Daily Respiratory Research Analysis
Analyzed 66 papers and selected 3 impactful papers.
Summary
Analyzed 66 papers and selected 3 impactful articles.
Selected Articles
1. Efficacy and safety of VPM1002 and Immuvac in preventing tuberculosis: phase 3 randomised clinical trial (PreVenTB trial).
In 12,717 TB household contacts followed for 38 months, neither VPM1002 nor Immuvac reduced overall or pulmonary microbiologically confirmed TB. VPM1002 showed a notable reduction in extrapulmonary TB (per-protocol efficacy 50.4%, 95% CI 0.8–75.2%), with efficacy signals in TST-positive participants for both vaccines; safety was acceptable with mostly mild local reactions.
Impact: This large, multicenter phase 3 RCT directly informs TB vaccine policy in high-burden settings, highlighting lack of efficacy for overall TB but a potential role in preventing extrapulmonary disease and in TST-positive contacts.
Clinical Implications: Do not expect overall TB prevention from VPM1002 or Immuvac in household contacts; consider that VPM1002 may reduce extrapulmonary TB, particularly among TST-positive contacts, pending confirmatory trials and policy review.
Key Findings
- No efficacy against overall microbiologically confirmed TB or pulmonary TB for either vaccine over 38 months.
- VPM1002 showed per-protocol efficacy of 50.4% (95% CI 0.8–75.2%) against extrapulmonary TB.
- In TST-positive participants, both VPM1002 and Immuvac showed efficacy signals against extrapulmonary TB (~65–66%).
- Both vaccines were well tolerated, with mild local reactions in about one-third of participants.
Methodological Strengths
- Large, multicenter, phase 3 randomized design with registry-listed protocol
- Per-protocol and modified intention-to-treat analyses with predefined secondary and exploratory outcomes
Limitations
- Primary endpoint not met; efficacy limited to extrapulmonary TB signals
- Potential heterogeneity by age, BMI, and TST status requires cautious interpretation
Future Directions: Confirmatory trials focusing on extrapulmonary TB and TST-positive subgroups, immunologic correlates of protection, and head-to-head comparisons with BCG revaccination are warranted.
OBJECTIVE: To evaluate the safety and efficacy of VPM1002 and Immuvac in reducing the incidence of microbiologically confirmed tuberculosis (TB; pulmonary TB and extrapulmonary TB), development of latent TB infection, and immunogenicity. DESIGN: Phase 3 randomised clinical trial (PreVenTB trial). SETTING: 18 sites across six states of India. PARTICIPANTS: 12 717 healthy household contacts (aged ≥6 years) of patients with a smear positive TB test. INTERVENTIONS: Participants were randomly assigned in a 1:1:1 ratio (using block randomisation with variable sample size) to receive an intradermal injection of VPM1002, Immuvac, or placebo in both arms. After one month, a second dose was administered in one arm to 11 829 healthy participants. OUTCOME MEASURES: The primary outcome was efficacy against confirmed TB (pulmonary TB and extrapulmonary TB) over 38 months of follow-up. Secondary outcomes were development of latent TB infection, adverse and serious adverse events, efficacy in predefined age groups, and immunogenicity. Exploratory outcomes were efficacy when considering tuberculin skin test status, and post hoc analyses of efficacy in participants aged 6-14 and according to body mass index. RESULTS: 252 and 227 participants developed microbiologically confirmed TB in modified intention-to-treat and per protocol groups, respectively. The per protocol analysis showed 65 (1.68%), 80 (2.09%), and 82 (2.13%) participants developed TB in the VPM1002, Immuvac, and placebo groups, respectively. Of these, 12 (0.31%), 16 (0.42%), and 24 (0.62%) developed extrapulmonary TB in the VPM1002, Immuvac, and placebo groups, respectively. In the per protocol analysis, VPM1002 showed vaccine efficacy of 21.4% (95% confidence interval (CI) -8.9% to 43.2%), 19.5% (-14.6% to 43.4%), and 50.4% (0.8% to 75.2%) against all TB, pulmonary TB, and extrapulmonary TB, respectively. Immuvac showed vaccine efficacy of 33.2% (-25.9% to 64.5%) against extrapulmonary TB. VPM1002 and Immuvac showed vaccine efficacy of 64.9% (-2% to 90.1%) and 66.3% (1.9% to 90.5%) against extrapulmonary TB in participants with tuberculin skin test positivity. Both vaccines were well tolerated with mild local reactions in about a third of participants. VPM1002 and Immuvac induced CONCLUSIONS: Both vaccines were safe but did not show any efficacy against all forms of microbiologically confirmed TB or pulmonary TB. VPM1002 showed considerable efficacy against extrapulmonary TB. Both vaccines showed efficacy against extrapulmonary TB in participants who had a positive tuberculin skin test. TRIAL REGISTRATION: Clinical Trials Registry India CTRI/2019/01/017026.
2. Performance of an antigen test for detection of SARS-CoV-2, influenza and respiratory syncytial virus - A prospective study.
In a 1,372-participant prospective study, the Triplex nasal-swab antigen test achieved sensitivities near Ct 30 of 87.0% (SARS-CoV-2), 79.0% (influenza A), 87.5% (influenza B), and 91.2% (RSV), with 100% specificity across pathogens. Performance characteristics and Ct-threshold analyses support its use as an infectiousness marker in acute care settings.
Impact: Provides practical, multiplex, point-of-care diagnostic data across four major respiratory viruses with implications for triage, isolation, and antiviral stewardship.
Clinical Implications: Use Triplex antigen testing to inform rapid triage and isolation when Ct levels are expected to be in an infectious range; confirm negatives in high-suspicion cases with PCR, especially when disease prevalence is high or symptom onset is late.
Key Findings
- Sensitivities at PCR Ct 30: SARS-CoV-2 87.0%, influenza A 79.0%, influenza B 87.5%, RSV 91.2%.
- Specificity was 100% (95% CI 99.7–100.0) for all four pathogens.
- Nasal swab absorbed less viral RNA than nasopharyngeal swab overall (significant for influenza A), though not observed in children.
- Feasibility in ED workflow with onsite antigen reading and central lab PCR confirmation.
Methodological Strengths
- Prospective design with large sample size across age groups including children
- Ct-threshold–anchored analysis and subset PCR of device medium to contextualize antigen performance
Limitations
- Different sampling sites for antigen (nasal) vs PCR (nasopharyngeal) may bias paired comparisons
- Sensitivity depends on viral load and timing; generalizability to self-testing not assessed
Future Directions: Evaluate real-world impact on ED throughput, transmission, and antiviral targeting; assess self-collection performance and cost-effectiveness across seasons and variants.
OBJECTIVES: Assess the performance of the ALL IN TRIPLEX rapid antigen-based test for SARS-CoV-2, influenza A, influenza B and respiratory syncytial virus (RSV). We focus on the potential of the test to be used in acute clinical settings as a marker of infectiousness, by determining the sensitivity at different real-time PCR Ct levels, as well as the quantity of absorbed viral RNA needed to produce an antigen band. METHODS: In total, 1372 patients with symptoms and signs of an acute respiratory infection were included in the study; 150 were children. All patients were tested using the nasal swab Triplex kit, as well as with PCR on a separately taken nasopharyngeal sample. The antigen test was analysed by emergency department staff, while PCR was performed at a central laboratory. In 226 cases, also the Triplex device medium was subjected to PCR. RESULTS: The sensitivity was 87.0% (95% CI, 66.4-97.7), 79.0% (95% CI, 72.7-84.4), 87.5% (95% CI, 67.6-97.3) and 91.2% (95% CI, 80.7-97.1) for SARS-CoV-2, influenza A, influenza B and RSV, respectively, using the nasopharyngeal sample PCR Ct 30 level as reference. Specificity was 100% (95% CI, 99.7-100.0) for all agents. A comparison with Triplex medium PCR Ct results showed a trend suggesting that less viral RNA is absorbed by the nasal swab than by the nasopharyngeal swab. While there was no sign of this trend in children, it reached significance among the total of patients for influenza A (mean Ct value 31.8 for the Triplex swab and 26.0 for the nasopharyngeal swab, p<0.0001). CONCLUSIONS: The observed performance of Triplex, for all four viruses and across all age groups, implies that Triplex may serve as a marker of infectiousness in acute clinical care settings.
3. What is the evidence for virtual wards or hospital-at-home care pathways for exacerbations of chronic obstructive pulmonary disease? A systematic review and meta-analysis.
Across 11 studies (1 VW, 10 HaH), there was no evidence of reduced all-cause mortality, short-term readmissions, or total hospital-led care time with virtual wards or hospital-at-home pathways for COPD exacerbations. The review, registered in PROSPERO, underscores the need for high-quality trials before widespread implementation.
Impact: This synthesis provides policy-relevant clarity that current evidence does not support mortality/readmission benefits of VW/HaH pathways for ECOPD, guiding resource allocation and future trial design.
Clinical Implications: Clinicians and health systems should be cautious in adopting VW/HaH for ECOPD as admission-avoidance strategies; prioritize enrollment in robust trials and ensure parity of monitoring intensity if implemented.
Key Findings
- Only one virtual ward study (two publications) and ten hospital-at-home studies met inclusion.
- No reduction in all-cause mortality or short-term (7–30 day) readmission with VW/HaH versus hospital admission.
- No evidence of reduction in total hospital-led care time when considering both home and in-hospital care.
- Comprehensive search with risk-of-bias assessment and random-effects meta-analysis; PROSPERO-registered.
Methodological Strengths
- Comprehensive multi-database search with predefined outcomes and random-effects meta-analysis
- Explicit risk-of-bias assessment and prospective protocol registration (PROSPERO)
Limitations
- Very limited virtual ward evidence (single study) and heterogeneity across HaH models
- Potential publication bias and variability in monitoring intensity and care components
Future Directions: Well-powered, CONSORT-adherent RCTs comparing standardized VW/HaH models with usual care, capturing patient-centered outcomes, safety, and cost-effectiveness.
OBJECTIVES: Given increasing interest in admission avoidance, we evaluated the evidence to support virtual wards (VW) and hospital at home (HaH) models of care during exacerbations of chronic obstructive pulmonary disease (ECOPD). DESIGN: A systematic review and meta-analysis. A comprehensive search of MEDLINE (1946 to March 2024), Embase (1974 to March 2024) and CENTRAL (searched 22 March 2024) was conducted. Risk of bias and a random effects meta-analysis were performed. POPULATION: Adults with an ECOPD presenting to the hospital or who require hospital-led care. INTERVENTIONS: VW: defined as assessments and interventions delivered remotely or HaH (defined as assessments and interventions delivered by healthcare professionals in patient's homes) care pathways, compared with hospital admission. PRIMARY AND SECONDARY OBJECTIVES: Safety (mortality rate of all causes, in-patient, 7 days and 30 days) and readmission rate in 7 and 30 days. Length of stay in hospital and changes in pulmonary function tests. RESULTS: One study assessed VWs (reported in two publications) and 10 assessed HaH. There were no changes in survival or short-term readmission rates attributable to the interventions and no evidence that VW or HaH care pathways reduced the total time a patient spent under hospital-led care, whether at home or in the hospital. CONCLUSIONS: More evidence is needed to support the widespread roll-out of HaH and especially VW pathways for ECOPD. PROSPERO REGISTRATION NUMBER: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024517565.