Objectives: To determine vaccine effectiveness against influenza infection among UK healthcare workers between 1 September 2023 and 31 March 2024.

Methods: We conducted a prospective cohort study, including hospital-based healthcare workers (HCWs) enrolled in the SARS-CoV-2 Immunity & Reinfection Evaluation (SIREN) study. Participants completed fortnightly influenza PCR testing and questionnaires. Influenza vaccination status was identified from national vaccination records and questionnaires. Vaccine effectiveness against PCR-positive influenza was estimated using Cox regression adjusted for age group, sex, chronic disease status, patient-facing role, and region. Case-control and test-negative case-control (TNCC) analyses, using multivariable logistic regression, were also performed.

Results: Among 4,934 participants, median age was 55 years (IQR 47-60 years) and most were female (78.7%) and white (85.6%). Overall, 3,857 (78.2%) received influenza vaccination and 266 (5.4%) tested positive for influenza, of which 227 (85.3%) reported acute respiratory infection symptoms. Adjusted vaccine effectiveness was 39.9% (95% confidence interval 21.8 - 53.8), and similar using case-control (41.2%, 22.5 - 55.2) and TNCC (45.9%, 21.8 - 62.2) approaches.

Conclusions: Influenza vaccine effectiveness was 40%, consistent with estimates for symptomatic patients. Applied to the combined UK healthcare workforce, this potentially translates to prevention of over 50,000 infections. These findings emphasise the importance of seasonal influenza vaccination to reduce healthcare workers infections and thereby protect patients and reduce workforce pressures.