This dataset contains anonymised clinical and laboratory data from 81 individuals who tested positive for SARS-CoV-2 by RT-PCR at MDS Lancet Laboratories in Accra, Ghana, between July and December 2022. The dataset includes demographic variables (age, sex), COVID-19 vaccination status, clinical presentation (symptomatic/asymptomatic and symptom type), RT-PCR cycle threshold (Ct) values for three viral gene targets (N, RdRP, E), and SARS-CoV-2 variant identification (Alpha, Delta, Omicron). Breakthrough infections were defined as positive cases occurring ≥14 days after full COVID-19 vaccination. The dataset was used to assess the virological and clinical features associated with breakthrough infections in a sub-Saharan African setting.