LAUSR

Abstract Background Mutations occurring during egg-based influenza vaccine production may affect vaccine effectiveness. The mammalian cell-based quadrivalent inactivated influenza vaccine (IIV4c) demonstrated improved protection relative to egg-based vaccines in prior seasons. This study estimated the relative vaccine effectiveness (rVE) of IIV4c versus standard-dose egg-based quadrivalent inactivated influenza vaccine (IIV4e) in preventing influenza-related medical encounters (IRMEs) in the 2019–2020 US influenza season. Methods This retrospective cohort study was conducted using a dataset linking electronic medical records with medical and pharmacy claims data among individuals ≥18 years vaccinated with IIV4c or IIV4e during 2019–2020. A doubly robust inverse probability of treatment weighting model was used to obtain odds ratios (ORs) adjusted for age, sex, race, ethnicity, region, vaccination week, health status, frailty, and baseline healthcare resource utilization. rVE was calculated by (1 – OR) × 100. An exploratory analysis evaluated IRMEs in inpatient and outpatient settings separately. Results The final study cohort included 1 499 215 IIV4c and 4 126 263 IIV4e recipients ≥18 years of age. Fewer IRMEs were reported in individuals with recorded IIV4c versus IIV4e. The rVE for IIV4c versus IIIV4e for any IRME was 9.5% (95% confidence interval [CI], 7.9%–11.1%). Inpatient and outpatient rVEs were 5.7% (95% CI, 2.1%–9.2%) and 11.4% (95% CI, 9.5%–13.3%), respectively. In age subgroup analyses, rVEs favored IIV4c except in adults aged ≥65 years. Conclusions Adults vaccinated with IIV4c had a lower risk of IRMEs versus IIV4e recipients in the 2019–2020 US influenza season. These results support IIV4c as a potentially more effective public health measure against influenza than egg-based vaccines.