A Retrospective Test-Negative Case-Control Study to Evaluate Influenza Vaccine Effectiveness in Preventing Influenza Among Immunocompromised Adults With a Solid Organ Transplant

Abstract

Vaccination may prevent influenza in solid organ transplant (SOT) recipients. This study evaluates the influenza vaccine effectiveness (VE) in this high-risk population in the Netherlands. We also compared disease progression and 30-day mortality between vaccinated and unvaccinated influenza patients. In this multicenter, test-negative case-control study, SOT recipients with respiratory symptoms were included when tested for viral respiratory infections during the respiratory seasons between 1 January 2013 and 1 July 2024. Cases had a positive influenza PCR, while controls tested negative. Influenza vaccination in cases (74/174) and controls (291/602) were compared after adjusting for potential confounders. VE was calculated as (1-adjusted odds ratio) x 100. The overall VE was 6.9% (95% CI -40.9 to 38.4), with considerable variation across seasons. For those aged ≥65 years, VE was higher (32.4%, 95% CI -56.5-70.8) compared to those aged 18-64 years (4.8%, 95% CI -56.5 to 42.1). The adjusted VE against influenza A [7.5% (-46.0 to 41.3)] was higher than against influenza B (-3.8% (-146.7 to 56.3)). No differences in influenza-related complications were observed between the vaccinated and unvaccinated cases. The observed seasonal influenza vaccine effectiveness in adult SOT recipients is limited; further investigation for improvement is warranted.

Keywords: Netherlands; influenza; influenza vaccination; influenza vaccine effectiveness; solid organ transplant patients.

FIGURE 1

Number of cases and controls, incidence of influenza in SOT recipients and influenza vaccine effectiveness each respiratory season. Presented in the figure are the amount of cases and controls each respiratory season. Below the figure, the adjusted VE in SOT recipients is presented each respiratory year, compared to the yearly influenza VE in the general population in the Netherlands, reported by the National Institute for Public Health and the Environment. In addition, incidence of influenza cases is calculated among all SOT recipients still alive during a respiratory season at January 1 of that season. *NA because no cases were detected (2020/2021) or the sample size was too small (2012/2013, 2013/2014). ^&Reported by the National Institute for Public Health and the Environment. ^{^}Adjusted for the confounders age, history of chronic pulmonary disease, history of rejection therapy, hospital of inclusion, season, use of cell division inhibitors, highly immunosuppressed status. Abbreviations: NA, not applicable; VE, vaccine effectiveness; PCR, polymerase chain reaction; SOT, solid organ transplant.

FIGURE 2

Estimation of vaccine effectiveness against laboratory confirmed influenza. Overall VE in SOT recipients, VE by age group and by influenza virus subtype. Errors bars represent 95% CI. *Corrected for age, history of chronic pulmonary disease, history of rejection therapy, hospital of inclusion, season, use of cell division inhibitors, highly immunosuppressed status. ^&Only cases with influenza A subtypes were included; cases with influenza B virus subtypes were excluded. ^Only cases with influenza B virus subtypes were included; patients with influenza A virus subtype were excluded. Abbreviations: OR, odds ratio; VE, vaccine effectiveness; CI, confidence interval.