Moderna’s Omicron-adapted COVID-19 vaccines appear to reduce the risk of hospitalization and death in adults who are not pregnant or have a weakened immune system, according to a rapid review published in the Annals of Internal Medicine.
The review, conducted for the American College of Physicians, evaluated evidence published from January 2022 to September 2025 on the effectiveness, comparative effectiveness, and harms of COVID-19 vaccines in adults. Researchers led by a team from Cochrane Austria identified five randomized controlled trials and 18 nonrandomized studies for inclusion.
Vaccines linked to reduced severe outcomes
Across the studies, Omicron-adapted vaccines were associated with reductions in both all-cause mortality and COVID-related hospitalizations compared with no Omicron-adapted vaccination. Vaccine effectiveness estimates ranged from 26.6% (95% confidence interval [CI], 5.5% to 42.3%) to 75.2% (95% CI, 70.6% to 79.9%) for all-cause mortality and from 16.6% (95% CI, 6.5% to 25.8%) to 67.8% (95% CI, 63.1% to 72.5%) for COVID-related hospitalization.
Omicron-adapted vaccines were associated with reductions in both all-cause mortality and COVID-related hospitalizations compared with no Omicron-adapted vaccination.
The evidence also suggested that vaccination timing may influence protection. When an Omicron-adapted vaccine was administered more than a year after the previous COVID vaccine dose, it likely reduced the risk of both death and hospitalization. When given sooner after the prior dose, however, the review found little or no difference in hospitalization risk compared with those who did not receive an Omicron-adapted dose.
The authors also compared different vaccine formulations. In adults of all ages, the bivalent (two-strain) mRNA-1283.222 vaccine showed no difference in all-cause mortality or serious adverse events compared with the mRNA-1273.222 vaccine.
Limited, low-certainty data on potential harms
Evidence on potential harms was more limited. One of the reviewed studies found that Omicron-adapted vaccines may be associated with about 2.7-fold higher rates of myocarditis compared with no Omicron-adapted vaccination among adults aged 50 years or older, but the confidence interval was wide (95% CI, 1.0 to 7.0), indicating low certainty about the findings.
The authors noted several limitations to the review, including the absence of randomized trials directly comparing Omicron-adapted vaccination with no vaccination, limited data on adverse effects, and a lack of consideration of cofounders such as sex and comorbidities.
Overall, the findings suggest that updated vaccines targeting Omicron variants continue to provide protection against severe outcomes from COVID. “Omicron-adapted vaccines improve protection compared with no Omicron-adapted vaccines, particularly when administered more than 365 days after the prior vaccination,” the authors conclude.
