bluuebunny/crossref_metadata_2025 huggingface dataset:
A recurrent mutation at position 26,340 of SARS-CoV-2 is associated with failure of the E-gene qRT-PCR utilised in a commercial dual-target diagnostic assay
Authors: Artesi Maria , Bontems Sébastien , Göbbels Paul , Franckh Marc , Maes Piet , Boreux Raphaël , Meex Cécile , Melin Pierrette , Hayette Marie-Pierre , Bours Vincent , Durkin Keith
Published: May 2020

Control of the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic requires accurate laboratory testing to identify infected individuals, while also clearing essential staff to continue work. At the current time a number of qRT-PCR assays have been developed to identify SARS-CoV-2, targeting multiple positions in the viral genome. While the mutation rate of SARS-CoV-2 is moderate, given the large number of transmission chains it is prudent to monitor circulating viruses for variants that might compromise these assays. Here we report the identification of a C-to-T transition at position 26,340 of the SARS-CoV-2 genome which is associated with failure of the cobas® SARS-CoV-2 E-gene qRT-PCR in eight patients. As the cobas® SARS-CoV-2 assay targets two positions in the genome, the individuals carrying this variant were still called as SARS-CoV-2 positive. Whole genome sequencing of SARS-CoV-2 showed all to carry closely related viruses. Examination of viral genomes deposited on GISAID showed this mutation has arisen independently at least four times. This work highlights the necessity of monitoring SARS-CoV-2 for the emergence of SNPs which might adversely affect RT-PCRs used in diagnostics. Additionally, it argues that two regions in SARS-CoV-2 should be targeted to avoid false negatives.
Ocular toxicity and Hydroxychloroquine: A Rapid Meta-Analysis
Authors: Michelson Matthew , Chow Tiffany , Martin Neil , Ross Mike , Tee Amelia , Minton Steven
Published: May 2020

Rapid access to evidence is crucial in times of evolving clinical crisis. To that end, we propose a novel mechanism to answer clinical queries: Rapid Meta-Analysis (RMA). Unlike traditional meta-analysis, RMA balances quick time-to-production with reasonable data quality assurances, leveraging Artificial Intelligence to strike this balance. This article presents an example RMA to a currently relevant clinical question: Is ocular toxicity and vision compromise a side effect with hydroxychloroquine therapy?

As of this writing, hydroxychloroquine is a leading candidate in the treatment of COVID-19. By combining AI with human analysis, our RMA identified 11 studies looking at ocular toxicity as a side effect and estimated the incidence to be 3.4% (95% CI: 1.11-9.96%). The heterogeneity across the individual study findings was high, and interpretation of the result should take this into account. Importantly, this RMA, from search to screen to analysis, took less than 30 minutes to produce.
Identification of Three Endotypes in Pediatric Acute Respiratory Distress Syndrome by Nasal Transcriptomic Profiling
Authors: Williams James Garrett , Joshi Rashika , Jones Rhonda , Yunger Toni , Stoneman Erin , Varisco Brian
Published: May 2020

1

Acute respiratory distress syndrome (ARDS) and pediatric ARDS (PARDS) can be triggered by multiple pulmonary and non-pulmonary insults and are the source of substantial morbidity and mortality. The nasal epithelium is similar to that of the lower conducting airways and nasal transcriptomic profiling identifies disease and endotypes in lung cancer, COPD, and asthma. We conducted a prospective trial of testing whether this technique could identify PARDS endotypes in 26 control and 25 PARDS subjects <18 admitted to the PICU extracting RNA from inferior turbinate brushings on days 1, 3, 7, and 14. Standard RNA processing and mRNA-seq yielded ~25% usable specimens and a modified, low-input RNA protocol yielded 95% usable specimens. Sixty-four low-input specimens from 10 control and 15 PARDS subjects were used for initial analysis. Control and some PARDS subjects clustered together in both by-day and combined analysis into Groups A while some day 1, 3, and 7 specimens from the same subjects clustered into Groups B and C with specimens from these subjects moving to Group A with PARDS resolution. In multivariate analysis, the only clinical variables predictive of Group B or C status was severity of lung injury or viral PARDS trigger. Compared to Group A, Group B had upregulation of innate immune processes and group C had upregulation of cilia-associated processes. Analysis of the 15 specimens processed and analyzed by standard techniques identified the same processes as differentiating Groups A, B, and C. Mortality appeared to be higher in group B (25%) and C subjects (28.6%) compared to A subject (5%, p=0.1). Our findings demonstrate three distinct PARDS endotypes which may be useful for prognostic and therapeutic enrichment. ClinicalTrials.gov Identifier NCT03539783
FOXP3 mRNA profile prognostic of T cell mediated rejection and human kidney allograft survival
Authors: Luan Danny , Dadhania Darshana M. , Ding Ruchuang , Muthukumar Thangamani , Lubetzky Michelle , Lee John R. , Sharma Vijay K. , August Phyllis , Mueller Franco B. , Schwartz Joseph E. , Suthanthiran Manikkam
Published: May 2020

Background and objectives

T cell mediated rejection (TCMR) is the most frequent type of acute rejection and is associated with kidney allograft failure. Almost 40% of TCMR episodes fail to respond to anti-rejection therapy. FOXP3 is a specification factor for regulatory T cells and our single center study of 83 kidney allograft recipients showed that urinary cell FOXP3 mRNA level is diagnostic of TCMR and predicts TCMR reversibility and allograft survival. The objective of the current study is to determine whether our original findings could be replicated in an independent cohort of 480 kidney allograft recipients enrolled in the multicenter Clinical Trials of Organ Transplantation (CTOT)-04.

Design, setting, participants, and measurements

We measured levels of FOXP3 mRNA and levels of mRNA for CD25, CD3E, and perforin, and 18S rRNA in 3559 urines from 480 kidney allograft recipients prospectively enrolled in CTOT-04. RNA was isolated from the urinary cells and preamplification-enhanced real-time quantitative PCR assays were used to measure mRNAs.

Results

18S rRNA normalized levels of mRNA for FOXP3 (P=0.01, Kruskal-Wallis test), CD25 (P=0.01), CD3E (P<0.0001), and perforin (P<0.0001) distinguished patients with TCMR biopsies from those with No Rejection biopsies and those with stable graft function. FOXP3 mRNA level, but not the levels of mRNA for CD25, CD3E, or perforin, predicted TCMR reversal (AUC=0.764; 95% confidence interval, 0.611 to 0.917; P=0.008). Multivariable logistic regression analysis showed that FOXP3 mRNA level remains predictive after adjustment for potential cofounders. Kaplan-Meier survival curve analysis showed that FOXP3 mRNA level (P=0.0306) but not the levels of mRNA for CD25, CD3E, or perforin, is associated with kidney allograft survival.

Conclusion

In the independent CTOT-04 cohort, we demonstrate that urinary cell level of FOXP3 mRNA is diagnostic of TCMR, predicts its reversibility, and is prognostic of kidney allograft survival following an episode of TCMR.
Proteogenomics of glioblastoma associates molecular patterns with survival
Authors: Yanovich-Arad Gali , Ofek Paula , Yeini Eilam , Danilevsky Artem , Shomron Noam , Grossman Rachel , Satchi-Fainaro Ronit , Geiger Tamar
Published: May 2020

Glioblastoma (GBM) is the most aggressive form of glioma, with poor prognosis exhibited by most patients, and a median survival time of less than two years. To examine survival-associated patterns, we assembled a cohort of 87 GBM patients whose survival ranges from less than 3 months and up to 10 years, most of which are not bearing isocitrate-dehyderogenase (IDH)-1 mutation and did not undergo prior treatment. We integrated high-resolution mass-spectrometry proteomics and RNA-sequencing to examine the yet unresolved proteomic contribution to poor patient outcome, and compared it to the more established transcriptomic contribution and to published single-cell RNA-sequencing data. Discovering both layer-specific and shared processes, we found that immune, metabolic and developmental processes distinguish short and long survival periods. Additionally, we observed a significant discrepancy in tumor classification between expression layers. Overall, our integrative findings establish proteomic heterogeneity in GBM as a gateway to understanding poor patient survival.
Molecular detection of SARS-CoV-2 using a reagent-free approach
Authors: Calvez Ronan , Taylor Andrew , Calvo-Bado Leo , Fink Colin
Published: May 2020

Shortage of reagents and consumables required for the extraction and molecular detection of SARS-CoV-2 RNA in respiratory samples has led many laboratories to investigate alternative approaches for sample preparation. Fomsgaard et al 20205 recently presented results using heat-processing of respiratory samples prior to RT-qPCR as an economical method enabling an extremely fast streamlining of the processes at virtually no cost.

Here, we present our results using this method and highlight some major pitfalls that diagnostics laboratories should be aware of before proceeding with this technique. We first investigated various treatments using different temperatures, incubation times and sample volumes based on the above study to optimise the heat-treatment conditions. Although the initial data confirmed the published results, further investigations revealed unexpected inhibitory properties of some commonly used virus transport media (VTMs) on some commercially available RT-qPCR mixes, emphasising the critical importance of a thorough validation process to determine the most adapted reagents to be used depending on the sample types to be tested.

In conclusion, although the method works, with very consistent Ct values and an excellent sensitivity when compared to a conventional RNA extraction method, it is critical to include an internal control to check each sample for potential inhibition.
Geographical identification of the vulnerable groups during COVID-19 crisis: the typhoon eye effect and its boundary conditions
Authors: Tang Pok Man , Zhang Stephen X. , Li Chi Hon , Wei Feng
Published: May 2020

Aim

Although some studies suggest the coronavirus disease (COVID-19) is associated with negative consequences on physical health, our knowledge about the detrimental effects of COVID-19 on people’s mental health is still nascent. This study uses typhoon eye theory to offer insights in helping clinical psychiatrists to screen people with well-being issues during COVID-19 outbreak.

Methods

We collected survey data from working adults across different geographical areas in China on 20 and 21 February 2020 during the outbreak of COVID-19. The sample contains 308 working adults, who were in various parts of China, with varying distance to the epicenter of Wuhan.

Results

Individual adults’ distance to the epicenter was negatively associated with life satisfaction (β = −0.235, 95% CI −0.450 to −0.020, p = 0.032). This association between distance and life satisfaction was significant only for adults who were young or had smaller family sizes. For example, the negative relationship was strongest when the individuals were in the age bracket of 20 years old (15.7%; β = −0.703, 95% CI −1.098 to −0.307; p = 0.001) and single (32.3%; β = −0.767, 95% CI −1.125 to −0.408; p < 0.001).

Conclusion

Our results that people’s well-being deteriorates by the distance from the epicenter for specific groups of people help guide mental healthcare providers towards the regions that are further away from the epicenter in the ongoing COVID-19 outbreak. Meanwhile, our results indicate the practitioners should be cautious of using typhoon eye effect for individuals who were older or had a larger family size.
Ultra-Sensitive High-Resolution Profiling of Anti-SARS-CoV-2 Antibodies for Detecting Early Seroconversion in COVID-19 Patients
Authors: Norman Maia , Gilboa Tal , Ogata Alana F. , Maley Adam M. , Cohen Limor , Cai Yongfei , Zhang Jun , Feldman Jared E. , Hauser Blake M. , Caradonna Timothy M. , Chen Bing , Schmidt Aaron G. , Alter Galit , Charles Richelle C. , Ryan Edward T. , Walt David R.
Published: May 2020

The COVID-19 pandemic continues to infect millions of people worldwide. In order to curb its spread and reduce morbidity and mortality, it is essential to develop sensitive and quantitative methods that identify infected individuals and enable accurate population-wide screening of both past and present infection. Here we show that Single Molecule Array assays detect seroconversion in COVID-19 patients as soon as one day after symptom onset using less than a microliter of blood. This multiplexed assay format allows us to quantitate IgG, IgM and IgA immunoglobulins against four SARS-CoV-2 targets, thereby interrogating 12 antibody isotype-viral protein interactions to give a high resolution profile of the immune response. Using a cohort of samples collected prior to the outbreak as well as samples collected during the pandemic, we demonstrate a sensitivity of 86% and a specificity of 100% during the first week of infection, and 100% sensitivity and specificity thereafter. This assay should become the gold standard for COVID19 serological profiling and will be a valuable tool for answering important questions about the heterogeneity of clinical presentation seen in the ongoing pandemic.
China’s effective control and other countries’ uncharted challenge against COVID-19: an epidemiological and modelling study
Authors: Zheng Lingling , Kang Qin , Liao Weiyao , Chen Xiujuan , Huang Shuai , Liu Dong , Xia Huimin , Tang Jinling , Liang Huiying
Published: May 2020

Background

On the present trajectory, COVID is inevitably becoming a global epidemic, leading to concerns regarding the pandemic potential in China and other countries.

Objective

In this study, we use the time-dependent reproduction number (Rt) to comprise the COVID transmissibility across different countries.

Methods

We used data from Jan 20, 2019, to Feb 29, 2020, on the number of newly confirmed cases, obtained from the reports published by the CDC, to infer the incidence of infectious over time. A two-step procedure was used to estimate the Rt. The first step used data on known index-secondary cases pairs, from publicly available case reports, to estimate the serial interval distribution. The second step estimated the Rt jointly from the incidence data and the information data in the first step. Rt was then used to simulate the epidemics across all major cities in China and typical countries worldwide.

Results

Based on a total of 126 index-secondary cases pairs from 4 international regions, we estimated that the serial interval for SARS-2-CoV was 4.18 (IQR 1.92 – 6.65) days. Domestically, Rt of China, Hubei province, Wuhan had fallen below 1.0 on 9 Feb, 10 Feb and 13 Feb (Rt were 0.99±0.02, 0.99±0.02 and 0.96±0.02), respectively. Internationally, as of 26 Feb, statistically significant periods of COVID spread (Rt >1) were identified for most regions, except for Singapore (Rt was 0.92±0.17).

Conclusions

The epidemic in China has been well controlled, but the worldwide pandemic has not been well controlled. Worldwide preparedness and vulnerability against COVID-19 should be regarded with more care.

What is already known on this subject?

The basic reproduction number (R0) and the-time-dependent reproduction number (Rt) are two important indicators of infectious disease transmission. In addition, Rt as a derivative of R0 could be used to assess the epidemiological development of the disease and effectiveness of control measures. Most current researches used data from earlier periods in Wuhan and refer to the epidemiological features of SARS, which are possibly biased. Meanwhile, there are fewer studies discussed the Rt of COVID-19. Current clinical and epidemiological data are insufficient to help us understand the full view of the potential transmission of this disease.

What this study adds?

We use up-to-data observation of the serial interval and cases arising from local transmission to calculate the Rt in different outbreak level area and every province in China as well as five-top sever outbreak countries and other overseas. By comparing the Rt, we discussed the situation of outbreak around the world.
Brazilian Modeling of COVID-19(BRAM-COD): a Bayesian Monte Carlo approach for COVID-19 spread in a limited data set context
Authors: Dana Samy , Simas Alexandre B. , Filardi Bruno A. , Rodriguez Rodrigo N. , Valiengo Leandro da Costa Lane , Gallucci-Neto Jose
Published: May 2020

1

1.1

Background

The new coronavirus respiratory syndrome disease (COVID-19) pandemic has become a major health problem worldwide. Many attempts have been devoted to modeling the dynamics of new infection rates, death rates, and the impact of the disease on health systems and the world economy. Most of these modeling concepts use the Susceptible-Infectious-Susceptible (SIS) and Susceptible-Exposed-Infected-Recovered (SEIR) compartmental models; however, wide imprecise outcomes in forecasting can occur with these models in the context of poor data, low testing levels, and a nonhomogeneous population.

1.2

Objectives

To predict Brazilian ICU beds demand over time and during COVID-19 pandemic “peak”.

1.3

Methods

In the present study, we describe a Bayesian COVID-19 model combined with a Hamiltonian Monte Carlo algorithm to forecast quantitative predictions of infections, number of deaths and the demand for critical care beds in the next month in the Brazilian context of scarce data availability. We also estimated COVID-19 spread tendency in the state of São Paulo and forecasted the demand for critical care beds, as São Paulo is the epicenter of the Latin America pandemic.

1.4

Results

Our model estimated that the number of infected individuals would be approximately 6.5 million (median) on April 25, 2020, and would reach 16 to 17 million (median) by the end of August 2020 in Brazil. The probability that an infected individual requires ICU-level care in Brazil is 0.5833%. Our model suggests that the current level of mitigation seen in São Paulo is sufficient to reach Rt < 1, thus attaining a “peak” in the short term. In São Paulo state, the total number of deaths is estimated to be around 9,000 (median) with the 2.5% quantile being 6,600 deaths and the 97.5% quantile being around 13,350 deaths. Also, São Paulo will not attain its maximum capacity of ICU beds if the current trend persists over the long term.

1.5

Conclusions

The COVID-19 pandemic should peak in Brazil between May 8 and May 20, 2020 with a fatality rate lower than that suggested in the literature. The northern and northeastern regions of Brazil will suffer from a lack of available ICU beds, the southern and central-western regions appear to have sufficient ICU beds, finally, the southeastern region seems to have enough ICU beds only if it shares private beds with the publicly funded Unified Health System (SUS). The model predicts that, if the current policies and population behavior are maintained throughout the forecasted period, by the end of August 2020, Brazil will have around 7.6% to 8.2% of its population immune to COVID-19.
Dominant extrafollicular B cell responses in severe COVID-19 disease correlate with robust viral-specific antibody production but poor clinical outcomes
Authors: Woodruff Matthew C. , Ramonell Richard P. , Cashman Kevin S. , Nguyen Doan C. , Saini Ankur Singh , Haddad Natalie , Ley Ariel M. , Kyu Shuya , Howell J. Christina , Ozturk Tugba , Lee Saeyun , Chen Weirong , Estrada Jacob , Morrison-Porter Andrea , Derrico Andrew , Anam Fabliha A. , Sharma Monika , Wu Henry , Le Sang N. , Jenks Scott A. , Tipton Christopher M. , Daiss John L. , Hu William T. , Lee F. Eun-Hyung , Sanz Ignacio
Published: May 2020

Abstract/Introduction

A wide clinical spectrum has become a hallmark of theSARS-CoV-2(COVID-19) pandemic, although its immunologic underpinnings remain to be defined. We have performed deep characterization of B cell responses through high-dimensional flow cytometry to reveal substantial heterogeneity in both effector and immature populations. More notably, critically ill patients displayed hallmarks of extrafollicular B cell activation as previously described in autoimmune settings. Extrafollicular activation correlated strongly with large antibody secreting cell expansion and early production of high levels ofSARS-CoV-2-specific antibodies. Yet, these patients fared poorly with elevated inflammatory biomarkers, multi-organ failure, and death. Combined, the findings strongly indicate a major pathogenic role for immune activation in subsets of COVID-19 patients. Our study suggests that, as in autoimmunity, targeted immunomodulatory therapy may be beneficial in specific patient subpopulations that can be identified by careful immune profiling.
Effect of magnesium supplementation on circulating biomarkers of cardiovascular disease
Authors: Alonso Alvaro , Chen Lin Y. , Rudser Kyle D. , Norby Faye L. , Rooney Mary R. , Lutsey Pamela L.
Published: May 2020

Background

Magnesium supplementation may be effective for the prevention of cardiometabolic diseases, but mechanisms are unclear. Proteomic approaches can assist in identifying underlying mechanisms.

Methods

We collected repeated blood samples in 52 individuals enrolled in a double-blind trial which randomized participants 1:1 to oral magnesium supplementation (400 mg magnesium / day in the form of magnesium oxide) or matching placebo for 10 weeks. Plasma levels of 91 proteins were measured in baseline and follow-up samples using the Olink Cardiovascular Disease III proximity extension assay panel, and modeled as arbitrary units in log2scale. We evaluated the effect of oral magnesium supplementation on changes in protein levels and the baseline association between serum magnesium and protein levels. The Holm procedure was used to adjust for multiple comparisons.

Results

Participants were 73% women, 94% white, and had a mean age of 62. Changes in proteins did not significantly differ between the two intervention groups after correction for multiple comparisons. The most statistically significant effects were on myoglobin [difference −0.319 log2units, 95% confidence interval (CI) (−0.550, −0.088), p = 0.008], tartrate-resistant acid phosphatase type 5 [−0.187, (−0.328, −0.045), p = 0.011], tumor necrosis factor ligand superfamily member 13B [−0.181, (−0.332, −0.031), p = 0.019], ST2 protein [−0.198, (−0.363, −0.032), p =0.020], and interleukin-1 receptor type 1 [−0.144, (−0.273, −0.015), p = 0.029]. Similarly, none of the associations of baseline serum magnesium with protein levels were significant after correction for multiple comparisons.

Conclusion

Though we did not identify statistically significant effects of oral magnesium supplementation in this relatively small study, this study demonstrates the value of proteomic approaches for the investigation of mechanisms underlying the beneficial effects of magnesium supplementation.

Clinical Trials Registration

ClinicalTrials.govNCT02837328
Sex differences and Psychological Stress: Responses to the COVID-19 epidemic in China
Authors: Song Kangxing , Xu Rui , Stratton Terry D. , Kavcic Voyko , Luo Dan , Hou Fengsu , Bi Fengying , Jiao Rong , Yan Shiyan , Jiang Yang
Published: May 2020

About 83000 COVID-19 patients were confirmed in China up to May 2020. The effects of this public health crisis - and the varied efforts to contains its spread - have altered individuals’ “normal” daily functioning. This impact on social, psychological, and emotional well-being remain relatively unexplored, especially the ways in which Chinese men and women experience and respond to potential behavioral-related stressors. A cross-sectional study was conducted in late February 2020. Demographic characteristics and residential living conditions were measured along with psychological stress and behavior responses to the COVID-19 epidemic. 3088 questionnaires were received: 1749 females (56.6%) and 1339 males (43.4%). The mean level of stress, as measured by a visual analog scale, was 3.4 (SD=2.4) - but differed significantly by sex. Besides sex, factors positively associated with stress included: age (≤45 years), employment (unsteady income, unemployed), risk infection population (exposed to COVID-19, completed medical observation), difficulties encountered (diseases, work/study, financial, mental), behaviors(higher desire for COVID-19 knowledge, more time spent on the COVID-19). “Protective” factors included frequently contact with colleagues, calmness, and psychological resilience. Males and females also differed significantly in adapting to current living/working status, coping with heating, and psychological support service needs. Among Chinese, self-reported stress related to the COVID-19 epidemic were significantly related to sex, age, employment, resilience and coping styles. Future responses to such public health threats may wish to provide sex- and/or age-appropriate supports for psychological health and emotional well-being to those at greatest risk of experiencing stress.
Reduced COVID-19-Related Critical Illness and Death, and High Risk of Epidemic Resurgence, After Physical Distancing in Ontario, Canada
Authors: Tuite Ashleigh , Greer Amy L , De Keninck Steven , Fisman David N
Published: May 2020

We explored the impact of physical distancing measures on COVID-19 transmission in the population of Ontario, Canada using a previously described age- and health-status stratified transmission model. The model was fit to confirmed cases occupying intensive care unit (ICU) beds and mortality among hospitalized COVID-19 cases for the time period 19 March to 26 April 2020. We projected that mortality would have been 4.6-fold what was observed had physical distancing measures not been implemented in the province. Relaxation of physical distancing measures without compensatory increases in case detection, isolation, and/or contact tracing was projected to result in resurgence of disease activity. Return to normal or near-normal levels of contact would rapidly result in cases exceeding ICU capacity. Maintaining physical distancing for a longer period of time, allowing for the initial wave of infections to subside, delayed this resurgence, but the level of contacts post-restrictive distancing was the major factor determining how quickly ICU capacity was expected to be overwhelmed. Using a model, we demonstrate the marked impact strong public health measures had in reducing ICU admissions and mortality in Ontario. We also show that this hard-earned success is tenuous: relaxation of physical distancing measures in the near-term is projected to result in a rapid resurgence of disease activity.
A surprising formula for the spread of Covid-19 under aggressive management
Authors: Cherednik Ivan
Published: May 2020

Abstract

We propose an algebraic-type formula that describes with high accuracy the total number of detected infections for the Covid-19 pandemic in many countries. Our 2-phase formula can be used as a powerful forecasting tool. It is based on the author’s new theory of momentum management of epidemics; Bessel functions are employed. Its 3 parameters are the initial transmission rate, reflecting the viral fitness and “normal” frequency of contacts in the infected areas, and the intensity of prevention measures at phases 1, 2. Austria, Brazil, Germany, Japan, India, Israel, Italy, the Netherlands, Sweden, Switzerland, UK, and the USA are considered. For the USA, all states are processed independently and some “interaction” is added; the forecasting software is provided.
Act early, save lives: managing COVID-19 in Greece
Authors: Ilias Gountas , Georgios Hillas , Kyriakos Souliotis
Published: May 2020

Objectives

To assess the impact of the implemented social distancing interventions (SD) in Greece.

Study Design

A dynamic, discrete time, stochastic individual-based model was developed to simulate COVID-19 transmission.

Methods

We fit the transmission model to the observed trends in deaths and ICU beds use.

Results

If Greece had not implemented the SD measures, the healthcare system would have been overwhelmed between 30 March and 4 of April. Additionally, the SD interventions averted 4360 deaths and prevent the healthcare system from overwhelmed.

Conclusions

The fast reflexes of the Greek government limit the burden of the Covid-19 outbreak.
Inflammatory markers in Covid-19 Patients: a systematic review and meta-analysis
Authors: Vaseghi Golnaz , Mansourian Marjan , Karimi Raheleh , Heshmat-Ghahdarijani Kiyan , Rouhi Paria , Shariati Mahfam , Javanmard Shaghayegh Haghjoo
Published: May 2020

Introduction

Diagnosis of COVID-19 is based on clinical manifestation, history of exposure, positive findings on chest CT and laboratory tests. It has been shown that inflammation plays a role in pathogenesis of COVID-19.

Method

We used the necessary transformations to convert the median and IQR to mean and SD Random-effect model using Der Simonian, and Laird methods was used if heterogeneity between studies was significant, the homogeneity among studies was assessed with I2 Statistic, values above 50%, and for the chi-square test, P-values <0.1 was supposed statistically significant

Results

Twelve studies were included in the analysis that all of which were conducted in China in the year 2020. The result of combining 12 articles with 772 participants showed that the pooled estimate of the mean of lymphocyte with 95% CI was (Mean: 1.01; 95% CI (0.76-1.26); p-value<0.001). About WBC the pooled result of 9 studies with 402 participants was (Mean: 5.11; 95% CI (3.90-6.32); p-value<0.001) Also the pooled mean estimate of 9 studies with 513 patients for the ratio of Neutrophil/lymphocyte was (Mean: 3.62; 95% CI (1.48-5.77); p-value=0.001). The pooled mean from the combination of 7 studies with 521 patients on CRP was (Mean: 28.75; 95% CI (8.04-49.46).

Conclusion

Inflammatory Markers increase in patients with Covid-19, which can be a good indicator to find patients.
Modeling and Dynamics in Epidemiology, COVID19 with Lockdown and Isolation Effect : Application to Moroccan Case
Authors: YAFIA Radouane
Published: May 2020

In this paper, we present a SIR mathematical model in order to study the dynamics and propagation of Covid19 and the effect of lockdown of susceptible population and isolation of infectious population. The basic reproduction number R0 depends on the lockdown and isolation rates. We prove that, R0 becomes smaller than one if the lockdown and isolation rates are higher and in this case, we have the extinction of the infectious population. We apply our results to the case of Morocco country. In the end we carried out some numerical simulations illustrating our results.
Using different epidemiological models to modeling the epidemic dynamics in Brazil
Authors: de Alcantara Lucas Ravellys Pyrrho , Silva Lucio , de Almeida Anderson Rodrigues , Pitta Maira Galdino da Rocha , Coutinho Artur Paiva
Published: May 2020

In this paper we provide forecasts of the cumulative number of confirmed reported cases in Brazil, specifically in Pernambuco and Ceara, by using the generalized logistic growth model, the Richards growth model and Susceptible, Un-quanrantined infected, Quarantined infected, Confirmed infected (SUQC) phenomenological model. We rely on the Nash-Sutcliffe efficiency (NSE), root-mean-square error (RMSE) and mean absolute relative error (MARE) to quantify the quality of the models fits during the calibrationAll of these analyzes have been valid until the present date, April 14, 2020. The different models provide insights of our scenario predictions.
How should hospitals manage the backlog of patients awaiting surgery following the COVID-19 pandemic? A demand modelling simulation case study for carotid endarterectomy
Authors: Martin Guy , Clarke Jonathan , Markar Sheraz , Carter Alexander W , Mason Sam , Purkayastha Sanjay , Darzi Ara , Kinross James , Collaborative PanSurg
Published: May 2020

Background
The COVID-19 pandemic presents unparalleled challenges for the delivery of safe and effective care. In response, many health systems have chosen to restrict access to surgery and reallocate resources; the impact on the provision of surgical services has been profound, with huge numbers of patient now awaiting surgery at the risk of avoidable harm. The challenge now is how do hospitals transition from the current pandemic mode of operation back to business as usual, and ensure that all patients receive equitable, timely and high-quality surgical care during all phases of the public health crisis.

Aims and Methods
This case study takes carotid endarterectomy as a time-sensitive surgical procedure and simulates 400 compartmental demand modelling scenarios for managing surgical capacity in the UK for two years following the pandemic.

Results
A total of 7,69 patients will require carotid endarterectomy. In the worst-case scenario, if no additional capacity is provided on resumption of normal service, the waiting list may never be cleared, and no patient will receive surgery within the 2-week target; potentially leading to >1000 avoidable strokes. If surgical capacity is doubled after 1-month of resuming normal service, it will still take more than 6-months to clear the backlog, and 30.8% of patients will not undergo surgery within 2-weeks, with an average wait of 20.3 days for the proceeding 2 years.

Conclusions
This case study for carotid endarterectomy has shown that every healthcare system is going to have to make difficult decisions for balancing human and capital resources against the needs of patients. It has demonstrated that the timing and size of this effort will critically influence the ability of these systems to return to their baseline and continue to provide the highest quality care for all. The failure to sustainably increase surgical capacity early in the post-COVID-19 period will have significant long-term negative impacts on patients and is likely to result in avoidable harm.
Beyond the Spike: identification of viral targets of the antibody response to SARS-CoV-2 in COVID-19 patients
Authors: Hachim Asmaa , Kavian Niloufar , Cohen Carolyn A , Chin Alex WH , Chu Daniel KW , Mok Chris Ka Pun , Tsang Owen TY , Yeung Yiu Cheong , Perera Ranawaka APM , Poon Leo LM , Peiris Malik JS , Valkenburg Sophie A
Published: May 2020

Background: The SARS-CoV-2 virus emerged in December 2019 and caused a pandemic associated with a spectrum of COVID-19 disease ranging from asymptomatic to lethal infection. Serology testing is important for diagnosis of infection, determining infection attack rates and immunity in the population. It also informs vaccine development. Although several serology tests are in use, improving their specificity and sensitivity for early diagnosis on the one hand and for detecting past infection for population-based studies, are priorities. Methods: We evaluated the anti-SARS-CoV-2 antibody profiles to 15 SARS-CoV-2 antigens by cloning and expressing 15 open reading frames (ORFs) in mammalian cells and screened antibody responses to them in COVID-19 patients using the Luciferase Immunoprecipitation System (LIPS). Results: The LIPS technique allowed us to detect antibody responses in COVID-19 patients to 11 of the 15 SARS-CoV-2 antigens tested, identifying novel immunogenic targets. This technique shows that antigens ORF3b and ORF8 allow detection of antibody early in infection in a specific manner and reveals the immuno-dominance of the N antigen in COVID-19 patients. Conclusion: Our report provides an unbiased characterization of antibody responses to a range of SARS-CoV-2 antigens. The combination of 3 SARS-CoV-2 antibody LIPS assays, i.e. N, ORF3b, and ORF8, is sufficient to identify all COVID-19 patients of our cohort even at early time-points of illness, whilst Spike alone fails to do so. Furthermore, our study highlights the importance of investigating new immunogens NSP1, ORF3b, ORF7a and ORF8 which may mediate immune functions other than neutralization which may be beneficial or harmful to the patient.
Early trends for SARS-CoV-2 infection in central and north Texas and impact on other circulating respiratory viruses
Authors: Mutnal Manohar B , Arroliga Alejandro C , Walker Kimberly , Mohammad Amin A , Brigmon Matthew M , Beaver Ryan M , Midturi John K , Rao Arundhati
Published: May 2020

Introduction: Rapid diagnosis and isolation are key to containing the rapid spread of a pandemic agent like SARS-CoV-2, which has spread globally since its initial outbreak in Wuhan province in China. SARS-CoV-2 is novel to most parts of the world including USA and the effect on normally prevalent viruses is just becoming apparent. We present our initial data on the prevalence of respiratory viruses in the month of March, 2020.
Methods: This is a retrospective cohort study post launching of SARS-CoV-2 testing at BSWH, Temple TX. Testing for SARS-CoV-2 was performed by real-time RT-PCR assay and results were shared with State public health officials for immediate interventions.
Results: More than 3500 tests were performed during the first two weeks of testing for SARS-CoV-2 and identified 168 (4.7%) positive patients. Sixty-two (3.2%) of the 1,912 ambulatory patients and 106 (6.3%) of the 1,659 ED/inpatients were tested positive. Higher rate of infection (6.9%) were noted in the patients belonging to age group 25-34 years and least number of positive cases were noted in <25 years old (2%) group. The TX State county specific patient demographic information was shared with respective public health departments for epidemiological interventions. Incidentally, this study showed that there was a sudden decrease in the occurrence of other infections due to seasonal viruses, perhaps due to increased epidemiological awareness, about SARS-CoV-2, among general public. Authors would also like to share a small study on SARS-CoV-2 serological assay for the detection of IgG antibodies.
Conclusions: This study was intended to provide an initial experience of dealing with a pandemic and the role of laboratories in crisis management. Epidemiological interventions depend on timely availability of accurate diagnostic tests and throughput capacity of such systems during large outbreaks like SARS-CoV-2.
Integrative genomic analysis in African American children with asthma finds 3 novel loci associated with lung function
Authors: Goddard Pagé C. , Keys Kevin L. , Mak Angel C.Y. , Lee Eunice Yujung , Liu Amy K. , Samedy-Bates Lesly-Anne , Risse-Adams Oona , Contreras María G. , Elhawary Jennifer R. , Hu Donglei , Huntsman Scott , Oh Sam S. , Salazar Sandra , Eng Celeste , Himes Blanca E. , White Marquitta J. , Burchard Esteban G.
Published: May 2020

Bronchodilator drugs are commonly prescribed for treatment and management of obstructive lung function present with diseases such as asthma. Administration of bronchodilator medication can partially or fully restore lung function as measured by pulmonary function tests. The genetics of baseline lung function measures taken prior to bronchodilator medication has been extensively studied, and the genetics of the bronchodilator response itself has received some attention. However, few studies have focused on the genetics of post-bronchodilator lung function. To address this gap, we analyzed lung function phenotypes in 1,103 subjects from the Study of African Americans, Asthma, Genes, and Environment (SAGE), a pediatric asthma case-control cohort, using an integrative genomic analysis approach that combined genotype, locus-specific genetic ancestry, and functional annotation information. We integrated genome-wide association study (GWAS) results with an admixture mapping scan of three pulmonary function tests (FEV1, FVC, and FEV1/FVC) taken before and after albuterol bronchodilator administration on the same subjects, yielding six traits. We identified 18 GWAS loci, and 5 additional loci from admixture mapping, spanning several known and novel lung function candidate genes. Most loci identified via admixture mapping exhibited wide variation in minor allele frequency across genotyped global populations. Functional fine-mapping revealed an enrichment of epigenetic annotations from peripheral blood mononuclear cells, fetal lung tissue, and lung fibroblasts. Our results point to three novel potential genetic drivers of pre- and post-bronchodilator lung function:ADAMTS1, RAD54B, andEGLN3.
A broad response to intracellular long-chain polyphosphate in human cells
Authors: Bondy-Chorney Emma , Abramchuk Iryna , Nasser Rawan , Holinier Charlotte , Denoncourt Alix , Baijal Kanchi , McCarthy Liam , Khacho Mireille , Lavallée-Adam Mathieu , Downey Michael
Published: May 2020

Polyphosphates (PolyP) are composed of long chains of inorganic phosphates linked together by phosphoanhydride bonds. They are found in all kingdoms of life, playing roles in cell growth, infection, and blood coagulation. A resurgence in interest in polyP has shown links to diverse aspects of human disease. However, unlike in bacteria and lower eukaryotes, the mammalian enzymes responsible for polyP metabolism are not known. Many studies have resorted to adding polyP to cell culture media, but it is not clear if externally applied polyP enters the cell to impact signaling events or whether their effect is mediated exclusively by extracellular receptors. For the first time, we use RNA-seq and mass spectrometry to define a broad impact of polyP produced inside of mammalian cells via ectopic expression of theE. colipolyP synthetase Ppk1. RNA-seq demonstrates that Ppk1 expression impacts expression of over 350 genes enriched for processes related to transcription and cell motility. Analysis of proteins via label-free mass spectrometry identified over 100 changes with functional enrichment in cell migration. Follow up work suggests a role for internally-synthesized polyP in promoting activation of mTOR and ERK1/2-EGR1 signaling pathways implicated in cell growth and stress. Finally, fractionation analysis shows that polyP accumulated in multiple cellular compartments and was associated with the relocalization several nuclear/cytoskeleton proteins, including chromatin bound proteins DEK, TAF10, GTF2I and translation initiation factor eIF5b. Our work is the first to demonstrate that internally produced polyP can activate diverse signaling pathways in human cells.

Significance Statement

For many years following its discovery in 1890, polyphosphates (polyP) were dismissed as evolutionary fossils. Best understood for its role in bacteria and yeast, our understanding of polyP in mammals remains rudimentary because the enzymes that synthesize and degrade polyP in mammalian systems are currently unknown. In our work, we carried out large-scale transcriptome and proteome approaches on human cells designed to accumulate internally produced polyP via ectopic expression of a bacterial polyP synthetase. Our work is the first to systematically assess the impact of increased intracellular polyP.
Impact of long- and short-range fiber depletion on the cognitive deficits of fronto-temporal dementia
Authors: Savard Melissa , Pascoal Tharick A. , Dhollander Thijs , Iturria-Medina Yasser , Vitali Paolo , Therriault Joseph , Mathotaarachchi Sulantha , Benedet Andrea L. , Gauthier Serge , Rosa-Neto Pedro ,   for the Frontotemporal Lobar Degeneration Neuroimaging Initiative
Published: May 2020

Fronto-temporal dementia (FTD) is a neurodegenerative disease characterized by focal atrophy of the gray matter (GM), especially in the frontal and temporal regions. Recent studies suggest a framework where white matter (WM) atrophy plays an important role in FTD pathophysiology. However, these studies often overlook the fact that WM tracts bridging different brain regions may have different vulnerabilities to the disease and the relative contribution of GM atrophy to this WM model, resulting in a less comprehensive understanding of the relationship between clinical symptoms and pathology. Here, by leveraging the sensitivity of advanced diffusion MRI modelling and metrics to precise white matter microstructural properties, we aim to clarify the relative contributions of WM fibers and GM atrophy to the cognitive symptoms typically found in FTD. A total of 155 participant from the Frontotemporal Lobar Degeneration Neuroimaging Initiative (FTLDNI) were analysed, including 68 normal elderly controls (CN), 28 behavioral variants (BV), 26 sematic variants (SV) and 30 progressive non fluent aphasia variants (PNFA) of FTD. Diffusion MRI analysis was performed using two complementary techniques: whole brain fixel-based analysis (FBA) and structural connectivity based on probabilistic tractography. Whole brain GM atrophy was assessed using voxel-based morphometry (VBM). Using a common factor analysis to extract a semantic and an executive factor, we aim to test the relative contribution of WM and GM of specific tracts in predicting cognition. We found that semantic symptoms were mainly dependent on short-range WM fiber disruption, while damage to long-range WM fibers was preferentially associated to executive dysfunction with the GM contribution to cognition being predominant for local processing. Our results support the importance of the disruption of specific WM tracts to the core cognitive symptoms associated with FTD. As large-scale WM tracts, which are particularly vulnerable to vascular disease, were highly associated with executive dysfunction, our findings highlight the importance of controlling for risk factors associated with deep white matter disease, such as vascular risk factors, in patients with FTD in order not to potentiate underlying executive dysfunction.