Clinical Scorecard: Evaluating Biomarkers of Host Resistance, Disease Tolerance, and Tissue Damage in Human Sepsis: A Prospective Cohort Investigation
At a Glance
Category
Detail
Condition
Sepsis
Key Mechanisms
Host resistance (immune response to reduce pathogen load), disease tolerance (tissue-protective stress responses and metabolic adaptations), and tissue damage (injury from pathogen or immune response)
Target Population
Adults with community-onset sepsis meeting Sepsis-3 criteria
Care Setting
Emergency department and tertiary care center
Key Highlights
Biomarkers grouped into host resistance, disease tolerance, and damage signatures are associated with 90-day mortality and sepsis subtypes.
The sepsis subtype with highest mortality showed low disease tolerance and high tissue damage.
Disease tolerance-targeted strategies may complement traditional host resistance-focused sepsis care.
Guideline-Based Recommendations
Diagnosis
Use Sepsis-3 criteria within 6 hours of ED presentation for sepsis identification.
Measure plasma and urinary biomarkers linked to host resistance, disease tolerance, and damage for mechanistic insights.
Management
Continue early antimicrobial administration, source control, and organ support as standard care.
Consider development and future use of disease tolerance-targeted therapies alongside host resistance approaches.
Monitoring & Follow-up
Monitor biomarkers such as IL-6, IL-8, IL-10, Ang-1, Ang-2, Syndecan-1, HMGB1, and [TIMP-2]·[IGFBP7] to assess host response domains.
Assess clinical sepsis subtypes using tools like SENECA to stratify risk and tailor management.
Risks
High tissue damage and low disease tolerance signatures are associated with increased mortality risk.
Heterogeneity in sepsis biology may limit response to uniform treatments.
Patient & Prescribing Data
Adults with community-onset sepsis receiving emergency care
Current treatments focus on antimicrobial and organ support; biomarker signatures may guide future personalized therapies targeting disease tolerance mechanisms.
Clinical Best Practices
Apply structured expert consensus to categorize biomarkers into mechanistic domains for better understanding of sepsis heterogeneity.
Use early identification and biomarker measurement within 6 hours of ED presentation to inform prognosis.
Incorporate sepsis subtyping (e.g., SENECA) to identify patients at higher risk and tailor interventions accordingly.
by Arnab Chowdhury, Rachel E. Powell, Jason N. Kennedy, Kelly L. Urbanek, Derek C. Angus, Chung-Chou H. Chang, Lu Tang, Sebastian Weis, Michael Bauer, Manu Shankar-Hari, Christopher W. Seymour
