Daily Respiratory Research Analysis
Three high-impact respiratory studies stand out today: an individual participant data meta-analysis of 14 RCTs shows awake prone positioning in COVID-19 acute hypoxemic respiratory failure reduces intubation and mortality; a test-negative study confirms strong real-world effectiveness of nirsevimab against infant RSV, especially severe disease; and a national cohort comparison finds RSV hospitalizations in adults are more severe than influenza and comparable to boosted COVID-19 for some outcomes
Summary
Three high-impact respiratory studies stand out today: an individual participant data meta-analysis of 14 RCTs shows awake prone positioning in COVID-19 acute hypoxemic respiratory failure reduces intubation and mortality; a test-negative study confirms strong real-world effectiveness of nirsevimab against infant RSV, especially severe disease; and a national cohort comparison finds RSV hospitalizations in adults are more severe than influenza and comparable to boosted COVID-19 for some outcomes, informing vaccination and surge planning.
Research Themes
- Noninvasive respiratory support optimization (awake prone positioning)
- Effectiveness of RSV immunoprophylaxis in infants
- Comparative severity and health-system impact of respiratory viruses
Selected Articles
1. Awake Prone Positioning in Adults With COVID-19: An Individual Participant Data Meta-Analysis.
Across 14 RCTs (n=3019), awake prone positioning increased survival without intubation, reduced intubation (OR 0.70) and hospital mortality (OR 0.77), and delayed time to intubation. Sustained APP ≥10 hours/day within the first 3 days yielded the greatest benefit.
Impact: This IPD meta-analysis resolves conflicting trial results and provides actionable thresholds for APP duration, supporting protocolized implementation during hypoxemic respiratory failure surges.
Clinical Implications: Implement APP early and target ≥10 hours/day in adults with COVID-19 AHRF receiving advanced respiratory support to reduce intubation and mortality; invest in protocols, staffing, and comfort strategies to achieve adherence.
Key Findings
- APP improved survival without intubation (OR 1.42; 95% CI 1.20–1.68).
- APP reduced intubation (OR 0.70; 95% CI 0.59–0.84) and hospital mortality (OR 0.77; 95% CI 0.63–0.95).
- Time to intubation increased by 0.93 days (95% CI 0.43–1.42).
- APP ≥10 hours/day within the first 3 days was associated with higher survival without intubation (OR 1.85; 95% CI 1.37–2.49).
- Benefits were consistent across subgroups; no significant interaction by baseline characteristics.
Methodological Strengths
- Individual participant data meta-analysis of 14 randomized controlled trials (PRISMA-IPD compliant).
- Dose–response assessment by APP duration with prespecified outcomes and adjusted models.
Limitations
- Heterogeneity in APP protocols, adherence, and co-interventions across trials.
- Applicability beyond COVID-19 AHRF remains to be established.
Future Directions: Pragmatic implementation trials to optimize APP delivery (comfort, sedation-sparing strategies), evaluate non-COVID AHRF, and integrate APP with other noninvasive supports.
2. Estimated Effectiveness of Nirsevimab Against Respiratory Syncytial Virus.
In a test-negative analysis of 3090 infants, nirsevimab reduced medically attended RSV by 68%, hospitalizations by 81%, and severe disease by 85%, with effectiveness waning from ~79% at 2 weeks to ~55% at 14 weeks post-immunization. Benefits were consistent across doses and extended to all-cause LRTI during peak RSV circulation.
Impact: Provides timely, real-world effectiveness estimates after initial US rollout, informing infant immunization strategies and timing relative to RSV seasonality.
Clinical Implications: Support broad infant immunization with nirsevimab prior to peak RSV season; counsel families on strong protection against severe outcomes and modest waning, and plan catch-up efforts amid supply constraints.
Key Findings
- Adjusted effectiveness against medically attended RSV infection: 68.4% (95% CI 50.3–80.8).
- Effectiveness against RSV hospitalization: 80.5% (95% CI 52.0–93.5); severe disease: 84.6% (95% CI 58.7–95.6).
- Effectiveness waned from 79.3% at 2 weeks to 54.8% at 14 weeks post-immunization, remaining significant.
- No substantial differences by dosage; effectiveness against all-cause LRTI and LRTI hospitalizations during peak RSV circulation.
Methodological Strengths
- Test-negative case-control design with multivariable adjustment and registry-verified immunization.
- Stratified analyses by severity, setting, dosage, and time since immunization.
Limitations
- Single health system with relatively low uptake (10.7%), leading to wide CIs in some strata.
- Residual confounding and misclassification remain possible despite adjustment.
Future Directions: Multi-center effectiveness and safety surveillance across seasons and populations, evaluation of indirect effects, and optimal timing strategies amid evolving RSV epidemiology.
3. Severity of respiratory syncytial virus versus SARS-CoV-2 Omicron and influenza infection amongst hospitalized Singaporean adults: a national cohort study.
In 12,811 adult hospitalizations, RSV carried higher severity and healthcare utilization than influenza, with 5.4% 28-day mortality and median LOS of 5 days. Compared with unboosted COVID-19, RSV was less severe (lower 28-day mortality), but versus recently boosted COVID-19, RSV had higher ICU admission odds, underscoring substantial RSV burden in older adults and those with diabetes.
Impact: Quantifies RSV burden relative to influenza and COVID-19 in a vaccinated era at national scale, guiding adult RSV vaccination prioritization and hospital surge planning.
Clinical Implications: Prioritize RSV vaccination/monoclonal strategies for older adults and those with diabetes; anticipate higher ICU demand during RSV surges despite widespread COVID-19 boosting.
Key Findings
- RSV hospitalizations had 5.4% 28-day mortality and 3.8% ICU admission; median LOS 5.0 days.
- RSV severity and healthcare utilization were higher than influenza in multivariable analyses.
- RSV was less severe than unboosted COVID-19 (lower 28-day mortality; aOR 0.56).
- Compared with recently boosted COVID-19, RSV had higher odds of ICU admission (aOR 1.80).
- Older age and diabetes independently increased 28-day mortality risk in RSV hospitalizations.
Methodological Strengths
- Nationwide population-based cohort with contemporaneous comparator groups and multivariable adjustment.
- Use of generalized linear models to estimate excess length-of-stay and costs.
Limitations
- Observational design with potential confounding and misclassification of vaccination status.
- Temporal differences in variant circulation and healthcare practices may influence comparisons.
Future Directions: Evaluate vaccine impact on adult RSV severity across diverse settings, refine risk stratification for targeted immunization, and model ICU capacity needs during RSV peaks.