bluuebunny/crossref_metadata_2025_split huggingface dataset:
Encephalopathies associated with severe COVID-19 present specific neurovascular unit alterations without evidence of strong neuroinflammation
Authors: Bernard-Valnet Raphaël , Perriot Sylvain , Canales Mathieu , Pizzarotti Beatrice , Caranzano Leonardo , Castro-Jiménez Mayté , Epiney Jean-Benoit , Vijiala Sergiu , Chiabotti Paolo Salvioni , Anichini Angelica , Salerno Alexander , Jaton Katia , Vaucher Julien , Perreau Matthieu , Greub Gilbert , Pantaleo Giuseppe , Du Pasquier Renaud 
Published: November 2020

ABSTRACTObjectiveCoronavirus disease (COVID-19) has been associated with a large variety of neurological disorders. However the mechanisms underlying these neurological complications remain elusive. In this study we aimed at determining whether neurological symptoms were caused by SARS-CoV-2 direct infection or by either systemic or local pro-inflammatory mediators.MethodsWe checked for SARS-CoV-2 RNA by RT-qPCR, SARS-CoV-2-specific antibodies and for 49 cytokines/chemokines/growth factors (by Luminex) in the cerebrospinal fluids (CSF) +/-sera of a cohort of 22 COVID-19 patients with neurological presentation and 55 neurological control patients (inflammatory [IND], non-inflammatory [NIND], multiple sclerosis [MS]).ResultsWe detected SARS-CoV-2 RNA and virus-specific antibodies in the CSF of 0/22 and 10/21 COVID-19 patients, respectively. Of the four categories of tested patients, the CSF of IND exhibited the highest level of cytokines, chemokines and growth factors. In contrast, COVID-19 patients did not present overall upregulation of inflammatory mediators in the CSF. However, the CSF of patients with severe COVID-19 (ICU patients) exhibited higher concentrations of CCL2, CXCL8, and VEGF-A in the CSF than patients with a milder form of COVID-19. In addition, we could show that intrathecal CXCL8 synthesis was linked to an elevated barrier index and correlated to the increase of peripheral inflammation (serum HGF and CXCL10).ConclusionOur results point at an absence of massive SARS-CoV-2 infection or inflammation of the central nervous system, but highlight a specific impairment of the neurovascular unit linked to intrathecal production of CXCL8.
Rapid homogeneous assay for detecting antibodies against SARS-CoV-2
Authors: Rusanen Juuso , Kareinen Lauri , Levanov Lev , Mero Sointu , Pakkanen Sari H. , Kantele Anu , Amanat Fatima , Krammer Florian , Hedman Klaus , Vapalahti Olli , Hepojoki Jussi 
Published: November 2020

AbstractAccurate and rapid diagnostic tools are needed for management of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Antibody tests enable detection of individuals past the initial phase of infection and will help to examine possible vaccine responses. The major targets of human antibody response in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are the spike glycoprotein (S) and nucleocapsid protein (N). We have developed a rapid homogenous approach for antibody detection termed LFRET (protein L-based time-resolved Förster resonance energy transfer immunoassay). In LFRET, fluorophore-labeled protein L and antigen are brought to close proximity by antigen-specific patient immunoglobulins of any isotype, resulting in TR-FRET signal generation.We set up LFRET assays for antibodies against S and N and evaluated their diagnostic performance using a panel of 77 serum/plasma samples from 44 individuals with COVID-19 and 52 negative controls. Moreover, using a previously described S construct and a novel N construct, we set up enzyme linked immunosorbent assays (ELISAs) for antibodies against SARS-CoV-2 S and N. We then compared the LFRET assays with these enzyme immunoassays and with a SARS-CoV-2 microneutralization test (MNT).We found the LFRET assays to parallel ELISAs in sensitivity (90-95% vs. 90-100%) and specificity (100% vs. 94-100%). In identifying individuals with or without a detectable neutralizing antibody response, LFRET outperformed ELISA in specificity (91-96% vs. 82-87%), while demonstrating an equal sensitivity (98%).In conclusion, this study demonstrates the applicability of LFRET, a 10-minute ‘mix and read’ assay, to detection of SARS-CoV-2 antibodies.
Precision shielding for COVID-19: metrics of assessment and feasibility of deployment
Authors: Ioannidis John P.A. 
Published: November 2020

ABSTRACTBackgroundThe ability to preferentially protect high-groups in COVID-19 is hotly debated. Here, the aim is to present simple metrics of such precision shielding of people at high-risk of death after infection by SARS-CoV-2; demonstrate how they can estimated; and examine whether precision shielding was successfully achieved in the first COVID-19 wave.MethodsThe shielding ratio, S, is defined as the ratio of prevalence of infection among people at a high-risk group versus among people in a low-risk group. The contrasted risk groups examined here are according to age (>=70 versus <70 years), and institutionalized (nursing home) setting. For age-related precision shielding, data were used from large seroprevalence studies with separate prevalence data for elderly versus non-elderly and with at least 1000 assessed people >=70 years old. For setting-related precision shielding, data were analyzed from 10 countries where information was available on numbers of nursing home residents, proportion of nursing home residents among COVID-19 deaths, and overall population infection fatality rate.FindingsAcross 17 seroprevalence studies, the shielding ratio S for elderly versus non-elderly varied between 0.4 (substantial shielding) and 1.6 (substantial inverse protection, i.e. low-risk people being protected more than high-risk people). Five studies in USA all yielded S=0.4-0.8, consistent with some shielding being achieved, while two studies in China yielded S=1.5-1.6, consistent with inverse protection. Assuming 25% infection fatality rate among nursing home residents, S values for nursing home residents ranged from 0.07 to 3.1. The best shielding was seen in South Korea (S=0.07) and modest shielding was achieved in Israel, Slovenia, Germany, and Denmark. No shielding was achieved in Hungary and Sweden. In Belgium (S=1.9), UK (S=2.2) and Spain (S=3.1), nursing home residents were far more frequently infected that the rest of the population.InterpretationThe experience from the first wave of COVID-19 suggests that different locations and settings varied markedly in the extent to which they protected high-risk groups. Both effective precision shielding and detrimental inverse protection can happen in real-life circumstances. COVID-19 interventions should seek to achieve maximal precision shielding.
Seroprevalence of SARS-CoV-2 antibodies in Saint Petersburg, Russia: a population-based study
Authors: Barchuk Anton , Skougarevskiy Dmitriy , Titaev Kirill , Shirokov Daniil , Raskina Yulia , Novkunkskaya Anastasia , Talantov Petr , Isaev Artur , Pomerantseva Ekaterina , Zhikrivetskaya Svetlana , Barabanova Lubov , Volkov Vadim 
Published: November 2020

BackgroundEstimates from initial SARS-CoV-2 serological surveys were likely to be biased due to convenience sampling whereas large-scale population-based serosurveys could be biased due to non-response. This study aims to estimate the seroprevalence of SARS-CoV-2 infection in Saint Petersburg, Russia accounting for non-response bias.MethodsWe recruited a random sample of adults residing in St. Petersburg with random digit dialling. Computer-assisted telephone interview was followed by an invitation for an antibody test with randomized rewards for participation. Blood samples collected between May 27, 2020 and June 26, 2020 were assessed for anti-SARS-CoV-2 antibodies using two tests — CMIA and ELISA. The seroprevalence estimates were corrected for non-response bias, test sensitivity, and specificity. Individual characteristics associated with seropositivity were assessed.Findings66,250 individuals were contacted, 6,440 adults agreed to be interviewed and were invited to participate in the serosurvey. Blood samples were obtained from 1038 participants. Naïve seroprevalence corrected for test characteristics was 9.0% [95% CI 7.2–10.8] by CMIA and 10.8% [8.8–12.7] by ELISA. Correction for non-response bias decreased seroprevalence estimates to 7.4% [5.7–9.2] for CMIA and to 9.3% [7.4–11.2] for ELISA. The most pronounced decrease in non-response bias-corrected seroprevalence was attributed to the history of any illnesses in the past 3 months and COVID-19 testing. Besides that seroconversion was negatively associated with smoking status, self-reported history of allergies and changes in hand-washing habits.InterpretationThese results suggest that even low estimates of seroprevalence in Europe’s fourth-largest city can be an overestimation in the presence of non-response bias. Serosurvey design should attempt to identify characteristics that are associated both with participation and seropositivity. Further population-based studies are required to explain the lower seroprevalence in smokers and participant reporting allergies.FundingPolymetal International plc
Advancing Human Genetics Research and Drug Discovery through Exome Sequencing of the UK Biobank
Authors: Szustakowski Joseph D. , Balasubramanian Suganthi , Sasson Ariella , Khalid Shareef , Bronson Paola G. , Kvikstad Erika , Wong Emily , Liu Daren , Davis J. Wade , Haefliger Carolina , Loomis A. Katrina , Mikkilineni Rajesh , Noh Hyun Ji , Wadhawan Samir , Bai Xiaodong , Hawes Alicia , Krasheninina Olga , Ulloa Ricardo , Lopez Alex , Smith Erin N. , Waring Jeff , Whelan Christopher D. , Tsai Ellen A. , Overton John , Salerno William , Jacob Howard , Szalma Sandor , Runz Heiko , Hinkle Greg , Nioi Paul , Petrovski Slavé , Miller Melissa R. , Baras Aris , Mitnaul Lyndon , Reid Jeffrey G. 
Published: November 2020

AbstractThe UK Biobank Exome Sequencing Consortium (UKB-ESC) is a unique private/public partnership between the UK Biobank and eight biopharma companies that will sequence the exomes of all ∼500,000 UK Biobank participants. Here we describe early results from the exome sequence data generated by this consortium for the first ∼200,000 UKB subjects and the key features of this project that enabled the UKB-ESC to come together and generate this data.Exome sequencing data from the first 200,643 UKB enrollees are now accessible to the research community. Approximately 10M variants were observed within the targeted regions, including: 8,086,176 SNPs, 370,958 indels and 1,596,984 multi-allelic variants. Of the ∼8M variants observed, 84.5% are coding variants and include 2,139,318 (25.3%) synonymous, 4,549,694 (53.8%) missense, 453,733 (5.4%) predicted loss-of-function (LOF) variants (initiation codon loss, premature stop codons, stop codon loss, splicing and frameshift variants) affecting at least one coding transcript. This open access data provides a rich resource of coding variants for rare variant genetic studies, and is particularly valuable for drug discovery efforts that utilize rare, functionally consequential variants.Over the past decade, the biopharma industry has increasingly leveraged human genetics as part of their drug discovery and development strategies. This shift was motivated by technical advances that enabled cost-effective human genetics research at scale, the emergence of electronic health records and biobanks, and a maturing understanding of how human genetics can increase the probability of successful drug development. Recognizing the need for large-scale human genetics data to drive drug discovery, and the unique value of the open data access policies and contribution terms of the UK Biobank, the UKB-ESC was formed. This precompetitive collaboration has further strengthened the ties between academia and industry and provided teams an unprecedented opportunity to interact with and learn from the wider research community.
Ultra-rapid on-site detection of SARS-CoV-2 infection using simple ATR-FTIR spectroscopy and analysis algorithm: high sensitivity and specificity
Authors: Barauna Valério G. , Singh Maneesh N. , Barbosa Leonardo Leal , Marcarini Wena Dantas , Vassallo Paula Frizera , Mill Jose Geraldo , Ribeiro-Rodrigues Rodrigo , Warnke Patrick H. , Martin Francis L 
Published: November 2020

AbstractThere is an urgent need for ultra-rapid testing regimens to detect the SARS-CoV-2 [Severe Acute Respiratory Syndrome Coronavirus 2] virus infections in real-time within seconds to stop its spread. Current testing approaches for this RNA virus focus primarily on diagnosis by RT-qPCR, which is time-consuming, costly, often inaccurate and impractical for general population rollout due to the need for laboratory processing. The latency until the test result arrives with the patient has led to further virus spread. Furthermore, latest antigen rapid tests still require 15 to 30 min processing time and are challenging to handle. Despite increased PCR-test and antigen-test efforts the pandemic has entered the worldwide second stage. Herein, we applied a superfast reagent-free and non-destructive approach of attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy with subsequent chemometric analysis to the interrogation of virus-infected samples. Contrived samples with inactivated gamma-irradiated Covid-19 virus particles at levels down to 1582 copies/ml generated infrared (IR) spectra with good signal-to-noise ratio. Predominant virus spectral peaks are associated with nucleic acid bands, including RNA. At low copy numbers, the presence of virus particle was found to be capable of modifying the IR spectral signature of saliva, again with discriminating wavenumbers primarily associated with RNA. Discrimination was also achievable following ATR-FTIR spectral analysis of swabs immersed in saliva variously spiked with virus. Following on, we nested our test system in a clinical setting wherein participants were recruited to provide demographic details, symptoms, parallel RT-qPCR testing and the acquisition of pharyngeal swabs for ATR-FTIR spectral analysis. Initial categorisation of swab samples into negativeversuspositive Covid-19 infection was based on symptoms and PCR results. Following training and validation of a genetic algorithm-linear discriminant analysis (GA-LDA) algorithm, a blind sensitivity of 95% and specificity of 89% was achieved. This prompt approach generates results within two minutes and is applicable in areas with increased people traffic that require sudden test results such as airports, events or gate controls.
Caspases in COVID-19 Disease and Sequela and the Therapeutic Potential of Caspase Inhibitors
Authors: Plassmeyer Matthew , Alpan Oral , Corley Michael J. , Lillard Kimberleigh , Coatney Paige , Vaziri Tina , Michalsky Suzan , Premeaux Thomas A. , Pang Alina P.S. , Bukhari Zaheer , Yueng Stephen T. , Evering Teresa H , Naughton Gail , Latterich Martin , Mudd Philip , Spada Alfred , Rindone Nicole , Loizou Denise , Ndhlovu Lishomwa C. , Gupta Raavi 
Published: November 2020

AbstractCurrently, there is no effective vaccine and only one FDA approved early-stage therapy against SARS-CoV-2 infection as an indication to prevent disease progression. Cellular caspases play a role in the pathophysiology of a number of disorders that the co-morbid conditions seen in severe COVID-19 disease. In this study, we assessed transcriptional states of caspases in blood cells from COVID-19 patients. Gene expression levels of select caspases were increased inin vitroSARS-CoV-2 infection models and single cell RNA-Seq data of blood from COVID-19 patients showed a distinct caspase expression in T cells, neutrophils, and dendritic cells. Flow cytometric evaluation of CD4 T cells showed up-regulation of caspase-1 in hospitalized COVID-19 patients compared to unexposed controls. Convalescent COVID-19 patients with lingering symptoms (“long haulers”) showed persistent up-regulation of caspase-1 in CD4 T cells that was attenuatedex vivofollowing co-culture with a select pan-caspase inhibitor. Further, we observed elevated caspase-3 levels in red blood cells from COVID-19 patients compared to controls that were responsive to caspase inhibition. Our results expose an exuberant caspase response in COVID-19 that may facilitate immune-related pathological processes leading to severe outcomes. Pan-caspase inhibition could emerge as a therapeutic strategy to ameliorate or prevent severe COVID-19 outcomes.
Systematic review and meta-analysis of evidence on the efficacy of e-cigarette use for sustained smoking and nicotine cessation
Authors: Banks E , Yazidjoglou A , Brown S , Ford L , Zulfiqar T , Baenziger O , Joshy G. 
Published: November 2020

AbstractObjectiveTo systematically review and meta-analyse evidence regarding the efficacy of electronic nicotine delivery systems (ENDS) as smoking cessation aids.Data SourcesPubMed, Scopus, Web of Science, PsycINFO, MEDLINE and Cochrane Library were searched up to February-March 2020 (PROSPERO registration CRD42020170692).Study selectionPublished peer-reviewed randomised controlled trials (RCTs) of the efficacy of ENDS for sustained cessation of combustible tobacco smoking and/or nicotine use, compared with no intervention, placebo or nicotine replacement therapy (NRT) by intention-to-treat, with a minimum of four months follow-up.Data ExtractionData were extracted independently into a pre-specified template. Risk of bias was assessed with the Cochrane Collaboration’s tool and evidence quality rated using GRADE.Data SynthesisFrom 3,973 titles identified, nine RCTs were identified; 330 of 5,445 smokers randomised quit. Smoking cessation did notPublic health consequences differ significantly for randomisation to ENDS versus: no intervention (three studies, random-effects meta-analysis RR 1.95; 95%CI 0.90-4.22); placebo (three studies, 1.61; 0.93-2.78) or NRT (three studies; 1.25; 0.74-2.11). Fixed-effects sensitivity analyses showed significant results for ENDS vs NRT (1.43; 1.10-1.86). Smokers randomised to ENDS were substantially more likely than control to use nicotine at follow-up. Overall evidence quality was low. Considering only studies without potential competing interests further limited evidence but did not materially change conclusions.ConclusionsThere is insufficient evidence that ENDS are efficacious for smoking cessation compared to no intervention, placebo or NRT. Results are promising, particularly for therapeutic use, but vary according to analytic method. ENDS may lead to greater ongoing nicotine exposure than other smoking cessation methods.ImplicationsThis systematic review and meta-analysis consolidates current evidence on the efficacy of ENDS as an aid to sustained smoking and nicotine cessation and considers these findings in the context of potential competing interests. While findings are promising more research - preferably independent of industry funding - is needed to provide robust evidence of the efficacy of ENDS for smoking cessation. Future research should investigate nicotine cessation in addition to smoking cessation.
High attack rates of SARS-CoV-2 infection through household-transmission: a prospective study
Authors: Kuwelker Kanika , Zhou Fan , Blomberg Bjørn , Lartey Sarah , Brokstad Karl Albert , Trieu Mai Chi , Madsen Anders , Krammer Florian , Mohn Kristin GI , Tøndel Camilla , Linchausen Dagrunn Waag , Cox Rebecca J. , Langeland Nina , Bansal Amit , Corydon Annette , Real Francisco , Bredholt Geir , Bartsch Hauke , Sandnes Helene Heitmann , Vahokoski Juha , Jacobsen Kjerstin , Eidsheim Marianne , Sævik Marianne , Ertesvåg Nina Urke , Hauge Synnøve Ygre , Onyango Therese Bredholt 
Published: November 2020

AbstractBackgroundHousehold attack rates of SARS-CoV-2 ranging from 7% to 38% have been reported, using reverse transcription polymerase chain reaction (RT-PCR) of respiratory samples. Lower attack rates were described in children, but the importance of age in household transmission dynamics remains to be clarified.MethodsDuring the first month of the outbreak, we enrolled 112 households (291 participants) in a prospective case-ascertained study, collecting demographic and clinical data from index cases and household members. Sera were collected 6-8 weeks after index case symptom onset, to measure SARS-CoV-2-specific antibodies.FindingsT Local Ethics Committee (#118664). he overall household attack rate was 45% assessed by seroconversion, and 47% when also including RT-PCR positives. Serology identified a significantly higher number of infected household members than RT-PCR. Attack rates were equally high in children (43%) and young adults (46%), but highest among household members aged ≥60 years (72%). The attack rate was 16% in asymptomatic household members, and 42% in RT-PCR negative household members. Older adults generally had higher antibody titres than younger adults. The risk of household transmission was higher when the index case had fever or dyspnoea during acute illness but not associated with cough.InterpretationSerological assays provide more accurate estimates of household secondary attack rate than RT-PCR, especially among children who have a lower RT-PCR positivity rate. Children are equally susceptible to infection as adults, but elderly show higher attack rates. Negative RT-PCR or lack of symptoms are not sufficient to rule out infection in household members.FundingHelse Vest (F-11628), Trond Mohn Foundation (TMS2020TMT05).
Are Mobile Phones part of the chain of transmission of SARS-CoV-2 in the hospital?
Authors: Sánchez Espinoza Evelyn Patricia , Farrel Marina Cortes , Nogueira Saidy Vasconez , de Paula Anderson Vicente , Guimarães Thais , Villas Boas Lucy Santos , Park Marcelo , da Silva Cristina Carvalho , Morales Ingra , Perdigão Neto Lauro Vieira , Tozetto-Mendoza Tania Regina , Boszczowski Icaro , Sabino Ester , Mendes-Correa Maria Cássia , Shafferman Levin Anna Sara , Costa Silvia Figueiredo 
Published: November 2020

AbstractSARS-CoV-2 cross-transmission has become an concern in hospitals. We investigate healthcare workers(HCWs) knowledge about SARS-CoV-2 cross-transmission and conceptions whether the virus can remain on HCWs mobile phones(MPs) and be part of the chain of transmission.A cross-sectional study was conducted at a COVID-19 Intensive Care Unit of a teaching-hospital. Fifty-one MPs were swabbed and a questionnaire about hand hygiene and MP use and disinfection was applied after an educational campaign. Although most of HCWs believed on the importance of cross-transmission and increased hand hygiene adhesion and MP disinfection during the pandemic, SARS-CoV-2 RNA was detected in two MPs(culture of the samples was negative).Implementation of official hospital policies to guide HCWs regarding disinfection and care of personal MP are needed.
Effectiveness of quarantine and testing to prevent COVID-19 transmission from arriving travelers
Authors: Russell W. Alton , Buckeridge David L. 
Published: November 2020

ABSTRACTObjectiveTo assess the efficacy of policies designed to reduce the risk of international travelers importing SARS-CoV-2 into a country.MethodWe developed a simulation model and compared mandatory quarantine, testing, and combined quarantine and testing. We assessed the sensitivity of policy effectiveness to the timing of testing, compliance with quarantine and isolation, and other factors.ResultsIn the base scenario, a 2-day quarantine reduced more risk than testing alone. The effectiveness of a 5-day quarantine requirement with perfect compliance was similar to a 14-day quarantine with moderate compliance. Testing 72h before arrival reduced less than 10% of in-country transmission risk across all scenarios. The addition of testing to quarantine added value for shorter quarantine lengths, when testing compliance was enforced, and when testing was performed near the end of quarantine.ConclusionsQuarantine is more effective at preventing SARS-CoV-2 transmission from arriving travelers than testing alone, but testing combined with quarantine can add value if longer quarantine requirements are infeasible. Enforcing compliance with quarantine and isolation is critical. Requiring a negative test up to 72h before arrival may have limited effectiveness.