Waning 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-Control Study

Abstract

Background: Brazil and Scotland have used mRNA boosters in their respective populations since September, 2021 with Omicron’s emergence accelerating their booster programme.  Despite this, both countries have reported substantial recent increases in COVID-19 cases. The duration of the protection conferred by the booster dose against symptomatic Omicron cases and severe outcomes is unclear.

Methods: Using a test-negative design, we analysed national databases to estimate the vaccine effectiveness (VE) of a primary series (with ChAdOx1 or BNT162b2) plus a mRNA vaccine booster (with BNT162b2 or mRNA-1273) against symptomatic SARS-CoV-2 infection and severe COVID-19 outcomes (hospitalisation or death) during the period of Omicron dominance in Brazil and Scotland. We also stratified analyses by age and primary series vaccine type.

Findings: At 2-4 weeks after the mRNA booster, VE of ChAdOx1 or BNT162b2 vaccines plus a mRNA booster against symptomatic SARS-CoV-2 infection was 42.3% (95% confidence interval [CI] 41.6-42.9) in Brazil and 53.4% (95%CI 51.4-55.3) in Scotland, waning to 5.4% (95%CI 3.2-7.5) in Brazil and 29.2% (95%CI 25.0-33.1) in Scotland at ≥13 weeks. VE against severe outcomes in Brazil was 89.8% (95%CI 88.9-90.6) at 2-4 weeks post-booster, decreasing to 80.2% (95%CI 78.0-82.2) at ≥13 weeks (p for trend <0.0001). During the same period in Scotland, VE went from 81.8% (95%CI 69.1-89.3) to 75.8% (95%CI 55.0-87.0) (p for trend = 0.127). In Brazil, individuals aged ≥65 years showed evidence of waning with VE dropping from 83.1% (95%CI 80.3-85.4) at 2-4 weeks after booster to 76.9% (95%CI 74.0-79.5) at ≥13 weeks.

Interpretation: mRNA boosters after a primary vaccination schedule 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 13 weeks.

Funding: Fiocruz, "Fazer o Bem Faz Bem Programme" JBS; Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundação de Apoio à Pesquisa do Estado da Bahia, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro. UK Research and Innovation (Medical Research Council), Scottish Government, Industrial Strategy Challenge Fund, Health Data Research UK and National Core Studies - Data and Connectivity.

Declaration of Interest: 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 reports grants from the Medical Research Council (MRC) and Public Health Scotland, during the conduct of the study, and 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. 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 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 have nothing to declare.

Ethical Approval: For Brazil, ethics approvals were obtained from the Brazilian National Commission in Research Ethics (CONEP approval number: 4.921.308). In Scotland, the National Research Ethics Service Committee, Southeast Scotland 02 (reference number: 12/SS/0201) and Public Benefit and Privacy Panel for Health and Social Care (reference number: 1920-0279) approved the study

Keywords: COVID-19, Vaccines, ChAdOx1, mRNA, booster, BNT162b2, Omicron, waning