bluuebunny/crossref_metadata_2025 huggingface dataset:
Lockdowns exert selection pressure on overdispersion of SARS-CoV-2 variants
Authors: Nielsen Bjarke Frost , Eilersen Andreas , Simonsen Lone , Sneppen Kim
Published: July 2021

The SARS-CoV-2 ancestral strain has caused pronounced super-spreading events, reflecting a disease characterized by overdispersion, where about 10% of infected people causes 80% of infections. New variants of the disease have different person-to-person variations in viral load, suggesting for example that the Alpha (B.1.1.7) variant is more infectious but relatively less prone to superspreading. Meanwhile, mitigation of the pandemic has focused on limiting social contacts (lockdowns, regulations on gatherings) and decreasing transmission risk through mask wearing and social distancing. Using a mathematical model, we show that the competitive advantage of disease variants may heavily depend on the restrictions imposed. In particular, we find that lockdowns exert an evolutionary pressure which favours variants with lower levels of overdispersion. We find that overdispersion is an evolutionarily unstable trait, with a tendency for more homogeneously spreading variants to eventually dominate.

Significance

One of the most important and complex properties of viral pathogens is their ability to mutate. The SARS-CoV-2 pandemic has been characterized by overdispersion – a propensity for superspreading, which means that around 10% of those who become infected cause 80% of infections. However, evidence is mounting that this is not a stable property of the virus and that the Alpha variant spreads more homogeneously. We use a mathematical model to show that lockdowns exert a selection pressure, driving the pathogen towards more homogeneous transmission. In general, we highlight the importance of understanding how non-pharmaceutical interventions exert evolutionary pressure on pathogens. Our results imply that overdispersion should be taken into account when assessing the transmissibility of emerging variants.
Angiotensin II receptor I auto-antibodies following SARS-CoV-2 infection
Authors: Harrington Whitney E. , Jiang Yonghou , Duffy Fergal , Hadlock Jennifer , Raappana Andrew , Styrchak Sheila , Beck Ingrid , Chour William , Houck John , Duvvuri Venkata , Yeung Winnie , Haglund Micaela , Wallner Jackson , Wallick Julie A. , Hardy Samantha , Oldroyd Alyssa , Ko Daisy , Gervassi Ana , Murray Kim M. , Kaplan Henry , Aitchison John D. , Heath James R. , Sather D. Noah , Goldman Jason D. , Frenkel Lisa
Published: July 2021

BACKGROUND

Coronavirus disease 2019 (COVID-19) is associated with endothelial activation and coagulopathy, which may be related to pre-existing or infection-induced pro-thrombotic autoantibodies such as those targeting angiotensin II type I receptor (AT1R-Ab).

METHODS

We compared prevalence and levels of AT1R-Ab in COVID-19 cases with mild or severe disease to age and sex matched negative controls.

RESULTS

There were no significant differences between cases and controls. However, there were trends toward a higher proportion with AT1R-Ab positivity among severe cases versus controls (32% vs. 11%, p=0.1) and higher levels in those with mild COVID-19 compared to controls (median 9.5U/mL vs. 5.9U/mL, p=0.06).

CONCLUSIONS

These findings suggest that AT1R-Ab are not consistently associated with COVID-19 but do not exclude a contribution to endothelial pathology in a subset of people.
A cross-sectional cohort study of prevalence of antibodies to COVID-19 in Port-au-Prince, Haiti
Authors: DeGennaro Vincent , Schwartz Timothy , Henderson Rebecca , Elie Marie-Carmelle
Published: July 2021

Intro

As of January 14, 2021, Haiti has had 10,781 confirmed (first case March 19th) and 45,927 suspected cases of COVID-19, with 240 official deaths.

Methods

From May until September, 2020, we tested visitors to 20 clinics, for COVID-19 in five neighborhoods of Port-au-Prince as part of a public health effort to determine prevalence of COVID-19 in the general community. In order to estimate changes in number of deaths, the team visited eighteen funeral homes to solicit data on the number of funerals conducted for each month in 2019 and through October 2020. We also sought to evaluate the attitudes of Port-au-Prince citizens towards a generic COVID-19 vaccine in April 2021.

Results

In May and July 2020, 11.4% and 9.1% of those tested were positive for antibodies to COVID-19, respectively. The number of funerals held in the Port-au-Prince area increased by 69.6.% (CI 95% 56.1-83.1) since the official arrival of COVID-19 on March 19th. We found high rates of vaccine hesitancy with 76% saying they would not take a free COVID-19 vaccine. Further research is needed to validate the findings here, but there are strong suggestions that COVID-19 has had more of an impact than previously reported.

‘What is already known on this subject?’

Very little is known about the true epidemiology of COVID-19 in Haiti due to lack of testing, stigma, and lack of resources. The Ministry of Health reports Haiti has had 10,781 confirmed (first case March 19th) and 45,927 suspected cases of COVID-19, with 240 official deaths. Most officials accept these numbers as vast underestimates.

‘What does this study add?’’

This study estimates a prevalence of 10% for COVID-19 antibodies in the population of Port-au-Prince in May to August 2020. Only 19-38% of those surveyed with confirmed antibodies reported experiencing symptoms in the last few months prior to the survey. We found a 69% increase in funerals per month in Port-au-Prince for the first six months post-COVID (March 2020) compared to the 14 months prior.

Finally, we found significant vaccine hesitancy with only 24% reporting “Yes” or “Maybe” when asked if they’d take a free of charge vaccine.
Social isolation, loneliness and all-cause dementia: a longitudinal and imaging-genetic study in the UK Biobank cohort
Authors: Shen Chun , Sahakian Barbara J. , Cheng Wei , Kang Jujiao , Dong Guiying , Xie Chao , Zhao Xing-Ming , Feng Jianfeng
Published: July 2021

INTRODUCTION

Current findings of the relative influence of social isolation and loneliness on dementia are contradictory, and the potential neurobiological mechanisms are unclear.

METHODS

We utilized the UK Biobank to investigate the relationships of social isolation and loneliness with dementia (n = 462,619). Neuroanatomical correlates were identified in a subset of participants (n = 32,263). The transcriptomic signatures of related brain changes were characterized by gene enrichment analysis.

RESULTS

After full adjustment, social isolation but not loneliness was associated with dementia (hazard ratio: 1.28, 95% confidence interval: 1.17-1.39). Isolated individuals had reduced gray matter volumes in temporal, frontal, occipital and subcortical regions (e.g., hippocampus and amygdala). Relevant brain changes were spatially correlated with genes involved in mitochondrial dysfunction and oxidative phosphorylation, and down-regulated Alzheimer’s disease-related genes.

DISCUSSION

Social isolation is an independent risk factor for dementia, which could be partly explained by related structural changes coupling with altered molecular functions.
Indirect impact on number of admitted children with COVID-19 in the first three months of emergency use of two vaccines, in Rio de Janeiro, Brazil
Authors: Fonseca CGB , Costa ALTG , Esteves MDM , de Carvalho BRR , Souza CV , Teixeira CH , Araujo da Silva AR
Published: July 2021

Introduction

Since January 19, 2021, two vaccines against SARS-COV-2 are available in Brazil for emergency use for selected groups, not including children.

Aim

To describe indirect impact on the number of hospitalized children with COVID-19 in the first three months after beginning of emergency use of two vaccines.

Methods

A retrospective study was conducted in children (0-18 years), admitted in two pediatric hospitals of Rio de Janeiro city, between January and April 2021 with confirmed COVID-19 by reverse transcription polymerase chain reaction or serological tests. Number of cases, clinical signs, symptoms and outcomes were compared with the first wave of disease (April-June 2020). A p value of less than .05 were considered was significant.

Results

The number of total admitted patients (with all diseases) were 1097 in 2020 period, being 46 (4.2%) of them with confirmed COVID-19, and 2187 in the 2021 period, with 47 (2.1%) cases (p=0.006). Predominant respiratory symptoms were present in 29/46 (63%) as the main presentation in 2020 patients and 37/47 (78.7%) in 2021 children (p=0.09). The main symptoms were fever, cough and dyspnoea in both periods. The median of lenght of stay after diagnosis were 4 days in 2020 and 2021 (p=0.9). Just one patient died in 2021.

Conclusion

There was reduction of relative percentage of admitted confirmed pediatric cases in the the first three months of emergency use of two vaccines against SARS-COV-2, but it’s uncertain to atribute this finding to vaccination due to high circulation of the virus in the city.
Simulating the impact of non-pharmaceutical interventions limiting transmission in COVID-19 epidemics using a membrane computing model
Authors: Campos M , Sempere JM , Galán JC , Moya A , Llorens C , de-los-Angeles C , Baquero-Artigao F , Cantón R , Baquero F
Published: July 2021

Epidemics caused by microbial organisms are part of the natural phenomena of increasing biological complexity. The heterogeneity and constant variability of hosts, in terms of age, immunological status, family structure, lifestyle, work activities, social and leisure habits, daily division of time, and other demographic characteristics make it extremely difficult to predict the evolution of epidemics. Such prediction is, however, critical for implementing intervention measures in due time and with appropriate intensity. General conclusions should be precluded, given that local parameters dominate the flow of local epidemics. Membrane computing models allows us to reproduce the objects (viruses, hosts) and their interactions (stochastic but also with defined probabilities) with an unprecedented level of detail. Our LOIMOS model helps reproduce the demographics and social aspects of a hypothetical town of 10,320 inhabitants in an average European country where COVID-19 is imported from the outside. The above-mentioned characteristics of hosts and their lifestyle are minutely considered. The dynamics of the epidemics are reproduced and include the effects on viral transmission of innate and acquired immunity at various ages. The model predicts the consequences of delaying the adoption of non-pharmaceutical interventions (between 15 and 45 days after the first reported cases) and the effect of those interventions on infection and mortality rates (reducing transmission by 20%, 50%, and 80%) in immunological response groups. The lockdown for the elderly population as a single intervention appears to be effective. This modelling exercise exemplifies the application of membrane computing for designing appropriate interventions in epidemic situations.
ANTI - SARS-CoV-2 ANTIBODY SCREENING IN HEALTH CARE WORKERS AND ITS CORRELATION WITH CLINICAL PRESENTATION
Authors: Aryal Suraj , Pandit Sanskriti , Pokhrel Sushant , Chhusyabaga Mandira , Bista Pabitra , Bhatt Mahendra Psd. , Subedi Dharma Datta , Rijal Basista Psd.
Published: July 2021

Background

Antibody titration and the life span of the antibody against SARS-CoV-2 have been found to be determined by the clinical presentation as well. The extent of exposure of health care workers and the general public to SARS-CoV-2 needs to be assessed to monitor the COVID-19 pandemic. Thus, this study is an attempt in assessing the anti-SARs-COV-2 antibody in health care workers.

Methods

This laboratory-based cross-sectional study was performed in Manmohan Memorial Medical College and Teaching Hospital, Kathmandu from November 2020 to January 2021. A total of 185 HCWs were screened for anti-SARS-CoV-2 antibody in the blood serum specimens. A structured questionnaire was administered to collect information from HCWs. Anti-SARS- CoV-2 antibody screening was performed using a lateral flow immunoassay. Data were analyzed according to standard statistical methods using SPSS version 20.

Results

A total of 185 HCWs were participated in the study, among which 41 (22.2%) of them tested positive for anti-SARS-CoV-2 antibody. Among the 41 individuals who tested positive, 37 of them tested positive for IgG only and 4 of them tested positive for both IgM and IgG antibodies. Presence of history of SARS-CoV-2 infection (p<0.001), presence of flu-like symptoms within the last 6 months (p<0.001), and presence of positive contact history (p=0.002) were statistically significant with antibody screening among HCWs.

Conclusion

The burden of SARS-CoV-2 infection among healthcare workers seems to be high and HCWs are at risk of acquiring infection in the workplace. Anti-SARS-CoV-2 antibody screening among health care workers is highly recommended in multiple healthcare settings that can help in monitoring transmission dynamics and evaluation of infection control policies.
Individual-Level Heterogeneity in Mask-wearing During the COVID-19 Pandemic in Malaysia
Authors: Zhang Stephen X. , Looi Kim Hoe , Li Nicolas , Wan Xue , Li Jizhen
Published: July 2021

Wearing a face mask has been a key approach to contain or slow down the spread of COVID-19 in the ongoing pandemic. However, there is huge heterogeneity among individuals in their willingness to wear face masks during an epidemic. This research aims to investigate the individual heterogeneity to wear face masks and its associated predictors during the COVID-19 pandemic when mask-wearing was not mandatory but individuals’ choices. Based on a survey of 708 Malaysian adults and a multivariate least-squares fitting analysis, the results reveal a significant variance among individuals in wearing masks, as 34% of the individual adults did not always wear masks in public places. Female, individuals who wash their hands more frequently, and those who reported more availability of personal protective equipment were more likely to practice mask-wearing. The identification of less compliant groups of mask-wearing has critical implications by enabling more specific health communication campaigns.
Comorbidity accounts for severe COVID-19 risk, but how do we measure it? Retrospective assessment of the performance of three measures of comorbidity using 4,607 hospitalizations
Authors: Monterde David , Carot-Sans Gerard , Cainzos-Achirica Miguel , Abilleira Sònia , Coca Marc , Vela Emili , Clèries Montse , Valero Damià , Comin-Colet Josep , Garcia-Eroles Luis , Sust Pol Perez , Arrufat Miquel , Lejardi Yolanda , Piera Jordi
Published: July 2021

Background

Comorbidity burden has been identified as a relevant predictor of critical illness in patients hospitalized with coronavirus disease 2019 (COVID-19). However, comorbidity burden is often represented by a simple count of few conditions that may not fully capture patients’ complexity.

Purpose

To evaluate the performance of a comprehensive index of the comorbidity burden (Queralt DxS), which includes all chronic conditions present on admission, as an adjustment variable in models for predicting critical illness in hospitalized COVID-19 patients and compare it with two broadly used measures of comorbidity.

Patients and methods

We analyzed data from all COVID-19 hospitalizations reported in eight public hospitals of Catalonia (North-East Spain) between June 15 and December 8 2020. The primary outcome was a composite of critical illness that included the need for invasive mechanical ventilation, transfer to ICU, or in-hospital death. Predictors included age, sex, and comorbidities present on admission measured using three indices: the Charlson index, the Elixhauser index, and the Queralt DxS index for comorbidities on admission. The performance of different fitted models was compared using various indicators, including the area under the receiving operating characteristics curve (AUC).

Results

Our analysis included 4,607 hospitalized COVID-19 patients. Of them, 1,315 experienced critical illness. Comorbidities significantly contributed to predicting the outcome in all summary indices used. The AUC for prediction of critical illness was 0.641 (95% CI 0.624-0.660) for the Charlson index, 0.665 (0.645-0.681) for the Elixhauser index, and 0.787 (0.773-0.801) for Queralt DxS. Other metrics of model performance also showed Queralt DxS being consistently superior to the other indices.

Conclusion

In our analysis, the ability of comorbidity indices to predict hospital outcomes in hospitalized COVID-19 patients increased with their exhaustivity. The comprehensive Queralt DxS index may improve the accuracy of predictive models for resource allocation and clinical decision-making in the hospital setting.
Prevalence of Long COVID symptoms in Bangladesh: A Prospective Inception Cohort Study of COVID-19 survivors
Authors: Hossain Mohammad Anwar , Hossain K M Amran , Saunders Karen , Uddin Zakir , Walton Lori Maria , Raigangar Veena , Sakel Mohamed , Shafin Rubayet , Hossain Mohammad Sohrab , Kabir Md. Feroz , Faruqui Rafey , Rana Shohag , Ahmed Md. Shahoriar , Chakrovorty Sonjit Kumar , Hossain Md. Anwar , Jahid Iqbal Kabir
Published: July 2021

Objective

The objective of this study was to identify the prevalence of ‘Long COVID’ symptoms (LCS) in a large cohort of survivors and identify any potential associated risk factors.

Design

A prospective survey was undertaken of an inception cohort of confirmed COVID-19 survivors (Aged 18 to 87 years).

Participants and Setting

14392 participants were recruited from 24 testing facilities across Bangladesh between June, and November 2020. All participants had a previously confirmed positive COVID-19 diagnosis, and reported persistent symptoms and difficulties in performing daily activities.

Main Outcome Measures

Participants who consented, were contacted by face-to-face interview, and were interviewed regarding LCS, and restriction of activities of daily living using Post COVID-19 functional scale. Cardio-respiratory parameters were also measured.

Results

Among 2198 participants, the prevalence of LCS at 12 weeks was 16.1%. Overall, eight LCS were identified and in descending order of prominence are: fatigue, pain, dyspnea, cough, anosmia, appetite loss, headache, and chest pain. COVID survivors experienced between 1 to 5 LCS with an overall duration period of 21.8 ± 5.2 weeks. SEM predicted the length of LCS to be related to younger age, female gender, rural residence, prior functional limitation and smoking.

Conclusion

In this cohort of survivors, at 31 weeks post diagnosis, the prevalence of LCS was 16.1%. The risk factors identified for presence and longer length of LCS warrant further research and consideration to support public health initiatives.
A SARS-CoV-2 nucleocapsid protein TR-FRET assay amenable to high-throughput screening
Authors: Gorshkov Kirill , Vasquez Desarey Morales , Chiem Kevin , Ye Chengjin , Tran Bruce Nguyen , de la Torre Juan Carlos , Moran Thomas , Chen Catherine Z. , Martinez-Sobrido Luis , Zheng Wei
Published: July 2021

Drug development for specific antiviral agents against coronavirus disease 2019 (COVID-19) is still an unmet medical need as the pandemic continues to spread globally. Although huge efforts for drug repurposing and compound screens have put forth, only few compounds remain in late stage clinical trials. New approaches and assays are needed to accelerate COVID-19 drug discovery and development. Here we report a time-resolved fluorescence resonance energy transfer-based assay that detects the severe acute respiratory syndrome coronavirus 2 (SARS-CoV‑2) nucleocapsid protein (NP) produced in infected cells. It uses two specific anti-NP monoclonal antibodies (MAbs) conjugated to donor and acceptor fluorophores that produces a robust ratiometric signal for high throughput screening of large compound collections. Using this assay, we measured a half maximal inhibitory concentration (IC50) for Remdesivir of 9.3 μM against infection with SARS-CoV-2 USA/WA1/2020 (WA-1). The assay also detected SARS-CoV-2 South African (Beta, β), Brazilian/Japanese variant P.1 (Gamma, γ), and Californian (Epsilon, ε), variants of concern or interest (VoC). Therefore, this homogeneous SARS-CoV-2 NP detection assay can be used for accelerating lead compound discovery for drug development and for evaluating drug efficacy against emerging SARS-CoV-2 VoC.
Generation of false positive SARS-CoV-2 antigen results with testing conditions outside manufacturer recommendations: A scientific approach to pandemic misinformation
Authors: Patriquin Glenn , Davidson Ross J. , Hatchette Todd F. , Head Breanne M. , Mejia Edgard , Becker Michael G. , Meyers Adrienne , Sandstrom Paul , Hatchette Jacob , Block Ava , Smith Nicole , Ross John , LeBlanc Jason J.
Published: July 2021

Objectives

Antigen-based rapid diagnostics tests (Ag-RDTs) are useful tools for SARS-CoV-2 detection. However, misleading demonstrations of the Abbott Panbio COVID-19 Ag-RDT on social media claimed that SARS-CoV-2 antigen could be detected in municipal water and food products. To offer a scientific rebuttal to pandemic misinformation and disinformation, this study explored the impact of using the Panbio SARS-CoV-2 assay with conditions falling outside of manufacturer recommendations.

Methods

Using Panbio, various water and food products, laboratory buffers, and SARS-CoV-2-negative clinical specimens were tested, with and without manufacturer buffer. Additional experiments were conducted to assess the role of each Panbio buffer component (tricine, NaCl, pH, and tween-20), as well as the impact of temperatures (4°C, 20°C, and 45°C) and humidity (90%) on assay performance.

Results

Direct sample testing (without the kit buffer), resulted in false positive signals resembling those obtained with SARS-CoV-2-positive controls tested under proper conditions. The likely explanation of these artifacts is non-specific interactions between the SARS-CoV-2-specific conjugated and capture antibodies, as proteinase K treatment abrogated this phenomenon, and thermal shift assays showed pH-induced conformational changes under conditions promoting artifact formation. Omitting, altering, and reverse engineering the kit buffer all supported the importance of maintaining buffering capacity, ionic strength, and pH for accurate kit function. Interestingly, the Panbio assay could tolerate some extremes of temperature and humidity outside of manufacturer claims.

Conclusions

Our data support strict adherence to manufacturer instructions to avoid false positive SARS-CoV-2 Ag-RDT reactions, otherwise resulting in anxiety, overuse of public health resources, and dissemination of misinformation.
Relating SARS-CoV-2 shedding rate in wastewater to daily positive tests data: A consistent model based approach
Authors: Petala M. , Kostoglou M. , Karapantsios Th. , Dovas Ch. , Lytras Th. , Paraskevis D. , Roilides E. , Koutsolioutsou-Benaki A. , Panagiotakopoulos G. , Sypsa V. , Metallidis S. , Papa A. , Stylianidis E. , Papadopoulos A. , Tsiodras S. , Papaioannou N.
Published: July 2021

During the COVID-19 pandemic, wastewater-based epidemiology (WBE) has been engaged to complement medical surveillance and in some cases to also act as an early diagnosis indicator of viral spreading in the community. Most efforts worldwide by the scientific community and commercial companies focus on the formulation of protocols for SARS CoV-2 analysis in wastewater and approaches addressing the quantitative relationship between WBE and medical surveillance are lacking. In the present study, a mathematical model is developed which uses as input the number of daily positive medical tests together with the highly non-linear shedding rate curve of individuals to estimate the evolution of virus shedding rate in wastewater along calendar days. A comprehensive parametric study by the model using as input actual medical surveillance and WBE data for the city of Thessaloniki (∼700,000 inhabitants, North Greece) during the outbreak of November 2020 reveals the conditions under which WBE can be used as an early warning tool for predicting pandemic outbreaks. It is shown that early warning capacity is different along the days of an outbreak and depends strongly on the number of days apart between the day of maximum shedding rate of infected individuals in their disease cycle and the day of their medical testing. The present data indicate for Thessaloniki an average early warning capacity of around 2 days. Moreover, the data imply that there exists a proportion between unreported cases (asymptomatic persons with mild symptoms that do not seek medical advice) and reported cases. The proportion increases with the number of reported cases. The early detection capacity of WBE improves substantially in the presence of an increasing number of unreported cases. For Thessaloniki at the peak of the pandemic in mid-November 2020, the number of unreported cases reached a maximum around 4 times the number of reported cases.

HIGHLIGHTS

Model estimates viral load evolution in wastewater from infected people dynamics

Identifying actual conditions for which WBE can be used as an early warning tool

Early warning capacity increases with an increasing number of unreported cases

In Thessaloniki Nov20 outbreak, the early warning capacity of WBE was about 2 days

In Thessaloniki Nov20 outbreak, unreported cases were up to 4 times reported cases
Pneumococcal exposure routes for infants, a nested cross-sectional survey in Nha Trang, Vietnam
Authors: Qian George , Toizumi Michiko , Clifford Sam , Le Lien Thuy , Papastylianou Tasos , Quilty Billy , Iwasaki Chihiro , Kitamura Noriko , Takegata Mizuki , Nguyen Trang Minh , Nguyen Hien Anh Thi , Dang Duc Anh , van Hoek Albert Jan , Yoshida Lay Myint , Flasche Stefan
Published: July 2021

Background

Infants are at highest risk of pneumococcal disease. Their added protection through herd effects is a key part in the considerations on optimal pneumococcal vaccination strategies. Yet, little is currently known about the main transmission pathways to this vulnerable age group.

Methods and findings

We conducted a nested cross-sectional contact and nasopharyngeal swabbing survey in randomly selected infants across all 27 communes of Nha Trang, Vietnam. Bayesian logistic regression models were used to estimate age specific carriage prevalence in the population, a proxy for the probability that a contact of a given age could lead to pneumococcal exposure for the infant. We used another Bayesian logistic regression model to estimate the correlation between infant carriage and the probability that at least one of their reported contacts carried pneumococci, controlling for age and locality. In total 1583 infants between 4 and 13 months old participated, with 7428 contacts reported. Few infants (5%) attended day care and carriage prevalence was 22%. Most infants (61%) had less than a 25% probability to have had close contact with a pneumococcal carrier on the surveyed day. Pneumococcal infection risk and contact behavior were highly correlated: if adjusted for age and locality the odds of an infant’s carriage increased by 22% (95%CI:15-29) per 10 percentage points increase in the probability to have had close contact with at least one pneumococcal carrier. Two to six year old children contributed 51% (95%CI: 39-63) to the total pneumococcal exposure risks to infants in this setting.

Conclusions

Cross-sectional contact and infection studies can help identify pneumococcal transmission routes. In Nha Trang, preschool age children are the largest reservoir for pneumococcal transmission to infants.
Death profiling of hospitalized patients with COVID-19: Experience from a specialized hospital in Bangladesh
Authors: Shahed-Morshed Md. , Mosabbir Abdullah Al , Hossain Mohammad Sorowar
Published: July 2021

Background

The information on characteristics and causes of mortality in deceased patients with coronavirus disease 2019 (COVID-19) is scarce in the literature. This study aimed to document the clinical profile with causes of death in deceased patients admitted in a COVID-19 dedicated hospital in Dhaka, Bangladesh.

Methods

This cross-sectional retrospective study included 108 COVID-19 associated deceased patients admitted in Kurmitola general hospital, Dhaka, Bangladesh between 25 March 2020 and 24 June 2020) Data were collected from hospital record. Causes of death were categorized into early and late with cut-off of 48 hours of hospitalization.

Results

Among 809 hospitalized cases of COVID-19, 108 patient died (13.35%) over three months of study period. The mean age of the deceased patients was 60.22±13.94 years; 86.1% were male. About 85% had at least one comorbidity with diabetes mellitus (65.7%) was the most common one. The most common symptoms were breathlessness (88.0%), fever (65.7%) and cough (43.5%). Nearly 75% presented with severe disease. Patients had altered biochemical profiles and treated with different drugs including antibiotics and steroids. Young age and malnutrition were two characteristic features. Only one third got intensive care support. The most common cause of death was acute respiratory syndrome (95.37%). Septic shock & acute myocardial infarction were predominantly early and uremia, hepatic failure & hyperglycemic crisis were the predominant causes of late hospital death.

Conclusions

The findings of this study will help clinicians as well as policy makers to take necessary steps to prevent death from COVID-19 in Bangladeshi population.
Real time scalable data acquisition of COVID-19 in six continents through PySpark - a big data tool
Authors: Patel Tanvi S. , Patel Daxesh P. , Patel Chirag N.
Published: July 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was declared as a global emergency in January 2020 due to its pandemic outbreak. To examine this Coronavirus disease 2019 (COVID-19) effects various data are being generated through different platforms. This study was focused on the clinical data of COVID-19 which relied on python programming. Here, we proposed a machine learning approach to provide a insights into the COVID-19 information. PySpark is a machine learning approach which also known as Apache spark an accurate tool for the searching of results with minimum time intervals as compare to Hadoop and other tools. World Health Organization (WHO) started gathering corona patients’ data from last week of the February 2020. On March 11, 2020, the WHO declared COVID-19 a global pandemic. The cases became more evident and common after mid-March. This paper used the live owid (our world in data) dataset and will analyse and find out the following details on the live COVID-19 dataset. (1) The daily Corona virus scenario on various continents using PySpark in microseconds of Processor time. (2) After the various antibodies have been implemented, how they impact new cases on a regular basis utilizing various graphs. (3) Tabular representation of COVID-19 new cases in all the continents.
Incorporating family disease history and controlling case-control imbalance for population based genetic association studies
Authors: Zhuang Yongwen , Wolford Brooke N , Nam Kisung , Bi Wenjian , Zhou Wei , Willer Cristen J , Mukherjee Bhramar , Lee Seunggeun
Published: July 2021

In the genome-wide association analysis of population-based biobanks, most diseases have low prevalence, which results in low detection power. One approach to tackle the problem is using family disease history, yet existing methods are unable to address type I error inflation induced by increased correlation of phenotypes among closely related samples, as well as unbalanced phenotypic distribution. We propose a new method for genetic association test with family disease history, TAPE (mixed-model-based Test with Adjusted Phenotype and Empirical saddlepoint approximation), which controls for increased phenotype correlation by adopting a two-variance-component mixed model, accounts for case-control imbalance by using empirical saddlepoint approximation, and is flexible to incorporate any existing adjusted phenotypes such as phenotypes from the LT-FH method. We show through simulation studies and analysis of UK-Biobank data of white British samples and the Korean Genome and Epidemiology Study (KoGES) of Korean samples that the proposed method is robust and yields better calibration compared to existing methods while gaining power for detection of variant-phenotype associations.
Lipid peroxidation induced ApoE receptor-ligand disruption as a unifying hypothesis underlying sporadic Alzheimer’s disease in humans
Authors: Ramsden Christopher E. , Keyes Gregory S. , Calzada Elizabeth , Horowitz Mark S. , Zamora Daisy , Jahanipour Jahandar , Sedlock Andrea , Indig Fred E. , Moaddel Ruin , Kapogiannis Dimitrios , Maric Dragan
Published: July 2021

Structured Abstract

Background

Sporadic Alzheimer’s disease (sAD) lacks a unifying hypothesis that can account for the lipid peroxidation observed early in the disease, enrichment of ApoE in the central core of neuritic plaques, the hallmark plaques and tangles, and the selective vulnerability of entorhinal-hippocampal structures.

Objective

We hypothesized that (1) high expression of ApoER2 (receptor for ApoE and Reelin) could help explain the selective anatomical vulnerability; and (2) lipid peroxidation of ApoE and ApoER2 contributes to sAD pathogenesis, by disrupting ApoE delivery and Reelin-ApoER2 signaling cascades.

Methods

We conductedin vitrobiochemical experiments, single-marker immunohistochemistry (IHC), and multiplex fluorescence-IHC (MP-IHC) in postmortem specimens from 26 individuals who died cognitively normal, with Mild Cognitive Impairment or with sAD.

Results

In biochemical experiments, Lys- and His-enriched peptides within the binding domains of ApoE and ApoER2 and their corresponding recombinant proteins, were susceptible to attack by reactive lipid aldehydes, generating lipid-protein adducts and crosslinked ApoE-ApoER2 complexes. Usingin situhybridization alongside IHC and MP-IHC, we observed that: (1) ApoER2 is strongly expressed in terminal zones of the entorhinal-hippocampal ‘perforant path’ projections that underlie memory; (2) ApoE and lipid aldehyde-modified ApoE, Reelin, ApoER2 and several downstream components of Reelin-ApoER2 signaling cascades accumulated in the immediate vicinity of neuritic plaques in perforant path terminal zones in sAD cases; and (3) several ApoE/Reelin-ApoER2 pathway markers—including the ApoER2 ligand binding domain, Disabled homolog-1 (Dab1), and Thr19-phosphorylated PSD95 (marker of synaptic disassembly)—were higher in sAD cases than controls and positively correlated with histological progression and cognitive deficits.

Conclusion

Results provide proof-of-concept that ApoE and ApoER2 are vulnerable to lipid aldehyde induced adduction and crosslinking and demonstrate derangements in multiple ApoE/Reelin-ApoER2-Dab1 axis components in perforant path terminal zones in AD. Findings provide the foundation for a unifying hypothesis implicating lipid peroxidation of ApoE particles and ApoE receptors in sAD in humans.
Mathematical modelling of SARS-CoV-2 variant outbreaks reveals their probability of extinction
Authors: Schiøler Henrik , Knudsen Torben , Brøndum Rasmus Froberg , Stoustrup Jakob , Bøgsted Martin
Published: July 2021

When a virus spreads, it may mutate into, e.g., vaccine resistant or fast spreading lineages, as was the case for the Danish Cluster-5 mink variant (belonging to the B.1.1.298 lineage), the British B.1.1.7 lineage, and the South African B.1.351 lineage of the SARS-CoV-2 virus. A way to handle such spreads is through a containment strategy, where the population in the affected area is isolated until the spread has been stopped. Under such circumstances, it is important to monitor whether the mutated virus is extinct via massive testing for the virus sub-type. If successful, the strategy will lead to lower and lower numbers of the sub-type, and it will eventually die out. An important question is, for how long time one should wait to be sure the sub-type is extinct? We use a hidden Markov model for infection spread and an approximation of a two stage sampling scheme to infer the probability of extinction. The potential of the method is illustrated via a simulation study. Finally, the model is used to assess the Danish containment strategy when SARS-CoV-2 spread from mink to man during the summer of 2020, including the Cluster-5 sub-type. In order to avoid further spread and mink being a large animal virus reservoir, this situation led to the isolation of seven municipalities in the Northern part of the country, the culling of the entire Danish 17 million large mink population, and a bill to interim ban Danish mink production until the end of 2021.
Knowledge, attitude, and practice related to the COVID-19 pandemic among undergraduate medical students in Indonesia: a nationwide cross-sectional study
Authors: Adli Imam , Widyahening Indah S. , Lazarus Gilbert , Phowira Jason , Azzahra Lyanna , Ariffandi Bagas , Putera Azis Muhammad , Nugraha David , Gamalliel Nico , Findyartini Ardi
Published: July 2021

Introduction

The potential role of medical students in raising awareness during public health emergencies has been acknowledged. To further explore their potentials as public educators and role models for the communities during the coronavirus disease 2019 (COVID-19) pandemic, a study is conducted to assess the knowledge, attitude, and practice of these students toward COVID-19.

Methods

An online cross-sectional survey was conducted among undergraduate medical students in Indonesia. Socio-demographical characteristics, social interaction history, information-seeking behavior, as well as knowledge, attitude, and practice toward COVID-19 were collected through a self-reported questionnaire. A p-value of <0.05 indicated statistical significance.

Results

Out of 4870 respondents, 64.9% and 51.5% had positive attitude and practice toward COVID-19 while only 29.8% had adequate knowledge. Knowledge was slightly positively correlated with attitude and practice (ρ=0.074 and ρ=0.054, respectively; both p<0.001), while attitude was weakly correlated with practice (ρ=0.234, p<0.001). Several factors including age, sex, place of residence, institution type, academic level, family income, history of chronic illness, prior volunteering experience, and perceptual awareness on COVID-19 were significantly associated with either knowledge, attitude, and/or practice toward COVID-19. Furthermore, health institution’s and the government’s press releases, as well as health expert opinions were deemed as the most reliable sources of COVID-19-related information – yet trivially none of these sources were associated with knowledge, attitude, and practice in the study population.

Conclusion

Many undergraduate medical students in Indonesia had positive attitude and practice against COVID-19, yet only a few had adequate knowledge. This warrants further interventions to keep them updated with COVID-19 evidence to maximize their potentials in raising public awareness on COVID-19.
Giving birth in a Pandemic: Women’s Birth Experiences in England during COVID-19
Authors: Aydin Ezra , Glasgow Kevin A. , Weiss Staci M. , Khan Zahra , Austin Topun , Johnson Mark H. , Barlow Jane , Lloyd-Fox Sarah
Published: July 2021

Background

Expectant parents worldwide have experienced changes in the way they give birth as a result of COVID-19, including restrictions relating to access to birthing units and the presence of birthing partners during the birth, and changes to birth plans. This paper reports the experiences of women in England.

Methods

Data were obtained from both closed- and open-ended responses collected as part of the national COVID in Context of Pregnancy, Infancy and Parenting (CoCoPIP) Study online survey (n = 477 families) between 15th July 2020 – 29th March 2021. Frequency data are presented alongside the results of a sentiment analysis; the open-ended data was analysed thematically.

Results

Two-thirds of expectant women reported giving birth via spontaneous vaginal delivery (SVD) (66.1%) and a third via caesarean section (CS) (32.6%) or ‘other’ (1.3%). Just under half (49.7%) of the CS were reported to have been elective/planned, with 47.7% being emergencies. A third (37.4%) of participants reported having no changes to their delivery, with a further 25% reporting COVID-related changes, and 37.4% reporting non-COVID related changes (e.g., medical intervention). Experiences of COVID-related changes included limited birthing options and reduced feelings of control; difficulties accessing pain-relief and assistance, and feelings of distress and anxiety. Under half of the respondents reported not knowing whether there could be someone present at the birth (44.8%), with 2.3% of respondents reporting no birthing partner being present due to COVID-related restrictions. Parental experiences of communication and advice provided by the hospital prior to delivery were mixed, with significant stress and anxiety being reported in relation to both the fluctuating guidance and lack of certainty regarding the presence of birthing partners at the birth. The sentiment analysis revealed that participant experiences of giving birth during the pandemic were predominately negative (46.9%) particularly in relation to the first national lockdown, with a smaller proportion of positive (33.2%) and neutral responses (19.9%).

Conclusion

Parents reported an overall increase in birthing interventions (e.g., emergency CS), increased uncertainties related to the birth, and poor communication, leading to increased feelings of anxiety and high levels of negative emotions. The implications of these findings are discussed.
Special Issue: Demographic and Mental Health Assessments in the Adolescent Brain and Cognitive Development Study: Updates and Longitudinal Trajectories
Authors: Barch Deanna M. , Albaugh Matthew D. , Baskin-Sommers Arielle , Bryant Brittany E. , Clark Duncan B. , Dick Anthony Steven , Feczko Eric , Foxe John J. , Gee Dylan G. , Giedd Jay , Glantz Meyer D. , Hudziak James J. , Karcher Nicole R. , LeBlanc Kimberly , Maddox Melanie , McGlade Erin C. , Mulford Carrie , Nagel Bonnie J. , Neigh Gretchen , Palmer Clare E , Potter Alexandra S. , Sher Kenneth J. , Tapert Susan F. , Thompson Wesley K. , Xie Laili
Published: July 2021

The Adolescent Brain Cognitive Development (ABCD) Study of 11,880 youth incorporates a comprehensive range of measures assessing predictors and outcomes related to mental health across childhood and adolescence in participating youth, as well as information about family mental health history. We have previously described the logic and content of the mental health assessment battery at Baseline and Year 1. Here, we describe changes to that battery and issues and clarifications that have emerged, as well as additions to the mental health battery at the 2-, 3-, 4-, and 5-year follow-ups. We capitalize on the recent release of longitudinal data for caregiver and youth report of mental health data to evaluate trajectories of dimensions of psychopathology as a function of demographic factors. For both caregiver and self-reported mental health symptoms, males showed age-related decreases in internalizing and externalizing symptoms, while females showed an increase in internalizing symptoms with age. Multiple indicators of socioeconomic status (caregiver education, family income, financial adversity, neighborhood poverty) accounted for unique variance in both caregiver and youth-reported externalizing and internalizing symptoms. These data highlight the importance of examining developmental trajectories of mental health as a function of key factors such as sex and socioeconomic environment.
In vivo modelling of patient genetic heterogeneity identifies concurrent Wnt and PI3K activity as a potent driver of invasive cholangiocarcinoma growth
Authors: Younger Nicholas T. , Wilson Mollie L. , Jarman Edward J. , Meynert Alison M. , Grimes Graeme R , Gournopanos Konstantinos , Waddell Scott H. , Tennant Peter A. , Wilson David H. , Guest Rachel V. , Wigmore Stephen J. , Acosta Juan Carlos , Kendall Timothy J. , Taylor Martin S. , Sproul Duncan , Mill Pleasantine , Boulter Luke
Published: July 2021

Intrahepatic cholangiocarcinoma (ICC) is an aggressive and lethal malignancy of the bile ducts within the liver characterised by high levels of genetic heterogeneity. In the context of such genetic variability, determining which oncogenic mutations drive ICC growth has been difficult and developing modes of patient stratification and targeted therapies remains challenging. As a result, survival rates following a diagnosis with ICC have remained static since the late 1970s, whilst incidence of ICC has increased. Here, we performed the first functional in vivo study into the role that genetic heterogeneity plays in drivinga ICC via modelling of interactions between rare mutations with more common driver genes. By leveraging human ICC sequencing data to stratify and then model genetic heterogeneity in the mouse, we uncovered numerous novel tumour suppressors which, when lost, cooperate with the RAS oncoprotein to drive ICC growth. In this study, we specifically focus on a set of driver mutations that interact with KRAS to initiate aggressive, sarcomatoid-type ICC. We show that tumour growth of this cancer relies on both Wnt and PI3K signalling to drive proliferation and suppress apoptosis. Finally, we demonstrate that pharmacological co-inhibition of Wnt and PI3K in vivo substantially impedes the growth of ICC, regardless of mutational profile. As such, Wnt and PI3K activity should be considered as a signature by which patients can be stratified for treatment and inhibitors of these pathways should be levied as a treatment for patients diagnosed with ICC.
Construction of a new chromosome-scale, long-read reference genome assembly for the Syrian hamster, Mesocricetus auratus
Authors: Harris R. Alan , Raveendran Muthuswamy , Lyfoung Dustin T. , Sedlazeck Fritz J , Mahmoud Medhat , Prall Trent M. , Karl Julie A. , Doddapaneni Harshavardhan , Meng Qingchang , Han Yi , Muzny Donna , Wiseman Roger W. , O’Connor David H. , Rogers Jeffrey
Published: July 2021

Background

The Syrian hamster (Mesocricetus auratus) has been suggested as a useful mammalian model for a variety of diseases and infections, including infection with respiratory viruses such as SARS-CoV-2. The MesAur1.0 genome assembly was generated in 2013 using whole-genome shotgun sequencing with short-read sequence data. Current more advanced sequencing technologies and assembly methods now permit the generation of near-complete genome assemblies with higher quality and greater continuity.

Findings

Here, we report an improved assembly of the M. auratus genome (BCM_Maur_2.0) using Oxford Nanopore Technologies long-read sequencing to produce a chromosome-scale assembly. The total length of the new assembly is 2.46 Gbp, similar to the 2.50 Gbp length of a previous assembly of this genome, MesAur1.0. BCM_Maur_2.0 exhibits significantly improved continuity with a scaffold N50 that is 6.7 times greater than MesAur1.0. Furthermore, 21,616 protein coding genes and 10,459 noncoding genes are annotated in BCM_Maur_2.0 compared to 20,495 protein coding genes and 4,168 noncoding genes in MesAur1.0. This new assembly also improves the unresolved regions as measured by nucleotide ambiguities, where approximately 17.11% of bases in MesAur1.0 were unresolved compared to BCM_Maur_2.0 in which the number of unresolved bases is reduced to 3.00%.

Conclusions

Access to a more complete reference genome with improved accuracy and continuity will facilitate more detailed, comprehensive, and meaningful research results for a wide variety of future studies using Syrian hamsters as models.