����ֱ��

When it comes to assessing the risk of transmission of an infectious disease like COVID-19 and evaluating the effectiveness of measures like physical distancing, mathematics and mathematical modelling are crucial.

“How does the virus spread? How quickly does it multiply? What’s the impact of interventions like social distancing? Mathematical modelling looks at these kinds of questions,” says Vijaya Kumar Murty, a professor in the department of mathematics in the University of Toronto’s Faculty of Arts & Science.

To address such questions, mathematicians like Murty take into account numerous variables involved in the spread of a disease, including the age, occupation or pre-existing health conditions of an individual.

“So what you do is try to build a mathematical quantitative model – taking these factors into account – of what’s going to happen in terms of the propagation dynamics,” says Murty, who is also the director of the Fields Institute for Research in Mathematical Sciences at ����ֱ��.

Murty is the recipient of a $666,667 grant from the Canadian Institutes of Health Research (CIHR) that will go towards setting up the COVID-19 Mathematical Modelling Rapid Response Task Force, a network of experts who will work to predict outbreak trajectories for the disease, measure public health interventions and provide real-time advice to policy-makers.

It’s one of nine COVID-19 research projects at ����ֱ�� to receive support from a recent $25.8-million funding package , building on an earlier investment of $27 million on March 6 – nearly $6 million of which went to researchers who are based at ����ֱ�� or one of its affiliated hospitals.

Both rounds of funding are part of the federal government’s larger $275-million investment in research on COVID-19 counter-measures.

“From developing low-cost diagnostic tools to modelling disease transmission and exploring potential drug interventions, researchers at the University of Toronto are attacking the problems posed by COVID-19 from numerous angles,” says Vivek Goel, ����ֱ��’s vice-president, research and innovation, and strategic initiatives.

“This latest round of funding from the federal government will help our experts across several disciplines to accelerate research projects that could have a crucial impact in the global fight against this potentially deadly illness.”

(See below for the full list of researchers who received support from CIHR in the latest COVID-19 funding round).

Murty’s mathematical modelling task force was inspired by a similar network set up by Mitacs – a national non-profit that designs and delivers research and training programs in partnership with universities, governments and companies – during the 2003 outbreak of Severe Acute Respiratory Syndrome (SARS). It will comprise 14 academics from across the country as well as other partners, including the Public Health Agency of Canada and research institutes in China.

In addition to addressing the pressing issue of the coronavirus epidemic, Murty says mathematical modelling can be applied to the analysis of other infectious diseases as well as the study of social pathogens like opioid abuse.

“It explores the propagation of a pathogen in society or, in general, propagation in networks,” he says. “How something moves from node to node – or person to person – and what interventions will produce what effect on that transmission.”

“This work is of course time-sensitive and critically important right now because of the health situation we find ourselves in. But thinking beyond that, I’m envisaging that this task force will grow so that we can continue to analyze and model public health and disease from a mathematics point of view.”

Darrell Tan, a clinician-scientist at St. Michael’s Hospital and an associate professor in ����ֱ��’s Faculty of Medicine and the Institute of Health Policy, Management and Evaluation at the Dalla Lana School of Public Health, will look at whether the HIV drug Kaletra could be useful against COVID-19 (photo courtesy of Darell Tan)

While Murty and his collaborators crunch the numbers, Darrell Tan is preparing to run clinical trials to explore whether a popular anti-HIV drug could help prevent the spread of COVID-19.

Tan is an associate professor at the Faculty of Medicine and the Institute of Health Policy, Management and Evaluation at the Dalla Lana School of Public Health, and is a clinician-scientist in the infectious diseases division of St. Michael’s Hospital. He secured a $1-million CIHR grant for the trials, which will look at whether Kaletra – a drug that has been used in HIV treatment as well as for uninfected people with high risk of exposure – could be useful against COVID-19.

“In general, whenever we’re trying to actively find new therapies for any medical condition, one of the most efficient ways of doing that is to find existing available drugs that could potentially be re-purposed,” says Tan.

“Because obviously it saves all the steps in drug development and safety assessments if we already have a drug available that we understand the characteristics of very well.”

Tan says that in-vitro studies and animal experiments have suggested Kaletra may have an effect on COVID-19 and other types of coronaviruses such as SARS and MERS (Middle East Respiratory Syndrome), but that there’s a dearth of quality evidence from human studies.

His trial will deploy what’s known as a “ring design,” where “rings” of people who came into close contact with COVID-19 patients will be identified.

“Once we identify a case, one could draw a ring of close contacts surrounding that ‘index case,’ and, of course, those people would be the individuals who would be at greatest risk and therefore the ones we would most immediately want to intervene on in order to prevent transmission from happening,” says Tan.

Individuals selected for the study will be randomly assigned to a 14-day course of either Kaletra or a placebo and will be tested periodically to see if they develop COVID-19.

“If you have an intervention that does turn out to work, you can imagine effectively drawing a ring around a person and intervening on that ring of exposed contacts to create a buffer between the infection we already know about and the rest of the population,” said Tan.

The trials could begin as early as the first week of April, in what Tan said is a testament to the seriousness and speed of Canada’s regulatory authorities in supporting COVID-19 research projects.

“The process of having a clinical trial approved by Health Canada can usually take up to 30 days,” says Tan. “In this case, Health Canada received our application, reviewed it and issued approval within less than 24 hours over a weekend, which is quite remarkable.”

In a statement, federal Minister of Health Patty Hajdu emphasized the importance of research in tackling COVID-19 in Canada and around the world.

“The outbreak of COVID-19 evolves quickly, and protecting the health of Canadians is our priority. The additional teams of researchers receiving funding today will help Canada quickly generate the evidence we need to contribute to the global understanding of the COVID-19 illness,” Hajdu said.

“Their essential work will contribute to the development of effective vaccines, diagnostics, treatments, and public health responses.”

Here is the full list of ����ֱ�� researchers who received CIHR funding for their COVID-19-related projects:

• Roy Gillis of the department of applied psychology and human development at the Ontario Institute for Studies in Education: Responding to the stigma, fear, discrimination and misinformation related to the COVID-19 disease outbreak – a novel analyses and intervention for a novel coronavirus
• Shaf Keshavjee of the department of surgery in the Faculty of Medicine and the University Health Network: Reducing the health-care resource burden from COVID-19 (SARS-CoV-2) –Rapid diagnostics to risk-stratify for severity of illness
• Robert Maunder of the department of psychiatry in the Faculty of Medicine and Sinai Health System: Peer champion support for hospital health-care workers during and after a novel coronavirus outbreak: It's a marathon, not a sprint
• Vijaya Kumar Murty of the department of mathematics in the Faculty of Arts & Science and the Fields Institute for Research in Mathematical Sciences: Agent-based and multi-scale mathematical modelling of COVID-19 for assessments of sustained transmission risk and effectiveness of countermeasures
• James Rini of the departments of biochemistry and molecular genetics in the Faculty of Medicine: Neutralizing antibodies as SARS-CoV-2 therapeutics
• Simron Singh of the Dalla Lana School of Public Health and the department of medicine in the Faculty of Medicine and Sunnybrook Health Sciences Centre: Assessment of cancer patient and caregiver perspective on the novel coronavirus (COVID-19) and the impact on delivery of cancer care at an institution with a confirmed case of COVID-19
• Darrell Tan of the Institute of Health Policy, Management and Evaluation at the Dalla Lana School of Public Health and department of medicine in the Faculty of Medicine and St. Michael’s Hospital: COVID-19 ring-based prevention trial for undermining spread (CORPUS)
• Xiaolin Wei of the Institute of Health Policy, Management and Evaluation at the Dalla Lana School of Public Health: Developing integrated guidelines for health-care workers in hospital and primary health-care facilities in response to Covid-19 pandemic in low- and mddle-Income countries (LMICs)
• Xiao-Yan Wen of the department of physiology in the Faculty of Medicine and St. Michael’s Hospital: Therapeutic development for COVID-19 coronavirus-induced sepsis and ARDS targeting vascular leakage