An article published in Frontiers in Immunology suggests that sepsis can cause alterations in the functioning of defense cells that persist even after the patient is discharged from hospital. This cellular reprogramming creates a disorder the authors call post-sepsis syndrome, whose symptoms include frequent reinfections, cardiovascular alterations, cognitive disabilities, declining physical functions, and poor quality of life. The phenomenon explains why so many patients who survive sepsis die sooner after hospital discharge than patients with other diseases or suffer from post-sepsis syndrome, immunosuppression and chronic inflammation.
The article presents a review of studies conducted to investigate cases of septic patients who died up to five years after being discharged from hospital.
Considered one of the leading causes of death in intensive care units, sepsis is a life-threatening systemic organ dysfunction triggered by the organism's dysregulated response to an infectious agent, typically a bacterium or fungus. The defense system injures the body's own tissues and organs while combating the infectious agent.
If it is not promptly recognized and treated, the condition can lead to septic shock and multiple organ failure. Patients with severe COVID-19 and other infectious diseases run a heightened risk of developing and dying of sepsis.
New cases of sepsis are estimated to total some 49 million per year worldwide. Hospital mortality from septic shock exceeds 40% globally, reaching 55% in Brazil, according to the Sepsis Prevalence Assessment Database (SPREAD) study, conducted with support from FAPESP.
"The massive infection and the accompanying intense immune response with a cytokine outpouring during sepsis may promote irreversible cell metabolic reprogramming. Cell reprogramming is unlikely to occur in leukocytes or bone marrow only. This might happen in several tissues and cells that prompt systemic organ dysfunctions. Bacteria can transfer genetic material to host cell DNA as eukaryotic cells develop tools to protect themselves against the microorganism invasion. The latter may induce cell biology and metabolic reprogramming that remains even after the infection's elimination," the researchers state in the article.
According to first author, one of the hypotheses investigated by the group was that metabolic reprogramming starts in the bone marrow, whose cells acquire a pro-inflammatory profile. "This analysis of blood samples from patients even three years after ICU discharge showed that monocytes [a type of defense cell] were activated and ready for battle. They should have been neutral. Monocytes are normally activated only when they are 'recruited' to the tissue," said researchers.