Daily Ards Research Analysis
Electrical impedance tomography shows broadly similar regional lung mechanics between COVID-19-associated ARDS and non-COVID ARDS, suggesting convergent ventilator strategies. Translational analyses identify mitochondrial-related blood biomarkers (SLC2A1, IFI27) for ARDS, while a large multicenter validation confirms the ARC (Age, day-3 NLR, day-3 CRP) score predicts 28-day mortality in hospitalized COVID-19.
Summary
Electrical impedance tomography shows broadly similar regional lung mechanics between COVID-19-associated ARDS and non-COVID ARDS, suggesting convergent ventilator strategies. Translational analyses identify mitochondrial-related blood biomarkers (SLC2A1, IFI27) for ARDS, while a large multicenter validation confirms the ARC (Age, day-3 NLR, day-3 CRP) score predicts 28-day mortality in hospitalized COVID-19.
Research Themes
- Convergence of lung mechanics in COVID-19 vs non-COVID ARDS
- Mitochondria-related blood biomarkers for ARDS diagnosis
- External validation of pragmatic mortality risk scoring in COVID-19
Selected Articles
1. Comparison of regional lung mechanics using electrical impedance tomography in mechanically ventilated COVID-19 vs pre-pandemic patients: A retrospective study.
In 259 ICU patients undergoing EIT, regional dynamics (compliance, overdistension, collapse) were broadly similar between COVID-ARDS and non-COVID ARDS after mixed-effects adjustment. Findings argue against distinct ventilator phenotypes requiring different PEEP targets solely based on COVID status.
Impact: Addresses a central debate on whether COVID-ARDS is physiologically distinct, using bedside imaging across PEEP levels with rigorous modeling. Negative yet decisive findings can harmonize ventilator strategies.
Clinical Implications: Ventilator settings (e.g., PEEP titration) may be guided by EIT-derived parameters similarly in COVID and non-COVID ARDS, focusing on minimizing overdistension and collapse rather than etiology.
Key Findings
- Dynamic compliance, overdistension, and collapse patterns were similar between COVID-19 and non-COVID ARDS on EIT.
- Visual inspection suggested higher overdistension in COVID-19 early and late, but mixed-effects modeling showed no significant difference (estimate −1.0%, p=0.459).
- Results support applying comparable ventilation protocols irrespective of COVID status.
Methodological Strengths
- Use of bedside electrical impedance tomography across PEEP levels with polynomial visualization and mixed-effects modeling.
- Inclusion of sizable cohorts (131 COVID, 128 non-COVID) spanning a decade of ICU practice.
Limitations
- Retrospective design with potential selection bias (only patients who underwent EIT).
- Physiological endpoints only; no linkage to hard clinical outcomes such as mortality or ventilator-free days.
Future Directions: Prospective trials should test EIT-guided PEEP titration protocols across ARDS etiologies and evaluate clinical outcomes (mortality, ventilator-free days).
BACKGROUND: Whether coronavirus disease 2019 acute respiratory distress syndrome (COVID-ARDS) and acute respiratory distress syndrome (ARDS) have a different phenotype remains subject of research and debate. We aimed to study the differences and similarities of electrical impedance tomography (EIT) parameters in patients with and without COVID-19. METHODS: This retrospective observational study included patients with an EIT measurement during ICU admission. EIT variables, including dynamic compliance, alveolar overdistension and collapse, were visualized for each positive end-expiratory pressure (PEEP) level of the EIT measurement using polynomial regression. Two-level linear mixed-effects regression with random intercept and slope for PEEP was performed for alveolar overdistension per PEEP level during EIT measurement in COVID-19 and non-COVID-19 patients. RESULTS: From October 2013 until October 2023, 131 COVID-19 patients and 128 non-COVID-19 patients underwent an EIT measurement. The overall pattern of dynamic compliance, alveolar overdistension and collapse was similar in COVID-19 and non-COVID-19 patients. Visual inspection of EIT variables showed a higher mean alveolar overdistension in COVID-19 patients compared to the non-COVID-19 patients (day 1-3: maximum 43.2 % vs maximum 26.1 %, day 4-6: maximum 46.8 % vs maximum 25.2 %, ≥7 days: maximum 41.4 % vs maximum 33.0 %). However, two-level linear mixed-effects regression with random intercept and slope for PEEP showed no statistically significant difference between COVID-19 and non-COVID-19 patients (-1.0 % [-3.5; 1.6], p = 0.459). CONCLUSIONS: Regional lung dynamics were generally comparable in COVID-19 and non-COVID-19 patients when assessed by EIT. Based on these findings, mechanical ventilation protocols should be optimized for comparable parameters in COVID-19 and non-COVID-19 patients.
2. Identification of mitochondria-related biomarkers for acute respiratory distress syndrome.
Integrative transcriptomic analyses across sepsis-ARDS vs sepsis-non-ARDS prioritized 20 mitochondria-related DEGs and highlighted monocyte subsets. SLC2A1 and IFI27 emerged as candidate blood biomarkers, especially within CD14+ monocytes, with upregulated mRNA in sepsis patients compared to healthy controls.
Impact: Proposes mitochondria-linked, blood-based biomarkers for ARDS with cell-type specificity, advancing diagnostic development and pathobiological understanding.
Clinical Implications: If validated, peripheral blood SLC2A1 and IFI27 could enable earlier ARDS detection or enrichment of high-risk sepsis patients for trials, supporting precision diagnostics.
Key Findings
- Intersection of 2030 MRGs with 343 DEGs identified 20 mitochondria-related DEGs enriched in mitochondrial pathways.
- Monocytes (especially CD14+ subset) emerged as key cell types with differential expression of IFI27 and SLC2A1 in ARDS.
- Peripheral blood mRNA levels of IFI27 and SLC2A1 were upregulated in sepsis patients compared with healthy controls.
Methodological Strengths
- Integrative multi-gene prioritization linking ARDS status to mitochondria-related pathways.
- Cell-type–aware analysis highlighting monocyte subsets with orthogonal mRNA validation in patient blood.
Limitations
- Sample sizes and external multicenter validation are not specified; diagnostic performance metrics (e.g., AUC) are not reported.
- Cross-sectional design limits causal inference and temporal dynamics of biomarker expression.
Future Directions: Prospective, multicenter studies should quantify diagnostic performance (AUC, sensitivity/specificity), assess prognostic value, and test assay feasibility in clinical workflows.
Mitochondria-related genes (MRGs) are considered screening MRGs as biomarkers for important therapeutic targets, but their role in acute respiratory distress syndrome (ARDS) remains unclear. This study aimed to identify MRGs-related biomarkers for ARDS. Intersection of 2030 MRGs with 343 differentially expressed genes (DEGs) between sepsis-non-ARDS and sepsis-ARDS group yielded 20 MRGs-related DEGs enriched in mitochondrion-related pathways. Monocytes, T cells, natural killer (NK) T cells, NK cells, and innate lymphoid cells (ILCs) were screened as candidate key cell types. SLC2A1 and IFI27 were defined as biomarkers; naive B cells, resting NK cells, and naive CD4 T cells, as differential immune cells; and monocytes, as the key cell type, subdivided into the CD14 and CD16 subtypes. The sepsis-ARDS group exhibited enhanced CD14 Mono and B cells compared with the sepsis-non-ARDS group and CD16 had a higher percentage and score in the G2/M and S phases than CD14. IFI27 and SLC2A1 were mainly expressed differently in the CD14 monocytes in ARDS, and their mRNA expression levels in peripheral blood of the sepsis patients was upregulated compared with those of the healthy controls. Thus, our findings demonstrate that SLC2A1 and IFI27 represent novel MRGs-related diagnostic biomarkers for ARDS, providing theoretical references for its treatment.
3. Validation of the age, neutrophil to lymphocyte ratio, C reactive protein score on 28 day mortality in the National COVID cohort collaborative.
In 9,708 dexamethasone-treated hospitalized COVID-19 patients from the N3C, the ARC score using age, day-3 neutrophil-to-lymphocyte ratio, and day-3 CRP predicted 28-day mortality with AUC 0.77 and consistent performance across variants.
Impact: Provides large-scale, multicenter external validation of a simple, implementable mortality risk score relevant to severe COVID-19, a common ARDS precursor.
Clinical Implications: ARC scoring on hospital day 3 can stratify mortality risk to guide monitoring intensity, escalation decisions, and trial enrichment among hospitalized COVID-19 patients.
Key Findings
- Validated the ARC score (Age, day-3 NLR, day-3 CRP) in 9,708 hospitalized COVID-19 patients receiving dexamethasone.
- Achieved AUC 0.77 (95% CI 0.74–0.79) for predicting 28-day mortality.
- Performance was consistent across SARS-CoV-2 variants of concern.
Methodological Strengths
- Large, multicenter retrospective cohort (N=9,708) with training/validation cohorts.
- Consistent performance across viral variants, enhancing generalizability.
Limitations
- Restricted to patients treated with dexamethasone and requiring day-3 labs, limiting applicability to early triage.
- Retrospective EHR-based design; unmeasured confounding and treatment biases may persist.
Future Directions: Prospective implementation studies should test ARC-guided care pathways and evaluate causal impact on outcomes, and assess utility in ARDS-enriched cohorts.
Identifying patients at high mortality risk can improve outcomes in SARS-CoV-2 pneumonia (COVID-19). We validate a prognostic model for mortality in patients hospitalized with COVID-19 receiving dexamethasone using a retrospective multi-centered study. This is a retrospective cohort study using the National COVID Cohort Collaborative (NC3) including 9,708 adult patients admitted for COVID-19 who received dexamethasone within 24 h of admission and remained hospitalized for 72 h. Previous work from a single-center cohort informed selection of prognostic variables including Age, day 3 neutrophil-lymphocyte Ratio, and day 3 C-reactive protein level (ARC Score). Variables from the development cohort were analyzed in a training cohort, and the resulting model was tested in a validation cohort. Age and day 3 measures of the neutrophil-lymphocyte ratio and C-reactive protein level were included in a logistic regression model to predict 28-day mortality. The 28-day mortality in this patient population was 15.4%. The area under the curve for the ARC model was 0.77 (95% confidence interval, 0.74-0.79). The Age, neutrophil-lymphocyte Ratio, and C-reactive protein (ARC) score identifies COVID-19 patients with a high risk of mortality within 28 days of hospitalization using clinical information on day 3 of hospitalization. ARC scores perform well across all variants of concern.