Socio-demographic predictors of not having private dental insurance coverage: machine-learning algorithms may help identify the disadvantaged.

Background: For accessing dental care in Canada, approximately 62% of the population has employment-based insurance, 6% have some publicly funded coverage, and 32% have to pay out-of pocket. Those with no insurance or public coverage find dental care more unaffordable compared to those with private insurance. To support the development of more comprehensive publicly funded dental care programs, it is important to understand the socio-demographic attributes of all those, who find dental care unaffordable.

Comparing the transmission potential from sequence and surveillance data of 2009 North American influenza pandemic waves.

Technological advancements in phylodynamic modeling coupled with the accessibility of real-time pathogen genetic data are increasingly important for understanding the infectious disease transmission dynamics. In this study, we compare the transmission potentials of North American influenza A(H1N1)pdm09 derived from sequence data to that derived from surveillance data. The impact of the choice of tree-priors, informative epidemiological priors, and evolutionary parameters on the transmission potential estimation is evaluated.

Angiotensin-Converting Enzyme (ACE) Inhibitors May Moderate COVID-19 Hyperinflammatory Response: An Observational Study with Deep Immunophenotyping.

Background: Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-II receptor blockers (ARB), the most commonly prescribed antihypertensive medications, counter renin-angiotensin-aldosterone system (RAAS) activation via induction of angiotensin-converting enzyme 2 (ACE2) expression. Considering that ACE2 is the functional receptor for SARS-CoV-2 entry into host cells, the association of ACEi and ARB with COVID-19 outcomes needs thorough evaluation.

Methods: We conducted retrospective analyses using both unmatched and propensity score (PS)-matched cohorts on electronic health records (EHRs) to assess the impact of RAAS inhibitors on the risk of receiving invasive mechanical ventilation (IMV) and 30-day mortality among hospitalized COVID-19 patients.

Monkeypox Virus Detection in Different Clinical Specimen Types.

A global monkeypox outbreak began in May 2022. Limited data exist on specimen type performance in associated molecular diagnostics. Consequently, a diverse range of specimen sources were collected in the initial weeks of the outbreak in Ontario, Canada.

Risk factors for severe COVID-19 differ by age for hospitalized adults.

Risk stratification for hospitalized adults with COVID-19 is essential to inform decisions about individual patients and allocation of resources. So far, risk models for severe COVID outcomes have included age but have not been optimized to best serve the needs of either older or younger adults. Models also need to be updated to reflect improvements in COVID-19 treatments.

Multiple early factors anticipate post-acute COVID-19 sequelae.

Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data and patient-reported symptoms.

Angiotensin II receptor I auto-antibodies following SARS-CoV-2 infection.

Background: Coronavirus disease 2019 (COVID-19) is associated with endothelial activation and coagulopathy, which may be related to pre-existing or infection-induced pro-thrombotic autoantibodies such as those targeting angiotensin II type I receptor (AT1R-Ab).

Methods: We compared prevalence and levels of AT1R-Ab in COVID-19 cases with mild or severe disease to age and sex matched negative controls utilizing multivariate logistic and quantile regression adjusted for comorbidities including hypertension, diabetes, and heart disease.

Results: There were trends toward increased prevalence (50% vs.

Integrated analysis of plasma and single immune cells uncovers metabolic changes in individuals with COVID-19.

A better understanding of the metabolic alterations in immune cells during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may elucidate the wide diversity of clinical symptoms experienced by individuals with coronavirus disease 2019 (COVID-19). Here, we report the metabolic changes associated with the peripheral immune response of 198 individuals with COVID-19 through an integrated analysis of plasma metabolite and protein levels as well as single-cell multiomics analyses from serial blood draws collected during the first week after clinical diagnosis. We document the emergence of rare but metabolically dominant T cell subpopulations and find that increasing disease severity correlates with a bifurcation of monocytes into two metabolically distinct subsets.

Multi-Omics Resolves a Sharp Disease-State Shift between Mild and Moderate COVID-19.

We present an integrated analysis of the clinical measurements, immune cells, and plasma multi-omics of 139 COVID-19 patients representing all levels of disease severity, from serial blood draws collected during the first week of infection following diagnosis. We identify a major shift between mild and moderate disease, at which point elevated inflammatory signaling is accompanied by the loss of specific classes of metabolites and metabolic processes. Within this stressed plasma environment at moderate disease, multiple unusual immune cell phenotypes emerge and amplify with increasing disease severity.

Multiomic Immunophenotyping of COVID-19 Patients Reveals Early Infection Trajectories.

Host immune responses play central roles in controlling SARS-CoV2 infection, yet remain incompletely characterized and understood. Here, we present a comprehensive immune response map spanning 454 proteins and 847 metabolites in plasma integrated with single-cell multi-omic assays of PBMCs in which whole transcriptome, 192 surface proteins, and T and B cell receptor sequence were co-analyzed within the context of clinical measures from 50 COVID19 patient samples. Our study reveals novel cellular subpopulations, such as proliferative exhausted CD8 and CD4 T cells, and cytotoxic CD4 T cells, that may be features of severe COVID-19 infection.

Agricultural and geographic factors shaped the North American 2015 highly pathogenic avian influenza H5N2 outbreak.

The 2014-2015 highly pathogenic avian influenza (HPAI) H5NX outbreak represents the largest and most expensive HPAI outbreak in the United States to date. Despite extensive traditional and molecular epidemiological studies, factors associated with the spread of HPAI among midwestern poultry premises remain unclear. To better understand the dynamics of this outbreak, 182 full genome HPAI H5N2 sequences isolated from commercial layer chicken and turkey production premises were analyzed using evolutionary models able to accommodate epidemiological and geographic information.

Computational Approaches and Challenges to Developing Universal Influenza Vaccines.

The traditional design of effective vaccines for rapidly-evolving pathogens, such as influenza A virus, has failed to provide broad spectrum and long-lasting protection. With low cost whole genome sequencing technology and powerful computing capabilities, novel computational approaches have demonstrated the potential to facilitate the design of a universal influenza vaccine. However, few studies have integrated computational optimization in the design and discovery of new vaccines.

Global Distribution and Evolutionary History of Enterovirus D68, with Emphasis on the 2014 Outbreak in Ontario, Canada.

Despite its first appearance in 1962, human enterovirus D68 (EV-D68) has been recognized as an emerging respiratory pathogen in the last decade when it caused outbreaks and clusters in several countries including Japan, the Philippines, and the Netherlands. The most recent and largest outbreak of EV-D68 associated with severe respiratory illness took place in North America between August 2014 and January 2015. Between September 1 and October 31 2014, EV-D68 infection was laboratory confirmed among 153/907 (16.

Genetic diversity and evolutionary insights of respiratory syncytial virus A ON1 genotype: global and local transmission dynamics.

Human respiratory syncytial virus (RSV) A ON1 genotype, first detected in 2010 in Ontario, Canada, has been documented in 21 countries to date. This study investigated persistence and transmission dynamics of ON1 by grouping 406 randomly selected RSV-positive specimens submitted to Public Health Ontario from August 2011 to August 2012; RSV-A-positive specimens were genotyped. We identified 370 RSV-A (181 NA1, 135 NA2, 51 ON1 3 GA5) and 36 RSV-B positive specimens.

Human metapneumovirus prevalence and molecular epidemiology in respiratory outbreaks in Ontario, Canada.

Human metapneumovirus (hMPV) has been identified previously as a cause of respiratory outbreaks in adults, including the elderly. The objective of this study was to document respiratory outbreaks that were caused by hMPV in Ontario, Canada and to identify the various circulating genotypes during April 2009-February 2012. The majority of the outbreaks that were part of this study were in adults (>65 years).

The human immune system recognizes neopeptides derived from mitochondrial DNA deletions.

Mutations in mitochondrial (mt) DNA accumulate with age and can result in the generation of neopeptides. Immune surveillance of such neopeptides may allow suboptimal mitochondria to be eliminated, thereby avoiding mt-related diseases, but may also contribute to autoimmunity in susceptible individuals. To date, the direct recognition of neo-mtpeptides by the adaptive immune system has not been demonstrated.

Estimated effects of projected climate change on the basic reproductive number of the Lyme disease vector Ixodes scapularis.

Background: The extent to which climate change may affect human health by increasing risk from vector-borne diseases has been under considerable debate.

Objectives: We quantified potential effects of future climate change on the basic reproduction number (R0) of the tick vector of Lyme disease, Ixodes scapularis, and explored their importance for Lyme disease risk, and for vector-borne diseases in general.

Methods: We applied observed temperature data for North America and projected temperatures using regional climate models to drive an I.

Preexisting CD4+ T-cell immunity in human population to avian influenza H7N9 virus: whole proteome-wide immunoinformatics analyses.

In 2013, a novel avian influenza H7N9 virus was identified in human in China. The antigenically distinct H7N9 surface glycoproteins raised concerns about lack of cross-protective neutralizing antibodies. Epitope-specific preexisting T-cell immunity was one of the protective mechanisms in pandemic 2009 H1N1 even in the absence of cross-protective antibodies.

Genetic characterization of seasonal influenza A (H3N2) viruses in Ontario during 2010-2011 influenza season: high prevalence of mutations at antigenic sites.

Background: The direct effect of antigenic site mutations in influenza viruses on antigenic drift and vaccine effectiveness is poorly understood.

Objective: To investigate the genetic and antigenic characteristics of human influenza A (H3N2) viruses circulating in Ontario during the early 2010-2011 winter season.

Study Design: We sequenced the hemagglutinin (HA) and neuraminidase (NA) genes from 41 A(H3N2) viruses detected in nasopharyngeal specimens.

Challenges and opportunities for bacterial vaccine development in the 21(st) century.

With the convergence of modern technology in genomics, proteomics, carbohydrate, protein and lipid biochemistry as well as decades of experience in vaccine development and delivery of immunization programs, the Global Vaccine Action Plan has declared 2011 to 2020 as 'The Decade of Vaccines'. This review focuses on bacterial vaccines and summarises the current state of vaccinology in bacteriology and looks forward to the potential of how the newer technologies can impact our knowledge of bacterial diseases and their control through vaccine development. The major breakthroughs in the last couple of decades include low cost high throughput genomics, proteomics, cellular immunology and the delicate network of immune-cytokines, bioinformatics, immune-informatics, and disease modelling.

T cell memory to evolutionarily conserved and shared hemagglutinin epitopes of H1N1 viruses: a pilot scale study.

Background: The 2009 pandemic influenza was milder than expected. Based on the apparent lack of pre-existing cross-protective antibodies to the A (H1N1)pdm09 strain, it was hypothesized that pre-existing CD4+ T cellular immunity provided the crucial immunity that led to an attenuation of disease severity. We carried out a pilot scale study by conducting in silico and in vitro T cellular assays in healthy population, to evaluate the pre-existing immunity to A (H1N1)pdm09 strain.