A Genomic Counseling Model for Population-Based Sequencing: A Pre-Post Intervention Study.

BACKGROUND: Novel uses of genome sequencing (GS) present an opportunity for return of results to healthy individuals, prompting the need for scalable genetic counseling strategies. We evaluate the effectiveness of a genomic counseling model (GCM) and explore preferences for GS findings in the general population. METHODS: Participants (N=466) completed GS and our GCM (digital genomics platform and group-based webinar), and indicated results preferences. Surveys were administered pre- (T0) and post- (T1) GCM. Change in knowledge and decisional conflict (DC) were evaluated using paired-sample T and Wilcoxon tests. Factors influencing knowledge and results preferences were evaluated using linear and logistic regression models. RESULTS: Participants were 56% female, 58% white, and 53% ≥40 years of age. Mean knowledge scores increased (Limitations: 3.73 to 5.63; benefits: 3.73 to 5.48, p<0.0001) and DC decreased (-21.9, p<0.0001) at T1 versus T0. Eighty-six percent of participants wished to learn all GS findings at T1 vs 78% at T0 (p<0.0001). Older age, negative/mixed attitudes toward genetics, and greater DC were associated with change in preferences post-intervention. CONCLUSION: In a population-based cohort undergoing GS interested in learning GS findings, our GCM increased knowledge and reduced DC, illustrating the GCM's potential effectiveness for GS counseling in the general population.

Genome screening, reporting, and genetic counseling for healthy populations.

Rapid advancements of genome sequencing (GS) technologies have enhanced our understanding of the relationship between genes and human disease. To incorporate genomic information into the practice of medicine, new processes for the analysis, reporting, and communication of GS data are needed. Blood samples were collected from adults with a PCR-confirmed SARS-CoV-2 (COVID-19) diagnosis (target N = 1500). GS was performed. Data were filtered and analyzed using custom pipelines and gene panels. We developed unique patient-facing materials, including an online intake survey, group counseling presentation, and consultation letters in addition to a comprehensive GS report. The final report includes results generated from GS data: (1) monogenic disease risks; (2) carrier status; (3) pharmacogenomic variants; (4) polygenic risk scores for common conditions; (5) HLA genotype; (6) genetic ancestry; (7) blood group; and, (8) COVID-19 viral lineage. Participants complete pre-test genetic counseling and confirm preferences for secondary findings before receiving results. Counseling and referrals are initiated for clinically significant findings. We developed a genetic counseling, reporting, and return of results framework that integrates GS information across multiple areas of human health, presenting possibilities for the clinical application of comprehensive GS data in healthy individuals.

Establishing quality indicators for point of care glucose testing: recommendations from the Canadian Society for Clinical Chemists Point of Care Testing and Quality Indicators Special Interest Groups.

OBJECTIVES: Monitoring quality indicators (QIs) is an important part of laboratory quality assurance (QA). Here, the Canadian Society of Clinical Chemists (CSCC) Point of Care Testing (POCT) and QI Special Interest Groups describe a process for establishing and monitoring QIs for POCT glucose testing. METHODS: Key, error prone steps in the POCT glucose testing process were collaboratively mapped out, followed by risk assessment for each step. Steps with the highest risk and ability to detect a non-conformance were chosen for follow-up. These were positive patient identification (PPID) and repeat of critically high glucose measurements. Participating sites were asked to submit aggregate data for these indicators from their site(s) for a one-month period. The PPID QI was also included as part of a national QI monitoring program for which fifty-seven sites submitted data. RESULTS: The percentage of POCT glucose tests performed without valid PPID ranged from 0-87%. Sites without Admission-Discharge-Transfer (ADT) connectivity to POCT meters were among those with the highest percentage of POCT glucose tests performed without valid PPID. The percentage repeated critically high glucose measurements ranged from 0-50%, indicating low compliance with this recommendation. A high rate of discordance was also noted when critically high POCT glucose measurements were repeated, demonstrating the importance of repeat testing prior to insulin administration. CONCLUSIONS: Here, a process for establishing these QIs is described, with preliminary data for two QIs chosen from this process. The findings demonstrate the importance of QIs for identification and comparative performance monitoring of non-conformances to improve POCT quality.

Canadian health care providers' and education workers' hesitance to receive original and bivalent COVID-19 vaccines.

BACKGROUND: The demand for COVID-19 vaccines has diminished as the pandemic lingers. Understanding vaccine hesitancy among essential workers is important in reducing the impact of future pandemics by providing effective immunization programs delivered expeditiously. METHOD: Two surveys exploring COVID-19 vaccine acceptance in 2021 and 2022 were conducted in cohorts of health care providers (HCP) and education workers participating in prospective studies of COVID-19 illnesses and vaccine uptake. Demographic factors and opinions about vaccines (monovalent and bivalent) and public health measures were collected in these self-reported surveys. Modified multivariable Poisson regression was used to determine factors associated with hesitancy. RESULTS: In 2021, 3 % of 2061 HCP and 6 % of 3417 education workers reported hesitancy (p < 0.001). In December 2022, 21 % of 868 HCP and 24 % of 1457 education workers reported being hesitant to receive a bivalent vaccine (p = 0.09). Hesitance to be vaccinated with the monovalent vaccines was associated with earlier date of survey completion, later receipt of first COVID-19 vaccine dose, no influenza vaccination, and less worry about becoming ill with COVID-19. Factors associated with hesitance to be vaccinated with a bivalent vaccine that were common to both cohorts were receipt of two or fewer previous COVID-19 doses and lower certainty that the vaccines were safe and effective. CONCLUSION: Education workers were somewhat more likely than HCP to report being hesitant to receive COVID-19 vaccines but reasons for hesitancy were similar. Hesitancy was associated with non-receipt of previous vaccines (i.e., previous behaviour), less concern about being infected with SARS-CoV-2, and concerns about the safety and effectiveness of vaccines for both cohorts. Maintaining inter-pandemic trust in vaccines, ensuring rapid data generation during pandemics regarding vaccine safety and effectiveness, and effective and transparent communication about these data are all needed to support pandemic vaccination programs.

COVID-19 vaccine reactogenicity among participants enrolled in the GENCOV study.

BACKGROUND: GENCOV is a prospective, observational cohort study of COVID-19-positive adults. Here, we characterize and compare side effects between COVID-19 vaccines and determine whether reactogenicity is exacerbated by prior SARS-CoV-2 infection. METHODS: Participants were recruited across Ontario, Canada. Participant-reported demographic and COVID-19 vaccination data were collected using a questionnaire. Multivariable logistic regression was performed to assess whether vaccine manufacturer, type, and previous SARS-CoV-2 infection are associated with reactogenicity. RESULTS: Responses were obtained from n = 554 participants. Tiredness and localized side effects were the most common reactions across vaccine doses. For most participants, side effects occurred and subsided within 1-2 days. Recipients of Moderna mRNA and AstraZeneca vector vaccines reported reactions more frequently compared to recipients of a Pfizer-BioNTech mRNA vaccine. Previous SARS-CoV-2 infection was independently associated with developing side effects. CONCLUSIONS: We provide evidence of relatively mild and short-lived reactions reported by participants who have received approved COVID-19 vaccines.

Imprecision of high-sensitivity cardiac troponin assays at the female 99th-percentile.

BACKGROUND: An analytical benchmark for high-sensitivity cardiac troponin (hs-cTn) assays is to achieve a coefficient of variation (CV) of ≤ 10.0 % at the 99th percentile upper reference limit (URL) used for the diagnosis of myocardial infarction. Few prospective multicenter studies have evaluated assay imprecision and none have determined precision at the female URL which is lower than the male URL for all cardiac troponin assays. METHODS: Human serum and plasma matrix samples were constructed to yield hs-cTn concentrations near the female URLs for the Abbott, Beckman, Roche, and Siemens hs-cTn assays. These materials were sent (on dry ice) to 35 Canadian hospital laboratories (n = 64 instruments evaluated) participating in a larger clinical trial, with instructions for storage, handling, and monthly testing over one year. The mean concentration, standard deviation, and CV for each instrument type and an overall pooled CV for each manufacturer were calculated. RESULTS: The CVs for all individual instruments and overall were ≤ 10.0 % for two manufacturers (Abbott CVpooled = 6.3 % and Beckman CVpooled = 7.0 %). One of four Siemens Atellica instruments yielded a CV > 10.0 % (CVpooled = 7.7 %), whereas 15 of 41 Roche instruments yielded CVs > 10.0 % at the female URL of 9 ng/L used worldwide (6 cobas e411, 1 cobas e601, 4 cobas e602, and 4 cobas e801) (CVpooled = 11.7 %). Four Roche instruments also yielded CVs > 10.0 % near the female URL of 14 ng/L used in the United States (CVpooled = 8.5 %). CONCLUSIONS: The number of instruments achieving a CV ≤ 10.0 % at the female 99th-percentile URL varies by manufacturer and by instrument. Monitoring assay precision at the female URL is necessary for some assays to ensure optimal use of this threshold in clinical practice.

Public knowledge of SARS-CoV-2 serological and viral lineage laboratory testing and result interpretation: A GENCOV study cross-sectional survey.

OBJECTIVES: Concepts related to SARS-CoV-2 laboratory testing and result interpretation can be challenging to understand. A cross-sectional survey of COVID-19 positive adults residing in Ontario, Canada was conducted to explore how well people understand SARS-CoV-2 laboratory tests and their associated results. DESIGN AND METHODS: Participants were recruited through fliers or by prospective recruitment of outpatients and hospitalized inpatients with COVID-19. Enrolled participants included consenting adults with a positive SARS-CoV-2 polymerase chain reaction test result. An 11-item questionnaire was developed by researchers, nurses, and physicians in the study team and was administered online between April 2021 to May 2022 upon enrolment into the study. RESULTS: Responses were obtained from 940 of 1106 eligible participants (85% participation rate). Most respondents understood 1) that antibody results should not influence adherence to social distancing measures (n = 602/888, 68%), 2) asymptomatic SARS-CoV-2 infection following test positivity (n = 698/888, 79%), 3) serological test sensitivity in relation to post-infection timeline (n = 540/891, 61%), and 4) limitations of experts' knowledge related to SARS-CoV-2 serology (n = 693/887, 78%). Conversely, respondents demonstrated challenges understanding 1) conflicting molecular and serological test results and their relationship with immune protection (n = 162/893, 18%) and 2) the impact of SARS-CoV-2 variants on vaccine effectiveness (n = 235/891, 26%). Analysis of responses stratified by sociodemographic variables identified that respondents who were either: 1) female, 2) more educated, 3) aged 18-44, 4) from a high-income household, or 5) healthcare workers responded expectedly more often. CONCLUSIONS: We have highlighted concepts related to SARS-CoV-2 laboratory tests and associated results which may be challenging to understand. The findings of this study enable us to identify 1) misconceptions related to various SARS-CoV-2 test results, 2) groups of individuals at risk, and 3) strategies to improve people's understanding of their test results.

Characterizing Risk Factors for Hospitalization and Clinical Characteristics in a Cohort of COVID-19 Patients Enrolled in the GENCOV Study.

The GENCOV study aims to identify patient factors which affect COVID-19 severity and outcomes. Here, we aimed to evaluate patient characteristics, acute symptoms and their persistence, and associations with hospitalization. Participants were recruited at hospital sites across the Greater Toronto Area in Ontario, Canada. Patient-reported demographics, medical history, and COVID-19 symptoms and complications were collected through an intake survey. Regression analyses were performed to identify associations with outcomes including hospitalization and COVID-19 symptoms. In total, 966 responses were obtained from 1106 eligible participants (87% response rate) between November 2020 and May 2022. Increasing continuous age (aOR: 1.05 [95%CI: 1.01-1.08]) and BMI (aOR: 1.17 [95%CI: 1.10-1.24]), non-White/European ethnicity (aOR: 2.72 [95%CI: 1.22-6.05]), hypertension (aOR: 2.78 [95%CI: 1.22-6.34]), and infection by viral variants (aOR: 5.43 [95%CI: 1.45-20.34]) were identified as risk factors for hospitalization. Several symptoms including shortness of breath and fever were found to be more common among inpatients and tended to persist for longer durations following acute illness. Sex, age, ethnicity, BMI, vaccination status, viral strain, and underlying health conditions were associated with developing and having persistent symptoms. By improving our understanding of risk factors for severe COVID-19, our findings may guide COVID-19 patient management strategies by enabling more efficient clinical decision making.

Canadian Society of Clinical Chemists (CSCC) consensus guidance for testing, selection and quality management of SARS-CoV-2 point-of-care tests.

OBJECTIVES: A consensus guidance is provided for testing, utility and verification of SARS-CoV-2 point-of-care test (POCT) performance and implementation of a quality management program, focusing on nucleic acid and antigen targeted technologies. DESIGN AND METHODS: The recommendations are based on current literature and expert opinion from the members of Canadian Society of Clinical Chemists (CSCC), and are intended for use inside or outside of healthcare settings that have varied levels of expertise and experience with POCT. RESULTS AND CONCLUSIONS: Here we discuss sampling requirements, biosafety, SARS-CoV-2 point-of-care testing methodologies (with focus on Health Canada approved tests), test performance and limitations, test selection, testing utility, development and implementation of quality management systems, quality improvement, and medical and scientific oversight.

Implementation of serological and molecular tools to inform COVID-19 patient management: protocol for the GENCOV prospective cohort study.

INTRODUCTION: There is considerable variability in symptoms and severity of COVID-19 among patients infected by the SARS-CoV-2 virus. Linking host and virus genome sequence information to antibody response and biological information may identify patient or viral characteristics associated with poor and favourable outcomes. This study aims to (1) identify characteristics of the antibody response that result in maintained immune response and better outcomes, (2) determine the impact of genetic differences on infection severity and immune response, (3) determine the impact of viral lineage on antibody response and patient outcomes and (4) evaluate patient-reported outcomes of receiving host genome, antibody and viral lineage results. METHODS AND ANALYSIS: A prospective, observational cohort study is being conducted among adult patients with COVID-19 in the Greater Toronto Area. Blood samples are collected at baseline (during infection) and 1, 6 and 12 months after diagnosis. Serial antibody titres, isotype, antigen target and viral neutralisation will be assessed. Clinical data will be collected from chart reviews and patient surveys. Host genomes and T-cell and B-cell receptors will be sequenced. Viral genomes will be sequenced to identify viral lineage. Regression models will be used to test associations between antibody response, physiological response, genetic markers and patient outcomes. Pathogenic genomic variants related to disease severity, or negative outcomes will be identified and genome wide association will be conducted. Immune repertoire diversity during infection will be correlated with severity of COVID-19 symptoms and human leucocyte antigen-type associated with SARS-CoV-2 infection. Participants can learn their genome sequencing, antibody and viral sequencing results; patient-reported outcomes of receiving this information will be assessed through surveys and qualitative interviews. ETHICS AND DISSEMINATION: This study was approved by Clinical Trials Ontario Streamlined Ethics Review System (CTO Project ID: 3302) and the research ethics boards at participating hospitals. Study findings will be disseminated through peer-reviewed publications, conference presentations and end-users.