{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:20:02Z","timestamp":1785428402436,"version":"3.56.0"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T00:00:00Z","timestamp":1741910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Veterans Affairs Clinical Science Research and Development","award":["CX002417"],"award-info":[{"award-number":["CX002417"]}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["AI146268"],"award-info":[{"award-number":["AI146268"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Current coronavirus disease 2019 (COVID-19) vaccine recommendations in the United States (US) provide guidance for adults to receive at least annual variant-targeted vaccination. We sought to estimate the strength and durability of protection from annual variant-targeted vaccination against severe COVID-19 illness in individuals with vaccine-derived and hybrid immunity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We emulated a target trial using an electronic health record\u2013based, propensity score\u2013matched (1:1) cohort of US Veterans. Booster-vaccinated adults were eligible for a variant-targeted messenger RNA (mRNA) booster starting 1 September 2022. Matched sets of those who did and did not receive the variant-targeted booster dose were identified on a weekly basis, and the cohort was followed until 31 August 2023. Outcomes were hospitalization due to COVID-19 pneumonia and in-hospital severe illness. We fit Cox models, overall and stratified by last documented severe acute respiratory syndrome coronavirus 2 infection (pre-Omicron, Omicron), to estimate relative vaccine effectiveness (rVE).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The propensity score\u2013matched cohort consisted of 1 576 626 COVID-19 booster-vaccinated adults. Estimates of rVE from variant-targeted mRNA booster against hospitalization due to COVID-19 pneumonia were significant and similar in the cohort with vaccine-derived immunity (rVE, 29% [95% confidence interval {CI}, 25%\u201334%]) and cohort with hybrid immunity (rVE, 38% [95% CI, 27%\u201347%]). These protective gains were significant from 0 to 6 months but not 6 to 12 months after vaccination and during pre-XBB and XBB variant eras. Findings were similar for in-hospital severe illness.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>In cohorts with vaccine-derived and hybrid immunity, modest but significant gains in protection against hospitalization and severe COVID-19 illness were conferred by the annual variant-targeted booster dose but not sustained beyond 6 months.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciaf124","type":"journal-article","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T05:01:51Z","timestamp":1741928511000},"page":"222-230","source":"Crossref","is-referenced-by-count":8,"title":["Annual Variant-Targeted Vaccination to Prevent Severe COVID-19 in Cohorts With Vaccine-Derived and Hybrid Immunity"],"prefix":"10.1093","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7616-0321","authenticated-orcid":false,"given":"J Daniel","family":"Kelly","sequence":"first","affiliation":[{"name":"Center for Data to Discovery and Delivery Innovation (3DI), San Francisco Veterans Affairs Health Care System , San Francisco, California ,","place":["USA"]},{"name":"Department of Medicine, University of California , San Francisco, California ,","place":["USA"]},{"name":"Department of Epidemiology and Biostatistics, University of California , San Francisco, California ,","place":["USA"]},{"name":"F.I. Proctor Foundation, University of California , San Francisco, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine J","family":"Hoggatt","sequence":"additional","affiliation":[{"name":"Center for Data to Discovery and Delivery Innovation (3DI), San Francisco Veterans Affairs Health Care System , San Francisco, California ,","place":["USA"]},{"name":"Department of Medicine, University of California , San Francisco, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan C","family":"Lo","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University , Stanford, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Leonard","sequence":"additional","affiliation":[{"name":"Center for Data to Discovery and Delivery Innovation (3DI), San Francisco Veterans Affairs Health Care System , San Francisco, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W John","family":"Boscardin","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of California , San Francisco, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2574-0358","authenticated-orcid":false,"given":"Hye Sun","family":"Kim","sequence":"additional","affiliation":[{"name":"Center for Data to Discovery and Delivery Innovation (3DI), San Francisco Veterans Affairs Health Care System , San Francisco, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily N","family":"Lum","sequence":"additional","affiliation":[{"name":"Center for Data to Discovery and Delivery Innovation (3DI), San Francisco Veterans Affairs Health Care System , San Francisco, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles C","family":"Austin","sequence":"additional","affiliation":[{"name":"Center for Data to Discovery and Delivery Innovation (3DI), San Francisco Veterans Affairs Health Care System , San Francisco, California ,","place":["USA"]},{"name":"Department of Veterans Affairs Health Services and Development (HSR&D), Center for Health Information and Communication (CHIC), Richard L. Roudebush Veterans Affairs Medical Center , Indianapolis, Indiana ,","place":["USA"]},{"name":"Department of Medicine, Richard L. Roudebush Veterans Affairs Medical Center , Indianapolis, Indiana ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy L","family":"Byers","sequence":"additional","affiliation":[{"name":"Center for Data to Discovery and Delivery Innovation (3DI), San Francisco Veterans Affairs Health Care System , San Francisco, California ,","place":["USA"]},{"name":"Department of Psychiatry, Weill Institute for Neurosciences, University of California, San Francisco , California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phyllis C","family":"Tien","sequence":"additional","affiliation":[{"name":"Center for Data to Discovery and Delivery Innovation (3DI), San Francisco Veterans Affairs Health Care System , San Francisco, California ,","place":["USA"]},{"name":"Department of Medicine, University of California , San Francisco, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter C","family":"Austin","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Program, Institute for Clinical Evaluative Sciences , Toronto, Ontario ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn M","family":"Bravata","sequence":"additional","affiliation":[{"name":"Department of Veterans Affairs Health Services and Development (HSR&D), Center for Health Information and Communication (CHIC), Richard L. Roudebush Veterans Affairs Medical Center , Indianapolis, Indiana ,","place":["USA"]},{"name":"Department of Medicine, Richard L. Roudebush Veterans Affairs Medical Center , Indianapolis, Indiana ,","place":["USA"]},{"name":"Department of Medicine, Indiana University School of Medicine , Indianapolis, Indiana ,","place":["USA"]},{"name":"William M. Tierney Center for Health Services Research, Regenstrief Institute , Indianapolis, Indiana ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salomeh","family":"Keyhani","sequence":"additional","affiliation":[{"name":"Center for Data to Discovery and Delivery Innovation (3DI), San Francisco Veterans Affairs Health Care System , San Francisco, California ,","place":["USA"]},{"name":"Department of Medicine, University of California , San Francisco, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,3,14]]},"reference":[{"key":"2025091916594599700_ciaf124-B1","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1001\/jama.2024.7395","article-title":"Mortality in patients hospitalized for COVID-19 vs influenza in fall-winter 2023\u20132024","volume":"331","author":"Xie","year":"2024","journal-title":"JAMA"},{"key":"2025091916594599700_ciaf124-B2","author":"Centers for Disease Control and Prevention"},{"key":"2025091916594599700_ciaf124-B3","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/S0140-6736(22)02465-5","article-title":"Past SARS-CoV-2 infection protection against re-infection: a systematic review and meta-analysis","volume":"401","author":"COVID-19 Forecasting Team","year":"2023","journal-title":"Lancet"},{"key":"2025091916594599700_ciaf124-B4","doi-asserted-by":"crossref","first-page":"4333","DOI":"10.1016\/j.cell.2022.09.032","article-title":"Interval between prior SARS-CoV-2 infection and booster vaccination impacts magnitude and quality of antibody and B cell responses","volume":"185","author":"Buckner","year":"2022","journal-title":"Cell"},{"key":"2025091916594599700_ciaf124-B5","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/S1473-3099(22)00801-5","article-title":"Protective effectiveness of previous SARS-CoV-2 infection and hybrid immunity against the Omicron variant and severe disease: a systematic review and meta-regression","volume":"23","author":"Bobrovitz","year":"2023","journal-title":"Lancet Infect Dis"},{"key":"2025091916594599700_ciaf124-B6","doi-asserted-by":"crossref","first-page":"100451","DOI":"10.1016\/j.jvacx.2024.100451","article-title":"Reported effectiveness of COVID-19 monovalent booster vaccines and hybrid immunity against mild and severe Omicron disease in adults: a systematic review and meta-regression analysis","volume":"17","author":"Nealon","year":"2024","journal-title":"Vaccine X"},{"key":"2025091916594599700_ciaf124-B7","doi-asserted-by":"crossref","first-page":"e409","DOI":"10.1016\/S2666-7568(23)00099-5","article-title":"Effectiveness of previous infection-induced and vaccine-induced protection against hospitalisation due to Omicron BA subvariants in older adults: a test-negative, case-control study in Quebec, Canada","volume":"4","author":"Carazo","year":"2023","journal-title":"Lancet Healthy Longev"},{"key":"2025091916594599700_ciaf124-B8","doi-asserted-by":"crossref","first-page":"2169","DOI":"10.1093\/cid\/ciac327","article-title":"Coronavirus disease 2019 vaccine boosting in previously infected or vaccinated individuals","volume":"75","author":"Shrestha","year":"2022","journal-title":"Clin Infect Dis"},{"key":"2025091916594599700_ciaf124-B9","doi-asserted-by":"crossref","first-page":"e1004037","DOI":"10.1371\/journal.pmed.1004037","article-title":"Vaccine effectiveness against SARS-CoV-2 reinfection during periods of Alpha, Delta, or Omicron dominance: a Danish nationwide study","volume":"19","author":"Nielsen","year":"2022","journal-title":"PLoS Med"},{"key":"2025091916594599700_ciaf124-B10","doi-asserted-by":"crossref","first-page":"549","DOI":"10.15585\/mmwr.mm7115e2","article-title":"Effectiveness of COVID-19 mRNA vaccination in preventing COVID-19\u2013associated hospitalization among adults with previous SARS-CoV-2 infection\u2014United States, June 2021\u2013February 2022","volume":"71","author":"Plumb","year":"2022","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"2025091916594599700_ciaf124-B11","doi-asserted-by":"crossref","first-page":"e0299304","DOI":"10.1371\/journal.pone.0299304","article-title":"Protection of prior SARS-CoV-2 infection, COVID-19 boosters, and hybrid immunity against Omicron severe illness: a population-based cohort study of five million residents in Canada","volume":"19","author":"Wu","year":"2024","journal-title":"PLoS One"},{"key":"2025091916594599700_ciaf124-B12","doi-asserted-by":"crossref","first-page":"e13906","DOI":"10.1111\/eci.13906","article-title":"Does natural and hybrid immunity obviate the need for frequent vaccine boosters against SARS-CoV-2 in the endemic phase?","volume":"53","author":"Pilz","year":"2023","journal-title":"Eur J Clin Invest"},{"key":"2025091916594599700_ciaf124-B13","doi-asserted-by":"crossref","first-page":"112911","DOI":"10.1016\/j.envres.2022.112911","article-title":"SARS-CoV-2 reinfections: overview of efficacy and duration of natural and hybrid immunity","volume":"209","author":"Pilz","year":"2022","journal-title":"Environ Res"},{"key":"2025091916594599700_ciaf124-B14","author":"US Department of Veterans Affairs"},{"key":"2025091916594599700_ciaf124-B15","author":"DuVall"},{"key":"2025091916594599700_ciaf124-B16","author":"US Department of Veterans Affairs"},{"key":"2025091916594599700_ciaf124-B17","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1001\/jama.2022.17985","article-title":"Incidence of severe COVID-19 illness following vaccination and booster with BNT162b2, mRNA-1273, and Ad26.COV2.S vaccines","volume":"328","author":"Kelly","year":"2022","journal-title":"JAMA"},{"key":"2025091916594599700_ciaf124-B18","author":"The New York Times"},{"key":"2025091916594599700_ciaf124-B19","doi-asserted-by":"crossref","first-page":"2837","DOI":"10.1002\/sim.5705","article-title":"The performance of different propensity score methods for estimating marginal hazard ratios","volume":"32","author":"Austin","year":"2013","journal-title":"Stat Med"},{"key":"2025091916594599700_ciaf124-B20","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1093\/oxfordjournals.epirev.a017990","article-title":"Design and interpretation of vaccine field studies","volume":"21","author":"Halloran","year":"1999","journal-title":"Epidemiol Rev"},{"key":"2025091916594599700_ciaf124-B21","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1007\/s10654-022-00911-3","article-title":"Estimating conditional vaccine effectiveness","volume":"37","author":"Ioannidis","year":"2022","journal-title":"Eur J Epidemiol"}],"container-title":["Clinical Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/cid\/advance-article-pdf\/doi\/10.1093\/cid\/ciaf124\/62413640\/ciaf124.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/article-pdf\/81\/2\/222\/62413640\/ciaf124.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/article-pdf\/81\/2\/222\/62413640\/ciaf124.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T20:59:55Z","timestamp":1758315595000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cid\/article\/81\/2\/222\/8078340"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,14]]},"references-count":21,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,3,14]]},"published-print":{"date-parts":[[2025,9,16]]}},"URL":"https:\/\/doi.org\/10.1093\/cid\/ciaf124","relation":{},"ISSN":["1058-4838","1537-6591"],"issn-type":[{"value":"1058-4838","type":"print"},{"value":"1537-6591","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,8,15]]},"published":{"date-parts":[[2025,3,14]]}}}