Residency of study participants (n = 745).

Africa has reported lower COVID-19 morbidity and mortality compared to other regions. Yet, the flat COVID-19 trajectory remains to be fully explained. Nigeria, Africa’s most populous country, accounted for less than 1% of global COVID-19 cases. The present study evaluated SARS-CoV-2 seroprevalence, vaccine uptake, and methodological differences in serological threshold setting among febrile patients attending peri-urban and urban clinics in Southern Nigeria. Between October 2022 and February 2023, 745 febrile participants were recruited from Owo (Ondo State) and Ikorodu (Lagos State). Serum samples were tested for IgG antibodies against wild-type and variant SARS-CoV-2 antigens using a multiplex bead-based antibody assay. Seropositivity was calculated using two classification boundary methods: (i) the conventional three standard deviations above the mean of negative controls (3STDV) and (ii) the open-source SeroNIST tool. Vaccine uptake and risk factors for exposure were assessed. Vaccine uptake was 66.0% and significantly higher in peri-urban Owo (80.2%) than urban Ikorodu (52.6%, p-value