{"doi":"10.1093/ofid/ofad500.2470","title":"1939. Who to Boost When: An Analysis of Dosing Interval and Age on COVID-19 Outcomes in the COVE Trial During the Delta and Omicron Waves","abstract":"Abstract Background The effects of age and interval between vaccine doses on COVID-19 are incompletely understood, yet critical for public health policy. Methods This analysis evaluated the effectiveness of an mRNA-1273 50 μg booster (3rd dose) in ∼17,000 boosted participants in the phase 3 coronavirus efficacy (COVE) trial who previously received 2-doses of 100 µg mRNA-1273 during the randomized placebo-controlled phase (mRNA-1273, 1st dose July-Oct 2020), or open label phase (placebo-mRNA-1273, 1st dose Dec 2020-Apr 2021). A single 50 µg mRNA-1273 (original vaccine) booster was administered starting Sep 2021. The effect of boosting on COVID-19 risk was assessed in Cox models by the initially randomized arm, time since booster, and age groups (< 65, ≥ 65) between Sep 2021-May 2022 during the open label phase of COVE. Results The median dosing intervals (IQR) between primary series and booster were 8.2 (7.8-8.7) months for the placebo-mRNA-1273 and 12.9 (12.3-13.5) months for the mRNA-1273 arms. A booster dose provided substantial additional protection against COVID-19 during the Delta wave through 60 days and was high for Omicron (BA.1), then waned over time by 110 days (Figure). The risk of Omicron COVID-19 post booster was lower by 24% (95% CI: 16%, 32%) in the mRNA-1273 vs the placebo-mRNA arm indicating possible benefit of longer boost interval. In a separate analysis, among participants ≥ 65 years, the initial booster (95% CI) efficacy against Omicron was 86% (69%, 93%) which waned to 28% (-47%, 65%) after ∼4 months. For those < 65 years, the analogous estimates were 50% (36%, 61%) and 6% (-29%, 31%), indicating a larger boosting effect in those ≥ 65 years. When further stratified by arm, for those ≥ 65 years, the initial boost efficacy against Omicron was 79% (41%, 92%) for the placebo-mRNA arm and 91% (79%, 96%) for mRNA-1273. For those < 65, the analogous estimates were 52% (30%, 62%) and 55% (39%, 66%), suggesting the effect of booster interval was largely concentrated in those ≥ 65 years. Conclusion Boosting with mRNA-1273 provided additional COVID-19 protection during the Delta and Omicron variant waves. Overall, boosting reduced the risk of Omicron COVID-19 but waned over time (∼4 months). The effects of boosting and interval were more pronounced in those ≥ 65 years of age. Disclosures Xiaowei Wang, PhD, Moderna, Inc.: Stocks/Bonds Peter Gilbert, PhD, NIH NIAID: Grant/Research Support Lindsey R. Baden, MD, NIH/NIAID: Grant/Research Support Hana M. El Sahly, MD, NIH and/or NIAID: Grant/Research Support Holly Janes, PhD, National Institutes of Health: Grant/Research Support Weiping Deng, PhD, Moderna, Inc.: Stocks/Bonds Frances Priddy, MD, MPH, Moderna, Inc.: Stocks/Bonds|Moderna, Inc.: Stocks/Bonds Avika Dixit, MBBS, Moderna, Inc.: Stocks/Bonds Joanne Tomassini, Ph.D., Moderna, Inc.: Advisor/Consultant Rituparna Das, M.D., Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds Jacqueline Miller, MD, Moderna, Inc.: Employee|Moderna, Inc.: Stocks/Bonds Honghong Zhou, Ph.D., Moderna, Inc.: Stocks/Bonds","journal":"Open Forum Infectious Diseases","year":2023,"id":382778,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9558,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":655794,"name":"Xiaowei Wang","orcid":"0000-0002-5430-4777","position":1,"is_corresponding":false},{"id":96350,"name":"Peter B. 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Tomassini","orcid":"0000-0002-9399-2867","position":11,"is_corresponding":false},{"id":900991,"name":"Rituparna Das","orcid":"0000-0002-5166-0311","position":12,"is_corresponding":false},{"id":615321,"name":"Jacqueline M. Miller","orcid":"0000-0002-7083-2182","position":13,"is_corresponding":false},{"id":98417,"name":"Honghong Zhou","orcid":null,"position":14,"is_corresponding":false},{"id":390353,"name":"Dean Follmann","orcid":"0000-0003-4073-0393","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:17:20.969491Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}