bluuebunny/crossref_metadata_2025 huggingface dataset:
pyPOCQuant - A tool to automatically quantify Point-Of-Care Tests from images
Authors: Cuny Andreas P. , Rudolf Fabian , Ponti Aaron
Published: November 2020

Lateral flow Point-Of-Care Tests (POCTs) are a valuable tool for rapidly detecting pathogens and the associated immune response in humans and animals. In the context of the SARS-CoV-2 pandemic, they offer rapid on-site diagnostics and can relieve centralized laboratory testing sites, thus freeing resources that can be focused on especially vulnerable groups. However, visual interpretation of the POCT test lines is subjective, error prone and only qualitative. Here we present pyPOCQuant, an open-source tool implemented in Python 3 that can robustly and reproducibly analyze POCTs from digital images and return an unbiased and quantitative measurement of the POCT test lines.
Design and implementation of an international, multi-arm, multi-stage platform master protocol for trials of novel SARS-CoV-2 antiviral agents: Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3)
Authors: Murray Daniel D. , Babiker Abdel G. , Baker Jason V. , Barkauskas Christina E. , Brown Samuel M. , Chang Christina C. , Davey Victoria J. , Gelijns Annetine C. , Ginde Adit A. , Grund Birgit , Higgs Elizabeth , Hudson Fleur , Kan Virginia L. , Lane H. Clifford , Murray Thomas A. , Paredes Roger , Parmar Mahesh K.B. , Pett Sarah , Phillips Andrew N. , Polizzotto Mark N. , Reilly Cavan , Sandkovsky Uriel , Sharma Shweta , Teitelbaum Marc , Thompson B. Taylor , Young Barnaby E. , Neaton James D. , Lundgren Jens D.
Published: November 2020

Background

Safe and effective therapies for COVID-19 are urgently needed. In order to meet this need, the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership initiated the Therapeutics for Inpatients with COVID-19 (TICO). TICO is a multi-arm, multi-stage (MAMS) platform master protocol, which facilitates the rapid evaluation of the safety and efficacy of novel candidate anti-viral therapeutic agents for adults hospitalized with COVID-19. Four agents have so far entered the protocol, with rapid answers already provided for three of these. Other agents are expected to enter the protocol throughout 2021. This protocol contains a number of key design and implementation features that, along with challenges faced by the protocol team, are presented and discussed.

Protocol Design and Implementation

Three clinical trial networks, encompassing a global network of clinical sites, participated in the protocol development and implementation. TICO utilizes a MAMS design with an agile and robust approach to futility and safety evaluation at 300 patients enrolled, with subsequent expansion to full sample size and an expanded target population if the agent shows an acceptable safety profile and evidence of efficacy. Rapid recruitment to multiple agents is enabled through the sharing of placebo as well as the confining of agent-specific information to protocol appendices, and modular consent forms. In collaboration with the Food and Drug Administration, a thorough safety data collection and DSMB schedule was developed for the study of agents with limited in-human data.

Challenges

Challenges included ensuring drug supply and reliable recruitment allowing for changing infection rates across the global network of sites, the need to balance the collection of data and samples without overburdening clinical staff, and obtaining regulatory approvals across a global network of sites.

Conclusion

Through a robust multi-network partnership, the TICO protocol has been successfully used across a global network of sites for rapid generation of efficacy data on multiple novel antiviral agents. The protocol design and implementation features used in this protocol, and the approaches to address challenges, will have broader applicability. Mechanisms to facilitate improved communication and harmonization among country-specific regulatory bodies are required.
Host genetic liability for severe COVID-19 overlaps with alcohol drinking behavior and diabetic outcomes in over 1 million participants
Authors: Wendt Frank R , De Lillo Antonella , Pathak Gita A , De Angelis Flavio ,   COVID-19 Host Genetics Initiative, Polimanti Renato
Published: November 2020

To distinguish correlation from causation, we performedin-silicoanalyses of three COVID-19 outcomes (N>1,000,000). We show genetic correlation and putative causality with depressive symptoms, metformin use, and alcohol use. COVID-19 risk loci associated with several hematologic biomarkers. Comprehensive findings inform genetic contributions to COVID-19 epidemiology, molecular mechanisms, and risk factors.
HLAautoimmune risk alleles restrict the hypervariable region of T cell receptors
Authors: Ishigaki Kazuyoshi , Lagattuta Kaitlyn , Luo Yang , James Eddie , Buckner Jane , Raychaudhuri Soumya
Published: November 2020

Polymorphisms in thehuman leukocyte antigen(HLA) genes within themajor histocompatibility complex(MHC) locus strongly influence autoimmune disease risk1–5. Two non-exclusive hypotheses exist about the pathogenic role ofHLAalleles; i) the central hypothesis, whereHLArisk alleles influence thymic selection so that the probability of T cell receptors (TCRs) reactive to pathogenic antigens is increased6–8; and ii) the peripheral hypothesis, whereHLArisk alleles increase the affinity for pathogenic antigens9–11. The peripheral hypothesis has been the main research focus in autoimmunity, while human data on the central hypothesis are lacking. Here, we investigated the influence ofHLAalleles on TCR composition at the highly diverse complementarity determining region 3 (CDR3), where TCR recognizes antigens. We demonstrated unexpectedly powerfulHLA-CDR3 associations. The strongest association was found atHLA-DRB1amino acid position 13 (n = 628 subjects, explained variance = 9.4%;P= 4.1 x 10−138). This HLA position mediates genetic risk for multiple autoimmune diseases. In structural analysis of TCR-peptide-MHC complexes, we observed that HLA-DRB1 position 13 does not interact directly with CDR3, but is proximate to antigenic peptide residues that are also close to CDR3. We identified multiple CDR3 amino acid features enriched byHLArisk alleles; for example, the risk alleles of rheumatoid arthritis, type 1 diabetes, and celiac disease all increase the hydrophobicity of CDR3 position 109 (P< 2.1 x 10−5). In the setting of celiac disease, the CDR3 features favored byHLArisk alleles are more enriched among candidate pathogenic TCRs than control TCRs (P= 2.4 × 10−6for gliadin specific TCRs). Together, these results provide novel genetic evidence supporting the central hypothesis.
Cerebellar rTMS in PSP: a double blind sham-controlled study using mobile health technology
Authors: Pilotto Andrea , Rizzetti Maria Cristina , Lombardi Alberto , Hansen Clint , Biggi Michele , Verzeroli G Giacomo , Martinelli Antonella , Romijnders Robbin , Borroni Barbara , Maetzler Walter , Padovani Alessandro
Published: November 2020

There are no effective treatments for postural instability and falls in Progressive Supranuclear Palsy (PSP). Objective of the study was to test the efficacy of theta burst repetitive transcranial magnetic stimulation (rTMS) on postural instability in PSP. Twenty probable PSP patients underwent a session of sham or cerebellar rTMS in a cross-over design. Before and after stimulation, static balance was evaluated with instrumented (lower back accelerometer, Rehagait®, Hasomed, Germany) 30-seconds-trials in semitandem and tandem positions. In tandem and semitandem tasks, active stimulation was associated with longer time without support falls (both p=0.04). In the same tasks, device-extracted parameters revealed significant improvement in area (p=0.007), velocity (p=0.005) and acceleration and jerkiness of sway (p=0.008) in real versus sham stimulation. Cerebellar rTMS thus showed a significant effect on stability in PSP patients, when assessed with mobile digital technology, in a double-blind design. These results should motivate larger and longer trials using non-invasive brain stimulation for PSP patients.
Are women underrepresented in cerebrovascular disease clinical trials? A systematic review using the FDA database
Authors: Zhong Xiaobo , Hao Qing
Published: November 2020

BACKGROUND AND PURPOSE

Clinical trials provide essential evidence in the US Food and Drug Administration (FDA) drug approval process. Women were underrepresented in the enrollment of clinical trials for many medical conditions other than cerebrovascular disease (CVD). We investigated women’s participation in FDA-registered CVD-related interventional clinical trials and assessed whether women CVD patients in the United States were underrepresented. We also evaluated the association between the underrepresentation and the features of design and operation among these trials.

METHODS

We systematically reviewed the phase 2 and 3 CVD-related interventional trials started in 2002–2017 in the FDA database. The proportions of women enrolled in these trials and the proportion-to-prevalence ratios (PPRs), defined as the ratios of the proportions of women enrolled in these trials to the proportion of women prevalent among US CVD patients during the same period, were calculated and summarized by a meta-analysis approach. We used boosted regression tree, a machine learning model, to identify the determinants of women’s underrepresentation in CVD-related trials.

RESULTS

According to our selection criteria, we analyzed the data of 145 CVD-related trials, among which 40.9% (95% CI: 38.3–43.5%) of the patients enrolled were women. Their PPR was estimated to be 0.843 (95% CI: 0.796–0.890). We found that four factors substantially influenced women’s underrepresentation in these trials: the number of enrollment sites, the starting year, randomization, and academic institution sponsorship.

CONCLUSIONS

Generally, women with CVD in the United States were underrepresented in FDA registered trials started in 2002–2017. In addition, trials with greater numbers of enrollment sites, randomization, and non-academically sponsored trials had a higher risk of underrepresenting women with CVD in the United States. Investigators should take these factors into consideration in clinical trial design in the future, by either increasing women’s participation or stratifying the enrollment by gender.
Automatic Measurements of Smooth Pursuit Eye Movements by Video-Oculography and Deep Learning-Based Object Detection
Authors: Hirota Masakazu , Hayashi Takao , Watanabe Emiko , Mizota Atsushi
Published: November 2020

Purpose

The purpose of this study was to develop a technique combining video oculography (VOG) with single shot multibox detector (SSD) to accurately and quantitatively examine eye movements.

Methods

Eleven healthy volunteers (21.3 ± 0.9 years) participated in this study. Eye movements were recorded while tracking a target using a custom-made eye tracker. The subjects were asked to fixate their focus on the nose of the rabbit-like target (visual angle was 0.1°), which was manually moved to a distance of 1 meter by the examiner during the eye movement test. The test produced 500 images from the VOG external camera and these images were divided into 3 groups (300, 100, and 100) for training, verification, and testing. The performance of the SSD was evaluated with 75% average precision (AP75), and the relationship between the location of the fixated target (calculated by the SSD) and the positions of both eyes (recorded by the VOG) was analyzed.

Results

The AP75 of the SSD on one class of targets was 97.7%. The horizontal and vertical target locations significantly and positively correlated with the horizontal and vertical both eye positions (adjusted R2 ≥ 0.955, P < 0.001).

Conclusions

Our findings suggest that VOG with SSD is suitable for the evaluation of eye version movements in standard clinical assessments.

Translational Relevance

The combination of VOG and SSD can be used to evaluate the SPEM, and this method can be translated into clinical settings without changing the testing methods.
Mitigating Covid-19 outbreaks in workplaces and schools by hybrid telecommuting
Authors: Mauras Simon , Cohen-Addad Vincent , Duboc Guillaume , Dupre la Tour Max , Frasca Paolo , Mathieu Claire , Opatowski Lulla , Viennot Laurent
Published: November 2020

The COVID-19 outbreak has forced most countries to impose new contact-limiting restrictions at workplaces, universities, schools, and more roadly in our societies. Yet, the power and imitations of these unprecedented strategies or containing virus spread within the populations remain unquantified. Here, we develop a simulation study to analyze COVID-19 outbreak magnitudes on three real-life contact networks stemming from a workplace, a primary school and a high school in France.
Our study provides the first fine-grained analysis of the impact of contact-limiting strategies at work-places, schools and high schools, including (1) Rotating, in which workers are evenly split into two shifts that alternate on a daily or weekly basis; and (2) On-Off, where the whole group alternates periods of normal work interactions with complete telecommuting. We model epidemics spread in these different setups using an SEIR transmission model enriched with the coronavirus most salient specificities: super-spreaders, infec-tious asymptomatic individuals, and pre-symptomatic infectious periods. Our study yields clear results: The ranking of the strategies based on their ability to mitigate epidemic propagation in the network from a first index case is the same for all network topologies (work place, primary school and high school). Namely, from best to worst: Rotating week-by-week, Rotating day-by-day, On-Off week-by-week, and On-Off day-by-day. Moreover, our results show that when the baseline reproduction number R0 within the network is < 1:38, all four strategies efficiently control outbreak by decreasing effective Re to <1. These results can support public health decisions and telecommuting organization locally.
Conflict driven displacement and child health: Evidence from Jordan
Authors: Malik Manzoor Ahmad , Akhtar Saddaf Naaz , Albsoul Rania Ali , Alshyyab Muhammad Ahmed
Published: November 2020

Background

Armed conflicts result in greater vulnerability and socioeconomic inequality of populations besides risking their health and well-being. Conflict intensifies the health needs and risks the life and well-being of individuals at large through displacement. Therefore, our study aims to apprise the interventions to which children under-five living in Jordan are especially at risk for acute respiratory infections, diarrhea, and fever in the conflict circumstances.

Methods

Secondary data analysis is used in the present study. We used a weighted sample of around 9650 children from Jordan Population and Family Health Survey (JPFHS), 2017-18. Bivariate analysis including prevalence rates were used to examine the distribution of socio-demographic characteristics of children. The study has also used multinomial logistic regression model, in order to evaluate the variations in the probability of nationality of under-five children living in Jordan.

Results

“Syrian nationalist” children have a higher relative risk of ARI (RRR=1.19, [1.08, 1.32]), and “Other-nationalist” children have two times greater risk of ARI compared to “Jordanian children.” The relative risk of diarrhea is lower among “Syrian nationalist” and “Other-nationalist” children compared to “Jordanian children.” Children belong “Other-nationalist” are found to be less relative risk of fever (RRR=0.9, [0.80, 1.01]) than “Jordanian children.”

Conclusions

Our study concludes that conflict-driven displacement has an immediate effect on child health through access, availability, and affordability of health care services, resulting in more significant health care risks. Coordinated and effective measures are needed to provide the best health care services among the displaced populations to prevent health risks.
Active ingredient ‘Better gut microbiome function’
Authors: Kadosh Kathrin Cohen , Basso Melissa , Knytl Paul , Johnstone Nicola , Lau Jennifer Y F , Gibson Glenn
Published: November 2020

Background

The human gut microbiome and its effect on brain function and mental health is emerging as an area of intensive research. Both animal and human research point towards adolescence as a sensitive period when the gut-brain axis is fine-tuned, and when we can use dietary intervention to change the microbiome, with long-lasting consequences for mental health. Here we report the results of a systematic review/meta-analysis of microbiota-targeted (psychobiotics) interventions on anxiety in youth, together with a summary of consultation work of youth with lived experience.

Methods

Seven databases were searched (no date cut-offs), and controlled trials in clinical and healthy human samples (age range: 10-24) seeking to reduce anxiety were included. All data on between group-differences post intervention and outcomes were extracted as standard mean differences (SMDs) and pooled together based on a random-effects model.

Findings

5416 studies were identified, 14 were eligible for the qualitative summary, of which 10 were included in the meta-analyses (total of 324 experimental and 293 control subjects). The heterogeneity I2 was12% and the pooled SMD was −0.04 (95% CI: −0.21, 0.14). One study presented with low bias risk whereas 5 with high and 4 with uncertain risk, accounting for that, sensitivities analysis revealed a SMD of −0.16 (95%CI: −0.39, 0.06).

Interpretation

There is currently limited evidence for use of psychobiotics to treat anxiety in youth. However, future progress will require a multidisciplinary research approach, which gives priority to specifying mechanisms in the human models, providing causal understanding and addressing the wider context.
Impact of public and private sector COVID-19 diagnostics and treatments on US healthcare resource utilization
Authors: Sheinson Daniel , Wong William , Solon Caroline , Cheng Mindy , Elsea David , Meng Yang , Shah Anuj
Published: November 2020

Introduction

Coronavirus disease 2019 (COVID-19) has imposed a considerable burden on the United States (US) health system, with particular concern over healthcare capacity constraints.

Methods

We modeled the impact of public and private sector contributions to developing diagnostic testing and treatments on COVID-19-related healthcare resource use.

Results

We estimated that public sector contributions lead to ≥30% reductions in COVID-19-related healthcare resource utilization. Private sector contributions to expanded diagnostic testing and treatments lead to further reductions in mortality (−44%), intensive care unit (ICU) and non-ICU hospital beds (−30% and −28%, respectively), and ventilator use (−29%). The combination of lower diagnostic test sensitivity and proportions of patients self-isolating may exacerbate case numbers, and policies that encourage self-isolating should be considered.

Conclusion

While mechanisms exist to facilitate research, development, and patient access to diagnostic testing, future policies should focus on ensuring equitable patient access to both diagnostic testing and treatments which, in turn, will alleviate COVID-19-related resource constraints.
Patterns of resistance to antibiotics of Enterococcus faecalis in clinical isolates of diabetic foot and presence of culture resistant to linezolid
Authors: Almeida Villegas Jorge Angel , García Fernández Luis Enrique , Estrada Carrillo Iris Mellolzy , Reyes Harold Mondragon , Sánchez Mariana Aguilar , Peña Silvia Patricia
Published: November 2020

Introduction

High levels of hyperglycemia lead to diabetes, the same levels that if not controlled increase the risk of diabetic neuropathy, which over time translates into loss of sensation and lesions that progress and lead to diabetic foot may occur, microorganisms Mainly Gram positive cocci and Gram negative bacilli, as well as yeasts are those that are mainly found in this metabolic and infectious pathology.

Methods

Diabetic foot wounds were studied in patients aged 45-54 years, with a mean age of 50 years, who had different periods of time with a hyperglycemia problem and different complications associated with diabetic foot, and were not considered as exclusion criteria. With a total of 41 cultures, 25 belong to male patients and 16 to female patients. All of these in the Toluca Valley, Mexico. The primary swab was reseeded in chromogenic agar, BHI, Salt and mannitol, calf blood, EMB and MacConkey, after 6 hours after taking the sample. In addition to microbial reseeding, a Gram stain was performed on each of the samples. The Petri dishes were placed in an incubation oven for 18 hours at 35 ° C with ± 2 ° C. Bacterial identification was performed on automated equipment from Beckman Coulter, as well as antibiotic sensitivity tests.

Results

35 positive cultures were obtained, of which they had a single microbial agent and some cases with two agents, which could be bacteria-bacteria or bacteria-yeast. With 14 positive strains for Enterococcus faecalis, with 100% sensitivity for cell wall inhibitors, and high resistance to tetracycline with 85.71% and 92.86% resistance to the macrolide erythromycin. In addition, there is a strain that was resistant to linezolid, and variable resistance patterns in fluoroquinolones and other antibiotics.
6-month aerobic walking training increases T1w/T2w signal in the white matter of healthy older adults
Authors: Colmenares Andrea Mendez , Voss Michelle W , Fanning Jason , Salerno Elizabeth A , Gothe Neha P , Thomas Michael L , McAuley Edward , Kramer Arthur F , Burzynska Agnieszka Z
Published: November 2020

White matter (WM) deterioration is an important mechanism of cognitive decline in healthy aging and dementia. Engaging in aerobic exercise to improve cardiorespiratory fitness (CRF) is considered one of the most promising ways to improve cognitive and brain health in aging. Yet, no randomized controlled trials have reported benefits of aerobic exercise interventions on WM microstructure measured with diffusion tensor imaging. Here, we studied the effects of a 6-month exercise intervention (clinical trial NCT01472744) on WM of 180 cognitively healthy older adults (60–79 years) using the ratio of calibrated T1-weighted image to T2-weighted images (T1w/T2w). Participants were randomized to one of four groups including a low intensity activity with complex cognitive demands (Dance), Walking, Walking + nutritional supplement or an active control. Results showed that a 6-month aerobic walking and dance intervention produced positive changes in the T1w/T2w with significant time-by-group interactions in the total WM, the genu and splenium of the corpus callosum, forceps minor, cingulum, relative to an active control condition. In contrast, we observed a decline in T1w/T2w in the majority of WM regions in the active control group. Lastly, a positive change in the T1w/T2w in the genu of the corpus callosum correlated with a positive change in episodic memory in the Walking but not in the control group; however, there were no associations between change in the T1w/T2w and change in CRF. Together, our findings suggest that the T1w/T2w may be a sensitive metric to detect short-term within-person changes in the WM and intervention-induced WM plasticity in the adult human brain.
Patterns of neurodegeneration in dementia reflect a global functional state space
Authors: Jones D. , Lowe V. , Graff-Radford J. , Botha H. , Wiepert D. , Murphy M.C. , Murray M. , Senjem M. , Gunter J. , Wiste H. , Boeve B. , Knopman D. , Petersen R. , Jack C.
Published: November 2020

Disruption of mental functions in Alzheimer’s disease (AD) and related disorders is accompanied by selective degeneration of brain regions for unknown reasons. These regions comprise large-scale ensembles of cells organized into networks required for mental functioning. A mechanistic framework does not exist to explain the relationship between clinical symptoms of dementia, patterns of neurodegeneration, and the functional connectome. The association between dementia symptoms and degenerative brain anatomy encodes a mapping between mental functions and neuroanatomy. We isolated this mapping through unsupervised decoding of neurodegeneration in humans. This reflected a simple information processing-based functional description of macroscale brain anatomy, the global functional state space (GFSS). We then linked the GFSS to AD physiology, functional networks, and mental abilities. We extended the GFSS framework to normal aging and seven degenerative diseases of mental functions.

One Sentence Summary

A global information processing framework for mental functions links neuroanatomy, cognitive neuroscience and clinical neurology.
Retrospective Analysis of Interventions to Epidemics using Dynamic Simulation of Population Behavior
Authors: Osborn Jenna , Berman Shayna , Bender-Bier Sara , D’Souza Gavin , Myers Matthew
Published: November 2020

Retrospective analyses of interventions to epidemics, in which the effectiveness of strategies implemented are compared to hypothetical alternatives, are valuable for performing the cost-benefit calculations necessary to optimize infection countermeasures. SIR (susceptible-infected-removed) models are useful in this regard but are limited by the challenge of deciding how and when to update the numerous parameters as the epidemic changes in response to population behaviors. Behaviors of particular interest include facemasks adoption (at various levels) and social distancing. We present a method that uses a “dynamic spread function” to systematically capture the continuous variation in the population behavior, and the gradual change in infection evolution, resulting from interventions. No parameter updates are made by the user. We use the tool to quantify the reduction in infection rate realizable from the population of New York City adopting different facemask strategies during COVID-19. Assuming a baseline facemask of 67% filtration efficiency, calculations show that increasing the efficiency to 80% could have reduced the roughly 5000 new infections per day occurring at the peak of the epidemic to around 4000. Population behavior that may not be varied as part of the retrospective analysis, such as social distancing in a facemask analysis, are automatically captured as part of the calibration of the dynamic spread function.
Can we predict the severe course of COVID-19 – a systematic review and meta-analysis of indicators of clinical outcome?
Authors: Katzenschlager Stephan , Zimmer Alexandra J. , Gottschalk Claudius , Grafeneder Juergen , Seitel Alexander , Maier-Hein Lena , Benedetti Andrea , Larmann Jan , Weigand Markus A. , McGrath Sean , Denkinger Claudia M.
Published: November 2020

Background

COVID-19 has been reported in over 40million people globally with variable clinical outcomes. In this systematic review and meta-analysis, we assessed demographic, laboratory and clinical indicators as predictors for severe courses of COVID-19.

Methods

We systematically searched multiple databases (PubMed, Web of Science Core Collection, MedRvix and bioRvix) for publications from December 2019 to May 31st2020. Random-effects meta-analyses were used to calculate pooled odds ratios and differences of medians between (1) patients admitted to ICU versus non-ICU patients and (2) patients who died versus those who survived. We adapted an existing Cochrane risk-of-bias assessment tool for outcome studies.

Results

Of 6,702 unique citations, we included 88 articles with 69,762 patients. There was concern for bias across all articles included. Age was strongly associated with mortality with a difference of medians (DoM) of 13.15 years (95% confidence interval (CI) 11.37 to 14.94) between those who died and those who survived. We found a clinically relevant difference between non-survivors and survivors for C-reactive protein (CRP; DoM 69.10, CI 50.43 to 87.77), lactate dehydrogenase (LDH; DoM 189.49, CI 155.00 to 223.98), cardiac troponin I (cTnI; DoM 21.88, CI 9.78 to 33.99) and D-Dimer (DoM 1.29mg/L, CI 0.9 - 1.69). Furthermore, cerebrovascular disease was the co-morbidity most strongly associated with mortality (Odds Ratio 3.45, CI 2.42 to 4.91) and ICU admission (Odds Ratio 5.88, CI 2.35 to 14.73).

Discussion

This comprehensive meta-analysis found age, cerebrovascular disease, CRP, LDH and cTnI to be the most important risk-factors in predicting severe COVID-19 outcomes and will inform decision analytical tools to support clinical decision-making.

In this systematic review we meta-analyzed 88 articles for risk factors of ICU admission and mortality in COVID-19. We found age, cerebrovascular disease, CRP, LDH and cTnI are the most important risk-factors for ICU admission or mortality.
Corticosteroids are associated with increased survival in elderly presenting severe SARS-Cov2 infection
Authors: Laure Gallay , Viet-Thi Tran , Elodie Perrodeau , Nicolas Vignier , Matthieu Mahevas , Francesca Bisio , Emmanuel Forestier , Francois-Xavier Lescure
Published: November 2020

Objective

To assess the effectiveness of corticosteroids among elderly patients with COVID-19 pneumonia requiring oxygen.

Design

Comparative observational study based on routine care data. Baseline characteristics of patients were balanced using propensity-score inverse probability of treatment weighting.

Setting

Geriatric and infectious diseases wards from 36 hospitals in France and Luxembourg.

Participants

Adults > 80 years old PCR confirmed SARS-CoV-2 infection or typical CT-scan images, requiring oxygen ≥ 3L/min and with an inflammatory syndrome (C-reactive protein ≥ 40mg/L).

Measurements

The primary outcome was overall survival at day 14. The secondary outcome was the proportion of patients discharged from hospital to home/rehabilitation on day 14. Adverse events were abstracted from electronic health records.

Results

Among the 267 patients included in the analysis, 96 were assigned to the treatment group. Median age was 86, interquartile range 83 to 90 and 95% had a SARS-CoV-2 PCR-confirmed diagnosis. Use of corticosteroids was significantly associated with an increased survival (weighted hazard ratio [wHR] 0.66, 95% CI 0.44 to 0.97). There was no significant difference between the treatment and control groups regarding the proportion of patients discharged to home/rehabilitation at day 14 (wRR 1.11, 95% CI 0.68 to 1.81). Twenty-two (16.7%) patients receiving corticosteroids developed adverse events while only 11 (6.4%) from the control group did.

Conclusions

Corticosteroids were associated with a significant increase the day-14 overall survival of patients over 80 years old hospitalized for severe COVID-19.

Impact statement

We certify that this work is novel. As of today, studies on the efficacy of corticosteroids did not specifically target elderly patients.

Among older patients aged over 80 years old, the RECOVERY trial found no difference in the survival of patients treated or not with dexamethasone. However, the heterogeneity in the severity of infection within the latter subgroup limited the drawing of strong conclusions
Metabolomic/lipidomic profiling of COVID-19 and individual response to tocilizumab
Authors: Meoni Gaia , Ghini Veronica , Maggi Laura , Vignoli Alessia , Mazzoni Alessio , Salvati Lorenzo , Capone Manuela , Vanni Anna , Tenori Leonardo , Fontanari Paolo , Lavorini Federico , Peris Adriano , Bartoloni Alessandro , Liotta Francesco , Cosmi Lorenzo , Luchinat Claudio , Annunziato Francesco , Turano Paola
Published: November 2020

The current pandemic emergence of novel coronavirus disease (COVID-19) poses a relevant threat to global health. SARS-CoV-2 infection is characterized by a wide range of clinical manifestations, ranging from absence of symptoms to severe forms that need intensive care treatment. Here, plasma-EDTA samples of 30 patients compared with age- and sex-matched controls were analyzed via untargeted nuclear magnetic resonance (NMR)-based metabolomics and lipidomics. With the same approach, the effect of tocilizumab administration was evaluated in a subset of patients. Despite the heterogeneity of the clinical symptoms, COVID-19 patients are characterized by common plasma metabolomic and lipidomic signatures (91.7% and 87.5% accuracy, respectively, when compared to controls). Tocilizumab treatment resulted in at least partial reversion of the metabolic alterations due to SARS-CoV-2 infection. In conclusion, NMR-based metabolomic and lipidomic profiling provides novel insights into the pathophysiological mechanism of human response to SARS-CoV-2 infection and to monitor treatment outcomes.

Author summary

The current COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is markedly affecting the world population. Here we report about the small-molecule profile of patients hospitalized during the first wave of the COVID-19 pandemic. Using magnetic resonance spectroscopy, we showed that the infection induces profound changes in the metabolome. The analysis of the specific metabolite changes and correlations with clinical data enabled the identification of potential biochemical determinants of the disease fingerprint. We also followed how metabolic alterations revert towards those of the control group upon treatment with tocilizumab, a recombinant humanised monoclonal antibody against the interleukin-6 receptor. These results open up possibilities for the monitoring of novel patients and their individual response to treatment.
Comparison of SARS-COV-2 nasal antigen test to nasopharyngeal RT-PCR in mildly symptomatic patients
Authors: Abdulrahman Abdulkarim , Mustafa Fathi , AlAwadhi Abdulla I , Alansari Qadar , AlAlawi Batool , AlQahtani Manaf
Published: November 2020

Introduction

COVID 19 has been vastly spreading since December 2019 and the medical teams worldwide are doing their best to limit its spread. In the absence of a vaccine the best way to fight it is by detecting infected cases early and isolate them to prevent its spread. Therefore, a readily available, rapid, and cost-effective test with high specificity and sensitivity for early detection of COVID 19 is required. In this study, we are testing the diagnostic performance of a rapid antigen detection test in mildly symptomatic cases. (RADT).

Methods

The study included 4183 patients who were mildly symptomatic. A nasal sample for the rapid antigen test and a nasopharyngeal sample was taken from each patient. Statistical analysis was conducted to calculate the sensitivity, specificity, positive predictive value, negative predictive value and kappa coefficient of agreement.

Results

The prevalence of COVID 19 in the study population was 17.5% (733/4183). The calculated sensitivity and specificity were 82.1% and 99.1% respectively. Kappa’s coefficient of agreement between the rapid antigen test and RT-PCR was 0.859 (p < 0.001). A stratified analysis was performed and it showed that the sensitivity of the test improved significantly with lowering the cutoff Ct value to 24.

Conclusion

The results of the diagnostic assessment of nasal swabs in the RADT used in our study are promising regarding the potential benefit of using them as a screening tool in mildly symptomatic patients. The diagnostic ability was especially high in cases with high viral load. The rapid antigen test is intended to be used alongside RT-PCR and not replace it. RADT can be of benefit in reducing the use of PCR.
The genetic risk for COVID-19 severity is associated with defective innate immune responses
Authors: Kuijpers Yunus , Chu Xiaojing , Jaeger Martin , Moorlag Simone J.C.F.M. , Koeken Valerie A.C.M. , Zhang Bowen , de Nooijer Aline , Grondman Inge , Janssen Nico , Mourits Vera P. , J. de Bree L. Charlotte , de Mast Quirijn , van de Veerdonk Frank L. , Joosten Leo A.B. , Li Yang , Netea Mihai G. , Xu Cheng-Jian
Published: November 2020

Recent genome-wide association studies (GWASs) of COVID-19 patients of European ancestry have identified genetic loci significantly associated with disease severity (1). Here, we employed the detailed clinical, immunological and multi-omics dataset of the Human Functional Genomics Projects (HFGP) to explore the physiological significance of the host genetic variants that influence susceptibility to severe COVID-19. A genomics investigation intersected with functional characterization of individuals with high genetic risk for severe COVID-19 susceptibility identified several major patterns: i. a large impact of genetically determined innate immune responses in COVID-19, with increased susceptibility for severe disease in individuals with defective monocyte-derived cytokine production; ii. genetic susceptibility related to ABO blood groups is probably mediated through the von Willebrand factor (VWF) and endothelial dysfunction. We further validated these identified associations at transcript and protein levels by using independent disease cohorts. These insights allow a physiological understanding of genetic susceptibility to severe COVID-19, and indicate pathways that could be targeted for prevention and therapy.

One Sentence summary

In this study, we explore the physiological significance of the genetic variants associated with COVID-19 severity using detailed clinical, immunological and multi-omics data from large cohorts. Our findings allow a physiological understanding of genetic susceptibility to severe COVID-19, and indicate pathways that could be targeted for prevention and therapy.
Health spending and vaccination coverage in low-income countries
Authors: Castillo-Zunino Francisco , Keskinocak Pinar , Nazzal Dima , Freeman Matthew C
Published: November 2020

Background

Routine childhood immunization is a cost-effective way to save lives and protect people from disease. Some low-income countries (LIC) have achieved remarkable success in childhood immunization, despite lower levels of gross national income or health spending compared to other countries. We investigated the impact of financing and health spending on vaccination coverage across LIC and lower-middle income countries (LMIC).

Methods

Among LIC, we identified countries with high-performing vaccination coverage (LIC+) and compared their economic and health spending trends with other LIC (LIC-) and LMIC. We used cross-country multi-year linear regressions with mixed-effects to test financial indicators over time. We conducted three different statistical tests to verify if financial trends of LIC+ were significantly different from LIC- and LMIC; p-values were calculated with an asymptotic χ2 test, a Kenward-Roger approximation for F tests, and a parametric bootstrap method.

Findings

During 2014–18, LIC+ had a mean vaccination coverage between 91–96% in routine vaccines, outperforming LIC- (67–80%) and LMIC (83–89%). During 2000–18, gross national income and development assistance for health (DAH) per capita were not significantly different between LIC+ and LIC- (p > 0·13, p > 0·65) while LIC+ had a significant lower total health spending per capita than LIC- (p < 0·0001). Government health spending per capita per year increased by US$0·42 for LIC+ and decreased by US$0·24 for LIC- (p < 0·0001). LIC+ had a significantly lower private health spending per capita than LIC- (p < 0·012).

Interpretation

LIC+ had a difference in vaccination coverage compared to LIC- and LMIC that could not be explained by economic development, total health spending, nor aggregated DAH. The vaccination coverage success of LIC+ was associated with higher government health spending and lower private health spending, with the support of DAH on vaccines.
Poor odor identification predicts mortality risk in older adults without neurodegenerative diseases: the Shanghai Aging Study
Authors: Xiao Zhenxu , Zhao Qianhua , Liang Xiaoniu , Wu Wanqing , Cao Yang , Ding Ding
Published: November 2020

Background

Irrespective of neurodegeneration, the decline of olfactory function might also reflect a wider range of pathological conditions contributing to mortality. However, the potential explanations and their predictive values have rarely been reported.

Methods

A total of 1,433 older adults aged ≥ 60 years without neurodegenerative disease were administered a follow-up of 8.6 years on average. Sniffin’ Sticks Screening Test was used to assess the olfactory identification at baseline. Survival status during the follow-up was obtained from the local Center for Disease Control and Prevention. Bidirectional stepwise Cox proportional hazards regression was used to identify variables associated with mortality. Two predictive models were constructed by statistical learning methods.

Results

All-cause mortality rate was 1.1/100 person-years during the follow-up. Sex (HR = 0.65, 95%CI 0.46 - 0.93), age (HR = 1.12, 95%CI 1.10 - 1.15), chronic kidney disease (HR = 1.88, 95%CI 1.09 - 3.25), low density lipoprotein (HR = 0.81, 95%CI 0.67 - 0.99), anemia (HR = 2.74, 95%CI 1.19 - 6.30), and fail to identify coffee odor (HR = 1.96, 95%CI 1.19 - 3.23) were significantly associated with all-cause mortality. The logistic regression and the random forest predictive models showed similar predictive accuracy (0.91 and 0.90) and area under the receiver operating characteristic curve (0.77 and 0.75).

Conclusions

The association between poor olfactory and long-term mortality was verified among Chinese older population. Certain odors identification ability may contribute to the prediction of long-term mortality along with other important risk factors.
Impact of the COVID-19 nonpharmaceutical interventions on influenza and other respiratory viral infections in New Zealand
Authors: Huang Q. Sue , Wood Tim , Jelley Lauren , Jennings Tineke , Jefferies Sarah , Daniells Karen , Nesdale Annette , Dowell Tony , Turner Nikki , Campbell-Stokes Priscilla , Balm Michelle , Dobinson Hazel C , Grant Cameron C. , James Shelley , Aminisani Nayyereh , Ralston Jacqui , Gunn Wendy , Bocacao Judy , Danielewicz Jessica , Moncrieff Tessa , McNeill Andrea , Lopez Liza , Waite Ben , Kiedrzynski Tomasz , Schrader Hannah , Gray Rebekah , Cook Kayla , Currin Danielle , Engelbrecht Chaune , Tapurau Whitney , Emmerton Leigh , Martin Maxine , Baker Michael G. , Taylor Susan , Trenholme Adrian , Wong Conroy , Lawrence Shirley , McArthur Colin , Stanley Alicia , Roberts Sally , Ranama Fahimeh , Bennett Jenny , Mansell Chris , Dilcher Meik , Werno Anja , Grant Jennifer , van der Linden Antje , Youngblood Ben , Thomas Paul G. , Webby Richard J.
Published: November 2020

Stringent nonpharmaceutical interventions (NPIs) such as lockdowns and border closures are not currently recommended for pandemic influenza control. New Zealand used these NPIs to eliminate coronavirus disease 2019 during its first wave. Using multiple surveillance systems, we observed a parallel and unprecedented reduction of influenza and other respiratory viral infections in 2020. This finding supports the use of these NPIs for controlling pandemic influenza and other severe respiratory viral threats.
Early medical abortion using telemedicine – acceptability to patients
Authors: Erlank Chelsey Porter , Lord Jonathan , Church Kathryn
Published: November 2020

Introduction

The English government approved both stages of early medical abortion (EMA) for at-home use on 30th March 2020. MSI Reproductive Choices UK (MSUK), one of the largest service providers of abortion services in England, launched a telemedicine EMA pathway on 6th April 2020.

Methods

A sample of all MSUK’s telemedicine EMA patients between April and August 2020 were invited to opt in to a follow-up call to answer clinical and satisfaction questions. 1,243 (13.7% of all telemedicine EMAs) were successfully followed-up, on average within five days post-procedure. Responses were analysed quantitatively and descriptively. The sample was compared to the total telemedicine EMA population on nine sets of background characteristics to check sample validity, and all results were tested across the same nine characteristics for variation.

Results

Patients reported high confidence in telemedicine EMA and high satisfaction with the convenience, privacy and ease of managing their abortion at home. No patient reported that they were unable to consult privately. Over 80% of patients reported preferring the telemedicine pathway, and two-thirds that they would choose telemedicine again if COVID-19 were no longer an issue.

Discussion

Telemedicine EMA is a valued, private, convenient and easier option that is highly acceptable for patients seeking an abortion, especially those for whom in-clinic visits are logistically or emotionally challenging. Evidence that this pathway would be a first choice again in future for most patients supports the case to make access to telemedicine EMA permanent.

Key message points

On 30th March 2020, the English government approved both stages of early medical abortion (EMA) for at-home use, paving the way for telemedicine EMA provision.

MSUK patients receiving routine follow-up calls reported high confidence in telemedicine EMA and high satisfaction with the privacy, convenience and ease of this pathway.

Two-thirds of telemedicine EMA patients reported they would choose this pathway again in future, demonstrating that it should remain available after the COVID-19 pandemic.
Secondary Household Covid-19 Transmission Modelling of Students Returning Home from University
Authors: Harper Paul R. , Moore Joshua W. , Woolley Thomas E.
Published: November 2020

We estimate the number of secondary Covid-19 infections caused by potentially infectious students returning from university to private homes with other occupants. Using a Monte-Carlo method and data derived from UK sources, we predict that an infectious student would, on average, infect 0.94 other household members. Or, as a rule of thumb, each infected student would generate (just less than) one secondary within-household infection. The total number of secondary cases for all returning students is dependent on the virus prevalence within the student population at the time of their departure from campus back home. Correspondingly, we provide results for prevalence ranging from 0.5% to 15%, which is based on observed minimum and maximum estimates from Cardiff University’s asymptomatic testing service. Although the proposed estimation method is general and robust, the results are sensitive to the input data. We therefore provide Matlab code and a helpful online app (http://bit.ly/Secondary_infections_app) that can be used to estimate numbers of secondary infections based on local parameter values.