Sepsis Awareness: New Developments for Tackling a Global Health Priority

13th September 2024

Samantha Weetman, Science Writer.

Sepsis is a life-threatening condition that develops when the body’s response to infection becomes extreme, leading to organ failure, and in severe cases, death. With an estimation of 48,000 deaths attributed to sepsis in the UK alone each year [1], raising awareness about this global health priority is crucial. World Sepsis Day, marked annually on September 13th, serves to raise public sepsis awareness, educate about the symptoms of sepsis, and the importance of early diagnosis and treatment. In this blog, we will explore recent advances in medical research that are offering hope, with new therapies and technologies showing promise in the fight against this deadly condition.

What Is Sepsis and Why Is It Deadly?

Sepsis occurs when an infection triggers an abnormal immune response, leading to widespread inflammation, organ dysfunction, and potentially, septic shock. In 2016, sepsis was redefined as life-threatening organ dysfunction caused by a dysregulated host response to infection [2]. It can develop from bacterial, viral, or fungal infections and is particularly dangerous for vulnerable populations such as the elderly, infants, and individuals with compromised immune systems. Symptoms of sepsis include fever, rapid heart rate, confusion, and difficulty breathing. If not treated quickly, sepsis can escalate to septic shock, characterised by a dramatic drop in blood pressure, resulting in organ failure and death [3].

It is currently estimated from data recorded in 2017, that there are about 49 million cases of sepsis worldwide annually, and 11 million sepsis-related deaths, which accounts for approximately 20% of global deaths. In 2017 the World Health Organisation (WHO), declared sepsis a global health priority. Among the top five consistently reported causes of sepsis-related deaths are, lower respiratory infections (e.g. pneumonia), diarrheal diseases, neonatal disorders, and stroke [4].

Early diagnosis and treatment are critical, as sepsis has a mortality rate of 30-40% for those who experience septic shock [3]. This highlights the importance of raising sepsis awareness for recognising the symptoms and seeking prompt medical care.

The Ongoing Fight Against Sepsis: New Research and Trials

Advances in Immunomodulatory Therapies

The body’s overreaction to infection, which drives sepsis, makes it notoriously difficult to treat. This is because sepsis encompasses both a hyper-inflammatory and an immunosuppressive phase. Recent research explores the potential of immunotherapies to modulate the body’s immune response to sepsis. The aim of these therapies is to prevent excessive inflammation while preserving the immune system’s ability to combat infection. Several studies have explored the potential of targeting key pro-inflammatory cytokines, associated with the cytokine storm in sepsis. Inhibiting these cytokines has shown promise in reducing inflammation and minimising organ damage, although balancing immune suppression with infection control remains a significant challenge.

Additionally, another type of immunotherapy termed checkpoint inhibitors is being explored [5], [6]. Checkpoint inhibitors such as pembrolizumab have been used in cancer treatment to block the programmed cell death protein 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) interaction, allowing T-cells to then identify and kill tumour cells. The hope is that such inhibitors can be used to treat the immunosuppressive phase of sepsis.

Although still in its early stages, these therapies represent a promising avenue for more precise management and a significant shift in how sepsis might be treated in the future.

Promising Clinical Trials for New Therapies

Several clinical trials are providing optimism for new sepsis treatments. A groundbreaking trial led by researchers in Australia focuses on using high-dose sodium ascorbate (a vitamin C alternative with a physiological pH) to alleviate sepsis symptoms following positive results in pre-clinical studies with sheep [7].

The pilot, which was carried out at Austin Hospital in Melbourne has shown remarkable results in improving organ function in septic patients. Patients that received the high-dose sodium ascorbate treatment showed signs of improved kidney function, indicated from increased urine production; they also required less vasopressor (noradrenaline) to stabilise blood pressure, and showed a greater decrease in sequential organ failure assessment (SOFA) score over time [7]. The next stage larger clinical trial is now underway.

Further studies on high-dose sodium ascorbate by the same researchers have discovered that it could reverse sepsis-induced brain injuries. Results from their recent early-stage trial with sheep show that a megadose of sodium ascorbate can rapidly reverse cerebral ischaemia, hypoxia, hyperthermia, and sickness behavioural states caused by E. coli induced sepsis in ewes [8]. The findings are now being tested in a larger clinical trial across Australia. These discoveries suggest that sodium ascorbate could play a vital role in future sepsis treatment protocols.

Artificial Intelligence (AI) and Biomarker Innovations

Another exciting development involves the use of AI and digital twins to enhance early sepsis diagnosis and treatment. Researchers are exploring how AI may help clinicians interpret complex data from blood tests faster and identify biomarkers for earlier detection of sepsis, and for preventing disease progression[9].

Biomarkers also provide measurable indicators of disease presence and severity, which may aid in the use of more personalised interventions [6]. Machine learning (ML) is also being used to identify disease subgroups from clinical and omics data, and to discover new biomarkers. ML could be used in the future to predict how patients will respond to different treatments.

Digital technologies could revolutionise sepsis care by enabling healthcare professionals to intervene sooner, ultimately reducing the severity of the condition and improving survival rates.

Looking Forward: A Hopeful Future for Sepsis Care

Sepsis remains a complex and dangerous condition, but ongoing research and innovation are creating hope for better outcomes. Immunotherapies, high-dose sodium ascorbate treatments, and AI-based diagnostic tools are advancing the fight against sepsis, offering new ways to manage and potentially reverse its deadly effects. With promising clinical trial results and the development of early detection tools, the future of sepsis care is becoming brighter.

However, continued sepsis awareness, education, and research are critical for ensuring that these innovations become accessible to patients worldwide. As we mark World Sepsis Day, it’s important to remember that early diagnosis and treatment are key. By staying informed and supporting advancements in sepsis care, we can help reduce the devastating impact of this condition and improve patient outcomes.

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References
[1] ‘About sepsis – The UK Sepsis Trust’. Accessed: Sep. 11, 2024. [Online]. Available: https://sepsistrust.org/about-sepsis/
[2] M. Singer et al., ‘The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)’, JAMA, vol. 315, no. 8, p. 801, Feb. 2016, doi: 10.1001/JAMA.2016.0287.
[3] ‘Sepsis – Symptoms & causes – Mayo Clinic’. Accessed: Sep. 11, 2024. [Online]. Available: https://www.mayoclinic.org/diseases-conditions/sepsis/symptoms-causes/syc-20351214
[4] K. E. Rudd et al., ‘Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the Global Burden of Disease Study’, The Lancet, vol. 395, no. 10219, pp. 200–211, Jan. 2020, doi: 10.1016/S0140-6736(19)32989-7.
[5] A. Jain, A. Singam, and V. N. K. S. Mudiganti, ‘Recent Advances in Immunomodulatory Therapy in Sepsis: A Comprehensive Review’, Cureus, vol. 16, no. 3, Mar. 2024, doi: 10.7759/CUREUS.57309.
[6] E. Santacroce et al., ‘Advances and Challenges in Sepsis Management: Modern Tools and Future Directions’, Cells 2024, Vol. 13, Page 439, vol. 13, no. 5, p. 439, Mar. 2024, doi: 10.3390/CELLS13050439.
[7] F. Yanase et al., ‘Mega-dose sodium ascorbate: a pilot, single-dose, physiological effect, double-blind, randomized, controlled trial’, Crit Care, vol. 27, no. 1, pp. 1–12, Dec. 2023, doi: 10.1186/S13054-023-04644-X/FIGURES/6.
[8] ‘New trial therapy appears to rapidly reverse life-changing sepsis-induced brain injury | The Florey’. Accessed: Sep. 12, 2024. [Online]. Available: https://florey.edu.au/news/2024/07/new-trial-therapy-appears-to-rapidly-reverse-life-changing-sepsis-induced-brain-injury/
[9] A. M. Scott et al., ‘Population scale proteomics enables adaptive digital twin modelling in sepsis’, medRxiv, p. 2024.03.20.24304575, Mar. 2024, doi: 10.1101/2024.03.20.24304575.