Sepsis is an important disorder in intensive care medicine, and the emphasis is not on infections but the imbalance in body reactions and life-threatening organ dysfunction. The infection, the imbalance in the body's reaction, and the deadly organ dysfunction are three aspects of sepsis. Currently, there is still a debate on suitable criteria for the diagnosis of patients with sepsis with continuing changes in the guidelines on sepsis management. Here we summarize recent advances on the definitions, diagnosis, and treatment in the clinical practice of sepsis management in the emergency department. We also highlight future research directions on sepsis. In particular, given the global outbreak of coronavirus disease 2019 (COVID-19), we briefly describe the relationship between COVID-19 and sepsis. How to manage sepsis caused by emerging pathogens such as COVID-19 is a new challenge for care professionals in the emergency department.

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