Daily Respiratory Research Analysis

IMPORTANCE: A single respiratory syncytial virus (RSV) vaccine dose is recommended for older adults and persons at increased risk for severe RSV. Clinical information on the long-term effectiveness of RSV vaccines is needed. OBJECTIVE: To determine the effectiveness of RSV vaccination over 2 respiratory illness seasons. DESIGN, SETTING, AND PARTICIPANTS: This target trial emulation used data from the Veterans Health Administration and included veterans 60 years and older who were eligible for RSV vaccination from September 2023 to March 2024. EXPOSURE: A single dose of a recombinant stabilized prefusion F protein RSV vaccine vs no RSV vaccination. MAIN OUTCOMES AND MEASURES: Eligible vaccine recipients were matched with up to 4 unvaccinated individuals in 7 monthly, nested sequential trials from September 1, 2023, to March 31, 2024. Outcomes were ascertained through March 31, 2025. The primary outcome was any positive RSV test result from day 14 following the matched index date. Secondary outcomes included RSV-associated emergency department or urgent care visits, hospitalizations, or intensive care unit admissions. Vaccine effectiveness was estimated as 100 × (1 - risk ratio). RESULTS: A total of 288 111 vaccinated individuals were matched to 1 075 893 unique control individuals, weighted equally to represent 576 222 individuals, and followed up for a median of 15.8 months (IQR, 14.5-17.0). Across both groups, 544 364 of 576 222 veterans (94.5%) were male, and the median age was 76.1 years (IQR, 71.6-80.0). Vaccine effectiveness against documented RSV infections decreased from 82.5% (95% CI, 77.5%-86.9%) over 0 to 1 month to 59.4% (95% CI, 55.6%-63.5%) over 0 to 18 months of follow-up. During the same period, effectiveness decreased from 84.9% (95% CI, 78.4%-90.2%) to 60.5% (95% CI, 56.4%-65.7%) for emergency visits and 88.9% (95% CI, 77.9%-95.7%) to 57.3% (95% CI, 47.3%-66.4%) for hospitalizations and was 92.5% (95% CI, 61.1%-100.0%) and 71.9% (95% CI, 42.8%-90.0%) for intensive care unit admissions. Among immunocompromised individuals, protection against documented infections decreased from 75.2% (95% CI, 52.5%-89.3%) to 39.7% (95% CI, 23.9%-52.7%). CONCLUSIONS AND RELEVANCE: The study found that RSV vaccination was effective in preventing RSV illness and associated health care use but that protection decreased over 2 seasons. Reductions were most notable among immunocompromised persons, suggesting the need to review whether additional vaccine doses may benefit certain risk groups.

IMPORTANCE: The US Food and Drug Administration (FDA) has issued a warning and a label change regarding a potential association between trimethoprim-sulfamethoxazole (TMP-SMX) and acute respiratory failure in healthy adolescents and young adults. OBJECTIVE: To examine the 30-day risk of a hospital visit (ie, hospitalization or emergency department visit) with acute respiratory failure in adolescents and young adults aged 10 to younger than 25 years old newly dispensed oral TMP-SMX compared with new users of amoxicillin or a cephalosporin. DESIGN, SETTING, AND PARTICIPANTS: This retrospective, population-based, new-user cohort study in Ontario, Canada (2003-2023) used linked administrative health care data. The TMP-SMX vs amoxicillin and TMP-SMX vs cephalosporins cohorts both included adolescents and young adults aged 10 to younger than 25 years who were newly dispensed oral TMP-SMX, amoxicillin, or cephalosporins for 3 or more days from an outpatient pharmacy. Data were analyzed from January 1 to April 30, 2025. EXPOSURE: TMP-SMX for 3 days or more. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite outcome of the 30-day risk of a hospital visit with acute respiratory failure (defined as a diagnosis of acute respiratory failure or receipt of mechanical ventilation, tracheotomy, or extracorporeal membrane oxygenation). Secondary outcomes were the individual components of the composite outcome, all-cause hospitalization, and all-cause mortality. Overlap weighting on the propensity score was used to balance comparison groups on 84 indicators of baseline health. Weighted risk ratios were obtained using log-binomial regression and weighted risk differences using binomial regression. Sensitivity analyses using a negative control outcome, and case-crossover analysis were also performed. RESULTS: The TMP-SMX vs amoxicillin cohort included 575 218 individuals (44 801 TMP-SMX users and 530 417 amoxicillin users; median age after weighting, 19 years [IQR, 16-22 years]; 74.3% female). The TMP-SMX vs cephalosporins cohort included 248 236 individuals (51 197 TMP-SMX users and 197 039 cephalosporin users; median age after weighting, 19 years [IQR, 16-22 years]; 72.3% were female). The risk of the composite outcome occurred in 15 of 44 801 patients (0.03%) who started TMP-SMX and in 49 of 530 417 (0.01%) who started amoxicillin (number of weighted events, 7 of 21 579 [0.03%] for TMP-SMX and 2 of 21 579 [0.01%] for amoxicillin; weighted risk ratio, 2.79 [95% CI, 1.01-7.71]; weighted risk difference, 0.02% [95% CI, 0.001%-0.04%]). The risk of the composite outcome occurred in 17 of 51 197 patients (0.03%) who started TMP-SMX and in 21 of 197 039 (0.01%) who started cephalosporins (number of weighted events, 8 of 20 538 [0.04%] for TMP-SMX and 3 of 20 538 [0.01%] for cephalosporins; weighted risk ratio, 2.85 [95% CI, 1.11-7.31]; weighted risk difference, 0.02% [95% CI, 0.005%-0.05%]). Results were consistent in sensitivity analyses. CONCLUSIONS AND RELEVANCE: These findings suggest that the 30-day risk of a hospital visit with acute respiratory failure was higher among those receiving TMP-SMX compared with those receiving amoxicillin or cephalosporins. These findings supported the FDA warning, and if replicated, the risks should be carefully weighed against the benefits of TMP-SMX use. Regulatory agencies could reinforce the FDA warning, and product monographs and prescribing guidelines should be updated and revised accordingly.

Three critically ill or fatal avian influenza A(H5N1) human infections have been reported in North America since November 2024. Notably, all were infected with genotype D1.1 instead of B3.13, the dominant genotype before November 2024. Here, we demonstrated that D1.1 could replicate to higher titers in human nasal and airway organoid-derived transwell monolayers from 6 donors. D1.1 exhibited a better binding to α2,3- and α2,6-linked SA than B3.13. No significant differences in most inflammatory or antiviral cytokines/chemokines was observed. These observations suggest that D1.1 is better adapted to both the upper and lower human respiratory tract epithelium than B3.13.