bluuebunny/crossref_metadata_2025 huggingface dataset:
Verbal Communication using Intracortical Signals in a Completely Locked In-Patient
Authors: Chaudhary Ujwal , Vlachos Ioannis , Zimmermann Jonas B. , Espinosa Arnau , Tonin Alessandro , Jaramillo-Gonzalez Andres , Khalili-Ardali Majid , Topka Helge , Lehmberg Jens , Friehs Gerhard M. , Woodtli Alain , Donoghue John P. , Birbaumer Niels
Published: June 2020

Patients with amyotrophic lateral sclerosis (ALS) can lose all muscle-based routes of communication as motor neuron degeneration progresses, and ultimately, they may be left without any means of communication. While others have evaluated communication in people with remaining muscle control, to the best of our knowledge, it is not known whether neural-based communication remains possible in a completely locked-in state (CLIS). With consent and approval of the participant, family, and legal authority for this study, two 64 microelectrode arrays were implanted in the supplementary and primary motor cortex of a CLIS patient with ALS. The patient modulated neural firing rates based on auditory feedback, and he used this strategy to select letters one at a time to form words and phrases to communicate his needs and experiences. This case study provides novel evidence that brain-based volitional communication is possible even in a completely locked-in state.
High Coxiella burnetii seroconversion rate in veterinary students, the Netherlands, 2006-2010
Authors: de Lange Marit M.A. , van der Hoek Wim , Schneeberger Peter M. , Swart Arno , Heederik Dick J. J. , Schimmer Barbara , Wouters Inge M.
Published: June 2020

We examined seroconversion rates by measuring IgG antibodies against Coxiella burnetii among two cohorts of veterinary students. During follow-up of 118 seronegative veterinary students, 23 students seroconverted. Although the clinical significance of the presence of antibodies is unknown, students should be informed about the potential risks of Q fever.
The computational Patient has diabetes and a COVID
Authors: Barbiero Pietro , Lió Pietro
Published: June 2020

Abstract

Medicine is moving from a curative discipline to a preventative discipline relying on personalised and precise treatment plans. The complex and multi level pathophysiological patterns of most diseases require a systemic medicine approach and are challenging current medical therapies. On the other hand, computational medicine is a vibrant interdisciplinary field that could help move from an organ-centered approach to a process-oriented approach. The ideal computational patient would require an international interdisciplinary effort, of larger scientific and technological interdisciplinarity than the Human Genome Project. When deployed, such a patient would have a profound impact on how healthcare is delivered to patients. Here we present a computational patient model that integrates, refines and extends recent mechanistic or phenomenological models of cardiovascular, RAS and diabetic processes. Our aim is twofold: analyse the modularity and composability of the model-building blocks of the computational patient and to study the dynamical properties of well-being and disease states in a broader functional context. We present results from a number of experiments among which we characterise the dynamic impact of COVID-19 and type-2 diabetes (T2D) on cardiovascular and inflammation conditions. We tested these experiments under different exercise, meal and drug regimens. We report results showing the striking importance of transient dynamical responses to acute state conditions and we provide guidelines for system design principles for the inter-relationship between modules and components in systemic medicine. Finally this initial computational Patient can be used as a toolbox for further modifications and extensions.
Spatial and temporal regularization to estimate COVID-19 Reproduction Number R(t): Promoting piecewise smoothness via convex optimization
Authors: Abry Patrice , Pustelnik Nelly , Roux Stéphane , Jensen Pablo , Flandrin Patrick , Gribonval Rémi , Lucas Charles-Gérard , Guichard Eric , Borgnat Pierre , Garnier Nicolas , Audit Benjamin
Published: June 2020

Among the different indicators that quantify the spread of an epidemic, such as the on-going COVID-19, stands first the reproduction number which measures how many people can be contaminated by an infected person. In order to permit the monitoring of the evolution of this number, a new estimation procedure is proposed here, assuming a well-accepted model for current incidence data, based on past observations. The novelty of the proposed approach is twofold: 1) the estimation of the reproduction number is achieved by convex optimization within a proximal-based inverse problem formulation, with constraints aimed at promoting piecewise smoothness; 2) the approach is developed in a multivariate setting, allowing for the simultaneous handling of multiple time series attached to different geographical regions, together with a spatial (graph-based) regularization of their evolutions in time. The effective-ness of the approach is first supported by simulations, and two main applications to real COVID-19 data are then discussed. The first one refers to the comparative evolution of the reproduction number for a number of countries, while the second one focuses on French counties and their joint analysis, leading to dynamic maps revealing the temporal co-evolution of their reproduction numbers.
State heterogeneity of human mobility and COVID-19 epidemics in the European Union
Authors: Yuan Xiaoling , Hu Kun , Xu Jie , Zhang Xuchen , Bao Wei , Lynch Charles F. , Zhang Lanjing
Published: June 2020

Human mobility was associated with epidemic changes of coronavirus disease 2019 (COVID-19) in China, where strict public health interventions reduced human mobility and COVID-19 epidemics. But its association with COVID-19 epidemics in the European Union (EU) is unclear. In this quasi-experimental study, we modelled the temporal trends in human mobility and epidemics of COVID-19 in the 27 EU states between January 15 and May 9, 2020. COVID-19 and human mobility had 3 trend-segments, including an upward trend in COVID-19 daily incidence and a downward trend in most human mobilities in the middle segment. Compared with the EU states farther from Italy, the state-wide lockdown dates were more likely linked to turning points of human mobilities in the EU states closer to Italy, which were also more likely linked to second turning points of COVID-19 epidemics. Among the examined human mobilities, the second turning points in driving mobility and the first turning points in parks mobility were the best factors that connected lockdown dates and COVID-19 epidemics in the EU states closer to Italy. Our findings highlight the state- and mobility-heterogeneity in the associations of public health interventions and human mobility with changes of COVID-19 epidemics in the EU states.
Towards integration of 64Cu-DOTA-Trasztusumab PET-CT and MRI with mathematical modeling to predict response to neoadjuvant therapy in HER2+ breast cancer
Authors: Jarrett Angela M. , Hormuth David A. , Adhikarla Vikram , Sahoo Prativa , Abler Daniel , Tumyan Lusine , Schmolze Daniel , Mortimer Joanne , Rockne Russell C. , Yankeelov Thomas E.
Published: June 2020

While targeted therapies exist for human epidermal growth factor receptor 2 positive (HER2+) breast cancer, HER2+ patients do not always respond to therapy. We present the results of utilizing a biophysical mathematical model to predict tumor response for two HER2+ breast cancer patients treated with the same therapeutic regimen but who achieved different treatment outcomes. Quantitative data from magnetic resonance imaging (MRI) and 64Cu-DOTA-Trastuzumab positron emission tomography (PET) are used to estimate tumor density, perfusion, and distribution of HER2-targeted antibodies for each individual patient. MRI and PET data are collected prior to therapy, and follow-up MRI scans are acquired at a midpoint in therapy. Given these data types, we align the data sets to a common image space to enable model calibration. Once the model is parameterized with these data, we forecast treatment response with and without HER2-targeted therapy. By incorporating targeted therapy into the model, the resulting predictions are able to distinguish between the two different patient responses, increasing the difference in tumor volume change between the two patients by >40%. This work provides a proof-of-concept strategy for processing and integrating PET and MRI modalities into a predictive, clinical-mathematical framework to provide patient-specific predictions of HER2+ treatment response.
Relative Coronavirus Disease 2019 Mortality: A Swiss Population-based Study
Authors: Hothorn Torsten , Bopp Matthias , Günthard Huldrych F. , Keiser Olivia , Roelens Maroussia , Weibull Caroline E. , Crowther Michael J.
Published: June 2020

Objective

Severity of the coronavirus disease 2019 (covid-19) has been assessed in terms of absolute mortality in SARS-CoV-2 positive cohorts. An assessment of mortality relative to mortality in the general population is presented.

Design

Retrospective population-based study.

Setting

Individual information on symptomatic confirmed SARS-CoV-2 patients and subsequent deaths from any cause were compared to the all-cause mortality in the Swiss population of 2018. Starting February 23, 2020, mortality in covid-19 patients was monitored for 80 days and compared to the population mortality observed in the same time-of-year starting February 23, 2018.

Participants

5 160 595 inhabitants of Switzerland aged 35 to 95 without covid-19 (general population in spring 2018) and 20 769 persons tested positively for covid-19 (spring 2020).

Measurements

Sex- and age-specific mortality rates were estimated using Cox proportional hazards models. Absolute probabilities of death were predicted and risk was assessed in terms of relative mortality by taking the ratio between the sex- and age-specific absolute mortality in covid-19 patients and the corresponding mortality in the 2018 general population.

Results

A confirmed SARS-CoV-2 infection substantially increased the probability of death across all patient groups, ranging from nine (6 to 15) times the population mortality in 35-year old infected females to a 53-fold increase (46 to 59) for 95 year old infected males. The highest relative risks were observed among males and older patients. The magnitude of these effects was smaller compared to increases observed in absolute mortality risk. Male covid-19 patients exceeded the population hazard for males (hazard ratio 1.20, 1.00 to 1.44). Each additional year of age increased the population hazard in covid-19 patients (hazard ratio 1.04, 1.03 to 1.05).

Limitations

Information about the distribution of relevant comorbidities was not available on population level and the associated risk was not quantified.

Conclusions

Health care professionals, decision makers, and societies are provided with an additional population-adjusted assessment of covid-19 mortality risk. In combination with absolute measures of risk, the relative risks presented here help to develop a more comprehensive understanding of the actual impact of covid-19.
Identifying Non-traditional Epidemic Disease Risk Factors associated to major Health Events from WHO and World Bank Open Data
Authors: Lugo-Robles Roberta , Garges Eric C. , Olsen Cara H. , Brett-Major David M.
Published: June 2020

Objectives

Health events emerge from a multifactorial milieu involving host, community, environment, and pathogen factors. Therefore, developing accurate forecasting models to improve epidemic prediction towards better prevention and capabilities management is a complex task. Here, we describe an exploratory analysis to identify non-health risk factors that could improve the forecast and events risk signals using a feasible and practical approach by combining surveillance report data with non-health data from open data sources.

Methods

A line listing was developed using information from the World Health Organization Disease Outbreaks News from 2016-2018. A database was created merging the line listing data with non-health indicators from the World Bank. Poisson regression models employing forward imputations were used to establish relationships and predict values over the dependent variable (health event frequency); which are the health events reported by each country to WHO during 2016-2018.

Findings

The resulting regression model provided evidence that changes in non-health factors important to community experiences impact the risk of the number of major health events that a country could experience. Three non-health indicators (extrinsic factors) were associated significantly to event frequency (population urban change, gross domestic product change per capita—a novel factor, and average forest area). An exploratory analysis of the current COVID-19 pandemic suggested similar associations, but confounding by global disease burden is likely.

Conclusion

Continued development of forecasting approaches capturing available whole-of-society extrinsic factors (non-health factors); could improve the risk management process through earlier hazard identification, and as importantly inform strategic decision processes in multisectoral strategies to preventing, detecting, and responding to pandemic-threat events.
On the increasing role of older adolescents and younger adults during the SARS-CoV-2 epidemic in Mexico, April 20 – May 24, 2020
Authors: Stern D , Lajous M , Goldstein E
Published: June 2020

Background

The SARS-CoV-2 epidemic in Mexico is growing, and there is uncertainty regarding the role that different age groups play in propagating the epidemic.

Methods

We used data on hospitalizations with confirmed SARS-CoV-2 infection from the Mexican Ministry of Health in ten 5-year age groups: 10-14through 55-59 years. For each age group g, we computed the proportion E(g) of individuals in that age group among all hospitalized cases aged 10-59 years during the early period (between April 20 – May 3, 2020), the corresponding proportion L(g) during the later periods (May 11-24), as well as the relative risk RR(g)= L(g)/E(g). For each pair of age groups g1,g2, RR(g1)>RR(g2) is interpreted as a relative increase in SARS-CoV-2 infections in the age group g1 compared with g2 for the later vs. early period.

Results

The highest RR estimates belong to persons aged 15-19 years (RR=1.93(95% CI (1.19,3.12)) and 20-24 years (RR=1.40(1.07,1.83)). The RR estimates in persons aged over 30 years were significantly lower compared to persons aged 15-24 years.

Conclusions

Our results suggest a temporal increase in the incidence of SARS-CoV-2 infection in older adolescents and younger adults compared to other age groups. Targeted interventions, particularly public health messaging at those age groups to increase knowledge and risk awareness may be considered.
A Machine Learning Study to Improve Surgical Case Duration Prediction
Authors: Huang Ching-Chieh , Lai Jesyin , Cho Der-Yang , Yu Jiaxin
Published: June 2020

Predictive accuracy of surgical case duration plays a critical role in reducing cost of operation room (OR) utilization. The most common approaches used by hospitals rely on historic averages based on a specific surgeon or a specific procedure type obtained from the electronic medical record (EMR) scheduling systems. However, low predictive accuracy of EMR leads to negative impacts on patients and hospitals, such as rescheduling of surgeries and cancellation. In this study, we aim to improve prediction of operation case duration with advanced machine learning (ML) algorithms. We obtained a large data set containing 170,748 operation cases (from Jan 2017 to Dec 2019) from a hospital. The data covered a broad variety of details on patients, operations, specialties and surgical teams. Meanwhile, a more recent data with 8,672 cases (from Mar to Apr 2020) was also available to be used for external evaluation. We computed historic averages from EMR for surgeon- or procedure-specific and they were used as baseline models for comparison. Subsequently, we developed our models using linear regression, random forest and extreme gradient boosting (XGB) algorithms. All models were evaluated with R-squre (R2), mean absolute error (MAE), and percentage overage (case duration>prediction + 10 % & 15 mins), underage (case duration<prediction - 10 % & 15 mins) and within (otherwise). The XGB model was superior to the other models by having higherR2(85 %) and percentage within (48 %) as well as lowerMAE(30.2 mins). The total prediction errors computed for all the models showed that the XGB model had the lowest inaccurate percent (23.7 %). As a whole, this study applied ML techniques in the field of OR scheduling to reduce medical and financial burden for healthcare management. It revealed the importance of operation and surgeon factors in operation case duration prediction. This study also demonstrated the importance of performing an external evaluation to better validate performance of ML models.
Plasma levels of soluble ACE2 are associated with sex, Metabolic Syndrome, and its biomarkers in a large cohort, pointing to a possible mechanism for increased severity in COVID-19
Authors: Kornilov Sergey A. , Lucas Isabelle , Jade Kathleen , Dai Chengzhen L. , Lovejoy Jennifer C. , Magis Andrew T.
Published: June 2020

We examined the associations between plasma concentrations of soluble ACE2 and biomarkers of Metabolic Syndrome in a large (N=2,051) sample of individuals who participated in a commercial wellness program and who underwent deep molecular phenotyping. sACE2 levels were significantly higher in men, compared to women, and in individuals with Metabolic Syndrome, compared to controls. sACE2 levels showed reliable associations with all individuals components of Metabolic Syndrome, including obesity, hypertension, insulin resistance, hyperlipidemia, and as well as markers of liver damage. This profile of associations was statistically significantly stronger in men, compared to women, and points to preexisting cardiometabolic conditions as possible risk factors for increased severity of symptoms in some COVID-19 patients through increased expression of ACE2 in the liver.
Estimating the Impact of Control Measures to Prevent Outbreaks of COVID-19 Associated with Air Travel into a COVID-19-free country: A Simulation Modelling Study
Authors: Wilson Nick , Baker Michael G , Eichner Martin
Published: June 2020

Aims

We aimed to estimate the risk of COVID-19 outbreaks associated with air travel from a country with a very low prevalence of COVID-19 infection (Australia) to a COVID-19-free country (New Zealand; [NZ]), along with the likely impact of various control measures for passengers and cabin crew.

Methods

A stochastic version of the SEIR model CovidSIM v1.1, designed specifically for COVID-19 was utilized. It was populated with data for both countries and parameters for SARS-CoV-2 transmission and control measures. We assumed one Australia to NZ flight per day.

Results

When no interventions were in place, an outbreak of COVID-19 in NZ was estimated to occur after an average time of 1.7 years (95% uncertainty interval [UI]: 0.04-6.09). However, the combined use of exit and entry screening (symptom questionnaire and thermal camera), masks on aircraft and two PCR tests (on days 3 and 12 in NZ), combined with self-reporting of symptoms and contact tracing and mask use until the second PCR test, reduced this risk to one outbreak every 29.8 years (0.8 to 110). If no PCR testing was performed, but mask use was used by passengers up to day 15 in NZ, the risk was one outbreak every 14.1 years. However, 14 days quarantine (NZ practice in May 2020), was the most effective strategy at one outbreak every 34.1 years (0.06 to 125); albeit combined with exit screening and mask use on flights.

Conclusions

Policy-makers can require multi-layered interventions to markedly reduce the risk of importing the pandemic virus into a COVID-19-free nation via air travel. There is potential to replace 14-day quarantine with PCR testing or interventions involving mask use by passengers in NZ. However, all approaches require continuous careful management and evaluation.
ROBOCOV: An affordable open-source robotic platform for SARS-CoV-2 testing by RT-qPCR
Authors: Villanueva-Cañas José Luis , Gonzalez-Roca Eva , Unanue Aitor Gastaminza , Titos Esther , Martínez Yoldi Miguel Julián , Vergara Gómez Andrea , Puig Butillé Joan Antón
Published: June 2020

Current global pandemic due to the SARS-CoV-2 has struggled and pushed the limits of global health systems. Supply chain disruptions and scarce availability of commercial laboratory reagents have motivated worldwide actors to search for alternative workflows to cope with the demand.

We have used the OT-2 open-source liquid-handling robots (Opentrons, NY), RNA extraction and RT-qPCR reagents to set-up a reproducible workflow for RT-qPCR SARS-CoV-2 testing. We developed a framework with a template and several functions and classes that allow the creation of customized RT-qPCR automated circuits. As a proof of concept, we provide data obtained by a fully-functional tested code using the MagMax™ Pathogen RNA/DNA kit and the MagMax™ Viral/Pathogen II kit (Thermo Fisher Scientific, MA) on the Kingfisher™ Flex instrument (Thermo Fisher Scientific, MA). With these codes available is easy to create new stations or circuits from scratch, adapt existing ones to changes in the experimental protocol, or perform fine adjustments to fulfil special needs.

The affordability of this platform makes it accessible for most laboratories and hospitals with a bioinformatician, democratising automated SARS-CoV-2 PCR testing and increasing, temporarily or not, the capacity of carrying out tests. It also confers flexibility, as this platform is not dependant on any particular commercial kit and can be quickly adapted to protocol changes or other special needs.
A non-enveloped arbovirus released in lysosome-derived extracellular vesicles induces super-infection exclusion
Authors: Labadie Thomas , Roy Polly
Published: June 2020

Recent developments on extracellular vesicles (EVs) containing multiple virus particles challenge the rigid definition of non-enveloped viruses. However, how non-enveloped viruses hijack cell machinery to promote non-lytic release in EVs, and their functional roles, remain to be clarified. Here we used Bluetongue virus (BTV) as a model of a non-enveloped arthropod-borne virus and observed that the majority of viruses are released in EVs, bothin vitroand in the blood of infected animals. Based on the cellular proteins detected in these EVs, and use of inhibitors targeting the cellular degradation process, we demonstrated that these extracellular vesicles are derived from secretory lysosomes, in which the acidic pH is neutralized upon the infection. Moreover, we report that secreted EVs are more efficient than free-viruses for initiating infections, but that they trigger super-infection exclusion that only free-viruses can overcome.

Author summary

Recent discoveries of non-enveloped virus secreted in EVs opened the door to new developments in our understanding of the transmission and pathogenicity of these viruses. In particular, how these viruses hijack the host cellular secretion machinery, and the role of these EVs compared with free-virus particles remained to be explored. Here, we tackled these two aspects, by studying BTV, an emerging arthropod-borne virus causing epidemics worldwide. We showed that this virus is mainly released in EVs,in vivoand in the blood of infected animals, and that inhibition of the cell degradation machinery decreases the release of infectious EVs, but not free-virus particles. We found that BTV must neutralize the pH of lysosomes, which are important organelles of the cell degradation machinery, for efficient virus release in EVs. Our results highlight unique features for a virus released in EVs, explaining how BTV transits in lysosomes without being degraded. Interestingly, we observed that EVs are more infectious than free-virus particles, but only free-viruses are able to overcome the super-infection exclusion, which is a common cellular defense mechanism. In conclusion, our study stresses the dual role played by both forms, free and vesicular, in the virus life cycle.
Doxycycline has Distinct Apicoplast-Specific Mechanisms of Antimalarial Activity
Authors: Okada Megan , Guo Ping , Nalder Shai-anne , Sigala Paul A.
Published: June 2020

Doxycycline (DOX) is a key antimalarial drug thought to killPlasmodiumparasites by blocking protein translation in the essential apicoplast organelle. Clinical use is primarily limited to prophylaxis due to delayed second-cycle parasite death at 1-3 μM serum concentrations. DOX concentrations >5 μM kill parasites with first-cycle activity but have been ascribed to off-target mechanisms outside the apicoplast. We report that 10 μM DOX blocks apicoplast biogenesis in the first cycle and is rescued by isopentenyl pyrophosphate, an essential apicoplast product, confirming an apicoplast-specific mechanism. Exogenous iron rescues parasites and apicoplast biogenesis from first-but not second-cycle effects of 10 μM DOX, revealing that first-cycle activity involves a metal-dependent mechanism distinct from the delayed-death mechanism. These results critically expand the paradigm for understanding the fundamental antiparasitic mechanisms of DOX and suggest repurposing DOX as a faster-acting antimalarial at higher dosing whose multiple mechanisms would be expected to limit parasite resistance.
The conserved molting/circadian rhythm regulator NHR-23/NR1F1 serves as an essential co-regulator ofC. elegansspermatogenesis
Authors: Ragle James Matthew , Aita Abigail L. , Morrison Kayleigh N. , Martinez-Mendez Raquel , Saeger Hannah N. , Ashley Guinevere A. , Johnson Londen C. , Schubert Katherine A. , Shakes Diane C. , Ward Jordan D.
Published: June 2020

In sexually reproducing metazoans, spermatogenesis is the process by which uncommitted germ cells give rise to haploid sperm. Work in model systems has revealed mechanisms controlling commitment to the sperm fate, but how this fate is subsequently executed remains less clear. While studying the well-established role of the conserved nuclear hormone receptor transcription factor, NHR-23/NR1F1, in regulation ofC. elegansmolting, we discovered NHR-23/NR1F1 is also constitutively expressed in developing 1° spermatocytes and is a critical regulator of spermatogenesis. In this novel role, NHR-23/NR1F1 functions downstream of the canonical sex determination pathway. Degron-mediated depletion of NHR-23/NR1F1 within hermaphrodite or male germlines causes sterility due to an absence of functional sperm as depleted animals produce arrested primary spermatocytes rather than haploid sperm. These spermatocytes arrest in prometaphase I and fail to either progress to anaphase or attempt spermatid-residual body partitioning. They make sperm-specific membranous organelles (MOs) but fail to assemble their major sperm protein into fibrous bodies. NHR-23/NR1F1 appears to function independently of the known SPE-44 gene regulatory network, revealing the existence of an NHR-23/NR1F1-mediated module that regulates the spermatogenesis program.

Summary Statement

A well-characterized regulator ofC. elegansmolting also unexpectedly controls the spermatogenesis program; our work provides insights into the gene regulatory networks controlling spermatogenesis.
The arrival and spread of SARS-CoV2 in Colombia
Authors: Ramírez Juan David , Florez Carolina , Muñoz Marina , Hernández Carolina , Castillo Adriana , Gomez Sergio , Rico Angelica , Pardo Lisseth , Barros Esther C. , Castañeda Sergio , Ballesteros Nathalia , Martínez David , Vega Laura , Jaimes Jesús E. , Cruz-Saavedra Lissa , Herrera Giovanny , Patiño Luz H. , Teherán Aníbal A. , Gonzalez-Reiche Ana S. , Hernandez Matthew M. , Sordillo Emilia Mia , Simon Viviana , van Bakel Harm , Paniz-Mondolfi Alberto
Published: June 2020

We performed phylogenomic analysis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) from 88 infected individuals across different regions of Colombia. Eleven different lineages were detected, suggesting multiple introduction events. Pangolin lineages B.1 and B.1.5 were the most frequent, with B.1 being associated with prior travel to high-risk areas.

Article Summary Line

We sequenced 88 genomes of SARS-CoV2 from Colombia finding 11 lineages and eight different introduction events
Cost effective reusable gowns for routine use in hospital and laboratory: a necessity arising of COVID-19 Pandemic
Authors: Shahane-Kapse Priyanka , Patond Anjali , Deotale Vijayshri , Narang Rahul
Published: June 2020

COVID-19 pandemic caused by SARS-CoV-2 has started a paradigm shift in working in a hospital or laboratory and airborne precautions have become equally significant as universal blood and body fluid precautions. Use of PPE including surgical masks or N95FFR is becoming a norm and this has led to scarcity of PPE for healthcare workers. We have prepared gowns for healthcare and laboratory workers made from a reusable material and tested with various disinfectants and heat. The cloth could tolerate repeated exposures to heat, alcohol, hypochlorite and hydrogen peroxide, but was damaged by phenol. Since this impermeable material did not allow the air to pass, we used a cool vest made up of indigenous “Khadi” cloth with pockets containing phase change material. The cost of whole reusable assembly of gown and cap was Indian Rupees 250 (1USD=76INR). This can be used in healthcare workers in hospital and community as well as people in diagnostic and research laboratories as a cost effective PPE.
Angiotensin-converting enzyme (ACE1, ACE2) gene variants are associated with COVID19 severity depending on the hypertension status
Authors: Gómez Juan , Albaiceta Guillermo M , García-Clemente Marta , López-Larrea Carlos , Amado-Rodríguez Laura , Hermida Tamara , Enriquez Ana I. , Herrero Pablo , Melón Santiago , Alvarez-Argüelles Marta E. , Rojo-Alba Susana , Leal-Negredo Alvaro , Cuesta-Llavona Elías , Alvarez Victoria , Lorca Rebeca , Coto Eliecer
Published: June 2020

Background

The Angiotensin system is implicated in the pathogenesis of COVID19. First, ACE2 is the cellular receptor for SARS-COv-2, and expression of theACE2gene could regulate the individual’s susceptibility to infection. In addition, the balance between ACE1 and ACE activity has been implicated in the pathogenesis of respiratory diseases and could play a role in the severity of COVID19. FunctionalACE1/ACE2gene polymorphisms have been associated with the risk of cardiovascular and pulmonary diseases, and could thus also contribute to the outcome of COVID19.

Methods

We studied 204 COVID19 patients (137 non-severe and 67severe-ICU cases) and 536 age-matched controls. TheACE1insertion/deletion andACE2rs2285666 polymorphism were determined. Variables frequencies were compared between the groups by logistic regression. We also sequenced the ACE2 coding nucleotides in a group of patients.

Results

Severe COVID19 was associated with hypertension male gender (p<0.001), hypertension (p=0.006), hypercholesterolaemia (p=0.046), and the ACE1-DD genotype (p=0.049). In the multiple logistic regression hypertension (p=0.02, OR=2.26, 95%CI=1.12-4.63) and male gender (p=0.002; OR=3.15, 95%CI=1.56-6.66) remained as independent significant predictors of severity. TheACE2polymorphism was not associated with the disease outcome. TheACE2sequencing showed no coding sequence variants that could explain an increased risk of developing COVID19.

Conclusions

Adverse outcome of COVID19 was associated with male gender, hypertension, hypercholesterolemia and theACE1genotype. TheACE1-I/D was a significant risk factor for severe COVID19, but the effect was dependent on the hypertensive status.
Plasma (1→3) β-d-glucan levels are associated with host inflammatory responses and predict adverse clinical outcomes in critical illness
Authors: Kitsios Georgios D. , Kotok Daniel , Yang Haopu , Finkelman Malcolm , Zhang Yonglong , Britton Noel , Guo Rui , Evankovich John W. , Bain William , Shah Faraaz , Zhang Yingze , Benos Panayiotis V. , McVerry Bryan J. , Morris Alison
Published: June 2020

Background

The fungal cell-wall constituent (1,3)-β-d-glucan (BDG) is a pathogen-associated molecular pattern (PAMP) that can stimulate innate immunity. We hypothesized that BDG from colonizing fungi in critically-ill patients may translocate into the systemic circulation and thus be associated with host inflammatory responses and outcomes.

Methods

We enrolled 453 mechanically-ventilated patients with acute respiratory failure with no evidence of invasive fungal infection (IFI). From serial plasma samples, we measured BDG, innate immunity and epithelial permeability biomarkers. From lower respiratory tract and stool samples we quantified bacterial and fungal DNA load using culture-independent techniques.

Results

A positive BDG test (>60pg/ml) at baseline was detected in 19% of patients. BDG levels were significantly associated with markers of innate immunity (interleukin-6, tumor necrosis factor receptor-1 and procalcitonin), epithelial barrier disruption (receptor for advanced glycation end-products and fatty-acid binding protein-2, for lung and gut respectively) and with higher probability of classification in an adverse prognosis hyperinflammatory subphenotype (all p<0.05). No differences in fungal or bacterial DNA load were found by BDG test positivity. Positive BDG testing was associated with higher incidence of acute kidney injury, fewer ventilator free days and worse 30-day survival (adjusted p<0.05). Patients with positive BDG test on follow-up sampling (>3 days from intubation) had higher mortality than patients with persistently negative test on follow-up (p<0.05).

Conclusions

This is the first study to demonstrate the prognostic role of BDG in critically ill patients with no evidence of IFI. Translocation of BDG into systemic circulation may contribute to inflammation and clinical outcomes.

Funding support

National Institutes of Health [K23 HL139987 (GDK); U01 HL098962 (AM); P01 HL114453 (BJM); R01 HL097376 (BJM); K24 HL123342 (AM); U01 HL137159 (DVM, PVB); R01 LM012087 (DVM, PVB); R01 HL142084 (JSL); R01 HL136143 (JSL); F32 HL137258 (JWE); F32 HL142172 (WB); K08 HS025455 (IJB); K23 GM122069 (FS)].
Performance and health economic evaluation of the Mount Sinai COVID-19 serological assay identifies modification of thresholding as necessary to maximise specificity of the assay
Authors: Rushworth Stuart A , Johnson Benjamin B , Ashurst Karen , Davidson Rose , Paddy Paige , Mistry Jayna J , Moore Jamie A , Hellmich Charlotte , Edwards Dylan R , Da Luz Afonso Daniela , Xydopoulos Georgios , Goodwin Richard , Gomez Javier , Prakash Reenesh , Dervisevic Samir , Fordham Richard , Bowles Kristian M , Smith James G W
Published: June 2020

We evaluated the FDA approved SARS-CoV-2 immunoassay (developed at Mount Sinai, by Krammer and colleagues) for the identification of COVID-19 seroconversion and potential cross-reactivity of the assay in a United Kingdom (UK) National Health Service (NHS) hospital setting. In our ‘set up’ cohort we found that the SARS-CoV-2 IgG was detectable in 100% of patients tested 14 days post positive COVID-19 nucleic acid test. Serum samples taken from pregnant women in 2018 were used as a negative control group with zero false positives. We also analysed samples from patients with non-COVID-19 viral infections, paraproteinaemia or autoantibodies and found false positive results in 6/179. Modification of the sensitivity threshold to five standard deviations from the mean of the control group eliminated all false positive result in the ‘set up’ cohort. We confirmed the validity of the test with a revised threshold on an independent prospective ‘validation cohort’ of patient samples. Taking data from both cohorts we report a sensitivity of the Mount Sinai assay of 96.6% (28/29) and specificity of 100% (299/299) using a revised threshold cut-off, at a time point at least 14 days since the diagnostic antigen test. Finally, we conducted a health economic probabilistic sensitivity analysis (PSA) on the costs of producing the tests, and the mean cost we estimate to be 13.63 pounds sterling (95%CI 9.63 - 18.40), allowing its cost effectiveness to be tested against other antibody tests. In summary, we report that the Mount Sinai IgG ELISA assay is highly sensitive test for SARS-Cov-2 infection, however modification of thresholding was required to minimise false positive results.
Profiling the positive detection rate of SARS-CoV-2 using polymerase chain reaction in different types of clinical specimens: a systematic review and meta-analysis
Authors: Bwire George M. , Majigo Mtebe V. , Njiro Belinda J. , Mawazo Akili
Published: June 2020

Background

Testing is one of the commendable preventive measures against coronavirus disease (COVID-19), and needs to be done using both most appropriate specimen and an accurate diagnostic test like real time reverse transcription polymerase chain reaction (qRT-PCR). However, the detection rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA from different clinical specimens after onset of symptoms is not yet well established. For guiding the selection of specimens for clinical diagnosis of COVID-19, a systematic review aiming at profiling the positive detection rate from different clinical specimens using PCR was conducted.

Methods

The systematic search was done using PubMed/MEDLINE, Science direct, Google Scholar, among others. The search included studies on laboratory diagnosis of SARS-CoV-2 from different clinical specimens using PCR. Data extraction was done using Microsoft Excel spread sheet 2010 and reported according to PRISMA-P guidelines. Using Open Meta Analyst software, DerSimonian–Laird random effects analysis was performed to determine a summary estimate (positive rate [PR]/proportions) and their 95% confidence interval (95%CI).

Results

A total of 8136 different clinical specimens were analyzed to detect SARS-CoV-2, with majority being nasopharyngeal swabs (69.6%). Lower respiratory tract (LRT) specimens had a PR of 71.3% (95%CI:60.3%-82.3%) while no virus was detected from the urinogenital specimens. Bronchoalveolar lavage fluid (BLF) specimen had the PR of 91.8% (95%CI:79.9-103.7%), followed by rectal swabs, 87.8 % (95%CI:78.6%-96.9%) then sputum, 68.1% (95%CI:56.9%-79.4%). Low PR was observed in oropharyngeal swabs, 7.6% (95%CI:5.7%-9.6%) and blood samples, 1.0% (95%CI: -0.1%-2.1%), whilst no SARS-CoV-2 was detected in urine samples. Nasopharyngeal swab, a widely used specimen had a PR of 45.5% (95%CI:31.2%-59.7%).

Conclusion

In this study, SARS-CoV-2 was highly detected in lower respiratory tract specimens while there was no detected virus in urinogenital specimens. Regarding the type of clinical specimens, bronchoalveolar lavage fluid had the highest positive rate followed by rectal swab then sputum. Nasopharyngeal swab which is widely used had a moderate detection rate. Low positive rate was recorded in oropharyngeal swab and blood sample while no virus was found in urine samples. More importantly, the virus was detected in feces, suggesting SARS-CoV-2 transmission by the fecal route.
Design of the Play & Grow Cohort: A prospective study of parent-child mealtime interactions
Authors: Parrott Andria , Zvara Bharahi J. , Keim Sarah A. , Andridge Rebecca , Anderson Sarah E.
Published: June 2020

Early childhood is a critical period of life when nutritional choice and mealtime routines develop and obesogenic tendencies may be established. There is a need for greater understanding of toddlers and how parent-child interactions over time and across contexts relate to development of obesity. The purpose of this protocol paper is to describe the recruitment strategy, protocol, and characteristics of participants in the Play & Grow cohort. Between December 2017 and May 2019, three-hundred caregivers and their 16- to 19-month-old toddler (57% male) were recruited from records of the major pediatric provider in Central Ohio and enrolled in an ongoing 2-year prospective study. The cohort is diverse in race and ethnicity, parent education and age, household income, and family composition. Thirty-seven percent of children were born preterm (<37 weeks’ gestation). The first visit, completed by 299 families at mean (SD)18.2 (0.7) months child calendar age, included video-recorded parent-child interaction during play, anthropometric measurements, and caregiver questionnaire. Six months later, a home visit completed by 284 families included observation and video-recording of parent-child interaction in mealtime and non-mealtime contexts. This diverse cohort is being followed prospectively through ongoing home and laboratory visits at child ages 36 and 42 months. Growth trajectories of children will be analyzed in relation to self-regulation and quality of parent-child interaction.
Coronavirus and birth in Italy: results of a national population-based cohort study
Authors: Maraschini Alice , Corsi Edoardo , Salvatore Michele Antonio , Donati Serena ,   ItOSS COVID-19 working group
Published: June 2020

Introduction

The study was implemented to provide guidance to decision-makers and clinicians by describing hospital care offered to women who gave birth with confirmed COVID-19 infection.

Materials and methods

National population-based prospective cohort study involving all women with confirmed COVID-19 who gave birth between February 25 and April 22, 2020 in any Italian hospital.

Results

The incidence rate of confirmed SARS-CoV-2 infection in women who gave birth was 2.1 per 1000 maternities at a national level and 6.9/1000 in the Lombardy Region. Overall one third of the women developed a pneumonia and 49.7% assumed at least one drug. Caesarean section rate was 32.9%, no mothers nor newborns died. Six percent of the infants tested positive for SARS – CoV-2 at birth.

Conclusions

Clinical features and outcomes of COVID-19 in women who gave birth are similar to those described for the general population, most women developing mild to moderate illness.
Rotational Thromboelastometry predicts care level in COVID-19
Authors: Almskog Lou M. , Wikman Agneta , Svensson Jonas , Wanecek Michael , Bottai Matteo , van der Linden Jan , Ågren Anna
Published: June 2020

Background

High prevalence of thrombotic events in severely ill COVID-19 patients have been reported. Pulmonary embolism as well as microembolization of vital organs may in these individuals be direct causes of death. The identification of patients at high risk of developing thrombosis may lead to targeted, more effective prophylactic treatment.

Objectives

To test whether Rotational Thromboelastometry (ROTEM) indicates hypercoagulopathy in COVID-19 patients, and whether patients with severe disease have a more pronounced hypercoagulopathy compared with less severely ill patients.

Methods

The study was designed as a prospective observational study where COVID-19 patients over 18 years admitted to hospital were eligible for inclusion. Patients were divided into two groups depending on care level: 1) regular wards or 2) wards with specialized ventilation support. ROTEM was taken after admission and the data were compared with ROTEM in healthy controls.

Results

The ROTEM variables Maximum Clot Firmness (EXTEM-/FIBTEM-MCF) were higher in COVID-19 patients compared with healthy controls (p<0.001) and higher in severely ill patients compared with patients at regular wards (p<0.05). Coagulation Time (EXTEM-CT) was longer and Clot Formation Time (EXTEM-CFT) shorter in COVID-19 patients compared with healthy controls. Our results suggest that hypercoagulopathy is present in hospitalized patients with mild to severe COVID-19 pneumonia.

Conclusion

ROTEM variables were significantly different in COVID-19 patients early after admission compared with healthy controls. This pattern was more pronounced in patients with increased disease severity, suggesting that ROTEM-analysis may be useful to predict thromboembolic complications in these patients.
Stability of SARS-CoV-2 on Critical Personal Protective Equipment
Authors: Kasloff Samantha B , Strong James E , Funk Duane , Cutts Todd
Published: June 2020

The spread of COVID-19 in healthcare settings is concerning, with healthcare workers representing a disproportionately high percentage of confirmed cases. Although SARS-CoV-2 virus has been found to persist on surfaces for a number of days, the extent and duration of fomites as a mode of transmission, particularly in healthcare settings, has not been fully characterized. To shed light on this critical matter, the present study provides the first comprehensive assessment of SARS-CoV-2 stability on experimentally contaminated personal protective equipment (PPE) widely used by healthcare workers and the general public. Persistence of viable virus was monitored over 21 days on eight different materials, including nitrile medical examination gloves, reinforced chemical resistant gloves, N-95 and N-100 particulate respirator masks, Tyvek®, plastic, cotton, and stainless steel. Unlike previous reports, viable SARS-CoV-2 in the presence of a soil load persisted for up to 21 days on experimentally inoculated PPE, including materials from filtering facepiece respirators (N-95 and N-100 masks) and a plastic visor. Conversely, when applied to 100% cotton fabric, the virus underwent rapid degradation and became undetectable in less than 24 hours. These findings underline the importance of appropriate handling of contaminated PPE during and following use in high-risk settings and provide interesting insight into the potential utility of cotton, including cotton masks, in limiting COVID-19 transmission.