Dr. Xiangfei Meng is one of a group of researchers launching a study to investigate which factors are responsible for the severity of COVID-19 among elderly individuals in long-term care facilities.
Across Canada, but particularly in Quebec, long-term care facilities have accounted for a disproportionate number of COVID-19 deaths. The Government of Canada, through its COVID-19 Immunity Task Force (CITF), is supporting a new $2.7 million study aimed at identifying the factors putting each person at risk of developing severe COVID-19 symptoms and medical complications that may lead to a fatal disease.
“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 Donald Vinh, MD, an infectious disease and immunity expert at the Research Institute of the McGill University Health Centre (RI-MUHC) and an associate professor at McGill University. “Our study brings together immunological, biochemical, and psychosocial expertise to identify key factors that determine severe COVID-19 symptoms and complications in the elderly. If we can identify elderly people at greater risk of developing medical complications from COVID-19, it can guide better infection control measures and prioritize medical care to increase the chance that these people will have better treatment outcomes. The hope is to help avoid unnecessary hospitalization and in so doing, reduce the use of health care resources.”
The research team is multi-institutional and multi-disciplinary, involving the Research Institute of the McGill University Health Centre (RI-MUHC), Université de Montréal, Institut Universitaire de Gériatrie de Montréal (IUGM) and its Research Center (CRIUGM), Douglas Research Centre, McGill University’s Department of Psychiatry, and Concordia University's Department of Psychology. The study is being carried out in partnership with two health networks (CIUSSS Centre Sud and CIUSSS de l’Ouest-de-l’Île-de-Montréal).
The study aims to recruit 850 participants in public residential and long-term care facilities and in private seniors’ homes in Montreal. The team will take blood samples to compare the immune response in residents who were never infected, residents who were infected but had no or few symptoms, residents who had moderate cases of COVID-19, and residents who had severe cases of the disease.
The study will also look at the relationship between immune status, markers of inflammation, psychosocial factors and the severity of COVID-19 symptoms.
“In public residential and long-term care facilities, a large proportion of patients present some form of cognitive impairment,” explains Jean-Philippe Gouin, PhD, Associate Professor, Psychology, Concordia University. “We will first examine whether there is a correlation between psychosocial issues and more severe cases of COVID-19, and second,” Dr. Gouin continues, “whether a COVID-19 infection is associated with increased psychiatric symptoms, sleep disturbances, and cognitive impairment among long-term care residents.”
Cardiovascular issues, including arterial hypertension and coagulation dysfunction (not being able to properly control blood clotting), can lead to more severe cases of COVID-19. According to a study published in the European Heart Journal1, patients with high blood pressure admitted to hospital with COVID-19 are twice as likely to die as those without the condition. It is estimated that almost 20% of patients with COVID-19 have significant coagulation disorders. In addition, some vaccinated patients may develop blood clots (thrombosis) after healing from COVID-19. A team led by Hélène Girouard, PhD, Professor, Faculty of Medicine, Université de Montréal, will seek to identify measurable indicators associated with high blood pressure and coagulation dysfunction that could be predictors of more severe COVID-19 cases. This will inform treatments to prevent COVID-19 complications.
“COVID-19 has been catastrophic among the elderly in long-term care facilities and studies like this one are needed so that we can better protect them going forward,” says Dr. Catherine Hankins, CITF Co-Chair. “Vaccines will help to make an enormous difference in protecting Canadians from COVID-19.”
“Vaccines are being rolled-out in long-term care facilities across Canada to help protect the elderly, who have been disproportionately impacted by the COVID-19 pandemic,” says Dr. Theresa Tam, Canada’s Chief Public Health Officer. “This study will help provide greater insight into the early immune response of elderly Canadians to this viral infection, and how the immune response—and the subsequent severity of COVID-19 and variants of concern—is affected by cardiovascular and psycho- social factors.”
1. “Association of hypertension and antihypertensive treatment with COVID-19 mortality: a retrospective observational study”, by Chao Gao et al. European Heart Journal. doi:10.1093/eurheartj/ehaa433
Q & A with the study team
1. Who is involved in this study?
The research team is multi-institutional and multi-disciplinary, involving the Research Institute of the McGill University Health Centre, Université de Montréal, Institut Universitaire de Gériatrie de Montréal (IUGM) and its Research Center (CRIUGM), Douglas Research Centre, McGill University’s Department of Psychiatry, and Concordia University's Department of Psychology. The study is being carried out in partnership with two health networks (CIUSSS Centre Sud and CIUSSS de l’Ouestde-l’Île-de-Montréal).
2. How many long-term care facilities are involved and which ones?
The study aims to recruit about 850 participants in public residential and long-term care centres (CHSLDs) and in private seniors’ homes in two vast areas of Montreal that are part of two Integrated Health and Social Services University Networks (CIUSSS): Centre Sud and l’Ouest-de-l’Île-de-Montréal).
3. How many blood samples are being taken?
The long-term care facilities and private senior’s residences will be collecting samples for PCR tests that detect an active COVID-19 infection in their residents on a regular basis. Once a long-term care resident tests positive for SARS-CoV-2, they will be asked if they’d like to participate in a study. For willing participants, the research team will be called in to take a first blood sample, which we will call “Day 0”. They will take subsequent blood samples on days 5, 10, and months 1, 3, 6 and 12. The study team is looking at the possibility of taking blood samples at months 18 and 24, if funding allows. The study team will also take at least one blood sample from residents who test negative for SARS-CoV-2 as a comparison group.
4. Are you taking blood samples from long-term care residents who have been vaccinated?
Yes. In the DISCoVER project, researchers will be collecting blood samples from any willing resident who has tested positive for SARS-CoV-2, whether they have been vaccinated or not. These residents may not have had a vaccine yet, may have had only one dose, or may have had two doses. The researchers will analyze how vaccination affects the severity of illness.
5. Why would residents who have been vaccinated test positive for COVID-19?
There are three main reasons that someone who has been vaccinated could still test positive for SARS-CoV-2. First, the vaccines take 10-14 days to start having any protective effect. So, if a person was already exposed to SARS-CoV-2 in the days before vaccination or in the period after the vaccination before protection kicks in, they can develop COVID-19. Second, COVID-19 vaccine trials showed that the vaccines approved for use in Canada are highly effective at preventing severe COVID disease. How effective they are at reducing the chances of infection is not yet known, but studies from countries that are ahead of Canada in vaccine rollout are showing that transmission is slowing. We expect that people who have been vaccinated will still have a risk of infection if they are exposed. Studies are showing that they generally have no or few symptoms and they have decreased viral load which will make them less likely to transmit. Third, it’s possible the existing vaccines do not ward off all the variants showing up.
6. Are you looking at the immune response to vaccines?
The team is not studying the immune response to vaccines in this study, but they are in discussions to do so in another study.
7. Have there been many residents in long-term care facilities who have been exposed to COVID-19 but who have not contracted SARS-CoV-2?
The short answer is: "we don't know". What we do know is that, during each wave, outbreaks have occurred in long-term care facilities. Unfortunately, an unacceptably large number of these elderly people contract the infection and become severely sick or die from it. However, within any given long-term care facility, not every person gets infected or becomes sick. The researchers in this study want to accurately determine the number of elderly residents who get infected but do not become sick, as well as the number who are in close contact with someone who has COVID-19 – and who have a high risk of becoming infected – but who never test positive for the virus or become sick. Importantly, they want to look at the immune, cardiovascular, and psychosocial factors that differentiate these groups.
8. With vaccination underway, how will the study team manage to get blood samples pre-vaccination?
There are still residents of some long-term care facilities who have not been vaccinated, although it is unclear how many. In addition, this study team is interested in obtaining blood samples from any resident who tests positive as an active case of COVID-19, whether vaccinated or not.
9. Will the researchers be looking at people’s immunity over time?
Yes, this study will continue taking blood samples from participants who test positive over the course of a year. This give researchers enough information to compare the immune responses in residents who were never infected, residents who were infected but had no or few symptoms, residents who had moderate cases of COVID-19, and residents who had severe cases of the disease. The team aims to identify factors in the immune system that make certain elderly people more prone to develop severe cases of COVID-19.
10. Can you elaborate on the details of the portion of the study involving cardiovascular research?
Arterial hypertension and coagulation dysfunction (not being able to properly control blood clotting) are important risk factors for COVID-19 severity. Indeed, patients with high blood pressure admitted to hospital with COVID-19 are twice as likely to die as those without the condition, according to a study published in the European Heart Journal. In addition, it is estimated that almost 20% of patients with COVID-19 have significant coagulation disorders, and about a quarter of those hospitalized in intensive care units are prone to develop thrombosis events even when being treated with anticoagulants. Among patients who have been immunized after healing from a SARSCoV-2 infection, some have a hypercoagulable state and are prone to develop thrombosis. Consequently, a team led by Hélène Girouard, PhD, Professor, Faculty of Medicine, Université de Montréal, will identify blood biomarkers associated with high blood pressure and coagulation dysfunction that could be predictors of COVID-19 severity. This will inform therapeutic approaches to prevent COVID-19 complications.
11. Why would psychosocial issues affect a person’s COVID-19 disease severity?
Psychosocial stressors, such as chronic stress, loneliness, or poor sleep, are known to influence immune function. Notably, chronic stress has been associated with increased inflammatory responses. Greater exposure to psychosocial stressors may thus shift the immune response in a way that increases COVID-19 severity. This project will help to untangle how different aspects of psychological and social functioning may be related to COVID-19 among the elderly.
12. When will you start recruitment?
We will begin recruitment over the next few weeks.
13. How are you recruiting participants?
We are recruiting participants by identifying those who received a positive COVID-19 result and inviting them to take part in our study.
14. When do you expect results?
We expect the results of our project by Spring 2022.
About the COVID-19 Immunity Task Force
In late April 2020, the Government of Canada established the COVID-19 Immunity Task Force with a two-year mandate. The Task Force is overseen by a Leadership Group of volunteers that includes leading Canadian scientists and experts from
universities and healthcare facilities across Canada who are focused on understanding the nature of immunity arising from the novel coronavirus that causes COVID-19. To that end, the CITF is supporting numerous studies to determine the
extent of SARS-CoV-2 infection in Canada (in the general population as well as in specific communities and priority populations), understand the nature of immunity following infection, develop improved antibody testing methods, and help monitor
the effectiveness and safety of vaccines as they are rolled out across Canada. The Task Force and its Secretariat work closely with a range of partners, including governments, public health agencies, institutions, health organizations, research teams, other task forces, and engages communities and stakeholders. Most recently, the Task Force has been asked to support vaccine surveillance, effectiveness and safety as part of its overall objective to generate data and ideas that inform interventions aimed at slowing—and ultimately stopping—the spread of SARS-CoV-2 in Canada. For more information visit: www.covid19immunitytaskforce.ca.