Gaps and opportunities in sepsis translational research

Infection initiates sepsis, but the clinical disease arises through the innate immune response of the host. A rapidly evolving understanding of the biology of that response has not been paralleled by the development of successful new treatment. The COVID-19 pandemic has begun to change this revealing the promise of distinct therapeutic approaches and the feasibility of new approaches to evaluate them. We review the history of mediator-targeted therapy for sepsis and explore the conceptual, biological, technological, and organizational challenges that must be addressed to enable the development of effective treatments for a leading cause of global morbidity and mortality.