bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paired nasopharyngeal and deep lung testing for SARS-CoV2 reveals a viral gradient in critically ill patients: a multi-centre study
Authors: Hamed Islam , Shaban Nesreen , Nassar Marwan , Cayir Dilek , Love Sam , Curran Martin D , Webb Stephen , Yang Huina , Watson Katherine , Rostron Anthony , Navapurkar Vilas , Mahroof Razeen , Morris Andrew Conway 
Published: July 2020

AbstractSamples for diagnostic tests for SARS-CoV-2 can be obtained from the upper (nasopharyngeal/oropharyngeal swabs) or lower respiratory tract (sputum or tracheal aspirate or broncho-alveolar lavage - BAL). Data from different testing sites indicates different rates of positivity. Reverse-transcriptase polymerase chain reaction (RT-PCR) allows for semi-quantitative estimates of viral load as time to crossing threshold (Ct) is inversely related to viral load.ObjectivesThe objective of our study was to evaluate SARS-CoV2 RNA loads between paired nasopharyngeal (NP) and deep lung (endotracheal aspirate or BAL) samples from critically ill patients.MethodsSARS-CoV-2 RT-PCR results were retrospectively reviewed for 51 critically ill patients from 5 intensive care units in 3 hospitals ; Addenbrookes Hospital Cambridge (3 units), Royal Papworth Cambridge (1 unit), and Royal Sunderland Hospital (1 unit). At the times when paired NP and deep lung samples were obtained, one patient had been on oxygen only, 6 patients on non-invasive ventilation, 18 patients on ECMO, and 26 patients mechanically ventilated.ResultsResults collected showed significant gradient between NP and deep lung viral loads. Median Ct value was 29 for NP samples and 24 for deep lung samples. Of 51 paired samples, 16 were negative (below limit of detection) on NP swabs but positive (above limit of detection) on deep lung sample, whilst 2 were negative on deep sample but positive on NP (both patients were on ECMO).ConclusionsIt has been suggested that whilst SARS-CoV1 tends to replicate in the lower respiratory tract, SARS-CoV2 replicates more vigorously in the upper respiratory tract. These data challenge that assumption. These data suggest that viral migration to, and proliferation in, the lower respiratory tract may be a key factor in the progression to critical illness and the development of severe acute respiratory syndrome (SARS). Factors which promote this migration should be examined for association with severe COVID-19. From a practical point of view, patients with suspected severe COVID-19 should have virological samples obtained from the lower respiratory tract where-ever possible, as upper respiratory samples have a significant negative rate.
Creating and validating a DNA methylation-based proxy for Interleukin-6
Authors: Stevenson Anna J. , Gadd Danni A. , Hillary Robert F. , McCartney Daniel L. , Campbell Archie , Walker Rosie M. , Evans Kathryn L. , Harris Sarah E. , Spires-Jones Tara L , MacRae Allan F. , Visscher Peter M. , McIntosh Andrew M , Deary Ian J , Marioni Riccardo E 
Published: July 2020

ABSTRACTChronic inflammation is a pervasive feature of ageing and may be linked to age-related cognitive decline. However, population studies evaluating its relationship with cognitive functioning have produced heterogeneous results. A potential reason for this is the variability of inflammatory mediators which could lead to misclassifications of individuals’ persisting levels of inflammation. The epigenetic mechanism DNA methylation has shown utility in indexing environmental exposures and could potentially be leveraged to provide proxy signatures of chronic inflammation.We conducted an elastic net regression of interleukin-6 (IL-6) in a cohort of 895 older adults (mean age: 69 years) to develop a DNA methylation-based predictor. The predictor was tested in an independent cohort (n=7,028 [417 with measured IL-6], mean age: 51 years).We examined the association between the DNA methylation IL-6 score and serum IL-6, its association with age and established correlates of circulating IL-6, and with cognitive ability.A weighted score from 12 DNA methylation sites optimally predicted IL-6 (independent test set R2=5.1%). In the independent test cohort, both measured IL-6, and the DNA methylation proxy, increased as a function of age (serum IL-6: n=417, β=0.02, SE=0.004 p=1.3×10−7; DNAm IL-6 score: n=7,028, β=0.02, SE=0.0009, p<2 × 10−16). Serum IL-6 was not found to associate with cognitive ability (n=417, β=-0.06, SE=0.05, p=0.19); however, an inverse association was identified between the DNA methylation score and cognitive functioning (n=7,028, β=-0.14, SE=0.02, pFDR=1.5 × 10−14).These results suggest DNA methylation-based predictors can be used as proxies for inflammatory markers, potentially allowing for reliable insights into the relationship between chronic inflammation and pertinent health outcomes.
The Neurological Symptoms of ‘Long’ COVID-19: A Comparison with other Neurological Conditions and Implications for Healthcare Services
Authors: Wildwing T , Holt N 
Published: July 2020

AbstractObjectiveIn response to the rapid spread of COVID-19, this paper provides health professionals with better accessibility to available evidence, summarising findings from a systematic overview of systematic reviews of the neurological symptoms seen in patients with COVID-19. Implications of so-called ‘Long Covid’ on neurological services and primary care and similarities with other neurological disorders are discussed.MethodsFirstly, a systematic overview of current reviews of neurological symptoms of COVID-19 was conducted. Secondly the implications of these findings are discussed in relation to the potential effect on neurological services and the similarities in the experience of patients with COVID-19 and those with other neurological disorders.ResultsTwenty-nine systematic reviews were identified within seven databases, published between 11thApril 2020 and 27thAugust 2020. The results indicated (so far), that COVID-19 exhibits two types of neurological symptoms; life threatening symptoms such as Guillain Barre Syndrome and encephalitis, and less devastating symptoms such as fatigue and myalgia. These so-called lesser symptoms appear to be emerging as longer-term for some sufferers and have been recently labelled Long Covid. When compared, these Long Covid symptoms are very similar to other neurological conditions such as Chronic Fatigue Syndrome (CFS) and Functional Neurological Disorder (FND).ConclusionsImplications for neurological healthcare services in the UK may include longer waiting times and a need for more resources (including more qualified health professionals). There is also a possible change-effect on health professionals’ perceptions of other neurological conditions such as CFS and FND. Future research is recommended to explore changes in health professionals’ perceptions of neurological symptoms because of COVID-19.
An Analysis of Outbreak Dynamics and Intervention Effects for COVID-19 Transmission in Europe
Authors: Wang Wei 
Published: July 2020

AbstractAs of March 13, 2020, Europe became the center of COVID-19 pandemic. In order to prevent further spread and slow down the increase in confirmed cases and deaths, many countries in European Union have taken some interventions since mid-March. In this study, a metapopulation model was used to model the outbreak of COVID-19 in Europe and the effectiveness of these interventions were also estimated. The findings suggested that many countries successfully kept the reproduction number Rt less than 1 (e.g., Belgium, Germany, Spain, and France) while other countries exhibited Rt greater than 1 (e.g., United Kingdom, Cyprus). Based on the assumed reopen strategy, this study also revealed that a 2-week delay in response predicted approximately 2,000 deaths and 200,000 cases (daily peak value), while a 3-week delay predicted approximately 5,000 deaths and 600,000 cases (daily peak value). Therefore, a quick response upon signs of a re-emerging pandemic in the world is highly imperative to mitigate potential loss of life and to keep transmission of Covid-19 under control.
Stringent thresholds for SARS-CoV-2 IgG assays result in under-detection of cases reporting loss of taste/smell
Authors: Eyre David W , Lumley Sheila F , O’Donnell Denise , Stoesser Nicole E , Matthews Philippa C , Howarth Alison , Hatch Stephanie B , Marsden Brian D , Cox Stuart , James Tim , Cornall Richard J , Stuart David I , Screaton Gavin , Ebner Daniel , Crook Derrick W , Conlon Christopher P , Jeffery Katie , Walker Timothy M , Peto Timothy EA 
Published: July 2020

AbstractThresholds for SARS-CoV-2 antibody assays have typically been determined using samples from symptomatic, often hospitalised, patients. Assay performance following mild/asymptomatic infection is unclear. We assessed IgG responses in asymptomatic healthcare workers with a high pre-test probability of Covid-19, e.g. 807/9292(8.9%) reported loss of smell/taste. The proportion reporting anosmia/ageusia increased at antibody titres below diagnostic thresholds for both an in-house ELISA and the Abbott Architect chemiluminescent microparticle immunoassay (CMIA): 424/903(47%) reported anosmia/ageusia with a positive ELISA, 59/387(13.2%) with high-negative titres, and 324/7943(4.1%) with low-negative results. Adjusting for the proportion of staff reporting anosmia/ageusia suggests the sensitivity of both assays is lower than previously reported: Oxford ELISA 90.8% (95%CI 86.1-92.1%) and Abbott CMIA 80.9% (77.5-84.3%). However, the sensitivity may be lower if some anosmia/ageusia in those with low-negative titres is Covid-19-associated. Samples from individuals with mild/asymptomatic infection should be included in SARS-CoV-2 immunoassay evaluations. Reporting equivocal SARS-CoV-2 antibody results should be considered.
The Global Health Security Index is not predictive of coronavirus pandemic responses among Organization for Economic Cooperation and Development countries
Authors: Abbey E.J. , Khalifa B.A.A. , Oduwole M.O. , Ayeh S.K. , Nudotor R.D , Salia E.L. , Lasisi O. , Bennett S. , Yusuf H.E. , Agwu A.L. , Karakousis P.C. 
Published: July 2020

ABSTRACTThe ongoing COVID-19 pandemic has devastated many countries with ripple effects felt in various sectors of the global economy. In November 2019, the Global Health Security (GHS) Index was released as the first detailed assessment and benchmarking of 195 countries to prevent, detect, and respond to infectious disease threats. This paper presents the first comparison of Organization for Economic Cooperation and Development OECD countries’ performance during the pandemic, with the pre-COVID-19 pandemic preparedness as determined by the GHS Index. Using a rank-based analysis, four indices were compared between select countries, including total cases, total deaths, recovery rate, and total tests performed, all standardized for comparison. Our findings suggest a discrepancy between the GHS index rating and the actual performance of countries during this pandemic, with an overestimation of the preparedness of some countries scoring highly on the GHS index and underestimation of the preparedness of other countries with relatively lower scores on the GHS index.
Impact of Restrictions on Parental Presence in Neonatal Intensive Care Units Related to COVID-19
Authors: Darcy-Mahoney Ashley , White Robert D. , Velasquez Annalyn , Barrett Tyson S. , Clark Reese H. , Ahmad Kaashif A. 
Published: July 2020

ABSTRACTObjectivesTo determine the relationship between the emergence of COVID-19 and neonatal intensive care unit (NICU) family presence as well as how NICU design affects these changes.Study DesignA cross-sectional survey from April 21 to 30, 2020. We queried sites regarding NICU demographics, NICU restrictions on parental presence, and changes in ancillary staff availability.ResultsGlobally, 277 facilities responded to the survey. NICU policies preserving 24/7 parental presence decreased (83% to 53%, p<0.001) and of preserving full parental participation in rounds fell (71% to 32%, p<0.001). Single family room design NICUs best preserved 24/7 parental presence after the emergence of COVID-19 (single family room 65%, hybrid-design 57%, open bay design 45%, p=.018). In all, 120 (43%) NICUs reported reductions in therapy services, lactation medicine, and/or social work support.ConclusionsHospital restrictions have significantly limited parental presence for NICU admitted infants, although single family room design may attenuate this effect.
Air pollution, sociodemographic and health conditions effects on COVID-19 mortality in Colombia: an ecological study
Authors: Rodriguez-Villamizar Laura A. , Belalcazar-Ceron Luis Carlos , Fernández-Niño Julián Alfredo , Marín-Pineda Diana Marcela , Rojas-Sánchez Oscar Alberto , Acuña-Merchán Lizbeth Alexandra , Ramirez-Garcia Nathaly , Mangones-Matos Sonia Cecilia , Vargas-Gonzalez Jorge Mario , Herrera-Torres Julián , Agudelo-Castañeda Dayana Milena , Piñeros Jiménez Juan Gabriel , Rojas-Roa Néstor Y. , Herrera-Galindo Victor Mauricio 
Published: July 2020

AbstractObjectiveTo determine the association between chronic exposure to fine particulate matter (PM2.5), sociodemographic aspects, and health conditions and COVID-19 mortality in Colombia.MethodsEcological study using data at the municipality level, as units of analysis. COVID-19 data were obtained from official reports up to and including July 17th, 2020. PM2.5 long-term exposure was defined as the 2014-2018 average of the estimated concentrations at municipalities obtained from the Copernicus Atmospheric Monitoring Service Reanalysis (CAMSRA) model. We fit a logit-negative binomial hurdle model for the mortality rate adjusting for sociodemographic and health conditions.ResultsEstimated mortality rate ratios (MRR) for long-term average PM2.5 were not statistically significant in either of the two components of the hurdle model (i.e., the likelihood of reporting at least one death or the count of fatal cases). We found that having 10% or more of the population over 65 years of age (MRR=3.91 95%CI 2.24-6.81), the poverty index (MRR=1.03 95%CI 1.01-1.05), and the prevalence of hypertension over 6% (MRR=1.32 95%CI1.03-1.68) are the main factors associated with death rate at the municipality level. Having a higher hospital beds capacity is inversely correlated to mortality.ConclusionsThere was no evidence of an association between long-term exposure to PM2.5 and mortality rate at the municipality level in Colombia. Demographics, health system capacity, and social conditions did have evidence of an ecological effect on COVID-19 mortality.
Weak association of coinfection by SARS-CoV-2 and other respiratory viruses with severe cases and death
Authors: Fernandes-Matano L , Monroy-Muñoz IE , Uribe-Noguez LA , Hernández-Cueto MA , Sarquiz-Martínez B , Pardavé-Alejandre HD , Santos Coy-Arechavaleta A , Alvarado-Yaah JE , Rojas-Mendoza T , Santacruz-Tinoco CE , Grajales-Muñiz C , Borja-Aburto VH , Muñoz-Medina JE 
Published: July 2020

ABSTRACTBackgroundSARS-CoV-2 is a novel coronavirus described for the first time in China in December 2019. This virus can cause a disease that ranges in spectrum from asymptomatic to severe respiratory disease with multiorgan failure, and the most severe cases are associated with some comorbidities and patient age. However, there are patients who do not have those risk factors who still develop serious disease.MethodsIn this study, we identified the presence of other respiratory viruses in positive cases of COVID-19 in Mexico to determine if any coinfections were correlated with more severe manifestations of COVID-19. We analysed 103 confirmed cases of COVID-19 using RT-qPCR for the detection of 16 other respiratory viruses.ResultsOf the cases analysed, 14 (13.6%) were cases of coinfection, and 92% of them never required hospitalization, even when comorbidities and advanced age were involved. There weren’t significant differences between the presence of comorbidities and the mean ages of the groupsConclusionsThese results suggest that coinfection is not related to more severe COVID-19 and that, depending on the virus involved, it could even lead to a better prognosis. We believe that our findings may lay the groundwork for new studies aimed at determining the biological mechanism by which this phenomenon occurs and for proposing corresponding strategies to limit the progression to severe cases of COVID-19.CLINICAL TRIAL REGISTRATIONNot apply
One in seven pathogenic variants can be challenging to detect by NGS: An analysis of 450,000 patients with implications for clinical sensitivity and genetic test implementation
Authors: Lincoln Stephen E. , Hambuch Tina , Zook Justin M. , Bristow Sara L. , Hatchell Kathryn , Truty Rebecca , Kennemer Michael , Shirts Brian H. , Fellowes Andrew , Chowdhury Shimul , Klee Eric W. , Mahamdallie Shazia , Cleveland Megan H. , Vallone Peter M. , Ding Yan , Seal Sheila , DeSilva Wasanthi , Tomson Farol L. , Huang Catherine , Garlick Russell K. , Rahman Nazneen , Salit Marc , Kingsmore Stephen F. , Ferber Matthew J. , Aradhya Swaroop , Nussbaum Robert L. 
Published: July 2020

ABSTRACTPurposeTo evaluate the impact of technically challenging variants on the implementation, validation, and diagnostic yield of commonly used clinical genetic tests. Such variants include large indels, small CNVs, complex alterations, and variants in low-complexity or segmentally duplicated regions.MethodsAn interlaboratory pilot study used novel synthetic specimens to assess detection of challenging variant types by various NGS-based workflows. One well-performing workflow was further validated and used in clinician-ordered testing of more than 450,000 patients.ResultsIn the interlaboratory study, only two of 13 challenging variants were detected by all 10 workflows, and just three workflows detected all 13. Limitations were also observed among 11 less-challenging indels. In clinical testing, 21.6% of patients carried one or more pathogenic variants, of which 13.8% (17,561) were classified as technically challenging. These variants were of diverse types, affecting 556 of 1,217 genes across hereditary cancer, cardiovascular, neurological, pediatric, reproductive carrier screening, and other indicated tests.ConclusionThe analytic and clinical sensitivity of NGS workflows can vary considerably, particularly for prevalent, technically challenging variants. This can have important implications for the design and validation of tests (by laboratories) and the selection of tests (by clinicians) for a wide range of clinical indications.
Dynamic Analysis on Simultaneous iEEG-MEG Data via Hidden Markov Model
Authors: Zhang Siqi , Cao Chunyan , Quinn Andrew , Vivekananda Umesh , Zhan Shikun , Liu Wei , Sun Bomin , Woolrich Mark , Lu Qing , Litvak Vladimir 
Published: July 2020

AbstractBackgroundIntracranial electroencephalography (iEEG) recordings are used for clinical evaluation prior to surgical resection of the focus of epileptic seizures and also provide a window into normal brain function. While these recordings afford detailed information about local brain activity, putting this activity in context and comparing results across patients is challenging. Non-invasive whole-brain Magnetoencephalography (MEG) could help translate iEEG in the context of overall brain activity, and thereby aid group analysis and interpretation.MethodsSimultaneous MEG-iEEG recordings were performed at rest on 11 patients with epilepsy. Pre-processed MEG sensor data was projected to source space. The time delay embedded hidden Markov model (HMM) technique was applied to find recurrent sub-second patterns of network activity in a completely data-driven way. To relate MEG and iEEG results, correlations were computed between HMM state time courses and iEEG power envelopes in equally spaced frequency bins and presented as correlation spectra for the respective states and iEEG channels.ResultsFive HMM states were inferred from MEG. Two of them corresponded to the left and right temporal activations and had a spectral signature primarily in the theta/alpha frequency band. The majority of iEEG contacts were also located in left and right temporal areas and the theta/alpha power of the local field potentials (LFP) recorded from these contacts correlated with the time course of the HMM state corresponding to the temporal lobe of the respective hemisphere.DiscussionOur findings are consistent with the fact that most subjects were diagnosed with temporal epilepsy and implanted with temporal electrodes. As the placement of electrodes between patients was inconsistent, their modulation by HMM states could help group the contacts into functional clusters. This is the first time that HMM was applied to simultaneously recorded iEEG-MEG and our pipeline could be used in future similar studies.
SARS-CoV-2 antibodies, serum inflammatory biomarkers and clinical severity of hospitalized COVID-19 Patients
Authors: Gozalbo-Rovira Roberto , Gimenez Estela , Latorre Víctor , Francés-Gómez Clara , Albert Eliseo , Buesa Javier , Marina Alberto , Blasco María Luisa , Signes-Costa Jaime , Rodríguez-Díaz Jesús , Geller Ron , Navarro David 
Published: July 2020

ABSTRACTBackgroundThe involvement of SARS-CoV-2 antibodies in mediating immunopathogenetic events in COVID-19 patients has been suggested. By using several experimental approaches, we investigated the potential association between SARS-CoV-2 IgGs recognizing the spike (S) protein receptor-binding domain (RBD), neutralizing antibodies (NtAb) targeting S, and COVID-19 severity.Patients and MethodsThis unicenter, retrospective, observational study included 51 hospitalized patients (24 at the intensive care unit; ICU). A total of 93 sera from these patients collected at different time points from the onset of symptoms were analyzed. SARS-CoV-2 RBD IgGs were quantitated by ELISA and NtAb50titers were measured in a GFP reporter-based pseudotyped virus platform. Demographic and clinical data, complete blood counts, as well as serum levels of ferritin, Dimer-D, C reactive protein (CRP), lactose dehydrogenase (LDH), and interleukin-6 (IL-6) were retrieved from clinical charts.ResultsThe overall correlation between levels of both antibody measurements was good (Rho=0.79;P=0<0.001). SARS-CoV-2 RBD IgG and NtAb50levels in sera collected up to day 30 after the onset of symptoms were comparable between ICU and non-ICU patients (P=>0.1). The percentage of patients who exhibited high NtAb50titers (≥ 160) was similar (P=0.20) in ICU (79%) and non-ICU (60%) patients. Four ICU patients died; two of these achieved NtAb50titers ≥ 1/160 while the other two exhibited a 1/80 titer. Very weak (Rho=>0.0-<0.2) or weak (Rho=>0.2-<0.4) correlations were observed between anti-RBD IgGs, NtAb50,and serum levels pro-inflammatory biomarkers.ConclusionsThe data presented herein do not support an association between SARS-CoV-2 RBD IgG or NtAb50levels and COVID-19 severity.