Daily Respiratory Research Analysis
Durability of protection after RSV vaccination in older adults decreased over two seasons, especially among immunocompromised individuals, supporting consideration of booster dosing in high‑risk groups. A large population-based study found a higher short-term risk of acute respiratory failure after TMP-SMX versus comparators in adolescents and young adults, reinforcing safety warnings. Mechanistic work showed the emergent H5N1 D1.1 genotype replicates better in human nasal and airway organoids t
Summary
Durability of protection after RSV vaccination in older adults decreased over two seasons, especially among immunocompromised individuals, supporting consideration of booster dosing in high‑risk groups. A large population-based study found a higher short-term risk of acute respiratory failure after TMP-SMX versus comparators in adolescents and young adults, reinforcing safety warnings. Mechanistic work showed the emergent H5N1 D1.1 genotype replicates better in human nasal and airway organoids than the prior dominant B3.13, underscoring heightened zoonotic risk.
Research Themes
- RSV vaccine durability and booster strategy in older adults
- Drug safety and acute respiratory failure risk with TMP-SMX
- Zoonotic influenza adaptation in human respiratory epithelium
Selected Articles
1. Durability of Respiratory Syncytial Virus Vaccine Effectiveness Among US Veterans.
In a target trial emulation of over 288,000 vaccinated US veterans, RSV vaccine effectiveness waned from 82.5% in the first month to 59.4% by 18 months against documented infection, with similar declines for emergency visits and hospitalizations. Protection remained high against ICU admission but decreased notably in immunocompromised individuals.
Impact: Large-scale effectiveness data across two seasons inform booster policy and shared decision-making for older and immunocompromised adults.
Clinical Implications: Counsel older adults on waning protection and consider additional dosing for immunocompromised patients; maintain layered prevention during peak seasons.
Key Findings
- VE against documented RSV infection declined from 82.5% (0–1 month) to 59.4% over 0–18 months.
- VE against ED/urgent care visits decreased from 84.9% to 60.5%; against hospitalization from 88.9% to 57.3%.
- Immunocompromised individuals had greater waning (75.2% to 39.7% against infection).
Methodological Strengths
- Target trial emulation with sequential matching across months and long follow-up (median 15.8 months).
- Very large, integrated health system cohort with multiple clinically relevant outcomes.
Limitations
- Predominantly older male veteran population may limit generalizability.
- Residual confounding possible despite matching and design.
Future Directions: Evaluate optimal timing and target groups for booster dosing, and assess effectiveness against severe disease in diverse populations.
2. Trimethoprim-Sulfamethoxazole and Acute Respiratory Failure in Adolescents and Young Adults.
In two large new-user cohorts of adolescents and young adults, TMP-SMX was associated with a significantly higher 30-day risk of a hospital visit with acute respiratory failure compared with amoxicillin or cephalosporins, albeit with a small absolute risk difference (~0.02%). Findings align with and support the FDA warning.
Impact: Provides high-quality pharmacoepidemiologic evidence to guide antibiotic selection in young populations and informs labeling and stewardship.
Clinical Implications: Prefer amoxicillin or cephalosporins when appropriate; if TMP-SMX is used, counsel patients on early respiratory symptoms and ensure close follow-up.
Key Findings
- TMP-SMX vs amoxicillin: weighted RR 2.79 (95% CI 1.01–7.71); absolute risk difference 0.02%.
- TMP-SMX vs cephalosporins: weighted RR 2.85 (95% CI 1.11–7.31); absolute risk difference 0.02%.
- Results were robust across sensitivity analyses, including negative control and case-crossover.
Methodological Strengths
- Very large population-based new-user cohorts with propensity score overlap weighting across 84 baseline covariates.
- Multiple sensitivity analyses, including negative control outcome and case-crossover.
Limitations
- Administrative data may miss clinical nuance; outcome is rare with small absolute risk difference.
- Residual confounding and misclassification are possible despite robust methods.
Future Directions: Replicate in other settings and explore mechanisms; identify high-risk subgroups and evaluate risk mitigation strategies.
3. Avian influenza virus A(H5N1) genotype D1.1 is better adapted to human nasal and airway organoids than genotype B3.13.
Using human nasal and airway organoid-derived monolayers from six donors, H5N1 D1.1 replicated to higher titers and bound both α2,3- and α2,6-linked sialic acids better than B3.13, without marked cytokine differences. These data suggest enhanced adaptation of D1.1 to human upper and lower respiratory epithelium.
Impact: Provides mechanistic evidence explaining recent severe human cases and signals increased zoonotic potential of a newly emergent H5N1 genotype.
Clinical Implications: Heightened surveillance and risk assessment for genotype D1.1 are warranted; findings support preparedness for upper and lower airway infection potential.
Key Findings
- D1.1 replicated to higher titers than B3.13 in human nasal and airway organoid monolayers from six donors.
- D1.1 showed stronger binding to both α2,3- and α2,6-linked sialic acids than B3.13.
- No major differences in inflammatory/antiviral cytokine profiles between genotypes.
Methodological Strengths
- Use of primary human nasal and airway organoid-derived monolayers from multiple donors.
- Comparative receptor-binding assessment (α2,3 and α2,6 sialic acids) and replication kinetics.
Limitations
- In vitro organoid model without in vivo transmission or pathogenicity data.
- Small donor number may limit generalizability.
Future Directions: Assess transmissibility and pathogenicity in animal models; integrate genomic surveillance to monitor D1.1 spread and evolution.