Fall 2020: DSEN Researchers advancing knowledge on COVID-19

DSEN Researchers Advancing Knowledge on COVID-19

DSEN funded teams are involved in the pan-Canadian and global response to the COVID-19 crisis. This edition of the DSEN newsletter focuses on the various ways DSEN researchers contribute to these efforts.

Canadian Network for Observational Drug Effect studies

DSEN- Canadian Network for Observational Drug Effect studies (CNODES)

Supporting health system capacity and decision-making in Ontario

In March 2020, with the emergence of COVID-19 and demand for rapid public health decision-making at the highest level, ICES, the home of the Ontario site of CNODES, received multiple Applied Health Research Questions (AHRQs) designed to better inform health system planning, policy and program development.

In relation to COVID-19, these requests helped support health system capacity planning and decision-making on the strategies and resources needed for laboratory testing and health care. Multiple COVID-19 AHRQ requests have been received ranging from descriptive studies of COVID-19 testing patterns and test recipients to modelling exercises to support hospital capacity planning. In the weeks ahead, ICES will inevitably receive AHRQ requests on COVID-19 patient outcomes and factors affecting those outcomes, as well as requests regarding fall 2020 testing and surveillance activities surrounding Ontarians' return to school and work.

HDRN Canada’s COVID-19 testing data survey

Health Data Research Network (HDRN) Canada, under the leadership of Dr. Lisa Lix, Chair of the Network’s Working Group on Algorithms and Harmonized Data, and CNODES Database team lead, conducted a survey of data centres across Canada in June and July 2020 to compile information about COVID-19 laboratory testing data. HDRN Canada reports that COVID-19 laboratory testing data are currently available for research purposes in five Canadian provinces: British Columbia, Alberta, Manitoba, Ontario, and Newfoundland, and includes the following information:

  1. The availability of selected variables/fields in the COVID-19 lab testing data in these provinces, and
  2. An overview of the data, including frequency of data updates and the dates of testing currently captured in the data.

This compilation of information about COVID-19 laboratory testing data across Canada supports researchers who are interested in conducting multi-jurisdictional research. Access to these resources accelerates and improves the quality of COVID-19 analytics, predictive models and research studies that include multiple provinces and territories.

McGill University’s CNODES contributions to Canada’s COVID-19 response at the forefront of a variety of COVID-19 related research and initiatives, including:

  • The development of Canada’s largest biobank of severe COVID-19 infected patients: Biobanque Québec COVID-19

    Over 1100 patients who presented symptoms consistent with COVID-19 have been recruited to provide samples for an Open Science-based resource project. Patients who were divided between SARS-CoV-2 positive participants and negative controls have consented to sharing data and samples widely within the academic and industrial scientific communities. The research project has received funding to recruit up to 5,000 participants with a broad range of disease severity, and for genome-wide genotyping, whole genome sequencing, proteomics and viral sequencing. Samples are collected at various intervals in the hospital and follow-up visits up to one year. Dr. Samy Suissa, CNODES Executive, is a member of the Governance Committee for this project, which is being led in his Center for Clinical Epidemiology at the Jewish General Hospital, in Montreal, by Dr. Brent Richards.

  • The effectiveness of anticoagulants at improving COVID-19-related outcomes using the Korean Nationwide Healthcare Database

    Emerging evidence suggests abnormal blood clotting may occur among COVID-19 patients, and this clotting is associated with worse prognosis and decreased survival. The body’s immune system may be responding to the SARS-CoV-2 infection by activating a series of physiologic reactions that promote coagulation. The use of anticoagulants may therefore be associated with beneficial effects among patients with COVID-19. This ongoing study is led by Dr. Kristian Filion (CNODES, Clinical Practice Research Datalink (CPRD) site co-lead) and his team, with collaborators at Sungkyunkwan University in South Korea. Results are expected later this year.

  • A critical review of studies of COVID-19 treatments

    CNODES investigators, Drs. Christel Renoux, Laurent Azoulay and Samy Suissa, led a thorough review of several observational studies conducted and published related to the COVID-19 crisis. During this pandemic, an unprecedented effort to generate real-world evidence on the effects of various treatments for patients hospitalized for COVID-19 has led to a growing number of studies evaluating the effectiveness of certain drugs (such as hydroxychloroquine) and risks of other drugs (such as angiotensin converting enzyme inhibitors and angiotensin II receptor blockers). This review, to be published in the American Journal of Epidemiology, illustrates how immortal time bias and selection bias were present in several studies, leading to incorrect conclusions. This research presents important methodologic principles to consider for future observational studies on potentially promising drugs in the midst of the COVID-19 pandemic. This study was submitted for publication to the American Journal of Epidemiology.

Canadian Network for Advanced Interdisciplinary Methods for Comparative Effectiveness Research

DSEN - Canadian Network for Advanced Interdisciplinary Methods for Comparative Effectiveness Research (CAN-AIM)

Evidence-based COVID-19 decision-making starts in Canada’s emergency departments

While COVID-19 was rapidly emerging as the greatest public health threat in a century, an emergency physician, front-line care provider and CAN-AIM researcher, Dr. Corinne Hohl from the University of British Columbia, was struck by the gaps in knowledge concerning emergency care. In response, Dr. Hohl is now leading investigators from 51 emergency departments across eight Canadian provinces to conduct a CIHR-funded multi-centre national cohort study.

This cohort study is enrolling patients who repeatedly visit emergency rooms with suspected COVID-19. Standardized prospective data is collected and linked to electronic patient records to provide answers about key outcomes such as COVID-19 test results, hospitalization, ICU stays, ventilation requirements, mortality, discharge safety, and other patient-centred data. The results will develop and validate clinical decision rules regarding suspected COVID-19 cases. This will allow personalized evidence-based recommendations to improve COVID-19 treatment and outcomes right from the time of presentation. The Canadian COVID-19 Emergency Department Rapid Response Network will impact Canadian guidelines and may also inform international guidelines. It is anticipated that it will generate 30-50 sub-studies of high relevance to the Canadian pandemic response.

CONCEPTION: Short and long-term impacts of COVID-19 public health guidelines and hospital policies on maternal and child mental and physical health

Dr. Anick Berard, Sainte-Justine Research Centre researcher and professor at the Université de Montréal and CAN-AIM researcher and director of its pillar on drug safety in pregnancy and offspring, launched an international, multi-province, and multi-university COVID-19 research initiative called CONCEPTION. The scientific teams from Canada, the United States, and Europe assess measures such as confinement, physical distancing, school closures, quarantine and restrictions on companions during medical appointments and labor have physical and mental health impacts on expecting mothers and their babies. The study provides a timely portrait of the consequences of COVID-19 related public health decisions and changes in healthcare provision during the peri- and post-natal period, and the effect of the unprecedented public health crisis on pregnant and post-partum women and newborns.

Hydroxychloroquine: Enthusiasm for a potential COVID-19 cure affects patients

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that can lead to serious organ complications and even death. Hydroxychloroquine (HCQ) is one of the safest, most effective drugs for SLE, and is used by almost every SLE patient in North America. At the start of the COVID-19 pandemic, the unprecedented public and scientific optimism for HCQ as a potential treatment created urgent concern about shortages of this inexpensive medication, a cornerstone of SLE therapy.

CAN-AIM members Drs. Evelyne Vinet, Arielle Mendel, and Sasha Bernatsky (McGill) quickly organized a national and an international survey of rheumatologists to learn about their experience of HCQ shortages. The national results reveal that a majority of respondents reported difficulties in accessing or renewing the drug. The problem was much more apparent in Quebec, where 90% of rheumatologists reported HCQ access issues. This was potentially an unintended consequence of provincial regulations to tightly control HCQ prescriptions.

The international survey revealed similar problems in Europe and the USA, though respondents from four countries (Sweden, Denmark, Singapore, South Korea) reported no HCQ access issues. Drs. Mendel, Vinet and Bernatsky have since established the CAnadian Network for REsearch on COVID-19 in Rheumatology (CAN-RECOVR) to better understand how the pandemic affects rheumatic disease care.  This collaborative network will connect Canadian rheumatology researchers to study priority COVID-19 related questions with harmonized data collection.

Drug Safety and Effectiveness Cross-Disciplinary Training

DSEN - Drug Safety and Effectiveness Cross-Disciplinary Training (DSECT)

The effects of COVID-19 on drug supply shortages

Due to COVID-19, governments around the world have implemented interim public health measures to limit the spread of the disease. Such measures have contributed to a disruption of global supply lines and exposed vulnerabilities in the global pharmaceutical supply chain. Due to the potential serious respiratory effects of COVID-19 on those who are infected, there was an increase in global demand of certain drugs used in critical care, which led to significant strain and shortage of supply of essential medications. To address this developing concern, Dr. Mina Tadrous, a Scientist Women’s College Hospital and a DSECT Alumni will be co-leading an international collaboration with an award from the IQVIA, to determine the effect of COVID-19 on drug supply chain and shortages across 70 countries, as well as the effectiveness of country-level drug shortage policy. 

Science communication COVID-19 articles

Academic publications are the primary venue for sharing research findings, but they are often inaccessible to those without journal access or subject matter expertise. Science communication aims to translate research or complex scientific concepts using language that is easily understandable by the general population. Dan Harris, a doctoral candidate at the Dalla Lana School of Public Health, University of Toronto and a DSECT trainee along with co-authors at the University of Toronto and University of British Columbia, published two science communication articles to educate the public on topics related to public health and COVID-19.  Published early in the COVID-19 pandemic, Dan Harris and fellow PhD candidate, Catharine Chambers, discussed the importance of social distancing and the potential risks associated with typical social encounters. With Dr. Kate Weinberger, Associate Professor at the University of British Columbia, Dan Harris published a second science communication article  on heat related death, and how the summer heat and COVID-19 are likely to interact and impact population health (associated publication). 

Mental health resources at the University of Toronto during COVID-19

Under the guidance of Dr. Lisa Dolovich, Professor and Dean at the Leslie Dan Faculty of Pharmacy University of Toronto), Andrea Massey, Master of Science Candidate and DSECT Program Coordinator, is working to improve the University of Toronto’s resources for students dealing with complex mental health medication management issues during the pandemic. Through a needs assessment project, this study aims to understand how the current pandemic has affected students’ mental health medication management by understanding if a student’s self-declared wellbeing and level of comfort/confidence in their medication treatment has a correlation.  The project will provide an action plan for how the university can implement programs and resources to address specific mental health and well-being medication management needs.

Methods and Applications Group for Indirect Comparisons

DSEN - Methods and Applications Group for Indirect Comparisons (MAGIC)

Diagnostic testing for COVID-19 in Canada

Diagnostic testing for COVID-19 has been lauded by the World Health Organization (WHO) as being critical in tracking the virus, understanding epidemiology, informing case management, and suppressing transmission. In Canada, nucleic acid-based testing is considered best practice; however, this form of testing is resource intensive. Point-of-care diagnostic tests can deliver results in minutes to hours and can be administered in a wide-range of settings. A rapid review: Rapid and POC Diagnostic Test for SARS-COV-2 (COVID-19) was commissioned by the Ontario Ministry of Health and Long-Term Care through the CIHR SPOR Evidence Alliance and conducted by Ms. Shannon Kelly and Dr. George Wells from the University of Ottawa Heart Institute. The objective was to provide a summary of the nucleic acid-based POC diagnostic tests authorized for use in Canada (as of June 4, 2020), the characteristics of tests available, the evidence of diagnostic test accuracy, as well as guidelines available on diagnosis of patients with suspected COVID-19. Results informed an Ontario Ministry of Health report on strategies for testing asymptomatic individuals for COVID-19 in June 2020. Findings will be distributed through the SPOR Evidence Alliance.

Rapid scoping review of the effectiveness and safety of treatments for COVID-19 and other coronaviruses that cause serious respiratory tract infections

Led by Drs. Andrea Tricco and Sharon Straus from Unity Health Toronto, a rapid scoping review was conducted to identify pharmaceutical interventions for adult patients with COVID-19 for Health Canada. The two research questions were as follows:

  1. What pharmacologic interventions to treat COVID-19, SARS, or MERS have been studied in human trials?
  2. What treatments for COVID-19 are currently under study in registered/ongoing human trials? The most commonly studied interventions were antiviral drugs, followed by hydroxychloroquine / chloroquine, corticosteroids, monoclonal antibodies, convalescent plasma, immunoglobulins, and interferons. Reported outcomes included admission to intensive care unit or need for mechanical ventilation, changes in pneumonia symptoms, morality, and adverse events.

Overall results from the studies were inconclusive or conflicted with one another, preventing any clearly effective treatment candidates from being identified. Additionally, some potentially serious adverse events such as ventricular arrhythmia have been reported in relation to interventions such as hydroxychloroquine/chloroquine; highlighting the need to carefully evaluate the safety of interventions as well as their effectiveness.

COVID-19 atypical presentation

A retrospective chart review project investigating atypical presentations of COVID-19 in older adults (age >65) who are admitted to one of the academic hospitals in Toronto has been undertaken. The MAGIC team is looking at the correlation between atypical presentations (e.g. falls, delirium, functional decline) and outcomes (e.g. death, ICU admission, complications). The study also looks at the characteristics of older adults with delirium who have COVID-19.

Factors associated with virtual care access in older adults

The MAGIC team (Dr. Jennifer Watt, a DSECT trainee along with Dr. Eric Wong, a Vanier Doctoral student, and Dr. Sharon Straus) completed a cross-sectional study of the medical records of all older adults assessed virtually in geriatric medicine clinics in academic health science centres in Toronto between March 17, 2020 (the first day of virtual assessments) and July 13, 2020 due to an increase in virtual care during COVID-19. The study included 330 patients (227 telephone and 103 videoconference assessments). Frailty and absence of a caregiver to facilitate a virtual assessment were associated with lower odds of receiving a videoconference compared to telephone-based assessment. Only 32 of 98 (32.7%) patients who could independently use a computer participated in videoconference assessments. This is important given the concerns around polypharmacy in older adults and reflects the challenge in our ability to adequately monitor these patients in a virtual platform.

COVID-19 and long-term care homes

Issues in long-term care (LTC) in Canada have been brought to light during the COVID-19 pandemic, including the quality of life and care of residents, and deaths of both caregivers and LTC residents. The Royal Society of Canada issued recommendations in June 2020 to address these issues. Funded by the Strategy for Patient-Oriented Research (SPOR) Evidence Alliance, Drs. Brian Hutton and David Moher from the Ottawa Hospital undertook a rapid scoping review in July 2020 to address the following research questions:

  1. What care provider models or services in LTC homes have been evaluated to improve quality of life, quality of care, and health outcomes of residents?
  2. What interventions delivered by care providers in LTC homes have been evaluated to improve quality of life, quality of care, and health outcomes of residents?

Studies were mapped to groups representing different models of care related to their focus and the types of care providers involved to establish areas of strength and gaps in the literature. Regarding healthcare service delivery models, the team identified studies related to models of care regarding several strategies: access to care specialists, provision of primary care, provision of direct care, access to allied care, support for avoidance of acute hospitalizations, and condition-specific approaches. The team is now mapping further characteristics of this literature to establish the basis for in-depth systematic reviews that can be pursued to identify models of care that can improve long-term care for residents in Canada and elsewhere. Findings will be distributed through the SPOR Evidence Alliance.

Restoring trust: COVID-19 and the future of long-term care

Dr. Sharon Straus co-led this Policy Briefing Report, which reviewed the research context and policy environment in Canada’s long-term care sector before the arrival of COVID-19. It summarized the existing knowledge base for far-sighted and integrated solutions to challenges in the long-term care sector. The report then outlined profound, long-standing deficiencies in the long-term care sector that contributed to the magnitude of the COVID-19 crisis. Equally important contributors to this crisis are the characteristics of the older adults living in nursing homes, their caregivers and the physical environment of nursing homes. The long-standing deficiencies in Canada’s long-term care sector and the characteristics of the key players had direct impact on the immediate causes of the COVID-19 crisis in our nursing homes. The report made specific recommendations for the federal and provincial/territorial governments to implement based on the evidence.

LTC commission cost project

Dr. Eric Wong and Dr. Sharon Straus completed a cost analysis of existing Canadian long-term care reports, commissions, and inquiries over the past 50 years. This analysis built on the Restoring Trust report. The direct and indirect costs were estimated from these existing reports and the number of repeated recommendations in reports were summarized. The project contextualized the cost of repeatedly studying the same issues in long-term care compared with implementing actual change, especially during COVID-19.

Barriers and facilitators associated with virtual care access in older adults

Dr. Jennifer Watt (a DSECT trainee) working with Dr. Sharon Straus and others is completing a qualitative study to understand barriers/facilitators to accessing virtual care by older adults during COVID-19. With the move to virtual platforms during the pandemic, disparities in access to care including monitoring of medication adverse effects were identified in various populations including older adults with frailty and without a caregiver.  

Rapid review of telemedicine interventions for reducing depressive symptoms in community-dwelling older adults

Dr. Jennifer Watt (a DSECT trainee) is leading work with Dr. Sharon Straus and others on telemedicine interventions for older adults. There is an exponential use of telemedicine during COVID-19, yet the effectiveness of these interventions for depression is unclear. This rapid review included 14 randomized trials of nonpharmacologic interventions for reducing depressive symptoms in community-dwelling older adults. Cognitive behavioral therapy delivered by telephone or online, compared to an in-person intervention or usual care, reduced depressive symptoms among older adults in six randomized trials. This is critical work because of the challenge of monitoring medication use in the older adult receiving virtual care.

Systematic review and meta-analysis comparing the diagnostic accuracy of virtual cognitive tests

Dr. Jennifer Watt (a DSECT trainee) is leading work with Dr. Sharon Straus and others on a systematic review that included 121 studies and 84 different virtual cognitive tests. The Telephone Interview for Cognitive Status was the most extensively validated virtual cognitive test. Results indicated moderate to strong correlations between in-person and virtual versions of the Montreal-Cognitive Assessment and Mini-Mental State Examination - two cognitive tests that were widely used in clinical practice before the COVID-19 pandemic. This work will inform cognitive assessment of older adults using a virtual platform.

Dose sparing using intradermal versus intramuscular administration of Influenza Vaccinations

The interest in intradermal vaccines has been increasing as a solution to mitigate potential vaccine shortages, which could occur from unanticipated loss of expected supplies or from excessive demand due to high rates of infection, such as during pandemics. With the approval of new intradermal vaccines, new delivery devices, including mini-needles, microneedles, patches and disposable-syringe jet injectors, have become available. The Public Health Agency of Canada requested a rapid review to understand what is known about the immunogenicity and safety of the influenza vaccine at reduced or regular intradermal doses compared with a full intramuscular dose. The Health Technology Assessment Unit at the University of Calgary completed this work.

Safety and effectiveness of dose-sparing strategies for seasonal influenza vaccine: rapid scoping review of fractional dosing of the Intramuscular influenza Vaccine

The purpose of this review is to identify potentially safe and effective dose-sparing strategies for administration of seasonal influenza vaccines in healthy individuals of all ages that have been evaluated in human trials. With the resource-constraints for the upcoming influenza season, there is a need to scope the evidence on the safety and effectiveness of dose-sparing strategies for intramuscular administration of seasonal influenza vaccines. The results of this rapid review will be shared with the Centre for Immunization and Respiratory Infectious Diseases of the Public Health Agency of Canada (PHAC) to address their query on the safety and effectiveness of fractional dosing of seasonal influenza vaccines. PHAC commissioned this review due to the anticipated influenza vaccine shortages due to COVID-19.

DSEN – Active Surveillance and Evaluation of Adverse Reactions in Canadian Healthcare Team and Pharmacogenomics of Adverse Events National Team (SEARCH&PREVENT)

Does Ibuprofen Worsen COVID-19?

In March 2020, the French authorities warned against the use of ibuprofen in patients with coronavirus disease 2019 (COVID-19) symptoms. The World Health Organization initially recommended not using ibuprofen, then relented. Similarly, the Medicines and Healthcare products Regulatory Agency in the UK reversed their initial recommendation to avoid nonsteroidal anti-inflammatory drugs (NSAIDs), concluding “There is currently no evidence that the acute use of NSAIDs causes an increased risk of developing COVID-19 or of developing a more severe COVID-19 disease.” The Italian Society of Pharmacology released a statement along the same lines. Among all NSAIDs, ibuprofen was probably targeted because it is widely used and available over the counter (OTC), unlike other NSAIDs in France.

SEARCH&PREVENT team published a study examining the question of worsening COVID-19 by Ibuprofen intake

General COVID-19 Updates

CIHR is closely monitoring the evolution and impact of the novel coronavirus (COVID-19), and is taking action to support grants, scholarships and awards recipients, as well as applicants, peer reviewers and employees. Please consult CIHR’s website for all COVID-19 information related to CIHR. Check back often, as CIHR updates this page regularly.

CIHR has created a webpage to showcase CIHR-funded COVID-19 research, including projects completed by DSEN teams.

Strategy for Patient-Oriented Research (SPOR) COVID-19 related activities in response to the pandemic.

We also invite you to consult the Government of Canada website for more information on national initiatives that might be relevant to you.

Additional Updates

Other DSEN research

For a listing of all DSEN queries, please visit the DSEN research webpage

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