Temporal trends of SARS-CoV-2 exposure in adolescents: a longitudinal pilot study nested in a Uganda birth cohort [version 1; peer review: awaiting peer review]

Background: COVID-19 remains a significant global public health concern, contributing to hospitalization and Intensive Care Unit (ICU) admissions. However, SARS-CoV-2 exposure in adolescents remains poorly understood. 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).

Methods: We analysed stored blood samples from a subset of participants enrolled in the Entebbe Mother and Baby Study (EMaBS), a long-standing Ugandan birth cohort established in 2003 as a randomized trial (ISRCTN32849447). Samples were drawn from three studies: pre-pandemic samples (2014–2016) collected during a blood pressure study; pandemic-era samples collected during the POPVAC C trial (2020–2021), 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. Blood samples were collected at multiple study timepoints. SARS-CoV-2 IgG spike antibodies were measured using an in-house enzyme-linked immunosorbent assay (ELISA).

Results: None of the 47 participants were seropositive for SARS-CoV-2 in pre-pandemic samples (2014–2016). In pandemic-era samples (2020–2022), seropositivity increased over time. At POPVAC C screening, 2 (4%) participants were seropositive, increasing to 3 (6%) at week 4, 5 (11%) at week 8, and 36 (77%) at week 52, which also served as the CoHost baseline. At the CoHost 6-month timepoint, 40 (85%) of participants were seropositive, increasing to 45 (96%) at 12 months timepoint. SARS-CoV-2 seropositivity progressively increased, with a marked rise during the Delta wave (May‒July 2021) and peaking in the Omicron wave (November 2021 - February 2022).

Conclusions: Our findings indicate increased SARS-CoV-2 exposure among adolescents during later pandemic waves, likely driven by the emergence of highly transmissible variants and changes in public health measures. These preliminary findings highlight the need for age-specific mitigation strategies.