Influenza vaccine effectiveness in inpatient and outpatient settings in the United States, 2015 - 2018.


Demonstration of influenza vaccine effectiveness (VE) against hospitalization for severe illness in addition to milder outpatient illness may strengthen vaccination messaging and improve suboptimal uptake in the U.S. Our objective was to compare patient characteristics and VE between U.S. inpatient and outpatient VE networks.

We tested adults ≥18-years with acute respiratory illness (ARI) for influenza within two VE networks, one outpatient- and the other hospital-based, from 2015-2018. We compared age, sex, and chronic high-risk conditions between populations. The test-negative design was used to compare vaccination odds in influenza-positive cases versus influenza-negative controls. We estimated VE using logistic regression adjusting for site, age, sex, race/ethnicity, peak influenza activity, time-to-testing from symptom-onset, season (overall VE) and underlying conditions. VE differences (ΔVE) were assessed with 95% confidence intervals (CI) determined through bootstrapping with significance defined as excluding the null.

Inpatients and outpatients with ARI represent distinct populations. Despite comparatively poor health status among inpatients, influenza vaccination was effective in preventing hospitalizations associated with influenza.

The VE networks enrolled 14,573 (4144 influenza-positive) outpatients and 6769 (1452 influenza-positive) inpatients. Inpatients were older (median 62-years vs. 49-years) and had more high-risk conditions (median 4 vs. 1). Overall influenza VE across seasons was 31% (95%CI:26%-37%) among outpatients and 36% (27%-44%) among inpatients. Strain-specific VE among outpatients versus inpatients was 37% (25%-47%) vs. 53% (37%-64%) against H1N1pdm09, 19% (9%-27%) vs. 23% (8%-35%) against H3N2, and 46% (38%-53%) vs. 46% (31%-58%) against B-viruses. ΔVE was not significant for any comparison across all sites.

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