bluuebunny/crossref_metadata_2025_split huggingface dataset:
Healthcare disparities among anticoagulation therapies for severe COVID-19 patients in the multi-site VIRUS registry
Authors: Kirkup Christian , Pawlowski Colin , Puranik Arjun , Conrad Ian , O’Horo John C. , Gomaa Dina , Banner-Goodspeed Valerie M. , Mosier Jarrod M , Zabolotskikh Igor Borisovich , Daugherty Steven K. , Bernstein Michael A. , Zaren Howard A. , Bansal Vikas , Pickering Brian , Badley Andrew D. , Kashyap Rahul , Venkatakrishnan AJ , Soundararajan Venky 
Published: November 2020

AbstractCOVID-19 patients are at an increased risk of thrombosis and various anticoagulants are being used in patient management without an established standard-of-care. Here, we analyze hospitalized and ICU patient outcomes from the Viral Infection and Respiratory illness Universal Study (VIRUS) registry. We find that severe COVID patients administered unfractionated heparin but not enoxaparin have a higher mortality-rate (311 deceased patients out of 760 total patients = 41%) compared to patients administered enoxaparin but not unfractionated heparin (214 deceased patients out of 1,432 total patients = 15%), presenting a risk ratio of 2.74 (95% C.I.: [2.35, 3.18]; p-value: 1.4e-41). This difference persists even after balancing on a number of covariates including: demographics, comorbidities, admission diagnoses, and method of oxygenation, with an amplified mortality rate of 39% (215 of 555) for unfractionated heparin vs. 23% (119 of 522) for enoxaparin, presenting a risk ratio of 1.70 (95% C.I.: [1.40, 2.05]; p-value: 2.5e-7). In these balanced cohorts, a number of complications occurred at an elevated rate for patients administered unfractionated heparin compared to those administered enoxaparin, including acute kidney injury (227 of 642 [35%] vs. 156 of 608 [26%] respectively, adjusted p-value 0.0019), acute cardiac injury (40 of 642 [6.2%] vs. 15 of 608 [2.5%] respectively, adjusted p-value 0.01), septic shock (118 of 642 [18%] vs. 73 of 608 [12%] respectively, adjusted p-value 0.01), and anemia (81 of 642 [13%] vs. 46 of 608 [7.6%] respectively, adjusted p-value 0.02). Furthermore, a higher percentage of Black/African American COVID patients (375 of 1,203 [31%]) were noted to receive unfractionated heparin compared to White/Caucasian COVID patients (595 of 2,488 [24%]), for a risk ratio of 1.3 (95% C.I.: [1.17, 1.45], adjusted p-value: 1.6e-5). After balancing upon available clinical covariates, this difference in anticoagulant use remained statistically significant (272 of 959 [28%] for Black/African American vs. 213 of 959 [22%] for White/Caucasian, adjusted p-value: 0.01, relative risk: 1.28, 95% C.I.: [1.09, 1.49]). While retrospective studies cannot suggest any causality, these findings motivate the need for follow-up prospective research in order to elucidate potential socioeconomic, racial, or other disparities underlying the use of anticoagulants to treat severe COVID patients.
Human cardiac stromal cells exposed to SARS-CoV-2 evolve into hyper-inflammatory/pro-fibrotic phenotype and produce infective viral particles depending on the levels of ACE2 receptor expression
Authors: Amendola Alessandra , Garoffolo Gloria , Songia Paola , Ferrari Silvia , Bernava Giacomo , Canzano Paola , Myasoedova Veronika , Colavita Francesca , Castilletti Concetta , Sberna Giuseppe , Capobianchi Maria Rosaria , Agrifoglio Marco , Colombo Gualtiero I. , Poggio Paolo , Pesce Maurizio 
Published: November 2020

AbstractPatients with severe respiratory syndrome caused by SARS-CoV-2 undergo cardiac complications due to hyper-inflammatory conditions. Although the presence of the virus has been detected in the myocardium of infected patients, and infection of cardiac cells may involve ACE2 receptor, the underlying molecular/cellular mechanisms are still uncharacterized. We analyzed expression of ACE2 receptor in primary human cardiac stromal cells using proteomic and transcriptomic methods before exposing them to SARS-CoV-2 in vitro. Using conventional and high sensitivity PCR methods, we measured virus production in the cellular supernatants and monitored the intracellular viral bioprocessing. We performed high-resolution imaging to show the sites of intracellular viral production. We finally used Q-RT-PCR assays to detect genes linked to innate immunity and fibrotic pathways coherently regulated in cells exposed to virus. Our findings indicate that human cardiac stromal cells have a susceptibility to SARS-CoV-2 infection and produce variable viral yields depending on the extent of cellular ACE2 receptor expression. Interestingly, these cells also evolved toward hyper-inflammatory/pro-fibrotic phenotypes independently of ACE2 levels, suggesting a dual cardiac damage mechanism that could account for the elevated numbers of cardiac complications in severe COVID-19 cases.
Testosterone and socioeconomic position: Mendelian Randomization in 306,248 men and women participants of UK Biobank
Authors: Harrison Sean , Davies Neil M , Howe Laura D , Hughes Amanda 
Published: November 2020

AbstractMen with more advantaged socioeconomic position (SEP) and better health have been observed to have higher levels of testosterone. It is unclear whether these associations arise because testosterone has a causal impact on SEP and health. In 306,248 participants of UK Biobank, we performed sex- stratified genome-wide association analysis to identify genetic variants associated with testosterone. Using the identified variants, we performed Mendelian randomization analysis of the influence of testosterone on socioeconomic position, including income, employment status, area-level deprivation, and educational qualifications; on health, including self-rated health and BMI, and on risk-taking behaviour. We found little evidence that testosterone affected socioeconomic position, health, or risk-taking. Our results therefore suggest it is unlikely that testosterone meaningfully affects these outcomes in men or women. Differences between Mendelian randomization and multivariable-adjusted estimates suggest previously reported associations with socioeconomic position and health may be due to residual confounding or reverse causation.
Interventions targeting nonsymptomatic cases can be important to prevent local outbreaks: SARS-CoV-2 as a case-study
Authors: Lovell-Read Francesca A. , Funk Sebastian , Obolski Uri , Donnelly Christl A. , Thompson Robin N. 
Published: November 2020

AbstractDuring infectious disease epidemics, an important question is whether cases travelling to new locations will trigger local outbreaks. The risk of this occurring depends on the transmissibility of the pathogen, the susceptibility of the host population and, crucially, the effectiveness of surveillance in detecting cases and preventing onward spread. For many pathogens, transmission from presymptomatic and/or asymptomatic (together referred to as nonsymptomatic) infectious hosts can occur, making effective surveillance challenging. Here, using SARS-CoV-2 as a case-study, we show how the risk of local outbreaks can be assessed when nonsymptomatic transmission can occur. We construct a branching process model that includes nonsymptomatic transmission, and explore the effects of interventions targeting nonsymptomatic or symptomatic hosts when surveillance resources are limited. We consider whether the greatest reductions in local outbreak risks are achieved by increasing surveillance and control targeting nonsymptomatic or symptomatic cases, or a combination of both. We find that seeking to increase surveillance of symptomatic hosts alone is typically not the optimal strategy for reducing outbreak risks. Adopting a strategy that combines an enhancement of surveillance of symptomatic cases with efforts to find and isolate nonsymptomatic infected hosts leads to the largest reduction in the probability that imported cases will initiate a local outbreak.
Associations Between Major Psychiatric Disorder Polygenic Risk Scores and Blood-Based Markers in UK Biobank
Authors: Sewell Michael D.E. , Shen Xueyi , Jiménez-Sánchez Lorena , Edmondson-Stait Amelia J. , Green Claire , Adams Mark J. , McIntosh Andrew M. , Lyall Donald M. , Whalley Heather C. , Lawrie Stephen M. 
Published: November 2020

AbstractBackgroundMajor depressive disorder (MDD), schizophrenia (SCZ), and bipolar disorder (BD) have both shared and discrete genetic risk factors and abnormalities in blood-based measures of inflammation and blood-brain barrier (BBB) permeability. The relationships between such genetic architectures and blood-based markers are however unclear. We investigated relationships between polygenic risk scores for these disorders and peripheral biomarkers in the UK Biobank cohort.MethodsWe calculated polygenic risk scores (PRS) for samples of n = 367,329 (MDD PRS), n = 366,465 (SCZ PRS), and n = 366,383 (BD PRS) individuals from the UK Biobank cohort. We examined associations between each disorder PRS and 62 blood markers, using two generalized linear regression models: ‘minimally adjusted’ controlling for variables including age and sex, and ‘fully adjusted’ including additional lifestyle covariates such as alcohol and smoking status.Results12/62, 13/62 and 9/62 peripheral markers were significantly associated with MDD, SCZ and BD PRS respectively for both models. Most associations were disorder PRS-specific, including several immune-related markers for MDD and SCZ. We also identified several BBB-permeable marker associations, including vitamin D for all three disorder PRS, IGF-1 and triglycerides for MDD PRS, testosterone for SCZ PRS, and HDL cholesterol for BD PRS.ConclusionsThis study suggests that MDD, SCZ and BD have shared and distinct peripheral markers associated with disorder-specific genetic risk. The results implicate BBB permeability disruptions in all three disorders and inflammatory dysfunction in MDD and SCZ, and enrich our understanding of potential underlying pathophysiological mechanisms in major psychiatric disorders.
Primary school staff perspectives of school closures due to COVID-19, experiences of schools reopening and recommendations for the future: a qualitative survey in Wales
Authors: Marchant Emily , Todd Charlotte , James Michaela , Crick Tom , Dwyer Russell , Brophy Sinead 
Published: November 2020

AbstractSchool closures due to the COVID-19 global pandemic are likely to have a range of negative consequences spanning the domains of child development, education and health, in addition to the widening of inequalities and inequities. Research is required to improve understanding of the impact of school closures on the education, health and wellbeing of pupils and school staff, the challenges posed during reopening and importantly to identify how countries can return to in-school education and to inform policy. This qualitative study aimed to reflect on the perspectives and experiences of primary school staff (pupils aged 3-11) in Wales regarding school closures and the initial reopening of schools and to identify recommendations for the future. A total of 208 school staff completed a national online survey through the HAPPEN primary school network, consisting of questions about school closures (March to June 2020), the phased reopening of schools (June to July 2020) and a return to full-time education. Thematic analysis of survey responses highlighted that primary school staff perceive that gaps in learning, health and wellbeing have increased and inequalities have widened during school closures. Findings from this study identified five recommendations; (i) prioritise the health and wellbeing of pupils and staff; (ii) focus on enabling parental engagement and support; (iii) improve digital competence amongst pupils, teachers and parents; (iv) consider opportunities for smaller class sizes and additional staffing; and (v) improve the mechanism of communication between schools and families, and between government and schools.
Temporal Variations in the Intensity of Care Provided to Community and Nursing Home Residents Who Died of COVID-19 in Ontario, Canada
Authors: Brown Kevin A. , Daneman Nick , Buchan Sarah A. , Chan Adrienne K. , Stall Nathan M. 
Published: November 2020

Introduction - Worldwide, nursing home residents have experienced disproportionately high COVID-19 mortality due to the intersection of congregate living, multimorbidity, and advanced age. Among 12 OECD countries, Canada has had the highest proportion of COVID-19 deaths in nursing home residents (78%), raising concerns about a skewed pandemic response that averted much transmission and mortality in community-dwelling residents, but did not adequately protect those in nursing homes. To investigate this, we measured temporal variations in hospitalizations among community and nursing home-dwelling decedents with COVID-19 during the first and second waves of the pandemic.Methods - We conducted a population-based cohort study of residents of Ontario, Canada with COVID-19 who died between March 11, 2020 (first COVID-19 death in Ontario) and October 28, 2020. We examined hospitalization prior to death as a function of 4 factors: community (defined as all non-nursing home residents) vs. nursing home residence, age in years (<70, 70-79, 80-89, ≥90), gender, and month of death (1st wave: March-April [peak], May, June-July 2020 [nadir], 2nd wave: August-October 2020).Results - A total of 3,114 people with confirmed COVID-19 died in Ontario from March to October, 2020 (Table 1), of whom 1,354 (43.5%) were hospitalized prior to death (median: 9 days before death, interquartile range: 4-19). Among nursing home decedents (N=2000), 22.4% were admitted to hospital prior to death, but this varied substantially from a low of 15.5% in March-April (peak of wave 1) to a high of 41.2% in June-July (nadir of wave 1). Among community-dwelling decedents (N=1,114), admission to acute care was higher (81.4%) and remained relatively stable throughout the first and second waves. Similar temporal trends for nursing home versus community decedents were apparent in age-stratified analyses (Figure 1). Women who died were less likely to have been hospitalized compared to men in both community (80% women vs 84% men) and nursing home (21% women vs 24% men) settings.Discussion - Only a minority of Ontario nursing home residents who died of COVID-19 were hospitalized prior to death, and that there were substantial temporal variations, with hospitalizations reaching their lowest point when overall COVID-19 incidence peaked in mid-April, 2020. While many nursing home residents had pre-pandemic advance directives precluding hospitalization, the low admission rate observed in March-April 2020 (15.5%) was inconsistent with both higher admission rates in subsequent months (>30%), and comparatively stable rates among community-dwelling adults. Our findings substantiate reports suggesting that hospitalizations for nursing home residents with COVID-19 were low during the peak of the pandemic’s first wave in Canada, which may have contributed to the particularly high concentration of COVID-19 mortality in Ontario’s nursing homes.
ConceptWAS: a high-throughput method for early identification of COVID-19 presenting symptoms
Authors: Zhao Juan , Grabowska Monika E , Kerchberger Vern Eric , Smith Joshua C. , Eken H. Nur , Feng QiPing , Peterson Josh F. , Rosenbloom S. Trent , Johnson Kevin B. , Wei Wei-Qi 
Published: November 2020

AbstractObjectiveIdentifying symptoms highly specific to COVID-19 would improve the clinical and public health response to infectious outbreaks. Here, we describe a high-throughput approach – Concept-Wide Association Study (ConceptWAS) that systematically scans a disease’s clinical manifestations from clinical notes. We used this method to identify symptoms specific to COVID-19 early in the course of the pandemic.MethodsUsing the Vanderbilt University Medical Center (VUMC) EHR, we parsed clinical notes through a natural language processing pipeline to extract clinical concepts. We examined the difference in concepts derived from the notes of COVID-19-positive and COVID-19-negative patients on the PCR testing date. We performed ConceptWAS using the cumulative data every two weeks for early identifying specific COVID-19 symptoms.ResultsWe processed 87,753 notes 19,692 patients (1,483 COVID-19-positive) subjected to COVID-19 PCR testing between March 8, 2020, and May 27, 2020. We found 68 clinical concepts significantly associated with COVID-19. We identified symptoms associated with increasing risk of COVID-19, including “absent sense of smell” (odds ratio [OR] = 4.97, 95% confidence interval [CI] = 3.21–7.50), “fever” (OR = 1.43, 95% CI = 1.28–1.59), “with cough fever” (OR = 2.29, 95% CI = 1.75–2.96), and “ageusia” (OR = 5.18, 95% CI = 3.02–8.58). Using ConceptWAS, we were able to detect loss sense of smell or taste three weeks prior to their inclusion as symptoms of the disease by the Centers for Disease Control and Prevention (CDC).ConclusionConceptWAS is a high-throughput approach for exploring specific symptoms of a disease like COVID-19, with a promise for enabling EHR-powered early disease manifestations identification.
Impact of Indolent Schistosomiasis on Morbidity and Mortality from Respiratory Tract Infections in Preschool Age Children from a Schistosomiasis Endemic Area
Authors: Mduluza-Jokonya Tariro L. , Vengesai Arthur , Jokonya Luxwell , Thakataka Amanda , Midzi Herald , Mduluza Takafira , Sibanda Elopy , Naicker Thajasvarie 
Published: November 2020

AbstractIntroductionPneumonia is the biggest child killer, after the neonatal period. This is especially so in children from developing countries who are exposed to other infections simultaneously. In this article we investigated the impact of indolentSchistosoma haematobiuminfection on background of a respiratory infectionMethodA cross sectional study with 237 preschool age children with a respiratory infection, was performed during winter months in a schistosomiasis endemic area. Participants were clinically examined and investigated appropriately. Upper respiratory tract infection (URTI) and pneumonia were defined and classified as per IMCI and WHO guidelines, respectively.S. haematobiuminfection diagnosis was by urine filtration on urine collected over three consecutive days. Data was analysed using SPSS.ResultsS haematobiuminfection prevalence was 29% (69). Prevalence of repiratory infections were as follows: common cold 79% (188), pneumonia 15% (36) and severe pneumonia 6% (15). Eighty-one percent of participants with the common cold wereS. haematobiumnegative, whilst 80 % of those with severe pneumonia were infected. Schistosomiasis infected children were at greater odds of developing; pneumonia (aOR=3.61 (95% CI 1.73-7.55) and severe pneumonia (aOR=21.13 (95% CI 4.65-95.89). High intensity S. haematobium infection was associated with an increased risk of severe pneumonia RR= 23.78(95% CI 6.86-82.32). Mortality from coinfection emanated from severe pneumonia and severeS. haematobiuminfection intensity (RR= 26.56 (95% CI 1.49 to 473.89). Number needed to harm (NNH) forS. haematobiuminfected children who develop respiratory tract infection was 4:1 for pneumonia and 5:1 for severe pneumonia.ConclusionThe study demonstrated that coinfection with Schistosomiasis increases morbidity and mortality from respiratory tract infections by up to 20 times in children less than five years old. There is need to cover schistosomiasis screening and treatment in children under 5 years old to avert mortality and morbidity due to coinfection with respiratory infections.
Seasonal human coronavirus antibodies are boosted upon SARS-CoV-2 infection but not associated with protection
Authors: Anderson Elizabeth M. , Goodwin Eileen C. , Verma Anurag , Arevalo Claudia P. , Bolton Marcus J. , Weirick Madison E. , Gouma Sigrid , McAllister Christopher M. , Christensen Shannon R. , Weaver JoEllen , Hicks Phillip , Manzoni Tomaz B. , Oniyide Oluwatosin , Ramage Holly , Mathew Divij , Baxter Amy E. , Oldridge Derek A. , Greenplate Allison R. , Wu Jennifer E. , Alanio Cécile , D’Andrea Kurt , Kuthuru Oliva , Dougherty Jeanette , Pattekar Ajinkya , Kim Justin , Han Nicholas , Apostolidis Sokratis A. , Huang Alex C. , Vella Laura A. ,   The UPenn COVID Processing Unit, Wherry E. John , Meyer Nuala J. , Cherry Sara , Bates Paul , Rader Daniel J. , Hensley Scott E. 
Published: November 2020

SUMMARYSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread within the human population. Although SARS-CoV-2 is a novel coronavirus, most humans had been previously exposed to other antigenically distinct common seasonal human coronaviruses (hCoVs) before the COVID-19 pandemic. Here, we quantified levels of SARS-CoV-2-reactive antibodies and hCoV-reactive antibodies in serum samples collected from 204 humans before the COVID-19 pandemic. We then quantified pre-pandemic antibody levels in serum from a separate cohort of 252 individuals who became PCR-confirmed infected with SARS-CoV-2. Finally, we longitudinally measured hCoV and SARS-CoV-2 antibodies in the serum of hospitalized COVID-19 patients. Our studies indicate that most individuals possessed hCoV-reactive antibodies before the COVID-19 pandemic. We determined that ∼23% of these individuals possessed non-neutralizing antibodies that cross-reacted with SARS-CoV-2 spike and nucleocapsid proteins. These antibodies were not associated with protection against SARS-CoV-2 infections or hospitalizations, but paradoxically these hCoV cross-reactive antibodies were boosted upon SARS-CoV-2 infection.
Asymptomatic Employee Screening for SARS-CoV-2: Implementation of and Reactions to an Employer-Based Testing Program
Authors: Goetz Laura H. , DeLaughder Tyler L. , Kennedy Kathleen L. , Schork Nicholas J. , McDaniel Timothy K. , Trent Jeffrey M. , Engelthaler David M. 
Published: November 2020

ABSTRACTIntroductionAsymptomatic testing for SARS-CoV-2 among healthcare workers or other essential personnel could remove infected carriers from the workforce, decreasing chances for transmission and workplace outbreaks. Results from one-time testing programs have been reported but data regarding longitudinal testing, including information about employee’s reactions to such programs, is not readily available.MethodsTo identify asymptomatic carriers of SARS-CoV-2, we implemented a longitudinal screening program for critical on-site employees within our research institute in early April 2020. We conducted a survey of both on-site employees and those working from home in order to measure their reactions to the testing program. Statistical analysis of the survey was conducted with general linear regression and Pearson’s Chi-Square tests.ResultsDespite an ongoing high community prevalence rate of COVID-19, to date only two asymptomatic employees tested positive out of 1050 tests run during 7 months of the program. However, 12 symptomatic employees not participating in the program have tested positive. The employee survey was completed by 132/306 (43%) employees, with 93% agreeing that asymptomatic employee screening led to a better and safer working environment and 75% agreeing with on-site public health measures to help contain the virus, but only 58% feeling COVID-19 was a serious threat to their health.ConclusionOur results suggest that a longitudinal asymptomatic employee screening program for SARS-CoV-2 can be accepted by employees and can be used to maintain the health of the workforce, potentially keeping positivity rates below community levels in the face of the ongoing COVID-19 pandemic.