Daily Sepsis Research Analysis
Global modeling shows sepsis cases and deaths surged in 2020–2021, reversing prior gains and highlighting rising burden among older adults and as a complication of non-infectious diseases. Integrative neonatal microbiome-metabolome data link probiotic-driven ecosystem shifts and bacterial fermentation products to late-onset sepsis risk. Preclinical work identifies dihydroartemisinin as a candidate therapy for sepsis-associated encephalopathy via microglial ferroptosis modulation.
Summary
Global modeling shows sepsis cases and deaths surged in 2020–2021, reversing prior gains and highlighting rising burden among older adults and as a complication of non-infectious diseases. Integrative neonatal microbiome-metabolome data link probiotic-driven ecosystem shifts and bacterial fermentation products to late-onset sepsis risk. Preclinical work identifies dihydroartemisinin as a candidate therapy for sepsis-associated encephalopathy via microglial ferroptosis modulation.
Research Themes
- Global sepsis epidemiology and policy prioritization
- Microbiome-metabolite signatures predicting neonatal late-onset sepsis
- Neuroinflammation and ferroptosis as targets in sepsis-associated encephalopathy
Selected Articles
1. Global, regional, and national sepsis incidence and mortality, 1990-2021: a systematic analysis.
Using GBD 2021 data across 149 million deaths and 250 million hospital admissions, the authors estimate 166 million sepsis cases and 21.4 million sepsis-related deaths (31.5% of all deaths) in 2021. Progress from 1990 to 2019 reversed in 2020–2021, with rising incidence and mortality among adults—especially those aged ≥70 years—and increasing sepsis as a complication of non-infectious underlying causes (e.g., stroke, COPD, cirrhosis).
Impact: Provides the most comprehensive, post-pandemic global update on sepsis burden, quantifying shifts by age, syndrome, and underlying causes. It reframes sepsis as a common terminal pathway of non-infectious diseases, informing policy and prevention priorities.
Clinical Implications: Guides resource allocation toward older adults and chronic disease populations, emphasizes prevention of bloodstream and lower respiratory infections (including COVID-19) in non-infectious disease care pathways, and underscores the need for surveillance systems that capture implicit sepsis.
Key Findings
- In 2021, an estimated 166 million sepsis cases and 21.4 million sepsis-related deaths occurred, accounting for 31.5% of all global deaths.
- Progress from 1990 to 2019 reversed, with a surge in sepsis burden in 2020–2021.
- Adults ≥15 years experienced increased incidence (230% since 1990) and mortality (26.3%), with 9.28 million deaths among those ≥70 years.
- Sepsis increasingly complicates non-infectious underlying causes (notably stroke, COPD, and cirrhosis).
- Bloodstream infections and lower respiratory infections (including COVID-19) are predominant infectious syndromes in sepsis-related deaths.
Methodological Strengths
- Integration of multiple data sources (cause-of-death, hospital, tissue sampling, linked records) across 4290 location-years.
- Explicit and implicit sepsis capture with age–sex–location modeling over 1990–2021.
Limitations
- Model-based estimates depend on data quality and assumptions; under-ascertainment likely in low-resource settings.
- Potential misclassification when identifying implicit sepsis from coding patterns.
Future Directions: Enhance sepsis surveillance linking hospital EHRs with vital statistics; target prevention for older adults and those with chronic non-infectious diseases; evaluate the impact of vaccination and infection control on sepsis endpoints.
2. Bacterial metabolite patterns of infants receiving multi-strain probiotics and risk of late-onset sepsis.
Leveraging a policy-driven natural experiment in VLBW infants, probiotic supplementation (B. longum subsp. infantis plus L. acidophilus) shifted gut communities toward beneficial taxa and away from nosocomial pathobionts. Notably, prior to LOS diagnosis, probiotic-exposed infants showed significantly lower concentrations of B. longum fermentation products (e.g., acetate) than matched non-LOS cases, linking metabolite signatures to imminent sepsis risk.
Impact: Integrates metagenomics and metabolomics to reveal pre-sepsis metabolic signatures and ecosystem shifts in a high-risk neonatal population, informing both mechanistic understanding and potential early-warning biomarkers.
Clinical Implications: Supports targeted microbiome monitoring and metabolite-based risk stratification for LOS in VLBW infants and suggests that probiotic strategies should consider functional metabolite outputs, not just taxonomic shifts.
Key Findings
- Unit policy to administer B. longum subsp. infantis plus L. acidophilus enabled a natural experiment (97 infants post-change, 78 pre-change; LOS cases 38 vs 32).
- Probiotic supplementation increased beneficial taxa and reduced nosocomial pathobionts such as Klebsiella spp.
- Before LOS diagnosis, probiotic-exposed infants exhibited significantly lower concentrations of B. longum fermentation products (e.g., acetate) than matched non-LOS cases.
Methodological Strengths
- Natural experiment leveraging a unit-level policy change.
- Integrated metagenomic and metabolomic profiling with matched comparisons.
Limitations
- Single-center design limits generalizability; observational nature precludes causal inference.
- Incomplete reporting of effect sizes and p-values in abstract; potential residual confounding.
Future Directions: Prospective multicenter validation of metabolite-based early warning models, mechanistic studies linking specific fermentation pathways to host immunity, and RCTs testing timing/formulation of probiotics in VLBW infants.
3. Dihydroartemisinin alleviates sepsis-associated encephalopathy by reducing microglial iron accumulation and mitochondrial dysfunction via HIF1A/HMOX1 pathway.
Dihydroartemisinin bound HIF1A, crossed the blood–brain barrier, and improved survival, sepsis scores, neuroinflammation, and cognition in CLP-induced SAE. It reduced microglial ferroptosis (lipid peroxidation, Fe2+, ROS) and mitochondrial dysfunction (TMRE, mtDNA) while downregulating HIF1A/HMOX1 and modulating SLC7A11/GPX4 in hippocampal microglia.
Impact: Identifies a mechanistic, druggable pathway—microglial ferroptosis via HIF1A/HMOX1—linking sepsis to brain dysfunction and demonstrates a repurposable compound with blood–brain barrier penetration and multi-system validation.
Clinical Implications: Positions dihydroartemisinin as a potential candidate for SAE, motivating dose-finding and safety trials, and supports ferroptosis-targeted strategies as adjuncts to sepsis care.
Key Findings
- Network pharmacology and transcriptomics identified HIF1A/HMOX1 as core DHA-related pathways; docking, MDS, and SPR confirmed strong DHA–HIF1A binding.
- LC/MS demonstrated DHA penetration into the hippocampus across the blood–brain barrier.
- In CLP-induced SAE, DHA improved survival, sepsis scores, cognitive function, and reduced neuroinflammation.
- DHA inhibited microglial ferroptosis (reduced lipid peroxidation, Fe2+, ROS) and mitochondrial dysfunction (improved TMRE, mtDNA content), with downregulation of HIF1A/HMOX1 and modulation of SLC7A11/GPX4.
Methodological Strengths
- Convergent validation across in silico (docking/MDS), biophysical (SPR), in vitro (BV2), and in vivo (CLP) systems.
- Behavioral, survival, histologic, and molecular endpoints enhance mechanistic rigor.
Limitations
- Preclinical study; human dosing, safety, and efficacy are unknown.
- Sample sizes and randomization/blinding details are not specified in the abstract.
Future Directions: Define pharmacokinetics/pharmacodynamics and optimal dosing in larger animal models, assess safety, and conduct early-phase clinical trials for SAE with ferroptosis-related biomarkers as endpoints.