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Features
Pandemic tales from a Respirologist at the forefront of COVID-19 Research
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By: Stacey J Butler
Like many of Toronto’s renowned respiratory disease researchers, Dr. Andrea Gershon feels it is her duty to study the emerging coronavirus. As lead of the CanBREATHE–Lung Health research group, her knowledge in the field of Respirology is highly relevant to COVID-19. An active member of both the Canadian Thoracic Society and the Canadian Respiratory Research Network, Dr. Gershon has years of experience conducting clinical and population health research with the common goal of improving health outcomes for people living with chronic respiratory disease. She is also a staff Respirologist at Sunnybrook Health Sciences Centre and has been working on the front-lines during the COVID-19 pandemic. Dr. Gershon has seen first-hand how healthcare workers have stepped up and supported each other despite the fear and anxiety that comes with their heightened risk of exposure to the novel coronavirus.
Throughout the pandemic, we have often heard the expression “these are unprecedented times”, but the early days of the COVID-19 pandemic felt like déjà vu for Dr. Gershon. In 2003, she was a young mother and a medical resident, ‘moonlighting’ at Scarborough Grace Hospital. She was asked to assess a patient in the emergency room who presented with an abnormal chest x-ray. No masks, no gowns–they were completely unaware that they were treating the first patient with severe-acute respiratory syndrome (SARS) in Canada. All they knew was that the patient’s relatives had also fallen ill, and one was in the intensive care unit (ICU) where Dr. Gershon later attended to a code blue–a medical emergency. As the investigation continued, they recognized the severity of the illness, and quickly became aware of the possibility that they were facing a new infectious disease. Dr. Gershon’s story highlights how the early days of the COVID-19 pandemic resembled the SARS era. The initial response was similar – quarantine anyone who may have been exposed. Dr. Gershon recalls being put in quarantine nearly a week after she treated the first SARS patient. To simply label this experience as frightening would be an understatement, yet it is one that many Canadians are all too familiar with today.
Dr. Gershon felt helpless in the early days of the COVID-19 pandemic. She wanted to find a way to apply her relevant experience in respiratory disease and
accelerate COVID-19 research. While looking for ways to pivot their research to study the new coronavirus, Dr. Gershon and her team realized they had already developed the perfect tool to monitor COVID-19 patients. Ironically, they had been testing this tool in patients with chronic respiratory disease at the beginning of the pandemic, but their study was put on hold when all clinical research came to a grinding halt. Along with an interdisciplinary team of clinicians and computer scientists, namely Dr. Robert Wu, Dr. Eyal de Lara, and Dr. Daniyal Liaqat, they had already created a smartphone application that allows health care providers to remotely monitor a patient’s health. With the support of the Canadian Institute of Health Research (CIHR), and the Physicians’ Services Incorporated (PSI) Foundation, they are now using this technology to quickly gather data that can improve our understanding of COVID-19 symptoms and disease progression.
One of the current issues with COVID-19 is not knowing when patients, who are isolating at home, need to be transitioned to hospital-based care. When someone tests positive with COVID-19 they are simply instructed to self-isolate and seek medical attention when needed. Not only can this leave patients in a state of panic, worrying about when their health will deteriorate, it also has the potential to overwhelm the healthcare system with unnecessary emergency department visits and hospitalizations. Dr. Gershon and her team’s COVIDFree@Home project uses cutting-edge technology to monitor the health of COVID-19 patients who are isolating at home. The team hopes to employ artificial intelligence and machine learning models to predict when patients need to be hospitalized. This technology allows them to do all of this without going within six feet of a patient.
The COVIDfree@Home study is enrolling patients who test positive for COVID-19 and are self-isolating in the community. Study participants are recruited from emergency departments and clinics which receive referrals from COVID-19 screening centres at the University Health Network and Sunnybrook Health Sciences Centre. The team hopes to extend the research study to enroll patients from centres in other COVID-19 hot-spots, such as the Humber area and Peel region. The study participants are mailed an
Dr. Andrea Gershon, MD, MSc
Associate Professor, Department of Medicine, University of Toronto Research Director & Staff Respirologist, Division of Respirology, Sunnybrook Health Sciences Centre Scientist, Evaluative Clinical Sciences, Trauma, Emergency & Critical Care Research Program, Sunnybrook Research Institute Senior Core Scientist & Lung Health Lead, ICES Photo Credit: Dorsa Derakhshan
Screenshots of the COVIDFree@Home App Photo Credit: Dorsa Derakhshan
oximeter and thermometer to measure their blood oxygen levels and temperature at home. They are asked to use an app on their smartphone to record their symptom severity, oxygen saturation, and temperature twice daily. The app can even measure respiratory rate and detect coughs, using advanced algorithms developed by the research team. Patients are monitored during the peak of their infection for two weeks.
The research team will use this data to predict the point at which patients need to be hospitalized. The benefit is obvious–it allows a large group of patients to be monitored remotely, in real-time, by only a small number of healthcare professionals. Widespread use of this tool will ultimately put less strain on the healthcare system, which has been the goal since the start of the pandemic. At this point, the only tools we have to mitigate the spread of COVID19 and prevent our healthcare systems from being overwhelmed are abiding
by social distancing protocols and other public health guidelines.
Currently, our brave healthcare workers have limited tools to treat patients with COVID-19. Preliminary research worldwide has assisted in identifying vulnerable groups with worse outcomes and improving hospital-based care, but little is being done for patients in the community. Research projects like Dr. Gershon’s COVIDFree@Home are vital to improve our understanding of COVID19, ensure patients are safe when isolating at home, and help the healthcare system adapt and move forward.
By Dorsa Derakhshan
Not all patients happen to take convenient residence in the heart of a metropolitan area. Some are living in remote areas of provinces. With a considerable distance to the closest urban centre, these patients have unique concerns regarding the lack of access to healthcare services. Even with the utilization of televideo conferencing, Dr. Sanjeev Sockalingam has realized that there are insufficient resources and services available.
“I remember several patients not having access to therapists or psychiatrists in their local settings, and they often suffered as a result since they couldn’t access proper care,” he explains. “These events inspired me to think: how can we remotely provide care, and more specifically, how can we continue to expand mental health services for those individuals so that it could help with their recovery and overall care? How can we do better for our patients and their family members?”
Dr. Sanjeev Sockalingam is Vice Chair and Professor of Psychiatry at the University of Toronto and Vice President of Education and Clinician Scientist at the Centre for Addiction and Mental Health. He is passionate about integrated care in Consultation-Liaison Psychiatry, a collaborative clinical approach that emphasizes the optimization of biopsychosocial care, as well as conducting research on the integration of physical and mental health.
Dr. Sockalingam’s research has been primarily inspired by his personal experiences treating patients in his clinical practice, many of whom have medical comorbidities, such as metabolic syndrome and mental illness. Quality improvement has been a major driving force in his career. Dr. Sockalingam has explored its possibilities in two avenues: 1) Development of accessible programs and interventions for patients living with mental illness and physical health comorbidities who are struggling with difficulties navigating access to treatments for both conditions; and 2) Promotion of education and knowledge translation to help prepare current and future healthcare providers for managing disparities in mental healthcare using integrated care models.
Dr. Sockalingam explains that the COVID19 pandemic has deepened the current gaps and disparities in care. He proposes a solution: technology. Using technology to deliver psychotherapy and train healthcare providers may help enhance healthcare education and make care more accessible to patients. The inspiration for this project originated from the current experiences of patients and frontline healthcare workers during the COVID-19 pandemic. Some patients in his clinical practice have been fortunate to receive virtual care through televideo conferencing since the
Dr. Sanjeev Sockalingam
B.Sc., B.A., M.D., MHPE Vice Chair, Education and Professor at Department of Psychiatry, University of Toronto VP, Education and Clinician Scientist at Centre for Addiction and Mental Health
onset of the pandemic. However, many patients were continually struggling with accessing resources and coping with the COVID-19 virus itself. These patients were presenting with a new onset of mental health distress or the exacerbation of their previous mental health conditions. In addition to virtual visits, patients were receiving limited guidance on how to self-manage their emerging mental health issues, such as anxiety, depression, and loneliness.
Likewise, frontline care providers have been striving to cope with personal distress. They have been provided with a space to share their current challenges through The Extension for Community Healthcare Outcomes (ECHO) program, which was initially implemented across Ontario and has now expanded on a national scale.1 One of the primary hindrances for these workers is the feeling of burnout due to the increased patient workload that needs traditional in-person care. ECHO exemplifies the utility of virtual programs and resources in the domain of healthcare and highlights the value that virtual care can provide by being a novel avenue for balancing care provision among many trained professionals.
There is a critical need to investigate the currently available digital interventions, ensure these tools are aligned with best practices, and curate a comprehensive resource which is accessible for use in clinical practice. Dr. Sockalingam emphasizes the significance of this project, “We wanted to make this resource accessible in the form of a consolidated toolkit that can actually be used for clinical purposes going forward”. Due to the urgency posed by COVID19, the development of this knowledge synthesis project has been quite rapid. The purpose of this research project is to investigate the efficacy of current digital interventions in mental health which aim to reduce mental health impacts of COVID-19, as well as identifying barriers to their access for underrepresented populations. The overarching goal is to curate an accessible, comprehensive resource that has been scientifically evaluated for its quality and is ready to be utilized effectively for clinical purposes going forward.
This project investigation went beyond curating papers describing digital interventions focused on diagnosable psychiatric interventions; it also included studies with a focus on mental health promotion and well-being. Studies of digital interventions’ target population included Canadian adults with clinical or subclinical symptoms of mental disorders. Dr. Sockalingam explains, “We didn’t limit our inquiry to diagnosable psychiatric conditions in order to capture tools to assist with mental health challenges more broadly. Based on COVID-19 literature, most individuals don’t develop full-blown clinical psychiatric conditions. Individuals are more likely to experience mental health distress”. Experimental variables explored in this research project included diversity of target patient population, accessibility factors such as cost of service, quality of assessment and reportable outcomes. Race, ethnicity and culture were key areas of focus related to equity and therefore the inclusion of indigenous patient populations and other underrepresented ethnicities was ensured. Advanced online searches were conducted to find sites and organizations with key stakeholders in digital health on the national scale in order to ensure the proper capturing of currently available organizations and services, as well as authentically assessing their service in terms of quality and criteria. In order to ascertain the digital interventions were contemporary, studies included were published as early as the year 2000. The studies outlined interventions regarding mental health assessment, treatment, and well-being promotion. The range of articles examined was comprehensive and inclusive of commentaries and reviews in which interventions were regarded as modern innovations. The American Psychiatric Association (APA) Assessment Tool was applied to these resources to ensure quality assessment with respect to each of these interventions. Furthermore, the digital interventions were required to be defined by World Health Organization (WHO) Classification of Digital Health Technologies.
Despite the initial illusion of abundant resources, the study team discovered that most of the currently available resources did not meet the criteria for adequately addressing mental health concerns. Regarding mental health interventions, there was limited published information for reportable outcomes of digital interventions during COVID-19. Furthermore, reports were highly diverse regarding the types of intervention and areas of focus. In relation to equity, inclusivity and diversity, there were only few resources targeting specific populations of high need. For instance, none of the reports addressed Indigenous concerns. These times call for
Photo credit: Mikaeel Valli
a heightened emphasis and consideration regarding equity and diversity issues, such as the critical inclusion and proper representation of the Indigenous patient population.2
Addressing the heterogeneity of the ‘quality’ of these resources posed a major issue. The following factors were taken into consideration: 1) Reliability: How can people access the resource in a reliable way? 2) Specificity: Is the intervention quite general or specific? How would people know whether they are meeting their specific needs? and 3) Diversity: Is there a limited number of available resources for specific patient populations? Diverse or underrepresented groups often have less access to more tailored versions of digital interventions. In addition, curating a resource that addresses diversity in terms of mental health needs is also essential.
Such prevalent challenges in virtual care reflect the obstacles that currently exist in traditional in-person care. Namely, in-person barriers are reflected in digital interventions.
This impact of this work, which was done in collaboration with co-principal investigators Drs. Strudwick and Crawford, is critical since patients, frontline workers and healthcare providers, as well as the general public are facing a plethora of online resources regarding mental health and COVID-19. Dr. Sockalingam emphasizes: “We went from initially having only few resources met with reluctance to witnessing an overwhelming sea of interventions being offered. Our team strived to curate, assess and synthesize all the available resources that are genuinely valid and appropriate for practical use.”
Preliminary findings are currently being disseminated with respect to knowledge synthesis.3 The team has reviewed the literature and has grouped the studies in terms of their outcomes, the geographical location in which they were developed, and their target populations.
The purpose of the knowledge translation is to share the results through the ECHO Ontario program to healthcare providers working on the frontlines, as well as with internal and external digital health groups on a national scale through webinars, such as the Evidence Exchange Network (EENet).4 The results also led to the development of an online knowledge hub located on the CAMH website in which the online interventions and applications can be searched for by the use of keywords to make these online resources accessible to target population patients and families.5
Future directions include more focus towards select populations that are underrepresented such as youths, refugees and other marginalized groups. Additionally, conducting more rigorous evaluations of these digital interventions is required. Clinically, it is vital to strive towards curating more inclusive interventions that address disparities in access to care, employ similar standards for assessment and ensure consistent quality when offered to various patient populations. As such, Dr. Sockalingam believes this project will have immense impact in advancing care in both clinical and academic realms.
With sincere appreciation for the impact of academic work in the ongoing state of the world, Dr. Sockalingam acknowledges the current challenges researchers may be facing during this pandemic. As a word of advice, he suggests IMS research students virtually network and collaborate with other groups on novel projects and initiatives by taking full advantage of virtual technology in assisting with recruitment, delivery of interventions, and knowledge dissemination and translation. Dr. Sockalingam has been deeply inspired by the dedication and commitment of the clinical and research teams towards finding creative modern solutions, and taking on roles outside of their usual responsibilities to assist frontline workers while caring for patients and supporting the public during these unprecedented times.
References
1. Project ECHO Ontario [Internet]. 2019. Available from: https:// www.echoontario.ca 2. Stranges J. Indigenous led COVID-19 testing centre opens in Toronto at Na-Me-Res [Internet]. St. Michael’s Hospital. 2020 [updated 2020 Oct 21]. Available from: http://www.stmichaelshospital.com/ media/detail.php?source=hospital_news%2F2020%2F1021 3. Digital Interventions to Support Population Mental Health during
COVID-19: A Knowledge Synthesis – CIHR [Internet]. Canadian
Institutes of Health Research. 2021 [updated 2021 Jan 22]. Available from: https://covid19mentalhealthresearch.ca/synthesis/digital-interventions-to-support-population-mental-health-during-covid-19 -a-knowledge-synthesis/ 4. EENet – Evidence Exchange Network [Internet]. 2021. Available from: https://www.eenet.ca 5. Digital COVID-19 and mental health resource list [Internet]. 2021.
Available from: http://www.camh.ca/en/health-info/mental-healthand-covid-19/information-for-professionals/covid-19-databasepage
Making strides in prophylactic treatment for COVID-19
By Nadia Boachie
In March 2020, the World Health Organization (WHO) declared COVID-19 a global pandemic. Researchers immediately began collaborating in efforts to develop a vaccine, find treatments, and better analyze the trajectory of the virus to help prepare for current and future outbreaks. In Toronto, a number of brilliant scientists have demonstrated their ability to perform quality research when the stakes are at their highest. Now, more than ever, there is immense pressure to yield useful scientific results.
The IMS Magazine had the pleasure of sitting down with one of these researchers, Professor Haibo Zhang, to discuss his ongoing studies on COVID-19. Dr. Zhang is a staff scientist in the Keenan Research Centre for Biomedical Science at St. Michael’s Hospital. He is a professor in the Anesthesia, Medicine, and Physiology Departments at the University of Toronto. His work is currently looking at a potential drug to treat COVID-19. Together with his team of researchers, students, and several collaborators, he is making great strides to uncover treatments that can be used globally in human patients.
Before COVID-19, Dr. Zhang’s translational research program focused on the mechanisms and therapy of acute lung injury and sepsis. “My research has been lung infection and stem cell therapy. I have been doing this for almost 20 years since I started my faculty appointment with the University of Toronto,” he recalls. Dr. Zhang has published over 250 peerreviewed articles and is the recipient of several large research grants, the latest being a one-million-dollar grant from CIHR for COVID-19 related research. His two-year study is one of 99 COVID-19 research projects that are funded by the Canadian federal government.1 Almost 20 years ago, the world faced a similar outbreak of Severe Acute Respiratory Syndrome (SARS)—the viral respiratory illness recognized as a global threat in 2003. Researchers identified a cell membrane protein called angiotensinconverting enzyme 2 (ACE2) that is a host cell receptor for SARS coronavirus (SARSCoV) infections. Researchers quickly realized that ACE2 has even higher binding affinity to SARS-CoV-2, which causes COVID-19.
ACE2 is currently an important target for COVID-19 treatments due to its key involvement in the mechanism behind the infection. It can be considered the cellular door in which SARS-CoV-2 infects its host. Dr. Zhang describes the process by which COVID-19 infections occur, “there is receptor-ligand interaction between ACE2 on host cells and the surface spike protein on SARS-CoV-2 virus that allows the virus to penetrate into the host. The virus then replicates and causes injury to different organs through the blood stream.”
In collaboration with Professor Penninger of University of British Columbia, who co-founded a company called Apeiron Biologics located in Vienna, they produced a soluble form of ACE2 named APN01. Dr. Zhang hopes that if a soluble form of ACE2 is administered in the infected sites, it can act as a decoy and competitively bond with the virus so that it can no longer enter cells. The immune system will then be able to tackle the already infected virus while it remains at manageable levels.
In a paper published earlier this year, Dr. Zhang and his group discussed the rationale for targeting ACE2 receptors as a specific target to treat COVID-19. This paper was published in Intensive Care Medicine and was cited over 1,150 times in less than 10 months.2
Currently, Dr. Zhang and international collaborators are on track to complete clinical trials that are assessing the efficacy of the soluble form of ACE2. “We have a Phase IIb trial ongoing to treat 200 severely infected COVID-19 patients. The randomized, double-blind, controlled trial will compare APN01 to a placebo at different clinical centres in Austria, Denmark, Sweden, Germany and Russia. “We have just recruited the last patient a couple of weeks ago,” he shares.
The research group has also published a case report of a patient with a severe COVID-19 infection. They saw some promising effects, however, they “cannot make any affirmative conclusions because it is a case report,” Dr. Zhang explains. The patient described in the report is a 45-yearold woman who was diagnosed with a SARS-CoV-2 infection and 9 days after she had symptoms was treated with APN01 intravenous infusions for 5 min twice daily. The data shows that the virus disappeared rapidly. They concluded that it remains speculative whether this decrease in viral load reflects the effect of APN01 treatment or the of the virus’ natural progression, but the results were promising overall.3
Dr. Zhang expressed his excitement to get results from the upcoming clinical trials, “we cannot do any analysis now because we are not yet finished data collection, so we are anxious to see our results,” he clarifies.
Although there is a lot of focus and excitement on clinical trials, Dr. Zhang’s group is conducting a lot of pre-clinical work on COVID-19 in a CL3 lab – a Level 3 containment lab that maintains secure facilities for work with Risk Group
Dr. Haibo Zhang
Professor, Department of Anesthesia, University of Toronto Professor, Department of Medicine, University of Toronto Professor, Department of Physiology, University of Toronto Faculty Member, Institute of Medical Sciences, School of Graduate Studies, University of Toronto
Photo Credit: Krystal Jacques
3 pathogens such as emerging infectious diseases.4 “For clinical trials, you can only look at the outcome and you do not know exactly what the mechanisms are. The preclinical trials tell us what key cell signaling sources are responsible for these changes.” Prior to working at the CL3 lab of the Temerty Faculty of Medicine Dr. Zhang,in collaboration with an international team, found that the soluble human ACE2 can significantly inhibit the virus in humanengineered tissue. This earlier pre-clinical work was published in the journal Cell. The paper also demonstrated that the virus can directly infect and replicate itself in human blood vessel and kidney organoids.5
“The University of Toronto was pretty well known in the lung research field before COVID-19,” Dr. Zhang tells IMS Magazine. “However, through our analysis of the mechanism of COVID-19 and potential drugs for treatment, people have been far more connected with us,” he explains. Dr. Zhang elaborated how he had panel meetings every day at the beginning of the pandemic in order to figure out how to contain this virus. A lot of companies and physicians contacted his team when there were major outbreaks in countries like Italy.
Dr. Haibo Zhang is collaborating on COVID-19 related projects with several research groups and companies in and out of the Toronto community. Collaborators include team members at Stanford University, Southern California University, Columbia University, Medicago and Tailed Genes Inc., and yet Dr. Zhang seamlessly manages it all. When asked how he keeps up with everything, Dr. Zhang’s response was “you just keep going and, in the lab, we fortunately have a very strong senior research associate, research coordinator, physician-scientist fellows, PhD and master’s students, a great team. For all the different collaborations with different companies and groups I have to keep track of progress daily. It is pretty intense, but it is going well, so we keep going to fight the terrible COVID-19.”
References
1. Canadian Institutes of Health Research. Government of Canada [Internet]. Government of Canada funds 49 additional COVID-19 research projects – Details of the funded projects. Updated April 2020. [cited 2020 Dec 4]. Available from: https://www.canada.ca/ en/institutes-health-research/news/2020/03/government-of-canada-funds-49-additional-covid-19-research-projects-details-of-thefunded-projects.html. 2. Zhang H, Penninger JM, Li Y, et al. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Medicine. 2020;46(4):586-90. 3. ClinicalTrials.gov [Internet]. NIH: US National Library of Medicine (US). Identifier NCT04335136. Recombinant Human Angiotensin-converting Enzyme 2 (rhACE2) as a Treatment for Patients
With COVID-19 (APN01-COVID-19). 2020 Apr 6. [cited 2020 Dec 4]. Available from: https://clinicaltrials.gov/ct2/show/NCT04335136 4. Zoufaly A, Poglitsch M, Aberle JH, et al. Human recombinant soluble ACE2 in severe COVID-19. The Lancet Respiratory Medicine. 2020;8(11):1154-8. 5. Temerty Faculty of Medicine. [Internet]. [cited 2021 Jan 4].
Available from: https://medicine.utoronto.ca/combined-containment-level-3-unit
By Laura M. Best
The impact of COVID-19 has been anything but homogenous, yet the most commonly discussed solutions rest on assumptions of homogeneity and equity. The IMS Magazine recently had the opportunity to speak with Dr. Sharmistha Mishra, a clinician-scientist in the Li Ka Shing Knowledge Institute who is challenging these and other assumptions amid the COVID-19 pandemic. She is expanding perspectives beyond standardized solutions to complex, heterogeneous questions by leading a team of interdisciplinary experts who are challenged by the communities they serve.
Dr. Mishra did her undergraduate studies at Laurentian University, and then trained as an infectious disease physician at University of Toronto before heading abroad to continue her graduate school education. Though her first passion was clinical infectious diseases, Dr. Mishra was eager to expand her perspective to include public health, and it was while in India for a clinical elective that she was inspired by her future graduate supervisor’s work. She went on to complete both her Master’s and Doctoral work with them at Imperial College London, and when asked to describe her graduate school experience, Dr. Mishra reminisced, “That led to falling in love with my second thing after clinical infectious diseases, which was studying transmission dynamics and modelling.” She went on to clarify that her interests are specifically in better understanding how infectious diseases differentially affect various populations and what factors play a role here. “It was great because now I have a job I love: I’m a clinician-scientist… No matter what we do, there’s always this sort of element of asking questions, and the science allows me to pause to be methodical about answering those questions.”
Flash forward to the present day and Dr. Mishra can be found helping provide care for patients at St. Michael’s Hospital or in her lab in the MAP Centre for Urban Health Solutions. She leads a team of interdisciplinary experts that thrives in collaboration and focuses on infectious disease outbreaks and epidemics in low- and middle-income settings including HIV, sexually transmitted infections, and now, COVID-19.
By incorporating the expertise of engineers, epidemiologists, mathematical modellers and social scientists, Dr. Mishra’s team is “challenging some of the narratives [of homogeneity] around transmission dynamics and response to epidemics and outbreaks” with data-driven approaches to highlight the mechanisms that underpin
Dr. Sharmistha Mishra
BSc, MD, MSc, PhD, DTMH Scientist, MAP Centre for Urban Health Solutions, Li Ka Shing Knowledge Institute, St. Michael’s Hospital Assistant Professor, Faculty of Medicine, Institute of Medical Sciences Assistant Professor, IHPME
heterogeneity. When asked about her overall vision, Dr. Mishra explained that her team uniquely approaches questions informed by the needs of the communities they partner with and/or serve. Each project is comprised of small, highly technical tasks, which ultimately come together and provide answers rooted in data. “The goal is… to have some impact [on these communities], and very acutely and precisely address the specificity that people who are implementing programs and services are looking for,” Dr. Mishra continued, referring to the fact that the needs of different organizations and communities are diverse. She hopes to provide information that will help them perform better in the context of infection control.
Given this unique expertise, a new opportunity presented itself in the early stages of the COVID-19 pandemic. Questions were being raised by St. Michael’s and other hospitals, and Dr. Mishra approached her team about leveraging their strengths and expanding their research interests. “What we realized as we were doing some of the early COVID-19 modelling, was that if we take a similar lens to that which we took with HIV, there are complete parallels when we think of inequities, and think about heterogeneity when it comes to risks and resilience and intervention reach or access and uptake,” Dr. Mishra explained, referring to the fact that heterogeneity exists across population groups that determine how vulnerable they might be to infection, or how accessible treatment and public health interventions might be for a given disease.
For example, the city of Toronto has recognized within its TO Supports: COVID-19 Equity Action Plan1 that some communities and populations are at greater risk for negative impacts from COVID-19 and are working to differentially support these vulnerable communities. “We took what we’re trained in [examining heterogeneity] and said, you know, that this is how we can contribute. And by that, it meant expanding to investigate COVID-19 from this perspective,” concluded Dr. Mishra.
Embodying this expansive approach to research is Jesse Knight1, an IMS PhD student working with Dr. Mishra. While taking some time to work on COVID19-related modelling, Jesse developed a “thoughtful way of estimating the reproductive rate based on infections where transmission can happen before someone becomes symptomatic…it’s a contribution that a lot of people are using,” praised Dr. Mishra.
Dr. Mishra and her team are now involved in multiple collaborative projects focused on COVID-19. One is a CIHR-funded, multi-provincial project on which she is the nominated Principal Investigator. “It’s a great team of folks…across five provinces, Quebec, Ontario, Manitoba, Alberta and British Columbia…who are epidemiologists, modellers, public health scientists, working together on questions that are both province-specific as well as these multi-provincial analyses and comparisons.” She continued, “As a wider team, we want to understand why the size and trajectory of epidemics varied within and between provinces, how impact of interventions varied across subgroups and by social determinants of health (including occupations and household density), and what were some of the consistent patterns across provinces, and that’s what led to this multiprovincial work and analyses that now is really focused on data and
Estimated distribution of SARS-CoV-2 infectiousness (generation time) based on the distributions of time to symptom onset (incubation period) and time between symptom onset in infector-infectee pairs (serial interval)1 .
Photo credit: Krystal Jacques
transmission modelling to understand heterogeneity in COVID-19.”
Other ongoing projects are more focused, using transmission modelling to evaluate interventions and future incidence rates for vulnerable populations that have been hit harder by the effects of the pandemic. One is supporting the work of colleague Dr. Stephen Hwang looking at COVID-19 among persons experiencing homelessness in Toronto, while another is in support of Chiefs of Ontario, looking at intervention strategies for First Nations communities on reserve. A third is supporting an effort to assist frontline workers in reducing infection rates in long-term care homes across the GTA and Champlain regions using spatial analyses combined with transmission modelling.
“So, as you can see, we’ve expanded quite a bit…” Dr. Mishra laughed. “But, you know, it’s also a lot in terms of great work that we’re excited to do, that we feel we can contribute to and that we’re going to try to do in partnership with folks that are implementing strategies in the shelter system, in long term care homes. So it’s very much in parallel to how we do our HIV work and that’s why it felt natural to join those projects and grants.”
Dr. Mishra continued, “And I think that’s what’s been fantastic about working with folks here who are very community engaged and working with frontline organizations and supportive to that response. It’s a little like microsystem modelling versus modelling for all of Canada - the former is much more in our wheelhouse.”
And when asked about the intended significance of this work, Dr. Mishra explained that she hopes for “contextually responsive” and “tailored” public health responses rather than “top-down mandates which often sometimes cannot reach everybody or may not be accessible or equitable for everybody.” This is what the early data seems to suggest, as well. “What we’re finding in the data and in our models is that inequity and intervention access (be it reach or feasibility) undermines this assumption that a one size fits all is going to work to control the COVID-19 epidemic. We are definitely finding evidence to suggest that without being tailored when there’s underlying heterogeneity…we’re likely going to continue to be in a similar situation as we are facing now and amplify inequities in COVID-19 risks.”
In a landscape as rapidly evolving as COVID-19, Dr. Mishra acknowledged that it can be both inspiring and overwhelming trying to keep up with the rapid influx of new information and resources. She challenges others working in this environment to become comfortable with uncertainty and encourages the exploration of data as they are being collected. And for those aspiring to contribute, she suggests embodying humility, asking high-risk questions and considering what your unique contribution and perspective could be.
Reflecting on the entire experience, Dr. Mishra explained that it has expanded the scope of her lab’s vision as well as her own imagination. “For us, it was that central theme of heterogeneity that aligned and weaved through all of this. I feel that I’ve learned more than I’ve contributed.” At the end of it all, Dr. Mishra exuded gratitude and appreciation for her team and collaborators, who keep this work both fun and rewarding.
References
1. Knight J, Mishra S. Estimating effective reproduction number using generation time versus serial interval, with application to covid-19 in the Greater Toronto Area, Canada. Infect Dis Model. 2020;5:889-96.
