Daily Ards Research Analysis
Among today’s ARDS-related findings, a mechanistic study identifies loss of IGFBP2 in alveolar type 2 cells as a driver of COVID-19-associated lung inflammation, suggesting a potential localized therapeutic strategy. A neonatal cross-sectional study highlights high prevalence of admission hypothermia and associated maternal/neonatal risk factors, linking hypothermia to mortality and ventilatory support.
Summary
Among today’s ARDS-related findings, a mechanistic study identifies loss of IGFBP2 in alveolar type 2 cells as a driver of COVID-19-associated lung inflammation, suggesting a potential localized therapeutic strategy. A neonatal cross-sectional study highlights high prevalence of admission hypothermia and associated maternal/neonatal risk factors, linking hypothermia to mortality and ventilatory support.
Research Themes
- IGF axis and epithelial inflammation in COVID-19-associated ARDS
- Risk stratification for neonatal hypothermia and early outcomes
- Cytokine/chemokine signaling in lung injury
Selected Articles
1. Alveolar epithelial type 2 cell specific loss of IGFBP2 activates inflammation in COVID-19.
IGFBP2 is markedly reduced in alveolar type 2 cells from COVID-19-ARDS lungs and associates with heightened inflammatory programs. Restoring IGFBP2 expression dampens cytokine/chemokine signaling in spike protein–injured epithelial cells, supporting IGFBP2 as a potential locally deliverable anti-inflammatory target in COVID-19.
Impact: Identifies a cell type–specific anti-inflammatory pathway in COVID-19 lung injury and proposes IGFBP2 replacement as a therapeutic concept. Integrates human tissue profiling with functional validation.
Clinical Implications: While preclinical, findings suggest that localized IGFBP2 delivery to alveolar epithelium could modulate inflammation in COVID-19-associated ARDS. This supports exploring IGFBP2-based therapies and companion biomarkers in early-phase trials.
Key Findings
- IGFBP2 mRNA is significantly downregulated in primary AEC2 from COVID-19-ARDS fibrotic regions compared with IPF alone or IPF with prior COVID-19.
- Multicolor immunohistochemistry shows reduced IGFBP2, IGF1, and IGF2 in AEC2 from COVID-ARDS, IPF, and IPF with COVID history versus donor controls.
- Lentiviral Igfbp2 expression suppresses S2 spike–induced proinflammatory genes (Tnf-α, Il1β, Il6, Stat3/6) and chemokine receptors (Ccr2, Ccr5) in mouse lung epithelial cells.
- AEC2 from COVID-ARDS patients exhibit higher TNF-α, IL-6, and CCR5 than AEC2 from IPF and IPF with COVID history.
Methodological Strengths
- Integration of human AEC2 transcriptomics with multicolor immunohistochemistry
- Functional validation via lentiviral IGFBP2 expression in spike-injured epithelial cells
Limitations
- Sample sizes and patient-level covariates are not reported in detail
- In vitro spike protein injury model may not fully recapitulate in vivo SARS-CoV-2 infection; lack of in vivo therapeutic testing
Future Directions: Quantify AEC2 IGFBP2 across larger COVID-19-ARDS cohorts, test localized IGFBP2 delivery in animal models, and evaluate safety/PK in early-phase clinical trials with biomarker-guided selection.
The coronavirus disease 2019 (COVID-19) global pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, our understanding of SARS-CoV-2-induced inflammation in alveolar epithelial cells remains very limited. The contributions of intracellular insulin-like growth factor binding protein-2 (IGFBP2) to SARS-CoV-2 pathogenesis are also unclear. In this study, we have uncovered a critical role for IGFBP2, specifically in alveolar epithelial type 2 cells (AEC2), in the immunopathogenesis of COVID-19. Using bulk RNA sequencing, we show that IGFBP2 mRNA expression is significantly downregulated in primary AEC2 cells isolated from fibrotic lung regions from patients with COVID-19-acute respiratory distress syndrome (ARDS) compared to those with idiopathic pulmonary fibrosis (IPF) alone or IPF with a history of COVID-19. Using multicolor immunohistochemistry, we demonstrated that IGFBP2 and its selective ligands IGF1 and IGF2 were significantly reduced in AEC2 cells from patients with COVID-ARDS, IPF alone, or IPF with COVID history than in those from age-matched donor controls. Further, we demonstrated that lentiviral expression of Igfbp2 significantly reduced mRNA expression of proinflammatory cytokines-Tnf-α, Il1β, Il6, Stat3, Stat6 and chemokine receptors-Ccr2 and Ccr5-in mouse lung epithelial cells challenged with SARS-CoV-2 spike protein injury (S2; 500 ng/mL). Finally, we demonstrated higher levels of cytokines-TNF-α; IL-6 and chemokine receptor-CCR5 in AEC2 cells from COVID-ARDS patients compared to the IPF alone and the IPF with COVID history patients. Altogether, these data suggest that anti-inflammatory properties of IGFBP2 in AEC2 cells and its localized delivery may serve as potential therapeutic strategy for patients with COVID-19.
2. Prevalence and associated factors of admission hypothermia among neonates admitted to the premature baby unit of a secondary care hospital in Sri Lanka: a cross-sectional analytical study.
In a single-center cross-sectional analysis of 407 neonates, admission hypothermia was prevalent (38.6%) and independently associated with teenage pregnancy, multiple pregnancy, hypertension in pregnancy, and admission age <24 hours. Hypothermia correlated with markedly higher odds of mortality and ventilatory support.
Impact: Quantifies a high burden of neonatal hypothermia and identifies actionable maternal/neonatal risk factors in a resource-limited setting, informing targeted prevention.
Clinical Implications: Strengthen thermal care immediately post-birth and during transport/admission, prioritize high-risk dyads (e.g., teenage or hypertensive pregnancies, multiples), and implement checklists to reduce hypothermia, potentially lowering mortality and ventilation needs.
Key Findings
- Admission hypothermia prevalence was 38.6% (157/407; 95% CI 33.9–43.4).
- Independent associations: admission age <24 hours (aOR 3.3, 95% CI 1.9–5.8), teenage pregnancy (aOR 8.2, 95% CI 1.8–37.2), multiple pregnancy (aOR 2.8, 95% CI 1.1–7.1), hypertension in pregnancy (aOR 2.3, 95% CI 1.2–4.7).
- Hypothermia associated with mortality (OR 5.2, 95% CI 1.8–14.6) and need for ventilatory support (OR 4.9, 95% CI 2.8–8.5).
- Significant associations with infant respiratory distress syndrome, metabolic acidosis, and neonatal jaundice.
Methodological Strengths
- Consecutive sampling and multivariable logistic regression to adjust confounding
- Clear reporting of effect sizes with 95% confidence intervals
Limitations
- Single-center retrospective record review with potential measurement and selection biases
- Cross-sectional design limits causal inference and generalizability
Future Directions: Prospective multi-center studies to validate risk factors, evaluate bundled thermal care interventions, and assess impact on survival and neurodevelopment.
BACKGROUND: Hypothermia is defined as core body temperature being below 36.5°C. This study aimed to identify the prevalence, associated factors and outcomes of hypothermia among neonates admitted to the premature baby unit (PBU) of a secondary care hospital in Nawalapitiya, Sri Lanka. METHODS: In a cross-sectional analytical study, medical records of neonates admitted to the PBU were selected retrospectively from 31 March 2022 to 1 April 2021 using consecutive sampling. The recorded axillary temperatures on admission, sociodemographic and clinical data were extracted. Following bivariate analysis, multivariable logistic regression was performed. RESULTS: Among 407 neonates, the median admission age was 1 day. The majority were male (52.6%), were term (59%) and had a normal birth weight (52.5%). The number of babies with hypothermia was 157 with a prevalence of 38.6% (95% CI: 33.9 to 43.4). Maternal factors like teenage pregnancy, multiple pregnancy, hypertension during pregnancy, premature rupture of membranes and lower-segment caesarean sections; neonatal factors like age on admission being less than 24 hours, prematurity, corrected gestational age on admission being less than 37 weeks, low birth weight, weight on admission being less than 2.5 kg and having been resuscitated at birth had statistically significant associations with hypothermia on the bivariate analysis. Hypothermia showed no significant association with the month of admission. Following multivariable analysis, age on admission being less than 24 hours (adjusted OR (aOR): 3.3, 95% CI: 1.9 to 5.8), teenage pregnancy (aOR: 8.2, 95% CI: 1.8 to 37.2), multiple pregnancy (aOR: 2.8, 95% CI: 1.1 to 7.1) and hypertension in pregnancy (aOR: 2.3, 95% CI: 1.2 to 4.7) remained statistically significant. Neonates with hypothermia had 5.2 times (95% CI: 1.8 to 14.6) odds of mortality and 4.9 times (95% CI: 2.8 to 8.5) odds of receiving ventilatory support compared with normothermic neonates. Hypothermia also showed statistically significant associations with infant respiratory distress syndrome, metabolic acidosis and neonatal jaundice. CONCLUSIONS: Nearly two out of five neonates admitted to the PBU were hypothermic. There were significant maternal and neonatal associations to be addressed. Hypothermia on admission may indicate serious neonatal morbidity and mortality.