Aug. 17, 2020

UCalgary researchers part of Pan-Canadian network to improve treatment and recovery from sepsis

Sepsis is a leading cause of death in COVID-19
Paul Kubes in the lab
Paul Kubes in the lab Riley Brandt, University of Calgary

A recent global report published in The Lancet estimates 75,000 cases of sepsis occur in Canada every year, likely causing 18,000 deaths. For those seriously ill with COVID-19, it is a real threat to their survival, when a person’s immune response becomes out of control and leads to tissue damage, organ failure or death. It can happen at any age, to children and adults.

“Before COVID-19, many people hadn’t heard about sepsis or acute respiratory distress syndrome — people knew about blood poisoning, but I think most don’t realize that so many Canadians die from this condition,” says Dr. Paul Kubes, PhD, director of the Snyder Institute for Chronic Diseases at the Cumming School of Medicine (CSM) and member of Sepsis Canada, a new research network focused on improving our understanding of this deadly infection. 

Sepsis is caused by a microbial pathogen such as a virus or bacterium. The new coronavirus that leads to COVID-19 is now on the list of pathogens that can result in sepsis. Most patients who are critically ill with COVID-19 develop sepsis, which becomes a major threat to their survival.

“All too often, people are sick and don’t even realize that they are septic. The pathogen gets into the bloodstream and hyperactivates the immune system, and then the immune system has difficulty getting rid of the pathogen,” says Kubes, pictured above.

Sepsis’ attack on the body

Kubes says there is no magic bullet to cure sepsis, but a multidisciplinary approach is necessary to help people survive and have better long-term outcomes to go back to a normal life.

“We have patients with hypotension, or low blood pressure, and they need the right physicians to help with those specific issues. Some will have liver failure, kidney disease, brain dysfunction known as delirium — many organs can be infected, and you need to understand each of them to treat them properly.”

Kubes says you can survive sepsis and a year later, you might not feel quite right. You could have trouble understanding what you used to understand without a problem, because you are cognitively impaired, an extenuating circumstance of sepsis.

“We don't understand this at all. These patients don't fully recover cognitively and it's happening during their time in ICU. Delirium or inflammation of the brain perhaps affects their long-term outcome — this network will help us understand how acute septic response can translate into much longer-term problems.”

Building a network

Sepsis Canada owes its start to $5.7 million in federal funding.

“The importance of understanding how to track and treat sepsis has never been as important as it is now,” says Patty Hajdu, federal minister of health. “We are proud to help bring together this impressive group of clinicians, researchers, and patients from across the country. They will collaborate to produce knowledge that will improve the health of Canadians and contribute to a more sustainable health-care system.”

Led by Dr. Alison Fox-Robichaud at McMaster University and Dr. François Lamontagne at Université de Sherbrooke, the network brings together 190 clinicians, scientists and patient representatives across the country in true multi-disciplinary fashion. Organized around three themes, UCalgary scientists are well represented in this project due to the depth of sepsis research that has taken place over the years in Calgary.

“This investment is critically important for the health of not only Canadians, but also our global community,” says Dr. William Ghali, vice-president (research) at UCalgary. “This multi-disciplinary group will bring the best minds together to study and challenge how we treat sepsis and increase our awareness of it, with the potential for major advances.”

A path forward for sepsis treatment

Because COVID-19 is a single pathogen, Kubes believes the research done to date will help advise on the best approach for COVID-19 and finding a treatment that will work. “I am an optimist and I think COVID is treatable, but we need to do the research,” says Kubes.

The harder part is treating the diversity of patients who end up with sepsis from different situations in their lives.

“The problem with sepsis is that it ranges from a 90-year-old that falls down, breaks a hip and gets an infection in the hospital, to the 20-year-old fit person that gets into a car crash and ends up with an infection. These two very different conditions are usually included in the same trial, but the chances of finding a drug that works for both of them is unlikely, because there are very different issues at play.”

Sepsis Canada research teams

Each team will focus on two or more objectives, with the teams organized around their specific expertise, in children and adults. Together, they will work toward the vision to “suspect sepsis, save lives and support recovery.” The multidisciplinary UCalgary team members represent a number of departments and institutes within the CSM and Faculty of Kinesiology.

Team 1: Population Health, Economics and Policy

Focusing on evaluations at the population level, this team seeks to understand the burden of sepsis in Canada and systematically ascertain and improve long-term sepsis outcomes. The team includes Dr. Hude Quan, MD, PhD, (CSM) and Dr. Daniel Niven, MD, PhD, (CSM).

Team 2: Advocacy, Health Literacy and Knowledge Transfer

This team will work to improve public awareness and mobilize stakeholders concerned with sepsis surveillance, to create a culture of sepsis awareness and inform practices for monitoring, preventing and detecting sepsis earlier. The team includes Dr. Jeanna Parsons Leigh, PhD, team co-lead, (CSM), Dr. Kirsten Fiest, PhD, team co-lead, (CSM), Dr. Ian Blanchard, PhD, (CSM), and Dr. Daniel Lane, PhD, (collaborator).

Team 3: Translation Biology and Clinical Trials

Team 3 will provide new insights on pathogenesis and effective therapies, to better understand the pathogenic mechanisms leading to sepsis and to allocate cost-effective sepsis therapies based on patients’ individual risk profiles. This team includes Dr. Paul Kubes, PhD, team co-lead, (CSM), Dr. Braedon McDonald, MD, PhD, (CSM), Dr. Raylene Reimer, PhD, (CSM and Kinesiology), Dr. Graham Thompson, MD, (CSM), and Dr. Brent Winston, MD, (CSM).

Sepsis Canada members also include: Marlyn Gill (Patient and Community Engagement Research, PaCER, Alberta Health Services) and Dr. Bryan Yipp, MD, (CSM) on the Training Committee; as well as Dr. Christopher (Chip) Doig, MD, (CSM) and Dr. Tom Stelfox, MD, (CSM) on the International Senior Advisory Board.

Infections, Inflammation and Chronic Diseases

The University of Calgary is uniquely positioned to find solutions to key global challenges. Through the research strategy for Infections, Inflammation, and Chronic Diseases in the Changing Environment (IICD), top scientists lead multidisciplinary teams to understand and prevent the complex factors that threaten our health and economies.

Paul Kubes is a professor in the CSM’s Department of Physiology and Pharmacology, Medicine, Critical Care Medicine, and Microbiology, Immunology and Infectious Diseases, director of the Snyder Institute for Chronic Diseases, and the Canada Research Chair in Leukocyte Recruitment in Inflammatory Disease.