Abstract Background Asthma is a chronic inflammatory airway disease affecting millions of adults in the United States. While COVID-19 vaccination reduces severe outcomes in the general population, its impact on asthma-specific outcomes remains unclear when chronic obstructive pulmonary disease (COPD) is excluded. Understanding vaccination benefits in this group is essential for evidence-based prevention strategies. Research Question Does COVID-19 vaccination reduce all-cause mortality, asthma exacerbations, and mechanical ventilation among adults with asthma independent of COPD? Methods We conducted a retrospective, propensity-score-matched cohort study using the TriNetX US Collaborative Network. Adults ≥18 years with asthma (ICD-10 J45) and preserved spirometry (FEV₁/FVC ≥ 70%) were included. Vaccinated patients were identified using COVID-19 vaccine CPT and RxNorm codes (91300-91301, 0001A-0012A, 2468231) and compared with unvaccinated controls. Patients with COPD, interstitial lung disease, or pneumoconioses were excluded. One-to-one propensity matching balanced demographics, comorbidities, and medications. Primary outcome was all-cause mortality; secondary outcomes included asthma exacerbation (J45.901) and mechanical ventilation (ICD-10-PCS 5A1945Z). Risk ratios (RR), risk differences (RD), Kaplan-Meier (KM) curves, and hazard ratios (HR) were calculated. Results Before matching, 24,873 unvaccinated and 10,052 vaccinated adults met criteria. After matching, 6,990 per group remained balanced. Mortality: 3.3% unvaccinated vs 1.1% vaccinated (RD 2.2%, 95% CI 1.7-2.7; RR 0.33, 95% CI 0.25-0.43). KM survival: 89.81% vs 97.58%, log-rank χ² = 29.896, p 0.001; HR 2.094 (95% CI 1.597-2.745). Asthma exacerbation: 8.7% vs 5.5% (RD 3.2%, 95% CI 2.4-4.1; RR 0.63, 95% CI 0.56-0.71); log-rank p 0.001; HR 0.75 (95% CI 0.66-0.86). Mechanical ventilation: 0.4% vs 0.2% (RD 0.2%, 95% CI 0.1-0.4; RR 0.41, 95% CI 0.20-0.82); log-rank p = 0.092; HR 0.54 (95% CI 0.26-1.12). Median follow-up: 1,199 days (IQR 1,769) unvaccinated vs 974 days (IQR 1,090) vaccinated. Conclusions Among adults with asthma and preserved lung function, COVID-19 vaccination was associated with markedly improved survival and fewer exacerbations, with a non-significant reduction in ventilation. Despite shorter follow-up in vaccinated individuals, consistent risk and survival trends support a protective role of vaccination in asthma populations. This abstract is funded by: None
Lohana et al. (Fri,) studied this question.