Daily Respiratory Research Analysis
Durable respiratory protection and therapeutics advanced today: a phase 3 trial shows the RSVPreF3 OA vaccine maintains efficacy against RSV lower respiratory tract disease across three seasons in adults 60+, while a pediatric phase 3 trial demonstrates clinical benefit of the antiviral ziresovir in hospitalized infants ≤6 months. A nationwide cohort from Brazil quantifies persistent excess mortality up to 10 years after tuberculosis diagnosis, with risk concentrating in specific subgroups and c
Summary
Durable respiratory protection and therapeutics advanced today: a phase 3 trial shows the RSVPreF3 OA vaccine maintains efficacy against RSV lower respiratory tract disease across three seasons in adults 60+, while a pediatric phase 3 trial demonstrates clinical benefit of the antiviral ziresovir in hospitalized infants ≤6 months. A nationwide cohort from Brazil quantifies persistent excess mortality up to 10 years after tuberculosis diagnosis, with risk concentrating in specific subgroups and causes shifting to cardiovascular, cancer, and non-TB respiratory diseases.
Research Themes
- RSV immunization durability and revaccination strategy
- Pediatric RSV antiviral therapy effectiveness
- Long-term excess mortality after tuberculosis and risk stratification
Selected Articles
1. Efficacy, safety, and immunogenicity of the AS01
In a multinational, phase 3, randomized, observer-blind trial in adults ≥60 years, a single dose of RSVPreF3 OA conferred 62.9% cumulative efficacy against RSV-LRTD over three consecutive seasons, with efficacy against both RSV A and B. Protection waned over time, and revaccination at one year produced efficacy in the same range as a single dose. Safety was clinically acceptable.
Impact: This is among the first rigorous demonstrations of multi-season durability for an RSV vaccine in older adults, directly informing immunization policy and revaccination strategies.
Clinical Implications: Supports adoption of RSVPreF3 OA for adults ≥60 with expected protection across at least three seasons; clinicians should anticipate waning and watch for forthcoming guidance on optimal revaccination timing.
Key Findings
- Single-dose RSVPreF3 OA showed 62.9% cumulative efficacy against RSV-LRTD over three seasons (median follow-up 30.6 months).
- Efficacy was demonstrated against both RSV A (69.8%) and RSV B (58.6%) related LRTD.
- Efficacy waned over time; revaccination at 1 year yielded efficacy within the same range as a single dose; safety profile was acceptable with <1% serious adverse events judged related.
Methodological Strengths
- Randomized, observer-blind, placebo-controlled, multicountry phase 3 design across 17 countries and 275 sites
- Pre-specified analyses by subtype and sustained multi-season follow-up with adequate power
Limitations
- Efficacy waned over time; optimal revaccination interval remains undefined.
- Severe outcomes and subgroup safety signals are not fully detailed in the abstract and require full-text appraisal.
Future Directions: Define optimal revaccination schedules (interval and target subgroups), assess durability against severe RSV-LRTD and hospitalization, and evaluate coadministration with other seasonal vaccines.
2. Efficacy and safety of ziresovir in hospitalised infants aged 6 months or younger with respiratory syncytial virus infection in China: findings from a phase 3 randomised trial with 24-month follow-up.
In hospitalized infants ≤6 months with PCR-confirmed RSV, oral ziresovir produced a greater improvement in the Wang bronchiolitis clinical score at day 3 versus placebo (LS mean difference −1.2, p=0.0004) with no drug-related serious adverse events. This prespecified subgroup analysis demonstrates early clinical benefit and a favorable safety profile over a 5-day treatment window with 24 months of follow-up.
Impact: High-quality randomized evidence for an RSV antiviral in the most vulnerable age group is rare; these findings open the door to therapeutic options complementing prevention in infants.
Clinical Implications: Ziresovir may offer an early clinical benefit for hospitalized infants with RSV and a favorable safety profile; larger global trials powered for hard outcomes (oxygen requirement, LOS, ICU) should guide adoption.
Key Findings
- At day 3, ziresovir improved WBCS more than placebo (LS mean change −3.5 vs −2.2; difference −1.2; p=0.0004) in the ITT-infected population ≤6 months.
- No drug-related serious adverse events or deaths occurred; drug-related TEAEs were 18% (ziresovir) vs 11% (placebo).
- Trial included 24-month safety follow-up; the prespecified infant subgroup analysis supports early symptomatic benefit.
Methodological Strengths
- Randomized, double-blind, placebo-controlled phase 3 design across 28 hospitals
- Prespecified analysis of infants ≤6 months with PCR-confirmed RSV and standardized clinical scoring
Limitations
- Primary endpoint is a short-term clinical score at 48 hours post-baseline, not hard outcomes (e.g., oxygen days, hospitalization length).
- Subgroup limited to infants ≤6 months in China; generalizability and effect in severe disease require confirmation.
Future Directions: Conduct larger, multinational trials powered for clinically meaningful endpoints (oxygen use, LOS, ICU admission, mortality), evaluate resistance, and define optimal timing with supportive care.
3. Long-term mortality trends among individuals with tuberculosis: a retrospective cohort study of individuals diagnosed with tuberculosis in Brazil.
Linkage of national TB notifications with mortality records in Brazil (n=834,594; 4.1 million person-years) shows markedly elevated mortality after TB diagnosis: MRR 11.28 in year 1, declining to 1.46 by year 10, with cumulative excess mortality of 9.9% at 10 years. Excess risk concentrates in ages 30–44, relapse, loss to follow-up, and co-prevalent HIV and alcohol use disorder; causes of death shift over time to cardiovascular, cancer, and non-TB respiratory diseases.
Impact: This large-scale, nationally representative analysis quantifies persistent excess mortality after TB and identifies modifiable risk factors, informing post-TB care models and health policy.
Clinical Implications: Post-TB care should extend beyond treatment completion to long-term risk management, including cardiovascular prevention, malignancy screening as appropriate, optimized HIV care, and addressing alcohol use; targeted surveillance is warranted for relapse and those lost to follow-up.
Key Findings
- Mortality rate ratio was 11.28 in year 1 after TB diagnosis, declining to 3.59 in year 2 and 1.46 by year 10.
- Cumulative excess mortality reached 6.12% at 1 year and 9.90% at 10 years post-diagnosis.
- Excess mortality was highest among ages 30–44, and associated with relapse, loss to follow-up, HIV, and alcohol use disorder; causes of death shifted toward CVD, cancer, and non-TB respiratory diseases over time.
Methodological Strengths
- Very large national cohort (834,594 individuals) with 4.1 million person-years and linked mortality data
- Age/sex/year/state matched comparisons to general population and cause-of-death characterization
Limitations
- Observational retrospective design with potential residual confounding and misclassification of causes of death.
- Generalizability beyond Brazil may vary due to healthcare system differences; some risk factors may be under-ascertained.
Future Directions: Implement and evaluate post-TB care packages targeting cardiovascular risk, mental health and substance use, and track long-term outcomes; investigate causal pathways and interventions in high-risk subgroups.