Daily Ards Research Analysis
Three studies advance ARDS-related science across discovery and clinical care. An in silico repurposing screen nominates TGFBR1 inhibitors for ARDS, a COVID-19 ARDS ECMO cohort quantifies high mortality with age as the key predictor, and a pediatric Omicron cohort identifies CT (CO-RADS), PELOD-2, and AST as predictors of poor outcomes.
Summary
Three studies advance ARDS-related science across discovery and clinical care. An in silico repurposing screen nominates TGFBR1 inhibitors for ARDS, a COVID-19 ARDS ECMO cohort quantifies high mortality with age as the key predictor, and a pediatric Omicron cohort identifies CT (CO-RADS), PELOD-2, and AST as predictors of poor outcomes.
Research Themes
- Therapeutic target discovery and drug repurposing in ARDS
- ECMO outcomes and prognostication in COVID-19 ARDS
- Risk stratification in severe pediatric SARS-CoV-2 infection
Selected Articles
1. Computational Drug Repurposing Screening Targeting Profibrotic Cytokine in Acute Respiratory Distress Syndrome.
The study prioritizes TGFBR1 as a therapeutic target in ARDS and identifies candidate inhibitors via ligand-based virtual screening and molecular docking, including two FDA-approved drugs (galunisertib, vactosertib) and several analogs. Docking suggested strong binding for DB08387 and CHEMBL14297639, and ADME filtering supported their drug-like profiles, motivating experimental validation.
Impact: Introduces a plausibly druggable pathway (TGF-β/TGFBR1) for ARDS with concrete repurposing candidates, potentially accelerating translational pipelines.
Clinical Implications: No immediate practice change; suggests testing TGFBR1 inhibitors (e.g., galunisertib, vactosertib) in preclinical ARDS models before considering early-phase trials.
Key Findings
- TGFBR1 was prioritized as a major ARDS target using STRING and KEGG pathway analyses.
- Galunisertib and vactosertib, two FDA-approved drugs, were nominated as repurposing candidates.
- Ligand-based virtual screening identified seven additional candidates; DB08387 and CHEMBL14297639 showed the strongest docking affinities with key hydrogen bonds.
- ADME screening supported acceptable drug-like properties for most candidates, with limited CYP inhibition for CHEMBL14297639.
Methodological Strengths
- Integrated multi-database target prioritization (STRING, KEGG) with docking and ADME filtering
- Inclusion of FDA-approved agents to accelerate translational feasibility
Limitations
- Purely in silico; no biochemical, cellular, or in vivo validation
- Docking affinity may not translate to efficacy or safety in ARDS
- Potential off-target and pharmacodynamic uncertainties in acute critical illness
Future Directions: Validate TGFBR1 inhibition in ARDS-relevant in vitro (alveolar epithelial/endothelial) and in vivo injury models; assess pharmacodynamics, safety, and timing of intervention; explore structure–activity optimization.
Acute Respiratory Distress Syndrome (ARDS) is a severe lung disease with a high fatality rate and few treatment options. Targeting certain signalling pathways, notably the Transforming Growth Factor-beta (TGF-beta) signalling pathway, has emerged as a promising option for ARDS therapy. We identified TGF-beta Receptor 1 (TGFBR1) as a major target for ARDS treatment using the STRING and KEGG databases and validated TGFBR1's critical function in the TGF-beta signalling pathway, which is important in ARDS pathogenesis. To find prospective TGFBR1 inhibitors, we selected two FD
2. Experience with ECMO therapy for acute respiratory distress syndrome treatment throughout the COVID-19 pandemic.
In a single-center cohort of 81 COVID-19 ARDS patients on ECMO, in-hospital mortality was 75%. Multivariable analysis identified age as the only independent predictor of death (OR 1.24 per year). Among survivors, 40% reported respiratory or motor sequelae limiting return to normal life at follow-up up to 18 months.
Impact: Provides real-world mortality and prognostic data for ECMO in COVID-19 ARDS across multiple pandemic waves, informing selection and counseling.
Clinical Implications: Supports careful age-informed selection and emphasizes need for structured post-ICU rehabilitation given high sequelae burden among survivors.
Key Findings
- Among 81 ECMO-treated COVID-19 ARDS patients, in-hospital mortality was 75%.
- Age was the only independent predictor of mortality in multivariable analysis (OR 1.24; 95% CI 1.027–1.5; P=0.025).
- Mortality was higher during pandemic waves 2, 3, and 6.
- At up to 18 months follow-up, no deaths occurred post-discharge, but 40% had respiratory or motor sequelae.
Methodological Strengths
- Covers multiple pandemic waves with consistent data capture
- Multivariable modeling to identify independent predictors and post-discharge functional follow-up
Limitations
- Single-center retrospective design without a comparator group
- Potential temporal confounding across waves and selection bias for ECMO
- Limited power for wave-specific analyses
Future Directions: Prospective, multicenter registries to refine selection criteria, integrate age and comorbidity risk, and evaluate standardized post-ICU rehabilitation pathways.
OBJECTIVE: To analyze our experience with extracorporeal membrane oxygenation (ECMO) therapy for acute respiratory distress syndrome (ARDS) treatment during the COVID-19 pandemic. DESIGN: Retrospective, observational, single center study. SETTING: Third-level hospital in Spain. PATIENTS: Adult patients with COVID-19 ARDS treated with an ECMO system in our center between March 2020 and March 2023. INTERVENTIONS: Retrospective collection of variables during hospital admission and follow-up. MAIN VARIABLES OF INTEREST: Demograph
3. Characteristics and outcomes in severe and critically ill children with first wave SARS-CoV-2 Omicron infection in Northeast China.
In 38 severe/critical pediatric Omicron cases, respiratory failure was common (66%), ARDS occurred in 16%, and 47% required IMV. CO-RADS-based chest CT score independently predicted IMV, while PELOD-2 and admission AST predicted death or prolonged PICU stay.
Impact: Identifies actionable imaging and clinical predictors for escalation and outcomes in severe pediatric SARS-CoV-2, aiding triage during surges.
Clinical Implications: Incorporating CO-RADS CT scoring with PELOD-2 and AST at admission may improve early risk stratification and ventilatory planning in pediatric severe COVID-19.
Key Findings
- Among 38 cases, 66% had respiratory failure and 16% developed ARDS.
- 47% required invasive mechanical ventilation.
- CO-RADS chest CT score independently predicted need for IMV (OR 2.781; 95% CI 1.021–7.571).
- PELOD-2 score and admission AST independently predicted death or prolonged PICU stay.
Methodological Strengths
- Use of multivariable logistic regression to adjust for confounding
- Clearly defined primary and secondary outcomes with objective imaging and laboratory predictors
Limitations
- Single-center with a small sample size limiting precision
- First-wave Omicron period only; limited generalizability to other variants and care phases
- Only a minority had ARDS, reducing power for ARDS-specific inference
Future Directions: External validation of CO-RADS, PELOD-2, and AST thresholds in larger multicenter pediatric cohorts and integration into pragmatic triage tools.
AIM: To describe the characteristics of severe and critically ill children with first-wave SARS-CoV-2 Omicron infection admitted to the pediatric intensive care unit (PICU) at the National Children's Regional Medical Center in Northeast China and to explore factors associated with poor outcomes. METHODS: This observational cohort study was conducted in a PICU in northeastern China and included children under 18 years of age who were severely and critically ill due to SARS-CoV-2 Omicron infection between December 2022 and February 2023. Patients were categorized into two groups: the invasive mechanical ventilation (IMV) group and the non-IMV group. The primary outcome measured was the need for IMV, while secondary outcomes included death or prolonged PICU stay. Univariate and multivariate logistic regression analyses were performed to identify risk factors for poor outcomes. RESULTS: A total of 38 severe and critically ill children were included in the study. Of these, 25 (66%) were diagnosed with respiratory failure, and four (16%) developed acute respiratory distress syndrome. Additionally, 21 (55%) were diagnosed with COVID-19-associated neurological disorders, and 18 (47%) received IMV. Multivariate logistic regression analysis identified the chest computed tomography (CT) score, based on the COVID-19 Risk Assessment and Diagnosis System (CO-RADS), was statistically significant as an independent predictor for IMV in severe and critically ill children (odds ratio [OR]: 2.781 [95% confidence interval (CI): 1.021-7.571]). Furthermore, the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score and serum aspartate aminotransferase (AST) levels at admission were found to be independent predictors of death or prolonged PICU stay. CONCLUSIONS: Respiratory failure and COVID-19-associated neurological disorders were the most common complications among severe and critically ill children with first-wave SARS-CoV-2 Omicron infection. Chest CT score, PELOD-2 score, and serum AST levels may serve as important indicators of poor outcomes in this patient population.