Background: During the 2023-2024 season, the influenza epidemic in South Korea peaked earlier, and the influenza vaccination rate among individuals aged ≥ 65 was high (82.2%). However, data on real-world vaccine effectiveness against influenza are lacking.

Methods: From November 2023 to April 2024, we conducted a multicenter retrospective case-control study on adult patients aged ≥ 18 years who presented with influenza-like illness at seven medical centers as a part of a hospital-based influenza morbidity and mortality surveillance (HIMM) program in South Korea. Demographic and clinical data were collected from questionnaire surveys and electronic medical records. Using a test-negative design, we assessed the effectiveness of the 2023-2024 seasonal influenza vaccine, with age, sex, and comorbidities included as covariates.

Results: A total of 3390 participants were enrolled through the HIMM system, including 1695 patients with either rapid antigen test (RAT) or real-time reverse-transcription polymerase chain reaction (RT-PCR) positive results and controls matched for age, sex, and months of registration. Among the 1696 influenza-positive patients, 1584 (93.5%) underwent RAT, with 88.9% testing positive for influenza A and 11.1% for influenza B. During the study periods, the overall vaccine effectiveness (VE) was 24.3% (95% confidence interval (CI), 11.5 to 35.2). The VE was insignificant when limited to older adults aged ≥ 65 years (13.5%; 95% CI, -17.9 to 36.6). In the subgroup analysis by subtype, the VE was 19.0% (95% CI, 5.0 to 31.0) for influenza A and 56.3% (95% CI, 35.3 to 70.6) for influenza B. Notably, influenza VE was 20.4% (95% CI, 2.9 to 34.8) in the early period (November to December) but decreased to 12.4% (95% CI, -14.9 to 33.2) in the late period (January to April).

Conclusion: During the 2023-2024 season, the influenza vaccine showed a modest effectiveness (24.3%) against laboratory-confirmed influenza, which was particularly higher for influenza B. Because the VE was insignificant in older adults, particularly during the late period, better immunogenic influenza vaccines with longer-lasting protection should be considered.