The COSI BAIR trial will involve approximately 60 children, aged 5 to 8 years old, comprising a subset of participants from the Melbourne Infant Study BCG for Allergy and Infection Reduction (MIS BAIR) randomised controlled trial. The overall aim of this trial is to investigate the specific and heterologous effects of COVID-19 vaccination on immunity in children. COSI BAIR will aim to recruit its participants from the MIS BAIR Bacillus Calmette-Guérin (BCG)-naïve group. These children will be followed up until 28 days after their final Coronavirus Disease 2019 (COVID-19) vaccination.

Venous blood samples will be collected at two study visits, at Murdoch Children's Research Institute (MCRI):

1. Day 0 - baseline (day of COVID-19 vaccination #1), and
2. Day 84 (28 days after COVID-19 vaccination #2).

Inclusion Criteria:

• Age between five and eleven years (i.e. prior to the twelfth birthday) at the time of enrolment,

• Participant who was randomised in the MIS BAIR trial, and

  • Was randomly allocated to receive and received BCG as part of the MIS BAIR trial, OR,
  • Was randomly allocated to not receive and did not receive BCG;

• Is an individual whose parent/legally acceptable representative (LAR) consented to be contacted about future ethically approved research, during the MIS BAIR trial consent process, AND

• Has a parent/LAR capable of understanding the parent/LAR information statement and consent form (PICF) document and providing consent on the participant's behalf.

Exclusion Criteria:

• Has a known hypersensitivity to the active ingredient or any of the excipients in tozinameran,
• Has a prior polymerase chain reaction (PCR)-confirmed diagnosis of COVID-19 whether symptomatic or not,
• Has received a COVID-19 vaccine (approved by the TGA or otherwise) prior to trial enrolment,
• An individual and/or parent/legally acceptable representative who is unwilling or unable to give written informed consent,
• An individual and/or parent/legally acceptable representative who is unwilling or unable to consent to attend all scheduled study visits,
• An individual and/or parent/LAR who is unwilling or unable to give consent for blood samples to be taken from the trial participant at each study visit, and
• Has or has had a clinically significant medical morbidity (e.g. immunocompromised because of congenital or acquired disorders or immunosuppressive medical treatment; a bleeding disorder; a recent history of inflammatory cardiac illness within the past 6 months, e.g., myocarditis, pericarditis, endocarditis, acute rheumatic fever (with active myocardial inflammation) or acute rheumatic heart disease, or acute decompensated heart failure), and
• Has received BCG at any other time than as part of the MIS BAIR trial.

At the time of article publication, the following will be made available long-term for use by future researchers from a recognised research institution whose proposed use of the data has been ethically reviewed and approved by an independent committee and who accept MCRI's conditions for access:

• Individual participant data that underlie the results reported in this article after deidentification (text, tables, figures and appendices), and
• Trial protocol, PICF, analytic code

We may share the information and samples we collect with other researchers within Australia and/or overseas to increase our understanding of COVID-19 and COVID-19 vaccination and other infections. The location of data/samples sent overseas is not yet determined. Data and samples would be sent identifiable only by a study number so that the child's identity is not disclosed to these researchers. Any data or samples sent to researchers outside of Australia will not be covered by Australian regulations.

Following the completion and analysis of the trial, the data will be retained long-term following the mandatory archive period for use in future research projects. The retention period will be for at least 15 years post-trial completion or until the child is aged 25 years (whichever is later). The Sponsor-Investigator and/or delegate will be the custodians during the archive period. Following the end of the archival period, the data will be disposed of.

• Must pertain to ethically approved research
• Must be from a recognised institution
• Must be willing to share the aims, outcomes and outcomes measures of the secondary analyses
• Must ask for consent from the COSI BAIR principal investigators
• Must be approved by the COSI BAIR Sponsor-Investigator