Cerqueira-Silva T, Shah SA, Robertson C, Sanchez M, Katikireddi SV, de Araujo Oliveira V, Paixão ES, Rudan I, Junior JB, Penna GO, Pearce N, Werneck GL, Barreto ML, Boaventura VS, Sheikh A, and Barral-Netto M
Background: Brazil and Scotland have used mRNA boosters in their respective populations since September 2021, with Omicron's 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., Methods and Findings: 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, ≥65). 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], p < 0.001) in Brazil and 67.1% (95% CI [65.5, 68.5], p < 0.001) in Scotland. At ≥4 months, protection against symptomatic infection waned to 4.2% (95% CI [0.7, 7.6], p = 0.02) in Brazil and 37.4% (95% CI [33.8, 40.9], p < 0.001) in Scotland. VE against severe outcomes in Brazil was 93.5% (95% CI [93.0, 94.0], p < 0.001) at 14 to 29 days post-booster, decreasing to 82.3% (95% CI [79.7, 84.7], p < 0.001) and 98.3% (95% CI [87.3, 99.8], p < 0.001) to 77.8% (95% CI [51.4, 89.9], p < 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., Conclusions: 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., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: VdAO, VB, MLB, and MB-N are employees of Fiocruz, a federal public institution, which manufactures Vaxzevria in Brazil, through a full technology transfer agreement with AstraZeneca. Fiocruz allocates all its manufactured products to the Ministry of Health for the public health service use. SVK was a member of the UK Government’s Scientific Advisory Group on Emergencies subgroup on ethnicity, the Cabinet Office’s International Best Practice Advisory Group, and was co-chair of the Scottish Government’s Expert Reference Group on Ethnicity and COVID-19. CR is a member of the Scottish Government Chief Medical Officer’s COVID-19 Advisory Group, Scientific Pandemic Influenza Group on Modelling, and Medicines and Healthcare products Regulatory Agency Vaccine Benefit and Risk Working Group. CR reports the followings: “Research Grants to Strathclyde University from Public Health Scotland, UK Medical Research Council, Scotland Chief Scientist Office, Health Data Research UK. Advisory Bodies: Member of UK SPI-M committee, Scottish Government Scientific Advisory Committee, MHRA Covid vaccine benefit and risk expert working group.” IR is the member of the Advisory scientific committee on COVID-19 of the Government of Croatia and co-Editor-in-Chief of the Journal of Global Health. AS is an Academic Editor on PLOS Medicine’s editorial board, and is a member of the Scottish Government Chief Medical Officer’s COVID-19 Advisory Group and its Standing Committee on Pandemics; he is also a member of the UK Government’s New and Emerging Respiratory Virus Threats Risk Stratification Subgroup and a member of AstraZeneca’s Thrombotic Thrombocytopenic Taskforce. All roles are unremunerated. All other authors declare no competing interests., (Copyright: © 2023 Cerqueira-Silva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)