RI-MUHC ANNUAL REPORT 2021
CHARTING THE COURSE TO A POST-PANDEMIC WORLD
“We need a global vision to tackle a global pandemic,” says infectious diseases physician and medical microbiologist Dr. Don Sheppard. “This virus is brand new to the human population, and what we’re seeing is evolution in action.”
Charting our pandemic response since the outset, scientists at the Research Institute of the McGill University Health Centre (RI‑MUHC) have risen to the challenge with unparalleled outreach at local, national and international levels. This overview explores some of the many ways in which their efforts are helping to realize that global vision.
- BOLSTERING OUR LINES OF DEFENCE
- UNDERSTANDING THE VIRUS
- PROTECTING THE VULNERABLE
- OVERCOMING VACCINE HESITANCY
From outside the laboratory and within, RI-MUHC scientists are providing the tools we need to navigate toward a viable post-pandemic world. “This virus is learning to live in us as a new species, mutating to infect us better,” Dr. Don Sheppard reminded viewers of a national newscast more than a year into the battle against COVID-19. And, on the cusp of one or more waves of variants, he said, “it is not the time to be thinking locally.”
Dr. Sheppard is one of the RI-MUHC scientists who have taken the lead in calling for more equitable COVID-19 vaccine distribution globally, while urging Canadians to use their first and best line of defence—the vaccines now available—to drive home an advantage against the virus.
At McGill and the RI-MUHC, “we were among the first in Canada to detect the arrival of the Alpha variant in this country, which signalled a change in the pandemic,” he says. “We now realize that without equitable and global access to vaccines, we will continue to force the emergence of new variants in areas of high transmission that will rapidly make their way to Canadian shores.
“Our work in identifying and tracking variants is part of this global approach. So is the work of our researchers pioneering clinical trials.”
Our voices on Canada’s COVID-19 Therapeutics Task Force
Intense research activity during the pandemic has competed with the need for scientists and public health experts to participate in public health ventures, policy-making and outreach. Yet, in a period defined by social distancing, many have found working with their counterparts across Canada invigorating.
Drs. Don Sheppard, Makeda Semret and Don Vinh, all members of the Infectious Diseases and Immunity in Global Health Program at the RI-MUHC and leaders in the McGill Interdisciplinary Initiative in Infection and Immunity (MI4), joined forces in an important line of defence against COVID. In the summer of 2020, the Canadian government launched the COVID-19 Therapeutics Task Force to assess treatments under development and provide expert advice about which drugs to procure and which scientific projects to support. The three colleagues served as science advisors.
In this role they helped review over 35 applications to the Strategic Innovation Fund for Innovation, Science and Economic Development Canada (ISED), all relating to the development of COVID-19 therapeutics. They also advised the federal government on securing supplies of other therapeutic agents for treating COVID-19.
“Even after the public health crisis passes, patients with COVID-19 will continue to arrive in the clinic—possibly for years to come, if SARS‑CoV-2 becomes a seasonal virus—and physicians will need therapeutics to help them,” said Dr. Semret early in her mandate. By the time the task force completed its work in mid-2021, she reports, “The number of hospitalizations and deaths have significantly decreased with vaccination efforts. At the individual case management level, I would say we certainly have a better handle on how to treat severe infections than we did at the start of the pandemic—though this will continue to evolve.”
Task force participants underscored the value of looking ahead to ensure that Canada is better equipped for future pandemics. Their work led to the creation of the Therapeutics Advisory Group for ISED on which Drs. Vinh and Sheppard continue to serve.
Dr. Vinh embraced this chance to help patients and the country. As a researcher and physician who cares for individuals hospitalized with severe COVID-19, he says, “Bringing both the medical perspective and the research angle—contributing to our scientific understanding of COVID—to a populational level, and providing guidance to the government, has been a real honour.”
Dr. Sheppard concludes, “Seeing science move from concept to clinical application in record time reinforced my belief in the power of research to save and change lives.”
Testing the virulence of variants is a top strategy in the battle against COVID-19. In this and other pivotal work to understand and get ahead of the virus, basic research depends on a secure environment for study. In the months following February 2020, when the first COVID-19 case was reported in Quebec, Dr. Marcel Behr lost no time in spearheading the effort to repurpose existing facilities and create a space for the many McGill and RI-MUHC researchers who had already formulated plans to advance COVID-19 research.
Certification to study SARS COV-2 … in record time
A senior scientist in the Infectious Diseases and Immunity in Global Health Program at the RI-MUHC, Dr. Behr directs one of two McGill-affiliated sites, the Centre for Translational Biology Containment Level 3 (CL3) Platform housed within the RI-MUHC. Created to support research in tuberculosis, influenza and HIV, and with three independent pods that met the second-highest level of biosafety standards defined by Canadian Biosafety Standards and Guidelines, the potential of these premises to accommodate COVID-19 research was clear. The catch was the exacting certification process to conduct research on infectious human pathogens like SARS COV-2, the virus that causes COVID-19.
As the public health emergency escalated into a pandemic, CL3 staff, with stakeholders from the McGill and RI-MUHC animal facilities and environmental and health offices, were more than motivated to secure this special certification in record time. Their joint success proved a milestone for COVID-19 research in Quebec and Canada.
With its licence amended by the end of March 2020, the CL3 facility at the RI-MUHC was ready to receive the first batch of viral samples from laboratories in Quebec, Winnipeg and Toronto. “We originally obtained three different strains in May 2020. After that, we also obtained some of the strains now known as variants of concern,” says Dr. Behr.
Rapid progress founded upon partnerships
Working closely with Dr. Behr to expand opportunities for research is Silvia Vidal, PhD, a colleague from the IDIGH Program. Director of the McGill University Centre on Complex Traits, she oversees the McGill-affiliated CL3 located at the Bellini Life Sciences Complex, where researchers are primarily invested in discovering antiviral therapies. “The bread and butter of their research has been to identify mechanisms that prevent the spread of infection,” explains Silvia Vidal. “We had already created a CL3 facility to study tuberculosis, so much of our initial effort in mid-2020 went toward designing the repurposed facility in a way that serves the needs of our researchers.”
In both CL3 locations, McGill researchers, affiliated collaborators and external companies are conducting a range of COVID-19-related projects. As summarized by Dr. Behr, “Some research groups are working to modify an immune response to the infection, which informs vaccine development, while others are testing compounds as part of an antiviral treatment strategy. A third set of groups is requesting extracted viral RNA to develop new diagnostic tools.”
Strong RI-MUHC, MUHC and McGill partnerships made rapid progress possible from an idea to a platform for urgent new research. Dr. Behr is also founding director of the McGill International TB Centre and co-director of the McGill Interdisciplinary Initiative in Infection and Immunity (MI4), which partnered with the MUHC Foundation to fund many of the pioneering COVID-19 research projects featured in the 2020 RI-MUHC Annual Report. Also helped by a grant from MI4, McGill’s CL3 facilities will continue to provide a secure location for research as long as COVID-19 remains a relevant pathogen.
Who’s most at risk—and why?
COVID-19 is often more severe in people older than 60 or with health conditions like lung or heart disease, diabetes, or conditions that affect their immune system, according to the World Health Organization. Across Canada, but particularly in Quebec, people in long-term care facilities have accounted for a disproportionate number of COVID-19 deaths. Treating MUHC patients hospitalized with the disease since the outset of the pandemic, clinician-scientist Dr. Don Vinh knew it was imperative to understand why some people are more vulnerable to COVID-19.
Dr. Vinh was part of an international consortium of researchers who provided a first answer to that crucial question. Two studies published by the group in Science in October 2020 showed that about 15 percent of patients who suffer from life-threatening COVID‑19 have one thing in common: a defect in the activity of type I interferons (IFNs), molecules of the immune system that normally have a powerful antiviral activity. The defect is caused either by the presence of autoantibodies directed against those antiviral molecules, or by genetic abnormalities that decrease their production. These findings could make it possible to detect people at risk of developing a severe form of the disease in all age groups and to better treat patients with these conditions.
Dr. Vinh is now collaborating in a study that will help the federal government identify risk factors for developing severe COVID-19 symptoms and medical complications that may lead to a fatal disease. This multi-institutional research study for Canada’s COVID-19 Immunity Task Force is looking at the relationship between immune status, markers of inflammation, psychosocial factors and severity of COVID-19 symptoms.
“We still do not understand why some long-term care residents have gotten so sick and died of COVID-19, whereas others, at the same facility, have had milder versions of the disease or have not been infected at all,” says Dr. Vinh. “Our study brings together immunological, biochemical and psychosocial expertise to identify key factors that determine severe COVID 19 symptoms and complications in the elderly.” The goal is to guide better infection control measures, improve treatment outcomes, prioritize medical care and avoid unnecessary hospitalization.
CLSA COVID-19 Seroprevalence Study
As a principal investigator of the Canadian Longitudinal Study on Aging (CLSA), RI-MUHC researcher Christina Wolfson, PhD, has a leading role in another initiative funded by Canada’s COVID-19 Immunity Task Force. The task force invested $4 million in fall 2020 to conduct a SARS-CoV-2 seroprevalence study focused on older Canadians. A national platform for research on aging in Canada led by principal investigators at McMaster University and Dalhousie University, together with Christina Wolfson at McGill, the CLSA was uniquely qualified to carry out this work.
The COVID-19 Seroprevalence Study paints a comprehensive picture of the prevalence of the SARS-CoV-2 virus and the impact of COVID-19 among older adults in Canada. The CLSA is not only collecting blood samples, but also linking information about the presence of antibodies and other immune markers obtained from blood sample analyses to questionnaire findings from more than 18,000 CLSA participants in 10 provinces. The questionnaire explores symptoms, risks factors, healthcare use and the psychosocial and economic impacts of COVID-19. The information collected in the seroprevalence study can also be linked to data collected on the same participants in two previous waves of data collection before the pandemic.
“Our best means of ascertaining how close we are to containing the pandemic is to track the presence of antibodies in the population,” explains Christina Wolfson, a member of the Brain Repair and Integrative Neuroscience Program at the RI-MUHC. “The devastating effects of COVID-19 at all ages with higher levels of mortality at older ages make it imperative that we give particular attention to the evolution of the antibody profiles of older adults which will, very likely, be different from those of the younger population.”
The intent of this seroprevalence study, according to Dr. Theresa Tham, Chief Public Health Officer of Canada, is to plan and target public health approaches by improving our understanding of immunity among high-risk populations.
Active testing of priority groups
In early fall 2020 a team of RI-MUHC researchers and their colleagues recommended widespread testing for COVID-19 in priority groups, including healthcare workers, school students and staff, and essential services employees. Postdoctoral fellow Jonathon Campbell was first author, and Dr. Dick Menzies of the Translational Research in Respiratory Diseases Program, senior author, of an influential cost-analysis study published in the Canadian Medical Association Journal.
“As workplaces and schools reopened after the first wave of COVID-19 in Canada, testing priorities and strategies were needed to prevent surges in community transmission of SARS-CoV-2,” says Dr. Menzies. The benefit of widespread testing, as outlined in the study, would be detection and isolation of asymptomatic people infected with SARS-CoV-2.
The researchers calculated the costs, staffing needs and laboratory capacity required for systematic testing of five groups. These included contacts of people who are positive for SARS-CoV-2 along with four at-risk populations: hospital employees, community healthcare workers and people in long-term care facilities, essential business employees, and schoolchildren and staff.
“We believe that a strategy of actively testing large population groups who are at increased risk of acquiring SARS-CoV-2 is feasible and affordable in Canada,” the authors concluded. “This testing approach should be an integral component of a broad strategy to allow all Canadians to return safely to work and school.”
Protecting mental health in vulnerable families
The ravages of COVID-19 extend to mental health, and age is no barrier to stress. Dr. Lily Hechtman, a psychiatrist and senior scientist in the Child Health and Human Development Program at the RI-MUHC, has explored socio-economic and demographic factors that mediate poor family functioning, anxiety and depressive symptoms, in response to quarantine measures in Canadian parents and children.
Most families who responded to her study questionnaire experienced significant stress due to the pandemic and lockdown. The stress was expressed through high rates of depression and anxiety in both parents and children, and poorer family functioning. Vulnerable families included those with prior medical and/or psychiatric conditions in either children or parents, as well as families with younger parents, lower incomes and children over the age of five. “We therefore need to be aware of the stress that the pandemic and the lockdown cause in children, parents and families,” says Dr. Hechtman, “and provide treatment and support, particularly to vulnerable families.”
Protecting patients with other diseases
The fight against COVID-19 has depleted healthcare resources worldwide and reduced the availability of care for patients with other diseases. Being also at heightened risk for COVID-19, the immunocompromised and those living with other health conditions are doubly vulnerable.
A member of the Cancer Research Program at the RI-MUHC, Dr. Nathaniel Bouganim is concerned by higher mortality rates from COVID‑19 in cancer patients, particularly those with lung cancer. He and two MUHC colleagues, Dr. Suzanne Kazandjian and Dr. Arielle Elkrief, tracked and evaluated changes in treatment plans for the protection of lung cancer patients seen in the thoracic oncology clinic at the Cedars Cancer Centre of the MUHC in the early months of the pandemic. Published in JAMA Oncology, their findings underscore that “all oncology clinics should track these changes occurring in cancer care, because it will become important to evaluate the effect of these changes on clinical outcomes.”
“Now we know which measures need to be taken to protect patients who come to the hospital, and more importantly, no clear evidence has emerged that cancer treatments increase the risk of severe COVID-19 outcomes,” says Dr. Elkrief, first author of the study.
Dr. Madhukar Pai, senior scientist in the Infectious Diseases in Global Health Program at the RI-MUHC, has been advocating a damage control plan to help mitigate the disruptive effects of the pandemic on essential tuberculosis (TB) services in low- and middle-income countries. During 2020 over 1.4 million people with TB were missed by health systems, and this, he says, has set back progress by nearly a decade.
With funding from the Bill & Melinda Gates Foundation, Dr. Pai, who is associate director of the McGill International TB Centre, has helped track disruptions caused by the pandemic in TB services in India, Indonesia and Nigeria. He has emphasized the syndemic nature of TB and COVID-19 in India in a BMJ Global Health publication and offered suggestions in Lancet Microbe on learning, from COVID-19, how to reimagine TB care.
Dr. Pai also received a grant from the Canadian Institutes of Health Research and the International Development Research Centre to evaluate an integrated approach to testing for COVID-19, as well as TB, in Peru. Since cough and fever are symptoms of both infections, an integrated testing approach might help ensure that TB is not missed during this crisis. More than 500 people have been recruited in this project.
“In 2021, do we need to really justify that we are part of a global society?” asks Dr. Pai. His efforts to end TB and achieve a more equitable global access to health care—including access to COVID-19 vaccines—led to his appointment to two World Health Organization expert groups in mid-2021.
Thanks to decades of intense background research telescoped into a single year of development, the first vaccines against COVID-19 were fully authorized for use in Canada by the end of 2020. Knowing that this would neither reduce the risk nor eliminate COVID-19 unless most people agreed to be vaccinated, four RI-MUHC researchers from the Infectious Diseases in Global Health Program had the foresight to launch early projects seeking to overcome barriers to vaccination. Dr. Nadine Kronfli focused on uptake in incarcerated Canadian populations and Dr. Abhinav Sharma, in cardiovascular patients. Dr. Inés Colmegna and Dr. Moshe Ben-Shoshan considered uptake in adults and children, respectively.
Preparing adults for the COVID-19 vaccine
Dr. Colmegna’s “PROVIDE-A” study in adults adapted measures shown effective to enhance vaccine uptake in non-COVID vaccines. Using knowledge gained from work at the MUHC on influenza vaccine acceptance in people living with rheumatic diseases, her team’s first goal was to identify attitudes, beliefs and behaviours with regard to COVID-19 vaccines. Next, they aimed to engage McGill community members and MUHC healthcare workers to actively promote COVID-19 vaccine uptake.
The team surveyed 1,793 people immunized for influenza, including MUHC healthcare workers, to assess acceptance rate of a future COVID‑19 vaccine and flag potential determinants of non-acceptance. Vaccine safety concerns and opposition to mandatory vaccination were found to be the strongest predictors of vaccination refusal. These findings, along with a survey on reasons for refusing to be scheduled to receive a COVID-19 vaccine among MUHC personnel, helped determine the optimal ways to address misconceptions and conduct intervention strategies.
“Since the COVID-19 vaccines were initially available, there has been an increase in uptake of vaccines by MUHC personnel as well as other groups,” says Dr. Colmegna. “The individual effects of multiple interventions promoting vaccine acceptance, together with reassuring global safety data and an understanding of the risks associated with COVID-19, have encouraged vaccine acceptance.”
Barriers to vaccinating children
Dr. Moshe Ben-Shoshan, a pediatric allergist and immunologist, anticipated the eligibility of children for vaccination when he conceived the COvid Vaccine Evaluation of Resources and Solutions (COVERS) study with colleagues in Canada and Sweden. The study aimed to identify potential barriers related to vaccine acceptance, distribution and administration in a family context.
Parents of children at the Allergy Clinic at the Montreal Children’s Hospital and at a private allergy office were invited to complete an anonymous online survey on COVID-19 in mid-2021. Over three-quarters of the 97 respondents indicated they would vaccinate their children against COVID-19. Fear of side effects was identified as the most common barrier for vaccination (49.5%). More than half of participants reported that receiving more information would increase their willingness to get the vaccination, with the preferred method being videos.
“There are still substantial knowledge gaps among parents regarding vaccination of children,” Dr. Ben-Shoshan concludes. “In particular, almost a third of our respondents still had fears to vaccinate when there is a history of allergy, although recommendations by the Canadian Society of Allergy and Clinical Immunology show that this is not a contra-indication.” A video addressing parental concerns voiced in the study will be available in September 2021.
The imperative for outreach
As we navigate new waves of the pandemic driven by variants of the virus, research alone cannot address the trust issues integral to vaccine hesitancy. The RI-MUHC community is also invested in restoring faith in science and scientists. Its research trainees are natural ambassadors.
“It’s particularly important for members of different communities to be represented during national or regional vaccination campaigns and to see themselves represented in healthcare settings as well,” says Adam Hassan, a doctoral student at the RI-MUHC. He and MD-PhD candidate Lashanda Skerritt, another RI-MUHC trainee, and researchers Momar Ndao, DVM, PhD, and Dr. Makeda Semret, were panelists in a national outreach webinar for the Black community, opening a series of events held by the Federation of Black Canadians in March 2021. McGill Family Medicine student Khandideh Williams moderated the webinar on “Black Health and COVID-19,” which aimed to tackle vaccine misinformation and community concerns.
The questions that the panelists fielded from participants in several provinces targeted topics ranging from specific health concerns to contradictory or confusing media reports.
“We also had the opportunity to address specific questions related to the impact of COVID-19 on Black communities in Quebec,” says Lashanda Skerritt. “For example, we discussed why data at the time indicated that racialized and immigrant communities in Montreal had higher rates of COVID-19 and why it was particularly important for people to get the vaccine as soon as it was available to them.”
She adds, “It seemed appreciated that the panel of experts were also members of the Black community. The event highlighted the value of supporting community-led initiatives and culturally sensitive approaches to encourage vaccine uptake.”
- Tracking the emerging COVID-19 variants of concern in Canada
- Behind the scenes on Canada’s COVID-19 Therapeutics Task Force
- Containment Level 3 facilities advance COVID-19 research at the RI-MUHC and McGill
- COVID-19: Our researchers answer the call
- New study in Quebec long-term care facilities
- From silent infection to rapid death: Why are some people more vulnerable to COVID-19?
- The COVID-19 Immunity Task Force funds comprehensive new SARS-CoV-2 seroprevalence study focused on aging Canadians
- Systematic testing of groups at increased risk of SARS-CoV-2: an affordable and reasonable approach
- Protecting lung cancer patients from COVID-19 – and learning from the experience
- $2M funding to mitigate COVID-19 impact on tuberculosis services
- India’s syndemic of tuberculosis and COVID-19
- Learning from COVID-19 to reimagine tuberculosis diagnosis
- Overcoming vaccine hesitancy
- Results of MI4 Overcoming Barriers to COVID-19 Vaccination Research Funding Program
- RI-MUHC researcher Sasha Bernatsky leads nationwide COVID-19 vaccination study
- COVID-19 Vaccination: This is our shot (MUHC video on YouTube)
- COVID-19 vaccine for children: an explanatory video (MUHC video on YouTube)
- Research trainees are bridging the gap between science and the public