Real-world effectiveness of COVID-19 XBB.1.5 monovalent mRNA vaccine: Analysis over nine months

Abstract

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve, with each new strain becoming immunologically distinct from previous strains. The updated vaccine formulation for the 2023/24 season contained the mRNA of the XBB.1.5 sublineage. As the coronavirus disease-2019 (COVID-19) has become an endemic disease, a yearly assessment of updated COVID-19 vaccines is necessary. Methods: This test-negative case-control study included patients who underwent COVID-19 testing between November 2023 and April 2024, and between July and August 2024, at eight university hospitals. To assess the change in VE over time, the study was divided into periods 1 (November–December 2023), 2 (January–April 2024), and 3 (July–August 2024) to assess the change of vaccine effectiveness (VE). VE (against laboratory-confirmed COVID-19 and COVID-19-related hospitalization) was calculated using adjusted odds ratios (OR) derived from multivariable logistic regression models. Results: A total of 6198 patients were included (1671, 1811, and 2716 in period 1, 2, and 3, respectively), out of which 1115 (18.0%) underwent XBB.1.5 monovalent vaccination. The adjusted VE against laboratory-confirmed COVID-19 during each study period was 57.1% (95% confidence interval [CI]: 38.0–70.6, p < 0.001), 18.8% (95% CI -4.7–37.2, p = 0.110), and 3.3% (95% CI -15.4–19.1, p = 0.707), respectively. The corresponding statistics against COVID-19-related hospitalization were 74.0% (95% CI 40.7–78.6, p < 0.001), 34.2% (−6.8–46.4, p = 0.114), and 26.1% (4.7–42.8, p = 0.020), respectively. Conclusion: Despite waning VE against laboratory-confirmed COVID-19 over time, XBB.1.5 mRNA vaccines conferred sustained protection against COVID-19-related hospitalizations throughout the year. © 2025 Elsevier Ltd