Jun 23, 2021

Why do some patients infected with SARS-CoV-2 end up in the ICU and others not? A multidisciplinary study of COVID-19

Research: Infectious diseases & immunopathology, COVID-19

Why do two healthy 30-year-olds with COVID-19 have different outcomes, where one ends up on a ventilator and one has mild flu-like symptoms? Is there a genetic reason?

These are some of the questions Dr. Jordan Lerner-Ellis, Associate Professor in the Department of Laboratory Medicine and Pathobiology at the Temerty Faculty of Medicine and Head and Director of the Advanced Molecular Diagnostics Laboratory at Mount Sinai Hospital, was asking himself.

As a geneticist, he wanted to study any genomic data related to COVID-19 patients but knew that this would not give a full picture. He approached his LMP colleague, Dr. Jennifer Taher, Assistant Professor in LMP and Clinical Biochemist at Mount Sinai Hospital, who was asking similar questions but from an immunology and biochemistry perspective, and an idea for a study grew.

The study also includes LMP faculty Dr. Saranya Arnoldo, Dr. Tony Mazzulli, and Dr. Allison McGeer.

We spoke to them about what they plan to do.

What are you studying and what do you hope to find out?

Jordan: We are working with 25 co-investigators and collaborators across 6 hospital sites to study 1,500 patients who have contracted COVID-19. To assess the long-term effects, we will be studying this cohort over a 12-month period which requires giving blood at certain time intervals. We will also assess their past medical history and run a number of different laboratory tests. We also have a control cohort who has not been infected with COVID-19 but has received a Health Canada approved COVID-19 vaccine. In this cohort, we will study the immune response and how it differs from those infected with COVID-19. We’ll be sequencing their entire genome – all 3 billion DNA nucleotide pairs that comprise your genetic makeup as well as T and B- cell receptor sequencing – as well as sequencing the virus so we know the viral variant they were infected with.

Jennifer: By collecting bloodwork, we will be able to assess a variety of biochemistry and hematology tests and also measure Covid-19 antibodies. We will do a thorough investigation of the Covid-19 antibody response including assessing the different isotypes of antibodies, such as IgG, IgA IgM, assessing which antigen on the virus each antibody targets and if it's neutralizing or not. We will also be looking at their T cells (thymus cells) and B cells (bone marrow- or bursa-derived cells) which are the major cellular components of the adaptive immune response. Combined, this data will help us to understand their immune response.

How will this help us in the fight against COVID-19?

Jennifer: If we can understand the factors that contribute to variability in clinical symptoms and outcomes among COVID-19 patients, we can achieve multiple outcomes. It can help us to improve patient management within the hospital, identify at-risk patients, predict how a patient will respond to treatment, and could also inform on the development of new treatments as we see new viral lineages arise.

Jordan: The data sharing potential is also exciting. All the genome sequencing data we’re gathering will be made available in a databank (called HostSeq) through a permission-based access system so other researchers and universities can ask their own research questions, which is the first of its kind in Canada.

What makes this study unique?

Jennifer: We’re bringing together genetic, biochemistry, virology and immunology results. By forming a team of people with various areas of expertise, we can investigate all of these different aspects and tie them together. This is the key to being able to answer so many important questions. It must involve a multi-disciplinary team.

Jordan: It's turned into quite a large team of co-investigators and collaborators, which includes clinical/medical biochemists, geneticists, microbiologists, laboratory research professionals, infectious disease specialists, as well as ER, ICU and family medicine doctors and nurses. We’re also collaborating closely with other international initiatives. It's been nice to bring people together to tackle this problem. Everyone is eager to understand the pathogenesis of COVID-19.

Jennifer: We’re also seeing this as a patient-researcher partnership by sharing knowledge with participants taking part in the study. We do analysis on their antibodies and their genetics, and we return that information back to them. This isn’t simply done by returning results back in paper format. They have access to various team members from whom they can ask questions to help them understand their results and we also pair them with a genetic counsellor. Helping to transfer this knowledge to our participants is an important aspect of the knowledge translation portion of our project.

Jordan: Participants are meant to be engaged in the research and receive genetic counseling, working through a tailored web-based decision-aid module so they understand the implications of the genetic information they can access. Some of it will be clinically actionable, some of it not, so they need to be aware of what they could learn. They could also discover other unexpected diagnoses including that they have hereditary cancer or cardiovascular risks, their ancestry and blood groupings. We’re also interested in assessing the impact of sharing these results with participants – what do they do with that information? What downstream effect does that have on their health and the health care system? This study has so much potential to advance our understanding in so many areas.

Find out more about the study

Follow the study on Twitter @GencovStudy

Email the team if you are interested in being a participant: GEN.COV@sinaihealth.ca

This study is funded by an operating grant from the Canadian Institutes of Health Research (CIHR), in-kind funding through Genome Canada (CanCOGeN) and has received additional support from Roche.

Image credit: Mufid Majnun via Unsplash

The LMP COVID-19 hub: find out how LMP is impacting how we understand, treat, and live with COVID-19

The study team

The team working with Dr. Taher and Dr. Lerner-Ellis.

Main research team

Selina Casalino, Mount Sinai Hospital and Lunenfeld-Tanenbaum Research Institute, Sinai Health
Sunakshi Chowdhary, Mount Sinai Hospital and Lunenfeld-Tanenbaum Research Institute, Sinai Health
Erika Frangione, Mount Sinai Hospital and Lunenfeld-Tanenbaum Research Institute, Sinai Health
Jordan Fung, Mount Sinai Hospital and Lunenfeld-Tanenbaum Research Institute, Sinai Health
Chloe Mighton, Mount Sinai Hospital and Lunenfeld-Tanenbaum Research Institute, Sinai Health, University of Toronto, Genomics Health Services Research Program, St. Michael’s Hospital, Unity Health Toronto
Greg Morgan, Mount Sinai Hospital and Lunenfeld-Tanenbaum Research Institute, Sinai Health, University of Toronto
Michael Puopolo, Mount Sinai Hospital and Lunenfeld-Tanenbaum Research Institute, Sinai Health

Co-investigators or Collaborators

Saranya Arnoldo, Assistant Professor in the Department of Laboratory Medicine & Pathobiology, University of Toronto; Clinical Biochemist, William Osler Health System
Erin Bearss, Emergency & Family Physician and Associate Chief of Family Medicine, Mount Sinai Hospital; Assistant Professor, University of Toronto
Alexandra Binnie, Intensive Care Physician and ICU Research Lead, William Osler Health System
Yvonne Bombard, Associate Professor in the Institute of Health Policy Management and Evaluation, University of Toronto, Genomics Health Services Research Program, St. Michael’s Hospital, Unity Health Toronto
Bjug Borgundvaag, Associate Professor in the Department of Family & Community Medicine, University of Toronto; Emergency Physician, Mount Sinai Hospital
Howard Chertkow, Chair in Cognitive Neurology and Innovation and Senior Scientist, Baycrest and Rotman Research Institute; Director of Kimel Centre for Brain Health and Wellness and Clinical Trials Unit, Baycrest; Adjunct Professor, Dept. of Neurology and Neurosurgery, McGill University; Professor of Neurology (Medicine), University of Toronto
Marc Clausen, Senior Research Program Manager, Genomics Health Services and Policy Research, St. Michael’s Hospital, Unity Health Toronto
Luke Devine, Assistant Professor in the Department of Medicine, University of Toronto; Division Head of General Internal Medicine, Mount Sinai Hospital
Hanna Faghfoury, Associate Professor in the Department of Medicine, University of Toronto; Medical Geneticist, Mount Sinai Hospital and University Health Network
Steven Marc Friedman, Associate Professor in the Department of Family & Community Medicine, University of Toronto; Emergency Physician, University Health Network
Anne-Claude Gingras, Professor in the Department of Molecular Genetics, University of Toronto, Mount Sinai Hospital and Lunenfeld-Tanenbaum Research Institute
Zeeshan Khan, Emergency Nurse, Mackenzie Health
Tony Mazzulli, Professor in the Department of Laboratory Medicine & Pathobiology, University of Toronto; Microbiologist in Chief, Mount Sinai Hospital and University Health Network
Allison McGeer, Professor in the Department of Laboratory Medicine & Pathobiology, University of Toronto; Infectious Disease Physician, Mount Sinai Hospital
Shelley McLeod, Assistant Professor in the Department of Family & Community Medicine, University of Toronto; Emergency Physician, Mount Sinai Hospital
Trevor J. Pugh, Associate Professor in the Department of Medical Biophysics, University of Toronto, University Health Network, Ontario Institute for Cancer Research
David Richardson, Infectious Disease and Medical Microbiology Physician, William Osler Health System
Jared Simpson, Assistant Professor in the Computational Biomedicine group, University of Toronto, University Health Network, Ontario Institute for Cancer Research
Seth Stern, General Internal Medicine Physician, Mackenzie Health
Lisa Strug, Canada Research Chair in Genome Data Sciences, Professor of Statistical Sciences, Computer Science and Biostatistics at the University of Toronto, Senior Scientist, Program in Genetics and Genome Biology, The Hospital for Sick Children
Ahmed Taher, Assistant Professor in the Department of Medicine, University of Toronto; Emergency Physician, University Health Network and Mackenzie Health
Iris Wong, Post Anesthetic Care Unit (PACU) Nurse, Mackenzie Health