Survival after sepsis has improved over recent decades, resulting in a growing population of sepsis survivors. Survivorship after sepsis is frequently marked by significant long-term morbidity, including new functional dependence, cognitive impairment, anxiety, depression, post-traumatic stress symptoms, recurrent hospitalization, and excess long-term mortality. This article presents the current knowledge on the epidemiology of long-term outcomes among critically ill adult sepsis survivors, with particular emphasis on patient-centered outcomes, their prevalence, and contributing factors, and a discussion of the emerging role of biomarkers, immunologic profiling, and artificial intelligence in individualized prediction and post-sepsis care pathways.
Sepsis-induced immunosuppression contributes to mortality, increased susceptibility to secondary infections and long-term complications. Myeloid cells undergo functional reprogramming, while adaptive immune cells, particularly T lymphocytes, show altered composition and lymphopenia. This immunosuppression is driven by several mechanisms. Therapies, including immune-stimulating cytokines, checkpoint inhibitors, and mesenchymal stem cells, are under investigation to restore immune function, but their effectiveness in clinical practice is still unclear.
Prompt recognition and appropriate early management of sepsis reduces mortality. There are 2 major goals of early sepsis management, which should be pursued urgently and in parallel-(1) infection control and (2) hemodynamic resuscitation. Treating infection involves timely antimicrobial therapy, and for some infections, source control. Hemodynamic resuscitation should start with a rapid bolus of balanced crystalloid followed by personalized approaches that tailor fluid and vasopressor therapy to evolving patient physiology. In patients who do not improve with initial antibiotic therapy and resuscitation, it is essential to reassess adequacy of infection control and resuscitation.
Sepsis continues to be a leading public health challenge, accounting for almost 20% of annual global deaths. Here, we review the evolving pathophysiological understanding of this syndrome by highlighting the central role of immunometabolism. We move beyond the biphasic model to argue that hyperinflammation and immunosuppression coexist across different biological compartments. Recognition of danger through the signal triad of pathogen-associated molecular patterns, damage-associated molecular patterns, and homeostasis-altering molecular processes induces profound intracellular metabolic reprogramming toward a predominantly aerobic glycolysis pattern. This shift supports early effector functions but leads to bioenergetic insufficiency, cytopathic hypoxia, and mitochondrial dysfunction.
The immunocompromised host represents a growing and heterogeneous population within the intensive care unit. Advances in oncologic therapies, organ transplantation, and immunomodulatory treatments for autoimmune diseases have expanded survival but altered host immune architecture. Sepsis in this population is not merely sepsis with an added risk factor; rather, immune changes may fundamentally modify host-pathogen interactions, inflammatory phenotypes, diagnostic accuracy, and therapeutic response. This article focuses on sepsis in patients with solid and hematologic malignancies, organ transplantation, autoimmune and vasculitic conditions. We conclude with priorities for research aimed at developing immune-informed precision approaches to sepsis in the immunocompromised host.
Sepsis survivorship is increasing, but many survivors develop post-sepsis syndrome, marked by high early readmission rates and new-onset conditions, notably recurrent infections, cardiovascular, psychiatric, and kidney disease. Persistent physical, cognitive, and psychological sequelae may further impair daily functioning. Emerging evidence suggests lasting immune dysregulation, likely interacting with mitochondrial dysfunction, immunosuppression, endothelial injury, low-grade inflammation, and microbiome disruption. While evidence for targeted postdischarge interventions remains limited and yields mixed results, much can still be done. Several strategies can begin during hospitalization, and after discharge a primary-care-centered, risk-stratified follow-up pathway may support recovery and reduce readmissions and complications.
Critical illness and intensive care unit admission are common occurrences in the immune-mediated inflammatory disease (IMID) patient cohort. This article specifically focuses on inflammatory rheumatic musculoskeletal disease within IMIDs. Understanding the aetiology, risk factors, co-morbidities, and management of these conditions in critical care are the key points discussed here. We have compiled the most common anti-rheumatic therapeutics in this article for management in these situations.
