Daily Sepsis Research Analysis
Multi-omics profiling in lung transplant recipients reveals a baseline immune state resembling severe COVID-19 and sepsis, linked to impaired SARS-CoV-2 mRNA vaccine responses. A mechanistic mouse study identifies acitretin as an NLRP3 inflammasome inhibitor that mitigates sepsis-induced acute lung injury. Longitudinal surveillance across 55 hospitals shows shifting epidemiology of catheter-related bacteremia toward peripheral devices, informing prevention strategies.
Summary
Multi-omics profiling in lung transplant recipients reveals a baseline immune state resembling severe COVID-19 and sepsis, linked to impaired SARS-CoV-2 mRNA vaccine responses. A mechanistic mouse study identifies acitretin as an NLRP3 inflammasome inhibitor that mitigates sepsis-induced acute lung injury. Longitudinal surveillance across 55 hospitals shows shifting epidemiology of catheter-related bacteremia toward peripheral devices, informing prevention strategies.
Research Themes
- Sepsis-like immunoparalysis and vaccine responsiveness in transplantation
- Inflammasome-targeted drug repurposing for sepsis-induced organ injury
- Healthcare-associated bacteremia surveillance and prevention priorities
Selected Articles
1. Altered baseline immunological state and impaired immune response to SARS-CoV-2 mRNA vaccination in lung transplant recipients.
Using systems immunology, the study shows that lung transplant recipients have a baseline immune state akin to sepsis and severe COVID-19 (high EN-RAGE/IL-6, low HLA-DR), and mount blunted antibody, B-cell, T-cell, and innate responses to mRNA vaccination. Single-cell and plasma analyses link these baseline features to impaired vaccine responsiveness.
Impact: This study unifies sepsis-like immunoparalysis and vaccine hyporesponsiveness in transplantation with multi-omics depth, providing mechanistic targets and stratification markers for precision immunization strategies.
Clinical Implications: Suggests individualized vaccine schedules, adjuncts (e.g., adjuvants), and immune monitoring (e.g., HLA-DR, EN-RAGE) in lung transplant recipients; informs risk assessment for infections including sepsis-like complications.
Key Findings
- Baseline immune profile in lung transplant recipients mirrors severe COVID-19/sepsis: high EN-RAGE (S100A12) and IL-6, reduced HLA-DR on monocytes/dendritic cells, impaired cytokine production, and elevated plasma microbial products.
- Single-cell RNA-seq reveals an expanded monocyte cluster with high S100A family expression and reduced cytokine/antigen presentation gene expression.
- Post-vaccination, antibody, B-cell, T-cell, and innate immune signatures are diminished compared to healthy controls.
- Integrative analysis links baseline immune dysregulation to impaired vaccine responses.
Methodological Strengths
- Multi-omics integration (plasma proteomics, single-cell RNA-seq, cellular phenotyping).
- Comparison with healthy controls and pre/post-vaccination profiling.
- Linking baseline immune states to functional vaccine responses.
Limitations
- Sample size and center-level details are not specified in the abstract, limiting assessment of generalizability.
- Observational design precludes causal inference; immunosuppressive regimens may confound associations.
Future Directions: Test immunomodulatory or adjuvant strategies to enhance vaccine responses; validate biomarkers (HLA-DR, EN-RAGE/S100A12) for risk stratification across transplant centers.
2. Modulating the NLRP3 Inflammasome: Acitretin as a potential treatment for Sepsis-induced acute lung injury.
Acitretin, a clinically used retinoid, suppresses NLRP3 inflammasome activation by blocking ASC oligomerization, thereby reducing IL-1β maturation and pyroptosis. In LPS-induced sepsis models, it mitigates acute lung injury and improves survival, with effects dependent on NLRP3/GSDMD signaling.
Impact: Demonstrates a mechanistic basis for repurposing acitretin as an inflammasome-targeted therapy in sepsis-induced lung injury, validated with genetic knockouts and transcriptomics.
Clinical Implications: While preclinical, findings support exploring acitretin in early-phase trials for sepsis-related lung injury or hyperinflammation, with careful safety and dosing evaluation.
Key Findings
- Acitretin reduced mortality and attenuated lung inflammation and edema in LPS-induced septic mice.
- Transcriptomics and in vitro assays showed suppression of the NLRP3 inflammasome pathway, with decreased IL-1β, caspase-1 p20, and GSDMD cleavage.
- Acitretin blocked ASC oligomerization and interaction with NLRP3, inhibiting inflammasome assembly.
- Protective effects were lost in Nlrp3 and Gsdmd knockout mice, confirming target dependence.
Methodological Strengths
- Convergent in vivo and in vitro evidence with dose-response testing.
- Use of Nlrp3 and Gsdmd knockout mice to establish pathway dependence.
- Transcriptome sequencing to identify and confirm pathway modulation.
Limitations
- Relies on LPS-induced models; lacks polymicrobial or CLP models of sepsis.
- No pharmacokinetic/safety data in sepsis context; clinical translatability and dosing remain unknown.
Future Directions: Validate efficacy in polymicrobial sepsis (e.g., CLP), assess lung-targeted delivery, and conduct early-phase clinical trials with biomarker-guided selection (IL-1β, inflammasome signatures).
3. Surveillance of catheter-related bacteremia in VINCat program.
A 15-year, 55-hospital surveillance cohort (10,212 CRB episodes) shows declining ICU/central-line CRB but significant increases in peripheral venous and PICC-associated bacteremia. Findings refocus prevention on peripheral devices, especially in non-ICU wards.
Impact: High-quality, multicenter longitudinal surveillance identifies a shift toward peripheral-device bacteremia, directly informing infection prevention priorities and sepsis reduction strategies.
Clinical Implications: Implement targeted bundles for peripheral IVs and PICCs (asepsis, dwell time, securement, surveillance) in non-ICU settings; sustain central-line bundle adherence in ICUs.
Key Findings
- 55 hospitals (2008–2023) reported 10,212 nosocomial CRB episodes; overall incidence 0.21/1000 patient-days (ICU 1.13; medical 0.16; surgical 0.15).
- Gram-positive organisms caused 68.3% of CRB episodes.
- ICU-acquired and central venous catheter-associated CRB rates decreased over time, while peripheral venous catheter and PICC-associated CRB significantly increased (p<0.001).
Methodological Strengths
- Large, multicenter, longitudinal surveillance with standardized incidence metrics.
- Stratified analyses across care areas and device types with IRR comparisons.
Limitations
- Surveillance data may be affected by underreporting or changes in diagnostics and documentation over time.
- Limited patient-level covariates restrict adjustment for confounders and severity.
Future Directions: Develop and evaluate PVC/PICC-specific prevention bundles and monitor outcomes with standardized metrics; explore device- and unit-level risk factors.