Twenty percent of deaths worldwide are caused by sepsis, and there are currently no treatments that tackle it directly. Now, researchers at the University of British Columbia demonstrate how systems immunology can help provide insights into understanding and treating sepsis, and how this could cut the death toll of future pandemics.
The findings are published in Frontiers in Science in an article titled, “Deciphering sepsis: transforming diagnosis and treatment through systems immunology.”
“We need to adopt a concerted approach to tackle sepsis,” said Robert Hancock, PhD, professor at the University of British Columbia and lead author of the article. “Only a very small amount of funding is currently invested in sepsis research and product development—and yet sepsis is as prominent a cause of death as heart disease and cancer, and the major cause of death in pandemics.”
One of the reasons it’s so hard to understand and treat sepsis is that it is multifaceted. Sepsis arises when the immune system fails to control an infection and malfunctions, causing multi-organ failure.
Systems immunology could offer a potential solution to diagnosing sepsis by using mathematical and computational modeling to study the immune system in the context of all the body’s other systems. It does this by using different types of clustering analysis to identify patterns in large volumes of omics data, ranging from transcriptomic data (what genes show altered expression) to proteomic and metabolomic data.
These patterns help us work out the patterns and basis for the immune dysregulation that drives sepsis, come up with new hypotheses that we can research and use to develop new treatments, and identify diagnostic markers that we can use to catch sepsis early, the researchers noted. In the future, the researchers believe we could build on these advances to diagnose different subtypes of sepsis earlier and treat them with the right drugs when we do.
However, systems immunology analysis is not yet in widespread use because it is expensive and demands significant volumes of data.
“In sepsis, we lack the depth of information required to enable more effective systems immunology and machine learning approaches,” urged Hancock. “We hope to encourage the development of large, in-depth omics-oriented patient studies that will trigger a new generation of insights.”
Successfully treating sepsis would be a multipurpose life-saver, preventing mortality regardless of the illness that triggered it. Viral sepsis is a major cause of death triggered by severe COVID-19, while many deaths in historical pandemics like the 1919 influenza pandemic and the bubonic plague are thought to have resulted from sepsis. If we can tackle sepsis, we might be able to protect ourselves against the worst consequences and the highest death tolls in future pandemics, no matter what kind of infection causes them. Since immune dysregulation linked to sepsis can linger, causing symptoms similar to post-viral syndromes like long COVID-19, learning to treat this could also benefit some chronic illness patients.
But to make this happen, the researchers caution, more funding and larger studies will be needed.
“The omics methods that underlie systems immunology are relatively expensive on a per-patient basis,” said Hancock. “It will require a concerted drive from stakeholders to generate the data needed for further insights. We need to invest in larger omics studies of patients, develop new animal and organoid models that reflect sepsis heterogeneity, and invest in early diagnostics for sepsis and treatments that correct or supplement defective immunity in sepsis patients.”
