{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:25:19Z","timestamp":1792121119503,"version":"4.4.0"},"reference-count":124,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>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\u2014type 2 diabetes and obesity, heart failure and cerebrovascular disease, COPD, chronic kidney disease, cancer\/HIV, and severe mental illness\u2014reshape 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\u2014immunity\/inflammation, endothelium, barriers\/microbiota, neuroaxis, and immunometabolism\u2014clarifying 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.<\/jats:p>","DOI":"10.3389\/fmed.2026.1827818","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:58:22Z","timestamp":1777373902000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Sepsis in multimorbidity: a domain-based framework for systemic vulnerability and precision care"],"prefix":"10.3389","volume":"13","author":[{"given":"Jhan S.","family":"Saavedra-Torres","sequence":"first","affiliation":[{"name":"Grupo de Investigaci\u00f3n en Educaci\u00f3n y Salud (GINEYSA), Facultad de Salud, Universidad Santiago de Cali","place":["Cali, Colombia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Humberto Alejandro","family":"Nati-Castillo","sequence":"additional","affiliation":[{"name":"Grupo de Investigaci\u00f3n en Educaci\u00f3n y Salud (GINEYSA), Facultad de Salud, Universidad Santiago de Cali","place":["Cali, Colombia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Gaibor-Pazmi\u00f1o","sequence":"additional","affiliation":[{"name":"One Health Research Group, Universidad de Las Am\u00e9ricas","place":["Quito, Ecuador"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilder Fernando","family":"Ortiz Erazo","sequence":"additional","affiliation":[{"name":"Interinstitutional Group on Internal Medicine (GIMI 1), Department of Internal Medicine, Universidad Libre","place":["Cali, Colombia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Alejandra","family":"Mart\u00ednez Casta\u00f1o","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias de la Salud, Universidad del Quind\u00edo","place":["Armenia, Colombia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristhian Camilo","family":"Nieto Brandon","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias de la Salud, Universidad del Quind\u00edo","place":["Armenia, Colombia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana Catalina","family":"Parra Ramos","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias de la Salud, Universidad del Quind\u00edo","place":["Armenia, Colombia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Villamil","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias de la Salud, Corporacion Universitaria Alexander von Humboldt","place":["Armenia, Colombia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"S\u00e1nchez S.","sequence":"additional","affiliation":[{"name":"One Health Research Group, Universidad de Las Am\u00e9ricas","place":["Quito, Ecuador"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9s","family":"L\u00f3pez-Cort\u00e9s","sequence":"additional","affiliation":[{"name":"Cancer Research Group, Universidad de las Am\u00e9ricas","place":["Quito, Ecuador"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan S.","family":"Izquierdo-Condoy","sequence":"additional","affiliation":[{"name":"One Health Research Group, Universidad de Las Am\u00e9ricas","place":["Quito, Ecuador"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"e48307","DOI":"10.1371\/journal.pone.0048307","article-title":"Chronic medical conditions and risk of Sepsis","volume":"7","author":"Wang","year":"2012","journal-title":"PLoS One"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1007\/s40520-019-01375-4","article-title":"Infections in the older 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