Daily Respiratory Research Analysis
Analyzed 255 papers and selected 3 impactful papers.
Summary
Real‑world comparative effectiveness data show nirsevimab at birth reduces 6‑month RSV-related LRTI hospitalizations versus maternal RSVpreF vaccination, with maternal protection approaching nirsevimab when given ≥8 weeks pre‑delivery. Two mechanistic studies advance respiratory science: platelet–leukocyte P‑selectin/PSGL‑1 interactions drive MMP‑mediated tissue damage in tuberculosis, and human iPSC‑derived respiratory organoids identify ICAM‑1 and nucleolin as key RSV host factors whose dual inhibition lowers infection efficiency.
Research Themes
- RSV prevention strategies: monoclonal antibody vs maternal vaccination
- Host–pathogen mechanisms driving lung injury (TB and RSV)
- Translational models (human organoids) to nominate antiviral targets
Selected Articles
1. Effectiveness of nirsevimab immunisation after birth versus RSVpreF maternal vaccination in preventing RSV-related hospitalisations in infants: a population-based retrospective cohort study.
In a national matched cohort of 84,196 infants, nirsevimab administered at birth was associated with a 22% reduction in the odds of RSV-related LRTI hospitalization by 6 months compared with maternal RSVpreF vaccination overall. When maternal RSVpreF was given ≥8 weeks before delivery, effectiveness approached that of nirsevimab.
Impact: This comparative-effectiveness study directly informs national RSV prevention policy by quantifying trade-offs between two approved strategies and highlighting critical timing for maternal vaccination.
Clinical Implications: Prefer nirsevimab at birth for broad protection; if using maternal RSVpreF programs, target vaccination ≥8 weeks before expected delivery to optimize infant protection. Health systems can tailor supply and scheduling based on these data.
Key Findings
- Matched cohort (42,098 per group) showed lower RSV LRTI hospitalization with nirsevimab vs maternal RSVpreF (adjusted OR 0.78, 95% CI 0.70–0.86).
- Maternal RSVpreF administered ≥8 weeks before delivery yielded no significant difference versus nirsevimab (OR 1.01, 95% CI 0.77–1.32).
- Findings robust across subgroups and propensity score adjustment.
Methodological Strengths
- Large, population-based dataset with rigorous matching on birth date, region, and sex
- Propensity score adjustment and timing-stratified secondary analyses
Limitations
- Observational design with potential residual confounding
- Outcome limited to hospitalization; non-hospitalized LRTI not captured
Future Directions: Head-to-head pragmatic trials in diverse settings; cost-effectiveness analyses under supply constraints; evaluation of combination or sequential strategies across RSV seasons.
BACKGROUND: Maternal respiratory syncytial virus (RSV) prefusion F (RSVpreF) vaccine and nirsevimab immunisation are two products recently implemented to reduce RSV-related lower respiratory tract infection (LRTI) in infants (nirsevimab since 2023 and RSVpreF since 2024). We aimed to assess the effectiveness of nirsevimab immunisation at birth versus RSVpreF maternal vaccination in preventing RSV-related LRTI hospitalisations in children before age 6 months. METHODS: This population-based retrospective cohort study used data from the French National Health Data System and included all children born across metropolitan France between Sept 1, 2024, and Feb 28, 2025, who either received nirsevimab at birth (nirsevimab group) or whose mothers received RSVpreF vaccine between 28 weeks and 36 weeks of gestation (RSVpreF group). Children who received neither immunisation, those born from mothers not aged 13-50 years, and those who could not be linked to their mother in the database were not included. Children were matched on birth date, region of birth, and sex. The primary outcome was RSV-related LRTI hospitalisation at age 6 months. Propensity score analysis adjusted for baseline characteristics. Secondary analyses were performed, notably assessing the influence of the timing of RSVpreF maternal vaccination during pregnancy on the main outcome. FINDINGS: During the study period, 164 140 children were included, of whom 83 978 (51·2%) were male and 80 162 (48·8%) female; mean gestation at birth was 39·4 weeks...
2. Platelet-leucocyte interactions drive MMP-mediated tissue damage in tuberculosis.
Across in vitro, tissue, and ex vivo patient studies, platelet P‑selectin–monocyte PSGL‑1 interactions amplified MMP‑1/10 expression and secretion, correlating with platelet–leukocyte aggregates independent of thrombotic pathways. These data identify a platelet–leukocyte inflammatory axis as a driver of tissue‑destructive pathology in TB and nominate P‑selectin/PSGL‑1 as a host‑directed therapeutic target.
Impact: Provides mechanistic, human‑relevant evidence linking platelet–leukocyte signaling to TB tissue damage, opening a tractable, druggable host-directed pathway (P‑selectin/PSGL‑1) beyond antimicrobials.
Clinical Implications: Adjunctive blockade of P‑selectin/PSGL‑1 or modulation of platelet–leukocyte aggregation could mitigate lung tissue destruction in TB without impairing bacterial killing, warranting early-phase trials.
Key Findings
- Platelets increased MMP‑1/10 secretion and upregulated mmp1 (4.7‑fold) in M.tb‑infected monocytes.
- Immunofluorescence showed platelet localization to PSGL‑1+ monocytic cells in infected lymph nodes, absent in non‑TB controls.
- TB patients had increased platelet–monocyte and platelet–neutrophil aggregates with unchanged GPIIb/IIIa, indicating dissociation from classical thrombosis.
Methodological Strengths
- Triangulation across co-culture, human tissue imaging, and patient ex vivo assays
- Receptor‑ligand specificity tested (P‑selectin/PSGL‑1) and soluble mediator effects
Limitations
- Modest clinical sample sizes limit outcome correlations
- Causality for in vivo tissue destruction not established in interventional models
Future Directions: Test P‑selectin/PSGL‑1 antagonists or anti‑platelet strategies as host‑directed adjuncts in TB; define safety windows to avoid bleeding; validate in lung tissue and clinical endpoints.
Tuberculosis causes inflammation and excess matrix metalloproteinase (MMP) activity which lead to tissue damage and adverse patient outcomes. Platelets are emerging as key drivers of inflammation, and platelet-leucocyte aggregate formation via interactions between platelet P-selectin and monocyte PSGL-1 receptors may regulate tissue destruction in tuberculosis. First, a platelet-monocyte co-culture model was utilised to assess platelet-leucocyte interactions. We then examined M.tb-infected and control lymph node tissue using immunofluorescence microscopy. Finally, we investigated tuberculosis patients (TB, n = 17), healthy controls (HC, n = 14), and patients undergoing bronchoscopy subsequently classified as TB (n = 10) or respiratory symptomatic (RS, n = 14). Whole blood was collected to quantify platelet aggregation using light transmission aggregometry, and platelet-monocyte aggregates (PMA), platelet-neutrophil aggregates (PNA), and platelet receptor expression using flow cytometry. In M.tb-infected monocytes, addition of platelets significantly increased secretion of MMP-1 and MMP-10 and upregulated mmp1 gene expression 4.7-fold. MMP-1 secretion was also increased by addition of platelet-derived soluble factors, and by monocyte PSGL-1 receptor ligation. We observed abundant platelets in M.tb-infected lymph node tissue, localising to PSGL-1 receptors on monocytic cells, and this was not seen in M.tb-uninfected control tissue from patients with reactive hyperplasia or with lymphoma. Ex vivo platelet aggregation in response to stimulation with platelet agonist ADP (3µM, 10µM, and 30µM) was reduced in patients with TB versus HC...
3. Dual inhibition of intercellular adhesion molecule-1 and nucleolin reduces RSV infection efficiency in human respiratory organoids.
Using human iPSC-derived respiratory organoids, the study demonstrates that ICAM‑1 and nucleolin are critical host factors for RSV infection. Genetic depletion or antibody blockade of these proteins—and especially dual inhibition—significantly reduces infection efficiency under physiologic airway architecture.
Impact: Establishes human-relevant organoid evidence for actionable RSV host targets, bridging prior cell-line observations to a physiologic airway context and informing host-directed antiviral strategies.
Clinical Implications: Therapeutic strategies that block ICAM‑1 and nucleolin interactions with RSV could complement or enhance current prophylaxis/vaccines, especially in high‑risk populations.
Key Findings
- CRISPR-Cas9 depletion of ICAM‑1 reduced RSV infection in human respiratory organoids.
- Antibody inhibition of nucleolin likewise reduced infection; combined inhibition further decreased infection efficiency.
- Organoid platform confirmed host factor roles under physiologically relevant airway architecture.
Methodological Strengths
- Use of human iPSC-derived respiratory organoids for physiologic relevance
- Genetic (CRISPR) and pharmacologic (neutralizing antibodies) perturbations for convergent validation
Limitations
- Abstracted results do not report quantitative effect sizes
- Findings require in vivo validation and safety profiling for host-targeted interventions
Future Directions: Define structural interfaces for ICAM‑1/NCL–RSV binding; develop dual‑target inhibitors; test efficacy with current mAbs/vaccines; extend to primary human airway tissues and in vivo models.
Respiratory syncytial virus (RSV) is one of the major causes of lower respiratory tract infections, particularly in infants and older adults. However, the host factors mediating infection remain poorly defined. It has been suggested that four host surface proteins, namely intercellular adhesion molecule-1 (ICAM-1), epidermal growth factor receptor (EGFR), nucleolin (NCL), and insulin-like growth factor 1 receptor (IGF1R), may interact with the RSV fusion (F) protein. To investigate these roles under physiologically relevant conditions, we employed human induced pluripotent stem cell (iPSC)-derived respiratory organoids as a model for RSV infection. In this model, ICAM-1 and EGFR were genetically depleted using the CRISPR-Cas9 genome editing technique, while NCL and IGF1R were inhibited with neutralizing antibodies. Suppression of ICAM-1 or NCL significantly reduced