{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T19:20:27Z","timestamp":1780514427879,"version":"3.54.1"},"update-to":[{"DOI":"10.1371\/journal.pmed.1004156","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T00:00:00Z","timestamp":1674691200000}}],"reference-count":30,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2023,1,11]],"date-time":"2023-01-11T00:00:00Z","timestamp":1673395200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006507","name":"Fiocruz","doi-asserted-by":"crossref","award":["VigiVac project"],"award-info":[{"award-number":["VigiVac project"]}],"id":[{"id":"10.13039\/501100006507","id-type":"DOI","asserted-by":"crossref"}]},{"name":"JBS","award":["\"Fazer o Bem Faz Bem\" programme"],"award-info":[{"award-number":["\"Fazer o Bem Faz Bem\" programme"]}]},{"DOI":"10.13039\/501100006181","name":"FAPESB","doi-asserted-by":"crossref","award":["PNX0008\/2014"],"award-info":[{"award-number":["PNX0008\/2014"]}],"id":[{"id":"10.13039\/501100006181","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004586","name":"FAPERJ","doi-asserted-by":"crossref","award":["E-26\/210.180\/2020"],"award-info":[{"award-number":["E-26\/210.180\/2020"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"crossref"}]},{"name":"MRC","award":["MC_PC_19075"],"award-info":[{"award-number":["MC_PC_19075"]}]},{"DOI":"10.13039\/100014013","name":"UK Research and Innovation","doi-asserted-by":"crossref","award":["MC_PC_20058"],"award-info":[{"award-number":["MC_PC_20058"]}],"id":[{"id":"10.13039\/100014013","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Public Health Scotland and Scottish Government Director General Health and Social Care"},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"crossref","award":["11\/46\/23"],"award-info":[{"award-number":["11\/46\/23"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000272","name":"NIHR","doi-asserted-by":"crossref","award":["GHRG \/16\/137\/99"],"award-info":[{"award-number":["GHRG \/16\/137\/99"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NHS Research Scotland","award":["SCAF\/15\/02"],"award-info":[{"award-number":["SCAF\/15\/02"]}]},{"name":"MRC","award":["MC_UU_00022\/2"],"award-info":[{"award-number":["MC_UU_00022\/2"]}]},{"name":"Scottish Government Chief Scientist Office","award":["SPHSU17"],"award-info":[{"award-number":["SPHSU17"]}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"crossref","award":["GHRG \/16\/137\/99"],"award-info":[{"award-number":["GHRG \/16\/137\/99"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]}],"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>Brazil and Scotland have used mRNA boosters in their respective populations since September 2021, with Omicron\u2019s emergence accelerating their booster program. Despite this, both countries have reported substantial recent increases in Coronavirus Disease 2019 (COVID-19) cases. The duration of the protection conferred by the booster dose against symptomatic Omicron cases and severe outcomes is unclear.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods and findings<\/jats:title>\n<jats:p>Using a test-negative design, we analyzed national databases to estimate the vaccine effectiveness (VE) of a primary series (with ChAdOx1 or BNT162b2) plus an mRNA vaccine booster (with BNT162b2 or mRNA-1273) against symptomatic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 outcomes (hospitalization or death) during the period of Omicron dominance in Brazil and Scotland compared to unvaccinated individuals. Additional analyses included stratification by age group (18 to 49, 50 to 64, \u226565). All individuals aged 18 years or older who reported acute respiratory illness symptoms and tested for SARS-CoV-2 infection between January 1, 2022, and April 23, 2022, in Brazil and Scotland were eligible for the study. At 14 to 29 days after the mRNA booster, the VE against symptomatic SARS-CoV-2 infection of ChAdOx1 plus BNT162b2 booster was 51.6%, (95% confidence interval (CI): [51.0, 52.2], <jats:italic>p<\/jats:italic> &lt; 0.001) in Brazil and 67.1% (95% CI [65.5, 68.5], <jats:italic>p<\/jats:italic> &lt; 0.001) in Scotland. At \u22654 months, protection against symptomatic infection waned to 4.2% (95% CI [0.7, 7.6], <jats:italic>p<\/jats:italic> = 0.02) in Brazil and 37.4% (95% CI [33.8, 40.9], <jats:italic>p<\/jats:italic> &lt; 0.001) in Scotland. VE against severe outcomes in Brazil was 93.5% (95% CI [93.0, 94.0], <jats:italic>p<\/jats:italic> &lt; 0.001) at 14 to 29 days post-booster, decreasing to 82.3% (95% CI [79.7, 84.7], <jats:italic>p<\/jats:italic> &lt; 0.001) and 98.3% (95% CI [87.3, 99.8], <jats:italic>p<\/jats:italic> &lt; 0.001) to 77.8% (95% CI [51.4, 89.9], <jats:italic>p<\/jats:italic> &lt; 0.001) in Scotland for the same periods. Similar results were obtained with the primary series of BNT162b2 plus homologous booster. Potential limitations of this study were that we assumed that all cases included in the analysis were due to the Omicron variant based on the period of dominance and the limited follow-up time since the booster dose.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>We observed that mRNA boosters after a primary vaccination course with either mRNA or viral-vector vaccines provided modest, short-lived protection against symptomatic infection with Omicron but substantial and more sustained protection against severe COVID-19 outcomes for at least 3 months.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pmed.1004156","type":"journal-article","created":{"date-parts":[[2023,1,11]],"date-time":"2023-01-11T18:46:18Z","timestamp":1673462778000},"page":"e1004156","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["Effectiveness of mRNA boosters after homologous primary series with BNT162b2 or ChAdOx1 against symptomatic infection and severe COVID-19 in Brazil and Scotland: A test-negative design case\u2013control study"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4534-2509","authenticated-orcid":true,"given":"Thiago","family":"Cerqueira-Silva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5672-0443","authenticated-orcid":true,"given":"Syed Ahmar","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6848-5241","authenticated-orcid":true,"given":"Chris","family":"Robertson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0472-1804","authenticated-orcid":true,"given":"Mauro","family":"Sanchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6593-9092","authenticated-orcid":true,"given":"Srinivasa Vittal","family":"Katikireddi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7858-9650","authenticated-orcid":true,"given":"Vinicius","family":"de Araujo Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4797-908X","authenticated-orcid":true,"given":"Enny S.","family":"Paix\u00e3o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Rudan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juracy Bertoldo","family":"Junior","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerson O.","family":"Penna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Pearce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1169-1436","authenticated-orcid":true,"given":"Guilherme Loureiro","family":"Werneck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauricio L.","family":"Barreto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7241-6844","authenticated-orcid":true,"given":"Viviane S.","family":"Boaventura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aziz","family":"Sheikh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5823-7903","authenticated-orcid":true,"given":"Manoel","family":"Barral-Netto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,1,11]]},"reference":[{"key":"pmed.1004156.ref001","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.1038\/s41591-021-01583-4","article-title":"BNT162b2 and mRNA-1273 COVID-19 vaccine effectiveness against the SARS-CoV-2 Delta variant in Qatar","volume":"27","author":"P Tang","year":"2021","journal-title":"Nat Med"},{"key":"pmed.1004156.ref002","first-page":"100154","article-title":"Influence of age on the effectiveness and duration of protection of Vaxzevria and CoronaVac vaccines: A population-based study","volume":"6","author":"T Cerqueira-Silva","year":"2022","journal-title":"Lancet Reg Health\u2014Am"},{"key":"pmed.1004156.ref003","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1056\/NEJMoa2117128","article-title":"Effectiveness of Covid-19 Vaccines over a 9-Month Period in North Carolina","volume":"386","author":"D-Y Lin","year":"2022","journal-title":"N Engl J Med"},{"key":"pmed.1004156.ref004","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1016\/S0140-6736(22)00089-7","article-title":"Risk of infection, hospitalisation, and death up to 9 months after a second dose of COVID-19 vaccine: a retrospective, total population cohort study in Sweden","volume":"399","author":"P Nordstr\u00f6m","year":"2022","journal-title":"Lancet"},{"key":"pmed.1004156.ref005","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0140-6736(21)02754-9","article-title":"Two-dose ChAdOx1 nCoV-19 vaccine protection against COVID-19 hospital admissions and deaths over time: a retrospective, population-based cohort study in Scotland and Brazil","volume":"399","author":"SV Katikireddi","year":"2022","journal-title":"Lancet"},{"key":"pmed.1004156.ref006","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1056\/NEJMoa2114255","article-title":"Protection of BNT162b2 Vaccine Booster against Covid-19 in Israel","volume":"385","author":"YM Bar-On","year":"2021","journal-title":"N Engl J Med"},{"key":"pmed.1004156.ref007","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.1004156.ref008","doi-asserted-by":"crossref","first-page":"3082","DOI":"10.1038\/s41467-022-30895-3","article-title":"Duration of mRNA vaccine protection against SARS-CoV-2 Omicron BA.1 and BA.2 subvariants in Qatar.","volume":"13","author":"H Chemaitelly","year":"2022","journal-title":"Nat Commun."},{"key":"pmed.1004156.ref009","article-title":"High vaccine effectiveness against severe Covid-19 in the elderly in Finland before and after the emergence of Omicron.","author":"U Baum","year":"2022","journal-title":"medRxiv."},{"issue":"16","key":"pmed.1004156.ref010","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1056\/NEJMoa2119451","article-title":"Covid-19 Vaccine Effectiveness against the Omicron (B.1.1.529) Variant.","volume":"386","author":"N Andrews","year":"2022","journal-title":"N Engl J Med"},{"key":"pmed.1004156.ref011","doi-asserted-by":"crossref","first-page":"3203","DOI":"10.1038\/s41467-022-30884-6","article-title":"Waning effectiveness of the third dose of the BNT162b2 mRNA COVID-19 vaccine","volume":"13","author":"T Patalon","year":"2022","journal-title":"Nat Commun"},{"key":"pmed.1004156.ref012","first-page":"S2213","article-title":"Durability of BNT162b2 vaccine against hospital and emergency department admissions due to the omicron and delta variants in a large health system in the USA: a test-negative case-control study.","author":"SY Tartof","year":"2022","journal-title":"Lancet Respir Med"},{"key":"pmed.1004156.ref013","unstructured":"COVID-19 Map. Johns Hopkins Coronavirus Resour. Cent. Available from: https:\/\/coronavirus.jhu.edu\/us-map [cited 2022 Apr 8]."},{"key":"pmed.1004156.ref014","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1097\/EDE.0000000000001088","article-title":"Test-Negative Designs: Differences and Commonalities with Other Case-Control Studies with \u201cOther Patient\u201d Controls.","volume":"30","author":"JP Vandenbroucke","year":"2019","journal-title":"Epidemiol Camb Mass"},{"key":"pmed.1004156.ref015","volume-title":"Guia de vigil\u00e2ncia epidemiol\u00f3gica : emerg\u00eancia de sa\u00fade p\u00fablica de import\u00e2ncia nacional pela doen\u00e7a pelo coronav\u00edrus 2019","author":"S. Brasil M da","year":"2022"},{"key":"pmed.1004156.ref016","doi-asserted-by":"crossref","first-page":"e425","DOI":"10.1016\/S2589-7500(21)00080-7","article-title":"An external validation of the QCovid risk prediction algorithm for risk of mortality from COVID-19 in adults: a national validation cohort study","volume":"3","author":"V Nafilyan","year":"2021","journal-title":"England. Lancet Digit Health"},{"key":"pmed.1004156.ref017","article-title":"Waning Immune Humoral Response to BNT162b2 Covid-19 Vaccine over 6 Months","author":"EG Levin","year":"2021","journal-title":"N Engl J Med"},{"key":"pmed.1004156.ref018","doi-asserted-by":"crossref","first-page":"100716","DOI":"10.1016\/j.xcrm.2022.100716","article-title":"Protective antibodies and T cell responses to Omicron variant after the booster dose of BNT162b2 vaccine.","volume":"3","author":"P Naaber","year":"2022","journal-title":"Cell Rep Med."},{"key":"pmed.1004156.ref019","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/S1473-3099(22)00135-9","article-title":"Durability of omicron-neutralising serum activity after mRNA booster immunisation in older adults","volume":"22","author":"K Vanshylla","year":"2022","journal-title":"Lancet Infect Dis"},{"issue":"14","key":"pmed.1004156.ref020","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1056\/NEJMc2202542","article-title":"Efficacy of a Fourth Dose of Covid-19 mRNA Vaccine against Omicron","volume":"386","author":"G Regev-Yochay","year":"2022","journal-title":"N Engl J Med"},{"key":"pmed.1004156.ref021","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1016\/j.cell.2022.01.011","article-title":"SARS-CoV-2 breakthrough infections elicit potent, broad, and durable neutralizing antibody responses","volume":"185","author":"AC Walls","year":"2022","journal-title":"Cell"},{"key":"pmed.1004156.ref022","article-title":"Potency and Breadth of Neutralization after 3 doses of mRNA vaccines in COVID-19 Convalescent and Na\u00efve individuals.","author":"J Luczkowiak","year":"2022","journal-title":"medRxiv"},{"key":"pmed.1004156.ref023","article-title":"Protective antibodies and T cell responses to Omicron variant three months after the booster dose of BNT162b2 vaccine.","author":"P Naaber","year":"2022","journal-title":"medRxiv."},{"key":"pmed.1004156.ref024","doi-asserted-by":"crossref","first-page":"abm0829","DOI":"10.1126\/science.abm0829","article-title":"mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern","volume":"374","author":"RR Goel","year":"2021","journal-title":"Science"},{"key":"pmed.1004156.ref025","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1038\/s41591-022-01700-x","article-title":"Ancestral SARS-CoV-2-specific T cells cross-recognize the Omicron variant","volume":"28","author":"Y Gao","year":"2022","journal-title":"Nat Med"},{"key":"pmed.1004156.ref026","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1016\/j.cell.2022.01.029","article-title":"T cell reactivity to the SARS-CoV-2 Omicron variant is preserved in most but not all individuals","volume":"185","author":"V Naranbhai","year":"2022","journal-title":"Cell"},{"key":"pmed.1004156.ref027","article-title":"Protection by a Fourth Dose of BNT162b2 against Omicron in Israel","author":"YM Bar-On","year":"2022","journal-title":"N Engl J Med"},{"key":"pmed.1004156.ref028","doi-asserted-by":"crossref","first-page":"3295","DOI":"10.1016\/j.vaccine.2017.04.037","article-title":"Case-control vaccine effectiveness studies: Preparation, design, and enrollment of cases and controls","volume":"35","author":"JR Verani","year":"2017","journal-title":"Vaccine"},{"key":"pmed.1004156.ref029","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1016\/S1473-3099(22)00309-7","article-title":"COVID-19 vaccine effectiveness against the omicron (BA.2) variant in England.","volume":"22","author":"FCM Kirsebom","year":"2022","journal-title":"Lancet Infect Dis."},{"key":"pmed.1004156.ref030","doi-asserted-by":"crossref","first-page":"2526","DOI":"10.1056\/NEJMc2206725","article-title":"Neutralization of the SARS-CoV-2 Omicron BA.4\/5 and BA.2.12.1 Subvariants","volume":"386","author":"P Qu","year":"2022","journal-title":"N Engl J Med"}],"updated-by":[{"DOI":"10.1371\/journal.pmed.1004156","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T00:00:00Z","timestamp":1674691200000}}],"container-title":["PLOS Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pmed.1004156","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T18:52:05Z","timestamp":1674759125000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pmed.1004156"}},"subtitle":[],"editor":[{"given":"Amitabh Bipin","family":"Suthar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,1,11]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1,11]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pmed.1004156","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pmed.1004156","asserted-by":"object"}]},"ISSN":["1549-1676"],"issn-type":[{"value":"1549-1676","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,11]]}}}