Primer Part 1 - Preparing a laboratory quality improvement project.

Quality in laboratory medicine encompasses multiple components related to total quality management, including quality control (QC), quality assurance (QA), quality indicators, and quality improvement (QI). Together, they contribute to minimizing errors (pre-analytical, analytical, or post-analytical) in clinical service delivery and improving process appropriateness and efficiency. In contrast to static quality benchmarks (QC, QA, quality indicators), the QI paradigm is a continuous approach to systemic process improvement for optimizing patient safety, timeliness, effectiveness, and efficiency. Healthcare institutions have placed emphasis on applying the QI framework to identify and improve healthcare delivery. Despite QI's increasing importance, there is a lack of guidance on preparing, executing, and sustaining QI initiatives in the field of laboratory medicine. This has presented a significant barrier for clinical laboratorians to participate in and lead QI initiatives. This three-part primer series will bridge this knowledge gap by providing a guide for clinical laboratories to implement a QI project that issuccessful and sustainable. In the first article, we introduce the steps needed to prepare a QI project with focus on relevant methodology and tools related to problem identification, stakeholder engagement, root cause analysis (e.g., fishbone diagrams, Pareto charts and process mapping), and SMART aim establishment. Throughout, we describe a clinical vignette of a real QI project completed at our institution focused on serum protein electrophoresis (SPEP) utilization. This primer series is the first of its kind in laboratory medicine and will serve as a useful resource for future engagement of clinical laboratory leaders in QI initiatives.

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.

Evaluation of a New NT-proBNP Immunoassay on an Automated Core Laboratory System.

BACKGROUND: Heart failure remains a major cause of morbidity and mortality despite improvements in treatment. This study aimed to evaluate the Alere N-terminal pro B-type natriuretic peptide (NT-proBNP) immunoassay on the Abbott Alinity i platform. METHODS: The analytical performance including precision, linearity, limit of quantitation (LOQ), carryover, dilution-recovery, and stability was evaluated. A method comparison between the Abbott Alere NT-proBNP assay and Roche Elecsys proBNP II assay was performed using 70 residual plasma samples. RESULTS: Total imprecision was 4.1%, 3.5%, and 2.3% for low (120.9 ng/L), medium (333.9 ng/L), and high (4767.4 ng/L) QC levels, respectively. The manufacturer's claimed LOQ of 8.3 ng/L was verified. Method comparison between the Alere NT-proBNP assay and the Elecsys proBNP II assay showed good agreement between assays with an R value of 0.998, a slope of 1.05 (95% CI, 1.03-1.06), and an intercept of 45.81 (95% CI, -46.6.84 to 138.22). The Bland-Altman plot showed an absolute bias of 250 ng/L or 6.02%. Subrange analysis (NT-proBNP <2000 ng/L) showed good agreement with an R value of 0.998, a slope of 1.04 (95% CI, 1.02-1.06), and an intercept of -4.83 (95% CI, -26.95 to 17.28), with a mean bias of 26 ng/L or 3.2%. The stability of NT-proBNP was also verified in lithium heparin plasma samples stored at 4°C over a 7-day period. Hemolysis and lipemia interference thresholds were verified, but icterus impacted NT-proBNP recovery by >20% at low analyte concentrations. CONCLUSIONS: The Alere NT-proBNP assay demonstrated acceptable analytical performance and very good clinical concordance with the Elecsys proBNP II assay.

Preparing for another Ebola Outbreak: The impact of viral inactivation methods on commonly measured biochemistry analytes in plasma and urine.

INTRODUCTION: Infectious specimens containing viruses like Ebola require sample manipulation to ensure the safety of laboratory staff, which may negatively impact biochemistry test results. We evaluated the impact of viral inactivation methods on 25 biochemistry analytes in plasma, and seven biochemistry analytes in urine. METHODS: Fifteen lithium heparinized plasma specimens with and without gel underwent the following viral inactivation methods: 1) untreated, 2) Triton X-100 treatment, 2) heated for 60 min then Triton X-100 treatment, 3) heated for 60 min, 4) heated for 75 min, and 5) heated for 90 min. Electrolytes, protein, enzymes, glucose, as well as hepatic and renal markers were measured on the Roche Cobas e601, c502 or c702. Urinalysis analytes were measured on the Siemens CLINITEK. Acceptable recovery was based on Institute for Quality Management in Healthcare 2021 guidelines or ± 1 for urinalysis. RESULTS: Potassium and lactate dehydrogenase were impacted by the presence of gel. Viral inactivation with Triton X-100 had minimal impact on the biochemistry results. Heat inactivation resulted in significant negative bias in alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, creatinine, total protein, amylase, lactate dehydrogenase and creatine kinase. Positive bias in phosphate, aspartate transaminase, total bilirubin, and uric acid were observed after heat inactivation. CONCLUSION: Reliable results for commonly measured electrolytes, enzymes and proteins can be obtained after viral inactivation by Triton X-100 treatment at room temperature. However, heat inactivation has significant negative impact on routine biochemistry enzymes and alternative testing processes should be explored.

Applications of SARS-CoV-2 serological testing: impact of test performance, sample matrices, and patient characteristics.

Laboratory testing has been a key tool in managing the SARS-CoV-2 global pandemic. While rapid antigen and PCR testing has proven useful for diagnosing acute SARS-CoV-2 infections, additional testing methods are required to understand the long-term impact of SARS-CoV-2 infections on immune response. Serological testing, a well-documented laboratory practice, measures the presence of antibodies in a sample to uncover information about host immunity. Although proposed applications of serological testing for clinical use have previously been limited, current research into SARS-CoV-2 has shown growing utility for serological methods in these settings. To name a few, serological testing has been used to identify patients with past infections and long-term active disease and to monitor vaccine efficacy. Test utility and result interpretation, however, are often complicated by factors that include poor test sensitivity early in infection, lack of immune response in some individuals, overlying infection and vaccination responses, lack of standardization of antibody titers/levels between instruments, unknown titers that confer immune protection, and large between-individual biological variation following infection or vaccination. Thus, the three major components of this review will examine (1) factors that affect serological test utility: test performance, testing matrices, seroprevalence concerns and viral variants, (2) patient factors that affect serological response: timing of sampling, age, sex, body mass index, immunosuppression and vaccination, and (3) informative applications of serological testing: identifying past infection, immune surveillance to guide health practices, and examination of protective immunity. SARS-CoV-2 serological testing should be beneficial for clinical care if it is implemented appropriately. However, as with other laboratory developed tests, use of SARS-CoV-2 serology as a testing modality warrants careful consideration of testing limitations and evaluation of its clinical utility.

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.

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.

Reference Interval Harmonization: Harnessing the Power of Big Data Analytics to Derive Common Reference Intervals across Populations and Testing Platforms.

BACKGROUND: Harmonization in laboratory medicine is essential for consistent and accurate clinical decision-making. There is significant and unwarranted variation in reference intervals (RIs) used by laboratories for assays with established analytical traceability. The Canadian Society of Clinical Chemists (CSCC) Working Group on Reference Interval Harmonization (hRI-WG) aims to establish harmonized RIs (hRIs) for laboratory tests and support implementation. METHODS: Harnessing the power of big data, laboratory results were collected across populations and testing platforms to derive common adult RIs for 16 biochemical markers. A novel comprehensive approach was established, including: (a) analysis of big data from community laboratories across Canada; (b) statistical evaluation of age, sex, and analytical differences; (c) derivation of hRIs using the refineR method; and (d) verification of proposed hRIs across 9 laboratories with different instrumentation using serum and plasma samples collected from healthy Canadian adults. RESULTS: Harmonized RIs were calculated for all assays using the refineR method, except free thyroxine. Derived hRIs met proposed verification criterion across 9 laboratories and 5 manufacturers for alkaline phosphatase, albumin (bromocresol green), chloride, lactate dehydrogenase, magnesium, phosphate, potassium (serum), and total protein (serum). Further investigation is needed for some analytes due to failure to meet verification criteria in one or more laboratories (albumin [bromocresol purple], calcium, total carbon dioxide, total bilirubin, and sodium) or concern regarding excessively wide hRIs (alanine aminotransferase, creatinine, and thyroid stimulating hormone). CONCLUSIONS: We report a novel data-driven approach for RI harmonization. Findings support feasibility of RI harmonization for several analytes; however, some presented challenges, highlighting limitations that need to be considered in harmonization and big data analytics.

Analytical Unreliability of 25 Hydroxy Vitamin D Measurements in Pre-Term Neonates.

BACKGROUND: Vitamin D supplementation is common practice for neonates and infants due to limited stores of vitamin D at birth. Although not commonly encountered, vitamin D toxicity can occur due to over-supplementation. However, toxic concentrations are often not included in method validation experiments, and assays often are not validated in the neonatal population. METHODS: We compared serial 25 hydroxy vitamin D [25(OH)D] measurements in pre-term neonates receiving 25(OH)D supplementation and identified 12 patients wherein concentrations of 25(OH)D were above 50 ng/mL (125 nM) that required additional investigations as the 25(OH)D results did not match the clinical picture. Available samples were compared across 4 immunoassay platforms (LIAISON XL, Roche Cobas e602, Abbott Alinity i, and Siemens Centaur XP) and LC-MS/MS. RESULTS: Concentrations of 25(OH)D observed on one individual immunoassay platform (LIAISON XL) fluctuated substantially between subsequent blood draws in select neonates with elevated concentrations. Serum samples from these patients showed variable agreement between LC-MS/MS and other immunoassay platforms. These fluctuations were not explained by the presence of 3-epimer-25(OH)D or 24,25(OH)2D. CONCLUSIONS: Although we were unable to identify a cause for the variable elevated results, our findings suggest that neonatal 25(OH)D measurements alone should not be used for assessment of nutritional monitoring, and that clinical correlation and other laboratory parameters including ionized calcium should be considered.

HLA Variation and SARS-CoV-2 Specific Antibody Response.

Differences in SARS-CoV-2-specific immune responses have been observed between individuals following natural infection or vaccination. In addition to already known factors, such as age, sex, COVID-19 severity, comorbidity, vaccination status, hybrid immunity, and duration of infection, inter-individual variations in SARS-CoV-2 immune responses may, in part, be explained by structural differences brought about by genetic variation in the human leukocyte antigen (HLA) molecules responsible for the presentation of SARS-CoV-2 antigens to T effector cells. While dendritic cells present peptides with HLA class I molecules to CD8+ T cells to induce cytotoxic T lymphocyte responses (CTLs), they present peptides with HLA class II molecules to T follicular helper cells to induce B cell differentiation followed by memory B cell and plasma cell maturation. Plasma cells then produce SARS-CoV-2-specific antibodies. Here, we review published data linking HLA genetic variation or polymorphisms with differences in SARS-CoV-2-specific antibody responses. While there is evidence that heterogeneity in antibody response might be related to HLA variation, there are conflicting findings due in part to differences in study designs. We provide insight into why more research is needed in this area. Elucidating the genetic basis of variability in the SARS-CoV-2 immune response will help to optimize diagnostic tools and lead to the development of new vaccines and therapeutics against SARS-CoV-2 and other infectious diseases.

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.

Genome Reporting for Healthy Populations-Pipeline for Genomic Screening from the GENCOV COVID-19 Study.

Genome sequencing holds the promise for great public health benefits. It is currently being used in the context of rare disease diagnosis and novel gene identification, but also has the potential to identify genetic disease risk factors in healthy individuals. Genome sequencing technologies are currently being used to identify genetic factors that may influence variability in symptom severity and immune response among patients infected by SARS-CoV-2. The GENCOV study aims to look at the relationship between genetic, serological, and biochemical factors and variability of SARS-CoV-2 symptom severity, and to evaluate the utility of returning genome screening results to study participants. Study participants select which results they wish to receive with a decision aid. Medically actionable information for diagnosis, disease risk estimation, disease prevention, and patient management are provided in a comprehensive genome report. Using a combination of bioinformatics software and custom tools, this article describes a pipeline for the analysis and reporting of genetic results to individuals with COVID-19, including HLA genotyping, large-scale continental ancestry estimation, and pharmacogenomic analysis to determine metabolizer status and drug response. In addition, this pipeline includes reporting of medically actionable conditions from comprehensive gene panels for Cardiology, Neurology, Metabolism, Hereditary Cancer, and Hereditary Kidney, and carrier screening for reproductive planning. Incorporated into the genome report are polygenic risk scores for six diseases-coronary artery disease; atrial fibrillation; type-2 diabetes; and breast, prostate, and colon cancer-as well as blood group genotyping analysis for ABO and Rh blood types and genotyping for other antigens of clinical relevance. The genome report summarizes the findings of these analyses in a way that extensively communicates clinically relevant results to patients and their physicians. © 2022 Wiley Periodicals LLC. Basic Protocol 1: HLA genotyping and disease association Basic Protocol 2: Large-scale continental ancestry estimation Basic Protocol 3: Dosage recommendations for pharmacogenomic gene variants associated with drug response Support Protocol: System setup.

Bias in IGF-1 concentrations and interpretation across three different clinical laboratory assays.

In this study, we compared the DiaSorin LiaisonXL IGF-1 immunoassay to both the Roche Elecsys IGF-1 immunoassay and to the liquid chromatography-high resolution mass spectrometry (LC-MS) IGF-1 assay. Our study shows a constant positive bias in DiaSorin compared to the Roche immunoassay (mean 42 µg/L, 24%), and a proportional positive bias in DiaSorin compared to the LC-MS method (mean 49 µg/L, 29%). Further, we demonstrate the potential clinical impact of this bias by evaluating 43 adult samples, collected over a 2-month period, which were shown to be discrepant based on a chart review. Despite the positive analytical bias in the Diasorin assay compared to the LC-MS assay, the Diasorin assay upper reference limits were lower than those of the LC-MS assay. This effect caused nine out of forty-three samples to show falsely elevated results when they were clinically diagnosed as negative for acromegaly. Discussed in the context of previous literature, our findings emphasize the importance of adjusting reference intervals for IGF-1 assays based on the clinical needs of a patient population.

Vitamins and Infusion of Levodopa-Carbidopa Intestinal Gel.

Levodopa-carbidopa intestinal gel infusion (LCIG) is an established therapy for advanced Parkinson disease (PD), resulting in a significant improvement of quality of life. With increased LCIG adoption worldwide, potential complications due to abnormal vitamin absorption or metabolism have been reported in these patients. Neurologists are unfamiliar with vitamins physiology and pathophysiological mechanisms in case of their deficiency. Unfortunately, clinical and laboratory guidelines related to vitamin monitoring and supplementation in the context of treatment with LCIG are not available. We herein summarize the current knowledge on three vitamins that are reduced with LCIG therapy reporting on their physiology, laboratory testing, and clinical impact of their deficiency/excess. In addition, we proposed an opinion-based recommendation for clinicians treating LCIG patients. Patients and caregivers should be informed about the risk of vitamin deficiency. Vitamin B12, homocysteine, and methylmalonic acid (MMA) should be tested before starting LCIG, six months after and once/year thereafter. Vitamin B6 and folate testing is not universally available but it should be considered if homocysteine is elevated but MMA and/or total vitamin B12 are normal. Prophylaxis of vitamin deficiency should be started as soon as LCIG is implemented, possibly even before. Dietary recommendations are enough in most patients although a subgroup of patients is at higher risk and should receive Vitamin B12 regularly and cycles of B6. Finally, once diagnosed a vitamin deficiency should be readily treated and accompanied by clinical and laboratory monitoring. Resistant cases should receive non-oral routes of administration and possibly discontinue LCIG, even temporarily.

A Diagnostic Dilemma from a Presentation of Shortness of Breath and Chest Pain.

INTRODUCTION: A patient presented to hospital with chest pain and shortness of breath on 2 occasions 4 weeks apart. Clinical examination revealed an elevated jugular venous pressure consistent with heart failure or elevated filling pressures. METHODS: The patient was investigated through various modalities including electrocardiogram (ECG), transthoracic echocardiogram, coronary angiography, MRI, cardiac catheterization, positron emission tomography, and an extensive laboratory workup. RESULTS: Serial hs TnI measurements consistently revealed grossly elevated troponin I (>10 000 ng/L). In-lab investigation of increased high sensitivity troponin I (hsTnI) showed evidence of falsely increased troponin due to the presence of heterophilic antibodies. DISCUSSION: This case demonstrates a complex patient presentation and the value of involving the laboratory medicine team when dealing with potentially discrepant results. This is a rare report of grossly elevated troponin due to heterophilic antibodies for high-sensitivity troponin Abbott assay.

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.

Rapid COVID-19 testing: Speed, quality and cost. Can you have all three?

KEY MESSAGES.