Sepsis often manifests as a systemic inflammatory response syndrome (SIRS), begun by the host's inability to confine an infection. Consequently, it has become a significant cause of major health-associated economic problems, through an increase in patient deaths in the intensive care units of hospitals due to sepsis-related complications. Expectedly, it causes multiple organ dysfunction in later stages, for example, kidney failure, liver, and lung dysfunction. Altogether, this is called multiple organ dysfunction syndrome (MODS), which ultimately leads to the death of patients. During sepsis, the mortality rate is between 30–50% on average. Early and accurate diagnosis of sepsis is a crucial task because of the narrow window before it may shift towards shock, organ failure, or death. The delay in delivering proper care by every hour results in a 7.6% reduction in the survival rate of sepsis patients. Hence, the search for novel biomarkers and advanced techniques to diagnose sepsis at an early time point are of paramount importance in the clinical management of sepsis.

Excessive free radical generation (reactive oxygen species or reactive nitrogen intermediates), hyperactivation of immune cells and pro-inflammatory cytokines, or improper resolution of inflammation during sepsis can result in cytotoxicity that leads to dysfunction or failure of cardiovascular, respiratory, renal, neurological, hematological, and hepatic systems. Identifying the mechanisms underlying this process will not only help better our understanding of the pathophysiology of sepsis but will also help in the identification of drug targets combating sepsis. A major hurdle in sepsis management is the development of multiple drug-resistant strains of pathogen. Current therapeutics, including antibiotics, are inadequate in combating multi-drug resistant (MDR) pathogens. Rational structure-based drug design, utilizing state-of-the-art techniques like X-ray crystallography, nuclear magnetic resonance (NMR), and mass spectroscopy to solve the three-dimensional structure of target proteins will assist in searching for novel therapeutics to target MDR pathogens and parasites.

This Special Issue is dedicated to integrating our current understanding with new developments in the field of sepsis, including diagnosis, pathophysiology, and novel therapeutics. We invite researchers and scientists to contribute both their original research and review articles to the Special Issue.

Potential topics include but are not limited to the following:

• State-of-the-art techniques for the early diagnosis of sepsis
• The discovery of novel biomarkers of sepsis based upon animal models or clinical samples
• Pathogenesis of sepsis at the cellular and molecular level
• Mechanistic perspectives of cytotoxicity and organ damage
• Molecular targeted sepsis therapies
• The discovery of new effective drug targets for multidrug-resistant pathogens or parasites causing sepsis
• Structure-aided drug development for control of MDR infections during sepsis