Early detection, smarter treatment: Mapping the next big advances in sepsis research

Sepsis is a life-threatening condition triggered by a dysregulated host response to infection, leading to organ dysfunction. Accounting for nearly 20% of deaths globally, it remains one of the most critical challenges in global health, especially in resource-limited settings where mortality is disproportionately high. Despite advances in medical care and global efforts like the Surviving Sepsis Campaign, significant gaps persist in how sepsis is detected, managed, and studied.

To help advance sepsis research and care, a special editorial was authored by Dr. Craig Coopersmith, Professor of Surgery and Director of the Emory Critical Care Center, Emory University School of Medicine, USA. The article, titled “Future Directions in Sepsis Research,” provides a comprehensive analysis of the limitations in current sepsis management and outlines priorities for future progress. It advocates for moving beyond broad treatment protocols toward more predictive, personalized, and integrative approaches. The editorial was made available online on April 19, 2025, and was published in Volume 5, Issue 3 of the Journal of Intensive Medicine on July 1, 2025.

One major challenge is the failure to apply existing clinical guidelines effectively at the bedside. Many clinicians are unaware of current protocols or face difficulties implementing them due to low-quality supporting evidence, lack of adaptation to local needs, or inadequate healthcare infrastructure. The editorial underscores the importance of implementation science in narrowing this gap between knowledge and practice. Practical solutions include developing dynamic “living” guidelines, translating them into more languages, tailoring them to region-specific pathogens such as dengue and tuberculosis, and expanding education and support for clinicians in underserved areas.

Improving early prediction is also critical to reducing mortality. Although early antibiotic use improves survival, recognizing infection before it proceeds to sepsis remains difficult. The editorial highlights the potential of artificial intelligence (AI) and machine learning (ML) to fill this gap. “Advanced tools such as AI and ML hold promise for analyzing vast amounts of patient data to detect subtle, early indicators of sepsis that may elude human observation,” he explains. “However, these innovations must overcome significant hurdles, including data privacy concerns, ethical considerations, and the risk of overtreatment due to false positives,” states Dr. Coopersmith.

Diagnostics are another weak link. Traditional methods like blood cultures are slow and unreliable. Although newer rapid diagnostic tools exist, none have become standard practice, and their impact on outcomes remains unclear. At the same time, the specificity of the current Sepsis-3 definition and SOFA score is being questioned, calling for more precise diagnostic frameworks.

On the therapeutic front, antibiotics remain essential, but no treatment has successfully modulated the body’s dysregulated host response. Despite over 100 clinical trials, no immunotherapy has improved survival. A deeper understanding of host-pathogen dynamics, including inflammation, immune suppression, the microbiome, and neural-immune signaling is needed. Multi-omics approaches combined with machine learning may help identify new therapeutic targets.

Traditional clinical trial designs are also under scrutiny. The biological diversity among sepsis patients means a one-size-fits-all model often fails. Personalized strategies based on phenotypes and endotypes, along with adaptive platform trials that can adjust to real-time data, offer more efficient paths to progress.

The article also looks ahead to emerging technologies such as wearable immune monitoring, nanotechnology, and RNA-based therapies that may allow more precise and less toxic interventions. These tools could usher in a future where sepsis care is not only timely, but fully tailored to each patient’s unique biology.

Dr. Coopersmith concludes, “Tackling the global burden of sepsis demands more than new drugs or technologies. It calls for a coordinated, multifaceted approach that integrates timely diagnosis, personalized treatment, equitable implementation, and innovative trial design.”

Grounded in clinical evidence and real-world experience, the editorial outlines both incremental and transformative opportunities to reduce global sepsis mortality—bringing precision medicine in sepsis care closer to reality.

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Reference
DOI: https://doi.org/10.1016/j.jointm.2025.03.004

About Professor Craig M. Coopersmith
Dr. Craig M. Coopersmith is Director of the Emory Critical Care Center and Professor of Surgery at Emory University School of Medicine. He is Principal Investigator or co-Principal Investigator on multiple NIH-funded grants focused on the gut and host response in sepsis, as well as a T32 training grant in critical care. He co-chairs the Surviving Sepsis Campaign and served on the NIH COVID-19 guidelines panel. A past president of the Society of Critical Care Medicine, he has received numerous honors, including the 2023 ACCM Distinguished Investigator Award and Emory’s 2024 Dean’s Distinguished Faculty Lecture and Award.