Who to Boost When: The Effect of Age and Dosing Interval on Delta and Omicron COVID-19 Incidence in the Open-label Phase of the COVE Trial

Open Forum Infect Dis. 2024 Nov 25;11(12):ofae689. doi: 10.1093/ofid/ofae689. eCollection 2024 Dec.

Abstract

Background: To help inform COVID-19 vaccination recommendations, we evaluated the impact of age and dosing interval on clinical benefit of a third dose of mRNA-1273.

Methods: Approximately 17 000 participants from the phase 3 Coronavirus Efficacy trial who previously received 2 doses of 100 µg mRNA-1273 were evaluated for COVID-19 between September 2021 and April 2022 during uptake of a third booster dose of 50 µg of mRNA-1273. Cox models assessed booster relative efficacy of a third dose.

Results: Initial booster relative efficacy against Delta COVID-19 was 83% (95% confidence interval, 60-93) 14 days postdose and 83% (67-91) 60 days later. Initial booster efficacy against Omicron COVID-19 was 56% (44-65) at 14 days postdose and 4% (-27 to 28) 120 days later. For those aged ≥65 years, initial booster efficacy against Omicron COVID-19 was 86% (69-93) compared with 50% (36-61) for those <65 years. Placebo crossover to 2 doses of mRNA-1273 induced a median 5-month difference from the second to third dose between the original randomized arms. Postboost, the mRNA-1273 arm had a 24% (16%, 32%) lower risk of Omicron COVID-19 compared to the placebo-mRNA-1273 arm. Modeling predicted a 41% postboost reduction in Omicron COVID-19 for a 15- versus 7-month interval between the second and third doses.

Conclusions: Boosting reduced Delta COVID-19 risk by 83% through 2 months and reduced Omicron COVID-19 risk by 56% but declined by 4 months. A 15- versus 7-month dosing interval predicted a 41% postboost reduction in Omicron COVID-19 but increased preboost risk.

Primary funding source: The National Institutes of Health/National Institute of Allergy and Infectious Diseases. Registration for the COVE Trial. ClinicalTrials.gov ID# NCT04470427.

Keywords: COVID-19 vaccine; SARS-CoV2; booster dose; mRNA-1273.

Associated data

  • ClinicalTrials.gov/NCT04470427