Daily Respiratory Research Analysis
Three impactful studies span mechanistic immunology, biomarker-driven prognosis, and infection control. Interstitial macrophages were shown to restrain SARS-CoV-2 via type I interferon signaling in a rigorous preclinical study. In clinical domains, soluble Galectin-9 and TIM-3 stratified cancer mortality risk in obstructive sleep apnea, and a time-series analysis showed hospital masking alone was insufficient to sustain near-zero health care–associated respiratory viral infections post-pandemic.
Summary
Three impactful studies span mechanistic immunology, biomarker-driven prognosis, and infection control. Interstitial macrophages were shown to restrain SARS-CoV-2 via type I interferon signaling in a rigorous preclinical study. In clinical domains, soluble Galectin-9 and TIM-3 stratified cancer mortality risk in obstructive sleep apnea, and a time-series analysis showed hospital masking alone was insufficient to sustain near-zero health care–associated respiratory viral infections post-pandemic.
Research Themes
- Tissue-resident macrophage regulation of respiratory viral pathogenesis
- Immune checkpoint biomarkers linking sleep apnea hypoxemia to cancer outcomes
- Hospital infection control policies and health care–associated respiratory viral infections
Selected Articles
1. Nerve- and airway-associated interstitial macrophages mitigate SARS-CoV-2 pathogenesis via type I interferon signaling.
In a mouse model of SARS-CoV-2, depletion of nerve- and airway-associated interstitial macrophages caused uncontrolled viral spread, hyperinflammation, and 100% mortality. NAM-intrinsic type I interferon receptor signaling was essential to limit inflammation and viral dissemination, highlighting NAMs as key tissue-resident regulators of coronavirus pathogenesis.
Impact: This study uncovers a cell-type–specific interferon mechanism by tissue-resident macrophages that restrains SARS-CoV-2 pathogenesis, offering a precise target for host-directed therapy. It advances fundamental understanding of local immune regulation in viral pneumonia.
Clinical Implications: Therapeutic strategies that preserve or augment NAM IFNAR signaling may mitigate severe COVID-19 by limiting lung viral dissemination and hyperinflammation. Conversely, interventions that broadly suppress type I IFN signaling in the lung could be harmful.
Key Findings
- NAM depletion in mice led to enhanced lung viral spread, heightened inflammation, and 100% mortality after MA-10 infection.
- Control mice restricted viral distribution and survived, indicating a protective role of NAMs.
- NAM-intrinsic type I interferon receptor (IFNAR) signaling was critical for limiting inflammation and viral dissemination.
Methodological Strengths
- Use of a mouse-adapted SARS-CoV-2 strain with targeted depletion of NAMs to assess causal roles.
- Cell-type–specific interrogation of IFNAR signaling to define mechanisms limiting inflammation and viral spread.
Limitations
- Findings are from mouse models using a mouse-adapted strain and may not fully translate to humans.
- Human validation and therapeutic modulation of NAMs/IFNAR signaling were not tested.
Future Directions: Validate NAM phenotypes and IFNAR signaling in human lung tissues during COVID-19 and test strategies to selectively boost NAM antiviral programs without exacerbating inflammation.
2. Immune Checkpoint Biomarkers Galectin-9 and TIM-3 Predict Melanoma and Lung Cancer Mortality in Obstructive Sleep Apnoea.
Across three cohorts (n=684), higher plasma sGalectin-9 and sTIM-3 identified severe OSA patients with melanoma or lung cancer at increased mortality risk. In vitro and ex vivo data indicated intermittent hypoxia upregulates these checkpoints, correlating with inflammation and reduced T-cell proliferation/infiltration, linking OSA hypoxemia to tumor immune evasion.
Impact: Introduces immune checkpoint biomarkers for prognostic stratification in OSA-related cancer, supported by mechanistic data linking hypoxemia to immune suppression.
Clinical Implications: sGalectin-9 and sTIM-3 could guide risk stratification and prioritization of aggressive OSA management and cancer surveillance. They may also inform selection for immunomodulatory strategies, pending validation.
Key Findings
- In severe OSA with melanoma or lung cancer, higher sGalectin-9 and sTIM-3 associated with tumor aggressiveness and increased mortality risk.
- Biomarker levels were higher in severe OSA across three cohorts; monocyte intracellular Galectin-9 and T-cell membrane TIM-3 were upregulated.
- Intermittent hypoxia induced biomarker expression, positively correlated with inflammatory mediators and inversely with T-cell proliferation/infiltration.
Methodological Strengths
- Prospective multicohort design with consistent biomarker assessments across cohorts.
- Mechanistic support via in vitro and ex vivo models linking intermittent hypoxia to biomarker upregulation and immune effects.
Limitations
- Observational design limits causal inference and generalizability to all OSA populations.
- Optimal clinical cut-offs and integration with existing prognostic models were not established.
Future Directions: Validate prognostic thresholds in larger, diverse cohorts; test whether biomarker-guided OSA treatment intensity or cancer therapies improve outcomes.
3. Trends in health care-associated non-SARS-CoV-2 respiratory viral infections in conjunction with masking policies during and after the COVID-19 pandemic: A time-series analysis.
Across two hospitals (2016–2024), HA-RVI dropped to near-zero during universal masking plus other measures, but rebounded postpandemic when other measures were withdrawn, despite continued masking. Interrupted time-series showed an immediate decrease with combined measures and an immediate, sustained increase after stand-down, indicating masking alone was insufficient.
Impact: Provides long-horizon, policy-relevant evidence that hospital masking, without accompanying measures, does not sustain near-zero HA-RVI rates postpandemic.
Clinical Implications: Hospitals should consider layered infection-prevention strategies (e.g., symptom screening, ventilation, cohorting, testing) rather than relying on masking alone to control non–SARS-CoV-2 respiratory viruses.
Key Findings
- HA-RVI rates fell to near-zero during universal masking combined with other mitigation measures.
- Postpandemic, with other measures stood down but masking continued, HA-RVI rebounded with an immediate and increasing trend.
- Interrupted time-series confirmed immediate level changes at both the introduction and withdrawal of broader measures.
Methodological Strengths
- Longitudinal dataset spanning pre-, during-, and postpandemic periods across two hospitals.
- Use of interrupted time-series analysis to assess immediate and trend effects of policy changes.
Limitations
- Ecological design with potential confounding from unmeasured concurrent changes.
- Lack of pathogen-specific breakdown and limited generalizability beyond the two hospitals.
Future Directions: Quantify contributions of specific interventions (ventilation, testing, cohorting) and evaluate optimized, layered bundles to sustainably reduce HA-RVI.