bluuebunny/crossref_metadata_2025 huggingface dataset:
A comprehensive human minimal gut metagenome extends the host’s metabolic potential
Authors: Parras-Moltó Marcos , Aguirre de Cárcer Daniel
Published: November 2020

Accumulating evidence suggests that humans could be considered as holobionts in which the gut microbiota play essential functions. Initial metagenomic studies reported a pattern of shared genes in the gut microbiome of different individuals, leading to the definition of the minimal gut metagenome as the set of microbial genes necessary for homeostasis and present in all healthy individuals. This study analyses the minimal gut metagenome of the most comprehensive dataset available, including individuals from agriculturalist and industrialist societies, also embodying highly diverse ethnic and geographical backgrounds. The outcome, based on metagenomic predictions for community composition data, resulted in a minimal metagenome comprising 3412 genes, mapping to 1856 reactions and 128 metabolic pathways predicted to occur across all individuals. These results were substantiated by the analysis of two additional datasets describing the microbial community compositions of larger Western cohorts, as well as a substantial shotgun metagenomics dataset. Subsequent analyses showed the plausible metabolic complementarity provided by the minimal gut metagenome to the human genome.
Pharmacokinetics of remdesivir in a COVID-19 patient with end-stage renal disease on intermittent hemodialysis
Authors: Sörgel Fritz , Malin Jakob J. , Hagmann Henning , Kinzig Martina , Bilal Muhammad , Eichenauer Dennis A. , Scherf-Clavel Oliver , Simonis Alexander , Tabei Lobna El , Fuhr Uwe , Rybniker Jan
Published: November 2020

Remdesivir, a drug with provisional approval for the treatment of COVID-19, is not recommended in patients with an estimated glomerular filtration rate ≤ 30 mL/min. Here we provide a first detailed pharmacokinetic assessment of remdesivir and its major metabolites in a patient with end stage renal disease on hemodialysis.
A Predictive Model for Severe Covid-19 in the Medicare Population: A Tool for Prioritizing Scarce Vaccine Supply
Authors: Experton Bettina , Tetteh Hassan A. , Lurie Nicole , Walker Peter , Carroll Colin J. , Elena Adrien , Hein Christopher S. , Schwendiman Blake , Vincent Justin L. , Burrow Christopher R.
Published: November 2020

Background

Recommendations for prioritizing populations for COVID-19 vaccination have focused on front-line health care personnel and residents in long term care, followed by other individuals at higher risk for severe disease. Existing models for identifying higher risk individuals including those over age 65 lack the needed integration of socio-demographic and clinical risk factors to ensure equitable vaccine allocation.

Methods

We developed a predictive model for severe COVID-19 using clinical data from de-identified Medicare claims for 16 million Medicare fee-for-service beneficiaries, including 1 million COVID-19 cases, and socio-economic data from the CDC Social Vulnerability Index. To identify risk factors for severe COVID-19, we used multivariate logistic regression and random forest modeling. Predicted individual probabilities of COVID-19 hospitalization were then calculated for population risk stratification and COVID-19 vaccine prioritization, and for mapping of population risk levels at the county and zip code levels on a nationwide dashboard.

Results

The leading Covid-19 hospitalization risk factors driving the risk model were: Non-white ethnicity (particularly North American Native, Black, and Hispanic), end-stage renal disease, advanced age (particularly age over 85), prior hospitalization, leukemia, morbid obesity, chronic kidney disease, lung cancer, chronic liver disease, pulmonary fibrosis or pulmonary hypertension, and chemotherapy. However, previously reported risk factors such as chronic obstructive pulmonary disease and diabetes conferred modest hospitalization risk. Among all social vulnerability factors analyzed, residence in a low-income zip code was the only risk factor independently predicting Covid-19 hospitalization. The mapped hospitalization risk levels showed significant correlations with the cumulative COVID-19 case hospitalization rates at the zip code level in the fifteen most populous U.S. major metropolitan areas.

Conclusion

This multi-factor risk model which predicts severe Covid-19and its population risk dashboard can be used to optimize Covid-19 vaccine allocation in the higher risk Medicare population where socio-demographic and comorbidity risk factors need to be considered concurrently.
Genetically downregulated interleukin-6 signaling is associated with a favorable cardiometabolic profile: a phenome-wide association study
Authors: Georgakis Marios K. , Malik Rainer , Li Xue , Gill Dipender , Levin Michael G. , Vy Ha My T. , Judy Renae , Ritchie Marylyn , Verma Shefali S. ,   Regeneron Genetics Center, Nadkarni Girish N. , Damrauer Scott M. , Τheodoratou Evropi , Dichgans Martin
Published: November 2020

Background

Interleukin-6 (IL6) signaling is a key inflammatory pathway widely implicated in the pathogenesis of multiple diseases including autoimmune, vascular, and metabolic disorders. While IL6-receptor (IL6R) inhibitors are already in use for the treatment of autoimmune diseases, their repurposing potential and safety profile is still debated.

Methods

We used 7 genetic variants at theIL6Rlocus as proxies for IL6 signaling downregulation and explored their effects on 1,428 clinical outcomes in a phenome-wide association study (PheWAS) using data from the UK Biobank (339,256 unrelated individuals). Significant associations were meta-analyzed with data from the Penn Medicine (10,244 individuals) and BioMe (9,054 individuals) Biobanks for validation. We further investigated associations between genetically downregulated IL6 signaling and 366 biomarkers and endophenotypes of human disease in the UK Biobank and other phenotype-specific consortia. All associations were examined by Mendelian randomization (MR) analyses scaled to the effects of tocilizumab, a monoclonal antibody targeting IL6R.

Results

The PheWAS-MR analyses showed significant associations with 16 clinical outcomes and 17 biomarkers following correction for multiple comparisons. Genetically downregulated IL6 signaling was associated with a lower risk of several atherosclerotic phenotypes including ischemic heart disease (OR: 0.84, 95%CI: 0.77-0.90) and abdominal aortic aneurysm (OR: 0.44, 95%CI: 0.29-0.67). We further found significant associations with lower risk of type 2 diabetes (OR: 0.80, 95%CI: 0.73-0.88), lower glycated hemoglobin A1c (HbA1c) levels (beta: −0.07, 95%CI: −0.08 to −0.05), and higher HDL-cholesterol levels (beta: 0.04, 95%CI: 0.02-0.06). In accord with clinical trials examining pharmacological IL6 blockade, genetically downregulated IL6 signaling was associated with higher risk of neutropenia and bacterial infections (cellulitis and urinary tract infections) and with higher hemoglobin concentrations. We further found significant associations with higher risk of atopic dermatitis and higher levels of the pro-allergic cytokine interleukin-4.

Conclusions

Genetic IL6 signaling downregulation associates with a lower risk of vascular outcomes and a more favorable cardiometabolic profile. These findings further support a repurposing of IL6R blockade for lowering cardiovascular risk while also informing on potential side effects.
Performance of EasyBreath® Decathlon Snorkeling mask for Delivering Continuous Positive Airway Pressure
Authors: Noto Alberto , Crimi Claudia , Cortegiani Andrea , Giardina Massimiliano , Benedetto Filippo , Princi Pietro , Carlucci Annalisa , Appendini Lorenzo , Gregoretti Cesare
Published: November 2020

Background

During the COVID-19 pandemic, the need for noninvasive respiratory support devices has dramatically increased, sometimes exceeding hospital capacity. The full-face Decathlon snorkeling mask, EasyBreath® (EB® mask), has been adapted to deliver continuous positive airway pressure (CPAP) as an emergency respiratory interface. We aimed to assess the performance of this modified EB® mask.

Methods

CPAP set at 5, 10, and 15 cmH2O was delivered to 10 healthy volunteers with a high-flow system generator set at 40, 80, and 120 L min-1 and with a turbine-driven ventilator during both spontaneous and loaded (resistor) breathing. Inspiratory CO2 partial pressure (PiCO2), pressure inside the mask, breathing pattern and electrical activity of the diaphragm (EAdi) were measured at all combinations of CPAP/flows delivered, with and without the resistor.

Results

Using the high-flow generator set at 40 L min-1, the PiCO2 significantly increased and the system was unable to maintain the target CPAP of 10 and 15 cmH2O and a stable pressure within the respiratory cycle; conversely, the turbine-driven ventilator did. EAdi significantly increased with flow rates of 40 and 80 L min-1 but not at 120 L min-1 and with the turbine-driven ventilator.

Conclusions

EB® mask can be safely used to deliver CPAP only under strict constraints, using either a high-flow generator at a flow rate greater than 80 L min-1, or a high-performance turbine-driven ventilator.
Role of cytokines and other prophetic variables in the development and progression of disease in patients suffering from COVID-19
Authors: Malik Arif , Iqbal Saima , Waquar Sulayman , Hafeez Muhammad Mansoor
Published: November 2020

INTRODUCTION

Outbreak of the novel COVID-19 infection identifies both causative agents that threaten global pandemic in 2003 and 2011. It is an enveloped virus with spike (S) protein attached that facilitates its receptor binding on the surface. Although it has brought about the global interest for the researchers and medical practitioner in the identification of potential targets that may be addressed in order to cope up with the situation. In the current study potential role of cytokines and related inflammatory markers have been identified that interplays in the progression of disease in COVID-19 patients.

MATERIALS AND METHODS

Current study substitutes hundred and fifty (n=150) patients with novel-COVID-19 and hundred (n=100) healthy controls. After getting informed consent serum samples of the participants were collected and analyzed for their significance in the disease progression. Levels of Interleukins i.e., (IL- 1,6,8,10,11) and tumor necrosis factor-alpha (TNF-α) were determined with help of their specific spectrophotometric and ELISA methods.

RESULTS

Findings of study show significant increase in the levels of interleukins and TNF-α that signifies the presence of “cytokine storm” in worsening the condition in respect to the exposure of COVID-19. Levels of IL-1 and 6 were significantly higher in patients (98.69±39.35pg/ml and 71.95±28.41 pg/ml) as compared to controls (30.06±14.19pg/ml and 9.46±3.43pg/ml) where, (p=0.001 and 0.007). It also suggests that IL-6 is most sensitive test with about (98%) sensitivity in comparison with 96%,95%, 95%,93% and 92% in case of IL-10,1,8,11 and TNF-α respectively.

CONCLUSION

Current study elucidate the effects of cytokines and respective inflammatory markers in the progression of the COVID-19. Findings show that activation of macrophages and neutrophils have significant role in the worsening of the symptoms and progression of the viral infection. Thus, use of certain blockers in initial stages could serve with potent benefits in coping up the infectious condition.
The Role of Societal Aspects in the Formation of Official COVID-19 Reports: A Data-Driven Analysis
Authors: Tamás Kurbucz Marcell , Katona Attila Imre , Lantos Zoltán , Kosztyán Zsolt Tibor
Published: November 2020

This paper investigates the role of socioeconomic considerations in the formation of official COVID-19 reports. To this end, we employ a dataset that contains 1,159 preprocessed indicators from the World Bank Group GovData360 and TCdata360 platforms and an additional 8 COVID-19 variables generated based on reports from 138 countries. During the analysis, a rank-correlation-based complex method is used to identify the time- and space-varying relations between pandemic variables and the main topics of World Bank Group platforms. The results not only draw attention to the importance of factors such as air traffic, tourism, and corruption in report formation but also support further discipline-specific research by mapping and monitoring a wide range of such relationships. To this end, an R Notebook is attached that allows for the customization of the analysis and provides up-to-date results.
Frequency and profile of objective cognitive deficits in hospitalized patients recovering from COVID-19
Authors: Jaywant Abhishek , Vanderlind W. Michael , Alexopoulos George S. , Fridman Chaya B. , Perlis Roy H. , Gunning Faith M.
Published: November 2020

Background

Cognitive impairment is common following critical illness. A number of case reports and case series have suggested that cognitive deficits occur in patients with COVID-19. This study evaluated the frequency, severity, and profile of cognitive dysfunction in hospitalized patients recovering from COVID-19.

Methods

We obtained and analyzed cross-sectional neuropsychological data from a cohort of N=57 patients participating in inpatient rehabilitation. Our primary outcome measure was the Brief Memory and Executive Test (BMET). We calculated the frequency of impairment based on clinician diagnosis and by the BMET subtests using age-normed classification of impairment. We explored associations with intubation and extubation as markers of illness severity and complications, as well as psychiatric diagnosis.

Outcomes

Our sample was 75% male, 61% non-white, with a mean age of 64.5 (SD = 13.9) years. Patients were evaluated at a mean of 43.2 days post-admission. 88% had documented hypoxemic respiratory failure and 77% required intubation. 81% of patients had cognitive impairment, ranging from mild to severe. Deficits were most common in working memory (55% of patients impaired), set-shifting (47%), divided attention (46%), and processing speed (40%). Executive dysfunction was not significantly associated with intubation length or the time from extubation to assessment, nor was it associated with the presence of a psychiatric diagnosis.

Interpretation

Medically stable inpatients recovering from COVID-19 commonly have deficits in attention and executive functions. These deficits were not significantly correlated with length of intubation or time since extubation. Findings provide an early benchmark for studying the evolution of cognitive difficulties after COVID-19 and suggest that easy to disseminate interventions that remediate attention and executive dysfunctions may be important in this population.

Funding

The authors have no funding for this study to report.
Gastroenterological and Hepatic Manifestations of Patients with COVID-19, Prevalence, Mortality by Country, and Intensive Care Admission Rate: Systematic Review and Meta-analysis
Authors: Shehab Mohammad , Alrashed Fatema , Shuaibi Sameera , Alajmi Dhuha , Barkun Alan
Published: November 2020

Background & Aims

Patient infected with the SARS-COV2 usually report fever and respiratory symptoms. However, multiple gastrointestinal (GI) manifestations such as diarrhea and abdominal pain has been described. The aim of this study was to evaluate the prevalence of GI, liver function test (LFT) abnormalities, and mortality of COVID-19 patients.

Methods

We performed a systematic review and meta-analysis of published studies that included cohort of patients infected with SARS-COV2 from December 1st, 2019 to July 1st, 2020. We collected data from the cohort of patients with COVID-19 by conducting a literature search using PubMed, Embase, Scopus, and Cochrane according to the preferred reporting Items for Systematic Reviews and MetaAnalyses (PRISMA) guidelines. We analyzed pooled data on the prevalence of overall and individual gastrointestinal symptoms, LFTs abnormalities and performed subanalyses to investigate the relationship between gastrointestinal symptoms, geographic location, fatality, and ICU admission.

Results

The available data of 17,802 positive patients for SARS-COV2 from 120 studies were included in our analysis. The most frequent manifestations were diarrhea (13.3%, 95% CI 12-16), nausea (9.1%, 95% CI 9-13) and elevated LFTs (23.7%, 95% CI 21- 27). The overall and GI fatality were 7.2% (95% CI 6 -10), and 1% (95% CI 1- 4) respectively. Subgroup analysis showed non statistically significant associations between GI symptoms/LFTs abnormalities and ICU admissions (OR=3.41, 95% CI 0.87 – 13.4). The GI mortality rate was 0.58% in China and 3.5% in the United States (95% CI 2 - 5).

Conclusion

Digestive symptoms and LFTs abnormalities are common in COVID-19 patients. Our subanalysis shows that the presence of gastrointestinal and liver manifestations does not appear to affect mortality, or ICU admission rate. However, the mortality rate was higher in the United States compared to China.
A chest-CT and clinical chemistry based flowchart for rapid COVID-19 triage at emergency departments – a multicenter study
Authors: Kurstjens Steef , Göttgens Eva-Leonne , Smit Bob , Postma Bent , Kluge Carl , van der Horst Armando , Lamboo Eva H.J. , – Te Slaa Caroline M.M. Janssen , Herpers Robert , Kluiters-de Hingh Yvette C.M. , Mée Arthur du , Veuger Marjan , van Marum Rob , de Jager Peter , Elisen Marc G. L. M. , Kusters Ron , Schuijt Martin , Thelen Marc H. M.
Published: November 2020

Background

Due to the large number of patients with coronavirus disease 19 (COVID-19), rapid diagnosis at the emergency department (ED) is of critical importance. In this study we have developed a flowchart based on two well-known diagnostic methods: the ‘corona-score’ and the ‘CO-RADS’. This flowchart can be used in hospitals that use chest-CT, instead of chest X-ray, for COVID-19 suspected patients at the ED.

Methods

ED patients (n=1904) from the Jeroen Bosch Hospital, Amphia Hospital, HagaHospital, Elisabeth TweeSteden Hospital, Bernhoven Hospital and Slingeland Hospital were included. A laboratory-based ‘corona-score’, without radiology, called the ‘lab-corona-score’ was combined with a chest-CT based radiology scoring system (CO-RADS), to develop a flowchart. The performance was assessed by sensitivity/specificity analyses using the RT-PCR outcome or the physician’s final diagnosis as golden standard.

Results

Out of the 1904 patients, 611 (32.1%) patients tested positive for the SARS-CoV-2 virus. The lab-corona-score alone had an AUC of 0.86, a sensitivity of 87% and a specificity of 88% using cut-off values of 0-2 (negative) and 8-10 (positive). Of 255 patients, from the Amphia and Slingeland Hospitals, a CO-RADS score was determined. The flowchart, which combined the ‘CO-RADS’ with the ‘lab-corona-score’, was developed based on data from Slingeland Hospital (sensitivity 97%, specificity 96%). Hereafter, the performance of the flowchart was validated using an independent dataset from Amphia hospital, and reached a sensitivity of 98% and specificity of 93%. A decision could be made in 79% of the patients, which was correct in 95% of the cases.

Conclusion

This flowchart, based on radiology (CO-RADS) and clinical chemistry parameters (lab-corona-score), results in a rapid and accurate diagnosis of COVID-19 at the ED.
Method development and characterization of the low molecular weight peptidome of human wound fluids
Authors: van der Plas Mariena J.A. , Cai Jun , Petrlova Jitka , Saleh Karim , Kjellström Sven , Schmidtchen Artur
Published: November 2020

Wound infections are significant challenges globally, and there is an unmet need for better diagnosis of wound healing status and infection. The wound healing process is characterized by proteolytic events that are the result of basic physiological processes, but also dysfunctional activations by endogenous and bacterial proteases. Peptides, downstream reporters of these proteolytic actions, could therefore serve as a promising tool for diagnosis of wounds.

Here, we demonstrate a method for the characterisation of the peptidome of wound fluids. We compare acute non-infected wound fluids obtained post-surgery with plasma samples and find significantly higher protein and peptide numbers in wound fluids, which typically were also smaller in size as compared to plasma-derived peptides. Furthermore, we analyse wound fluids collected from dressings after facial skin graft surgery and compare three uninfected, healing wounds with three inflamed Staphylococcus aureus infected wounds. The results identify unique peptide patterns of various proteins, including coagulation and complement factors, proteases and antiproteinases.

Together, the work defines a workflow for analysis of peptides derived from wound fluids and demonstrate a proof-of-concept that such fluids can be used for analysis of qualitative differences of peptide patterns from larger patient cohorts, providing potential biomarkers for wound healing and infection.
Estimation of the severeness rate, death rate, household attack rate and the total number of COVID-19 cases based on 16 115 Polish surveillance records
Authors:   The MOCOS International Research Group, Adamik Barbara , Bawiec Marek , Bezborodov Viktor , Biecek Przemyslaw , Bock Wolfgang , Bodych Marcin , Burgard Jan Pablo , Krueger Tyll , Migalska Agata ,   MOCOS, Ożański Tomasz , Pabjan Barbara , Rosińska Magdalena , Sadkowska-Todys Malgorzata , Sobczyk Piotr , Szczurek Ewa
Published: November 2020

Background

Estimating the actual number of COVID-19 infections is crucial for steering through the COVID-19 pandemic crisis. It is, however, notoriously difficult, as many cases have no or only mild symptoms. Surveillance data for in-household secondary infections offers unbiased samples for COVID-19 prevalence estimation.

Methods

We analyse 16 115 Polish surveillance records to obtain key figures of the COVID-19 pandemic. We propose conservative upper and lower bound estimators for the number of SARS-CoV-2 infections. Further, we estimate age-dependent bounds on the severe case rate, death rate, and the in-household attack rate.

Results

By maximum likelihood estimates, the total number of COVID-19 cases in Poland as of July 22nd, 2020, is at most around 13 times larger and at least 1.6 times larger than the recorded number. The lower bound on the severeness rate ranges between 0.2% for the 0–39 year-old to 5.7% for older than 80, while the upper bound is between 2.6% and 34.1%. The lower bound on the death rate is between 0.04% for the age group 40–59 to 1.34% for the oldest. Overall, the severeness and death rates grow exponentially with age. The in-household attack ratio is 8.18% for the youngest group and 16.88% for the oldest.

Conclusions

The proposed approach derives highly relevant figures on the COVID-19 pandemic from routine surveillance data, under assumption that household members of detected infected are tested and all severe cases are diagnosed.

MOCOS

The MOCOS (MOdellingCOronaSpread) international research group is an interdisciplinary scientific consortium. The following authors are MOCOS members: Barbara Adamik, Marek Bawiec, Viktor Bezborodov, Przemyslaw Biecek, Wolfgang Bock, Marcin Bodych, Jan Pablo Burgard, Tyll Krueger, Agata Migalska, Tomasz Ożański, Barbara Pabjan, Magdalena Rosińska, Piotr Sobczyk and Ewa Szczurek
Maternal late-pregnancy serum unmetabolized folic acid concentrations are not associated with infant allergic disease - A prospective cohort study
Authors: Best Karen P , Green Tim J , Sulistyoningrum Dian , Sullivan Thomas R , Aufreiter Susanne , Prescott Susan L , Makrides Maria , Skubisz Monika , O’Connor Deborah L , Palmer Debra J
Published: November 2020

Background

The increase in childhood allergic disease in recent decades has coincided with increased folic acid intakes during pregnancy. Circulating unmetabolized folic acid (UMFA) has been proposed as a biomarker of excessive folic acid intake.

Objective

We aimed to determine if late-pregnancy serum UMFA and total folate concentrations were associated with allergic disease risk in the offspring at one year of age in a population at high risk of allergy.

Methods

The cohort consisted of 561 mother-infant pairs from Western Australia. To be eligible the infant had a first-degree relative (mother, father or sibling) with a history of medically diagnosed allergic disease. Maternal serum was collected between 36 and 40 weeks of gestation. UMFA concentrations were measured by tandem mass spectrometry using stable isotope dilution, folate concentrations were determined using the microbiological method with standardized kits. Infant allergic disease outcomes of medically diagnosed eczema, steroid treated eczema, atopic eczema, IgE-mediated food allergy, allergen sensitization and medically diagnosed wheeze were assessed at 1 year of age.

Results

Median (IQR) for UMFA and serum folate was 1.6 (0.6-4.7) and 53.2 (32.6-74.5) nmol/L, respectively. Of the infants, 34.6% had medically diagnosed eczema, 26.4% allergen sensitization and 14.9% had an IgE-mediated food allergy. In both adjusted and unadjusted models there was little evidence of association between UMFA or serum folate and any of the infant allergy outcomes.

Conclusion

In this cohort of children at high risk for allergic disease there was no association between maternal UMFA or serum folate measured in late pregnancy and allergic disease outcomes at 1 year of age.
Features of α-HBDH in COVID-19 patients with different ages,outcomes and clinical types: a cohort study
Authors: Zhu Haoming , Qu Gaojing , Yu Hui , Huang Guoxin , Chen Lei , Zhang Meiling , Wan Shanshan , Pei Bin
Published: November 2020

Background

Coronavirus disease-2019 (COVID-19) has spread all over the world and brought extremely huge losses. At present, there is no study to systematically analyse the features of hydroxybutyrate dehydrogenase (α-HBDH) in COVID-19 patients with different ages, clinical types and outcomes.

Methods

Electronic medical records including demographics, clinical manifestation, α-HBDH test results and outcomes of 131 hospitalized COVID-19 patients, with confirmed result of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection, were extracted and analyzed.

Results

The α-HBDH value in ≥61 years old group, severe group and critical group, death group all increased at first and then decreased, while no obvious changes were observed in other groups. And there were significant differences of the α-HBDH value among different age groups (P<0.001), clinical type groups (P<0.001) and outcome groups (P<0.001). The optimal scale regression model showed that α-HBDH value (P<0.001) and age (P<0.001) were related to clinical type.

Conclusions

α-HBDH value increases in some COVID-19 patients, obviously in ≥61 years old, death and critical group, indicating that patients in these three groups suffer from more serious tissues and organs damage, higher α -HBDH value and risk of death. The obvious difference between death and survival group in early stage may provide a approach to judge the prognosis. The accuracy of the model to distinguish severe/critical type and other types is 85.84%, suggesting that α-HBDH could judge the clinical type of COVID-19 patients accurately. In brief, α-HBDH is an important indicator to judge the severity and prognosis of COVID-19.
Visual Scoring of Chest CT at Hospital Admission Predicts Hospitalization Time and Intensive Care Admission in Covid-19
Authors: Ahlstrand Erik , Cajander Sara , Cajander Per , Ingberg Edvin , Löf Erika , Wegener Matthias , Lidén Mats
Published: November 2020

Background

The extent and character of lung involvement on chest computerized tomography (CT) have a prognostic value in covid-19 but there is lack of consensus on how to assess and stage CT features. A scoring system of lung involvement in covid-19, Örebro covid-19 Scale (ÖCoS) was implemented in clinical routine on April 1 2020 in Örebro Region, Sweden. The ÖCoS-severity score measures the extent of lung involvement while ÖCoS-temporal stage characterizes the parenchymal involvement. The objective of the present study was to evaluate the ÖCoS scores in relation to clinical outcome of covid-19.

Methods

Population based study including data from all hospitalized patients with covid-19 in Örebro Region during March to July 2020. Chest CT scores at the time of hospital admission and ICU admission were analyzed in relation to hospital and intensive care unit (ICU) length of stay, time to ICU admission and admission to ICU or death.

Findings

In the 381 included patients, there was a close correlation of the ÖCoS-severity score on admittance to hospital and the hospital length of stay. The ÖCoS-severity score on hospital admittance was a strong predictor for both a severe outcome in regards to ICU admittance or death and the time to ICU admittance. On admittance to ICU, both ÖCoS-severity score and temporal stage were correlated with the ICU length of stay.

Interpretation

Chest CT visual scoring on admission to hospital predicts the clinical course in covid-19 pneumonia.

Funding

This work was supported by the Örebro Region, Sweden.
Growth of respiratory droplets in cold and humid air
Authors: Ng Chong Shen , Chong Kai Leong , Yang Rui , Li Mogeng , Verzicco Roberto , Lohse Detlef
Published: November 2020

The ambient conditions surrounding liquid droplets determine their growth or shrinkage. However, the precise fate of a liquid droplet expelled from a respiratory puff as dictated by its surroundings and the puff itself has not yet been fully quantified. From the view of airborne disease transmission, such as SARS-CoV-2, knowledge of such dependencies are critical. Here we employ direct numerical simulations (DNS) of a turbulent respiratory vapour puff and account for the mass and temperature exchange with respiratory droplets and aerosols. In particular, we investigate how droplets respond to different ambient temperatures and relative humidity (RH) by tracking their Lagrangian statistics. We reveal and quantify that in cold and humid environments, as there the respiratory puff is supersaturated, expelled droplets can first experience significant growth, and only later followed by shrinkage, in contrast to the monotonic shrinkage of droplets as expected from the classical view by William F. Wells (1934). Indeed, cold and humid environments diminish the ability of air to hold water vapour, thus causing the respiratory vapour puff to super-saturate. Consequently, the super-saturated vapour field drives the growth of droplets that are caught and transported within the humid puff. To analytically predict the likelihood for droplet growth, we propose a model for the axial RH based on the assumption of a quasi-stationary jet. Our model correctly predicts super-saturated RH conditions and is in good quantitative agreement with our DNS. Our results culminate in a temperature-RH map that can be employed as an indicator for droplet growth or shrinkage.

Significance Statement

Influence of environmental conditions on airborne diseases transmission is an important issue, especially during the pandemic of COVID-19. Human-to-human transmission is mediated by the transport of virus-laden respiratory droplets. Here we investigate the problem from a fluid mechanics perspective by conducting numerical simulations to quantify the fate of respiratory droplets in a warm humid coughing puff under different ambient conditions. We reveal a non-intuitive regime with considerable growth of respiratory droplets, dominated by a super-saturated vapour field, preferentially occurring in cold and humid environments. We further propose a theoretical model that accurately predicts the condition for droplet growth. Our work should inform socializing policies and ventilation strategies for controlling indoor ambient conditions to mitigate dispersion of droplets from asymptomatic individuals.
The Interplay between Maternal Smoking and Genes in Offspring Birth Weight
Authors: Pereira Rita Dias , Rietveld Cornelius A. , van Kippersluis Hans
Published: November 2020

It is well-established that both the child’s genetic endowments as well as maternal smoking during pregnancy impact offspring birth weight. In this paper we move beyond the natureversusnurture debate by investigating the interaction between genetic endowments and this critical prenatal environmental exposure – maternal smoking – in determining birth weight. We draw on longitudinal data from the Avon Longitudinal Study of Parents and Children (ALSPAC) study and replicate our results using data from the UK Biobank. Genetic endowments of the children are proxied with a polygenic score that is constructed based on the results of the most recent genome-wide association study of birth weight. We instrument the maternal decision to smoke during pregnancy with a genetic variant (rs1051730) located in the nicotine receptor gene CHRNA3. This genetic variant is associated with the number of cigarettes consumed daily, and we present evidence that this is plausibly the only channel through which the maternal genetic variant affects the child’s birth weight. Additionally, we deal with the misreporting of maternal smoking by using measures of cotinine, a biomarker of nicotine, collected from the mother’s urine during their pregnancy. We confirm earlier findings that genetic endowments as well as maternal smoking during pregnancy significantly affects the child’s birth weight. However, we do not find evidence of meaningful interactions between genetic endowments and an adverse fetal environment, suggesting that the child’s genetic predisposition cannot cushion the damaging effects of maternal smoking.
Differences and similarities in diagnostic methods and treatments for Coronavirus disease 2019 (COVID-19): a scoping review
Authors: Scholze Alessandro Rolim , Melo Emiliana Cristina , Major Carina Bortolato , Cruz Carolina Fordellone Rosa , de Souza Alcântara Léia Regina , Dalcol Camila , Ferreira Seiva Fábio Rodrigues , de Fátima Mantovani Maria , Mattei Ângela Tais , Silveira Henrique Spaulonci , de Almeida Chuffa Luiz Gustavo
Published: November 2020

Aims

We investigate a range of studies related to COVID-19 with focus on scientific evidence reporting the main diagnosis and treatments of the disease.

Main Methods

Scoping review conducted in the databases, MEDLINE, Cochrane, Embase, LILACS, Scopus, and Web of Science, and the gray Google Scholar literature, until May 2020. We follow PRISMA-SCR and the recommendations of the Joanna Briggs Institute. The identified studies were independently selected by peers. The qualitative data extracted were synthesized and organized into categories, and the quantitative data were generated through descriptive and inferential statistics.

Key-findings

6060 articles were identified, of which 30 were included in this review. The publications are predominantly from China (n=22, 73.3%), and with a type of cross-sectional study (n=12, 40.0%), followed by a cohort (n=7, 23.0%). Among them, 16 studies addressed the diagnosis, and computed tomography was considered as non-invasive complementary method for detecting and evaluating the progression of COVID-19. Laboratory tests have been used to detect enzymatic or viral activities, and to monitor the inflammation associated with COVID-19. 14 studies included different therapeutic associations, such as Lopinavir/Ritonavir (LPV/r) and Arbidol, Hydroxychloroquine, Azithromycin, Tocilizumab and Remdesivir, and Corticosteroids/Plasminogen.

Significance

The evidence related to diagnostic methods are clear, and include tomography and laboratory tests. Medicinal or associated medications for the treatment of COVID-19, although showing a reduction in signs and COVID-19-related symptoms, can cause adverse effects of mild or severe intensity depending on viral load and inflammatory activity. Additional studies should be performed to identify the most reliable treatment for COVID-19.
Rapid, simplified whole blood-based multiparameter assay to quantify and phenotype SARS-CoV-2 specific T cells
Authors: Riou Catherine , Schäfer Georgia , du Bruyn Elsa , Goliath Rene T. , Stek Cari , Mou Huihui , Hung Deli , Wilkinson Katalin A. , Wilkinson Robert J.
Published: November 2020

Rapid tests to evaluate SARS-CoV-2-specific T cell responses are urgently needed to decipher protective immunity and aid monitoring vaccine-induced immunity. Using a rapid whole blood assay requiring minimal amount of blood, we measured qualitatively and quantitatively SARS-CoV-2-specific CD4 T cell responses in 31 healthcare workers, using flow cytometry. 100% of COVID-19 convalescent participants displayed a detectable SARS-CoV-2-specific CD4 T cell response. SARS-CoV-2-responding cells were also detected in 40.9% of participants with no COVID-19-associated symptoms or who tested PCR negative. Phenotypic assessment indicated that, in COVID-19 convalescent participants, SARS-CoV-2 CD4 responses displayed an early differentiated memory phenotype with limited capacity to produce IFNγ. Conversely, in participants with no reported symptoms, SARS-CoV-2 CD4 responses were enriched in late differentiated cells, co-expressing IFNγ and TNFα and also Granzyme B. This proof of concept study presents a scalable alternative to PBMC-based assays to enumerate and phenotype SARS-CoV-2-responding T cells, thus representing a practical tool to monitor adaptive immunity in vaccine trials.

In this proof of concept study, we show that SARS-CoV-2 T cell responses are easily detectable using a rapid whole blood assay requiring minimal blood volume. Such assay could represent a suitable tool to monitor adaptive immunity in vaccine trials.
Sleep quality does not mediate the association between chronodisruption and metabolic syndrome
Authors: Carpio-Arias Tannia Valeria , Arias Diana Carolina Mogrovejo , Nicolalde-Cifuentes Tomas Marcelo , Tapia-Veloz Estephany Carolina , De Zeeuw Chris I. , Vinueza-Veloz María Fernanda
Published: November 2020

Aims

The objective of the present work was to determine to what extent sleep quality may mediate the association between CD, metabolic syndrome (MS) and body composition (BC).

Methodology

Cross-sectional study which included 300 adult health workers, 150 of whom were night shift workers and thereby exposed to CD. Diagnosis of MS was made based on Adult Treatment Panel III criteria. Sleep quality was measured using the Pittsburgh Sleep Quality Index. Body mass index (BMI), fat mass percentage, and visceral fat percentage were measured as indicators of BC. Data were analyzed using logistic, linear regression and structural equation models.

Results

The odds of health workers exposed to CD to suffer from MS was 22.13 (IC958.68 - 66.07) when the model was adjusted for age, gender, physical activity and energy consumption. CD was also significantly associated with an increase in fat mass and visceral fat percentages, but not to BMI. Surprisingly, there was not enough evidence supporting the hypothesis that sleep quality contributes to the association between CD and MS or BC.

Conclusions

Sleep quality does not mediate the negative effects of CD on health and BC.
Risk perceptions and preventive practices of COVID-19 among healthcare professionals in public hospitals in Ethiopia
Authors: Deressa Wakgari , Worku Alemayehu , Abebe Workeabeba , Gizaw Muluken , Amogne Wondwosson
Published: November 2020

Healthcare professionals are at higher risk of contracting the novel coronavirus due to their work exposure in the healthcare settings. Practicing appropriate preventive measures to control COVID-19 infection is one of the most important interventions that healthcare workers are expected to use. The aim of this study was to assess the level of risk perception and practices of preventive measures of COVID-19 among health workers in Addis Ababa, Ethiopia. A hospital-based cross-sectional study was conducted from 9th to 26th June 2020 among healthcare professionals working at six public hospitals in Addis Ababa. Data were collected using a self-administered structured questionnaire. Frequency, percentage, and mean were used to summarize the data. A binary logistic regression analyses were performed to identify factors associated with risk perception about COVID-19. A total of 1,134 participants were surveyed. Wearing facemask (93%), hand washing for at least 20 seconds (93%), covering mouth and nose while coughing or sneezing (91%), and avoiding touching eyes, nose, and mouth (91%) were the commonly self-reported preventive practices. About 88% perceived that they were worried about the risk of becoming infected with coronavirus, and majority (91%) worried about the risk of infection to their family. The mean score of overall fear and worry of COVID-19 was 2.37 on a scale of 1 to 3. Respondents who ever provided clinical care to COVID-19 patients were more likely to report fear and worry (adjusted OR=1.34, 95% CI:1.02-1.91), however those who ever participated in Ebola or SARS outbreaks were less likely to report fear and worry due to COVID-19 crisis (adjusted OR=0.66, 95% CI:0.48-0.90). This study has revealed widespread practices of preventive measures and the highest perceived risk of COVID-19 among healthcare workers. Therefore, an effective risk communication intervention should be implemented to ensure the maintenance of appropriate practices during the current COVID-19 pandemic.
Genetic diversity analysis of the D614G mutation in SARS-CoV-2
Authors: Felix Pierre Teodósio , Venâncio Dallynne Bárbara Ramos , Da Silva Eduarda Doralice Alves Braz , da Silva Ramos Robson
Published: November 2020

In this work, we evaluated the levels of genetic diversity in 18 genomes of SARS-CoV-2 carrying the D614G mutation, coming from Malaysia and Venezuela and publicly available at the National Center of Biotechnology and Information (NCBI). These haplotypes were previously used for phylogenetic analysis, following the LaBECom protocols. All gaps and unconserved sites were extracted for the construction of a phylogenetic tree. As specific methodologies for paired FST estimators, Molecular Variance (AMOVA), Genetic Distance, mismatch, demographic and spatial expansion analyses, molecular diversity and evolutionary divergence time analyses, 20,000 random permutations were always used. The results revealed the presence of only 57 sites of polymorphic and parsimonium-informative among the 29,827bp analyzed and the analyses based on FSTvalues confirmed the presence of two distinct genetic entities with fixation index of 22% and with a higher component of population variation (78.14%). Tau variations revealed a significant time of divergence, supported by mismatch analysis of the observed distribution (τ = 42%). It is safe to say that the small number of existing polymorphisms should not reflect major changes in the protein products of viral populations in both countries and this consideration provides the safety that, although there are differences in the haplotypes studied, these differences are minimal for both regions analyzed geographically and, therefore, it seems safe to extrapolate the levels of polymorphism and molecular diversity found in the samples for other mutant genomes of SARS-CoV-2 in other countries. This reduces speculation about the possibility of large differences between mutant strains of SARS-CoV-2 (D614G) and wild strains, at least at the level of their protein products, although the mutant form has higher transmission speed and infection. The analyses suggest that possible variations in protein products, of the wild virus in relation to its mutant form, should be minimal, bringing peace of mind as to the increased risk of death from the new form of the virus, as well as possible problems of gradual adjustments in some molecular targets for vaccines.
Ontology-Aware Deep Learning Enables Ultrafast, Accurate and Interpretable Source Tracking among Sub-Million Microbial Community Samples from Hundreds of Niches
Authors: Zha Yuguo , Chong Hui , Qiu Hao , Kang Kai , Dun Yuzheng , Chen Zhixue , Cui Xuefeng , Ning Kang
Published: November 2020

The taxonomical structure of microbial community sample is highly habitat-specific, making it possible for source tracking niches where samples are originated. Current methods face challenges when the number of samples and niches are magnitudes more than current in use, under which circumstances they are unable to accurately source track samples in a timely manner, rendering them difficult in knowledge discovery from sub-million heterogeneous samples. Here, we introduce a deep learning method based on Ontology-aware Neural Network approach, ONN4MST (https://github.com/HUST-NingKang-Lab/ONN4MST), which takes into consideration the ontology structure of niches and the relationship of samples from these ontologically-organized niches. ONN4MST’s superiority in accuracy, speed and robustness have been proven, for example with an accuracy of 0.99 and AUC of 0.97 in a microbial source tracking experiment that 125,823 samples and 114 niches were involved. Moreover, ONN4MST has been utilized on several source tracking applications, showing that it could provide highly-interpretable results from samples with previously less-studied niches, detect microbial contaminants, and identify similar samples from ontologically-remote niches, with high fidelity.
AC. elegansneuron both promotes and suppresses motor behavior to fine tune motor output
Authors: Li Zhaoyu , Zhou Jiejun , Wani Khursheed , Yu Teng , Ronan Elizabeth A. , Piggott Beverley J. , Liu Jianfeng , Xu X.Z. Shawn
Published: November 2020

How neural circuits drive behavior is a central question in neuroscience. Proper execution of motor behavior requires the precise coordination of many neurons. Within a motor circuit, individual neurons tend to play discrete roles by promoting or suppressing motor output. How exactly neurons function in specific roles to fine tune motor output is not well understood. InC. elegans, the interneuron RIM plays important yet complex roles in locomotion behavior. Here, we show that RIM both promotes and suppresses distinct features of locomotion behavior to fine tune motor output. This dual function is achieved via the excitation and inhibition of the same motor circuit by electrical and chemical neurotransmission, respectively. Additionally, this bi-directional regulation contributes to motor adaptation in animals placed in novel environments. Our findings reveal that individual neurons within a neural circuit may act in opposing ways to regulate circuit dynamics to fine tune behavioral output.
Control of neurogenic competence in mammalian hypothalamic tanycytes
Authors: Yoo Sooyeon , Kim Juhyun , Lyu Pin , Hoang Thanh V. , Ma Alex , Trinh Vickie , Dai Weina , Jiang Lizhi , Leavey Patrick , Won Jae-Kyung , Park Sung-Hye , Qian Jiang , Brown Solange P. , Blackshaw Seth
Published: November 2020

Hypothalamic tanycytes, radial glial cells that share many features with neuronal progenitors, generate small numbers of neurons in the postnatal hypothalamus, but the identity of these neurons and the molecular mechanisms that control tanycyte-derived neurogenesis are unknown. In this study, we demonstrate that tanycyte-specific disruption of the NFI family of transcription factors (Nfia/b/x) robustly stimulates tanycyte proliferation and tanycyte-derived neurogenesis. Single-cell RNA- and ATAC-Seq analysis reveals that NFI factors repress Shh and Wnt signaling in tanycytes, and small molecule modulation of these pathways blocks proliferation and tanycyte-derived neurogenesis inNfia/b/x-deficient mice. We show thatNfia/b/x-deficient tanycytes give rise to multiple mediobasal hypothalamic neuronal subtypes that can mature, integrate into hypothalamic synaptic circuitry, and selectively respond to changes in internal states. These findings identify molecular mechanisms that control tanycyte-derived neurogenesis, suggesting a new therapeutic approach to selectively remodel the hypothalamic neural circuitry that controls homeostatic physiological processes.