Updated COVID-19 mRNA Vaccine Did Not Increase Risk for Adverse Events

The updated COVID-19 mRNA vaccine that contained the Omicron JN.1 lineage did not increase the risk of adverse events (AEs) observed post vaccination, according to study data published in JAMA Network Open. Investigators analyzed 29 AEs of special interest for COVID-19 vaccinations.¹

In the study, eligible patients from Denmark who previously had 3 or more COVID-19 doses received the 2024-2025 JN.1 booster vaccination. The study took place from May 1, 2024, to March 31, 2025. The investigators analyzed each AE separately, and individuals were followed up until the first outcome event. Outcomes during the first 28 days after vaccination were compared with outcome rates during the remaining period, according to the study authors.¹

A total of 1,585,883 individuals, with a mean age of 66.8 years, were included. Slightly more than half (54.4%) were women, and 1,012,400 individuals received the updated COVID-19 vaccine during the follow-up period. The investigators found that there was no statistically significant increased rate for any of the 29 AEs during the 28-day risk period after receiving the vaccination. Specifically, the incidence rate ratio was 0.84 for ischemic cardiac events, 0.92 for intracranial bleeding, and 1.12 for myocarditis.¹

Other AEs included the following: anaphylaxis (incidence rate ratio, 0.85), cerebrovascular event (0.84), arterial thromboembolism (0.84), deep venous thrombosis (0.80), pulmonary embolism (0.75), pericarditis (0.42), traumatic coagulopathy and coagulative disorders (0.58), Guillain-Barré syndrome (0.57), Bell palsy (0.93), encephalomyelitis or encephalitis (1.2), appendicitis (0.96), aseptic arthritis (0.87), type 1 diabetes (0.95), subacute thyroiditis (0.26), heart failure (0.78), acute liver failure (0.78), acute kidney failure (0.67), acute pancreatitis (0.67), erythema multiforme (1.05), seizure (0.95), arterial aneurysm (1.01), and uveitis (0.69).¹

In data from another study published earlier in July 2025, investigators showed that the 2023-2024 COVID-19 vaccines were associated with fewer medically attended cases of COVID-19, but the effectiveness waned over time, which supported recommendations of a booster dose in the 2024-2025 season.² They found that 69% of cases occurred during a period of JN.1 predominance. The vaccine effectiveness was 24% in 7 to 299 days post vaccination. During 7 to 59 days post vaccination, vaccine effectiveness was 49%, decreasing by 7% at day 180 to 299.

The Advisory Committee on Immunization Practices (ACIP) discussed COVID-19 epidemiology and safety and efficacy for vaccination. For the 2025-2026 formula, the FDA Vaccines and Related Biological Products Advisory Committee recommended that the COVID-19 vaccines closely match currently circulating viruses, and the vaccine should include monovalent JN.1 lineage, preferably with the LP.8.1 strain.³

ACIP has not yet held a vote on the COVID-19 vaccine recommendations, despite conflicting information about who is eligible for the additional dose this upcoming respiratory season. However, the committee did discuss efficacy, including that 89% of children who were eligible for the COVID-19 vaccine and were hospitalized with the virus did not receive the most recently recommended COVID-19 vaccines.⁴

“The majority of children hospitalized with COVID-19 in October 2024 to March 2025 did not receive the most recently recommended COVID-19 vaccine,” Adam MacNeil, PhD, MBA, deputy branch chief for epidemiology in the CDC's Coronavirus and other Respiratory Viruses Epidemiology Branch, said in the panel.⁴ “Roughly 10% of children across all pediatric age groups have received their recommended COVID-19 [20]24-[20]25 dose.”

Recommendations for who should receive the newest dose are still conflicting, with the Department of Health and Human Services (HHS) and the CDC having different recommendations. HHS stated that healthy children and healthy pregnant women should be removed from the CDC’s recommended immunization schedule, but the CDC has different recommendations.⁵

“This particular change for pregnant individuals is the most perplexing and confusing. We know that pregnant and nonpregnant women who are healthy have the same risk for getting an infection,” Lauren Angelo, PharmD, MBA, associate dean of academic affairs at Rosalind Franklin University of Medicine and Science College of Pharmacy, said.⁵ “However, should a pregnant person get infected with the SARS-CoV-2 virus, there's a much higher risk for severe infection and hospitalization when compared [with] nonpregnant individuals who got COVID[-19], who had higher rates of ICU [intensive care unit] admission, requiring a ventilator, and death.”

READ MORE: COVID-19 Resource Center

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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. Gallagher A. 2023-2024 COVID-19 vaccine efficacy wanes over time. Drug Topics. July 21, 2025. Accessed July 29, 2025. https://www.drugtopics.com/view/2023-2024-covid-19-vaccine-efficacy-wanes-over-time

3. COVID-19 vaccines (2025-2026 formula) for use in the United States beginning in fall 2025. FDA. May 22, 2025. Accessed July 29, 2025. https://www.fda.gov/vaccines-blood-biologics/industry-biologics/covid-19-vaccines-2025-2026-formula-use-united-states-beginning-fall-2025

4. Gallagher A. ACIP votes against thimerosal vaccines for prevention of influenza. Drug Topics. June 27, 2025. Accessed July 29, 2025. https://www.drugtopics.com/view/acip-votes-against-thimerosal-vaccines-for-prevention-of-influenza

5. Gallagher A. New COVID-19 vaccine recommendations cause confusion among public, health care providers. Drug Topics. June 10, 2025. Accessed July 29, 2025. https://www.drugtopics.com/view/new-covid-19-vaccine-recommendations-cause-confusion-among-public-health-care-providers