Adverse Events After LP.8.1-Containing COVID-19 mRNA Vaccines

BackgroundThe LP.8.1-containing COVID-19 mRNA vaccines were recommended for the 2025 seasonal vaccination campaigns in Europe and the United States. Safety data on these vaccines are limited. MethodsWe conducted a nationwide register-based cohort study in Denmark including all adults aged 65 years and older or at high risk of severe COVID-19 who had received previous COVID-19 vaccine doses. The study period was July 1, 2025, to December 3, 2025. We estimated incidence rate ratios using Poisson regression comparing rates of 30 adverse events within 28 days following LP.8.1-containing vaccination with reference period rates, adjusted for age, sex, region of residence, high risk of severe COVID-19, calendar time, and comorbidities. Self-controlled case series analysis was conducted as a complementary approach. ResultsAmong 1,565,697 individuals (mean age 69.5 years; 53.8% female), 958,633 received an LP.8.1-containing vaccine. Receipt of an LP.8.1-containing vaccine was not associated with a statistically significant increased rate of any of the 30 adverse events within 28 days after vaccination. The incidence rate ratio was 0.95 (95% CI, 0.86-1.06) for ischemic cardiac event, 0.83 (95% CI, 0.76-0.92) for cerebrovascular event, and 0.32 (95% CI, 0.04-2.50) for myocarditis. Results from the self-controlled case series analysis were similar. ConclusionsIn a nationwide cohort of more than 1.5 million adults, no increased risk of 30 adverse events was observed following vaccination with LP.8.1-containing COVID-19 mRNA vaccines.