title: PesTrapp mobile app: A trap setting application for real-time entomological field and laboratory study

abstract: Zoonotic diseases such as malaria, dengue, Zika and chikungunya remain endemic in many countries. Setting and deploying trap to capture the host/vector species are fundamental to understand their density and distribution. Human effort to manage the trap data accurately and timely is an exhaustive endeavour when the study area expands and study period prolongs. One stop mobile app to manage and monitor the process of animal trapping, from field to laboratory level is still scarce. We developed a new mobile app named "PesTrapp" especially for medical entomologists to acquire the vector density index based on the mobile updates of ovitraps and species information in field and laboratory. This study aimed to highlight the mobile apps development and design, describe the user experience and evaluate the preliminary user assessment of the mobile app. The mobile app was developed using mobile framework and database. User evaluation of the mobile app was based on the adjusted Mobile App Rating Scale and Standardized User Experience Percentile Rank Questionnaire. The process flows of system design and detailed screen layouts were described. The user experiences of using the app in a project to study Aedes surveillance in six study sites in Selangor, Malaysia were described. The overall mean user evaluation score of the mobile app was 4.0 (SD=0.6), which showed its acceptability by the users. The PesTrapp, a one-stop solution, is anticipated to improve the entomological surveillance work processes. This new mobile app can contribute as a tool in the vector control countermeasure strategies.


title: The fragility index in randomised controlled trials of interventions for aneurysmal subarachnoid haemorrhage: a systematic review

abstract:
BackgroundFragility analysis supplements the p-value and risk of bias assessment in the interpretation of results of randomised controlled trials. In this systematic review we determine the fragility index (FI) and fragility quotient (FQ) of randomized trials in aneurysmal subarachnoid haemorrhage.

MethodsThis is a systematic review registered with PROSPERO (ID: CRD42020173604). Randomised controlled trials in adults with aneurysmal subarachnoid haemorrhage were analysed if they reported a statistically significant primary outcome of mortality, function (e.g. modified Rankin Scale), vasospasm or delayed neurological deterioration.

ResultsWe identified 3809 records with 17 randomized trials selected for analysis. The median fragility index was 3 (inter-quartile range 0-5) and the median fragility quotient was 0.012 (IQR 0-0.034). Six of nineteen trial outcomes (31.6%) had an fragility index of 0. In seven trials (36.8%), the number of participants lost to follow-up was greater than or equal to the fragility index. Only 17.6% of trials are at low risk of bias.

ConclusionsRandomised controlled trial evidence supporting management of aneurysmal subarachnoid haemorrhage is weaker than indicated by conventional analysis using p-values alone. Increased use of fragility analysis by clinicians and researchers could improve the translation of evidence to practice.

category: intensive care and critical care medicine


title: Ibrutinib as a Potential Therapeutic for Cocaine Use Disorder

abstract: Cocaine use presents a worldwide public health problem with high socioeconomic cost. Current treatments for cocaine use disorder (CUD) are suboptimal and rely primarily on behavioral interventions. To explore pharmaceutical treatments for CUD, we analyzed genome-wide gene expression data from publically availble human brain tissues (midbrain, hippocampus and prefrontal cortex neurons) from 71 individuals (mean age = 39.9, 100% male, 36 with CUD and 35 matched controls). We leveraged the L1000 database to investigate molecular associations between neuronal mRNA profiles from 825 repurposable compounds (e.g., FDA approved) with human CUD gene expression in the brain. We identified 16 compounds that were negatively associated with CUD gene expression patterns across all brain regions (padj < 0.05), all of which outperformed current targets undergoing clinical trials for CUD (all padj > 0.05). We tested the effectiveness of these compounds using independent transcriptome-wide in vitro (neuronal cocaine exposure; n=18) and in vivo (mouse cocaine self-administration; prefrontal cortex, hippocampus and midbrain; n = 12-15) datasets. Among these medications, Ibrutinib demonstrated negative associations with both neuronal cocaine exposure and mouse cocaine self-administration. To obtain experimental confirmation of therapeutic effects of Ibrutinib on CUD, we used the Drosophila melanogaster model, which enables highthroughput quantification of behavioral responses in defined genetic backgrounds and controlled environmental conditions. Ibrutinib altered cocaine-induced changes in startle response and reduced the occurrence of cocaine-induced seizures (n = 61-142 per group; sex: 51%female). Our results identify Ibrutinib, an FDA approved medication, as a potential therapeutic for cocaine neurotoxicity.

category: addiction medicine


title: The antibody response to SARS-CoV-2 increases over 5 months in patients with anosmia/dysgeusia

abstract: The factors involved in the persistence of antibodies to SARS-CoV-2 are unknown. We evaluated the antibody response to SARS-CoV-2 in personnel from 10 healthcare facilities and its association with individuals characteristics and COVID-19 symptoms in an observational study. We enrolled 4735 subjects (corresponding to 80% of all personnel) for three time points over a period of 8-10 months. For each participant, we determined the rate of antibody increase or decrease over time in relation to 93 features analyzed in univariate and multivariate analyses through a machine learning approach. In individuals positive for IgG ([≥] 12 AU/mL) at the beginning of the study, we found an increase [p= 0.0002] in antibody response in symptomatic subjects, particularly with anosmia/dysgeusia (OR 2.75, 95% CI 1.753 - 4.301), in a multivariate logistic regression analysis. This may be linked to the lingering of SARS-CoV-2 in the olfactory bulb.

category: allergy and immunology


title: The antibody response to SARS-CoV-2 infection persists over at least 8 months in symptomatic patients


title: Modelling the impact of contact tracing of symptomatic individuals on the COVID-19 epidemic

abstract:
OBJECTIVESWith declining numbers of COVID-19 cases in the State of Sao Paulo, Brazil, social distancing measures were gradually being lifted. The risk of an increase in the number of cases, however, cannot be overlooked. Even with the adoption of non-pharmaceutical interventions, such as restrictions on mass gatherings, wearing masks, and complete or partial closure of schools, other public health measures may help to control the epidemic. We aimed to evaluate the impact of the contact tracing of symptomatic individuals on the COVID-19 epidemic regardless of the use of diagnostic testing.

METHODSWe developed a mathematical model that includes isolation of symptomatic individuals and tracing of contacts to assess the effects of the contact tracing of symptomatic individuals on the COVID-19 epidemic in the State of Sao Paulo.

RESULTSFor a selection efficacy (proportion of isolated contacts who are infected) of 80%, cases and deaths may be reduced by 80% after 60 days when 5000 symptomatic individuals are isolated per day, each of them together with 10 contacts. On the other hand, for a selection efficacy of 20%, the number of cases and deaths may be reduced by approximately 40% and 50%, respectively, compared with the scenario in which no contact tracing strategy is performed.

CONCLUSIONContact tracing of symptomatic individuals may be a potential alternative strategy when the number of diagnostic tests available is not sufficient for a massive testing strategy.

category: epidemiology


title: Outdoor transmission of COVID-19: Analysis of windspeed

abstract:
BackgroundTo examine whether outdoor transmission may contribute to the COVID-19 epidemic, we hypothesized that slower outdoor wind speed is associated with increased risk of transmission when individuals socialize outside.

MethodsDaily COVID-19 incidence reported in Suffolk County, NY, between March 16th - December 31st, 2020, was the outcome. Average wind speed and maximal daily temperature were collated by the National Oceanic and Atmospheric Administration. Negative binomial regression was used to model incidence rates while adjusting for susceptible population size.

ResultsCases were very high in the initial wave but diminished once lockdown procedures were enacted. Most days between May 1st, 2020, and October 24th, 2020, had temperatures 16-28{degrees}C and wind speed diminished slowly over the year and began to increase again in December 2020. Unadjusted and multivariable-adjusted analyses revealed that days with temperatures ranging between 16-28{degrees}C where wind speed was <8.85 kilometers per hour (KPH) had increased COVID-19 incidence (aIRR=1.45, 95% C.I.=[1.28-1.64], P<0.001) as compared to days with average wind speed [≥]8.85 KPH.

ConclusionThroughout the U.S. epidemic, the role of outdoor shared spaces such as parks and beaches has been a topic of considerable interest. This study suggests that outdoor transmission of COVID-19 may occur by noting that the risk of transmission of COVID-19 in the summer was higher on days with low wind speed. Outdoor use of increased physical distance between individuals, improved air circulation, and use of masks may be helpful in some outdoor environments where airflow is limited.


title: A wind speed threshold for increased outdoor transmission of coronavirus: An ecological study


title: Modeling fractional order dynamics of Syphilis via Mittag-Leffler law

abstract:
Syphilis is one the most dangerous sexually transmitted disease which is common in the world. In this work, a mathematical model is formulated with an emphasis on treatment. The reproduction number which presents information on the spread of the disease is determined. The models steady states are established, and the disease free states local and global stability are studied. The existence and uniqueness of solutions for both Caputo-Fabrizio and Atangana-Baleanu derivative in the Caputo sense are established. Numerical simulations were carried out to support the analytical solution, which indicates that the fractional order derivatives influence the dynamics of the spread of the Syphilis in the community.

2010 MSC: 00-01, 99-00


title: UK and other SARS-CoV-2-Covariants - Simulation Modeling 70% Increase

abstract: CovidSIMVL, an agent-based contagion-based viral transmission simulation tool, was employed to simulate the effects of viral agents of differing levels of infectivity. The constructs "Velocity" and "Increase in Velocity" were operationalized in terms of rates of transmission events over successive iterations (generations) in a set of CovidSIMVL trials. Treating 40-70% increase in velocity as a target, based on reports in the literature for the UK variant (VUI 202012/01), the series of trials reported in the paper demonstrate the calibration of CovidSIMVL parameters to produce increases in transmission rates of 40-70% above a baseline value. A series of follow-up studies is proposed to evaluate three different possible explanations for reported increases in SARS-Cov2-2 infections that are being attributed to spread of the UK and other variants: (a) simulations where the inherent characteristics of the virus (infectivity) are varied (genomic studies); (b) simulations where the behaviour of agents is varied (e.g., movement within and between spaces) while inherent characteristics of the virus are held constant (behavioural studies); and (c) simulations where both inherent properties of the virus and the behaviour of agents are varying to "tease out" the interaction between biologically-based contributions to increased case counts, and contextual/behavioural contributions (epigenetic studies).


title: How effective was Newfoundland & Labrador's travel ban to prevent the spread of COVID-19? An agent-based analysis

abstract:
BackgroundTo prevent the spread of COVID-19 in Newfoundland & Labrador (NL), NL implemented a wide travel ban in May 2020. We estimate the effectiveness of this travel ban using a customized agent-based simulation (ABS).

MethodsWe built an individual-level ABS to simulate the movements and behaviors of every member of the NL population, including arriving and departing travellers. The model considers individual properties (spatial location, age, comorbidities) and movements between environments, as well as age-based disease transmission with pre-symptomatic, symptomatic, and asymptomatic transmission rates. We examine low, medium, and high travel volume, traveller infection rates, and traveller quarantine compliance rates to determine the effect of travellers on COVID spread, and the ability of contact tracing to contain outbreaks.

ResultsInfected travellers increased COVID cases by 2-52x (8-96x) times and peak hospitalizations by 2-49x (8-94x), with (without) contact tracing. Although contact tracing was highly effective at reducing spread, it was insufficient to stop outbreaks caused by travellers in even the best-case scenario, and the likelihood of exceeding contact tracing capacity was a concern in most scenarios. Quarantine compliance had only a small impact on COVID spread; travel volume and infection rate drove spread.

InterpretationNLs travel ban was likely a critically important intervention to prevent COVID spread. Even a small number of infected travellers can play a significant role in introducing new chains of transmission, resulting in exponential community spread and significant increases in hospitalizations, while outpacing contact tracing capabilities. With the presence of more transmissible variants, e.g., the UK variant, prevention of imported cases is even more critical.


title: Design and Estimation for the Population Prevalence of Infectious Diseases

abstract: Understanding the prevalence of infections in the population of interest is critical for making data-driven public health responses to infectious disease outbreaks. Accurate prevalence estimates, however, can be difficult to calculate due to a combination of low population prevalence, imperfect diagnostic tests, and limited testing resources. In addition, strategies based on convenience samples that target only symptomatic or high-risk individuals will yield biased estimates of the population prevalence. We present Bayesian multilevel regression and poststratification models that incorporate probability sampling designs, the sensitivity and specificity of a diagnostic test, and specimen pooling to obtain unbiased prevalence estimates. These models easily incorporate all available prior information and can yield reasonable inferences even with very low base rates and limited testing resources. We examine the performance of these models with an extensive numerical study that varies the sampling design, sample size, true prevalence, and pool size. We also demonstrate the relative robustness of the models to key prior distribution assumptions via sensitivity analyses.


title: INCLUSIVE HEALTH: MODELING COVID-19 IN CORRECTIONAL FACILITIES AND COMMUNITIES

abstract: Mass incarceration, commonly associated with overcrowding and inadequate health resources for incarcerated people, creates a fertile environment for the spread of the coronavirus disease 2019 (COVID-19) in U.S. correctional facilities. The exact role that correctional facilities play in enhancing COVID-19 spread and enabling community re-emergence of COVID-19 is unknown. We constructed a novel stochastic model of COVID-19 transmission to estimate the impact of correctional facilities, specifically jails and state prisons, for enhancing disease transmission and enabling disease re-emergence in local communities. Using our model, we evaluated scenarios of testing and quarantining infected incarcerated people at 0.0, 0.5, and 1.0 times the rate that occurs for infected people in the local community for population sizes of 5, 10, and 20 thousand people. Our results illustrate testing and quarantining an incarcerated population of 800 would reduce the probability of a major community outbreak by 6% and also prevent between 250 to 730 incidences of COVID-19 per year, depending on local community size. These findings illustrate that managing COVID-19 in correctional facilities is essential to mitigate risks to community health, and thereby stresses the importance of improving the health standards of incarcerated people.


title: ADHD in adults with recurrent depression

abstract:
BackgroundDepression is highly heterogeneous in its clinical presentation. Those with attention deficit/hyperactivity disorder (ADHD) may be at risk of a more chronic and impairing depression compared to those with depression alone according to studies of young people. However, no studies to date have examined ADHD in recurrently depressed adults in mid-life.

AimsTo investigate ADHD in women in mid-life with a history of recurrent depression.

MethodIn a sample of women in mid-life (n=148) taken from a UK based prospective cohort of adults with a history of recurrent depression, we investigated the prevalence of ADHD and the association of ADHD with clinical features of depression.

Results12.8% of the recurrently depressed women had elevated ADHD symptoms and 3.4% met DSM-5 diagnostic criteria for ADHD. None of the women reported having a diagnosis of ADHD from a medical professional. ADHD was associated with earlier age of depression onset, higher depression associated impairment, a greater recurrence of depressive episodes and increased persistence of subthreshold depression symptoms over the study period, higher levels of irritability and increased risk of self-harm or suicide attempt. ADHD symptoms were associated with increased risk of hospitalisation and receiving non-first line antidepressant medication.

ConclusionsHigher ADHD symptoms appear to index a worse clinical presentation for depression. Findings suggest that in women with early onset, impairing and recurrent depression, the possibility of underlying ADHD masked by depression needs to be considered.

category: psychiatry and clinical psychology


title: Modeling the Effect of Population-Wide Vaccination on the Evolution of COVID-19 Epidemic in Canada

abstract: Population-wide vaccination is critical for containing the COVID-19 pandemic when combined with effective testing and prevention measures. Since the beginning of the COVID-19 outbreak, several companies worked tirelessly for the development of an efficient vaccine that would put an end to this pandemic. Today, a number of COVID-19 vaccines have been approved for use by a number of national regulatory organizations. Vaccination campaigns have already started in several countries with different daily-vaccination rates depending on the countrys vaccination capacity. Therefore, we find it timely and extremely important to conduct a study on the effect of population-wide vaccination campaigns on the evolution of the COVID-19 epidemic. To this end, we propose a new deterministic mathematical model to forecast the COVID-19 epidemic evolution under the effect of vaccination and vaccine efficacy. This model, referred to as SIRV, consists of a compartmental SIR (susceptible, infectious and removed) model augmented with an additional state V representing the effectively vaccinated population as well as two inputs representing the daily-vaccination rate and the vaccine efficacy. Using our SIRV model, we predict the evolution of the COVID-19 epidemic in Canada and its most affected provinces (Ontario, Quebec, British Columbia, Alberta, Saskatchewan, and Manitoba), for different daily vaccination rates and vaccine efficacy. Projections suggest that, without vaccination, 219, 000 lives could be lost across Canada by the end of 2021 due to COVID-19. The ongoing vaccination campaign across Canada seems to unfold relatively slowly at an average daily rate close to 1/2 vaccine per 1, 000 population. At this pace, we could be saving more than 77, 496 lives by the end of the year. Doubling the current vaccination efforts (1 vaccine per day per 1, 000 population) could be sufficient to save 125, 839 lives in Canada during the current year 2021. We would like to point out that our study assumes that the vaccine is perfectly safe without any short or long term side-effects. This study has been conducted independently at arms length from vaccine manufacturers, using the available data from Canada health services. This study can be easily adapted to other places in the world.

category: public and global health


title: Engagement with COVID-19 Public Health Measures in the United States: A Cross-Sectional Social Media Analysis from June to November 2020

abstract:
BackgroundThe coronavirus disease 2019 (COVID-19) has continued to spread in the US and globally. Closely monitoring public engagement and perception of COVID-19 and preventive measures using social media data could provide important information for understanding the progress of current interventions and planning future programs.

ObjectiveTo measure the publics behaviors and perceptions regarding COVID-19 and its daily life effects during the recent 5 months of the pandemic.

MethodsNatural language processing (NLP) algorithms were used to identify COVID-19 related and unrelated topics in over 300 million online data sources from June 15 to November 15, 2020. Posts in the sample were geotagged, and sensitivity and specificity were both calculated to validate the classification of posts. The prevalence of discussion regarding these topics was measured over this time period and compared to daily case rates in the US.

ResultsThe final sample size included 9,065,733 posts, 70% of which were sourced from the US. In October and November, discussion including mentions of COVID-19 and related health behaviors did not increase as it had from June to September, despite an increase in COVID-19 daily cases in the US beginning in October. Additionally, counter to reports from March and April, discussion was more focused on daily life topics (69%), compared with COVID-19 in general (37%) and COVID-19 public health measures (20%).

ConclusionsThere was a decline in COVID-19-related social media discussion sourced mainly from the US, even as COVID-19 cases in the US have increased to the highest rate since the beginning of the pandemic. Targeted public health messaging may be needed to ensure engagement in public health prevention measures until a vaccine is widely available to the public.


title: Acute Medical Unit Healthcare workers interaction in a developing country: Social Network Analysis

abstract:
INTRODUCTIONSocial network analysis is used to increase the awareness of leaders about the power of networks, to further catalyze relationships and connections, and to strengthen the capacity of the network to act collectively. We focus on understanding and measuring the communication patterns in an acute medical unit team. We sought to use Social Network Analysis to describe the patterns of communications in teamwork of an acute medical unit.

METHODSNetwork Analysis was conducted to examine network structure in 58 teamwork professional communication in an AMU. Team members reported the frequency (0 to 10+ times) of professional discussion with every other coworker during the last 48-hoursk, density, degree and betweenness centralization, degree and betweenness centrality; and homophily were calculated. P-value was obtained based on 1000 quadratic assignment procedure QAP permutations of the network. The network analysis was used to construct network maps using multidimentional scaling and generates a visual representation of networks through network diagrams.

RESULTSthere were 460 connections (density=28%). The whole network has a moderate degree centralization (37%) and lower betweenness centralization (8%). Three senior physicians, the head nurse, the physiotherapist, the medical secretary and the archive manager were most central in network. There was evidence regarding heterophily in a network indicated by high level of E-I index value 0.34 (P<0.01, by QAP).

CONCLUSIONSNA provided a description of patterns of communications in teamwork in an acute medical unit. We used SNA statistics to reveal variation in patterns of team communication and teammate interconnectedness by shift.

category: occupational and environmental health


title: Behavioral Responses to Risk Promote Vaccinating High-contact Individuals First

abstract: If COVID-19s reproduction number was constant, vaccinating elderly first minimized deaths. However, incorporating risk-driven behavior/policy changes enhances fit to data and prioritizes vaccinating high-contact individuals. Deaths grow exponentially until people are compelled to reduce contacts, stabilizing at levels obliging higher-contact groups to sufficiently cut interactions. Vaccinating those groups out of transmission saves lives and speeds everybodys return to normal life.

category: health economics


title: Antibodies elicited by SARS-CoV-2 infection and boosted by vaccination neutralize an emerging variant and SARS-CoV-1

abstract: Emerging SARS-CoV-2 variants have raised concerns about resistance to neutralizing antibodies elicited by previous infection or vaccination. We examined whether sera from recovered and naive donors collected prior to, and following immunizations with existing mRNA vaccines, could neutralize the Wuhan-Hu-1 and B.1.351 variants. Pre-vaccination sera from recovered donors neutralized Wuhan-Hu-1 and sporadically neutralized B.1.351, but a single immunization boosted neutralizing titers against all variants and SARS-CoV-1 by up to 1000-fold. Neutralization was due to antibodies targeting the receptor binding domain and was not boosted by a second immunization. Immunization of naive donors also elicited cross-neutralizing responses, but at lower titers. Our study highlights the importance of vaccinating both uninfected and previously infected persons to elicit cross-variant neutralizing antibodies.

category: infectious diseases


title: A single mRNA immunization boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection


title: Immune cell residency in the nasal mucosa and COVID-19 severity across the age range

abstract: Severe coronavirus disease of 2019 (COVID-19) positively correlates with age (Centers for Disease Control), develops after progression of infection from the upper airway to the lower respiratory tract (LRT), and can worsen into acute respiratory distress syndrome (ARDS) (Shi et al., 2020). Why children seem to be less likely to develop severe disease remains unclear. As the nasal mucosa (NM) is the first site of contact and defense for respiratory pathogens such as SARS-CoV-2 before dissemination to the LRT (Casadei and Salinas, 2019), we hypothesized that differences in this tissue across the age range may help explain the disparity in COVID-19 severity. To this end, we profiled NM samples across the lifespan in health and disease. We find that global transcriptomic changes including the expression of SARS-CoV-2 and coronavirus-associated receptors and factors are not correlated with age or the novel virus type, since pediatric NM cells mount similar antiviral response to both SARS-CoV-2 or Influenza B. Rather, we find immune cell residency in NM decreases dramatically with age especially cells of the innate immune system. This includes a resident-memory-like T cell subset with antiviral properties. These observations give plausible biological explanation to the observed clinical differences in disease spectrum and provide a foundation for future experimental studies.


title: Mendelian randomization analysis identified genes potentially pleiotropically associated with periodontitis

abstract:
ObjectiveTo prioritize genes that were pleiotropically or potentially causally associated with periodontitis.

MethodsWe applied the summary data-based Mendelian randomization (SMR) method integrating genome-wide association study (GWAS) for periodontitis and expression quantitative trait loci (eQTL) data to identify genes that were pleiotropically associated with periodontitis. We performed separate SMR analysis using CAGE eQTL data and GTEx eQTL data. SMR analysis were done for participants of European and East Asian ancestries, separately.

ResultsWe identified multiple genes showing pleiotropic association with periodontitis in participants of European ancestry and participants of East Asian ancestry. PDCD2 (corresponding probe: ILMN_1758915) was the top hit showing pleotropic association with periodontitis in participants of European ancestry, and BX093763 (corresponding probe: ILMN_1899903) and AC104135.3 (corresponding probe: ENSG00000204792.2) were the top hits in participants of East Asian ancestry using CAGE eQTL data and GTEx eQTL data, respectively.

ConclusionWe identified multiple genes that may be involved in the pathogenesis of periodontitis in participants of European ancestry and participants of East Asian ancestry. Our findings provided important leads to a better understanding of the mechanisms underlying periodontitis and revealed potential therapeutic targets for the effective treatment of periodontitis.

category: dentistry and oral medicine


title: Emergence of an early SARS-CoV-2 epidemic in the United States

abstract: The emergence of the early COVID-19 epidemic in the United States (U.S.) went largely undetected, due to a lack of adequate testing and mitigation efforts. The city of New Orleans, Louisiana experienced one of the earliest and fastest accelerating outbreaks, coinciding with the annual Mardi Gras festival, which went ahead without precautions. To gain insight into the emergence of SARS-CoV-2 in the U.S. and how large, crowded events may have accelerated early transmission, we sequenced SARS-CoV-2 genomes during the first wave of the COVID-19 epidemic in Louisiana. We show that SARS-CoV-2 in Louisiana initially had limited sequence diversity compared to other U.S. states, and that one successful introduction of SARS-CoV-2 led to almost all of the early SARS-CoV-2 transmission in Louisiana. By analyzing mobility and genomic data, we show that SARS-CoV-2 was already present in New Orleans before Mardi Gras and that the festival dramatically accelerated transmission, eventually leading to secondary localized COVID-19 epidemics throughout the Southern U.S.. Our study provides an understanding of how superspreading during large-scale events played a key role during the early outbreak in the U.S. and can greatly accelerate COVID-19 epidemics on a local and regional scale.


title: Risk of hospitalisation with COVID-19 among teachers compared to healthcare workers and other working-age adults. A nationwide case-control study

abstract:
ObjectiveTo determine the risk of hospitalisation with COVID-19 and severe COVID-19 among teachers and their household members, overall and compared to healthcare workers and the general working-age population.

DesignPopulation-based nested case-control study.

SettingsScotland, March 2020 to January 2021. Before and after schools re-opened in early August 2020.

ParticipantsAll cases of COVID-19 in Scotland in adults ages 21 to 65 (n = 83,817) and a random sample of controls matched on age, sex and general practice (n = 841,708).

ExposureIndividuals identified as actively teaching in a Scottish school by the General Teaching Council for Scotland, and household members of such individuals identified via the Unique Property Reference Number.

ComparatorIndividuals identified as healthcare workers in Scotland, their household members, and the remaining "general population" of working-age adults.

Main outcomesThe primary outcome was hospitalisation with COVID-19 defined in anyone testing positive with COVID-19 in hospital, admitted to hospital within 28 days of a positive test, and/or diagnosed with COVID-19 on discharge from hospital. Severe COVID-19 was defined as individuals admitted to intensive care or dying within 28 days of a positive test or assigned COVID-19 as a cause of death.

ResultsMost teachers were young (mean age 42), female (80%) and had no underlying conditions (84%). The cumulative incidence (risk) of hospitalisation with COVID-19 was below 1% for all of the working age adults. In the period after school re-opening, compared to the general population, in conditional logistic regression models adjusting for age, sex, general practice, deprivation, underlying conditions and number of adults in the household, the relative risk in teachers (among 18,479 cases and controls) for hospitalisation was rate ratio (RR) 0.97 (95%CI 0.72-1.29) and for severe COVID-19 was RR 0.27 (95%CI 0.09-0.77). Equivalent rate ratios for household members of teachers were 0.97 (95%CI 0.74-1.27) and 0.67 (95%CI 0.36-1.24), and for healthcare workers were 1.82 (95%CI 1.55-2.14) and 1.76 (95%CI 1.22-2.56), respectively.

ConclusionCompared to working-age adults who are otherwise similar, teachers and their household members are not at increased risk of hospitalisation with COVID-19 and are at lower risk of severe COVID-19. These findings are broadly reassuring for adults engaged in face to face teaching.


title: Creating virtual H&E images using samples imaged on a commercial CODEX platform

abstract: Multiparametric fluorescence imaging via CODEX allows the simultaneous imaging of many biomarkers in a single tissue section. While the digital fluorescence data thus obtained can provide highly specific characterizations of individual cells and microenvironments, the images obtained are different from those usually interpreted by pathologists (i.e., H&E slides and DAB-stained immunohistochemistry slides). Having the fluorescence data plus co-registered H&E or similar data could facilitate adoption of multiparametric imaging into regular workflows, as well as facilitate the transfer of algorithms and machine learning previous developed around H&E slides. Since commercial CODEX instruments do not produce H&E-like images by themselves, we developed a staining protocol and associated image processing to make "virtual H&E" images that can be incorporated into the CODEX workflow. While there are many ways to achieve virtual H&E images, including use of a fluorescent nuclear stain and tissue autofluorescence to simulate eosin staining, we opted to combine fluorescent nuclear staining (via DAPI) with actual eosin staining. We also output images derived from fluorescent nuclear staining and autofluorescence images for additional evaluation.

category: pathology


title: Estimated SARS-CoV-2 Seroprevalence in Children and Adolescents in Mississippi, May Through September 2020

abstract: Case-based tracking of COVID-19 in children and adolescents may underestimate infection, and compared with adults there is little pediatric SARS-CoV-2 seroprevalence data. To assess evidence of previous SARS-CoV-2 infections among children and adolescents in Mississippi, serologic testing for antibodies to SARS-CoV-2 was conducted on a convenience sample of residual serum specimens collected for routine laboratory testing by an academic medical center laboratory during May 17 through September 19, 2020. Seroprevalence by calendar month was standardized to the state population by race/ethnicity; cumulative numbers of infections were estimated by extrapolating seroprevalence to all those aged <18 years in Mississippi. Serum specimens from 1,603 individuals were tested; 175 (10.9%) were positive for SARS-CoV-2 antibodies. Among 1,579 (98.5%) individuals for whom race/ethnicity was known, the number testing positive was 16 (23.2%) of 69 Hispanic individuals, 117 (13.0%) of 901 non-Hispanic Black individuals and 30 (5.3%) of 565 non-Hispanic White individuals. Population-weighted seroprevalence estimates among those aged <18 years increased from 2.6% in May to 16.9% in September 2020. Cumulative numbers of infections extrapolated from seroprevalence data, however, were estimated at 117,805 (95% confidence interval [CI] = 68,771-168,708), suggesting that cases in children and adolescents are much higher than what was reported to the Mississippi State Department of Health (9,044 cases during this period). Further data to appreciate the burden of pediatric disease to inform public health policy is urgently needed.

category: pediatrics


title: Cortical and subcortical grey matter micro-structure is associated with polygenic risk for schizophrenia

abstract:
BackgroundRecent discovery of approximately 270 common genetic variants associated with schizophrenia has enabled polygenic risk scores (PRS) to be measured in the population. We hypothesized that normal variation in PRS would be associated with magnetic resonance imaging (MRI) phenotypes of brain morphometry and tissue composition.

MethodsWe used the largest extant genome-wide association dataset (N = 69,369 cases and N = 236,642 healthy controls) to measure PRS for schizophrenia in a large sample of adults from the UK Biobank (Nmax = 29,878) who had multiple micro- and macro-structural MRI metrics measured at each of 180 cortical areas, seven subcortical structures, and 15 major white matter tracts. Linear mixed effect models were used to investigate associations between PRS and brain structure at global and regional scales, controlled for multiple comparisons.

ResultsPolygenic risk was significantly associated with reduced neurite density index (NDI) at global brain scale, at 149 cortical regions, five subcortical structures and 14 white matter tracts. Other micro-structural parameters, e.g., fractional anisotropy, that were correlated with NDI were also significantly associated with PRS. Genetic effects on multiple MRI phenotypes were co-located in temporal, cingulate and prefrontal cortical areas, insula, and hippocampus. Post-hoc bidirectional Mendelian randomization analyses provided preliminary evidence in support of a causal relationship between (reduced) thalamic NDI and (increased) risk of schizophrenia.

ConclusionsRisk-related reduction in NDI is plausibly indicative of reduced density of myelinated axons and dendritic arborization in large-scale cortico-subcortical networks. Cortical, subcortical and white matter micro-structure may be linked to the genetic mechanisms of schizophrenia.


title: Grey and white matter micro-structure is associated with polygenic risk for schizophrenia


title: Estimation of real-infection and immunity against SARS-CoV-2 in Indian populations

abstract: Infection born by Coronavirus SARS-CoV-2 has swept the world within a time of a few months. It has created a devastating effect on humanity with social and economic depression. Europe and America were the hardest hit continents. India has also lost lives, making the country fourth most deadly worldwide. However, the infection and death rate per million and the case fatality ratio in India were substantially lower than in many developed nations. Several factors have been proposed including genetics. One of the important facts is that a large chunk of Indian population is asymptomatic to the SARS-CoV-2 infection. Thus, the real infection in India is much higher than the reported number of cases. Therefore, the majority of people are already immune in the country. To understand the dynamics of real infection as well as the level of immunity against SARS-CoV-2, we have performed antibody testing (serosurveillance) in the urban region of fourteen Indian districts encompassing six states. In our survey, the seroprevalence frequency varied between 0.01-0.48, suggesting high variability of viral transmission between states. We also found out that the cases reported by the government were several fold lower than the real incidence of infection. This discrepancy is mainly driven by the higher number of asymptomatic cases. Overall, we suggest that with the high level of immunity developed against SARS-CoV-2 in the majority of the districts, the case fatality rate of second wave in India will be minor than first wave.


title: Substantial measurement error in a commercial multiple breath washout device

abstract:
RationaleNitrogen multiple-breath washout (N2MBW) is an established technique to assess functional residual capacity (FRC) and ventilation inhomogeneity in the lung. Accurate measurement of gas concentrations is essential for the appropriate calculation of clinical outcomes.

ObjectivesWe investigated the accuracy of oxygen and carbon dioxide measurements used for the indirect calculation of nitrogen concentration in a commercial MBW device (Exhalyzer D, Eco Medics AG, Duernten, Switzerland) and its impact on FRC and lung clearance index (LCI).

MethodsHigh precision calibration gas mixtures and mass spectrometry were used to evaluate sensor output. We assessed the impact of corrected signal processing on FRC and LCI in a dataset of healthy children and children with cystic fibrosis using custom analysis software.

ResultsWe found inadequate correction for the cross sensitivity of the oxygen and carbon dioxide sensors in the Exhalyzer D device. This results in an overestimation of expired nitrogen concentration, and consequently FRC and LCI outcomes. Breath-by-breath correction of this error reduced mean (SD) FRC by 8.9 (2.2)% and LCI by 11.9 (4.0)%. It also resulted in almost complete disappearance of the tissue nitrogen signal at the end of measurements.

ConclusionsInadequate correction for cross sensitivity between the oxygen and carbon dioxide gas sensors of the Exhalyzer D device leads to an overestimation of FRC and LCI. Correction of this error is possible and could be applied by re-analysing the measurements breath-by-breath in an updated software version.

Grants, Gifts, Equipment, DrugsEco Medics AG (Duernten, Switzerland) provided a research version of their commercial software Spiroware 3.2.1 including insight on signal processing algorithms and helped with the acquisition of mass spectrometry measurements. This project was funded by the Swiss National Science Foundation, Grant Nr. 182719 (P. Latzin) and 168173 (K. Ramsey)

category: respiratory medicine


title: Correction of measurement error in a commercial multiple-breath washout device


title: Chronic Obstructive Pulmonary Disease Does Not Impair Responses to Resistance Training

abstract:
RationaleSubjects with chronic obstructive pulmonary disease (COPD) are prone to accelerated decay of muscle strength and mass with advancing age. This is mediated by systemic pathophysiologies, which are also believed to impair responses to exercise training, a notion that remains largely unstudied.

ObjectivesTo investigate the presence of impaired training responsiveness in COPD, measured as responses to resistance training compared to healthy participants.

MethodsCOPD (GOLD grade II-III, n=20, age 69{+/-}5) and Healthy (n=58, age 67{+/-}4) conducted identical whole-body resistance training interventions, consisting of two weekly, supervised training sessions for 13 weeks. Leg exercises were performed unilaterally, with one leg conducting high-load training (10 repetitions maximum; RM) and the contralateral leg conducting low-load training (30RM).

Measurements and Main ResultsMeasurements included muscle strength (n=7), endurance performance (n=6), muscle mass (n=2), muscle quality, muscle biology (vastus lateralis; muscle fiber characteristics, RNA content including transcriptome) and health-related variables (body composition, blood). For core outcome domains, weighted combined factors were calculated from the range of singular assessments.

COPD showed marked improvements in lower-limb muscle strength/mass/quality and lower-limb/whole-body endurance performance, resembling or exceeding those of Healthy, measured as both relative and absolute change terms. This was accompanied by similar changes in muscle biological hallmarks (total RNA/rRNA content{uparrow}, muscle fiber cross-sectional area{uparrow}, type IIX proportions{downarrow}, changes in the mRNA transcriptome). Neither of the core outcome domains were differentially affected by resistance training load.

ConclusionsCOPD showed marked, unimpaired and hitherto unrecognized responsiveness to resistance training, rejecting the notion of disease-related impairments in training responsiveness.


title: A prospective double-blinded non-selection trial of reproductive outcomes and chromosomal normalcy of newborns derived from putative low/moderate-degree mosaic IVF embryos

abstract:
BackgroundNext generation sequencing (NGS) has increased detection sensitivity of intermediate chromosome copy number variations (CNV) consistent with chromosomal mosaicism. Recently, this methodology has found application in preimplantation genetic testing (PGT) of trophectoderm (TE) biopsies collected from IVF-generated human embryos. As a consequence, the detection rate of intermediate CNV states in IVF embryos has drastically increased, posing questions about the accuracy in identifying genuine mosaicism in highly heterogeneous biological specimens. The association between analytical values consistent with mosaicism and the reproductive potential of the embryo, as well as newborns chromosomal normalcy, have not yet been thoroughly determined.

MethodsWe conducted a multicentre, double-blinded, non-selection trial including 1,190 patients undergoing in a total of 1,337 IVF with preimplantation genetic testing for aneuploidies (PGT-A) treatment cycles. NGS was performed on clinical TE biopsies collected from blastocyst-stage embryos. All embryos were reported as euploid if all autosomes had a chromosomal copy number value below the threshold of 50% abnormal cells per sample. After embryo transfer, three comparative classes were analysed: uniformly euploid profiles (<20% aneuploid cells), putative low-degree mosaicism (20%-30% aneuploid cells) or putative moderate-degree mosaicism (30%-50% aneuploid cells). Primary outcome measure was live birth rate (LBR) per transfer and newborns karyotype.

ResultsLBR after transfer of uniformly euploid embryos, low-degree, and moderate-degree mosaic embryos were 43.4% (95% C.I. 38.9 - 47.9), 42.9% (95% C.I. 37.1 - 48.9) and 42% (95% C.I. 33.4 - 50.9), respectively. No difference was detected for this primary outcome between euploid and mosaic low/moderate categories (OR= 0.96; 95% CI 0.743 to 1.263; P=0.816). The non-inferiority endpoint was met as the confidence interval for the difference fell below the planned 7.5% margin (95% C.I. -5.7 - 7.3). Likewise, no statistically significant difference was observed comparing moderate versus low degree mosaic embryos (P=0.92). Neonatal karyotypes were also similar and no instances of mosaicism or uniparental disomies (UPDs) were detected in babies born following putative low or moderate-degree mosaic embryo transfer. Should the embryos with low or moderate-degree mosaic TE biopsies had been classified as chromosomally abnormal and thus discarded for clinical use, LBR per cycle would have decreased by 36% without any clinical benefit.

ConclusionsThis prospective non-selection trial provides substantial evidence that reporting and/or not transferring embryos with low/moderate-degree mosaicism for whole chromosomes have no clinical utility. Moreover, dismissing these embryos from clinical use has the counterproductive effect of reducing overall embryo availability, thus reducing the chance of successful outcome derived from an IVF treatment without any clinical benefit. (Funded by Igenomix; ClinicalTrials.gov number, NCT03673592)

category: sexual and reproductive health


title: Effects of Resistant Starch on Symptoms, Fecal Markers and Gut Microbiota in Parkinson's Disease -- The RESISTA-PD Trial

abstract: The composition of the gut microbiome is linked to multiple diseases, including Parkinsons disease (PD). Bacteria producing short-chain fatty acids (SCFAs) and fecal SCFA concentrations are reduced in PD. SCFAs exert various beneficial functions in humans. In the interventional, monocentric, open-label clinical trial RESISTA-PD (NCT02784145) we aimed at altering fecal SCFAs by an 8-week prebiotic intervention with resistant starch (RS). We enrolled 87 subjects in three study-arms: 32 PD patients receiving RS (PD + RS), 30 control subjects receiving RS, and 25 PD patients receiving solely dietary instructions. We performed paired-end 100 base pair length metagenomic sequencing of fecal samples using the BGISEQ platform at an average of 9.9 GB. RS was well-tolerated. In PD + RS, fecal butyrate concentrations increased significantly and fecal calprotectin concentrations dropped significantly after 8 weeks of RS. Clinically, we observed a reduction in non-motor symptoms load in PD + RS. The reference-based analysis of metagenomes highlighted stable alpha-diversity and beta-diversity across the three groups, including bacteria producing SCFAs. Reference-free analysis suggested punctual, yet pronounced differences in the metagenomic signature in PD + RS. RESISTA-PD highlights that a prebiotic treatment with RS is safe and well-tolerated in PD. The stable alpha-diversity and beta-diversity alongside altered fecal butyrate and calprotectin concentrations calls for long-term studies, also investigating whether RS is able to modify the clinical course of PD.

category: neurology


title: Plasma biomarker profiles and the correlation with cognitive function across the clinical spectrum of Alzheimer's disease

abstract:
BackgroundPlasma biomarkers showed a promising value in the disease diagnosis and management of Alzheimers disease (AD). However, profiles of the biomarkers and the association with cognitive domains along the spectrum of cognitive performance deterioration have seldom been reported.

MethodsWe recruited 320 individuals with cognitive impairment and 131 cognitively normal participants from a memory clinic and a community cohort. Participants were classified into 6 groups based on their Clinical Dementia Rating (CDR) scores and clinical diagnosis of AD, amnestic mild cognitive impairment, and normal cognition (NC). Each participant was administered the neuropsychological tests assessing the global and domain-specific cognition. Plasma A{beta}1-40, A{beta}1-42, A{beta}1-42/A{beta}1-40, total tau (t-tau), neurofilament protein light chain (NfL), and phosphorylated tau at threonine 181 (p-tau181) were quantified using the Single molecule array platform.

ResultsAlong with plasma A{beta}1-40, A{beta}1-42, A{beta}1-42/A{beta}1-40, t-tau, and NfL, p-tau181 significantly increased across the groups with the incremental CDR scores from NC (CDR = 0) to severe AD (CDR = 3). Compared with other biomarkers, p-tau181 had a stronger correlation with Global cognition (r = -0.494, P < 0.001), Memory (r = -0.417, P < 0.001), Attention (r = -0.388, P < 0.001), Visuospatial function (r = -0.328, P < 0.001), and Language (r = -0.123, P = 0.014). Among AD participants with CDR [≥] 1, higher p-tau181 was correlated with worse Global cognition (r = -0.295, P < 0.001), Memory (r = -0.172, P = 0.045), and Attention (r = -0.184, P = 0.031).

ConclusionsPlasma p-tau181 had a stronger correlation with cognitive domains than other biomarkers, especially in late-stage AD. It could reflect the AD pathology in vivo and may be a promising blood-based biomarker in clinical settings.


title: Characteristics that modify the effect of small-quantity lipid-based nutrient supplementation on child growth: an individual participant data meta-analysis of randomized controlled trials

abstract:
BackgroundMeta-analyses have demonstrated that small-quantity lipid-based nutrient supplements (SQ-LNS) reduce stunting and wasting prevalence among infants and young children. Identification of subgroups who benefit most from SQ-LNS may facilitate program design.

ObjectiveOur objective was to identify study-level and individual-level modifiers of the effect of SQ-LNS on child growth outcomes.

MethodsWe conducted a two-stage meta-analysis of individual participant data from 14 randomized controlled trials of SQ-LNS provided to children 6 to 24 months of age in low- and middle-income countries (n=37,066). We generated study-specific and subgroup estimates of SQ-LNS vs. control and pooled the estimates using fixed-effects models, with random-effects models as sensitivity analyses. We used random effects meta-regression to examine study-level effect modifiers. Heterogeneity was assessed using I2 and Tau2 statistics. Sensitivity analyses were conducted to examine whether results differed depending on inclusion criteria for arms within trials and types of comparisons.

ResultsSQ-LNS provision decreased stunting (length-for-age z-score < -2) by 12% (relative reduction), wasting (weight-for-length (WLZ) z-score < -2) by 14%, low mid-upper arm circumference (MUAC < 125 mm or MUACZ < -2) by 18%, acute malnutrition (WLZ < -2 or MUAC < 125 mm) by 14%, underweight (weight-for-age z-score < -2) by 13%, and small head size (head-circumference z-score < -2) by 9%. Effects of SQ-LNS on growth outcomes generally did not differ by study-level characteristics including region, stunting burden, malaria prevalence, sanitation, water quality, duration of supplementation, frequency of contact or average reported compliance with SQ-LNS. Effects of SQ-LNS on stunting, wasting, low MUAC and small head size were greater among girls than among boys; effects on stunting, underweight and low MUAC were greater among later-born (vs. first-born) children; and effects on wasting and acute malnutrition were greater among children in households with improved (vs. unimproved) sanitation. Results were similar across sensitivity analyses.

ConclusionsThe positive impact of SQ-LNS on growth is apparent across a wide variety of study-level contexts. Policy-makers and program planners should consider including SQ-LNS in the mix of interventions to prevent both stunting and wasting. This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592.

category: nutrition


title: Natural language processing for patient selection in phase I/II oncology clinical trials

abstract:
PurposeEarly discontinuation affects over one-third of patients enrolled in early-phase oncology clinical trials. Early discontinuation is deleterious both for the patient and for the study, by inflating its duration and associated costs. We aimed at predicting the successful screening and dose-limiting toxicity period completion (SSD) from automatic analysis of consultation reports.

Materials and methodsWe retrieved the consultation reports of patients included in phase I and/or phase II oncology trials for any tumor type at Gustave Roussy, France. We designed a pre-processing pipeline that transformed free-text into numerical vectors and gathered them into semantic clusters. These document-based semantic vectors were then fed into a machine learning model that we trained to output a binary prediction of SSD status.

ResultsBetween September, 2012 and July, 2020, 56,924 consultation reports were used to build the dictionary, and 1,858 phase I/II inclusion reports were used to train (75%), validate (15%) and test (15%) a Random Forest model. Pre-processing could efficiently cluster words with semantic proximity. On the unseen test cohort of 264 consultation reports, the performances of the model reached: F1 score 0.80, recall 0.81 and AUC 0.88. Using this model, we could have reduced the screen fail rate (including DLT period) from 39.8% to 12.8% (RR=0.322, 95%CI[0.209-0.498], p<0.0001) within the test cohort. Most important semantic clusters for predictions comprised words related to hematological malignancies, anatomo-pathological features and laboratory and imaging interpretation.

ConclusionMachine learning with semantic conservation is a promising tool to assist physicians in selecting patients prone to achieve SSD in early-phase oncology clinical trials.

category: oncology


title: COVID-19 increases age- and sex-controlled 21-day fatality rates for patients with melanoma, hematologic malignancies, uterine cancer, or kidney cancer

abstract:
IntroductionPrior research has reported an increased risk of fatality for cancer patients, but most studies investigated the risk by comparing cancer patients to non-cancer patients among COVID-19 infections. Only a few studies have compared the impact of a COVID-19 infection to non-infection with matched cancer patients and types.

Methods & MaterialsWe conducted survival analyses of 4,606 cancer patients with COVID-19 test results from March 16 to October 11, 2020 in UK Biobank and estimated the overall hazard ratio of fatality with and without COVID-19 infection. We also examined the hazard ratios of thirteen specific cancer types with at least 100 patients.

ResultsCOVID-19 resulted in an overall hazard ratio of 7.76 (95% CI: [5.78, 10.40], p<10-10) by studying the survival rate of 4,606 cancer patients for 21-days after the tests. The hazard ratio was shown to vary among cancer type, with over a 10-fold increase in fatality rate (false discovery rate[≤]0.02) for melanoma, hematologic malignancies, uterine cancer, and kidney cancer using a stratified analysis on each of the cancer types. Although COVID-19 imposed a higher risk for localized cancers compared to distant metastasis ones, those of distant metastasis yielded higher fatality rates due to their multiplicative effects.

ConclusionThe results highlight the importance of timely care for localized and hematological cancer patients and the necessity to vaccinate uninfected patients as soon as possible, particularly for the cancer types influenced most by COVID-19.


title: Molecular Mechanism of Parosmia

abstract: The molecular stimuli that trigger a parosmic response have been identified. Parosmia is a debilitating disease in which familiar smells become distorted and unpleasant. Often a result of post infectious smell loss, incidences are increasing as the number of COVID-19 cases escalates worldwide. Little is understood of its pathophysiology, but the prevailing hypothesis for the underlying mechanism is a mis-wiring of olfactory sensory neurons. We identified 15 different molecular triggers in coffee using GC-Olfactometry as a relatively rapid screening tool for assessment of both quantitative olfactory loss and parosmia. This provides evidence for peripheral causation, but places constraints on the mis-wiring theory.

category: otolaryngology


title: Global impact and cost-effectiveness of one-dose versus two-dose human papillomavirus vaccination schedules: a comparative modelling analysis

abstract:
BackgroundTo eliminate cervical cancer as a public health problem, WHO currently recommends routine vaccination of adolescent girls with two doses of the human papillomavirus (HPV) vaccine before sexual debut. However, many countries have yet to implement this because of financial or logistical barriers to delivering two doses outside the infant immunisation programme.

MethodsUsing three independent HPV transmission models, we estimated the long-term health benefits and cost-effectiveness of one-dose versus two-dose HPV vaccination, in 192 countries, assuming that one dose of the vaccine gives either a shorter duration of full protection (20 or 30 years) or lifelong protection but lower vaccine efficacy (e.g., 80%) compared to two doses. We simulated routine vaccination with the 9-valent HPV vaccine in 10-year-old girls at 80% coverage for the years 2021-2120, with a one-year catch-up of 80% 11-14-year-old girls on the first year of the programme.

FindingsOver the next century, one-dose vaccination at 80% coverage could avert 64 million (80%UI 62{middle dot}2-64{middle dot}8) and 66{middle dot}6 million (80%UI 63{middle dot}4-69{middle dot}1) cervical cancer cases should one dose of the vaccine confer 20 and 30 years of protection, respectively. Should one dose of the vaccine provide lifelong protection at 80% vaccine efficacy, 68{middle dot}4 million (80%UI 63{middle dot}8-69{middle dot}4) cervical cancer cases could be prevented. Across all country income groups, two-dose schedules conferring lifelong protection would avert only slightly more cases (2{middle dot}1-8{middle dot}7 million) than the one-dose scenarios explored. Around 330 to 5230 additional girls need to be vaccinated with the second dose to prevent one cervical cancer case, depending on the epidemiological profiles of the country.

InterpretationResults were consistent across the three independent models and suggest that one-dose vaccination has similar health benefits to a two-dose programme while simplifying vaccine delivery, reducing costs and alleviating vaccine supply constraints.

FundingBill & Melinda Gates Foundation

Research in contextO_ST_ABSEvidence before this studyC_ST_ABSPrimary prevention of cervical cancer is now available with human papillomavirus (HPV) vaccination. Initially administered as a three-dose regimen, the HPV vaccine schedule recommended by WHO has now switched to two doses for individuals below the age of 15 years. Although WHO recommends all countries to routinely immunise adolescent girls with two doses, many low- and middle-income countries, with high disease burden, have yet to implement national HPV vaccination programmes because of the challenges of delivering two vaccine doses to adolescent females. Recently, HPV vaccine implementation in many countries has been further delayed due to constraints in vaccine supply and difficulties in access during COVID-19 epidemics. These financial, logistical, and supply constraints have motivated research into one-dose vaccination schedules. Evidence emerging from trials and observational studies suggests that one dose may also provide a high level of protection against incident and persistent HPV infections. If proven effective, the one-dose HPV vaccination schedule would simplify vaccine delivery and lower costs of national vaccination programmes, potentially enabling more countries to implement one and as a result, facilitating global cervical cancer prevention. We searched PubMed for trials, cohort and modelling studies published in 2018 and 2020, with the terms "(health impact OR impact OR modelling OR cost-effectiveness OR CEA OR durability OR effectiveness) AND (HPV OR human papillomavirus OR cervical cancer)" and identified 151 results. Ten published articles--four trials, three cohort studies, two modelling analyses, one systematic review of trials--evaluated the population impact of one dose of the vaccine on cervical cancer disease outcome among females and all studies showed one dose of the vaccine might be as effective as two doses in preventing HPV infection. However as the trials and cohorts were single-country studies in select populations, the global impact remains unknown. Both published modelling analyses only used one model to estimate the impact of one-dose vaccination, and only examined a few countries. To our knowledge, no published article has modelled the global impact of routine one-dose vaccination on cervical cancer prevention by synthesising the results from more than one model.

Added value of this studyThis study presents the first evidence on the potential global impact of a routine one-dose regimen, from a comparative modelling analysis that synthesises results from three published dynamic models calibrated to countries with varying epidemiological and demographic profiles. We found consistent results across all models suggesting that routine one-dose vaccination provides the majority of health benefits to the two-dose programme should a single dose of the vaccine confer more than 20 years of protection at full potential efficacy or 80% efficacy with lifelong protection.

Implications of all the available evidenceFindings suggest that routine one-dose vaccinations could avert almost as many cervical cancer cases as a two-dose programme. The one-dose regimen would be cheaper and easier to implement for most countries while alleviating vaccine supply constraints. To cope with the COVID-19 pandemic, many governments have had to implement stringent physical distancing measures, which has led to the suspension of routine immunisation programmes. Public health authorities grapple with the logistic challenges of delivering immunisation services while minimising the risk of SARS-CoV-2 transmission. Compared to the two-dose vaccination schedule, a one-dose vaccination schedule would reduce interactions between vaccinees and health workers, simplifying vaccine delivery while also decreasing SARS-CoV-2 exposure.


title: Antibody Tests: They Are More Important Than We Thought

abstract: Antibody testing is a non-pharmaceutical intervention - not recognized so far in the literature - to prevent COVID-19 contagion. I show this in a simple economic model of an epidemic in which agents choose social activity under health state uncertainty. In the model, susceptible and asymptomatic agents are more socially active when they think they might be immune. And this increased activity escalates infections, deaths, and welfare losses. Antibody testing, however, prevents this escalation by revealing that those agents are not immune. Through this mechanism, I find that antibody testing prevents about 12% of COVID-19 related deaths within 12 months.


title: Automated Detection of COVID-19 through Convolutional Neural Network using Chest x-ray images

abstract: The COVID-19 epidemic appears to have a catastrophic impact on global well-being and public health. More than 10 million confirmed cases have been reported worldwide until now. Due to the growing number of confirmed cases, timely and accurate classification of healthy and infected patients is essential to control and treat COVID-19. To this end, in this paper, we aim to develop a deep learning-based system for the persuasive classification and reliable detection of COVID-19 using chest radiography. Firstly, we evaluate the performance of various state-of-the-art convolutional neural networks (CNNs) proposed over recent years for medical image classification. Secondly, we develop and train CNN from scratch. In both cases, we use a recently published public X-Ray dataset for training and validation purposes. For transfer learning, we obtain 100% accuracy for binary classification (i.e., Normal/COVID-19) and 87.50% accuracy for tertiary classification (Normal/COVID-19/Pneumonia). With the CNN trained from scratch, we achieve 93.75% accuracy for tertiary classification. We observe, in the case of transfer learning, the classification accuracy drops with an increased number of classes. Our comprehensive ROC and confusion metric analysis with 10-fold cross-validation strongly underpin our findings.

category: health informatics


title: Disparities After Discharge: The Association of Limited English Proficiency and Post-Discharge Patient Reported Issues

abstract:
BackgroundPatients with limited English proficiency (LEP) experience worse outcomes following hospital discharge. Care transition programs are common, yet little is known about the disparities in quality (process and outcome measures) experienced by patients with LEP.

MethodsWe conducted a retrospective cohort study to determine the association of LEP and care transition quality at an urban, US academic hospital. We examined all adults discharge home from the hospital from May 2018 through April 2019. All patients received a multilingual, automated telephone call three days after discharge to assess and address patient-reported issues. We determined care transition quality using process measures (reach rate, time to resolve reported issue) and outcome measures (discharge instructions questions, difficulty obtaining prescriptions, medication concerns, follow up care questions, new or worsening symptoms, any other clinical issues). All results were adjusted for measured confounders; we used predicted probabilities and average marginal effect (AME) to describe associations.

Results13,860 patients were included in the study; 11% had LEP. The program reached most patients regardless of LEP status but was less likely to reach patients with LEP (AME 3.3%; 95% CI, 1.4% to 5.1%). After adjustment, patients with LEP reported high rates of all measured patient-reported outcomes: discharge instruction (AME 4.8%; 95% CI, 2.7% to 6.9%), obtaining prescriptions (AME 2.9%; 95% CI, 0.6% to 5.1%), medications concerns (AME 2.3%; 95% CI, 0.0% to 4.6%), follow up questions (AME 2.8%; 95% CI, 0.3% to 5.3%), new or worsening symptoms (AME 3.2%; 95% CI, 0.7% to 5.8%), and any other clinical issues (AME 3.6%; 95% CI, 1.1% to 6.1%). When issues were identified, the association between LEP and time to resolution of an issue was statistically, but not clinically, significant.

Conclusion and RelevanceAmong patients with LEP, substantial disparities exist in patient-reported post-discharge outcome measures indicating a need for better discharge processes that focus on quality and health equity. Following discharge, relatively minor disparities were observed in the processes of a care transitions program that supports non-English languages.

category: health systems and quality improvement


title: Clinical and Economic Impact of Widespread Rapid Testing to Decrease SARS-CoV-2 Transmission

abstract:
BackgroundThe value of frequent, rapid testing to reduce community transmission of SARS-CoV-2 is poorly understood.

ObjectiveTo define performance standards and predict the clinical, epidemiological, and economic outcomes of nationwide, home-based, antigen testing.

DesignA simple compartmental epidemic model estimated viral transmission, clinical history, and resource use, with and without testing.

Data SourcesParameter values and ranges informed by Centers for Disease Control guidance and published literature.

Target PopulationUnited States population.

Time Horizon60 days.

PerspectiveSocietal.Costs include: testing, inpatient care, and lost workdays.

InterventionHome-based SARS-CoV-2 antigen testing.

Outcome MeasuresCumulative infections and deaths, numbers isolated and/or hospitalized, and total costs.

Results of Base-Case AnalysisWithout a testing intervention, the model anticipates 15 million infections, 125,000 deaths, and $10.4 billion in costs ($6.5 billion inpatient; $3.9 billion lost productivity) over a 60-day horizon. Weekly availability of testing may avert 4 million infections and 19,000 deaths, raising costs by $21.5 billion. Lower inpatient outlays ($5.9 billion) would partially offset additional testing expenditures ($12.0 billion) and workdays lost ($13.9 billion), yielding incremental costs per infection (death) averted of $5,400 ($1,100,000).

Results of Sensitivity AnalysisOutcome estimates vary widely under different behavioral assumptions and testing frequencies. However, key findings persist across all scenarios: large reductions in infections, mortality, and hospitalizations; and costs per death averted roughly an order of magnitude lower than commonly accepted willingness-to-pay values per statistical life saved ($5-17 million).

LimitationsAnalysis restricted to at-home testing and limited by uncertainties about test performance.

ConclusionHigh-frequency home testing for SARS-CoV-2 using an inexpensive, imperfect test could contribute to pandemic control at justifiable cost and warrants consideration as part of a national containment strategy.

Primary Funding SourcesDr. Paltiel was supported by grant R37DA015612 from the National Institute on Drug Abuse of the National Institutes of Health.

Dr. Sax was supported by grant R01AI042006 from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.


title: Performance of three SARS-CoV-2 immunoassays, three rapid lateral flow tests and a novel bead-based affinity surrogate test for the detection of SARS-CoV-2 antibodies in human serum

abstract:
For the control of immunity in COVID-19 survivors and vaccinated subjects there is an urgent need for reliable and rapid serological assays.

Based on samples from 63 COVID-19 survivors up to seven months after symptom onset, and on 50 serum samples taken before the beginning of the pandemic, we compared the performance of three commercial immunoassays for the detection of SARS-CoV-2 IgA and IgG antibodies (Euroimmun SARS-COV-2 IgA/IgG, Mikrogen recomWell SARS-CoV-2 IgA/IgG, and SERION ELISA agile SARS-CoV-2 IgA/IgG) and three rapid lateral flow (immunochromatographic) tests (Abbott Panbio COVID-19 IgG/IgM, NADAL COVID-19 IgG/IgM, and Cleartest Corona 2019-nCOV IgG/IgM) with a plaque-reduction neutralization test (PRNT50) representing the gold standard. In addition, we report and validate a novel, non-commercial flow cytometry bead-based surrogate test.

57 out of 63 PCR-confirmed COVID-19 patients (90 %) showed neutralizing antibodies. The sensitivity of the seven assays ranged from 7.0 % to 98.3 %, the specificity from 86.0 % to 100.00 %. Only one commercial immunoassay showed a sensitivity and specificity of greater than 98 %. These data indicate abundant interassay variability.


title: Decreased SARS-CoV-2 viral load following vaccination

abstract: Beyond their substantial protection of individual vaccinees, it is hoped that the COVID-19 vaccines would reduce viral load in breakthrough infections thereby further suppress onward transmission. Here, analyzing positive SARS-CoV-2 test results following inoculation with the BNT162b2 mRNA vaccine, we find that the viral load is reduced 4-fold for infections occurring 12-28 days after the first dose of vaccine. These reduced viral loads hint to lower infectiousness, further contributing to vaccine impact on virus spread.


title: The changing characteristics of COVID-19 presentations: A regional comparison of SARS-CoV-2 hospitalised patients during the first and second wave.

abstract:
BackgroundThis study assesses COVID-19 hospitalised patient demography and outcomes during wave 1 and wave 2, prior to new variants of the virus.

MethodsAll patients with a positive SARS-CoV-2 swab between 10th March 2020 and 5th July 2020 (wave 1) and 1st September 2020 and 16th November 2020 (wave 2) admitted to University Hospitals Birmingham NHS Foundation Trust were included (n=4856), followed for 28 days.

ResultsWave 2 patients were younger, more ethnically diverse, had less co-morbidities and disease presentation was milder on presentation. After matching for these factors, mortality was reduced, but without differences in intensive care admissions.

ConclusionPrior to new SARS-CoV-2 variants, outcomes for hospitalised patients with COVID-19 were improving but with similar intensive care needs.


title: Assessment & mitigation of O2 therapy driven spread of COVID-19

abstract:
BACKGROUNDExhalation exposure from patients to healthcare workers (HCWs), while using a nasal cannula or simple O2 mask used in treating COVID-19 and other respiratory diseases, is a present and future risk. Little is known on exhalation dispersal through these devices, and on mitigating the viral exposure to those in the vicinity.

METHODSRespiration through O2 therapy devices was studied with a supine manikin equipped with a controllable mechanical lung by measuring aerosol density and flow with direct imaging. Dispersal direction and distances were quantified while placing a surgical mask loosely over the devices and contrasted with unmitigated oxygenation device use. Exhalation jets were examined over the entire range of oxygenation rates used in treatment.

RESULTSExhalation jets travel 0.35 {+/-} 0.02 m upward while wearing a nasal cannula, and 0.29 {+/-} 0.02 m laterally while wearing a simple O2 mask posing significant inhalation risk. Placing a surgical facemask loosely over the oxygenation device is demonstrated to alleviate exposure by reducing and deflecting the exhalation jets from being launched forward, and by reducing exhalations from being launched directly higher over a supine patient. Less than 12% of the exhaled breath is observed to reach above a masked face where HCWs would be present, independent of oxygen flow rates.

CONCLUSIONSExhalation jets from both the nasal cannula or simple O2 mask were found to concentrate aerosol-laden exhalations directly in front of a patients face. Exposure is effectively mitigated with a surgical mask which reduces and redirects the exhalation downward away from HCWs.


title: Gastrointestinal carriage of Klebsiella pneumoniae in a general adult population in Norway: a cross-sectional study of risk factors and bacterial genomic diversity

abstract:
BackgroundKlebsiella pneumoniae is a leading public health threat due to its increasing prevalence of antibiotic resistance. Gastrointestinal carriage of K. pneumoniae is a risk factor for subsequent infections in hospitalised patients. We determined risk factors for gastrointestinal carriage and the genomic population structure of K. pneumoniae colonising humans in a representative sample of a general population.

Methods2,975 individuals (54% women) [≥]40y participating in the population-based Tromso Study 7 (2015-2016) were included. Faecal samples were screened for K. pneumoniae which were characterised using whole-genome sequencing. Risk factors for carriage were analysed using data from the Norwegian Prescription Database and questionnaires, using multivariable logistic regression.

FindingsPrevalence of K. pneumoniae gastrointestinal carriage was 16{middle dot}3% (95% CI 15{middle dot}0-17{middle dot}7%) with no gender difference. Risk factors associated with carriage included age [≥]60y, travel to Greece or Asia past 12 months (adjusted odds ratio 1{middle dot}49, 95% CI 1{middle dot}11-2{middle dot}00), Crohns disease/ulcerative colitis (2{middle dot}26, 1{middle dot}20-4{middle dot}27), use of protein pump inhibitors (1{middle dot}62, 1{middle dot}18-2{middle dot}22) and non-steroidal anti-inflammatory drugs past six months (1{middle dot}38, 1{middle dot}04-1{middle dot}84), and antibiotic use last month (1{middle dot}73, 1{middle dot}05-2{middle dot}86). Prevalence was higher among those having used combinations of drug classes and decreased over time with respect to preceding antibiotic use. The K. pneumoniae population was diverse with 300 sequence types among 484 isolates distributed across four phylogroups. Among the isolates, 5{middle dot}2% and 11{middle dot}6% harboured acquired resistance and virulence factors, respectively.

InterpretationIdentification of risk factors for gastrointestinal carriage in a representative sample of a general population allows for identification of individuals that may have a higher risk of extraintestinal infection during hospitalisation. The diverse population structure of K. pneumoniae carriage isolates reflects the ecologically adaptive capacity of the bacterium, and the low antibacterial consumption probably contributes to the low prevalence of resistance in clinical isolates in Norway.


title: Chronic COVID-19 Syndrome and Chronic Fatigue Syndrome (ME/CFS) following the first pandemic wave in Germany: a first analysis of a prospective observational study

abstract:
ObjectiveCharacterization of the clinical features of patients with persistent symptoms after mild to moderate COVID-19 infection and exploration of factors associated with the development of Chronic COVID-19 Syndrome (CCS).

MethodsSetting: Charite Fatigue Center with clinical immunologists and rheumatologist, neurologists and cardiologists at Charite University hospital.

Participants: 42 patients who presented with persistent moderate to severe fatigue six months following a mostly mild SARS-CoV-2 infection at the Charite Fatigue Center from July to November 2020.

Main outcome measures: The primary outcomes were clinical and paraclinical data and meeting diagnostic criteria for Chronic Fatigue Syndrome (ME/CFS). Relevant neurological and cardiopulmonary morbidity was excluded.

ResultsThe median age was 36.5, range 22-62, 29 patients were female and 13 male. At six months post acute COVID-19 all patients had fatigue (Chalder Fatigue Score median 25 of 33, range 14-32), the most frequent other symptoms were post exertional malaise (n=41), cognitive symptoms (n=40), headache (n=38), and muscle pain (n=35). Most patients were moderately to severely impaired in daily live with a median Bell disability score of 50 (range 15-90) of 100 (healthy) and Short Form 36 (SF-36) physical function score of 63 (range 15-80) of 100. 19 of 42 patients fulfilled the 2003 Canadian Consensus Criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). These patients reported more fatigue in the Chalder Fatigue Score (p=0.006), more stress intolerance (p=0.042) and more frequent and longer post exertional malaise (PEM) (p=0.003), and hypersensitivity to noise (p=0.029), light (p=0.0143) and temperature (p=0.024) compared to patients not meeting ME/CFS criteria. Handgrip force was diminished in most patients compared to healthy control values, and lower in CCS/CFS compared to non-CFS CCS (Fmax1 p=0.085, Fmax2, p=0.050, Fmean1 p=0.043, Fmean2 p=0.034, mean of 10 repeat handgrips, 29 female patients). Mannose-binding lectin (MBL) deficiency was observed frequently (22% of all patients) and elevated IL-8 levels were found in 43% of patients.

ConclusionsChronic COVID-19 Syndrome at months 6 is a multisymptomatic frequently debilitating disease fulfilling diagnostic criteria of ME/CFS in about half of the patients in our study. Research in mechanisms and clinical trials are urgently needed.


title: Dynamics of neutralizing antibody responses in acute-phase COVID-19: A potential relationship between disease progression and rapid neutralizing antibody response

abstract:
IntroductionAdaptive immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dynamics remain largely unknown. The neutralizing antibody (NAb) levels in patients with coronavirus disease 2019 (COVID-19) are helpful for understanding the pathology.

Patients and MethodsUsing SARS-CoV-2 pseudotyped virus, serum sample neutralization values in symptomatic COVID-19 patients were measured using the chemiluminescence reduction neutralization test (CRNT). At least two sequential serum samples collected during hospitalization were analyzed to assess NAbs neutralizing activity dynamics at different time points.

ResultsOf the 11 patients, four (36.4%), six (54.5%), and one (9.1%) had moderate, severe, and critical disease, respectively. Fifty percent neutralization (N50%-CRNT) was observed upon admission in 90.9% (10/11); all patients acquired neutralizing activity 2-12 days after onset. In patients with moderate disease, neutralization was observed at earliest within two days after symptom onset. In patients with severe-to-critical disease, neutralization activity increased, plateauing 9-16 days after onset. Neutralization activity on admission was significantly higher in patients with moderate disease than in patients with severe-to-critical disease (relative % of infectivity, 6.4% vs. 41.1%; P=.0011).

ConclusionsNeutralization activity on admission inversely correlated with disease severity. The rapid NAb response may play a crucial role in preventing the progression of COVID-19.


title: Discovery of cardiac imaging biomarkers by training neural network models across diagnostic modalities

abstract: Machines can be readily trained to automate medical image interpretation, with the primary goal of replicating human capabilities. Here, we propose an alternative role: using machine learning to discover pragmatic imaging-based biomarkers by interpreting one complex imaging modality via a second, more ubiquitous, lower-cost modality. We applied this strategy to train convolutional neural network models to estimate positron emission tomography (PET)-derived myocardial blood flow (MBF) at rest and with hyperemic stress, and their ratio, coronary flow reserve (CFR), using contemporaneous two-dimensional echocardiography videos as inputs. The resulting parameters, echoAI-restMBF, echoAI-stressMBF, and echoAI-CFR modestly approximated the original values. However, using echocardiograms of 5,393 (derivation) and 5,289 (external validation) patients, we show they sharply stratify individuals according to disease comorbidities and combined with baseline demographics, are strong predictors for heart failure hospitalization (C-statistic derivation: 0.79, 95% confidence interval 0.77-0.81; validation: 0.81, 0.79-0.82) and acute coronary syndrome (C-statistic derivation: 0.77, 0.73-0.80; validation: 0.75, 0.73-0.78). Using echocardiograms of 3,926 genotyped individuals, we estimate narrow-sense heritability of 9.2%, 20.4% and 6.5%, respectively for echoAI-restMBF, echoAI-stressMBF, and echoAI-CFR. MBF indices show inverse genetic correlation with impedance-derived body mass indices, such as fat-free body mass (e.g., {rho}=-0.43, q=0.05 for echoAI-restMBF) and resolve conflicting historical data regarding body mass index and CFR. In terms of diseases, genetic association with ischemic heart disease is seen most prominently for echoAI-stressMBF ({rho}=-0.37, q=2.4x10-03). We hypothesize that interpreting one imaging modality through another represents a type of "information bottleneck", capturing latent features of the original physiologic measurements that have relevance across tissues. Thus, we propose a broader potential role for machine learning algorithms in developing scalable biomarkers that are anchored in known physiology, representative of latent biological factors, and are readily deployable in population health applications.

category: cardiovascular medicine


title: Prevention of Diabetic Foot Ulcer in High Risk Patient: The Role of Internist in Providing Adequate Foot Care

abstract:
Background and aimThe awareness and practice of diabetes foot prevention by internist through routine examination and patient education remains less than optimal. This study aimed to evaluate the quality of care of internist in performing foot care in high-risk patients.

MethodsA cross sectional study was conducted in a tertiary care hospital in Jakarta, Indonesia. Type 2 diabetes mellitus subjects with high-risk foot complication were included in this study. Each subject filled-in a questionnaire investigating whether they had received information about proper foot care practice and whether they have ever had their feet examined by an internist at their present consultation. Multivariate logistic regression were performed.

Results368 patients were recruited, 130 of them (35.3%) treated by endocrinologists. 71.20% patients did not received any information on foot care and 54.08% patients did not received any foot examination. Foot care information was 1.6 times more frequently provided to patient with longer diabetes duration and 2 times more frequently provided to those who had history of diabetic foot ulcer. Meanwhile, foot examination was 1.5 times more frequently provided to those with longer diabetes duration and had a history of Lower Extremity Amputation. Compare to non-endocrinologist internist, endocrinologists tend to provide foot education and perform foot examination 2.2 to 2.5 times more frequently than non-endocrinologists.

ConclusionMost of patients with high risk foot problems were not offered adequate foot care. It is necessary to develop strategies to improve the care and awareness among health professionals treating patients with diabetes especially internist.

category: endocrinology


title: SplitStrains, a tool to identify and separate mixed Mycobacterium tuberculosis infections from WGS data

abstract:
The occurrence of multiple strains of a bacterial pathogen such as M. tuberculosis or C. difficile within a single human host, referred to as a mixed infection, has important implications for both healthcare and public health. However, methods for detecting it, and especially determining the proportion and identities of the underlying strains, from WGS (whole-genome sequencing) data, have been limited.

In this paper we introduce SplitStrains, a novel method for addressing these challenges. Grounded in a rigorous statistical model, SplitStrains not only demonstrates superior performance in proportion estimation to other existing methods on both simulated as well as real M. tuberculosis data, but also successfully determines the identity of the underlying strains.

We conclude that SplitStrains is a powerful addition to the existing toolkit of analytical methods for data coming from bacterial pathogens, and holds the promise of enabling previously inaccessible conclusions to be drawn in the realm of public health microbiology.

Author summaryWhen multiple strains of a pathogenic organism are present in a patient, it may be necessary to not only detect this, but also to identify the individual strains. However, this problem has not yet been solved for bacterial pathogens processed via whole-genome sequencing. In this paper, we propose the SplitStrains algorithm for detecting multiple strains in a sample, identifying their proportions, and inferring their sequences, in the case of Mycobacterium tuberculosis. We test it on both simulated and real data, with encouraging results. We believe that our work opens new horizons in public health microbiology by allowing a more precise detection, identification and quantification of multiple infecting strains within a sample.

category: epidemiology


title: West Nile virus in Portugal

abstract:
West Nile virus (WNV) causes outbreaks with sustained spillover to humans in many European countries. Despite Portugals Mediterranean climate being adequate for WNV transmission, only four human infections have been detected there so far. Here, we offer an historical account of past WNV circulation and develop new, climate-driven insights on the geo-temporal suitability for WNV transmission in Portugal. WNV and vector related literature and database reviews were performed in the context of Portugal covering the time period 1966-2020, and local climate data were used to estimate WNV transmission suitability for the period 1981-2019. Reviewed data demonstrate that WNV-compatible vectors are abundant across the entire country, while molecular and serological evidence for WNV circulation has mostly been associated with the southern districts. Our estimated WNV transmission suitability was found to support geographical differences in transmission potential that favour the southern districts, with an increasing trend over the past forty years due to climate change. Empirical and theoretical evidence supports WNV circulation in Portugal, but it remains unclear whether the virus is endemic or sporadically transmitted. Given the recent public health emergencies related to WNV in other European countries and the findings herein described in relation to Portugal, our study supports a timely change towards a local WNV active surveillance.

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title: The impact of mobility network properties on predicted epidemic dynamics in Dhaka and Bangkok

abstract: 1Properties of city-level commuting networks are expected to influence epidemic potential of cities and modify the speed and spatial trajectory of epidemics when they occur. In this study, we use aggregated mobile phone user data to reconstruct commuter mobility networks for Bangkok (Thailand) and Dhaka (Bangladesh), two megacities in Asia with populations of 16 and 21 million people, respectively. We model the dynamics of directly-transmitted infections (such as SARS-CoV2) propagating on these commuting networks, and find that differences in network structure between the two cities drive divergent predicted epidemic trajectories: the commuting network in Bangkok is composed of geographically-contiguous modular communities and epidemic dispersal is correlated with geographic distance between locations, whereas the network in Dhaka has less distinct geographic structure and epidemic dispersal is less constrained by geographic distance. We also find that the predicted dynamics of epidemics vary depending on the local topology of the network around the origin of the outbreak. Measuring commuter mobility, and understanding how commuting networks shape epidemic dynamics at the city level, can support surveillance and preparedness efforts in large cities at risk for emerging or imported epidemics.


title: COVIDHunter: An Accurate, Flexible, and Environment-Aware Open-Source COVID-19 Outbreak Simulation Model

abstract:
MotivationEarly detection and isolation of COVID-19 patients are essential for successful implementation of mitigation strategies and eventually curbing the disease spread. With a limited number of daily COVID-19 tests performed in every country, simulating the COVID-19 spread along with the potential effect of each mitigation strategy currently remains one of the most effective ways in managing the healthcare system and guiding policy-makers. We introduce COVIDHunter, a flexible and accurate COVID-19 outbreak simulation model that evaluates the current mitigation measures that are applied to a region and provides suggestions on what strength the upcoming mitigation measure should be. The key idea of COVIDHunter is to quantify the spread of COVID-19 in a geographical region by simulating the average number of new infections caused by an infected person considering the effect of external factors, such as environmental conditions (e.g., climate, temperature, humidity) and mitigation measures.

ResultsUsing Switzerland as a case study, COVIDHunter estimates that the policy-makers need to keep the current mitigation measures for at least 30 days to prevent demand from quickly exceeding existing hospital capacity. Relaxing the mitigation measures by 50% for 30 days increases both the daily capacity need for hospital beds and daily number of deaths exponentially by an average of 23.8 x, who may occupy ICU beds and ventilators for a period of time. Unlike existing models, the COVIDHunter model accurately monitors and predicts the daily number of cases, hospitalizations, and deaths due to COVID-19. Our model is flexible to configure and simple to modify for modeling different scenarios under different environmental conditions and mitigation measures.

Availabilityhttps://github.com/CMU-SAFARI/COVIDHunter

Contactalserm@ethz.ch, omutlu@ethz.ch

Supplementary informationSupplementary data is available at Bioinformatics online.


title: A Quantitative Evaluation of COVID-19 Epidemiological Models

abstract: Quantifying how accurate epidemiological models of COVID-19 forecast the number of future cases and deaths can help frame how to incorporate mathematical models to inform public health decisions. Here we analyze and score the predictive ability of publicly available COVID-19 epidemiological models on the COVID-19 Forecast Hub. Our score uses the posted forecast cumulative distributions to compute the log-likelihood for held-out COVID-19 positive cases and deaths. Scores are updated continuously as new data become available, and model performance is tracked over time. We use model scores to construct ensemble models based on past performance. Our publicly available quantitative framework may aid in improving modeling frameworks, and assist policy makers in selecting modeling paradigms to balance the delicate trade-offs between the economy and public health.


title: Pre-pandemic cognitive function and COVID-19 mortality: prospective cohort study

abstract:
BackgroundPoorer performance on standard tests of cognitive function is related to an elevated risk of death from lower respiratory tract infections. Whether pre-pandemic measures of cognition are related to COVID-19 mortality is untested.

MethodsUK Biobank, a prospective cohort study, comprises around half a million people who were aged 40 to 69 years at study induction between 2006 and 2010 when a reaction time test was administered to the full sample, and verbal-numeric reasoning assessed in a subgroup. Death from COVID-19 was ascertained from participant linkage to a UK-wide national registry.

ResultsBetween April 1st and September 23rd 2020, there were 388 deaths (138 women) ascribed to COVID-19 in the 494,932 individuals (269,602 women) with a reaction time test result, and 125 such deaths (38 women) in the 180,198 (97,794 women) for whom there were data on verbal-numeric reasoning. In analyses adjusted for age, sex, and ethnicity, a one standard deviation (118.2 msec) slower reaction time was related to a higher rate of death from COVID-19 (hazard ratio; 95% confidence interval: 1.18; 1.09, 1.28). A one standard deviation disadvantage (2.16 point) on the verbal-numeric reasoning test was also associated with an elevated risk of death (1.32; 1.09, 1.59). Attenuation after adjustment for additional covariates followed a similar pattern for both measures of cognition. For verbal-numeric reasoning, for instance, the hazard ratios were 1.22 (0.98, 1.51) after control for socioeconomic status, 1.16 (0.96, 1.41) after lifestyle factors, 1.25 (1.04, 1.52) after co-morbidity, and 1.29 (1.01, 1.64) after physiological indices.

ConclusionsIn the present study, poorer performance on two pre-pandemic indicators of cognitive function, including reaction time, a knowledge-reduced measure, was related to death ascribed to COVID-19.