HostSeq Contributing Studies

HostSeq Contributing Studies

The following Study Partners are currently enrolled in the HostSeq initiative. This list will be updated as additional studies are on-boarded as part of the HostSeq initiative.

Study Title: COVID genMARK study

Principal Investigator: Upton Allen

Affiliation: The Hospital for Sick Children

Study Summary: The study intends to understand why some people get severe, while others get mild illness. This will be done through a study of the genetic and immune profile among individuals.

Study Design: Any individual who has a positive COVID diagnosis or has symptoms of COVID-19 or has household contact with a COVID-19 patient can participate in the study. Individuals will be required to answer a questionnaire, provide blood for genetic and immune testing and do a nasal brush test. Altogether 2000 individuals will be studied.

Genetic Assays Planned: Whole genome sequencing

Other Assays Planned: Immune profiling – cellular as well as humoral responses, including antibody testing. Immune responses will also be measured in respiratory epithelial cells.

Related Research: The genMARK study has affiliated projects including a targeted focus on susceptibility among North American and Caribbean Black populations.

Website: www.covidgenmark.ca

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Study Title: The Canadian COVID-19 Prospective Cohort Study (CanCOV)

Principal Investigators: Angela Cheung and Margaret Herridge

Affiliation: University Health Network

Summary: The Canadian COVID-19 Prospective Cohort Study (CANCOV) is the first Canadian study to provide a comprehensive evaluation of early to 1-year outcomes in patients with COVID-19 and their family caregivers. Built on the GEMINI and RECOVER networks, this study is a multi-centre one-year follow-up of COVID-19 patients across the spectrum of illness severity (non-hospitalized, hospitalized non-ICU and hospitalized ICU) in Ontario, Quebec, Alberta, and British Columbia. We are a consortium of interdisciplinary investigators and clinicians leading multiple COVID19 studies across Canada. Our research ranges from genomics and multi-omics, antibody testing and immune analyses, to physical and mental health outcomes. Our overall objectives are to better understand both short and long-term outcomes in patients and their caregivers, and the predictors of those outcomes. We aim to fully characterize their genetic and clinical risk factors, functional and neuropsychological status, return to work and pattern and cost of healthcare utilization.

Study Design: CANCOV is a prospective observational study of 1000 hospitalized patients (general wards + ICU) and their caregivers as well as 1000 non-hospitalized patients with COVID-19. Inclusion criteria includes positive COVID-19 test and older than 16 years of age. Exclusion criteria includes anticipated death or withdrawal of life sustaining treatment within 48 hours, catastrophic neurological injury, patients unlikely to comply with follow-up or lives greater than 300 km from centre, physician refusal, or no next of kin or SDM available (if patient unable to provide consent).

Genetic Assays Planned: Host whole genome sequencing, genome-wide association studies, epigenomic/transcriptomic profiling including analysis of changes in DNA methylation. T/B cell receptor sequencing and viral genome sequencing.

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Study Title: Implementation of serological and molecular tools to inform COVID-19 patient management (GENCOV)

Principal Investigators: Jordan Lerner-Ellis, Jennifer Taher

Affiliation: Sinai Health

Summary: There is considerable variability in symptom severity and outcomes among patients infected by SARS-CoV-2. Linking genome and viral sequencing information to antibody (immune) response and other biological information (sex, age, ancestry, symptom severity, comorbidities and outcome), may identify characteristics of patients that are associated with poor and favorable outcomes. This study will address three aims. Aim 1: Identify the characteristics of the antibody response that result in maintained immune response and better patient outcomes. Aim 2: Determine impact of genetic differences on COVID-19 infection severity and immune response. Aim 3: Determine impact of different viral strains on antibody response and patient outcomes. Evidence from this study will determine if immune response, viral strain and genome sequencing are effective for the diagnosis, prognosis and management of patients with COVID-19.

Study Design: Patients with COVID-19 will be recruited from six hospitals in Ontario. This is a prospective observational cohort study with a study size of 1500 patients, 18 years and above. The target population includes patients seen in the emergency department and COVID assessment centres with mild symptoms as well as hospital in-patients with severe symptoms. Samples will be obtained at baseline and at 1 month, 6 months and 1 year post COVID-19 diagnosis. Immunity will be assessed by measuring antibody response (isotype, titer, antigen target, and viral neutralization) and T/B Cell receptor sequencing. Genetic variation assessed by sequencing patient and viral genomes and physiological response characterized by biochemical laboratory parameters as well as from patient characteristics obtained from patient charts. Statistical analysis will be used to test for associations between antibody levels, genetic variation, viral genome variation, and patient characteristics including age, sex, ethnicity, comorbidities, outcome, treatment, and symptom severity. This study will link serological, genomic and patient characteristics to provide a comprehensive understanding of factors that contribute to variability in clinical symptoms and outcomes among COVID-19 patients.

Genetic Assays Planned: Host Genome Sequencing, Viral Genome Sequencing, T/B Cell Receptor Sequencing

Other Assays Planned: Immune profiling, Antibody characterization (ELISA assay), Biochemistry panel testing

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Study Title: The Genetics of Mortality in Critical Care (GenOMICC)

Principal Investigator: David Maslove

Affiliation: Queen’s University

Summary: GenOMICC is an international COVID study with collaborations in UK and Canada. Susceptibility to COVID-19 is almost certainly, in part, genetically determined. The GenOMICC study focuses on trying to find the genetic determinants of severe, life-threatening COVID-19 infections. All patients with confirmed COVID-19 admitted to intensive care units are eligible. By identifying genetic features that are associated with severe COVID-19, we will identify new targets for prevention and treatment, in order to respond to the global crisis.

Study Design: Patients with severe COVID-19 requiring ICU admission will be recruited. A single sample of whole blood will be collected and used for whole genome sequencing. The initial comparison group will be healthy controls, with comparisons to milder disease carried out according to data availability. The target enrollment is 1,000 patients in Canada.

Genetic Assays Planned: Whole genome sequencing

Other Assays Planned: Analysis of clonal hematopoiesis and its association with COVID-19

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Study Title: Host Genetic Factors Underlying Severe COVID-19

Principal Investigator: Catherine Biggs and Stuart Turvey 

Affiliation: University of British Columbia, BC Children’s Hospital Research Institute

Summary: SARS-CoV2 causes a wide range of symptoms–some individuals are asymptomatic, while others experience severe or fatal disease. Our study will determine which components of the immune system are critical for defending against SARS-CoV2. We will do so by looking for genetic changes affecting immune function in otherwise healthy patients who develop severe or unusual SARS-CoV2 complications. This work is part of an international initiative entitled the COVID human genetic effort (COVID-HGE), led by immunologists and geneticists from over 75 participating countries. Our goal is to recruit all patients from across BC who are eligible to participate, supported by Genome Canada’s CANCoGEN initiative to perform whole genome sequencing on Canadians affected by COVID-19. Understanding the host factors underlying susceptibility to severe or unusual COVID-19 complications is a critical step in identifying treatments for those affected. The urgency of this work has been further magnified by the identification of an emerging multisystem inflammatory syndrome in children (MIS-C) recently infected with SARS-CoV2. As clinical immunologists, we have a track record of success in identifying targeted therapies for patients based on the underlying molecular defect predisposing them to infection and immune dysregulation, and this study is crucial for applying this expertise to COVID-19.

Study Design: This translational research program will enrol previously healthy individuals in British Columbia who develop severe COVID-19. Severe disease is defined as any of the following: requiring ICU admission, cardiorespiratory support such as non-invasive or mechanical ventilation, extracorporeal membrane oxygenation, or unusual complications such as multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, encephalitis, other inflammatory complications. Whole genome sequencing of the study participants will be sponsored by the federally funded CanCOGeN (Canadian COVID Genomics Network) HostSeq project. Genetic sequencing data will be stored in the HostSeq COVID-19 databank and analyzed at our institution and in collaboration with the COVID human genetic effort. Candidate variants will undergo functional characterization, and precision medicine-based testing for treatments specific to the particular immune pathway affected by the individual’s underlying genetic variant.

Genetic Assays Planned: Whole genome sequencing

Other Assays Planned: Candidate variants will undergo functional characterization, and precision medicine-based testing for treatments specific to the particular immune pathway affected by the individual’s underlying genetic variant.

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Study Title: Genomic determinants of COVID-19: Integration of host and viral genomic data to understand the COVID-19 epidemiologic triangle.

Principal Investigator: Dr. Stuart Turvey

Summary: COVID-19, caused by the SARS-CoV-2 virus, is a global pandemic and a public health emergency worldwide. While the majority of cases present with mild or no symptoms at all, some progress to severe pneumonia, end-stage pulmonary disease and multi-organ failure. Mechanisms underlying susceptibility to disease and variability of health outcomes are unclear. As with any infectious disease, COVID-19 is a complex interaction between the pathogen (SARS-CoV-2), the host (human) and the environment (e.g., lifestyle). Integration and study of large-scale human and viral genomic data with the variable clinical outcomes and other epidemiological data is crucial for understanding the COVID-19 “infectious disease triangle” and to inform public health response. Leveraging federal support through the Canadian COVID-19 Genomic Network (CanCOGeN) and public health efforts at the British Columbia Centre for Disease Control (BCCDC), this study will test the hypothesis that underlying host and viral genomic factors, at least in part, contribute to COVID-19 disease susceptibility and variable health outcomes of infection and are likely influenced by environmental factors such as lifestyle and built environment.

Study Design: This is a genomic epidemiologic study to explore the genomic determinants of COVID-19 and how they contribute to disease susceptibility and health outcomes. The study will generate an integrated data set with viral and host genomic data linked with clinical and epidemiological data to investigate how host and viral genetic constitution contributes to the host immune response. Using public health generated data at the BCCDC, potential study participants (individuals of all ages with documented COVID-19 infection in BC) will be identified and invited to participate in the study. Following recruitment, individual consent and sample collection, we will perform host WGS on all study participants (HostSeq) and with explicit patient consent, link the host genomic data to the existing viral genomic data as well as other clinical, epidemiological data available through the BCC19C and other health authorities and research institutes. The integrated data set will be analysed to identify common and rare germline variants associated with host susceptibility and immune response in COVID-19 using case-case and nested case-control study designs.

Genetic Assays Planned: Whole genome sequencing

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Study Title: COVID-19 and Aging Adults (CLSA-COVID19 studies)

Principal Investigator: Parminder Raina

Affiliation: McMaster University

Summary: The CLSA is a large, national, long-term study of more than 50,000 individuals who were between the ages of 45 and 85 when recruited. These participants are being followed until 2033 or death. The aim of the CLSA is to find ways to help people live long and live well and understand why some people age in healthy fashion, while others do not. Participants of CLSA have been invited to participate in a few different COVID-19 studies. For participants who have tested +ve (diagnosis or antibody testing) for COVID-19  CLSA is partnering with HostSeq to gather whole genome sequencing information. The CLSA COVID-19 studies aim to better understand how widespread SARS-CoV-2 infection is among adults over age 50.

Study Design: The CLSA COVID-19 Antibody Study collects and analyzes blood samples from more than 19,000 CLSA participants in 10 provinces. Study participants also complete a questionnaire, either by phone, or online, that collects information about symptoms, risk factors, health- care use and the psychosocial and economic impacts of COVID-19.

Genetic assays planned: Whole genome sequencing

Other assays planned: Serological testing, immunoprofiling

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Study Title: CONvalescent Plasma for COVID-19 Research (CONCOR) Donor

Principal Investigator: Rulan Parekh

Affiliation: The Hospital for Sick Children

Summary: Convalescent Plasma for COVID-19 Research (CONCOR-Donor) study, is a Canada wide, natural history study investigating the protective effects of the immune system in people who have recovered from COVID-19. The CONCOR-Donor study will determine: a) the variability of antibody levels and if levels differ by clinical and demographic factors; b) duration of protective immunity in people who have recovered from COVID-19 over one year, and whether clinical and demographic factors impact this protection; c) genetic risk factors that predict the antibody response; d) assess for long-term outcomes of COVID-19 including long COVID, cardiovascular and respiratory outcomes; and e) create a biorepository available to researchers across Canada.

Study Design: CONCOR is a national longitudinal cohort study of persons recovered from COVID-19. Participants are recruited from those who registered to donate convalescent plasma at Canadian Blood Services or through social media announcements. Eligible to participate are persons ages 17-85 years old that tested positive and recovered from COVID-19 infection or have a household member that tested positive and experienced COVID-19 symptoms, both non-hospitalized and hospitalized from the community. We will address the longitudinal changes over the year including changes in COVID-19 symptoms as well as linking to national health databases to understand study long-term outcomes from COVID-19 infection.

Genetic assays planned: Whole genome sequencing 

Other assays planned: Antibody analysis, immune profiling with autoantibodies. Specimens will be available for proteomics, metabolomics, and other assays.

Study Website: https://cancovid19plasma.ca/concor-donor/

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Study Title: Long-term effect of SARS-CoV-2 infection on physio- and psychological health (LEFT Study)

Principal Investigator: Juthaporn Cowan

Affiliation: The Ottawa Hospital Research Institute

Summary: While researchers are beginning to understand what happens in the body during a severe COVID-19 infection, much less is known about the long-term effects in survivors. Based on what is known about other viral infections, the long-term effects could be serious, affecting the lungs, heart and muscles, as well as mental health. The purpose of this study is to understand these potential long-term effects of COVID-19 infection. 

Study Design: Adults who have previously tested positive for COVID-19 (mild, moderate and severe infections) were included in the study. The researchers are studying the long-term effects of COVID-19 in survivors, checking in on them three, six and 12 months after they were initially infected. At each visit participants performed breathing tests; had a non-invasive heart imaging test; completed an exercise test on a stationary bicycle and; filled-out questionnaires related to their mental health.

Genetic Assays Planned: Whole genome sequencing

Other Assays Planned: Immune profiling – exhaustion, tolerance, metabolism

Study Website: https://omc.ohri.ca/left/

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Study Title: Québec COVID-19 Biobank (BQC19)

Principal Investigator: Vincent Mooser

Affiliation: McGill University

Study Summary: The Biobanque québécoise de la COVID-19 (BQC19) is a pan-provincial initiative that collects, stores and shares data and blood samples from COVID-19 patients, both severe and non-severe cases and control cases, in an effort to respond effectively to the public health challenges posed by the pandemic.​

Supported by the Fonds de recherche du Québec – Santé (FRQS), Génome Québec and the Public Health Agency of Canada, the BQC19 collects a growing number of samples from ten locations around Quebec. Its ultimate goal is to contribute to the global efforts to better understand the evolution and determinants of the SARS-CoV-2 infection. ​BQC19 believes that better understanding the disease will help society in returning to social activities and in preparing for future pandemics. It sees access to high-quality samples and data as essential in fulfilling research and works to bring about national and international research collaborations.

Study Design: The Biobanque québécoise de la COVID-19 (BQC 19) is a prospective, observational, case-control and multicentre cohort study carried out at 10 test sites in Quebec. All BQC19 sites adhere to the Management Framework, procedures manual and Standard Operating Procedures that have been developed for the study.

Genetic Assays Planned: Genome-wide sequencing and genotyping (GWAS) 

These analyses are performed on genomic DNA extracted from snap-frozen whole blood aliquots. They include identification of all genetic variants in the host genome and genetic variations such as changes in copy number of certain genes (genome-wide sequencing), as well as common genetic variations across the genome (GWAS genotyping).

Other Assays Planned: The BQC19 performs a series of core analyses on its samples.

These analyses provide researchers with multi-omics experimental data that are generated on a large set of samples, all using the same protocols. This approach fosters cutting-edge research on the biological determinants of COVID-19. In addition, this approach slows down any rapid depletion of collected biological samples by avoiding redundancy of baseline analyses. The results of these baseline analyses can be obtained by filing a BQC19 data access request.

The core analyses include the following:

  • Two types of proteomics;
  • Metabolomics;
  • Immuno-serology;
  • Transcriptomics;
  • Genomics;
  • Clinical laboratory analyses performed on the ROCHE platform.

Website:  https://en.quebeccovidbiobank.ca/

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Study Title: Host genomic susceptibility to severe outcomes from COVID-19 (AB-HGS study)

Principal Investigator: Gerald Pfeffer, MD PhD

Affiliation: University of Calgary

Study Summary: We recruited participants who had COVID-19 and required hospitalisation, who were under age 60 and in otherwise good health. Family members with COVID-19 and mild clinical course were recruited as control participants. We will analyse genomic data to determine whether underlying genetic factors (such as unrecognised rare disease diagnoses) could have contributed to their outcome. Genetic findings will be correlated to clinical data.

Study Design: Retrospective recruitment of persons hospitalised with COVID-19. Written informed consent was obtained for all participants. Retrospective health records review. DNA collection from whole blood or saliva kits. Bioinformatic analysis of genomic data using established tools, with family-based analyses. Correlation to clinical data.

Genetic Assays Planned: Whole genome sequencing

Related Research: https://www.frontiersin.org/articles/10.3389/fneur.2022.914411/abstract

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More coming soon…