Sepsis from Science to Social Perspective

Djillali Annane, MD, PhD

Ricard Ferrer, MD, PhD

Sepsis carries a heavy social, economic, and health burden worldwide and is characterized by vital organ dysfunctions triggered by abnormal response to invading bacteria, viruses, fungi, or parasites. Among bacteria, Streptococcus pneumoniae, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa account for >2/3 of cases, with high prevalence of antimicrobial resistance. Sepsis, while a major threat for European Union (EU) and U.S. populations, disproportionally affects the most vulnerable and low- and middle-income countries populations with approximately 50 (3.4 in EU) million cases and approximately 11 (0.68 in EU) million deaths annually. With growing and aging of world population, sepsis cases will double by 2050.[1] New health problems occur in 3/4 of 3-year survivors, with annual costs of €6.8 billion. Almost half of all cases occur among children <5 years (⁓20 million cases, ⁓2.9 million deaths). Evidence-based guidelines with prompt source control, antimicrobials, and vital organ function support contributed in reducing sepsis mortality.[2] Except corticotherapy, immunotherapy attempts have failed in unselected sepsis. Hyper- and hypoinflammation are concurrent, sustained, and vary with pathogens and host characteristics. Coronavirus disease 2019 pandemic shed light on patients' heterogenous response to interventions and the need for bedside identification of treatable traits. Challenges for new trials are to provide dynamic characterization (prediction) of individual risks and response to treatments (enrichment).[3] In this issue of Seminars in Respiratory and Critical Care Medicine on “sepsis,” we have invited a group of world-class experts to synthetize the best of current knowledge about sepsis.

The articles cover the history of the definition of sepsis and a critical analysis of the epidemiological burden. The putative causal mechanisms of progression from infection to sepsis and of trajectory to death or recovery with or without sequels are described. A special emphasis is put on the deregulation of the immune response with spectrum varying from excessive inflammation to immune suppression. The readers will discover how advances in molecular biology has resulted in a new conceptual approach of sepsis based on subphenotypes, endotypes, and treatable traits. The articles also provide insightful information on early recognition and diagnosis of sepsis, highlighting the promising role of novel molecular-based diagnostic tests with fast turnaround, and the challenges of transferring them into user-friendly, nonexpensive point-of-care or near-patient tools. The practical evidence-based management is detailed for the early management and also readers will learn what to do beyond the first 24 hours, with a specific focus on acute kidney management. At last, but not at least, the perspective of both researchers and sepsis survivors is given about its social burden. Surviving sepsis may be not the end of the story for too many people who will continue suffering from a broad variety of disorders encompassing physical disabilities, cognitive, and psychosocial disorders. While the postsepsis syndrome is now well recognized, there is still much to learn about causal mechanisms, prevention, and treatment.

The guest editors are deeply grateful to the authors for their outstanding contributions to this issue of the journal. We are confident that regardless of who you are, a student, an attending physician, a nurse, a researcher, a policymaker, an entrepreneur, a patient, or a patient's family member, you will enjoy reading this issue that may change your perspectives on sepsis.

Publication History

Article published online:
29 August 2024

• References

• 1 Rudd KE, Johnson SC, Agesa KM. et al. Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the Global Burden of Disease Study. Lancet 2020; 395 (10219): 200-211
• 2 Evans L, Rhodes A, Alhazzani W. et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med 2021; 47 (11) 1181-1247
• 3 Fleuriet J, Heming N, Meziani F. et al; RECORDS consortium, CRICS TRIGGERSEP network. Rapid rEcognition of COrticosteRoiD resistant or sensitive Sepsis (RECORDS): study protocol for a multicentre, placebo-controlled, biomarker-guided, adaptive Bayesian design basket trial. BMJ Open 2023; 13 (03) e066496