Sepsis: When complications become life-threatening
Sepsis, also known as blood poisoning, is one of the most common causes of death worldwide. About every third affected person dies. Early detection is important, as is more understanding of the complex processes that take place in the body before, during and after sepsis. The disease needs our attention. That is why September is Sepsis Awareness Month.
Sepsis occurs when the immune system can no longer locally contain an infection and its consequences. An excessive defence reaction of the body occurs, which damages its own tissues and organs. The causes of sepsis are manifold. In the course of injuries, microorganisms can enter the bloodstream and thus trigger sepsis. But sepsis can also develop as a complication of diseases such as pneumonia, infections of the gastrointestinal tract or pathological tissue changes such as diabetic foot syndrome.
The problem for the clinic is that the disease is difficult to diagnose and treat. Priv.-Doz. Dr. Marcin Osuchowski is co-director and head of intensive care research at the Ludwig Boltzmann Institute for Traumatology, the research centre in cooperation with AUVA. Together with his team, the Polish-born scientist is researching the processes underlying sepsis. The events are investigated at the molecular level, from early signs to organ failure in septic shock. The scientists observe functional changes and damage to cells and changes in cell communication. In order to be able to detect sepsis earlier in the future, biomarkers are being sought that allow predictions about the development and course of the disease.
What happens in the course of sepsis is a complete deregulation of the immune system and the inflammatory reactions that accompany the body’s own defence. Cytokines, small signalling molecules in the body, play an important role in this. The immune system uses them for communication. In sepsis, the immune system literally panics: everyone shouts in confusion. This can trigger a downward spiral – a “cytokine storm” – in which the immune system lashes out wildly and also severely damages its own body. Or, the defences may be overridden because any strategy is lost in the confusion. Deregulation can happen in both directions. Depending on the course of the disease, the type of microorganisms that have invaded, or patient-specific criteria, one aspect or the other often predominates.
Other than that, the word “cytokine storm” often comes up in line with another disease that has been occupying the world for over two years now: COVID-19. However, this is a gross simplification of the processes of an entirely separate disease. Knowledge of the pathophysiology of COVID-19 has long led a background existence while epidemiology dominated the headlines. Public perception fluctuated between a “severe flu” and a particularly intractable pneumonia, the latter not least because of its name (SARS stands for severe acute respiratory syndrome). But the changes in the lungs are unfortunately only one piece of the puzzle of the complex clinical picture of COVID-19.
Here, Dr. Osuchowski succeeded in building bridges between disciplines to produce an extraordinary overview work together with experts from different fields of research. In “The COVID-19 Puzzle”, published in The Lancet Respiratory Medicine, they comprehensively describe the clinical picture of COVID-19 in and outside the lungs. The scientists illustrate the inflammatory mechanisms in the alveoli, dangerous vascular changes and the changes in the blood count. They also emphasise long-lasting late effects, the extent of which will only become apparent over time, and which will keep medicine and science on tenterhooks for a long time to come.
Dr Osuchowski explains: “SARS-CoV-2 is a new infectious pathogen that poses a new challenge to our immune system. It is becoming increasingly clear that the severity of COVID19 disease is associated with a dysregulated immune system response that differs from previously known mechanisms and causes of sepsis. We advise caution about the widespread notion of a systemic cytokine storm as the leading cause of the observed multi-organ reactions. The data on this is not yet clear.”
Speaking about the work on “The COVID-19 Puzzle”, Dr Osuchowski says: “What I am most proud of is not the first authorship, but that I managed to stir up this heated discussion. I’ve put some people on the spot, even more upset, but I’ve managed to turn that anger into something meaningful.”
Dr Osuchowski also showed his strength in networking people – be it out of anger at problems pointed out or simply the desire to pull together – in other projects. For example, the Wiggers-Bernard Initiative for Sepsis Research was launched through him. In preclinical sepsis research, there had never before been organised efforts to standardise it through guidelines. Every laboratory conducts its experiments a little differently. This leads to differences in quality and confusion due to poorly comparable data. This makes it difficult to translate research results to clinical application. The team of experts gathered in Vienna under the banner of the Wiggers-Bernard Initiative formulated the MQTiPSS (Minimum Quality Threshold in Pre-Clinical Sepsis Studies), 29 recommendations as a common denominator for the conduct of sepsis studies. This will enable scientists to conduct their research even more effectively.
In September 2023, Vienna will once again be the capital of sepsis research for a few days. This is when the 20th Congress of the European Shock Society will take place – a society whose presidency Dr. Osuchowski took over in September 2021