Staging and Personalized Intervention for Infection and Sepsis

Background: Sepsis is defined as a dysregulated host response to infection, resulting in life-threatening organ dysfunction. It is now understood that this dysregulation not only constitutes excessive inflammation, but also sustained immune suppression. Immune-modulatory therapies thus have great potential for novel sepsis therapies. Here, we provide a review of biomarkers and functional assays designed to immunologically stage patients with sepsis as well as therapies designed to alter the innate and adaptive immune systems of patients with sepsis beneficially. Methods: A search of PubMed/MEDLINE and clinicaltrials.gov was performed between October 1, 2019 and December 22, 2019 using search terms such as "sepsis immunotherapy," "sepsis biomarkers," "sepsis clinical trials," and variations thereof. Results: Despite more than 30 years of research, there is still no Food and Drug Administration (FDA)-cleared biomarker that has proven to be effective in either identifying patients with sepsis who are at an increased risk of adverse outcomes or responsive to specific interventions. Similarly, past clinical trials investigating new treatment strategies have rarely stratified patients with sepsis. Overall, the results of these trials have been disappointing. Novel efforts to properly gauge an individual patient's immune response and choose an appropriate immunomodulatory agent based on the results are underway. Conclusion: Our evolving understanding of the different mechanisms perturbing immune homeostasis during sepsis strongly suggests that future successes will depend on finding the right therapy for the right patient and administering it at the right time. For such a personalized medicine approach, novel biomarkers and functional assays to properly stage the patient with sepsis will be crucial. The growing repertoire of immunomodulatory agents at our disposal, as well as re-appraisal of agents that have already been tested in unstratified cohorts of patients with sepsis, may finally translate into successful treatment strategies for sepsis.