JN.1 COVID-19 Booster Safety Confirmed in Danish Study of More than 1 Million Older Adults

A nationwide Danish cohort study of more than 1 million older adults found no increased risk of 29 serious adverse events during the first 28 days after administration of an updated mRNA COVID-19 vaccine targeting the Omicron JN.1 lineage.

The analysis included adults with a mean age of approximately 67 years who received the 2024–2025 seasonal booster, according to the research letter published in JAMA Network Open. Adjusted incidence rate ratios (IRRs) for all monitored events did not indicate elevated risk compared with reference periods, investigators said.1

Research Rationale

The JN.1 subvariant of Omicron became the dominant SARS-CoV-2 strain in late 2024, prompting US and European regulators to authorize updated mRNA vaccines incorporating the JN.1 (KP.2) strain.2,3 While immunogenicity and effectiveness data are emerging, postmarketing safety data have been limited. Given prior concerns over rare but serious adverse events following COVID-19 vaccination, Danish researchers sought to assess short-term safety signals in a real-world, population-wide setting.

For the study data, lead author Anders Peter Hviid, head of department and professor in the department of epidemiology research at Statens Serum Institut, Copenhagen, Denmark, and colleagues, drew on linked national health registries covering all Danish adults recommended for the 2024–2025 JN.1 booster, ie, individuals aged 65 years and older and those in high-risk groups (eg, pulmonary and cardiovascular disease) with prior receipt of 3 or more COVID-19 vaccine doses. Follow-up ran from May 1, 2024, to March 31, 2025.

In their analysis, Hviid et al treated vaccination status as a time-varying exposure. They evaluated 29 predefined adverse events of special interest, adapted from international safety monitoring lists, using first hospital contact for a relevant diagnosis as the event definition, according to the study. The team compared rates during the 28-day risk window after JN.1 vaccination with rates during a reference period (prevaccination or more than 43 days postdose) using Poisson regression with multivariable adjustment for age, sex, region, vaccination priority group, calendar time, and comorbidity count.

Findings

The study cohort included 1,585,883 individuals (mean age 66.8 years; 54.4% women). Of this group, 1,012,400 (mean age 73.5 years) received the JN.1-containing booster. Hviid and colleagues stated that no outcome showed a statistically significant rate increase in the post-vaccination risk window.

Selected adjusted IRRs (95% CI) included:

• Ischemic cardiac events: 0.84 (0.76–0.94)
• Intracranial bleeding: 0.92 (0.76–1.13)
• Myocarditis: 1.12 (0.41–3.10)
• Guillain-Barré syndrome: 0.42 (0.20–0.89)
• Pulmonary embolism: 0.75 (0.62–0.90)

For 19 of the 29 outcomes, the upper CI bound was inconsistent with even a moderate to large relative risk increase (ie, greater than 1.5), a finding providing additional reassurance, authors wrote. They also reported that rare events such as transverse myelitis were too infrequent to estimate risk ratios reliably.

Limitations. Among the study's limitations the authors noted the findings are still subject to residual confounding and healthcare utilization bias despite the use of within-individual comparisons. In addition they pointed out that their results reflect short-term risk of adverse events only, not long-term vaccine safety.

Authors' Final Thoughts. In this large, registry-based analysis, receipt of a JN.1-updated mRNA COVID-19 vaccine was not associated with increased short-term risk for a range of serious adverse events. The results support the safety profile of the updated booster in older adults and high-risk populations. Continued monitoring remains important, particularly for rare events and for assessing longer follow-up intervals.

References

1. Andersson NW, Thiesson EM, Hviid A. Safety of JN.1-updated mRNA COVID-19 vaccines. JAMA Netw Open. 2025;8(7):e2523557. doi:10.1001/jamanetworkopen.2025.23557.

2. FDA approves and authorizes updated mRNA COVID-19 vaccines to better protect against currently circulating variants. News release. FDA. August 22, 2024. Accessed August 13, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-and-authorizes-updated-mrna-covid-19-vaccines-better-protect-against-currently

3. ETF recommends updating COVID-19 vaccines to target new JN.1 variant. News release. European Medicines Association. April 30, 2024. Accessed August 13, 2025. https://www.ema.europa.eu/en/news/etf-recommends-updating-covid-19-vaccines-target-new-jn1-variant