Systemic Inflammation in Severe Infectious Diseases

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Background

Hospital-acquired infections are common and often result in life-threatening complications, mostly facing critically ill patients in the intensive care unit. Patients with hospital-acquired infections may die from bacteremia/fungal/viral infection or hyperinflammatory complications because of an uncontrolled over-activation of the innate immune system with pathological levels of circulating proinflammatory cytokines, or from multiorgan failure. In addition to eliciting a robust inflammatory response, it paradoxically renders the host in an immunocompromised state at the late stage of the disease progression. Severe infectious diseases, including sepsis and septic shock are among the most common reasons for death in hospitals. Sepsis is an infection-induced syndrome characterized by a generalized inflammatory state and represents a frequent complication in surgical patients and in immunocompromised patients. Sepsis is a common, expensive, and frequently associated with a fatal outcome. Every 3 to 4 seconds somebody dies with sepsis, and it is one of the leading causes of death worldwide.

Clinical symptoms of patients suffering from infectious diseases are a culmination of complex interactions between the infecting microorganism and host immune responses. This in turns leads to an induction of overwhelming inflammatory reactions, systemic activation of the complement and coagulation systems, and impaired fibrinolysis. Currently, diagnosis relies on non-specific physiological criteria and culture-based pathogen detection. This results in diagnostic uncertainty, therapeutic delays, misuse and/or overuse of antibiotics, as well as the failure to identify patients who might benefit from immunomodulatory therapies. Traditional antibiotic treatments, however, are only able to remove the invading pathogen, but they cannot interfere with complications caused by pathologic host responses. Thus, it is obvious that there is an urgent need for novel therapeutic approaches addressing many invasive infections and sepsis.

Diagnosis- The concept of “personalized medicine” leads on to the idea of personalized or precision medicine, in which treatments are tailored to individuals. An immune biomarker is defined as any characteristic that can be objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention. Recent progress in genomics, molecular immunology and proteomics, coupled with an increasing focus on translational research, has given rise to a real expectation that we are entering an era of personalized medicine, in which non-invasive technologies are used to predict, diagnose, prevent and treat a diverse range of diseases. Nonetheless, the ability of a biomarker to distinguish between groups is measured by sensitivity, specificity and stability or similar variance estimates.

Treatment- Infections often lead to poor healing, there a risk of an unnecessary use of antibiotics that may contribute to the development of resistances and an increase in health care costs. Therefore, new knowledge on pathogenesis of infections and novel concepts dealing with innovative preventive measures are urgently needed. Moreover, there is clearly a demand for novel therapeutic strategies for sepsis, and correspondingly, also a need for increased knowledge on host defense molecules and their actions, like endogenously produced/generated proteins or peptide are interesting novel natural drug candidates against infectious diseases.

In this Research Topic, we welcome submissions in the form of Original Research articles, Reviews, Mini-Reviews, Clinical trials, and Perspectives that summarize and explore new insights focusing particularly on systemic inflammation observed in infectious diseases. We welcome manuscripts focusing on, but not limited to, the following sub-topics:

• Dysregulation of hemostatic functions in sepsis.
• Systemic modulation of inflammatory host reactions.
• Pathologic activation of complement.
• Biomarker as target for precision medicine approaches.
• Target identification for clinical therapy development.
• Dysfunctional innate immune reactions in severe infectious diseases.

Topic Editor Mukesh Pasupuleti is employed by Council of Scientific & Industrial Research, New Delhi, India. Topic Editor Julien Pottecher reports grants from LFB Biomedicaments Research grant, educational grant, advisory board (2019) during the conduct of the study; grants from Masimo Educational grant, grants from Edwards Lifesciences Educational grant, grants from AOP Orphan Educational grant, and grants from RDS Advisory board outside the scope of the Research Topic. The other Topic Editors in this editorial team declare no conflict of interest.

Keywords: Inflammation, Immunity, Biomarkers, Sepsis, Bacteria, Host Defense, Peptides, Proteins

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