Narrative review examines multimorbidity impact on sepsis morbidity and mortality outcomes

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Frontiers in Medicine Published April 29, 2026 Medically reviewed April 29, 2026 Study authors: Jhan S. Saavedra-Torres, Humberto Alejandro Nati-Castillo, Alice Gaibor-Pazmiño, Wilder Fernando Ort… DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider mechanism- and phenotype-aligned care for sepsis patients with multimorbidity including diabetes and heart failure.

This narrative review addresses sepsis in the context of multimorbidity. The scope encompasses patients with conditions such as type 2 diabetes, obesity, heart failure, cerebrovascular disease, COPD, chronic kidney disease, cancer, HIV, and severe mental illness. The authors do not report a sample size or specific setting for the synthesis or analysis.

The synthesis indicates that multimorbidity amplifies sepsis morbidity and mortality. Prevalent conditions reshape sepsis biology and outcomes. Pathophysiological mechanisms include low-grade inflammation, impaired innate and adaptive immunity, endothelial injury with immunothrombosis and NETosis, barrier disruption with dysbiosis, and neuroendocrine maladaptation. The sepsis trajectory involves an early hyperinflammatory peak followed by immunoparalysis.

Clinical risks involve increased susceptibility to secondary infection, multiorgan dysfunction, and death. Nosocomial sepsis contributes disproportionately to mortality. The authors note research needs include endotyping and trials testing mechanism-matched therapies. The source does not establish causation from primary data and lacks statistical results.

Practice relevance focuses on mechanism- and phenotype-aligned care. Recommendations include titrated fluids and vasoactives for limited cardiac or renal reserve. PK and PD optimization and timely antimicrobial de-escalation are noted for obesity and chronic kidney disease. Immune and organ monitoring along with prevention bundles for hospital-acquired sepsis and post-sepsis follow-up are suggested for clinicians.

Study Details

Study typeSystematic review

EvidenceLevel 1

PublishedApr 2026

View Original Abstract ↓

Sepsis is a leading cause of morbidity and mortality, amplified by multimorbidity. This narrative review synthesizes epidemiological, pathophysiological, and immunological evidence to show how prevalent conditions—type 2 diabetes and obesity, heart failure and cerebrovascular disease, COPD, chronic kidney disease, cancer/HIV, and severe mental illness—reshape sepsis biology and outcomes. Convergent mechanisms include low-grade inflammation, impaired innate and adaptive immunity, endothelial injury with immunothrombosis/NETosis, barrier disruption with dysbiosis, and neuroendocrine maladaptation. These processes drive an early hyperinflammatory peak followed by immunoparalysis, increasing risks of secondary infection, multiorgan dysfunction, and death. Malnutrition modulates trajectories, and nosocomial sepsis contributes disproportionately to mortality. We propose an integrative framework in which comorbidities differentially load risk across five domains—immunity/inflammation, endothelium, barriers/microbiota, neuroaxis, and immunometabolism—clarifying bedside heterogeneity and therapeutic tolerance. Clinical implications include mechanism- and phenotype-aligned care: titrated fluids and vasoactives for limited cardiac or renal reserve; PK/PD optimization and timely antimicrobial de-escalation in obesity and chronic kidney disease; and immune/organ monitoring (e.g., monocyte HLA-DR, NGAL/KIM-1). System priorities include stronger prevention bundles for hospital-acquired sepsis and post-sepsis follow-up. Research needs include endotyping and trials testing mechanism-matched therapies, alongside PK/PD studies and cohorts tracking neurocognitive and cardiometabolic outcomes. Viewing sepsis through multimorbidity enables personalized care and reduced long-term burden.