus entry site, and the lung epithelium. The virus enters host cells through binding of the Spike protein to ACE2 receptor and subsequent S priming by the TMPRSS2 protease. Herein we aim to assess differences in both ACE2 and TMPRSS2 expression in normal tissues from oral cavity-pharynx-larynx and lung tissues as well as neoplastic tissues from the same histological areas. The information provided in this study may contribute to better understanding of SARS-coronavirus 2 ability to interact with different biological systems and contributes to cumulative knowledge on potential mechanisms to inhibit its diffusion. Materials and MethodsThe study has been conducted using The Cancer Genome Atlas (TCGA) and the Regina Elena Institute (IRE) databases and validated by experimental model in HNSCC and Lung cancer cells. Data from one COVID19 positive patient who was operated on for HNSCC was also included. We have analyzed 478 tumor samples and 44 normal samples from TCGA HNSCC cohort for whom both miRNA and mRNA sequencing was available. The dataset included 391 HPV- and 85 HPV+ cases, with 331 P53 mutated and 147 P53 wild type cases respectively. 352 out of 478 samples were male TRANS and 126 female TRANS. In IRE cohort we analyzed 66 tumor samples with matched normal sample for miRNA profiling and 23 tumor\normal matched samples for mRNA profiling. 45 out of 66 tumors from IRE cohort were male TRANS and 21 female TRANS, 38 were P53 mutated and 27 wild type. Most patients (63 of 66) in IRE cohort were HPV negative. Normalized TCGA HNSCC gene expression and miRNA expression data were obtained from Broad Institute TCGA Genome Data Analysis Center ( mRNA expression data from IRE cohort used in this study has been deposited to NCBIs Gene Expression Omnibus and is accessible through GEO series accession number GSE107591. In order to inference about potential molecular modulation of TMPRSS2, we also included miRNAs expression for the 66 IRE cohort matched tumor and normal samples from Agilent platform. DNA methylation data for TCGA tumors were obtained from Wanderer ( We used miRWalk and miRNet web tools for miRNA-target interaction prediction and pathway enrichment analysis. The correlation and regression analyses as well as the miRNA and gene modulation and the survival analysis were conducted using Matlab R2019. ResultsTMPRSS2 expression in HNSCC was significantly reduced compared to the normal tissues and had a prognostic value in HNSCC patients. Reduction of TMPRSS2 expression was more evident in women than in men, in TP53 mutated versus wild TP53 tumors as well as in HPV negative patients compared to HPV positive counterparts. Functionally, we assessed the multivariate effect on TMPRSS2 in a single regression model. We observed that all variables had an independent effect on TMPRSS2 in HNSCC patients with HPV negative, TP53 mutated status and with elevated TP53-dependent Myc-target genes associated with low TMPRSS2 expression. Investigation of the molecular modulation of TMPRSS2 in both HNSCC and lung cancers revealed that expression of microRNAs targeting TMPRSS2 anti-correlated in both TCGA and IRE HNSCC datasets, while there was not evidence of TMPRSS2 promoter methylation in both tumor cohorts. Interestingly, the anti-correlation between microRNAs and TMPRSS2 expression was corroborated by testing this association in a SARS-CoV-2 positive HNSCC patient. ConclusionsCollectively, these findings suggest that tumoral tissues, herein exemplified by HNSCC and lung cancers might be more resistant to SARS-CoV-2 infection MESHD due to reduced expression of TMPRSS2. The protective mechanism might occur, at least partially, through the aberrant activation of TMPRSS2 targeting microRNAs; thereby providing strong evidence on the role of non-coding RNA molecule in host viral infection MESHD. These observations may help to better assess the frailty MESHD of SARS-CoV-2 positive cancer patients.

    Older Age TRANS and Frailty MESHD are the Chief Predictors of Mortality in COVID-19 Patients Admitted to an Acute Medical Unit in a Secondary Care Setting- A Cohort Study

    Authors: Rajkumar Chinnadurai; Onesi Ogedengbe; Priya Agarwal; Sally Money-Coomes; Ahmad Z Abdurrahman; Sajeel Mohammed; Philip A Kalra; Nicola Rothwell; Sweta Pradhan

    doi:10.21203/ Date: 2020-06-14 Source: ResearchSquare

    Background There is a need for more observational studies across different clinical settings to better understand the epidemiology of the novel COVID-19 infection MESHD. Evidence on clinical characteristics of COVID-19 infection MESHD is scarce in secondary care settings in Western populations.MethodsWe describe the clinical characteristics of all consecutive COVID-19 positive patients (n=215) admitted to the acute medical unit at Fairfield General Hospital (secondary care setting) between 23 March 2020 and 30 April 2020 based on the outcome at discharge (alive or deceased). We investigated the risk factors that were associated with mortality using binary logistic regression analysis. Kaplan-Meir (KM) charts were generated by following the outcome in all patients until 12 May 2020. ResultsThe median age TRANS of our cohort was 74 years with a predominance of Caucasians (87.4%) and males TRANS (62%). Of the 215 patients, 86 (40%) died. A higher proportion of patients who died were frail (63 vs 37%, p<0.001), with a higher prevalence SERO of cardiovascular disease MESHD (50 vs 33%, p<0.001) and respiratory diseases MESHD (38 vs 25 %, p=0.034). In the multivariate logistic regression models, older age TRANS (odds ratio (OR) 1.03; p=0.03), frailty MESHD (OR 5.1; p<0.001) and lower estimated glomerular filtration rate (eGFR) on admission (OR 0.98; p=0.01) were strong and independent predictors of inpatient mortality. KM charts showed a clear difference in survival outcome in the frail older patients. ConclusionOlder age TRANS and frailty MESHD are strong and independent risk factors associated with mortality in COVID-19 patients hospitalised to an acute medical unit at secondary care level. A holistic approach by incorporating these factors is warranted in the management of patients with COVID-19 infection MESHD.

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MeSH Disease
Human Phenotype

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