Association of In-Hospital Influenza Vaccination With Reduced 1-Year Mortality in Critically Ill Patients With Chronic Pulmonary Disease A Real-World Target Trial Emulation

Background: Influenza vaccination is recommended widely to reduce the risk of death and serious illness in vulnerable people, but in-hospital influenza vaccination for critically ill patients with chronic pulmonary disease (CPD) remains limited. Research Question: Is in-hospital influenza vaccination effective in improving the prognosis of critically ill patients with CPD? Study Design and Methods: We designed a target trial emulation using critically ill inpatients with CPD from the Medical Information Mart for Intensive Care IV database (2011-2022). Propensity score matching was used to balance baseline characteristics. The primary effectiveness outcome was 1-year mortality, with fever within 7 days after vaccination as an exploratory safety outcome. Associations with mortality were assessed using Cox and accelerated failure time models, whereas readmission or emergency department (ED) visits were assessed using logistic models. Vaccine effectiveness (VE) was estimated as (1 – hazard ratio or OR) × 100, and the number needed to vaccinate (NNV) was derived. Noninferiority for fever was defined as the risk difference (RD) with upper 95% CI of < 5%. Results: Among 7,734 patients, 3,803 patients (49.2%) received the influenza vaccine. Vaccination was associated with reduced 1-year mortality (VE, 12%; 95% CI, 3%-20%), with NNV to prevent 1 death of 30 (95% CI, 18-119). Furthermore, patients who were vaccinated showed 12% (95% CI, 1%-21%) lower 90-day mortality, 13% (95% CI, 3%-22%) reduced readmission risk, and 23% (95% CI, 12%-32%) less rate of ED visits. Noninferiority in fever incidence was demonstrated for the vaccinated group compared with the unvaccinated group according to the prespecified noninferiority criterion (RD, 2.22%; 95% CI, –0.02% to 4.47%). Interpretation: Our results show that in-hospital influenza vaccination is effective for critically ill patients with CPD, supporting its integration into routine inpatient care to improve long-term outcomes.