Daily Respiratory Research Analysis
Three high-impact studies advance respiratory prevention and epidemiology: a large randomized trial shows the RSV prefusion F vaccine markedly reduces RSV-related hospitalizations in adults ≥60 years; a mega-trial finds high-dose influenza vaccine does not significantly reduce influenza/pneumonia hospitalizations overall but lowers lab-confirmed influenza admissions; and a mechanistic analysis identifies influenza–RSV viral interference as the driver of disrupted biennial RSV patterns.
Summary
Three high-impact studies advance respiratory prevention and epidemiology: a large randomized trial shows the RSV prefusion F vaccine markedly reduces RSV-related hospitalizations in adults ≥60 years; a mega-trial finds high-dose influenza vaccine does not significantly reduce influenza/pneumonia hospitalizations overall but lowers lab-confirmed influenza admissions; and a mechanistic analysis identifies influenza–RSV viral interference as the driver of disrupted biennial RSV patterns.
Research Themes
- RSV vaccination effectiveness in older adults
- High-dose influenza vaccination and hospitalization outcomes
- Viral interference shaping RSV seasonality and epidemic dynamics
Selected Articles
1. RSV Prefusion F Vaccine for Prevention of Hospitalization in Older Adults.
In a nationwide, pragmatic randomized trial of 131,276 adults ≥60 years in Denmark, RSVpreF vaccination reduced RSV-related respiratory hospitalization by 83% and RSV-related lower respiratory tract hospitalization by 92% versus no vaccine, with similar serious adverse event rates. All-cause respiratory hospitalizations were modestly reduced.
Impact: This is the first large randomized evidence demonstrating substantial reductions in RSV-related hospitalizations among older adults, directly informing immunization policy.
Clinical Implications: Supports offering RSVpreF vaccination to adults ≥60 years as part of seasonal prevention strategies to reduce RSV hospitalization burden, with safety comparable to control.
Key Findings
- RSV-related respiratory hospitalization: 0.11 vs 0.66 events/1000 PY; vaccine effectiveness 83.3% (95% CI 42.9–96.9).
- RSV-related lower respiratory tract hospitalization: 1 vs 12 events; vaccine effectiveness 91.7% (95% CI 43.7–99.8).
- All-cause respiratory hospitalization reduced by 15.2% (95% CI 0.5–27.9).
- Serious adverse events occurred at similar rates between RSVpreF and control groups.
Methodological Strengths
- Pragmatic, individually randomized design with nationwide registry ascertainment of outcomes.
- Very large sample size enabling precise estimates for rare hospitalization events.
Limitations
- Open-label design could introduce behavior-related biases, although hospitalization endpoints mitigate this.
- Low absolute event numbers for RSV hospitalizations yield wide confidence intervals and a single-season setting limits generalizability.
Future Directions: Assess durability across multiple seasons, subgroup effects (e.g., frailty, comorbidities), coadministration strategies, and cost-effectiveness in diverse health systems.
2. High-Dose Influenza Vaccine Effectiveness against Hospitalization in Older Adults.
In a 332,438-participant pragmatic randomized trial across three seasons, high-dose influenza vaccine did not significantly reduce the composite of influenza or pneumonia hospitalizations versus standard dose. However, lab-confirmed influenza hospitalizations were reduced by 44%, and cardiorespiratory hospitalizations were modestly lower.
Impact: Provides definitive randomized evidence on high-dose influenza vaccine in general older adults, including an important negative primary outcome and clinically relevant secondary reductions.
Clinical Implications: Routine use of high-dose influenza vaccine may be prioritized to reduce lab-confirmed influenza hospitalizations, while expectations for broad pneumonia prevention should be tempered; policy should consider seasonality, strain match, and resource allocation.
Key Findings
- Primary composite (influenza or pneumonia hospitalization): RVE 5.9% (95.2% CI −2.1 to 13.4), not statistically significant.
- Lab-confirmed influenza hospitalization: 0.06% vs 0.11%; RVE 43.6% (95.2% CI 27.5 to 56.3).
- Cardiorespiratory hospitalization: RVE 5.7% (95.2% CI 1.4 to 9.9).
- Serious adverse events occurred at similar rates across groups.
Methodological Strengths
- Enormous randomized cohort with registry-based outcome capture across three seasons.
- Pragmatic design enhances generalizability to routine practice.
Limitations
- Open-label design and reliance on administrative codes may introduce misclassification.
- Low absolute incidence of influenza hospitalization limits power for some subgroup analyses.
Future Directions: Evaluate cost-effectiveness by season/strain match, identify subgroups (e.g., heart failure) deriving maximal benefit, and assess coadministration with other vaccines.
3. Unraveling the role of viral interference in disrupting biennial RSV epidemics in northern Stockholm.
An age-stratified mechanistic model fitted to 20 years of weekly RSV admissions in northern Stockholm showed that influenza–RSV viral interference, particularly from pandemic H1N1, uniquely explains the post-pandemic shift to early/large even-year and late/small odd-year RSV outbreaks. Birth rates and temperatures could not reproduce the observed pattern.
Impact: Provides mechanistic evidence for cross-virus interactions shaping RSV epidemiology, informing forecasting, vaccination timing, and non-pharmaceutical interventions.
Clinical Implications: Public health planning for RSV should consider concurrent influenza activity; vaccination/monoclonal deployment and hospital preparedness may be optimized based on anticipated interference-driven shifts.
Key Findings
- Only viral interference from influenza reproduced the post-pandemic shift in RSV biennial patterns in northern Stockholm.
- Pandemic H1N1 exerted the strongest interference effects on RSV, consistent with in vivo evidence.
- Birth rates and temperature changes failed to explain the observed epidemiologic transitions.
Methodological Strengths
- Age-stratified mechanistic modeling with explicit hypothesis testing against competing drivers.
- Model fitting to a long 20-year weekly hospitalization time series enables robust pattern attribution.
Limitations
- Findings are model-based and dependent on assumptions and data quality of hospital admissions.
- Generalizability beyond the studied region requires validation in other settings.
Future Directions: Validate interference estimates in other regions, integrate viral genomics and contact patterns, and quantify policy scenarios (e.g., vaccination timing) under interference.