bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance of At-Home Self-Collected Saliva and Nasal-Oropharyngeal Swabs in the Surveillance of COVID-19
Authors: Braz-Silva Paulo H. , Mamana Ana C. , Romano Camila M. , Felix Alvina C. , de Paula Anderson V. , Fereira Noeli E. , Buss Lewis F. , Tozetto-Mendoza Tania R. , Caixeta Rafael A. V. , Leal Fabio E. , Grespan Regina M. Z. , Bizário João C. S. , Ferraz Andrea B. C. , Sapkota Dipak , Giannecchini Simone , To Kelvin K. , Doglio Alain , Mendes-Correa Maria C.
Published: October 2020

SARS-CoV-2 quickly spread in the worldwide population by contact with oral and respiratory secretions of infected individuals, imposing social restrictions to control the infection. Massive testing is essential to breaking the chain of COVID-19 transmission. The aim of this study was to compare the performance of at-home self-collected samples - saliva and combined nasal-oropharyngeal swabs (NOP) - for SARS-CoV-2 detection in a telemedicine platform for COVID-19 surveillance. We analyzed 201 patients who met the criteria of suspected COVID-19. NOP sampling were combined (nostrils and oropharynx) and saliva collected using a cotton pad device. Detection of SARS-COV-2 was performed by using the Altona RealStar® SARS-CoV-2 RT-PCR Kit 1.0. According to our data, there was an overall significant agreement (κ coefficient value of 0.58) between the performances of saliva and NOP. Assuming that positive results in either sample represent true infections, 70 patients positive for SARS-CoV-2 were identified, with 52/70 being positive in NOP and 55/70 in saliva. This corresponds to sensitivities of 74.2% (95% CI; 63.7% to 83.1%) for NOP and 78.6% (95% CI; 67.6% to 86.6%) for saliva. We also found a strong correlation (β-coefficients < 1) between the cycle threshold values in saliva and NOP. Ageusia was the only symptom associated with patients SARS-CoV-2 positive only in NOP (p=0.028). In conclusion, our data show the feasibility of using at-home self-collected samples (especially saliva), as an adequate alternative for SARS-CoV-2 detection. This new approach of testing can be useful to develop strategies for COVID-19 surveillance and for guiding public health decisions.
Clinical and spatial characteristics of Severe Acute Respiratory Syndrome by COVID-19 in Indigenous of Brazil
Authors: Sardinha Daniele Melo , Lima Karla Valéria Batista , da Silva Ferreira Ana Lúcia , Garcez Juliana Conceição Dias , Ueno Thalyta Mariany Rêgo Lopes , Rodrigues Yan Corrêa , dos Santos Anderson Lineu Siqueira , de Loiola Rosane do Socorro Pompeu , e Guimarães Ricardo José de Paula Souza , Lima Luana Nepomuceno Gondim Costa
Published: October 2020

The new coronavirus (SARS-CoV-2) emerged in Wuhan in China in December 2019, causing severe pneumonias and deaths, soon in March 2020 it reached pandemic level, affecting several countries including Brazil. The disease was named COVID-19, with characteristics of most infected having mild and moderate symptoms and a part severe symptom. The disease has already reached 158 ethnic groups, which have high vulnerability and limited access to health services. The objective is to investigate the clinical and spatial characteristics of Severe Acute Respiratory Syndrome of COVID-19 in the indigenous peoples of Brazil. It is an epidemiological, cross-sectional, analytical ecological study, based on data from the OpenDataSUS platform from 01/01/2020 to 31/08/2020. Profile variables, signs and symptoms and risk factors/comorbidities. The data were analyzed by Bioestat 5.3. There were 1,207 cases and 470 deaths. Profile: male gender (59.48%) means age 53 years. Signs and symptoms: fever (74.23%), cough (77.71%), sore throat (35.62%), dyspnea (69.34%), respiratory discomfort (62.80%), O2 saturation <95% (56.42%); and associated with mortality: dyspnea (80.0%) and O2 saturation <95% (69.36%). Risk factors and comorbidities (45.89%) were associated with deaths (54.04%). Comorbidities: Chronic Cardiovascular Disease (18.97%) and Diabetes Mellitus (18.97%), and associated with deaths: Chronic Cardiovascular Disease (24.46%). Being admitted to the ICU has a risk of death in (OR-3.96-<0.0001-CI-2,913/5,383) followed by not being vaccinated against influenza (OR-1.85-<0.0001-CI-1,358/2,528). The public and health policies of Brazil should be directed to control the dissemination of COVID-19 in this population, that COVID-19 evolves in the same intensity, however, the indigenous have vulnerabilities that can increase the impact of the pan-demic in this population.
DNA methylation and gene expression pattern of ACE2 and TMPRSS2 genes in saliva samples of patients with SARS-CoV-2 infection
Authors: Misra Pratibha , Mukherjee Bhasker , Negi Rakhi , Marwah Vikas , Ghosh Arijit Kumar , Jindamwar Prashant , Singh Mukesh U , Vashum Y , Syamraj R , Chandra G Bala , Sibin M K
Published: October 2020

COVID-19 caused by SARS-CoV-2 became a pandemic affecting the health and economy of the world. Although it was known that this virus uses ACE2 protein along with TMPRSS2 to enter the host cell, the methylation pattern and gene expression of ACE2 and TMPRSS2 genes are not explored in saliva samples of patients infected with COVID-19. The study aimed to quantify promoter methylation of ACE2 and TMPRSS2 along with its mRNA expression in saliva samples of COVID-19 patients in order to understand the regulatory mechanism of these genes in SARS-CoV-2 infection. Saliva samples were collected from thirty male patients with SARS-CoV-2 infection and thirty age-matched healthy control male subjects. Q MS PCR and qRT PCR was performed to quantify the promoter DNA methylation and mRNA expression of ACE2 and TMPRSS2 respectively. Our study didn’t find any significant difference between methylation and expression of these two genes in cases compared to control subjects. However there was significant positive correlation between DNA methylation of ACE2 and its gene expression. Among cases, the sample collected ≥7 days after appearance of symptoms showed higher amount of methylation in both ACE2 and TMPRSS2 genes when compared to sample collected before 7 days. In conclusion, we found that ACE2 and TMPRSS2 methylation plays a role in COVID-19.
Finding the real COVID-19 case-fatality rates for SAARC countries
Authors: Tazir Shah Md. Rafil , Ahammed Tanvir , Anjum Aniqua , Chowdhury Anisa Ahmed , Suchana Afroza Jannat
Published: October 2020

Crude case fatality rate (CFR) is the most accurate when the pandemic is over. Adjustments to the crude CFR measure can better explain the pandemic situation by improving the CFR estimation. However, no study has thoroughly investigated COVID-19 adjusted CFR of the South Asian Association for Regional Cooperation (SAARC) countries. In this study, we estimated both survival interval and underreporting adjusted CFR of COVID-19 for the SAARC countries and observed the CFR changes due to the imposition of fees on COVID-19 tests in Bangladesh. Using the daily records up to 9th October, we implemented a statistical method to remove both the bias in crude CFR, i.e., the delay between disease onset and outcome bias and due to asymptomatic or mild symptomatic cases, reporting rates lower than 50% (95% CI: 10%-50%) bias. According to our findings, Afghanistan had the highest CFR, followed by Pakistan, India, Bangladesh, Nepal, Maldives, and Sri Lanka. Our estimated crude CFR varied from 3.71% to 0.29%, survival interval adjusted CFR varied from 3.77% to 0.3% and further underreporting adjusted CFR varied from 1.1% to 0.08%. We have also found that crude CFR increased from 1.261% to 1.572% after imposing the COVID-19 test fees in Bangladesh. Therefore, the authorities of countries with higher CFR should be looking for strategic counsel from the countries with lower CFR to equip themselves with the necessary knowledge to combat the pandemic. Moreover, caution is needed to report the CFR.
Associations between Alzheimer’s disease polygenic risk scores and hippocampal subfield volumes in 17,161 UK Biobank participants
Authors: Foo Heidi , Thalamuthu Anbupalam , Jiang Jiyang , Koch Forrest , Mather Karen A. , Wen Wei , Sachdev Perminder S.
Published: October 2020

Hippocampal volume is an important biomarker of Alzheimer’s disease (AD), and genetic risk of AD is associated with hippocampal atrophy. However, the hippocampus is not a uniform structure and has a number of subfields, the associations of which with age, sex, and polygenic risk score for AD (PRSAD) have been inadequately investigated. We examined these associations in 17,161 cognitively normal UK Biobank participants (44-80 years). Age was negatively associated with all the hippocampal subfield volumes and females had smaller volumes than men. Higher PRSAD was associated with lower volumes in the bilateral whole hippocampus, hippocampal-amygdala-transition-area (HATA), and hippocampal tail; right subiculum; left cornu ammonis (CA)1, CA4, molecular layer, and granule cell layer of dentate gyrus (CG-DG), with associations being greater on the left side. Older individuals (median age 63 years, n=8984) showed greater subfield vulnerability to high PRSAD compared to the younger group (n=8177), but the effect did not differ by sex. The pattern of subfield involvement in relation to the PRSAD in community dwelling healthy individuals sheds additional light on the pathogenesis of AD.
Clinical Outcome of Asymptomatic COVID-19 Infection Among a Large Nationwide Cohort of 5,621 Hospitalized Patients in Korea
Authors: Park Hayne Cho , Kim Do Hyoung , Cho Ajin , Kim Juhee , Yun Kyu-sang , Kim Jinseog , Lee Young-Ki
Published: October 2020

We investigated clinical outcome of asymptomatic coronavirus disease 2019 (COVID-19) and identified risk factors associated with high patient mortality using Korean nationwide public database of 5,621 hospitalized patients. The mortality rate and admission rate to intensive care unit were compared between asymptomatic and symptomatic patients. The prediction model for patient mortality was developed through risk factor analysis among asymptomatic patients. The prevalence of asymptomatic COVID-19 infection was 25.8%. The mortality rates were not different between groups (3.3% vs. 4.5%, p=0.17). However, symptomatic patients were more likely to receive ICU care compared to asymptomatic patients (4.1% vs. 1.0%, p<0.0001). The age-adjusted Charlson comorbidity index score (CCIS) was the most potent predictor for patient mortality in asymptomatic patients. The clinicians should predict the risk of death by evaluating age and comorbidities but not the presence of symptoms.

Article Summary Line

Since asymptomatic patients have similar mortality rate with symptomatic patients, the clinicians should not classify clinical severity according to initial presence of symptom.
Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development
Authors: Zhao Miao-Miao , Yang Wei-Li , Yang Fang-Yuan , Zhang Li , Huang Weijin , Hou Wei , Fan Changfa , Jin Ronghua , Feng Yingmei , Wang Youchun , Yang Jin-Kui
Published: October 2020

To discover new drugs to combat coronavirus disease 2019 (COVID-19), an understanding of the molecular basis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is urgently needed. Here, for the first time, we report the crucial role of cathepsin L (CTSL) in patients with COVID-19. The circulating level of CTSL was elevated and was positively correlated with disease course and severity in COVID-19 patients. Correspondingly, SARS-CoV-2 pseudovirus infection increasedCTSLexpression in human cell lines and humanACE2transgenic mice, whileCTSLoverexpression, in turn, enhanced pseudovirus infection. CTSL functionally cleaved the SARS-CoV-2 spike protein and enhanced virus entry, as evidenced by CTSL overexpression and knockdownin vitroand application of CTSL inhibitor drugsin vivo. Furthermore, amantadine, a licensed anti-influenza drug, significantly inhibited CTSL activity and prevented SARS-CoV-2 pseudovirus infection. Therefore, CTSL is a promising target for new anti-COVID-19 drug development.
Determinants of psychological distress during the COVID-19 pandemic and the lockdown measures: a nationwide on-line survey in Greece and Cyprus
Authors: Galanis Petros , Andreadaki Evangelia , Kleanthous Efrosyni , Georgiadou Anastasia , Evangelou Efi , Kallergis Georgios , Kaitelidou Daphne
Published: October 2020

A limited number of studies have investigated the distress during the COVID-19 pandemic and the lockdown measures in the general population. We studied psychological distress during the COVID-19 pandemic and the lockdown measures in the general population in Greece and Cyprus. Also, we investigated several demographic, clinical and job characteristics of the participants as possible determinants of distress. Data collection was performed during lockdown measures in Greece and Cyprus (from April 21stto May 4th2020). All participants provided informed consent to participate in the study. We used the Impact of Event Scale-Revised (IES-R) to measure the psychological distress in response to the COVID-19 pandemic and lockdown measures. Seventeen point four percent of the participants had overall IES-R score from 24 to 32 indicating that posttraumatic stress disorder (PTSD) is a clinical concern, while 33.5% had overall IES-R score >32 indicating that PTSD is a probable diagnosis. Females, Cyprus residents, participants that live with elderly people or patients with a chronic disease in home, participants with a mental health disease or/and chronic disease, participants under pharmaceutical treatment, participants that lost their work due to the pandemic and participants that work in hospital experienced greater distress. Also, increased age and decreased educational level was associated with increased distress. Findings suggest that our sample experienced great distress and this distress was affected by several demographic, clinical and job characteristics. Appropriate interventions should be established in order to support psychologically high risk groups and decrease their distress.
Wearable technologies for children with chronic illness: A Proof-of-Concept Study
Authors: McErlane Flora , Davies Elin Haf , Ollivier Cecile , Mayhew Anna , Anyanwu Obuchinezia , Harbottle Victoria , Donald Aimee
Published: October 2020

Objective

To determine the feasibility of wearable technologies in physical activity assessment in three paediatric diseases, namely Niemann-Pick C (NP-C), Juvenile Idiopathic Arthritis (JIA) and Duchenne Muscular Dystrophy (DMD).

Design

Proof of concept feasibility study

Setting and patients

Thirty children were recruited across three UK hospitals (Royal Manchester’s Children Hospital, Great Ormond Street Children’s Hospital and the Great North Children’s Hospital). Ten were diagnosed with NP-C, eight with DMD and twelve with JIA.

Intervention

All participants completed the 6-minute walk test (6MWT) at enrolment. Patients were provided with disease specific smartphone apps paired with a wearable device via Bluetooth. Ambulation was recorded in 30-minute epochs measuring average daily maximum (ADM), average daily steps (ADS), and average daily steps per 30-minute epoch (ASE).

Results

Median 6MWT results were 450m, 325m and 434.5m for the NP-C, DMD and JIA cohorts respectively. Wearable data capture was feasible in all three disease groups, although complete data capture was not sustained. A statistically significant between-cohort difference was identified for ADM, ADS and ASE. Statistically significant differences were found between DMD/JIA for ADM; NP-C/DMD for ADS and DMD/JIA for ASE.

Discussion

Wearable sensor technologies have the potential to add important information to our understanding of ambulation in chronic paediatric disease. The wearable devices were easy to use and popular with patients although key features need to be addressed to ensure higher engagement in future deployments. As the technology continues to evolve at a rapid pace, opportunities to implement child friendly solutions are already available.
Factors driving availability of COVID-19 convalescent plasma: Insights from a demand, production and supply model
Authors: Russell W. Alton , Grebe Eduard , Custer Brian
Published: October 2020

Background

COVID-19 Convalescent Plasma (CCP) is a promising treatment for COVID-19. Blood collectors have rapidly scaled up collection and distribution programs.

Methods

We developed a detailed simulation model of CCP donor recruitment, collection, production and distribution processes. Simulations based on epidemics in 11 U.S. states, in which key parameters were varied over wide ranges, allowed identification of the drivers of ability to calibrate collections capacity and ability to meet demand for CCP.

Results

Changes in collection capacity utilization lagged increases and decreases in COVID-19 hospital discharges, and never exceeded 75% in most simulations. Demand could be met for most of the simulation period in most simulations, but in states with early sharp increases in hospitalizations a substantial portion of demand went unmet during these early peaks. Modeled second wave demand could generally be met with stockpiles established during first epidemic peaks. Apheresis machine capacity (number of machines) and probability that COVID-19 recovered individuals are willing to donate were the most important supply-side drivers of ability to meet demand. Recruitment capacity was important in states with early peaks.

Conclusions

Epidemic trajectory was the most important determinant of ability to meet demand for CCP, although our simulations revealed several contributing operational drivers of CCP program success.
Capturing cultural and linguistic diversity in child health research in Australia
Authors: Rahim Razlyn Abdul , Pilkington Rhiannon , D’Onise Katina , Lynch John
Published: October 2020

The concept of Culturally and Linguistically Diverse (CALD) populations is unique to Australia. It was introduced in 1996 and is intended to refer to ethno-cultural groups that are neither Aboriginal or Torres Strait Islander nor considered from mainstream English-speaking Anglo-Celtic backgrounds. CALD children have been identified as a priority population by the Australian government because they may experience inequities in health outcomes compared to Anglo-Australian children. Inequities in the health and wellbeing of CALD children are driven by myriad processes including racial discrimination, socioeconomic disadvantage, and limited access to health services. But who are CALD children? Despite the availability of statistical standards for data collection on CALD characteristics such as country of birth and language spoken, the concept itself lacks an official operational definition. Applying definitions specified by various organisations to data from the 2016 Australian Census, the estimated proportion of CALD children ranged from 11% to 44% of Australian children aged 0 to 17 years. There are few published studies on CALD children in Australian child health research, with most studies focused on refugees. There is no consensus on how CALD is defined in child health research in Australia. We propose several considerations in the use of the CALD concept in child health research. This includes adhering to the Australian Bureau of Statistics standards on Cultural and Linguistic Diversity, use of multiple indicators to identify CALD, and acknowledging the significant heterogeneity of CALD communities which may contribute to observed differences in health. If we are to advance health and well-being equity for CALD children, we need a more carefully considered and consistent approach to understanding which children are CALD.
Ecological theory of mutualism: Models generalizing across different mechanisms
Authors: Hale Kayla R. S. , Maes Daniel P. , Valdovinos Fernanda S.
Published: October 2020

Mutualisms are ubiquitous in nature, provide important ecosystem services, and involve many species of interest for conservation. Theoretical progress on the population dynamics of mutualistic interactions, however, has comparatively lagged behind that of trophic and competitive interactions. Consequently, ecologists still lack a generalized framework to investigate the population dynamics of mutualisms. Here, we propose extensible models for two-species mutualisms focusing on nutritional, protection, and transportation mechanisms and evaluate the population-level consequences of those mechanisms. We introduce a novel theoretical framework that highlights characteristic dynamics when the effects of mutualism are directly dependent or independent of recipient density and when they saturate due to inter- or intra-specific density-dependence. We end by integrating our work into the broader historical context of population-dynamic models of mutualism and conclude that a general ecological theory of mutualism exists.
Comparison of the in vitro-efficacy of different mouthwash solutions targeting SARS-CoV-2 based on the European Standard EN 14476
Authors: Steinhauer Katrin , Meister Toni Luise , Todt Daniel , Krawczyk Adalbert , Paßvogel Lars , Becker Britta , Paulmann Dajana , Bischoff Birte , Pfaender Stephanie , Brill Florian H H , Steinmann Eike
Published: October 2020

The SARS-Cov-2 pandemic is triggering a global health emergency alert, and recent research is indicating the relevance of aerosols in the spread of SARS-CoV-2. Thus, in this study antiseptic mouthwashes based on the actives chlorhexidine (CHX) and octenidine (OCT) were investigated regarding their efficacy against SARS-CoV-2 using EN 14476. Based on the requirement of EN 14476 (i.e. reduction of viral titer by ≥ 4 log 10), the OCT-based formulation was effective within only 15 sec against SARS-CoV-2, and thus constitutes an interesting candidate for future clinical studies to prove its effectiveness in a potential prevention of SARS-CoV-2 transmission by aerosols.
Outcomes evaluated in controlled clinical trials on the management of COVID-19: A methodological systematic review
Authors: Mathioudakis Alexander G. , Fally Markus , Hashad Rola , Kouta Ahmed , Hadi Ali Sina , Knight Sean Blandin , Bakerly Nawar Diar , Singh Dave , Williamson Paula R. , Felton Timothy , Vestbo Jørgen
Published: October 2020

It is crucial that randomized controlled trials (RCTs) on the management of coronavirus disease 2019 (COVID-19) evaluate the outcomes that are critical to patients and clinicians, to facilitate relevance, interpretability, and comparability.

This methodological systematic review describes the outcomes evaluated in 415 RCTs on the management of COVID-19, that were registered with ClinicalTrials.gov, by 5/5/2020.

Significant heterogeneity was observed in the selection of outcomes and the instruments used to measure them. Mortality, adverse events and treatment success or failure are only evaluated in 64.4%, 48.4% and 43% of the included studies, respectively, while other outcomes are selected less often. Studies focusing on more severe presentations (hospitalized patients or requiring intensive care) most frequently evaluate mortality and adverse events, while hospital admission and viral detection/load are most frequently assessed in the community setting. Outcome measurement instruments are poorly reported and heterogeneous. In general, simple instruments that can control for important sources of bias are favoured. Follow-up does not exceed one month in 64.3% of these earlier trials, and long-term COVID-19 burden is rarely assessed.

The methodological issues identified could delay the introduction of potentially life-saving treatments in clinical practice. Our findings demonstrate the need for consensus in the design of RCTs.

Take home message

@ERSpublications: This systematic review describes the heterogeneity in outcomes evaluated in 415 RCTs on COVID-19 management and the instruments used to measure them. Our findings reveal a need for consensus in the design of future RCTs.
Speech cortical activation and connectivity in typically developing children and those with listening difficulties
Authors: Stewart Hannah J. , Cash Erin K. , Hunter Lisa L. , Maloney Thomas , Vannest Jennifer , Moore David R.
Published: October 2020

Listening difficulties (LiD) in people who have normal audiometry are a widespread but poorly understood form of hearing impairment. Recent research suggests that childhood LiD are cognitive rather than auditory in origin. We examined decoding of sentences using a novel combination of behavioral testing and fMRI with 43 typically developing children and 42 age matched (6-13 years old) children with LiD, categorized by caregiver report (ECLiPS). Both groups had clinically normal hearing. For sentence listening tasks, we found no group differences in fMRI brain cortical activation by increasingly complex speech stimuli that progressed in emphasis from phonology to intelligibility to semantics. Using resting state fMRI, we examined the temporal connectivity of cortical auditory and related speech perception networks. We found significant group differences only in cortical connections engaged when processing more complex speech stimuli. The strength of the affected connections was related to the children’s performance on tests of dichotic listening, speech-in-noise, attention, memory and verbal vocabulary. Together, these results support the novel hypothesis that childhood LiD reflects difficulties in language rather than in auditory or phonological processing.
Lung transplantation for pulmonary fibrosis secondary to severe COVID-19
Authors: Bharat Ankit , Querrey Melissa , Markov Nikolay S. , Kim Samuel , Kurihara Chitaru , Garza-Castillon Rafael , Manerikar Adwaiy , Shilatifard Ali , Tomic Rade , Politanska Yuliya , Abdala-Valencia Hiam , Yeldandi Anjana V. , Lomasney Jon W. , Misharin Alexander V. , Budinger G.R. Scott
Published: October 2020

Lung transplantation can potentially be a life-saving treatment for patients with non-resolving COVID-19 acute respiratory distress syndrome. Concerns limiting transplant include recurrence of SARS-CoV-2 infection in the allograft, technical challenges imposed by viral-mediated injury to the native lung, and potential risk for allograft infection by pathogens associated with ventilator-induced pneumonia in the native lung. Additionally, the native lung might recover, resulting in long-term outcomes preferable to transplant. Here, we report the results of the first two successful lung transplantation procedures in patients with non-resolving COVID-19 associated acute respiratory distress syndrome in the United States. We performed smFISH to detect both positive and negative strands of SARS-CoV-2 RNA in the explanted lung tissue, extracellular matrix imaging using SHIELD tissue clearance, and single cell RNA-Seq on explant and warm post-mortem lung biopsies from patients who died from severe COVID-19 pneumonia. Lungs from patients with prolonged COVID-19 were free of virus but pathology showed extensive evidence of injury and fibrosis which resembled end-stage pulmonary fibrosis. Single cell RNA-Seq of the explanted native lungs from transplant and paired warm post-mortem autopsies showed similarities between late SARS-CoV-2 acute respiratory distress syndrome and irreversible end-stage pulmonary fibrosis requiring lung transplantation. There was no recurrence of SARS-CoV-2 or pathogens associated with pre-transplant ventilator associated pneumonias following transplantation in either patient. Our findings suggest that some patients with severe COVID-19 develop fibrotic lung disease for which lung transplantation is the only option for survival.

Single sentence summary

Some patients with severe COVID-19 develop end-stage pulmonary fibrosis for which lung transplantation may be the only treatment.
Clinical Course and Outcomes of coronavirus disease 2019 (COVID-19) in Rheumatic Disease Patients on Immunosuppression: A case Cohort Study at a Single Center with a Significantly Diverse Population
Authors: Arleo Timothy , Tong David , Shabto Julie , O’Keefe Ghazala , Khosroshahi Arezou
Published: October 2020

Objectives

To determine clinical course and outcomes in rheumatic disease patients with coronavirus disease 2019 (COVID-19) and compare results to uninfected patients.

Methods

We conducted a case cohort study of autoimmune disease patients with COVID-19 (confirmed by severe acute respiratory syndrome coronavirus 2 PCR) from 02/01/2020 to 07/31/2020 and compared them in a 1:3 ratio with uninfected patients who were matched based on race, age, sex, and comorbidity index. Patient demographics, clinical course, and outcomes were compared among these patient groups.

Results

A total of 70 rheumatic disease patients with COVID-19 (mean age, 56.6 years; 64% African American) were identified. The 34 (49%) patients who were hospitalized used oral glucocorticoids more frequently (p<0.01). All 10 patients on anti-TNFα medications were treated as outpatients (p<0.01). Those hospitalized with COVID-19 more often required ICU admission (17 (50%) vs 27 (26%), OR=2.78 (95% CI: 1.24 to 6.20)) and intubation (10 (29%) vs 6 (6%), OR=6.67 (95% CI: 2.20 to 20.16)) than uninfected patients. They also had higher mortality rates (6 (18%) vs 3 (3%), OR=7.21 (95% CI: 1.70 to 30.69)). Of the six COVID-19 patients who died, one was of African ancestry (p=0.03).

Conclusions

Rheumatic disease patients infected with COVID-19 were more likely to require ICU admission, ventilation, and died more frequently versus uninfected patients with autoimmune disease. Patients on anti-TNFα medications were hospitalized less frequently while those on chronic glucocorticoids were hospitalized more frequently. These findings have important implications for medication choice in rheumatic disease patients during the ongoing spread of COVID-19.
Effects of New York’s Executive Order on Face Mask Use on COVID-19 Infections and Mortality: A Modeling Study
Authors: Shen Mingwang , Zu Jian , Fairley Christopher K. , Pagán José A. , Ferket Bart , Liu Bian , Yi Stella S. , Chambers Earle , Li Guoqiang , Guo Yuming , Rong Libin , Xiao Yanni , Zhuang Guihua , Zebrowski Alexis , Carr Brendan G. , Li Yan , Zhang Lei
Published: October 2020

Background

New York City (NYC) was the epicenter of the COVID-19 pandemic in the United States. On April 17, 2020, the State of New York implemented an Executive Order that requires all people in New York to wear a face mask or covering in public settings where social distancing cannot be maintained. It is unclear how this Executive Order has affected the spread of COVID-19 in NYC.

Methods

A dynamic compartmental model of COVID-19 transmission among NYC residents was developed to assess the effect of the Executive Order on face mask use on infections and deaths due to COVID-19 in NYC. Data on daily and cumulative COVID-19 infections and deaths were obtained from the NYC Department of Health and Mental Hygiene.

Results

The Executive Order on face mask use is estimated to avert 99,517 (95% CIs: 72,723-126,312) COVID-19 infections and 7,978 (5,692-10,265) deaths in NYC. If the Executive Order was implemented one week earlier (on April 10), the averted infections and deaths would be 111,475 (81,593-141,356) and 9,017 (6,446-11,589), respectively. If the Executive Order was implemented two weeks earlier (on April 3 when the Centers for Disease Control and Prevention recommended face mask use), the averted infections and deaths would be 128,598 (94,373-162,824) and 10,515 (7,540-13,489), respectively.

Conclusions

New York’s Executive Order on face mask use is projected to have significantly reduced the spread of COVID-19 in NYC. Implementing the Executive Order at an earlier date would avert even more COVID-19 infections and deaths.
PREVALENCE OF MOLECULAR AND SEROLOGICAL TESTS OF THE NEW CORONAVIRUS (SARS-CoV-2) IN CARLOS CHAGAS-SABIN LABORATORIES IN CUIABÁ
Authors: de Paula Cristiane Coimbra , Passos João Pedro Castoldo , Shimoya-Bittencour Walkiria , de Lamare Caroline Aquino Vieira , de Oliveira Ruberlei Godinho
Published: October 2020

BACKGROUND

COVID-19, the disease caused by the new coronavirus (SARS-CoV-2), became a pandemic in 2020 with mortality rate of 2% and high transmissibility, which makes studies with an epidemiological profile essential.

OBJECTIVES

To characterize the population that performed the SARS-CoV-2 molecular and serological tests in Carlos Chagas-Sabin laboratories in Cuiabá.

METHODS

A retrospective cross-sectional study was carried out with all the samples collected from nasal swab tested by RT-PCR and serological for SARM-CoV-2 IgM / IgG from the population served between April and July 2020.

FINDINGS

In the analyzed period, 11,113 PCR-Covid-19 exams were registered. Of this total of cases, 3,912 (35.20%) tested positive, while 6,889 (61.90%) did not detect viral RNA and 312 (2.80%) of the visits resulted as undetermined. The peak of positive RT-PCR performed in July (n = 5878), with 35.65% (n = 2096). A total of 6,392 tests performed on SOROVID-19, with a peak of 1161 (18.16%) of the positive tests for SARS-CoV-2 in July.

MAIN CONCLUSIONS

Molecular positivity and serological tests, both peaked in July 2020, were mostly present in women aged 20-39, characterizing Cuiabá as the epicenter of the Midwest region in this period due to the high rate of transmissibility of SARS-CoV-2.
Opioid Prescribing During Delivery Hospitalization Associated with Increased Postpartum Emergency Department Utilization
Authors: Bagwell Adams Grace , Yarbrough Courtney R. , Harris Samantha J. , Abraham Amanda J.
Published: October 2020

Structured Abstract

Background

Empirical evidence shows postpartum women are prescribed opioids at high rates following both cesarean and vaginal delivery. Beyond this, little is known about opioid prescribing to postpartum mothers following delivery hospitalization and the resulting impacts for maternal health. Postpartum women may be particularly vulnerable to adverse health effects from inappropriate prescribing.

Objectives

This study examines the effects of postpartum opioid prescribing on emergency department (ED) utilization, controlling for delivery type and other maternal characteristics.

Study Design

We conduct a retrospective cohort study using 2008-2016 data from the Medical Expenditure Panel Survey (MEPS).

Results

We find 31% of women received a new opioid prescription following delivery, and that receipt of an opioid prescription following delivery hospitalization is associated with a 67% increase in the odds of an ED visit.

Conclusion

This study is one of the first to test the relationship between opioid prescribing and healthcare utilization among this population, contributing critical information to our understanding of implications for opioid prescribing after childbirth for postpartum women.
Development of Multiplexed RT-LAMP for Detection of SARS-CoV-2 and Influenza Viral RNA
Authors: Zhang Yinhua , Tanner Nathan A.
Published: October 2020

The ongoing COVID-19 pandemic has demonstrated the utility of widespread molecular testing for surveillance and diagnostic detection of SARS-CoV-2. Reverse-transcription loop-mediated isothermal amplification (RT-LAMP) has enabled testing outside of the standard clinical laboratory PCR infrastructure, with simple and rapid tests supplementing the existing, standard methods. However, current LAMP tests have detected single targets and required separate reactions for controls or multiple targets. As flu season arrives in the Northern Hemisphere the ability to screen for multiple viral targets will be increasingly important, and the ability to include internal control assays in the RT-LAMP test allows for decreased resource use and increased throughput. Here we describe a multiplexing approach to RT-LAMP with four targets (SARS-CoV-2, Influenza A, Influenza B, and internal control human RNA) in a single reaction using real-time and endpoint fluorescence detection. This increase to the functionality of RT-LAMP will, we hope, enable even broader adoption of this power molecular testing approach to aid in the global fight against this continuing public health threat.
Epigenetic mechanisms mediating cell state transitions in chondrocytes
Authors: Wuelling Manuela , Neu Christoph , Thiesen Andrea M. , Kitanovski Simo , Cao Yingying , Lange Anja , Westendorf Astrid M. , Hoffmann Daniel , Vortkamp Andrea
Published: October 2020

Epigenetic modifications play critical roles in regulating cell lineage differentiation, but the epigenetic mechanisms guiding specific differentiation steps within a cell lineage have rarely been investigated. To decipher such mechanisms, we used the defined transition from proliferating (PC) into hypertrophic chondrocytes (HC) during endochondral ossification as a model. We established a map of activating and repressive histone modifications for each cell type. ChromHMM state transition analysis and Pareto-based integration of differential levels of mRNA and epigenetic marks revealed that differentiation associated gene repression is initiated by the addition of H3K27me3 to promoters still carrying substantial levels of activating marks. Moreover, the integrative analysis identified genes specifically expressed in cells undergoing the transition into hypertrophy.

Investigation of enhancer profiles detected surprising differences in enhancer number, location, and transcription factor binding sites between the two closely related cell types. Furthermore, cell type-specific upregulation of gene expression was associated with a shift from low to high H3K27ac decoration. Pathway analysis identified PC-specific enhancers associated with chondrogenic genes, while HC-specific enhancers mainly control metabolic pathways linking epigenetic signature to biological functions.
Phylum barrier andEscherichia coliintra-species phylogeny drive the acquisition of resistome inE. coli
Authors: Petitjean Marie , Condamine Bénédicte , Denamur Erick , Ruppé Etienne
Published: October 2020

Escherichia coliis a ubiquitous bacterium that has widely been exposed to antibiotics over the last 70 years. It has adapted by acquiring different antibiotic resistance genes (ARG), which we aim at characterizing the census here. To do so, we analysed 70,301E. coligenomes obtained from the EnteroBase database and detected 1,027,651 ARG using the AMRFinder, Mustard and ResfinderFG ARG databases. We observed a strong phylogroup/clonal lineage specific distribution of some ARG, arguing for epistasis between ARG and the strain genetic background. However, each phylogroup had ARG conferring a similar resistance pattern, indicating phenotypic convergence. The GC content or the type of ARG was not associated to the frequency of the ARG in the database. Besides, we identified ARG from anaerobic, non-Proteobacteria bacteria in four genomes ofE. colisupporting that the transfer between anaerobic bacteria andE. colican spontaneously occur but remain exceptional. In conclusion, we showed that phylum barrier and intra-species phylogenetic history are major drivers of the acquisition of resistome inE. coli.
Loss of erythroblasts in acute myeloid leukemia causes iron redistribution with clinical implications
Authors: Lopes Marta , Duarte Tiago L. , Teles Maria J. , Mosteo Laura , Chacim Sérgio , Aguiar Eliana , Pereira-Reis Joana , Oliveira Mónica , Silva André M. N. , Gonçalves Nuno , Martins Gabriela , Kong Isabella Y , Zethoven Magnus , Vervoort Stephin , Martins Sandra , Quintela Miguel , Hawkins Edwin D , Trigo Fernanda , Guimarães João T , Mariz José M , Porto Graça , Duarte Delfim
Published: October 2020

Acute myeloid leukemia (AML) is a heterogeneous disease with poor prognosis and limited treatment strategies. Determining the role of cell-extrinsic regulators of leukemic cells is vital to gain clinical insights into the biology of AML. Iron is a key extrinsic regulator of cancer but its systemic regulation remains poorly explored in AML. To address this question, we studied iron metabolism in AML patients at diagnosis and mechanisms involved using the syngeneic MLL-AF9-induced AML mouse model. We found that AML is a disorder with a unique iron profile not associated with inflammation or transfusion and characterized by high ferritin, low transferrin, high transferrin saturation (TSAT), and high hepcidin. The increased TSAT in particular, contrasts with observations in other cancer types and in anemia of inflammation. Using the MLL-AF9 mouse model of AML, we demonstrated that leukemic blasts take up iron and that the AML-induced loss of erythroblasts is responsible for iron redistribution and an increase in TSAT. We also show that elevated TSAT at diagnosis is independently associated with increased overall survival in AML and suggest that TSAT may be a relevant prognostic marker in AML.
The essential transcriptional regulator HDP1 drives expansion of the inner membrane complex during early sexual differentiation of malaria parasites
Authors: Morillo Riward Campelo , Tong Xinran , Xie Wei , Abel Steven , Orchard Lindsey M. , Daher Wassim , Patel Dinshaw J. , Llinás Manuel , Le Roch Karine G. , Kafsack Björn F.C.
Published: October 2020

Transmission of Plasmodium falciparum and other malaria parasites requires their differentiation from asexual blood stages into gametocytes, the non-replicative sexual stage necessary for transmission to the mosquito vector. This transition involves changes in gene expression and chromatin reorganization that result in the activation and silencing of stage-specific genes. However, the genomes of malaria parasites have been noted for their dearth of transcriptional and chromatin regulators and the molecular mediators of these changes remain largely unknown. We recently identified HomeoDomain Protein 1 (HDP1) as a DNA-binding protein that enhances the expression of key genes that are critical for early sexual differentiation. The discovery of a homeodomain-like DNA-binding protein marks a new class of transcriptional regulator in malaria parasites outside of the better-characterized ApiAP2 family. In this study, we show that HDP1 facilitates the necessary upregulation of inner membrane complex components during early gametocytogenesis that gives P. falciparum gametocytes they characteristic shape and is required for gametocyte maturation and parasite transmission.
Drosophilaclock cells use multiple mechanisms to transmit time-of-day signals in the brain
Authors: Barber Annika F. , Fong Shi Yi , Kolesnik Anna , Fetchko Michael , Sehgal Amita
Published: October 2020

Regulation of circadian behavior and physiology by theDrosophilabrain clock requires communication from central clock neurons to downstream output regions, but the mechanism by which clock cells regulate downstream targets is not known. We show here that thepars intercerebralis(PI), previously identified as a target of the morning cells in the clock network, also receives input from evening cells. We determined that morning and evening clock neurons have time of day dependent connectivity to the PI, which is regulated by specific peptides as well as by fast neurotransmitters. Interestingly, PI cells that secrete the peptide DH44, and control rest:activity rhythms, are inhibited by clock inputs while insulin-producing cells are activated, indicating that the same clock cells can use different mechanisms to drive cycling in output neurons. Inputs of morning cells to theDILP2+ neurons are relevant for the circadian rhythm of feeding, reinforcing the role of the PI as a circadian relay that controls multiple behavioral outputs. Our findings provide mechanisms by which clock neurons signal to non-clock cells to drive rhythms of behavior.

Significance Statement

Despite our growing understanding of how the fly clock network maintains free-running rhythms of behavior and physiology, little is known about how information is communicated from the clock network to the rest of the brain to regulate behavior. We identify glutamate and acetylcholine as key neurotransmitters signaling from clock neurons to thepars interecerebralis(PI), a clock output region regulating circadian rhythms of sleep and metabolism. We report a novel link betweenDrosophilaevening clock neurons and the PI, and find that the effect of clock neurons on output neuron physiology varies, suggesting that the same clock cells use multiple mechanisms simultaneously to drive cycling in output neurons.
Embrace heterogeneity to improve reproducibility: A perspective from meta-analysis of variation in preclinical research
Authors: Usui Takuji , Macleod Malcolm R. , McCann Sarah K. , Senior Alistair M. , Nakagawa Shinichi
Published: October 2020

The reproducibility of research results has been a cause of increasing concern to the scientific community. The long-held belief that experimental standardization begets reproducibility has also been recently challenged, with the observation that the reduction of variability within studies can lead to idiosyncratic, lab-specific results that are irreproducible. An alternative approach is to, instead, deliberately introduce heterogeneity; known as “heterogenization” of experimental design. Here, we explore a novel perspective in the heterogenization program in a meta-analysis of variability in observed phenotypic outcomes in both control and experimental animal models of ischaemic stroke. First, by quantifying inter-individual variability across control groups we illustrate that the samount of heterogeneity in disease-state (infarct volume) differs according to methodological approach, for example, in disease-induction methods and disease models. We argue that such methods may improve reproducibility by creating diverse and representative distribution of baseline disease-state in the reference group, against which treatment efficacy is assessed. Second, we illustrate how meta-analysis can be used to simultaneously assess efficacy and stability (i.e., mean effect and among-individual variability). We identify treatments that have efficacy and are generalizable to the population level (i.e. low inter-individual variability), as well as those where there is high inter-individual variability in response; for these latter treatments translation to a clinical setting may require nuance. We argue that by embracing rather than seeking to minimise variability in phenotypic outcomes, we can motivate the shift towards heterogenization and improve both the reproducibility and generalizability of preclinical research.
Status and targets for rebuilding the three major fish stocks in Lake Victoria
Authors: Musinguzi Laban , Olokotum Mark , Natugonza Vianny
Published: October 2020

We determined fisheries management reference points for three major fish stocks in Lake Victoria (Nile tilapia, Nile perch and Dagaa) for Uganda and the whole lake. The aim was to ascertain stock status and define reasonable objectives and targets for rebuilding to sustainable levels. Dagaa was found to be healthy in Uganda and the whole lake but tending to overfished status. In Uganda, the stock status of Nile tilapia and Nile perch was recruitment impaired but tending more towards collapsed and overfished status respectively. In the whole lake, the stock status of Nile tilapia and Nile perch was collapsed and overfished respectively with the latter tending more towards recruitment impaired. Estimates of maximum sustainable yield (MSY) showed that catches could be increased under good management. Rebuilding the Nile tilapia and Nile perch stock biomasses to MSY level (Bmsy) could respectively increase the catches above the current level by 9.2% and 29.5% in Uganda and by 72.8% and 15.1% in the whole lake. The immediate objective for fisheries management should be to rebuild biomass for the Nile tilapia and Nile perch stocks to Bmsy. Elimination of illegal fishing practices has proved to be effective. In addition, management needs to keep catches at low levels until biomass for the stocks is ≥Bmsyfor at least three consecutive years.