Article by Laura M. Best

Graphic design by Colleen Paris

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 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 COVID-19-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 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.

Reference

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.