title: Estimates of global SARS-CoV-2 infection exposure, infection morbidity, and infection mortality rates

abstract: We aimed to estimate, albeit crudely and provisionally, national, regional, and global proportions of respective populations that have been infected with SARS-CoV-2, and to assess infection morbidity and mortality rates, factoring both documented and undocumented infections. The estimates were generated by applying mathematical models to 159 countries and territories. The percentage of the worlds population that has been infected as of 31 December 2020 was estimated at 12.56% (95% CI: 11.17-14.05%). It was lowest in the Western Pacific Region at 0.66% (95% CI: 0.59-0.75%) and highest in the Americas at 41.92% (95% CI: 37.95-46.09%). The global infection fatality rate was 10.73 (95% CI: 10.21-11.29) per 10,000 infections. Globally per 1,000 infections, the infection acute-care bed hospitalization rate was 19.22 (95% CI: 18.73-19.51), the infection ICU bed hospitalization rate was 4.14 (95% CI: 4.10-4.18), the infection severity rate was 6.27 (95% CI: 6.18-6.37), and the infection criticality rate was 2.26 (95% CI: 2.24-2.28). If left unchecked with no interventions, the pandemic would eventually cause 8.18 million (95% CI: 7.30-9.18) deaths, 163.67 million (95% CI: 148.12-179.51) acute-care hospitalizations, 33.01 million (95% CI: 30.52-35.70) ICU hospitalizations, 50.23 million (95% CI: 46.24-54.67) severe cases, and 17.62 million (95% CI: 16.36-18.97) critical cases. The global population remains far below the herd immunity threshold and at risk of repeated waves of infection. Global epidemiology reveals immense regional variation in infection exposure and morbidity and mortality rates.


title: Listening to Bluetooth Beacons for Epidemic Risk Mitigation

abstract: During the ongoing COVID-19 pandemic, there have been burgeoning efforts to develop and deploy digital contact tracing systems to expedite contact tracing and risk notification. Unfortunately, the success of these systems has been limited, partly owing to poor interoperability with manual contact tracing, low adoption rates, and a societally sensitive trade-off between utility and privacy. In this work, we introduce a new privacy-preserving and inclusive system for epidemic risk assessment and notification that aims to address the above limitations. Rather than capturing pairwise encounters between user devices as done by existing systems, our system captures encounters between user devices and beacons placed in strategic locations where infection clusters may originate. Epidemiological simulations using an agent-based model demonstrate several beneficial properties of our system. By achieving bidirectional interoperability with manual contact tracing, our system may help reduce the effective reproduction number already at adoption levels of 10%. The use of location and environmental information provided by beacons allows our system to achieve significantly higher sensitivity and specificity than existing systems and thus may improve the efficacy of contact tracing under limited isolation and testing resources. Moreover, to achieve high utility, it is sufficient to deploy beacons in a small fraction of strategic locations. Finally, our simulations also show that existing systems could inherit these beneficial properties if they integrated the beacons used by our system.

category: epidemiology


title: Hepatitis E virus seroprevalence and associated risk factors in high-risk groups: A cross-sectional study from Turkey

abstract:
BackgroundThe renal transplant recipients (RT), allogeneic hematopoietic stem cell transplant recipients (allo-HSCT), patients with acute hepatitis (AH), and chronic hepatitis C patients (CHC) are at risk of hepatitis E virus (HEV) infection. However, seroepidemiology, risk factors to HEV exposure, and the prevalence of HEV viremia has not yet been investigated among these patients in Turkey.

Materials&MethodsIn this cross-sectional study, 292 consecutive serum samples were tested for HEV immunoglobulin IgG/IgM and HEV RNA using commercial ELISA and in-house nested PCR with Sanger sequencing, respectively. Sociodemographic, clinical, laboratory data, and risk factors were collected using a questionnaire and hospital database. Multiple logistic regression analysis was employed to identify independent predictors for anti-HEV seropositivity.

ResultsAmong all patients (n=292) tested for HEV RNA reactivity, only 2 patients (one RT recipient and one patient with AH) were identified as having HEV3 viremia. HEV viremia rate was 0.6% in whole group. These patients had shown no signs of chronic HEV infection for 6 months and was found to spontaneously seroconverted 6 months after enrollment. Anti-HEV IgG was positive in 29 patients yielding an HEV seroprevalence of 9.9%. Older age (aOR:1.03, 95% CI, 1.00-1.06; p:0.022) and eating undercooked meat (aOR:3.11, 95% CI, 1.08-8.92; p:0.034) were independent risk factors to anti-HEV seropositivity in all patients. Similarly, multiple logistic regression analysis demonstrated that age (aOR:1.03, 95% CI, 0.99-1.07, p:0.058) and eating undercooked meat (aOR:5.77, 95% CI, 1.49-22.25, p:0.011) were independent risk factors for anti-HEV IgG positivity in the non-immunosuppressive subgroup consisting of AH and CHC patients.

ConclusionThe HEV seroprevalence rate was high (9.9%), despite low viremia rate (0.6%) in high-risk patients. The emergence of HEV3 might indicate a serious problem for these patients. Future investigations are needed to elucidate foodborne transmission routes of HEV in Turkey.

category: gastroenterology


title: Association of patients' past misdiagnosis experiences with trust in their current physician: the TRUMP2-Net study

abstract:
BackgroundPrevious qualitative research has described that past misdiagnosis experiences may reduce patients own and their families trust in healthcare.

ObjectiveTo quantify the associations between patients or family members misdiagnosis experiences and the formers trust in their current physicians.

DesignA cross-sectional online survey.

ParticipantsAdult Japanese people with non-communicable diseases (cancer, diabetes, depression, heart disease, and connective tissue disease), recruited using a web-based panel survey.

Main MeasuresThe misdiagnosis experiences of patients and their family members were measured as exposures. The formers trust in their current physicians was measured using the Japanese version of the 11-item Trust in Physicians Scale modified by Thom, which was translated and validated by us for this study.

Key ResultsA total of 661 patients with a mean age of 62.7 years were analyzed. Overall, 23.2% had a history of misdiagnosis and 20.4% had a family member who had been misdiagnosed. The internal consistency (Cronbachs ) was 0.91. The factor analysis suggested unidimensionality with all 11 loadings being higher than 0.40. In a multivariable-adjusted general linear model, patients and family members misdiagnosis experiences were associated with lower confidence in their current physicians (mean difference -4.30, 95%CI -8.12 to -0.49 and -3.20, 95%CI -6.34 to -0.05, respectively). An additive effect was suggested for the associations of patients and familys experience of misdiagnosis on trust (P for interaction = 0.494).

ConclusionsThe individuals and family members misdiagnosis experiences were associated with reduced trust in their current physicians. Interventions specifically targeting misdiagnosed patients are needed to restore patients confidence in their current physicians.

category: primary care research


title: Phenotype Risk Scores: moving beyond cases and controls to classify psychiatric disease in hospital-based biobanks.

abstract:
Current phenotype classifiers for large biobanks with coupled electronic health records EHR and multi-omic data rely on ICD-10 codes for definition. However, ICD-10 codes are primarily designed for billing purposes, and may be insufficient for research. Nuanced phenotypes composed of a patients experience in the EHR will allow us to create precision psychiatry to predict disease risk, severity, and trajectories in EHR and clinical populations. Here, we create a phenotype risk score (PheRS) for major depressive disorder (MDD) using 2,086 cases and 31,000 individuals from Mount Sinais biobank BioMe . Rather than classifying individuals as  cases and  controls, PheRS provide a whole-phenome estimate of each individuals likelihood of having a given complex trait. These quantitative scores substantially increase power in EHR analyses and may identify individuals with likely  missing diagnoses (for example, those with large numbers of comorbid diagnoses and risk factors, but who lack explicit MDD diagnoses).

Our approach applied ten-fold cross validation and elastic net regression to select comorbid ICD-10 codes for inclusion in our PheRS. We identified 158 ICD-10 codes significantly associated with Moderate MDD (F33.1). Phenotype Risk Score were significantly higher among individuals with ICD-10 MDD diagnoses compared to the rest of the population (Kolgorov-Smirnov p<2.2e-16), and were significantly correlated with MDD polygenic risk scores (R2>0.182). Accurate classifiers are imperative for identification of genetic associations with psychiatric disease; therefore, moving forward research should focus on algorithms that can better encompass a patients phenome.

category: psychiatry and clinical psychology


title: Description of a community paediatric strategy offering a package of services to prevent malnutrition among children in one health district in Mali

abstract:
BackgroundWe present results from an intervention case study, the Soins Preventifs de lEnfant (SPE) project, in Konseguela health area, Mali. The intervention involved a network of community health workers providing a comprehensive preventive/therapeutic package, ultimately aiming at reducing under 24-month mortality. Associated costs were documented to assess the feasibility of replication and scale-up.

MethodsSPE program monitoring data were obtained from booklets specific to the program between 2010 and 2014. Data included sex, age, vaccination status, anthropometric measurements, Ready-To-Use-Supplementary Food distribution, morbidities reported by the mother between visits, hospitalizations over 18 months of follow-up. Cross-sectional surveys in the district of Koutiala, of which Konseguela is one health area, were conducted yearly between 2010 and 2014 for comparison, using difference-in-difference approach. Ethical approval was granted from the Malian Ethical Committee.

ResultsGlobal and Severe Acute Malnutrition prevalences decreased over time in Konseguela as well as in the rest of the district, but the difference between areas was not significant. Children reaching 24 months were 20% less stunted in Konseguela than children the same age outside (p<0.001). Mortality rates significantly decreased more in Konseguela, while vaccination coverage for all antigens significantly increased in the meantime. The package cost approximately USD 95 per child per year; 56% of which was for the RUSF.

ConclusionThe results of this case study suggest a sustained impact of a community based, comprehensive health package on major child health indicators. Most notably, while improvements in acute malnutrition were found in the district as a whole, those in the intervention area were more pronounced. Trends for other indicators suggest additional benefits.

category: public and global health


title: Trends, regional variation, and clinical characteristics of COVID-19 vaccine recipients: a retrospective cohort study in 23.4 million patients using OpenSAFELY.

abstract:
BackgroundOn December 8th 2020, NHS England administered the first COVID-19 vaccination as part of an ambitious vaccination programme during a global health emergency.

AimsTo describe trends and variation in vaccine coverage by key clinical and demographic groups; to create a framework for near-real-time monitoring of vaccine coverage in key subgroups.

MethodsWorking on behalf of NHS England we analysed 57.9 million patient records in situ and in near-real-time within the infrastructure of the Electronic Health Record (EHR) software vendors EMIS and TPP using OpenSAFELY. We describe vaccine coverage and time trends across a range of demographic and fine-grained clinical subgroups in eight Joint Committee on Vaccination and Immunisation (JCVI) priority cohorts.

Results20,852,692 patients (36%) received a COVID-19 vaccine between December 8th 2020 and March 17th 2021. Of patients aged [≥]80 not in a care home (JCVI group 2) 94.7% received a vaccine, but with substantial variation by ethnicity (White 96.2% vaccinated, Black 68.3%) and deprivation (least deprived 96.6%, most deprived 90.7%). Overall, patients with pre-existing medical conditions were equally or more likely to be vaccinated with two exceptions: severe mental illness (89.5% vaccinated) and learning disability (91.4%). 275,205 vaccine recipients were identified as care home residents (priority group 1; 91.2% coverage). 1,257,914 (6.0%) recipients have had a second dose. Detailed characteristics of recipients in all cohorts are reported.

ConclusionsThe NHS in England has rapidly delivered mass vaccination. We were able to deploy a data monitoring framework using publicly auditable methods and a secure, in-situ processing model, using linked but pseudonymised patient-level NHS data on 57.9 million patients with very short delays from vaccine administration to completed analysis. Targeted activity may be needed to address lower vaccination coverage observed among certain key groups: ethnic minorities, those living in deprived areas, and people with severe mental illness or learning disabilities.


title: Trends and clinical characteristics of COVID-19 vaccine recipients: a federated analysis of 57.9 million patients primary care records in situ using OpenSAFELY.


title: Factors influencing nursing students' intention to accept COVID-19 vaccination - A pooled analysis of seven countries

abstract:
Experiencing the second wave of COVID-19 pandemic, high vaccination coverage by a safe and effective vaccine globally would be a great achievement. Acceptance of vaccination by healthcare students is an important issue as they have a key role as future professionals in educating patients, informing and guiding them to the right clinical decision. The aim of this study was to explore the intention of nursing students to get vaccinated for SARS-CoV-2 infection and the factors acting either as motivators or barriers towards vaccination. A multicenter cross-sectional study was conducted in 7 countries (Greece, Albania, Cyprus, Spain, Italy, Czech Republic and Kosovo) through a web survey. In total 2249 undergraduate nursing students participated. Forty three point eight percent of students agreed to accept a safe and effective COVID-19 vaccine, while the acceptance was higher among Italian students. The factors for intention to get vaccinated were male gender (p=0.008), no working experience in healthcare facilities during the pandemic (p=0.001), vaccination for influenza in 2019 and 2020 (p<0.001), trust in doctors (p<0.001), governments and experts (p=0.012), high level of knowledge (p<0.001) and fear of COVID-19 (p<0.001). Understanding of factors that influence students decision to accept COVID-19 vaccination could increase the acceptance rate contributing to a management of the pandemic.

HighlightsO_LILess than half of the sample intended to accept COVID-19 vaccination
C_LIO_LIFactors that influenced nursing students to get vaccinated against COVID-19 were male gender, no working experience in healthcare facilities during the pandemic, vaccination for influenza in 2019 and 2020, trust in doctors, governments and experts, high level of knowledge and fear of COVID-19.
C_LI


title: Dynamic balance recovery in chronic Acquired Brain Injury participants following a perturbation training.

abstract:
BackgroundAcquired Brain Injury (ABI) is defined as a damage to the brain that occurs after birth. Subjects post-ABI suffer from dynamic balance impairments that persist years after the injury.

ObjectiveTo explore the effect of a perturbation method which is consisted of unexpected balance perturbations using Re-Step technology on the recovery of dynamic balance and gait velocity in chronic ABI participants.

MethodsIn a clinical trial, 35 chronic ABI participants (stroke and traumatic brain injury) participated in 22 sessions of perturbation-training, twice a week for 3 months. Dynamic balance was assessed pre and post-training using Community Balance and Mobility Scale (CB&M). Gait velocity was also assessed in the stroke participants using the 10-meter walk test (10MWT).

ResultsDynamic balance improved significantly post-training (p=0.001). This improvement was greater than the improvement that was observed in a sub-group that was tested twice before training (p=0.04). 16 participants (45.7%) out of 35 met or exceeded minimal detectable change (MDC) of the CB&M Scale. Self-paced velocity also improved significantly (p=0.02) but only 2 participants (9.5%) out of 21 exceeded the MDC of 10MWT post-stroke.

ConclusionsUnexpected balance perturbation-training using Re-Step technology led to an improvement in dynamic balance and gait velocity in chronic ABI participants. The advantage of Re-Step technology training compared to conventional balance training should be further examined.

category: rehabilitation medicine and physical therapy


title: Genome-wide meta-analysis of pneumonia suggests a role for mucin biology and provides novel drug repurposing opportunities

abstract: Pneumonia remains one of the leading causes of death worldwide, particularly amongst the elderly and young children. We performed a genome-wide meta-analysis of lifetime pneumonia diagnosis (N=266,277), that encompassed the largest collection of cases published to date. Genome-wide significant associations with pneumonia were uncovered for the first time beyond the major histocompatibility complex region, with three novel loci, including a signal fine-mapped to a cluster of mucin genes. Moreover, we demonstrated evidence of a polygenic effect of common and low frequency pneumonia associated variation impacting several other mucin genes and O-glycosylation, further suggesting a role for these processes in pneumonia pathophysiology. The pneumonia GWAS was then leveraged to identify drug repurposing opportunities, including evidence that supports the use of lipid modifying agents in the prevention and treatment of the disorder. We also propose how polygenic risk could be utilised for precision drug repurposing through pneumonia risk scores constructed using variants mapped to pathways with known drug targets. In summary, we provide novel insights into the genetic architecture of pneumonia susceptibility, with future study warranted to functionally interrogate novel association signals and evaluate the suitability of the compounds prioritised by this study as repositioning candidates.

category: respiratory medicine


title: Effects of stricter management guidelines on return-to-play timeframes following concussion in professional Australian Rules football

abstract:
BackgroundManagement of concussion remains a serious issue for professional sports, particularly with the growing knowledge on the consequences of repetitive concussion. One primary concern is the subjective assessment of recovery that dictates the time until a concussed athlete is returned to competition. In response to this concern, the Australian Football League (AFL) changed its policy in 2020 such that clearance for return-to-play was extended from one day, to a minimum of five days, prior to the next scheduled match.

ObjectiveWe sought to examine the impact of the AFL policy change by asking whether the time to return-to-play after concussion was increased in the 2020 season relative to previous years.

MethodsRetrospective data on injury and return-to-play were sourced from publicly available tables published on the AFL website. We compared the number of matches missed and the number of days missed in concussed players across 2017 to 2020 inclusive.

ResultsAnalysis of data from 166 concussed players revealed no increase in the number of matches missed in 2020 relative to previous years as would have been expected from an extend recovery protocol. Considering the number of days missed in 2020 relative to 2017-19 we found, paradoxically, that there was an overall reduction in the average time to return-to-play in 2020 (11.2 vs 16.2 days).

ConclusionThis study demonstrates that any policy change around concussion management requires ongoing auditing to ensure clearance meets policy objectives and highlights the need for objective measures for return-to-play after concussion.

category: sports medicine


title: The Forgotten Tract of Vision in Multiple Sclerosis: Vertical Occipital Fasciculus, Its Integrity, and Visuospatial Memory

abstract:
BackgroundVisual disturbances are a common disease manifestation and a major patient complaint in Multiple Sclerosis (MS) due to lesions damaging white matter tracts involved in vision. Vertical Occipital Fasciculus (VOF) connects ventral and dorsal visual streams and was neglected for more than a century. It has recently become under focus in brain-related disorders. Thus, its role in the visual dysfunction in MS needs to be clarified.

ObjectiveEvaluate the integrity of bilateral VOFs in MS and its association with clinical and visual evaluations.

Methods56 relapsing-remitting MS (RRMS) and 25 healthy controls (HC) were recruited. We acquired MS Functional Composite, Expanded Disability Status Scale (EDSS), and Brief Visuospatial Memory Test - Revised (BVMT-R), and structural and diffusion MRI scans. After VOF tractography, its integrity markers were statistically tested for between-group differences and clinical and visual tests associations.

ResultsRRMS patients had lower fiber integrity in bilateral VOFs compared to HC. Lower integrity of bilateral VOFs was associated with poor clinical outcomes, higher visual score in EDSS, and lower total immediate and delayed recall in BVMT-R.

ConclusionVOF damage is seen in RRMS and is associated with visual symptoms and visuospatial learning impairments.

category: neurology


title: Clinical Validation of a Proteomic Biomarker Threshold for Increased Risk of Spontaneous Preterm Birth

abstract: Preterm births are prevalent and a leading cause of neonatal death in the United States. Despite the availability of effective interventions, to date there is not a robust and widely applicable test to identify pregnancies at high risk for spontaneous preterm birth (sPTB). Previously, a sPTB predictor based on the ratio of two proteins, IBP4/SHBG, was validated as an accurate predictor of sPTB in the observational study Proteomic Assessment of Preterm Risk (PAPR). Here it is demonstrated that the same predictor threshold associated with 2-fold increased risk of sPTB, namely -1.4, is also statistically significant for predicting elevated risk of sPTB in the observational study Multicenter Assessment of a Spontaneous Preterm Birth Risk Predictor (TreeToP).

category: obstetrics and gynecology


title: Contamination of air and surfaces in workplaces with SARS-CoV-2 virus: a systematic review

abstract:
ObjectivesThis systematic review aimed to evaluate the evidence for air and surface contamination of workplace environments with SARS-CoV-2 RNA and the quality of the methods used to identify actions necessary to improve the quality of the data.

MethodsWe searched Web of Science and Google Scholar until 24th December 2020 for relevant articles and extracted data on methodology and results.

ResultsThe vast majority of data come from healthcare settings, with typically around 6 % of samples having detectable concentrations of SARS-CoV-2 RNA and almost none of the samples collected had viable virus. There were a wide variety of methods used to measure airborne virus, although surface sampling was generally undertaken using nylon flocked swabs. Overall, the quality of the measurements was poor. Only a small number of studies reported the airborne concentration of SARS-CoV-2 virus RNA, mostly just reporting the detectable concentration values without reference to the detection limit. Imputing the geometric mean air concentration assuming the limit of detection was the lowest reported value, suggests typical concentrations in health care settings may be around 0.01 SARS-CoV-2 virus RNA copies/m3. Data on surface virus loading per unit area were mostly unavailable.

ConclusionThe reliability of the reported data is uncertain. The methods used for measuring SARS-CoV-2 and other respiratory viruses in work environments should be standardised to facilitate more consistent interpretation of contamination and to help reliably estimate worker exposure.

Key messagesO_LIWhat is already known about this subject?
O_LILow level contamination of air and surfaces in hospitals with SARS-CoV-2 RNA have been reported during the Covid-19 pandemic.
C_LIO_LILimited data have published from non-healthcare settings.
C_LI
C_LIO_LIWhat are the new findings?
O_LITypically, around 6% of air and surface samples in hospitals were positive for SARS-COV-2 RNA, although there is very limited data for non-healthcare settings.
C_LIO_LIThe quality of the available measurement studies is generally poor, with little consistency in the sampling and analytical methods used.
C_LIO_LIFew studies report the concentration of SARS-CoV-2 in air or as surface loading of virus RNA, and very few studies have reported culture of the virus.
C_LIO_LIThe best estimate of typical air concentrations in health care settings is around 0.01 SARS-CoV-2 virus RNA copies/m3
C_LI
C_LIO_LIHow might this impact on policy or clinical practice in the foreseeable future?
O_LIThere should be concerted efforts to standardise the methods used for measuring SARS-CoV-2 and other respiratory viruses in work environments.
C_LI
C_LI

category: occupational and environmental health


title: Impulse dispersion of aerosols during playing wind instruments

abstract:
Musical activities especially singing and playing wind instruments have been singled out as potentially high-risk activities for transmission of SARS CoV-2, because of a higher rate of aerosol production and emission. Playing wind instruments can produce condensation water, droplets of saliva, and aerosol particles, which hover and convectional spread in the environmental air and can be potentially infectious.

The aim of this study is to investigate the primary impulse dispersion of aerosols during playing different wind instruments in comparison to breathing and speaking. Nine professional musicians (3 trumpeters, 3 cross flutists and 3 clarinetists) of the Bavarian Symphony Orchestra performed the main theme of Ludwig van Beethoven s 9th symphony, 4th movement in different pitches and loudness. Thereby, the inhaled air volume was marked with small aerosol particles produced with a commercial e-cigarette. The expelled aerosol cloud was recorded by cameras from different perspectives. Afterwards, the dimensions and dynamics of the aerosol cloud was measured by segmenting the video footage at every time point.

Overall, the cross flutes produced the largest dispersion at the end of task of up to maximum distances of 1.88 m in front direction. Thereby it was observed an expulsion of aerosol in different directions: upwards and downwards at the mouthpiece, at the end of the instrument and along the cross flute at the key plane. In comparison, the maximum impulse dispersion generated by the trumpets and clarinets were lower in frontal and lateral direction (1.2 m and 1.0 m in front-direction). The expulsion to the sides was also lower. Consequently, a distance of 3 m to the front and to the sides of 2 m for the cross flutes in an orchestral formation is proposed, for trumpets and clarinets a safety distance of 2 m to the front and 1.5 m between instrumentalists are recommendable.

category: otolaryngology


title: Novel COVID-19 phenotype definitions reveal phenotypically distinct patterns of genetic association and protective effects

abstract: INTRODUCTION PARAGRAPHMultiple large COVID-19 genome-wide association studies (GWAS) have identified reproducible genetic associations indicating that some infection susceptibility and severity risk is heritable.1-5 Most of these studies ascertained COVID-19 cases in medical clinics and hospitals, which can lead to an overrepresentation of cases with severe outcomes, such as hospitalization, intensive care unit admission, or ventilation. Here, we demonstrate the utility and validity of deep phenotyping with self-reported outcomes in a population with a large proportion of mild and subclinical cases. Using these data, we defined eight different phenotypes related to COVID-19 outcomes: four that align with previously studied COVID-19 definitions and four novel definitions that focus on susceptibility given exposure, mild clinical manifestations, and an aggregate score of symptom severity. We assessed replication of 13 previously identified COVID-19 genetic associations with all eight phenotypes and found distinct patterns of association, most notably related to the chr3/SLC6A20/LZTFL1 and chr9/ABO regions. We then performed a discovery GWAS, which suggested some novel phenotypes may better capture protective associations and also identified a novel association in chr11/GALNT18 that reproduced in two fully independent populations.

category: genetic and genomic medicine


title: A Hybrid Machine Learning Framework for Enhancing the Prediction Power in Large Scale Population Studies: TheATHLOS Project

abstract: The ATHLOS cohort is composed of several harmonized datasets of international cohorts related to health and aging. The healthy aging scale has been constructed based on a selection of particular variables from 16 individual studies. In this paper, we consider a selection of additional variables found in ATHLOS and investigate their utilization for predicting the healthy aging. For this purpose motivated by the datasets volume and diversity we focus our attention upon the clustering for prediction scheme, where unsupervised learning is utilized to enhance prediction power, showing the predictive utility of exploiting structure in the data by clustering. We show that imposed computation bottlenecks can be surpassed when using appropriate hierarchical clustering within a clustering for ensemble classification scheme while retaining prediction benefits. We propose a complete methodology which is evaluated against baseline methods and the original concept. The results are very encouraging suggesting further developments in this direction along with applications in tasks with similar characteristics. A strait-forward open source implementation is provided for the R project.

category: health informatics


title: A Hybrid Machine Learning Framework for Enhancing the Prediction Power in Large Scale Population Studies: The ATHLOS Project


title: Escape of SARS-CoV-2 501Y.V2 variants from neutralization by convalescent plasma

abstract: SARS-CoV-2 variants of concern (VOC) have arisen independently at multiple locations and may reduce efficacy of current vaccines targeted at the spike glycoprotein. We re-cently described the emergence of VOC in South Africa (501Y.V2 or PANGO lineage B.1.351) with mutations in the spike receptor-binding domain (RBD) and N-terminal domain (NTD). Here, using a live virus neutralization assay (LVNA), we compared neutralization of a first wave virus (B.1.1.117) versus the 501Y.V2 variant using plasma collected from adults hospitalized with COVID-19 from two South African infection waves, with the second wave dominated by 501Y.V2 infections. Sequencing demonstrated that infections in first wave plasma donors were with viruses harbouring none of the 501Y.V2-defining RBD or NTD mutations, except for one with E484K. 501Y.V2 virus was effectively neutralized by plasma from second wave infections and first wave virus was effectively neutralized by first wave plasma. In cross-neutralization, 501Y.V2 virus was poorly neutralized by first wave plasma, with an 8.4-fold drop in neutralization relative to first wave virus and a 15.1-fold drop relative to 501Y.V2 neutralization by second wave plasma. In contrast, second wave plasma neutralization of first wave virus was more effective, showing 4.1-fold decline relative to 501Y.V2 virus neutralization and 2.3-fold decline relative to first wave plasma neutralization. While we only tested one plasma elicited by E484K alone, this potently neutralized both variants. The observed effective neutralization of first wave virus by 501Y.V2 infection elicited plasma provides preliminary evidence that vaccines based on VOC sequences could retain activity against other circulating SARS-CoV-2 lineages.

category: infectious diseases


title: Biomarkers of endothelial dysfunction and outcomes in coronavirus disease 2019 (COVID-19) patients: a systematic review and meta-analysis

abstract:
BackgroundSeveral studies have reported that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can directly infect endothelial cells, and endothelial dysfunction is often found in severe cases of coronavirus disease 2019 (COVID-19). To better understand the pathological mechanisms underlying endothelial dysfunction in COVID-19-associated coagulopathy, we conducted a systematic review and meta-analysis to assess biomarkers of endothelial cells in patients with COVID-19.

MethodsA literature search was conducted on online databases for observational studies evaluating biomarkers of endothelial dysfunction and composite poor outcomes in COVID-19 patients.

ResultsA total of 1187 patients from 17 studies were included in this analysis. The estimated pooled means for von Willebrand Factor (VWF) antigen levels in COVID-19 patients was higher compared to healthy control (306.42 [95% confidence interval (CI) 291.37-321.48], p<0.001; I2:86%), with the highest VWF antigen levels was found in deceased COVID-19 patients (448.57 [95% CI 407.20-489.93], p<0.001; I2:0%). Meta-analysis showed that higher plasma levels of VWF antigen, tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 antigen (PAI-1) antigen, and soluble thrombomodulin (sTM) were associated with composite poor outcome in COVID-19 patients ([standardized mean difference (SMD) 0.74 [0.33-1.16], p<0.001; I2:80.4%], [SMD 0.55 [0.19-0.92], p=0.003; I2:6.4%], [SMD 0.33 [0.04-0.62], p=0.025; I2:7.9%], and [SMD 0.55 [0.10-0.99], p=0.015; I2:23.6%], respectively).

ConclusionThe estimated pooled means shows increased levels of VWF antigen in COVID-19 patients. Several biomarkers of endothelial dysfunction, including VFW antigen, t-PA, PAI-1, and sTM, are significantly associated with increased composite poor outcome in patients with COVID-19.

PROSPERO registration numberCRD42021228821


title: A Mathematical Model of Platelet Antiparasitic Action in Erythrocytes and Merozoites During Malaria Infection

abstract: Platelets have been seen traditionally as fragments of blood mediating coagulation. However, evidence during malaria infection suggests that platelets also act against merozoites, an infectious form of malaria in the bloodstream, and megakaryocytes can release giant platelets with a larger volume than normal platelets. We propose a mathematical model to study the interaction between red blood cells, merozoites, and platelets during malaria infection. We analyzed two cases of the interaction of platelets with malaria infection. In the first one, we considered the isolated action of normal platelets and, in the second one, the joint antiparasitic action of both normal and giant platelets. Numerical simulations were performed to evaluate the stability of the equilibrium points of the system of equations. The model showed that the isolated antiparasitic action of normal platelets corroborates malaria infection control. However, the system can converge to a presence-merozoite equilibrium point, or an oscillatory behavior may appear. The joint antiparasitic action of both normal and giant platelets eliminated the oscillatory behavior and drove the dynamics to converge to lower parasitic concentration than the case of isolated action of normal platelets. Moreover, the joint antiparasitic action of platelets proved more easily capable of eliminating the infection.


title: Non-Congruent SARS-CoV-2 Waves in England

abstract: Examination of the chronology, location and size of waves of SARS-CoV-2 infection across England could shed light on the inter-play between the 1st and the 2nd Waves. From mid-October onwards such an analysis becomes increasingly difficult due to the emergence of a new strain (VOC-202012/01) and in light of the differential implementation of lockdown measures and tiers. Therefore, we sought to examine trends and correlations in virus prevalence and covid-related deaths spanning the start of the UK pandemic in March 2020 through to early November 2020 - i.e., including the first growth period of the 2nd Wave. We found striking regional relationships between the 1st and the 2nd Wave that are difficult to explain other than by involving some role for changing levels of immunity in the population affecting the progression of the pandemic.


title: ESCAPE: An Open-Label Trial of Personalized Immunotherapy in Critically Ill COVID-19 Patients

abstract:
RationaleMacrophage activation syndrome (MAS) and complex immune dysregulation (CID) often underlie acute respiratory distress (ARDS) in COVID-19.

ObjectiveTo investigate the outcome of personalized immunotherapy in critical COVID-19.

MethodsIn this open-label prospective trial, 102 patients with SOFA (sequential organ failure assessment) score [≥]2 or ARDS by SARS-CoV-2 were screened for MAS (ferritin more than 4420 ng/ml) and CID (ferritin [≤]4420 ng/ml and low expression of HLA-DR on CD14-monocytes). Patients with MAS and CID with increased aminotransferases were assigned to intravenous anakinra; those with CID and normal aminotransferases to tocilizumab. The primary outcome was at least 25% decrease of SOFA score and/or 50% increase of respiratory ratio by day 8; 28-day mortality, change of SOFA score by day 28; serum biomarkers and cytokine production by mononuclear cells were secondary endpoints.

Measurements and Main ResultsThe primary study endpoint was met in 58.3% of anakinra-treated patients and in 33.3% of tocilizumab-treated patients (odds ratio 3.11; 95% CIs 1.29-7.73; P: 0.011). No differences were found in mortality and in SOFA score changes. By day 4, ferritin was decreased among anakinra-treated patients; interleukin (IL)-6, soluble urokinase plasminogen activator receptor (suPAR) and the expression of HLA-DR were increased among tocilizumab-treated patients. Anakinra increased capacity of mononuclear cells to produce IL-6. Survivors by day 28 who received anakinra were distributed to scales of the WHO clinical progression of lower severity. Greater incidence of secondary infections was found with tocilizumab treatment.

ConclusionsBiomarkers may guide favourable anakinra responses in critically ill patients with COVID-19.

Trial RegistrationClinicalTrials.gov, NCT04339712

category: intensive care and critical care medicine


title: Molecular epidemiology of SARS-CoV-2 - a regional to global perspective

abstract:
BackgroundAfter a year of the global SARS-CoV-2 pandemic, a highly dynamic genetic diversity is surfacing. Among nearly 1000 reported virus lineages, dominant lineages such as B.1.1.7 or B.1.351 attract media attention with questions regarding vaccine efficiency and transmission potential. In response to the pandemic, the Jena University Hospital began sequencing SARS-CoV-2 samples in Thuringia in early 2020.

MethodsViral RNA was sequenced in tiled amplicons using Nanopore sequencing. Subsequently, bioinformatic workflows were used to process the generated data. As a genomic background, 9,642 representative SARS-CoV-2 genomes (1,917 of German origin) were extracted from more than 300.000 genomes.

ResultsIn a comprehensive bioinformatics analysis, we have set Thuringian isolates in the German, European and global context. In Thuringia, a largely rural German region without an international airport and a population density below the German average, we discovered many of the common "EU lineages". German samples are scattered across eight major clades, and Thuringian samples occupy four of them.

ConclusionThe rapid emergence and spread of novel variants are of great concern as these lineages could transmit more efficiently, evade current vaccine efforts or undermine diagnostic test accuracy. To anticipate and mitigate these threats, a continuous molecular surveillance is essential.

Key messagesO_LIBioinformatics analysis of 1,917, 4,251, and 3,474 SARS-CoV-2 genomes from Germany, the EU (except Germany), and non-EU, respectively, subsampled from more than 300,000 public genomes and placed in the context of Thuringian sequences
C_LIO_LIConstant antigenic drift for SARS-CoV-2 and no clear pattern or clustering is visible in Thuringia based on the current number of samples
C_LIO_LICurrently over 100 described lineages are identified in Germany and only a subset (9) are detected in Thuringia so far, most likely due to genetic undersampling
C_LIO_LIFrom a national perspective, it is likely that high-frequency lineages, which are currently spreading throughout Europe, will eventually also reach Thuringia
C_LIO_LISystematic and dense molecular surveillance via whole-genome sequencing is needed to detect concerning new lineages early, limit spread and adjust vaccines if necessary
C_LI


title: PREVALENCE OF ABDOMINAL OBESITY AND ITS ASSOCIATION WITH CARDIOVASCULAR RISK AMONG THE ADULT POPULATION IN BURKINA FASO

abstract:
ObjectiveThe objective of this study is to determine the prevalence of abdominal obesity and its associated factors in Burkina Faso. We hypothesize that there is a high burden of abdominal obesity and it is significantly associated with sociodemographic and cardiovascular risk factors.

DesignWe performed secondary analysis of the survey conducted in Burkina Faso using the World Health Organization (WHO) STEPwise approach.

SettingThe study was conducted in Burkina Faso with all 13 regions of the country included.

ParticipantsOur study involved 4308 adults of both sexes aged 25 to 64 years.

Main outcomeOur primary outcome was the abdominal obesity which was could defined using a cut-off point of waist circumference (WC) of [≥]94 cm for men and [≥]80 cm for women.

ResultsThe overall age-standardized prevalence of abdominal obesity was 22.5% (95% CI: 21.3-23.7). This age-standardized prevalence was 35.9% (95% CI: 33.9-37.9) among women and 5.2% (95% CI: 4.3-6.2) among men (p < 0.001). In urban areas, the age-standardized prevalence of abdominal obesity was 42.8% (95% CI: 39.9-45.7) and 17.0% (95%CI: 15.7-18.2) in rural areas (p < 0.001). The overall age-standardized prevalence of very high WC (WC [≥]102 cm for men and [≥]88 cm for women) was 10.2% (95%CI: 9.3-11.1). According to the National Institute for Health and Clinical Excellence (NICE) BMI-WC matrix, which combines the body mass index (BMI) and WC to define different levels of cardiovascular health risk, 14.6% of adult Burkinabe had an increased cardiovascular health risk.

ConclusionOur study shows a high prevalence of abdominal obesity among the adult population in Burkina Faso. These findings suggest that the measurement of WC should be systematically incorporated in Burkina Faso primary healthcare centers for the early detection of high cardiovascular risk in order to reduce levels of premature death.

STRENGTHS AND LIMITATIONS OF THIS STUDY[tpltrtarr] This is the first national representative study on abdominal obesity in the context of an emerging epidemiological transition in Burkina Faso.
[tpltrtarr]A recommended cut-off point was used to define abdominal obesity among the adult population in Burkina Faso, which we found to be associated with "intermediate" cardiovascular risk factors.
[tpltrtarr]The waist circumference and risk factors used in this study were measured using the standard approach proposed by the WHO [1]. However, some risk factors such as physical inactivity, alcohol consumption, and type of fat were self-reported and may therefore be affected by information bias.
[tpltrtarr]This study was a cross-sectional study and must not be considered to make causal inference.

Target journalhttps://bmjopen.bmj.com/


title: Opportunistic Assessment of Ischemic Heart Disease Risk Using Abdominopelvic Computed Tomography and Medical Record Data: a Multimodal Explainable Artificial Intelligence Approach

abstract: Current risk scores for predicting ischemic heart disease (IHD) risk--the leading cause of global mortality--have limited efficacy. While body composition (BC) imaging biomarkers derived from abdominopelvic computed tomography (CT) correlate with IHD risk, they are impractical to measure manually. Here, in a retrospective cohort of 8,197 contrast-enhanced abdominopelvic CT examinations undergoing up to 5 years of follow-up, we developed improved multimodal opportunistic risk assessment models for IHD by automatically extracting BC features from abdominal CT images and integrating these with features from each patients electronic medical record (EMR). Our predictive methods match and, in some cases, outperform clinical risk scores currently used in IHD risk assessment. We provide clinical interpretability of our model using a new method of determining tissue-level contributions from CT along with weightings of EMR features contributing to IHD risk. We conclude that such a multimodal approach, which automatically integrates BC biomarkers and EMR data can enhance IHD risk assessment and aid primary prevention efforts for IHD.

category: radiology and imaging


title: Deep Learning for Predicting Cognitive Gap as a Reliable Biomarker of Dementia

abstract: Neuroimaging data may reflect the mental status of both cognitively preserved individuals and patients with neurodegenerative diseases. To find the relationship between cognitive performance and the difference between predicted and observed functional test results, we developed a Convolutional Neural Network (CNN) based regression model to estimate the level of cognitive decline from preprocessed T1-weighted MRI images. In this study, we considered the Predicted Cognitive Gap (PCG) as the biomarker to accurately classify Healthy Control (HC) subjects versus Alzheimer disease (AD) subjects. The proposed model was tested on a dataset that includes 422 HC and 377 AD cases. The performance of the proposed solution was measured using Receiver Operating Characteristic (ROC) Area Under the Curve (AUC) and achieved 0.987 (ADAS-cog), 0.978 (MMSE), 0.898 (RAVLT), 0.848 (TMT), 0.829 (DSST) for averaged brain images; and 0.985 (ADAS-cog), 0.987 (MMSE), 0.901 (RAVLT), 0.8474 (TMT), 0.796 (DSST) for middle slice skull stripped brain images. The results achieved indicate that PCG can accurately separate healthy subjects from demented ones and thus, the structure of the brain contributes to the level of human cognition and their functional abilities. Therefore, PCG could be used as a biomarker for dementia.


title: Post-Disease Divergence in SARS-CoV-2 RNA Detection between Nasopharyngeal, Anterior Nares and Saliva/Oral Fluid Specimens - Significant Implications for Policy & Public Health

abstract:
BackgroundPatients have been shown to shed SARS-CoV-2 viral RNA in nasopharyngeal (NP) specimens for over 100 days after resolution of clinical disease (1, 2). How this relates to anterior nares and oral fluid specimens has not previously been investigated.

MethodsWe prospectively collected oral fluid, anterior nares, NP swab and serum specimens from 1,326 individuals at 2 "drive-through" testing locations. The Curative SARS-CoV-2 Assay (Curative Assay)(3) on oral fluid and anterior nares specimens was compared to the EURORealTime SARS-CoV-2 Assay (EuroRT Assay)(4) on anterior nares and NP specimens. Viral culture and IgG serology were used to assess infectious potential and stage of disease.

Additionally we investigated differences in viral RNA detection between specimen types, both early (< 21 days) and late (> 21 days) in SARS-CoV-2 infection, by using an employee surveillance program with daily SARS-CoV-2 testing to precisely determine infection date, even without symptoms. We prospectively collected oral fluid, anterior nares and NP swab specimens from 165 subjects with early infections and 22 subjects with late infections. Specimens were tested using the Curative Assay with the "high-sensitivity" Hologic Aptima SARS-CoV-2 Assay (Hologic Assay)(5) on an NP swab used as the comparator. Late infection specimens were also tested with EuroRT and Zymo Quick SARS-CoV-2 rRT-PCR Kit (Zymo) (6) Assays.

ResultsThe "drive-through" study showed similar sensitivities of oral fluid and anterior nares specimens on the Curative Assay to anterior nares specimens tested with the EuroRT Assay. However NP specimens tested with the same EuroRT assay produced 20-30% more positives. Incorporating viral culture and serology data to exclude NP RT-PCR positives that are not infectious or late in the course of disease showed a Positive Percent Agreement (PPA) for of 98.2% and 96.2% and Negative Percent Agreement (NPA) of 97.6% and 98.1% for anterior nares and oral fluid specimens, respectively.

Within 21 days of infection, the Curative Assay showed a PPA and NPA of 100% and 100%, respectively for oral fluid; of 100% and 99% respectively for anterior nares; and of 98.2% and 99.0%, respectively in nasopharyngeal specimens compared to an NP specimen on the Hologic Assay. 29 positives were asymptomatic and showed 100% PPA and 100% NPA for all specimen types. After 21 days from infection onset, significant divergence between NP and other specimen types occurred on all 4 assays. Out of 22 paired sample sets, 18, 13, 8 and 4 NP specimens were positive on the Curative, Zymo, Hologic and EuroRT assays, respectively, compared to only 3, 2, 0 and 1 positive anterior nares specimens. Only one oral fluid sample was positive in both the Curative and Zymo assays.

ConclusionsWe used a unique population to show significant divergence between NP specimens and anterior nares or oral fluid specimens >21 days from SARS-CoV-2 infection, which appears to be biological variation and is independent of assay used. This has significant public health implications for the use of NP specimens in community testing programs and policy implications for evaluation of novel specimen types and tests where the use of NP swabs as a comparator may say more about the study population than the assay or specimen type to be evaluated and may unnecessarily limit access to testing.


title: High infection attack rates of SARS-CoV-2 in Dutch households revealed by dense sampling

abstract:
BackgroundIndoor environments are considered a main setting for transmission of SARS-CoV-2. Households in particular present a close-contact environment with high probability of transmission between persons of different ages and with different roles in society.

MethodsComplete households with a laboratory-confirmed SARS-CoV-2 positive case in the Netherlands (March-May 2020) were included. At least three home visits were performed during 4-6 week of follow-up, collecting naso- and oropharyngeal swabs, oral fluid, faeces and blood samples for molecular and serological analyses of all household members. Symptoms were recorded from two weeks before the first visit up to the last visit. Secondary attack rates (SAR) were estimated with logistic regression. A transmission model was used to assess transmission routes in the household.

ResultsA total of 55 households with 187 household contacts were included. In 17 households no transmission took place, and in 11 households all persons were infected. Estimated SARs were high, ranging from 35% (95%CI: 24%-46%) in children to 51% (95%CI: 39%-63%) in adults. Estimated transmission rates in the household were high, with reduced susceptibility of children compared to adolescents and adults (0.67; 95%CI: 0.40-1.1).

ConclusionEstimated SARs were higher than reported in earlier household studies, presumably owing to a dense sampling protocol. Children were shown to be less susceptible than adults, but the estimated SAR in children was still high. Our results reinforce the role of households as main multiplier of SARS-CoV-2 infection in the population.

Key pointsWe analyze data from a SARS-CoV-2 household study and find higher secondary attack rates than reported earlier. We argue that this is due to a dense sampling strategy that includes sampling at multiple time points and of multiple anatomical sites.


title: Force of infection: A determinant of vaccine efficacy?

abstract: Vaccine efficacy (VE) can vary in different settings. Of the many proposed setting-dependent determinants of VE, force of infection (FoI) stands out as one of the most direct, proximate, and actionable. As highlighted by the COVID-19 pandemic, modifying FoI through non-pharmaceutical interventions (NPIs) use can significantly contribute to controlling transmission and reducing disease incidence and severity absent highly effective pharmaceutical interventions, such as vaccines. Given that NPIs reduce the FoI, the question arises as to if and to what degree FoI, and by extension NPIs, can modify VE, and more practically, as vaccines become available for a pathogen, whether and which NPIs should continue to be used in conjunction with vaccines to optimize controlling transmission and reducing disease incidence and severity.


title: Adaptive immunity to human coronaviruses is widespread but low in magnitude

abstract: Endemic human coronaviruses (hCoV) circulate worldwide but cause minimal mortality. Although seroconversion to hCoV is near ubiquitous during childhood, little is known about hCoV-specific T cell memory in adults. We quantified CD4 T cell and antibody responses to hCoV spike antigens in 42 SARS-CoV-2 uninfected individuals. T cell responses were widespread within conventional memory and cTFH compartments but did not correlate with IgG titres. SARS-CoV-2 cross-reactive T cells were observed in 48% of participants and correlated with HKU1 memory. hCoV-specific T cells exhibited a CCR6+ central memory phenotype in the blood, but were enriched for frequency and CXCR3 expression in human lung draining lymph nodes. Overall, hCoV-specific humoral and cellular memory are independently maintained, with a shared phenotype existing among coronavirus-specific CD4 T cells. This understanding of endemic coronavirus immunity provides insight into the homeostatic maintenance of immune responses that are likely to be critical components of protection against SARS-CoV-2.


title: AngioNet: A Convolutional Neural Network for Vessel Segmentation in X-ray Angiography

abstract: AO_SCPLOWBSTRACTC_SCPLOWCoronary Artery Disease (CAD) is commonly diagnosed using X-ray angiography, in which images are taken as radio-opaque dye is flushed through the coronary vessels to visualize stenosis severity. Cardiologists typically use visual estimation to approximate the percent diameter reduction of the stenosis, and this directs therapies like stent placement. A fully automatic method to segment the vessels would eliminate potential subjectivity and provide a quantitative and systematic measurement of diameter reduction. Here, we have designed a convolutional neural network, AngioNet, for vessel segmentation in X-ray angiography images. The main innovation in this network is the introduction of an Angiographic Processing Network which significantly improves segmentation performance on multiple network backbones, with the best performance using Deeplabv3+ (Dice score 0.864, sensitivity 0.918, specificity 0.987). We have also demonstrated the interchangeability of our network in measuring vessel diameter with Quantitative Coronary Angiography. Our results indicate that AngioNet is a powerful tool for automatic angiographic vessel segmentation that could facilitate systematic anatomical assessment of coronary stenosis in the clinical workflow.

category: cardiovascular medicine


title: Effects of diet, activities, environmental exposures and trimethylamine metabolism on alveolar breath compounds: protocol for a retrospective case-cohort observational study

abstract:
BackgroundExhaled breath contains thousands of volatile organic compounds (VOCs) that reflect on biochemical and biophysical activities both outside and within the human body. Breath analysis could provide non-invasive, cost-effective, real time early disease diagnosis and monitoring of therapeutic responses.

ObjectivesThe primary objective of this study was to assess the effectiveness of alveolar breath testing in diagnosing idiopathic systemic body and breath odors. Key secondary objectives were to assess if breath tests can reliably differentiate subtypes of idiopathic malodor in different environments and dietary regimens, and to map metabolites to biomedical functions and pathways.

Study DesignThe basic design was to measure a cohort of idiopathic odor in order to identify potential molecular correlates with genotypic and phenotypic variables. Participants were subdivided in several different ways allowing for different cases and controls within the cohort, using prior and later test results and observations. Thus, this study was an observational retrospective case-cohort/nested case-control study.

Setting/ParticipantsParticipants were recruited online via MEBO and TMAU support groups and on site, during the 3rd Annual MEBO Research conference held at Miami South Beach on June 23, 2012 and local meetups of support groups (Miami, Florida; New York, New York; Chicago, Illinois, US and Birmingham, England). Study population is individuals self-reporting systemic idiopathic malodor production. Inclusion criteria were good general health, desire and ability to travel to one of the participating sites and pay the lab fee. Exclusion Criteria were medical conditions that could prevent participation and age under 18.

Study Interventions and MeasuresThe main study procedure was the application of a rapid point-of-care breath testing system to collect and concentrate alveolar breath VOCs on a sorbent trap, using breath collection apparatus (BCA) 5.0. Samples were sent to central laboratory and analyzed with gas chromatography and mass spectroscopy. In addition, the participants filled out food frequency questionnaires and were offered to use Aurametrix, online software tool based on a participant-initiated ecological momentary assessment approach, allowing to recall the events at any time later. The tool analyzed dietary intakes, activities and environmental exposures for both individual and aggregate level data.

The primary endpoint was the composition of VOCs in breath samples, while diet and activity data, and results of alternative testing assessments were secondary endpoints. The main study outcome measure is the diagnostic accuracy of alveolar breath test in differentiating profiles of two main pre-defined sub-cohorts. Index of concordance with accuracy, sensitivity, specificity, positive predictive value and negative predictive value will be reported. A number of factors was assessed for confounding.

category: endocrinology


title: Near real-time surveillance of the SARS-CoV-2 epidemic with incomplete data

abstract:
Designing public health responses to outbreaks requires close monitoring of population-level health indicators in real-time. Thus, an accurate estimation of the epidemic curve is critical. We propose an approach to reconstruct epidemic curves in near real time. We apply this approach to characterize the early SARS-CoV-2 outbreak in two Spanish regions between March and April 2020.

We address two data collection problems that affected the reliability of the available real-time epidemiological data, namely, the frequent missing information documenting when a patient first experienced symptoms, and the frequent retrospective revision of historical information (including right censoring). This is done by using a novel back-calculating procedure based on imputing patients dates of symptom onset from reported cases, according to a dynamically-estimated "backward" reporting delay conditional distribution, and adjusting for right censoring using an existing package, NobBS, to estimate in real time (nowcast) cases by date of symptom onset. This process allows us to obtain an approximation of the time-varying reproduction number (Rt) in real-time.

At each step, we evaluate how different assumptions affect the recovered epidemiological events and compare the proposed approach to the alternative procedure of merely using curves of case counts, by report day, to characterize the time-evolution of the outbreak. Finally, we assess how these real-time estimates compare with subsequently documented epidemiological information that is considered more reliable and complete that became available later in time. Our approach may help improve accuracy, quantify uncertainty, and evaluate frequently unstated assumptions when recovering the epidemic curves from limited data obtained from public health surveillance systems in other locations.

category: epidemiology


title: COVID-19 Test Positivity Rate as a marker for hospital overload

abstract:
The use of antigen tests for the diagnosis of COVID-19 in Italy has risen sharply in autumn 2020. Although, Italian regions like Alto Adige, Veneto, Toscana, Lazio, Piemonte and Marche did a large use of these tests for screening and surveillance purposes or for implementing diagnosis protocols, in addition to molecular tests, they were not reported in the statistics in the last months of 2020. As a consequence of this situation the test positivity rate (TPR) index, defined as the number of new positive cases divided by the number of tests, has lost in accuracy. Only in the recent days, starting from the 15th of January 2021, antigen tests have become part of the statistics for all the Italian regions. Despite the lack of data, we have noticed that TPR has a strong correlation with the number of patients admitted in hospitals, and that TPR peaks in general precede the peaks of hospitalized people which occur on average about 15 days later.

In this paper, we have deepened this intuition, analysing the TPR course and its relationship with the number of hospitalized people. To conduct the study we have defined a novel version of the TPR index which takes into account the number of tests done with respect to the population (considering both molecular and antigen tests), the number of infected individuals, and the number of patients healed. Successively, starting from a limited set of data which were made available in November 2020, we have reconstructed the antigen tests time series of four Italian regions, and we computed the TPR index for them.

The results show that TPR peaks precede peaks of hospitalized people in both the first and the second phases of the pandemic in Italy, provided that antigen tests are considered. Moreover, the TPR index trend, can be used to deduct important information on the course of the epidemic, and on the impact of COVID-19 in the health care system, which can be monitored in advance.


title: The epidemiology of herpes simplex virus type 2 in sub-Saharan Africa: systematic review, meta-analyses, and meta-regressions

abstract:
BackgroundHerpes simplex virus type 2 (HSV-2) infection is a prevalent sexually transmitted infection with a sizable disease burden that is highest in sub-Saharan Africa. This study aimed to characterize HSV-2 epidemiology in this region.

MethodsCochrane and PRISMA guidelines were followed to systematically review, synthesize, and report HSV-2 related findings. Meta-analyses and meta-regressions were conducted.

FindingsFrom 218 relevant publications, 451 overall outcome measures and 869 stratified measures were extracted. Pooled incidence rates ranged between 2.4-19.4 per 100 person-years across populations. Pooled seroprevalence was lowest at 37.3% (95% confidence interval (CI): 34.9-39.7%) in general populations and high in female sex workers and HIV positive individuals at 62.5% (95% CI: 54.8-70.0%) and 71.3% (95% CI: 66.5-75.9%), respectively. In general populations, pooled seroprevalence increased steadily with age. Compared to women, men had a lower seroprevalence with an adjusted risk ratio (ARR) of 0.61 (95% CI: 0.56-0.67).

Seroprevalence decreased in recent decades with an ARR of 0.98 (95% CI: 0.97-0.99) per year. Seroprevalence was highest in Eastern and Southern Africa. Pooled HSV-2 proportion in genital ulcer disease was 50.7% (95% CI: 44.7-56.8%) and in genital herpes it was 97.3% (95% CI: 84.4-100%).

InterpretationSeroprevalence is declining by 2% per year, but a third of the population is infected. Age and geography play profound roles in HSV-2 epidemiology. Temporal declines and geographic distribution of HSV-2 seroprevalence mirror that of HIV prevalence, suggesting sexual risk behavior has been declining for three decades. HSV-2 is the etiological cause of half of GUD and nearly all genital herpes cases.

FundingThis work was supported by pilot funding from the Biomedical Research Program at Weill Cornell Medicine in Qatar and by the Qatar National Research Fund [NPRP 9-040-3-008].


title: Super-Spreaders Out, Super-Spreading In: The Effects of Infectiousness Heterogeneity and Lockdowns on Herd Immunity

abstract:
Recently, [8] has proposed that heterogeneity of infectiousness (and susceptibility) across individuals in infectious diseases, plays a major role in affecting the Herd Immunity Thresh-old (HIT). Such heterogeneity has been observed in COVID-19 and is recognized as overdis-persion (or "super-spreading"). The model of [8] suggests that super-spreaders contribute significantly to the effective reproduction factor, R, and that they are likely to get infected and immune early in the process. Consequently, under R0 {approx} 3 (attributed to COVID-19), the Herd Immunity Threshold (HIT) is as low as 5%, in contrast to 67% according to the traditional models [1, 2, 4, 10].

This work follows up on [8] and proposes that heterogeneity of infectiousness (susceptibility) has two "faces" whose mix affects dramatically the HIT: (1) Personal-Trait-, and (2) Event-Based-Infectiousness (Susceptibility). The former is a personal trait of specific individuals (super-spreaders) and is nullified once those individuals are immune (as in [8]). The latter is event-based (e.g cultural super-spreading events) and remains effective throughout the process, even after the super-spreaders immune. We extend [8]s model to account for these two factors, analyze it and conclude that the HIT is very sensitive to the mix between (1) and (2), and under R0 {approx} 3 it can vary between 5% and 67%. Preliminary data from COVID-19 suggests that herd immunity is not reached at 5%.

We address operational aspects and analyze the effects of lockdown strategies on the spread of a disease. We find that herd immunity (and HIT) is very sensitive to the lock-down type. While some lockdowns affect positively the disease blocking and increase herd immunity, others have adverse effects and reduce the herd immunity.


title: Individual-level and neighborhood-level factors associated with longitudinal changes in cardiometabolic measures in participants of a care coordination program

abstract:
IntroductionIdentifying individual and neighborhood-level factors associated with less improvement or worsening cardiometabolic measures in participants of clinic-based interventions may help identify candidates for supplementary community-based interventions.

MethodsStudy design: Secondary data analysis of data from care coordination program cohort, Leveraging Information Technology to Guide High Tech, High Touch Care (LIGHT2). Participants: Medicare, Medicaid, or dual-eligible adults from the University of Missouri Health System enrolled in LIGHT2. Intervention: Nurse-led care coordination in ten primary care clinics. Outcomes: Hemoglobin A1C, low-density-lipoprotein (LDL) cholesterol, and blood pressure. Multivariable generalized linear regression models assessed changes in outcomes after adjusting for clinical and sociodemographic factors, neighborhood-level factors, and driving time to primary care clinics.

Results6378 participants had pre-and post-intervention cardiometabolic measures reported (61% women, 86.3% White, non-Hispanic ethnicity, mean age 62.7 [SD, 18.5] years). In adjusted models, pre-intervention measures and female gender were associated with worsening of all cardiometabolic measures. Womens LDL-cholesterol worsened compared to men irrespective of pre-intervention levels ({beta} 7.87, 95% CI 5.24 to 10.5, p<.001). Women with hemoglobin A1C> 6.8% had worsening hemoglobin A1C compared to men (main effect {beta} -1.28, 95% CI -1.95 to -0.61, p<.001; interaction effect {beta} 0.19, 95% CI 0.09 to 0.28, p<.001). Women with systolic blood pressure >121 mm of Hg had worsening diastolic blood pressure compared to men (main effect {beta} -5.42, 95% CI -9.8 to 0.098, p = 0.016; interaction effect {beta} 0.04, 95% CI 0.01 to 0.078, p = 0.009). Adding neighborhood-level factors or driving time to primary care clinics did not improve the overall fit of the models.

ConclusionsIn a solely clinic-based care coordination program, increasing baseline cardiometabolic measures and female gender were associated with worsening cardiometabolic outcomes. Further research to understand the causes of these associations may help tailor clinic-community-linked interventions.

category: primary care research


title: ARE GEOGRAPHIC FACTORS ASSOCIATED WITH POORER OUTCOMES IN PATIENTS DIAGNOSED WITH COVID-19?

abstract:
BackgroundThe prognosis of patients with COVID-19, with older age and comorbidities, is associated with a more severe course and higher fatality rates but no analysis has yet included factors related to the geographical area/municipality in which the affected patients live. So the objective of this study is to analyse the prognosis of patients with COVID-19 in terms of sex, age, comorbidities, and geographic variables.

MethodsA retrospective cohort of 6286 patients diagnosed with COVID-19 was analysed, considering demographic data, previous comorbidities and geographic variables. The main study variables were hospital admission, Intensive Care Unit (ICU) admission and death due to worsening symptoms; and the secondary variables were sex, age, comorbidities and geographic variables (size of the area of residence, distance to the hospital and the driving time to the hospital). A comparison analysis and a multivariate Cox model were performed.

ResultsThe multivariate Cox model showed that women had a better prognosis in any type of analysed prognosis. Most of the comorbidities studied were related to a poorer prognosis except for dementia, which is related to lower admissions and higher mortality. Suburban areas were associated with greater mortality and with less hospital or ICU admission. Distance to the hospital was also associated with hospital admission.

ConclusionsFactors such as type of municipality and distance to hospital act as social health determinants. This fact must be taken account in order to stablish specifics prevention measures and treatment protocols.


title: Implementation of predictive risk stratification to reduce emergency admissions to hospital: experiences of general practitioners and practice managers

abstract:
AimIn a trial evaluating the introduction of a predictive risk stratification model (PRISM) into primary care, we reported statistically significant increases in emergency hospital admissions and use of other NHS services without evidence of benefits to patients or the NHS. The aim of this study was to explore the views and experiences of general practitioners (GPs) and practice managers on incorporating PRISM into routine practice.

MethodsWe interviewed 22 GPs and practice managers in 18 participating practices at two timepoints: 3-6 months after PRISM was available in their practice; and at study end, up to 18 months later. We recorded and transcribed interviews and analysed data thematically using Normalisation Process Theory.

ResultsRespondents reported that the decision to use PRISM was based mainly on fulfilling reporting requirements for Quality and Outcome Framework (QOF) incentives. Most applied it to a very small number of patients for a short period. Using PRISM entailed technical tasks, information sharing within practice meetings and changes to patient care. These were diverse and generally small scale. Use was inhibited by PRISM not being integrated with practice systems. Respondents evaluation of PRISM was mixed: most doubted it had any large scale impact, but many cited examples of impact on individual patient care. They reported increased awareness of patients in high risk groups.

ConclusionsQualitative results suggest mixed views of predictive risk stratification in primary care and raised awareness of highest-risk patient groups, potentially affecting unplanned hospital attendance and admissions. To inform future policy, decision-makers need more information about implementation and effects of emergency admissions risk stratification tools in primary and community settings.

Trial registrationControlled Clinical Trials no. ISRCTN55538212.


title: A cross-sectional survey of the workplace factors contributing to symptoms of anxiety and depression among nurses and physicians during the first wave of COVID-19 pandemic in two US healthcare systems

abstract:
BackgroundAnxiety and depression among physicians and nurses during COVID-19 pandemic in the USA is not well described and its modifiable causes poorly understood.

MethodsWe conducted a cross-sectional survey of symptoms of anxiety and depression (Hospital Anxiety and Depression Scale) among physicians and nurses in two US healthcare systems June-Sept 2020. We ascertained features of work as well as its perceptions and associated concerns in relation to risk of anxiety and depression, while controlling for health history via regression and path analyses.

ResultsAbout a third of 684 nurses and 185 physicians surveyed showed symptoms of anxiety or depression, the excess was particularly prominent in nurses. Belief in having been infected was a dominant cause of anxiety and depression, more related to history of symptoms of pneumonia, then the contact with infected patients. Having confidence in competent use and access to personal protective equipment, maintaining usual working hours and being surrounded by colleagues who were both sufficient in numbers and not stressed, was protective. Having support of immediate family and religious communities lessened anxiety and depression after accounting for other factors. Involvement in aerosol-generating procedures with infected patients was linked with lower depression in nurses but higher among physicians. Likewise, the setting of recent patient encounters affected risk differently for physicians and nurses.

ConclusionsOur findings may help develop mitigation measures and underscore the need to help nurses and physicians bear the psychological burden of COVID-19 pandemic and similar events in the future.


title: REM: An Integrative Rule Extraction Methodology for Explainable Data Analysis in Healthcare

abstract: Deep learning models are receiving increasing attention in clinical decision-making, however the lack of explainability impedes their deployment in day-to-day clinical practice. We propose REM, an explainable methodology for extracting rules from deep neural networks and combining them with rules from non-deep learning models. This allows integrating machine learning and reasoning for investigating basic and applied biological research questions. We evaluate the utility of REM in two case studies for the predictive tasks of classifying histological and immunohistochemical breast cancer subtypes from genotype and phenotype data. We demonstrate that REM efficiently extracts accurate, comprehensible rulesets from deep neural networks that can be readily integrated with rulesets obtained from tree-based approaches. REM provides explanation facilities for predictions and enables the clinicians to validate and calibrate the extracted rulesets with their domain knowledge. With these functionalities, REM caters for a novel and direct human-in-the-loop approach in clinical decision-making.

category: oncology


title: Development of ADAF screening tool for emotional and coping problems in cancer patients

abstract:
PurposePsychological screening in patient with cancer is recommended by clinical guidelines, however most of scales have large number of items, difficulty detection and refer from routine consultations. The specific objective of the study was to develop and validate the ADAF screening for anxiety, depression and coping.

Methods/PatientsCross-sectional, multicenter study performed in the medical and radiotherapy oncology services of 5 hospitals in Madrid, coordinated by the Medical Oncology Service of the Hospital Clinico San Carlos (CEIC n{o}19 / 265-E). To determine the psychometric properties, the ADAF screening questionnaire ADAF was administered, including 5 items (one related to anxiety symptoms, two related to depressive symptoms, one for helplessness coping and one for avoidance coping), and as a gold-standard the HADS and the MiniMAC. Intraclass correlation coefficients and receiver operating characteristic curves were performed. The p value <0.05 was considered significant.

ResultsA total of 186 patients completed the evaluation. The correlation coefficients were significant for all dimensions (Anxiety, Depression, Helplessness coping, and Avoidance Coping), with p <0.001. The statistical analysis of ROC curves suggests that the cut-off point for screening is equivalent to a score > 2 points (3 in the case of depression, having two items), with a sensitivity and specificity between 62 and 90%, depending on the item, and an area under the curve above 0.8 for the first 4 items.

ConclusionsADAF screening has adequate reliability, good sensitivity and specificity. This instrument is useful and easy to use to identify emotional and coping problems in cancer patients.


title: Geographic Variation in Influenza Vaccination among US Nursing Home Residents: A National Study

abstract:
ObjectiveEstimates of influenza vaccine use are not available at the county level for U.S. nursing home (NH) residents but are critically necessary to guide implementation of quality improvement programs aimed at increasing vaccination rates. Furthermore, estimates that account for differences in resident characteristics between counties are unavailable. We estimated risk-standardized vaccination rates among short- and long-stay NH residents by U.S. county and identified drivers of geographic variation.

MethodsWe conducted a retrospective cohort study utilizing 100% of 2013-2015 fee-for-service Medicare claims, Minimum Data Set assessments, Certification and Survey Provider Enhanced Reports, and LTCFocUS. We separately evaluated short-stay (<100 days) and long-stay ([≥]100 days) residents aged [≥]65 years old across the 2013-2014 and 2014-2015 influenza seasons. We estimated county-level risk-standardized vaccination rates (RSVRs) via hierarchical logistic regression adjusting for 32 resident-level covariates. We then used multivariable linear regression models to assess associations between county-level NHs predictors and RSVRs.

ResultsThe overall study cohort consisted of 2,817,217 residents in 14,658 NHs across 2,798 counties. Short-stay residents had lower RSVRs than long-stay residents (2013-2014: median [IQR], 69.6% [62.8-74.5] vs 84.0% [80.8-86.4]). Counties with the highest vaccination rates were concentrated in the Midwestern, Southern, and Northeast US. Several modifiable facility-level characteristics were associated with increased RSVRs, including higher registered nurse to total nurse ratio and higher total staffing for licensed practical nurses, speech language pathologists, and social workers. Characteristics associated with lower RSVRs included higher percentage of residents restrained, with a pressure ulcer, and NH-level hospitalizations per resident-year.

ConclusionsSubstantial county-level variation in influenza vaccine use exists among short- and long-stay NH residents. Quality improvement interventions to improve vaccination rates can leverage these results to target NHs located in counties with lower risk-standardized vaccine use.

category: geriatric medicine


title: SARS-CoV-2 infection in pregnancy is associated with robust inflammatory response at the maternal-fetal interface

abstract: Pregnant women appear to be at increased risk for severe outcomes associated with COVID-19, but the pathophysiology underlying this increased morbidity and its potential impact on the developing fetus is not well understood. In this study of pregnant women with and without COVID-19, we assessed viral and immune dynamics at the placenta during maternal SARS-CoV-2 infection. Amongst uninfected women, ACE2 was detected by immunohistochemistry in syncytiotrophoblast cells of the normal placenta during early pregnancy but was rarely seen in healthy placentas at full term. Term placentas from women infected with SARS-CoV-2, however, displayed a significant increase in ACE2 levels. Using immortalized cell lines and primary isolated placental cells, we determined the vulnerability of various placental cell types to direct infection by SARS-CoV-2 in vitro. Yet, despite the susceptibility of placental cells to SARS-CoV-2 infection, viral RNA was detected in the placentas of only a subset ([~]13%) of women in this cohort. Through single cell transcriptomic analyses, we found that the maternal-fetal interface of SARS-CoV-2-infected women exhibited markers associated with pregnancy complications, such as preeclampsia, and robust immune responses, including increased activation of placental NK and T cells and increased expression of interferon-related genes. Overall, this study suggests that SARS-CoV-2 is associated with immune activation at the maternal-fetal interface even in the absence of detectable local viral invasion. While this likely represents a protective mechanism shielding the placenta from infection, inflammatory changes in the placenta may also contribute to poor pregnancy outcomes and thus warrant further investigation.


title: Covid-19 in end-stage renal disease patients with renal replacement therapies: a systematic review and meta-analysis

abstract:
IntroductionThe novel coronavirus (COVID-19), caused by SARS-CoV-2, showed various prevalence and case-fatality rates (CFR) among patients with different pre-existing chronic conditions. End-stage renal disease (ESRD) patients with renal replacement therapy (RRT) might have a higher prevalence and CFR due to reduced immune function from uremia and kidney tropism of SARS-CoV-2, but there was no systematic study on the infection and mortality of the SARS-CoV-2 infection in ESRD patients who are on RRT.

MethodsWe searched five electronic databases and performed a systematic review and meta-analysis up to June 30, 2020, to evaluate the prevalence and case fatality rate (CFR) of the COVID-19 infection among ESRD patients with RRT. The global COVID-19 data were retrieved from the international database on June 30, 2020, for estimating the prevalence and CFR of the general population as referencing points.

ResultsOf 3,272 potential studies, 34 were eligible studies consisted of 1,944 COVID-19 confirmed cases in 21,873 ESRD patients with RRT from 12 countries in four WHO regions. The overall pooled prevalence in ESRD patients with RRT was 3.10% [95% confidence interval (CI) 1.25-5.72] which was higher than referencing 0.14% global average prevalence. The overall estimated CFR of COVID-19 in ESRD patients with RRT was 18.06% (95%CI 14.09- 22.32) which was higher than the global average at 4.98%.

ConclusionsThis meta-analysis suggested high COVID-19 prevalence and CFR in ESRD patients with RRT. ESRD patients with RRT should have their specific protocol of COVID-19 prevention and treatment to mitigate excess cases and deaths.

Author summaryChronic kidney disease (CKD) was associated with increasing severity and mortality of COVID-19. End-stage renal disease (ESRD) patients were at the terminal stage of CKD and had reduced immune function due to uremia. Additionally, ESRD patients with kidney transplantation had a diminished immune system from immunosuppressive agents. Kidneys might be the secondary target of SARS-CoV-2 after the respiratory tract regardless of the previous history of kidney disease, preferably the glomerulus, which was associated with the richness of some specific protein-coding genes in the kidney. The overall pooled prevalence in ESRD patients with renal replacement therapy was approximately 22 times of the referencing global average prevalence. The overall estimated case fatality rate of COVID-19 in ESRD patients with renal replacement therapy was approximately 3.6 times the global average. ESRD patients with renal replacement therapy had high COVID-19 prevalence and case fatality rate. We suggested that ESRD patients with renal replacement therapy should have their specific protocol of COVID-19 prevention and treatment to mitigate excess cases and deaths.


title: Logistic advantage of two-step screening strategy for SARS-CoV-2 at airport quarantine

abstract:
BackgroundAirport quarantine is required to reduce the risk of entry of travelers infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, it is challenging for both high accuracy and rapid turn-around time to coexist in testing; polymerase chain reaction (PCR) is time-consuming with high accuracy, while antigen testing is rapid with less accuracy.

Methods88,924 (93.2%) of 95,457 arrivals at three international airports in Japan were tested for SARS-CoV-2 using self-collected saliva by a screening strategy with initial chemiluminescent enzyme immunoassay (CLEIA) followed by confirmatory nucleic acid amplification tests (NAAT) only for intermediate range antigen concentrations.

Results254 (0.27%) persons were found to be SARS-CoV-2 antigen positive ([≥] 4.0 pg/mL) by CLEIA. NAAT was required for confirmatory testing in 513 (0.54%) persons with intermediate antigen concentrations (0.67-4.0 pg/mL) whereby the virus was detected in 34 (6.6%) persons. This two-step strategy dramatically reduced the utilization of NAAT to approximately one out of every 200 test subjects.

Estimated performance of this strategy did not show significant increase in false negatives as compared to performing NAAT in all subjects. Further reduction in imported cases may be achieved by post-screening quarantine.

ConclusionsPoint of care testing by quantitative CLEIA using self-collected saliva is less labor-intensive and yields results rapidly, thus suitable as an initial screening test. Reserving NAAT for CLEIA indeterminate cases may prevent compromising accuracy while significantly improving the logistics of administering mass-screening at large venues.


title: Emergence and fast spread of B.1.1.7 lineage in Lebanon.

abstract:
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a rapid spread emerging disease. Recently, a new variant of this virus called SARS-CoV-2 VOC 202012/01 (or B.1.1.7 lineage), described in the United Kingdom (UK), has become highly prevalent in several countries. Its rate of transmission has been estimated to be greatly higher. B.1.1.7 lineage harbors 23 mutations co-existed for the first time in the same variant. Herein, we are interested only by the deletion mutation {Delta}H69/{Delta}V70 in the spike protein.

In the UK they were able to identify the increase of this new variant through the increase in the false negative result for the spike target of a three-target RT-PCR assay from Thermo Fisher Scientific (TaqPath kit). Later, the manufacturer announced that this false negative result is because of the deletion {Delta}H69/{Delta}V70 in the area targeted by the TaqPath Kit. Furthermore, The European CDC recommended that the use of this kit help to track the new variant.

Genome sequencing is the gold method to confirm the new variant, but observational studies provide also stronger evidence if similar models are observed in multiple countries, especially when randomized studies are not possible. In Lebanon, the highest number of confirmed cases were reported in first week of 2021. In the present study, we show the emergence and the fast spreading of the new variant in Lebanon and a relationship between SARS-CoV-2 transmission intensity and the frequency of the new variant during the first twelve days of January.


title: Prevalence of diabetes and prediabetes among Bangladeshi adults and associated factors: Evidence from the Demographic and Health Survey, 2017-18

abstract:
BackgroundTo estimate the age-standardized prevalence of diabetes and prediabetes and identify factors associated with these conditions at individual, household, and community levels.

MethodsData from 11952 Bangladeshi adults aged 18-95 years available from the most recent Bangladesh Demographic and Health Survey 2017-18 were used. Anthropometric measurements and fasting blood glucose samples were taken as part of the survey. Prevalence estimates of diabetes and prediabetes were age-standardized with direct standardization, and risk factors were identified using multilevel mix-effects Poisson regression models with robust variance.

ResultsThe overall age-standardised prevalence of diabetes was 9.2% (95%CI 8.7-9.7) (men: 8.8%, women: 9.6%), and prediabetes was 13.3% (95%CI 12.7-13.9) (men: 13.0%, women: 13.6%). Among people with diabetes, 61.5% were unaware that they had the condition. 35.2% were taking treatment regularly, and only 30.4% of them had controlled diabetes. Factors associated with an increased prevalence of having diabetes were increasing age, male, overweight/obesity, hypertension, being in the highest wealth quintile, and living in the Dhaka division. People currently employed and living in the Rangpur division were less likely to have diabetes than those currently not employed and living in the Barishal division.

ConclusionsDiabetes and prediabetes affect a substantial proportion (over one-quarter) of the Bangladeshi adult population. Continuing surveillance and effective prevention and control measures, focusing on obesity reduction and hypertension management, are urgently needed.


title: Estimation of the SARS-CoV-2 infection fatality rate in Germany

abstract: Assessing the infection fatality rate (IFR) of SARS-CoV-2 is one of the most controversial issues during the pandemic. Due to asymptomatic or mild courses of COVID-19, many infections remain undetected. Reported case fatality rates - COVID-19-associated deaths divided by number of detected infections - are therefore poor estimates of the IFR. Endogenous changes of the population at risk of a SARS-CoV-2 infection, changing test practices and an improved understanding of the pathogenesis of COVID-19 further exacerbate the estimation of the IFR. Here, we propose a strategy to estimate the IFR of SARS-CoV-2 in Germany that combines official data on reported cases and fatalities supplied by the Robert Koch Institute (RKI) with data from seroepidemiological studies in two infection hotspots, the Austrian town Ischgl and the German municipality Gangelt, respectively. For this purpose, we use the law of total probability to derive an approximate formula for the IFR that is based on a set of assumptions regarding data quality and test specificity and sensitivity. The resulting estimate of the IFR in Germany of 0.83% (95% CI: [0.69%; 0.98%]) that is based on a combination of the RKI and Ischgl data is notably higher than the IFR estimate reported in the Gangelt study (0.36% [0.29%; 0.45%]). It is closer to the consolidated estimate based on a meta-analysis (0.68% [0.53%; 0.82%]), where the difference can be explained by Germanys disadvantageous age structure. As a result of virus mutations, vaccination strategies, and improved therapy, a re-estimation of the IFR will eventually be mandated; the proposed method is able to account for such developments.


title: Community structured model for vaccine strategies to control COVID19 spread: a mathematical study

abstract: Efforts to mitigate the COVID-19 pandemic have relied heavily on non-pharmaceutical interventions (NPIs), including physical distancing, hand hygiene, and mask-wearing. However, an effective vaccine is essential to containing the spread of the virus. The first doses were distributed at the end of 2020, but the efficacy, period of immunity it will provide, and percentage of coverage still remain unclear. We developed a compartment model to examine different vaccine strategies for controlling the spread of COVID-19. Our framework accounts for testing rates, test-turnaround times, and vaccination waning immunity. Using reported case data from the city of Toronto, Canada between Mar-Dec, 2020 we defined epidemic phases of infection using contact rates, which depend on individuals duration of time spent within the household, workplace/school, or community settings, as well as the probability of transmission upon contact. We investigated the impact of vaccine distribution by comparing different permutations of waning immunity, vaccine coverage and efficacy throughout various stages of NPIs relaxation in terms of cases, deaths, and household transmission, as measured using the basic reproduction number (R0). We observed that widespread vaccine coverage substantially reduced the number of cases and deaths. In order for NPIs to be relaxed 8 months after vaccine distribution, infection spread can be kept under control with either 60% vaccine coverage, no waning immunity, and 70% efficacy, or with 60% coverage with a 12-month waning immunity and 90% vaccine efficacy. Widespread virus resurgence can result when the immunity wanes under 3 months and/or when NPIs are relaxed in concomitance with vaccine distribution. In addition to vaccination, our analysis of R0 showed that the basic reproduction number is reduced by decreasing the tests turnaround time and transmission in the household. While we found that household transmission can decrease following the introduction of a vaccine, public health efforts to reduce test turnaround times remain important for virus containment. Our findings suggest that vaccinating two-thirds of the population with a vaccine that is at least 70% effective may be sufficient for controlling COVID-19 spread, as long as NPIs are not immediately relaxed.


title: Disentangling sex differences in the shared genetic architecture of posttraumatic stress disorder, traumatic experiences, and social support with body size and composition

abstract: There is a well-known association of posttraumatic stress disorder (PTSD) and traumatic experiences with body size and composition, including consistent differences between sexes. However, the biology underlying these associations is unclear. To understand this complex relationship, we investigated large-scale datasets from the Psychiatric Genomic Consortium (12 823 cases and 35 648 controls), the UK Biobank (up to 360 000 individuals), and the GIANT (Genetic Investigation of Anthropometric Traits) Consortium (up to 339 224 individuals). We used genome-wide association statistics to estimate sex-specific genetic correlations (rg) among PTSD, traumatic experiences, social support, and multiple anthropometric traits. After multiple testing corrections (false discovery rate, FDR q<0.05), we observed 58 significant rg relationships in females (e.g., childhood physical abuse and body mass index, BMI rg=0.245, p=3.88x10-10) and 21 significant rg relationships in males (e.g., been involved in combat or exposed to warzone and leg fat percentage; rg=0.405, p=4.42x10-10). We performed causal inference analyses of these genetic overlaps using Mendelian randomization and latent causal variable approaches. Multiple female-specific putative causal relationships were observed linking body composition/size with PTSD (e.g., leg fat percentagePTSD; beta=0.319, p=3.13x10-9), traumatic experiences (e.g., childhood physical abusewaist circumference; beta=0.055, p=5.07x10-4), and childhood neglect (e.g., "someone to take you to doctor when needed as a child"BMI; beta=-0.594, p=1.09x10-5). In males, we observed putative causal effects linking anthropometric-trait genetic liabilities to traumatic experiences (e.g., BMIchildhood physical abuse; beta=0.028, p=8.19x10-3). In conclusion, our findings provide insights regarding sex-specific causal networks linking anthropometric traits to PTSD, traumatic experiences, and social support.

category: psychiatry and clinical psychology