{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T15:53:05Z","timestamp":1780588385979,"version":"3.54.1"},"reference-count":39,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Beatrice Kleinberg Neuwirth Fund"},{"DOI":"10.13039\/100020044","name":"Yale School of Public Health, Yale University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020044","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020044","name":"Yale School of Public Health, Yale University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020044","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009947","name":"Merck Sharp and Dohme","doi-asserted-by":"publisher","award":["60487"],"award-info":[{"award-number":["60487"]}],"id":[{"id":"10.13039\/100009947","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009947","name":"Merck Sharp and Dohme","doi-asserted-by":"publisher","award":["60487"],"award-info":[{"award-number":["60487"]}],"id":[{"id":"10.13039\/100009947","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sendas Family Fund"}],"content-domain":{"domain":["www.plosmedicine.org"],"crossmark-restriction":false},"short-container-title":["PLoS Med"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>The benefit of primary and booster vaccination in people who experienced a prior Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection remains unclear. The objective of this study was to estimate the effectiveness of primary (two-dose series) and booster (third dose) mRNA vaccination against Omicron (lineage BA.1) infection among people with a prior documented infection.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods and findings<\/jats:title>\n<jats:p>We conducted a test-negative case\u2013control study of reverse transcription PCRs (RT-PCRs) analyzed with the TaqPath (Thermo Fisher Scientific) assay and recorded in the Yale New Haven Health system from November 1, 2021, to April 30, 2022. Overall, 11,307 cases (positive TaqPath analyzed RT-PCRs with S-gene target failure [SGTF]) and 130,041 controls (negative TaqPath analyzed RT-PCRs) were included (median age: cases: 35 years, controls: 39 years). Among cases and controls, 5.9% and 8.1% had a documented prior infection (positive SARS-CoV-2 test record \u226590 days prior to the included test), respectively. We estimated the effectiveness of primary and booster vaccination relative to SGTF-defined Omicron (lineage BA.1) variant infection using a logistic regression adjusted for date of test, age, sex, race\/ethnicity, insurance, comorbidities, social venerability index, municipality, and healthcare utilization. The effectiveness of primary vaccination 14 to 149 days after the second dose was 41.0% (95% confidence interval (CI): 14.1% to 59.4%, <jats:italic>p<\/jats:italic> 0.006) and 27.1% (95% CI: 18.7% to 34.6%, <jats:italic>p<\/jats:italic> &lt; 0.001) for people with and without a documented prior infection, respectively. The effectiveness of booster vaccination (<jats:bold>\u2265<\/jats:bold>14 days after booster dose) was 47.1% (95% CI: 22.4% to 63.9%, <jats:italic>p<\/jats:italic> 0.001) and 54.1% (95% CI: 49.2% to 58.4%, <jats:italic>p<\/jats:italic> &lt; 0.001) in people with and without a documented prior infection, respectively. To test whether booster vaccination reduced the risk of infection beyond that of the primary series, we compared the odds of infection among boosted (<jats:bold>\u2265<\/jats:bold>14 days after booster dose) and booster-eligible people (<jats:bold>\u2265<\/jats:bold>150 days after second dose). The odds ratio (OR) comparing boosted and booster-eligible people with a documented prior infection was 0.79 (95% CI: 0.54 to 1.16, <jats:italic>p<\/jats:italic> 0.222), whereas the OR comparing boosted and booster-eligible people without a documented prior infection was 0.54 (95% CI: 0.49 to 0.59, <jats:italic>p<\/jats:italic> &lt; 0.001). This study\u2019s limitations include the risk of residual confounding, the use of data from a single system, and the reliance on TaqPath analyzed RT-PCR results.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>In this study, we observed that primary vaccination provided significant but limited protection against Omicron (lineage BA.1) infection among people with and without a documented prior infection. While booster vaccination was associated with additional protection against Omicron BA.1 infection in people without a documented prior infection, it was not found to be associated with additional protection among people with a documented prior infection. These findings support primary vaccination in people regardless of documented prior infection status but suggest that infection history may impact the relative benefit of booster doses.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pmed.1004136","type":"journal-article","created":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T19:01:59Z","timestamp":1669921319000},"page":"e1004136","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Association between primary or booster COVID-19 mRNA vaccination and Omicron lineage BA.1 SARS-CoV-2 infection in people with a prior SARS-CoV-2 infection: A test-negative case\u2013control analysis"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1572-4074","authenticated-orcid":true,"given":"Margaret L.","family":"Lind","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4607-4470","authenticated-orcid":true,"given":"Alexander J.","family":"Robertson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5588-7372","authenticated-orcid":true,"given":"Frederick","family":"Warner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5243-552X","authenticated-orcid":true,"given":"Andreas C.","family":"Coppi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Price","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chelsea","family":"Duckwall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peri","family":"Sosensky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5892-8253","authenticated-orcid":true,"given":"Erendira C.","family":"Di Giuseppe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Borg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2874-471X","authenticated-orcid":true,"given":"Mariam O.","family":"Fofana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Otavio T.","family":"Ranzani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3884-0921","authenticated-orcid":true,"given":"Natalie E.","family":"Dean","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5967-251X","authenticated-orcid":true,"given":"Jason R.","family":"Andrews","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6665-6825","authenticated-orcid":true,"given":"Julio","family":"Croda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Iwasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek A. T.","family":"Cummings","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9023-2339","authenticated-orcid":true,"given":"Albert I.","family":"Ko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2327-3557","authenticated-orcid":true,"given":"Matt D. T.","family":"Hitchings","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wade L.","family":"Schulz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,12,1]]},"reference":[{"key":"pmed.1004136.ref001","article-title":"Association Between 3 Doses of mRNA COVID-19 Vaccine and Symptomatic Infection Caused by the SARS-CoV-2 Omicron and Delta Variants","author":"EK Accorsi","year":"2022","journal-title":"JAMA"},{"key":"pmed.1004136.ref002","first-page":"2021","article-title":"Effectiveness of COVID-19 vaccines against the Omicron (B.1.1.529) variant of concern","author":"N Andrews","year":"2021","journal-title":"medRxiv"},{"key":"pmed.1004136.ref003","doi-asserted-by":"crossref","DOI":"10.15585\/mmwr.mm7104e2","article-title":"COVID-19 Incidence and Death Rates Among Unvaccinated and Fully Vaccinated Adults with and Without Booster Doses During Periods of Delta and Omicron Variant Emergence\u201425 U.S. Jurisdictions, April 4\u2013December 25, 2021","volume":"71","author":"AG Johnson","year":"2022","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"pmed.1004136.ref004","doi-asserted-by":"crossref","DOI":"10.15585\/mmwr.mm7104e3","article-title":"Effectiveness of a Third Dose of mRNA Vaccines Against COVID-19\u2013Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Adults During Periods of Delta and Omicron Variant Predominance\u2014VISION Network, 10 States, August 2021\u2013January 2022","volume":"71","author":"MG Thompson","year":"2022","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"pmed.1004136.ref005","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1016\/S0140-6736(21)01358-1","article-title":"SARS-CoV-2 Delta VOC in Scotland: demographics, risk of hospital admission, and vaccine effectiveness","volume":"397","author":"A Sheikh","year":"2021","journal-title":"Lancet"},{"key":"pmed.1004136.ref006","first-page":"2022","article-title":"Duration of mRNA vaccine protection against SARS-CoV-2 Omicron BA.1 and BA.2 subvariants in Qatar","author":"H Chemaitelly","year":"2022","journal-title":"medRxiv"},{"key":"pmed.1004136.ref007","first-page":"2021","article-title":"Effectiveness and durability of protection against future SARS-CoV-2 infection conferred by COVID-19 vaccination and previous infection; findings from the UK SIREN prospective cohort study of healthcare workers March 2020 to September 2021","author":"V Hall","year":"2021","journal-title":"medRxiv"},{"key":"pmed.1004136.ref008","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1056\/NEJMoa2118691","article-title":"Protection against SARS-CoV-2 after Covid-19 Vaccination and Previous Infection","volume":"386","author":"V Hall","year":"2022","journal-title":"N Engl J Med"},{"key":"pmed.1004136.ref009","doi-asserted-by":"crossref","DOI":"10.1016\/S1473-3099(22)00143-8","article-title":"Risk of SARS-CoV-2 reinfection and COVID-19 hospitalisation in individuals with natural and hybrid immunity: a retrospective, total population cohort study in Sweden","volume":"22","author":"P Nordstr\u00f6m","year":"2022","journal-title":"Lancet Infect Dis"},{"key":"pmed.1004136.ref010","first-page":"71","article-title":"COVID-19 Cases and Hospitalizations by COVID-19 Vaccination Status and Previous COVID-19 Diagnosis\u2014California and New York, May\u2013November 2021","volume":"2022","author":"TM Le\u00f3n","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"pmed.1004136.ref011","first-page":"2021","article-title":"Effectiveness of CoronaVac, ChAdOx1, BNT162b2 and Ad26.COV2.S among individuals with prior SARS-CoV-2 infection in Brazil","author":"T Cerqueira-Silva","year":"2021","journal-title":"medRxiv"},{"key":"pmed.1004136.ref012","first-page":"ciac022","article-title":"Necessity of COVID-19 Vaccination in Persons Who Have Already Had COVID-19","author":"NK Shrestha","year":"2022","journal-title":"Clin Infect Dis Off Publ Infect Dis Soc Am"},{"key":"pmed.1004136.ref013","first-page":"20585","article-title":"The test-negative design: validity, accuracy and precision of vaccine efficacy estimates compared to the gold standard of randomised placebo-controlled clinical trials","volume":"18","author":"G De Serres","year":"2013","journal-title":"Euro Surveill Bull Eur Sur Mal Transm Eur Commun Dis Bull"},{"key":"pmed.1004136.ref014","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1056\/NEJMe2113151","article-title":"Covid-19 Vaccine Effectiveness and the Test-Negative Design","volume":"385","author":"NE Dean","year":"2021","journal-title":"N Engl J Med"},{"key":"pmed.1004136.ref015","doi-asserted-by":"crossref","first-page":"6220","DOI":"10.1038\/s41467-021-26459-6","article-title":"Effectiveness of ChAdOx1 vaccine in older adults during SARS-CoV-2 Gamma variant circulation in S\u00e3o Paulo","volume":"12","author":"MDT Hitchings","year":"2021","journal-title":"Nat Commun"},{"key":"pmed.1004136.ref016","doi-asserted-by":"crossref","first-page":"n2015","DOI":"10.1136\/bmj.n2015","article-title":"Effectiveness of the CoronaVac vaccine in older adults during a gamma variant associated epidemic of covid-19 in Brazil: test negative case-control study","volume":"374","author":"OT Ranzani","year":"2021","journal-title":"BMJ"},{"key":"pmed.1004136.ref017","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1002\/gch2.1018","article-title":"Data, disease and diplomacy: GISAID\u2019s innovative contribution to global health","volume":"1","author":"S Elbe","year":"2017","journal-title":"Glob Chall"},{"key":"pmed.1004136.ref018","first-page":"2022","article-title":"Rapid emergence of SARS-CoV-2 Omicron variant is associated with an infection advantage over Delta in vaccinated persons","author":"C Chaguza","year":"2022","journal-title":"medRxiv"},{"key":"pmed.1004136.ref019","volume-title":"In: FDA","author":"Commissioner O of the","year":"2021"},{"key":"pmed.1004136.ref020","doi-asserted-by":"crossref","first-page":"e13043","DOI":"10.2196\/13043","article-title":"Health Care and Precision Medicine Research: Analysis of a Scalable Data Science Platform","volume":"21","author":"J McPadden","year":"2019","journal-title":"J Med Internet Res"},{"key":"pmed.1004136.ref021","doi-asserted-by":"crossref","first-page":"e18707","DOI":"10.2196\/18707","article-title":"Agile Health Care Analytics: Enabling Real-Time Disease Surveillance With a Computational Health Platform","volume":"22","author":"WL Schulz","year":"2020","journal-title":"J Med Internet Res"},{"key":"pmed.1004136.ref022","article-title":"Care Everywhere Network","author":"EPIC Systems Corporation","year":"2022","journal-title":"Verona, WI"},{"key":"pmed.1004136.ref023","article-title":"Methods for the detection and identification of SARS-CoV-2 variants, March 2021","author":"European Centre for Disease Prevention and Control, Europe WHORO for","year":"2021","journal-title":"World Health Organization. Regional Office for Europe;"},{"key":"pmed.1004136.ref024","doi-asserted-by":"crossref","first-page":"2686","DOI":"10.1093\/aje\/kwy163","article-title":"Measurement of Vaccine Direct Effects Under the Test-Negative Design","volume":"187","author":"JA Lewnard","year":"2018","journal-title":"Am J Epidemiol"},{"key":"pmed.1004136.ref025","author":"CDC","year":"2022","journal-title":"COVID-19 Booster Shot. In: Centers for Disease Control and Prevention"},{"key":"pmed.1004136.ref026","doi-asserted-by":"crossref","first-page":"e306","DOI":"10.1017\/S0950268819001961","article-title":"Depletion-of-susceptibles bias in influenza vaccine waning studies: how to ensure robust results","volume":"147","author":"M Lipsitch","year":"2019","journal-title":"Epidemiol Infect"},{"key":"pmed.1004136.ref027","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/0021-9681(87)90171-8","article-title":"A new method of classifying prognostic comorbidity in longitudinal studies: development and validation","volume":"40","author":"ME Charlson","year":"1987","journal-title":"J Chronic Dis"},{"issue":"42","key":"pmed.1004136.ref028","article-title":"A comparison of methods to adjust for continuous covariates in the analysis of randomised trials","volume":"16","author":"BC Kahan","year":"2016","journal-title":"BMC Med Res Methodol"},{"key":"pmed.1004136.ref029","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1503\/cmaj.120592","article-title":"Adjustment for continuous confounders: an example of how to prevent residual confounding","volume":"185","author":"RHH Groenwold","year":"2013","journal-title":"CMAJ Can Med Assoc J"},{"key":"pmed.1004136.ref030","author":"U.S. Department of Health & Human Services","year":"2021","journal-title":"CDC\/ATSDR SVI Data and Documentation Download | Place and Health | ATSDR"},{"key":"pmed.1004136.ref031","article-title":"R: A language and environment for statistical computing","author":"R Core Team","year":"2021","journal-title":"Vienna, Austria: R Foundation for Statistical Computing"},{"key":"pmed.1004136.ref032","first-page":"2021","article-title":"Use of recently vaccinated individuals to detect bias in test-negative case-control studies of COVID-19 vaccine effectiveness","author":"MDT Hitchings","year":"2021"},{"key":"pmed.1004136.ref033","volume-title":"Connecticut SARS-CoV-2 variant surveillance\u2013Report 2022-10-04","author":"ND Grubaugh","year":"2022"},{"key":"pmed.1004136.ref034","first-page":"2022","article-title":"Protection against Omicron conferred by mRNA primary vaccine series, boosters, and prior infection","author":"ET Chin","year":"2022","journal-title":"medRxiv"},{"key":"pmed.1004136.ref035","doi-asserted-by":"crossref","DOI":"10.15585\/mmwr.mm7107e2","article-title":"Waning 2-Dose and 3-Dose Effectiveness of mRNA Vaccines Against COVID-19\u2013Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Adults During Periods of Delta and Omicron Variant Predominance\u2014VISION Network, 10 States, August 2021\u2013January 2022","volume":"71","author":"JM Ferdinands","year":"2022","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"pmed.1004136.ref036","article-title":"STATE OF CONNECTICUT BY HIS EXCELLENCY NED LAMONT EXECUTIVE ORDER NO","author":"N. Lamont","year":"2021","journal-title":"13G"},{"key":"pmed.1004136.ref037","article-title":"Workplaces Subject to COVID-19 Vaccine Requirements","author":"Connecticut Government","year":"2022","journal-title":"In: CT.gov\u2014Connecticut\u2019s Official State Website"},{"key":"pmed.1004136.ref038","article-title":"COVID-19 Vaccinations by Age Group | Connecticut Data","author":"Connecticut Department of Health","year":"2022","journal-title":"In: data.ct.gov"},{"key":"pmed.1004136.ref039","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1056\/NEJMoa2203965","article-title":"Effects of Previous Infection and Vaccination on Symptomatic Omicron Infections","volume":"387","author":"HN Altarawneh","year":"2022","journal-title":"N Engl J Med"}],"container-title":["PLOS Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pmed.1004136","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T19:02:22Z","timestamp":1669921342000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pmed.1004136"}},"subtitle":[],"editor":[{"given":"Elvin Hsing","family":"Geng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,12,1]]},"references-count":39,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12,1]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pmed.1004136","relation":{},"ISSN":["1549-1676"],"issn-type":[{"value":"1549-1676","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,1]]}}}