This dataset comprises individual-level data of a subset of participants from a longitudinal study nested within the Entebbe Mother and Baby Study (EMaBS) birth cohort, based in Entebbe municipality, Uganda. Data were drawn from three studies that these participants took part in, where samples were collected: pre-pandemic samples (2014–2016) collected during a blood pressure study; pandemic-era samples collected during the POPVAC C trial (2020–2021) (ISRCTN32849447), which evaluated the impact of BCG revaccination on vaccine responses; and samples from the CoHost study (2021–2022), a 12-month longitudinal follow-up assessing SARS-CoV-2 infection and exposure from participants in the POPVAC B randomised controlled trial. The study aimed to analyse temporal trends in SARS-CoV-2 seropositivity in Ugandan adolescents using pre-pandemic (2014-2016) and pandemic-era samples (2020-2022). We utilised previously stored demographic and clinical data, along with bio-banked samples from these three studies.