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.
BACKGROUND: Respiratory syncytial virus (RSV) can cause serious illness in older adults. The bivalent RSV prefusion F protein-based vaccine (RSVpreF) has been shown to prevent RSV-associated respiratory illness, but data from randomized trials with regard to its effect on outcomes involving hospitalization are limited. METHODS: In this pragmatic, open-label trial with individual randomization, participants who were 60 years of age or older were assigned in a 1:1 ratio to receive the RSVpreF vaccine (the RSVpreF group) or no vaccine (the control group) during the 2024-2025 winter season. Baseline and outcome data were collected with the use of national registries. The primary end point was hospitalization for RSV-related respiratory tract disease. Secondary end points included hospitalization for RSV-related lower respiratory tract disease and hospitalization for respiratory tract disease from any cause. The prespecified criterion for success for the primary end point and RSV-related secondary end points was a minimum vaccine effectiveness of greater than 20%. RESULTS: Of 131,379 participants who underwent randomization, 131,276 were included in the intention-to-treat population. During follow-up, hospitalization for RSV-related respiratory tract disease occurred in 3 of 65,642 participants in the RSVpreF group and in 18 of 65,634 participants in the control group (0.11 events vs. 0.66 events per 1000 participant-years; vaccine effectiveness, 83.3%; 95% confidence interval [CI], 42.9 to 96.9; P = 0.007 for minimum effectiveness of >20%). The RSVpreF group also had fewer hospitalizations for RSV-related lower respiratory tract disease than the control group (1 vs. 12; vaccine effectiveness, 91.7%; 95% CI, 43.7 to 99.8; P = 0.009 for minimum effectiveness of >20%), as well as fewer hospitalizations for respiratory tract disease from any cause (284 vs. 335; vaccine effectiveness, 15.2%; 95% CI, 0.5 to 27.9; P = 0.04 for vaccine effectiveness of >0%). The incidence of serious adverse events was similar in the two groups. CONCLUSIONS: Among adults 60 years of age or older, the RSVpreF vaccine reduced the incidence of hospitalization for RSV-related respiratory tract disease as compared with no vaccine. (Funded by Pfizer; European Union Clinical Trials number, 2024-516600-42-00; DAN-RSV ClinicalTrials.gov number, NCT06684743.).
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.
BACKGROUND: High-dose inactivated influenza vaccine has been shown to provide protection against influenza that is superior to that with the standard dose. However, data from individually randomized trials on the effectiveness of the high-dose vaccine against severe outcomes are limited. METHODS: In this pragmatic, open-label, randomized, controlled trial conducted in Denmark during the 2022-2023, 2023-2024, and 2024-2025 influenza seasons, we assigned older adults (≥65 years of age) to receive the high dose of the inactivated influenza vaccine or the standard dose. Data collection relied on nationwide administrative health registries. The primary end point was hospitalization for influenza or pneumonia that occurred from 14 days after vaccination through May 31 of the following year. RESULTS: Of the 332,438 participants who underwent randomization, 166,218 were assigned to receive the high-dose vaccine and 166,220 to receive the standard-dose vaccine. The mean (±SD) age of the participants was 73.7±5.8 years, and 161,538 participants (48.6%) were women. A primary end-point event occurred in 1138 participants (0.68%) in the high-dose group and in 1210 (0.73%) in the standard-dose group (relative vaccine effectiveness, 5.9%; 95.2% confidence interval [CI], -2.1 to 13.4; P = 0.14). Hospitalization for influenza occurred in 0.06% of the participants in the high-dose group and in 0.11% of those in the standard-dose group (relative vaccine effectiveness, 43.6%; 95.2% CI, 27.5 to 56.3); hospitalization for pneumonia occurred in 0.63% and 0.63%, respectively (relative effectiveness, 0.5%; 95.2% CI, -8.6 to 8.8); hospitalization for cardiorespiratory disease in 2.25% and 2.38% (relative effectiveness, 5.7%; 95.2% CI, 1.4 to 9.9); hospitalization for any cause in 9.38% and 9.58% (relative effectiveness, 2.1%; 95.2% CI, -0.1 to 4.3), and death from any cause in 0.67% and 0.66% (relative effectiveness, -2.5%; 95.2% CI, -11.6 to 5.9). The incidence of serious adverse events was similar in the two groups. CONCLUSIONS: In this trial, a high-dose inactivated influenza vaccine did not result in a significantly lower incidence of hospitalization for influenza or pneumonia than a standard dose among older adults. (Funded by Sanofi; DANFLU-2 ClinicalTrials.gov number, NCT05517174; EU Clinical Trials Register number, 2022-500657-17-00.).
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.
Respiratory syncytial virus (RSV) primarily impacts infants and older adults, with seasonal winter outbreaks in temperate countries. Delayed RSV activity was reported worldwide during the 2009 influenza pandemic, and a disrupted biennial pattern of RSV activity was observed in northern Stockholm following the pandemic. Biennial patterns shifted to early/large outbreaks in even-numbered years and late/small outbreaks in odd-numbered years. However, the mechanisms underpinning this change in pattern remain unknown. In this work, we construct an age-stratified mechanistic model to explicitly test three factors that can lead to the change in RSV transmission dynamics: (1) birth rates, (2) temperatures, and (3) viral interference. By fitting the model to weekly RSV admission data over a 20-year period and comparing different models, we find that viral interference from influenza is the only mechanism that explains the shifted biennial pattern. We further demonstrate that the pandemic H1N1 virus has the strongest viral interference effects with RSV, aligning with a previous in vivo study. Our work demonstrates the complex interplay between different respiratory viruses, providing evidence that supports the presence of interactions between the H1N1 pandemic influenza virus and RSV at the population level, with implications for future public health interventions.