Six research projects from St. Michael’s Hospital have been awarded more than $2.6-million from the Canadian Institutes for Health Research (CIHR) to fill key knowledge gaps in the COVID-19 pandemic.

The Government of Canada, Health Canada, the Public Health Agency of Canada, the Chief Science Advisor, related expert panels, the National Advisory Council on Immunization and CIHR’s institutes set out to fund research in areas where key questions remain about the COVID-19 pandemic. They created the Emerging COVID-19 Research Gaps and Priorities Funding Opportunity to help seek out answers.

The six St. Michael’s projects are tackling important issues including the impact of COVID-19 vaccination in children and families, the supports personal support workers need in long-term care, the causes behind “Long COVID” and understanding vaccine uptake among people experiencing homelessness. Learn more about each funded project below.

Uncovering the role of immune responses in Long COVID

Led by Dr. Andrew Baker, scientist at the Keenan Research Centre for Biomedical Science

After recovering from COVID-19, many people suffer poor health outcomes with increased risk of hospitalizations and death compared to people who did not have COVID-19. Even if they don’t need to be hospitalized, many suffer long-term effects such as cognitive dysfunction (known as brain fog), sensory losses (taste, smell) and weakness.

This is known as “Long COVID” in the media, or post-COVID syndrome in the medical world. The reason for this illness is currently unknown. Dr. Baker and his team reason it is likely related to a similar syndrome that affects people after other severe diseases, called post-intensive care unit (ICU) syndrome.

In this project, Dr. Baker and his team will study post-COVID syndrome and its relationship with post-ICU syndrome. The team’s main hypothesis is that autoimmunity – the system of immune responses of an organism against its own healthy cells, tissues and other body functions – plays a role in post-COVID syndrome, and they intend to study it in three ways:

  1. Map the autoimmune landscape of severe COVID-19 by assessing a broad variety of autoantibodies – antibodies produced by the immune system that is directed against one or more of the individual’s own proteins – among severe COVID-19 patients over time, and their association with specific organ dysfunction;
  2. Study the development of these autoantibodies using immune mediators and measurements of immune cells; and,
  3. Validate their findings in long-term post-COVID patients, to see if the same autoantibodies and the same organ dysfunction happen to them as well.

Understanding the role of autoantibodies in post-COVID could enable clinicians to use existing related medications to help treat patients with post-COVID syndrome and even prevent it from happening.

How can targeted supports in long-term care homes improve experiences for personal support workers?

Led by Dr. Christine (Tina) Fahim, a scientist at the Knowledge Program

More than 80 per cent of people who died during the COVID-19 pandemic lived in long-term care homes and assisted living facilities, where most of the care is provided by Personal Support Workers (PSWs). PSWs’ essential, frontline work puts them at increased risk of COVID-19. PSWs are also an unregulated workforce who face many challenges due to systemic inequities and require access to supports and resources during the pandemic.

“Many PSWs feel they do not have the resources they need to navigate the pandemic safely,” said Dr. Fahim. “These challenges coupled with systemic equity gaps result in PSWs experiencing significant lack of wellness, burnout and other challenges during the pandemic.”

Dr. Fahim’s project will create evidence for a generalizable, adaptable model that can support this population’s evolving needs during the pandemic. The team will use a trial to evaluate the impact of providing PSWs working in long-term care with personalized, tailored support from a resource navigator and educational resources.

“By leveraging our ongoing work to support long-term care PSWs, our research will also maximize PSWs’ health benefits by providing access to wellness and mental health and infection prevention (including vaccine) related supports,” Dr. Fahim said. “This work presents a model of how knowledge translation methods can translate evidence into practice and inform policy and practice recommendations to support PSWs working in long-term care.”

Exploring vaccine uptake and hesitancy among people experiencing homelessness in Toronto

Led by Dr. Jesse Jenkinson, postdoctoral fellow at MAP Centre for Urban Health Solutions, and Dr. Stephen Hwang, director of MAP Centre for Urban Health Solutions

Homelessness is a public health crisis in Canada, exacerbated by the COVID-19 pandemic. People experiencing homelessness face disproportionate physical, mental, and social burdens, risk factors for poor outcomes if infected with COVID-19. Those living in shelters are at higher risk for contracting COVID-19 because of shared living spaces, crowding, difficulty physical distancing, and high population turnover.

Given increased risk for exposure and serious infection, homeless individuals who live in congregate settings are a priority population for the vaccine rollout in Canada. Vaccination rates among people experiencing homelessness, however, are historically lower than the general population, linked in part to vaccine misinformation and poor experiences with health-care systems and providers leading to mistrust.

In partnership with the City of Toronto, Anishnawbe Health Toronto, Women’s National Housing and Homelessness Network and Canadian Alliance to End Homelessness, Dr. Stephen Hwang and his team, including post-doctoral fellow Dr. Jesse Jenkinson, will lead one of the first Canadian studies to investigate COVID-19 vaccine uptake and hesitancy among this population.

“This funding from CIHR has ensured that we can hire peer research associates with lived experience of being unhoused or housing precarity, who will help guide the study and interpret the findings,” Dr. Jenkinson said. “We are also able to extend our participant recruitment into encampments, in partnership with Anishnawbe Health Toronto. This is vital, as encampment residents may have very different barriers to vaccination, and have different ways they are protecting themselves during the pandemic.”

As a sub-study of the COVENANT longitudinal cohort study, this work will help explain and expand on data captured in the COVENANT study on COVID-19 incidence, prevalence, risk factors and protective factors for COVID-19 infection and mortality, including vaccination rates for people living in physical distancing hotels, emergency shelters and encampments.  

From idea to reality: COVID-19 vaccination for children and youth,

Led by Dr. Jonathon Maguire, a scientist at MAP Centre for Urban Health Solutions

Children represent 21 per cent of the Canadian population. Vaccinating kids against COVID-19 will be vital to achieve herd immunity against the illness. Vaccines for children will soon be available and while serious acute COVID-19 in children is rare, it can occur, underscoring the importance of vaccinating children against COVID-19.

In April 2020, Dr. Maguire and his team directed Canada’s largest ongoing children’s cohort study, TARGet Kids!, to understand the effects of COVID-19 on Canadian children and families. The study involved 1,123 children to understand COVID-19 infection and symptoms, risk factors for infection, physical and mental health status and the prevalence of the virus among children and their parents.

“Through the Canadian COVID-19 Immunity Task Force funded TARGet Kids! COVID-19 Study of Children and Families, we will continue to answer urgent questions about real-world COVID-19 vaccine effectiveness and safety and evaluate immune response and adverse effects in children,” Dr. Maguire said. “We will also measure vaccine uptake and understand facilitators and barriers to COVID-19 vaccination among children, parents and their health-care providers.”

The study also aims to understand COVID-19 vaccine hesitancy and decision-making among parents and health-care providers. This high-quality evidence can guide family-based policy interventions for COVID-19 vaccination for children.

Building an international research response to COVID-19 variants

Led by Dr. John Marshall, a scientist at the Keenan Research Centre for Biomedical Science

Information about the best treatments for patients with COVID-19 is being generated at a record pace and large international clinical trials have been central to this process.

REMAP-CAP (the Randomized Embedded Multifactorial Adaptive Platform Trial in Community-Acquired Pneumonia) is one such trial; it focuses on the care of the sickest patients, those who are ill enough to need organ support in an ICU. REMAP-CAP is currently active in 330 sites across five continents. It has recruited more than 7,950 COVID-19 patients, and identified three treatments that improve patient outcomes: treatment with corticosteroids, inhibition of a protein called IL-6, and blood thinners in some, but not all patients.

This funding will allow the Canadian arm of REMAP-CAP to maintain a leadership role in the international effort to end the COVID-19 pandemic. The team, led by Dr. Marshall, aims to understand how to treat the new variants of the virus by:

  1. Focusing on treatments that seem to be more effective in patients with severe disease, and in particular, on treatments that interfere with interactions between the virus and a protein called ACE2 that the virus uses to enter cells.
  2. Using international variability in rates of variant disease to determine whether the effectiveness of treatment is influenced by the infecting variant.
  3. Expanding their network of 34 recruiting sites to ensure that the team is enrolling patients from across the country, and in particular where rates of infection are highest.

“REMAP-CAP has created an unprecedented international collaboration, and advanced the science of this type of trial,” Dr. Marshall said. “This CIHR funding will not only realize the potential of an idea that had its conception a decade ago at a meeting at St. Michael’s, it is building a new and powerful model of global research collaboration.”

Global Impact of COVID-19 in Cystic Fibrosis: An International Collaboration

Led by Dr. Anne Stephenson, a scientist at the Li Ka Shing Knowledge Institute

Cystic fibrosis (CF) is a multi-system genetic condition that affects nearly 90,000 people globally. There is no cure. In addition to managing other complications including CF-related diabetes, malnutrition, and progressive lung damage, those with CF are susceptible to frequent lung infections. To date, the impact of the COVID-19 pandemic on the CF population is not well understood, and little is known about the disease course and long-term effects of COVID-19 on this medically vulnerable population.

Using robust national patient databases, Dr. Stephenson and her team will address three areas in this work:

  1. What are the risk factors, including sex and other clinical parameters, that predict poor outcomes following SARS-CoV-2 infection?
  2. What are the medium and long-term impacts of COVID-19?
  3. What are the factors that influence CF health outcomes after COVID-19 in those who have received a transplant?

“Providing CIHR funding to support this program of research lays the foundation for future international projects and is a rare opportunity for Canada to make a real difference to those living with CF not just nationally, but on a global scale,” Dr. Stephenson says. “This work will provide vital knowledge about who is at highest risk for poor health outcomes so that clinical teams and people with CF (both pre- and post-transplant) can make informed choices about exposure risk and clinical decision-making including COVID-19 vaccination prioritization.”

The study will also contribute important information to the CF community about variables of interest to capture within CF registries beyond the pandemic. This will allow future research to study the impact of other viruses or vaccination effectiveness, for example.

By: Ana Gajic