Prospective cohort study of genomic newborn screening: BabyScreen+ pilot study protocol.

INTRODUCTION: Newborn bloodspot screening (NBS) is a highly successful public health programme that uses biochemical and other assays to screen for severe but treatable childhood-onset conditions. Introducing genomic sequencing into NBS programmes increases the range of detectable conditions but raises practical and ethical issues. Evidence from prospectively ascertained cohorts is required to guide policy and future implementation. This study aims to develop, implement and evaluate a genomic NBS (gNBS) pilot programme. METHODS AND ANALYSIS: The BabyScreen+ study will pilot gNBS in three phases. In the preimplementation phase, study materials, including education resources, decision support and data collection tools, will be designed. Focus groups and key informant interviews will also be undertaken to inform delivery of the study and future gNBS programmes. During the implementation phase, we will prospectively recruit birth parents in Victoria, Australia, to screen 1000 newborns for over 600 severe, treatable, childhood-onset conditions. Clinically accredited whole genome sequencing will be performed following standard NBS using the same sample. High chance results will be returned by genetic healthcare professionals, with follow-on genetic and other confirmatory testing and referral to specialist services as required. The postimplementation phase will evaluate the feasibility of gNBS as the primary aim, and assess ethical, implementation, psychosocial and health economic factors to inform future service delivery. ETHICS AND DISSEMINATION: This project received ethics approval from the Royal Children's Hospital Melbourne Research Ethics Committee: HREC/91500/RCHM-2023, HREC/90929/RCHM-2022 and HREC/91392/RCHM-2022. Findings will be disseminated to policy-makers, and through peer-reviewed journals and conferences.

Genetics providers' perspectives on the use of digital tools in clinical practice.

PURPOSE: Digital tools are increasingly incorporated into genetics practice to address challenges with the current model of care. Yet, genetics providers' perspectives on digital tool use are not well characterized. METHODS: Genetics providers across Canada were recruited. Semistructured interviews were conducted to ascertain their perspectives on digital tool use and the clinical practice factors that might inform digital tool integration. A qualitative interpretive description approach was used for analysis. RESULTS: Thirty-three genetics providers across 5 provinces were interviewed. Participants had favorable attitudes toward digital tool use. They were open to using digital tools in the pretest phase of the genetic testing pathway and for some posttest tasks or in a hybrid model of care. Participants expressed that digital tools could enhance efficiency and allow providers to spend more time practicing at the top of scope. Providers also described the need for careful consideration of the potential impact of digitalization on the clinician-patient dynamic, access to and equity of care, and unintended digital burden on providers. CONCLUSION: Genetics providers considered digital tools to represent a viable solution for improving access, efficiency, and quality of care in genetics practice. Successful use of digital tools in practice will require careful consideration of their potential unintended impacts.

Parents' attitudes towards research involving genome sequencing of their healthy children: a qualitative study.

With widespread genomic sequencing research efforts, there is increasing impetus to return results to participants. Parents of healthy children are increasingly asked to participate in genomic research, yet there are limited studies of parental expectations for the return of results amongst healthy children. We explored parental attitudes towards their healthy children's participation in genomic research and expectations for return of results. Data collection involved semi-structured telephone interviews with parents of healthy children participating in a primary care research network. Transcripts were analyzed thematically using constant comparison. A total of 26 parents were interviewed: 22 were female, 19 self-reported as White/European, and 20 were aged 30-39. Three themes emerged: (1) Reciprocity; Parents preferred to receive medically actionable, childhood-onset results and expected recontact overtime in exchange for their research participation. (2) Downstream impacts of testing; Parents expected future clinical benefits but were concerned about the risk of genetic discrimination. (3) Power and empowerment; Some parents felt empowered to take preventative action for their child and relatives, while others did not want to limit their child's autonomy. Considering these tensions may help to inform participant-centered approaches to optimize parental decision-making and participation, as well as maximize the utility of results.

"I just wanted more": Hereditary cancer syndromes patients' perspectives on the utility of circulating tumour DNA testing for cancer screening.

Hereditary cancer syndromes (HCS) predispose individuals to a higher risk of developing multiple cancers. However, current screening strategies have limited ability to screen for all cancer risks. Circulating tumour DNA (ctDNA) detects DNA fragments shed by tumour cells in the bloodstream and can potentially detect cancers early. This study aimed to explore patients' perspectives on ctDNA's utility to help inform its clinical adoption and implementation. We conducted a qualitative interpretive description study using semi-structured phone interviews. Participants were purposively sampled adult HCS patients recruited from a Canadian HCS research consortium. Thirty HCS patients were interviewed (n = 19 women, age range 20s-70s, n = 25 were white). Participants were highly concerned about developing cancers, particularly those without reliable screening options for early detection. They "just wanted more" than their current screening strategies. Participants were enthusiastic about ctDNA's potential to be comprehensive (detect multiple cancers), predictive (detect cancers early) and tailored (lead to personalized clinical management). Participants also acknowledged ctDNA's potential limitations, including false positives/negatives risks and experiencing additional anxiety. However, they saw ctDNA's potential benefits outweighing its limitations. In conclusion, participants' belief in ctDNA's potential to improve their care overshadowed its limitations, indicating patients' support for using ctDNA in HCS care.

"I don't need any more unknowns hanging over my head": Views of patients with cancer on variants of uncertain significance and low/moderate risk results from genomic sequencing.

PURPOSE: We sought to explore patient-reported utility of all types of cancer results from genomic sequencing (GS). METHODS: Qualitative study, using semi-structured interviews with patients who underwent GS within a trial. Thematic analysis employing constant comparison was used. Two coders coded transcripts, with use of a third coder to resolve conflicts. RESULTS: 25 patients participated: female (22), >50 years (18), European (12), Ashkenazi Jewish (5), Middle Eastern (3), or other ethnicity (5), with breast cancer history (20). Patients' perceptions of the utility of cancer GS results hinged on whether they triggered clinical action. For example, when patients were enrolled into high-risk breast cancer surveillance programs for low/moderate risk breast cancer genes, they perceived the results to be very "useful" and of moderate-high utility. In contrast, patients receiving low/moderate risk or primary variants of uncertain significance results without clinical action perceived results as "concerning," leading to harms, such as hypervigilance about cancer symptoms. Overall, having supportive relatives or providers enhanced perceptions of utility. CONCLUSION: Patients' perceptions of cancer GS results hinged on whether they triggered clinical management. Consequently, patients who received results without clinical action became hypervigilant, experiencing harms. Our findings call for a need to develop practice interventions to support patients with cancer undergoing GS.

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.

Two-step offer and return of multiple types of additional genomic findings to families after ultrarapid trio genomic testing in the acute care setting: a study protocol.

INTRODUCTION: As routine genomic testing expands, so too does the opportunity to look for additional health information unrelated to the original reason for testing, termed additional findings (AF). Analysis for many different types of AF may be available, particularly to families undergoing trio genomic testing. The optimal model for service delivery remains to be determined, especially when the original test occurs in the acute care setting. METHODS AND ANALYSIS: Families enrolled in a national study providing ultrarapid genomic testing to critically ill children will be offered analysis for three types of AF on their stored genomic data: paediatric-onset conditions in the child, adult-onset conditions in each parent and reproductive carrier screening for the parents as a couple. The offer will be made 3-6 months after diagnostic testing. Parents will have access to a modified version of the Genetics Adviser web-based decision support tool before attending a genetic counselling appointment to discuss consent for AF. Parental experiences will be evaluated using qualitative and quantitative methods on data collected through surveys, appointment recordings and interviews at multiple time points. Evaluation will focus on parental preferences, uptake, decision support use and understanding of AF. Genetic health professionals' perspectives on acceptability and feasibility of AF will also be captured through surveys and interviews. ETHICS AND DISSEMINATION: This project received ethics approval from the Melbourne Health Human Research Ethics Committee as part of the Australian Genomics Health Alliance protocol: HREC/16/MH/251. Findings will be disseminated through peer-review journal articles and at conferences nationally and internationally.

A model for the return and referral of all clinically significant secondary findings of genomic sequencing.

Secondary findings (SFs) identified through genomic sequencing (GS) can offer a wide range of health benefits to patients. Resource and capacity constraints pose a challenge to their clinical management; therefore, clinical workflows are needed to optimise the health benefits of SFs. In this paper, we describe a model we created for the return and referral of all clinically significant SFs, beyond medically actionable results, from GS. As part of a randomised controlled trial evaluating the outcomes and costs of disclosing all clinically significant SFs from GS, we consulted genetics and primary care experts to determine a feasible workflow to manage SFs. Consensus was sought to determine appropriate clinical recommendations for each category of SF and which clinician specialist would provide follow-up care. We developed a communication and referral plan for each category of SFs. This involved referrals to specialised clinics, such as an Adult Genetics clinic, for highly penetrant medically actionable findings. Common and non-urgent SFs, such as pharmacogenomics and carrier status results for non-family planning participants, were directed back to the family physician (FP). SF results and recommendations were communicated directly to participants to respect autonomy and to their FPs to support follow-up of SFs. We describe a model for the return and referral of all clinically significant SFs to facilitate the utility of GS and promote the health benefits of SFs. This may serve as a model for others returning GS results transitioning participants from research to clinical settings.

Great expectations: patients' preferences for clinically significant results from genomic sequencing.

We aimed to describe patient preferences for a broad range of secondary findings (SF) from genomic sequencing (GS) and factors driving preferences. We assessed preference data within a trial of the Genomics ADvISER, (SF decision aid) among adult cancer patients. Participants could choose from five categories of SF: (1) medically actionable; (2) polygenic risks; (3) rare diseases; (4) early-onset neurological diseases; and (5) carrier status. We analyzed preferences using descriptive statistics and drivers of preferences using multivariable logistic regression models. The 133 participants were predominantly European (74%) or East Asian or mixed ancestry (13%), female (90%), and aged > 50 years old (60%). The majority chose to receive SF. 97% (129/133) chose actionable findings with 36% (48/133) choosing all 5 categories. Despite the lack of medical actionability, participants were interested in receiving SF of polygenic risks (74%), carrier status (75%), rare diseases (59%), and early-onset neurologic diseases (53%). Older participants were more likely to be interested in receiving results for early-onset neurological diseases, while those exhibiting lower decisional conflict were more likely to select all categories. Our results highlight a disconnect between cancer patient preferences and professional guidelines on SF, such as ACMG's recommendations to only return medically actionable secondary findings. In addition to clinical evidence, future guidelines should incorporate patient preferences.

How do members of the public expect to use variants of uncertain significance in their health care? A population-based survey.

PURPOSE: Genomic sequencing can generate complex results, including variants of uncertain significance (VUS). In general, VUS should not inform clinical decision-making. This study aimed to assess the public's expected management of VUS. METHODS: An online, hypothetical survey was conducted among members of the Canadian public preceded by an educational video. Participants were randomized to 1 of 2 arms, VUS or pathogenic variant in a colorectal cancer gene, and asked which types of health services they expected to use for this result. Expected health service use was compared between randomization arms, and associations between participants' sociodemographic characteristics, attitudes, and medical history were explored. RESULTS: Among 1003 respondents (completion rate 60%), more participants expected to use each type of health service for a pathogenic variant than for a VUS. However, a considerable proportion of participants expected to request monitoring (73.4%) and consult health care providers (60.9%) for a VUS. There was evidence to support associations between expectation to use health services for a VUS with family history of genetic disease, family history of cancer, education, and attitudes toward health care and technology. CONCLUSION: Many participants expected to use health services for a VUS in a colorectal cancer predisposition gene, suggesting a potential disconnect between patients' expectations for VUS management and guideline-recommended care.

Finding the sweet spot: a qualitative study exploring patients' acceptability of chatbots in genetic service delivery.

Chatbots, web-based artificial intelligence tools that simulate human conversation, are increasingly in use to support many areas of genomic medicine. However, patient preferences towards using chatbots across the range of clinical settings are unknown. We conducted a qualitative study with individuals who underwent genetic testing for themselves or their child. Participants were asked about their preferences for using a chatbot within the genetic testing journey. Thematic analysis employing interpretive description was used. We interviewed 30 participants (67% female, 50% 50 + years). Participants considered chatbots to be inefficient for very simple tasks (e.g., answering FAQs) or very complex tasks (e.g., explaining results). Chatbots were acceptable for moderately complex tasks where participants perceived a favorable return on their investment of time and energy. In addition to achieving this "sweet spot," participants anticipated that their comfort with chatbots would increase if the chatbot was used as a complement to but not a replacement for usual care. Participants wanted a "safety net" (i.e., access to a clinician) for needs not addressed by the chatbot. This study provides timely insights into patients' comfort with and perceived limitations of chatbots for genomic medicine and can inform their implementation in practice.

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.

A comprehensive genomic reporting structure for communicating all clinically significant primary and secondary findings.

Genomic sequencing (GS) can reveal secondary findings (SFs), findings unrelated to the reason for testing, that can be overwhelming to both patients and providers. An effective approach for communicating all clinically significant primary and secondary GS results is needed to effectively manage this large volume of results. The aim of this study was to develop a comprehensive approach to communicate all clinically significant primary and SF results. A genomic test report with accompanying patient and provider letters were developed in three phases: review of current clinical reporting practices, consulting with genetic and non-genetics experts, and iterative refinement through circulation to key stakeholders. The genomic test report and consultation letters present a myriad of clinically relevant GS results in distinct, tabulated sections, including primary (cancer) and secondary findings, with in-depth details of each finding generated from exome sequencing. They provide detailed variant and disease information, personal and familial risk assessments, clinical management details, and additional resources to help support providers and patients with implementing healthcare recommendations related to their GS results. The report and consultation letters represent a comprehensive approach to communicate all clinically significant SFs to patients and providers, facilitating clinical management of GS results.

"Doctors shouldn't have to cheat the system": Clinicians' real-world experiences of the utility of genomic sequencing.

PURPOSE: Emerging genetic tests such as genomic sequencing (GS) can generate a broad range of benefits, but funding criteria only prioritize diagnosis and clinical management. There is limited evidence on all types of benefits obtained from GS in practice. We aimed to explore real-world experiences of Canadian clinicians across specialties on the full range of benefits obtained from the results from GS. METHODS: We conducted a qualitative study using semistructured interviews with Canadian clinicians. Transcripts were thematically analyzed using constant comparison. RESULTS: In total, 25 clinicians participated, including 12 geneticists, 7 genetic counselors, 4 oncologists, 1 neurologist, and 1 family physician. Although diagnoses and management were the most valued benefits of GS, clinicians also prioritized nontraditional utility, such as access to community supports. However, clinicians felt "restricted" by funding bodies, which only approved funding when GS would inform diagnoses and management. Consequently, clinicians sought ways to "cheat the system" to access GS (eg, research testing) but acknowledged workarounds were burdensome, drove inequity, and undermined patient care. CONCLUSION: Current governance structures undervalue real-world benefits of GS leading clinicians to adopt workarounds, which jeopardize patient care. These results support calls for the expansion of the definition of clinical utility and research to quantify the additional benefits.

"Game Changer": Health Professionals' Views on the Clinical Utility of Circulating Tumor DNA Testing in Hereditary Cancer Syndrome Management.

BACKGROUND: We explored health professionals' views on the utility of circulating tumor DNA (ctDNA) testing in hereditary cancer syndrome (HCS) management. MATERIALS AND METHODS: A qualitative interpretive description study was conducted, using semi-structured interviews with professionals across Canada. Thematic analysis employing constant comparison was used for analysis. 2 investigators coded each transcript. Differences were reconciled through discussion and the codebook was modified as new codes and themes emerged from the data. RESULTS: Thirty-five professionals participated and included genetic counselors (n = 12), geneticists (n = 9), oncologists (n = 4), family doctors (n = 3), lab directors and scientists (n = 3), a health-system decision maker, a surgeon, a pathologist, and a nurse. Professionals described ctDNA as "transformative" and a "game-changer". However, they were divided on its use in HCS management, with some being optimistic (optimists) while others were hesitant (pessimists). Differences were driven by views on 3 factors: (1) clinical utility, (2) ctDNA's role in cancer screening, and (3) ctDNA's invasiveness. Optimists anticipated ctDNA testing would have clinical utility for HCS patients, its role would be akin to a diagnostic test and would be less invasive than standard screening (eg imaging). Pessimistic participants felt ctDNA testing would add limited utility; it would effectively be another screening test in the pathway, likely triggering additional investigations downstream, thereby increasing invasiveness. CONCLUSIONS: Providers anticipated ctDNA testing will transform early cancer detection for HCS families. However, the contrasting positions on ctDNA's role in the care pathway raise potential practice variations, highlighting a need to develop evidence to support clinical implementation and guidelines to standardize adoption.

Genetics Adviser: a protocol for a mixed-methods randomised controlled trial evaluating a digital platform for genetics service delivery.

INTRODUCTION: The high demand for genetic tests and limited supply of genetics professionals has created a need for alternative service delivery models. Digital tools are increasingly being used to support multiple points in the genetic testing journey; however, none are transferable across multiple clinical specialties and settings nor do they encompass the entire trajectory of the journey. We aim to evaluate the effectiveness of the Genetics Adviser, an interactive, patient-facing, online digital health tool that delivers pre-test counselling, provides support during the waiting period for results, and returns results with post-test counselling, encompassing the entire patient genetic testing journey. METHODS AND ANALYSIS: We will compare the Genetics Adviser paired with a brief genetic counselling session to genetic counselling alone in a randomised controlled trial. One hundred and forty patients who previously received uninformative genetic test results for their personal and family history of cancer will be recruited from familial cancer clinics in Toronto and offered all clinically significant results from genomic sequencing. Participants randomised into the intervention arm will use the Genetics Adviser to learn about genomic sequencing, receive pre-test counselling, support during the waiting period and results, supplemented with brief counselling from a genetic counsellor. Participants in the control arm will receive standard pre-test and post-test counselling for genomic sequencing from a genetic counsellor. Our primary outcome is decisional conflict following pre-test counselling from the Genetics Adviser+genetic counsellor or counsellor alone. Secondary outcomes include: knowledge, satisfaction with decision-making, anxiety, quality of life, psychological impact of results, empowerment, acceptability and economic impact for patients and the health system. A subset of patients will be interviewed to assess user experience. ETHICS AND DISSEMINATION: This study has been approved by Clinical Trials Ontario Streamlined Research Ethics Review System (REB#20-035). Results will be shared through stakeholder workshops, national and international conferences and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04725565.

Widening the lens of actionability: A qualitative study of primary care providers' views and experiences of managing secondary genomic findings.

Most secondary genomic findings (SFs) fall in the scope of primary care practice. However, primary care providers' (PCPs) capacity to manage these findings is not well understood. We explored PCPs' views and experiences of managing SFs through a qualitative study. PCPs participated in semi-structured interviews about SFs from a patient in their practice or a hypothetical patient. The interpretive descriptive methodology was used to analyze transcripts thematically through constant comparison. Fifteen family physicians from Ontario, Canada participated (ten females; 6-40 years in practice across community and academic settings). PCPs made sense of SFs through the lens of actionability: they actively looked for clinical relevance by considering a wide range of immediate and future actions, including referrals, genetic testing, screening, lifestyle changes, counseling about family planning, informing family members, future medication choice, increased vigilance/surveillance, and managing results in the electronic medical record. PCPs saw clinical actionability as the main benefit mitigating the potential harms of learning SFs, namely patient anxiety and unnecessary investigations. PCPs conceptualized actionability more broadly than it is traditionally defined in medical genetics. Further research will be needed to determine if PCPs' emphasis on actionability conflicts with patients' expectations of SFs and if it leads to overutilization of healthcare resources.

Challenges and practical solutions for managing secondary genomic findings in primary care.

Primary care providers will increasingly be tasked with managing most secondary findings from genomic sequencing, but literature exploring their capacity to manage findings beyond conventional genetic testing is limited. This study aimed to explore primary care providers' challenges and potential solutions for managing secondary findings. Providers were recruited in two groups. Group 1 providers had a patient in their practice who received secondary findings and all potential group 1 providers were invited to participate. Group 2 providers were provided with the secondary findings of a hypothetical patient and were purposefully sampled for maximal variation in sex, practice setting, and geographic location. Providers were interviewed about their challenges and solutions managing secondary findings from a patient in their practice or a hypothetical patient. Using interpretive description methodology, transcripts were analysed thematically complemented by constant comparison. Out of the fifty-five providers invited, 15 family physicians participated across community and academic settings in Ontario, Canada (range 6-40 years in practice; 10/15 female). Providers described a responsibility to manage secondary findings, but limited capacity for this, describing practice, knowledge, and technical challenges. Providers expressed concern that compared to other incidental findings, secondary genomic findings might be reported directly to patients and result in longer-term anxiety. Potential solutions were a structured letter with categorized results and summary tables highlighting key secondary findings with follow-up recommendations and resources, as well as electronic medical records (EMRs) that store and integrate genomic information for prescribing or referrals. These solutions were deemed essential to address knowledge and technical challenges faced by primary care physicians and ultimately promote clinical utility of secondary findings.

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.