Estimates of SARS-CoV-2 transmission rates have significant public health policy implications since they shed light on the severity of illness in various groups and aid in strategic deployment of diagnostics, treatment and vaccination. Population-based investigations have not been conducted in Ghana to identify the seroprevalence of SARS-CoV-2. We conducted an age stratified nationally representative household study to determine the seroprevalence of SARS-CoV-2 and identify risk factors between February and December 2021. Study participants, 5 years and older regardless of prior or current infection COVID-19 infection from across Ghana were included in the study. Data on sociodemographic characteristics, contact with an individual with COVID-19-related symptoms, history of COVID-19-related illness, and adherence to infection prevention measures were collected. Serum obtained was tested for total antibodies with the WANTAI ELISA kit. The presence of antibodies against SAR-COV-2 was detected in 3,476 of 5,348 participants, indicating a seroprevalence of 67.10% (95% CI: 63.71–66.26). Males had lower seroprevalence (65.8% [95% CI: 63.5–68.04]) than females (68.4% [95% CI: 66.10–69.92]). Seroprevalence was lowest in >20 years (64.8% [95% CI: 62.36–67.19]) and highest among young adults; 20–39 years (71.1% [95% CI 68.83,73.39]). Seropositivity was associated with education, employment status and geographic location. Vaccination status in the study population was 10%. Exposure is more likely in urban than rural areas thus infection prevention protocols must be encouraged and maintained. Also, promoting vaccination in target groups and in rural areas is necessary to curb transmission of the virus.

A significant proportion of SARS-CoV-2 infections in Africa were identified as asymptomatic. With the surge of the Omicron variant, asymptomatic participants in epidemiological surveys were key to accurately estimating seroprevalence and true infections in the population. This study assessed seroprevalence, active infections, and circulating variants in Accra, Ghana, during the Omicron wave. Secondary objectives included assessing the association between seroprevalence and sociodemographic factors, vaccination, and adherence to recommended SARS-CoV-2 prevention and control measures. We conducted a cross-sectional survey in Greater Accra in December 2021 using a standardized questionnaire. Serum and naso-oropharyngeal swab samples were collected from 1027 individuals aged ≥ 5 years for the estimation of total antibodies and detection of infection. The study found an overall seroprevalence of 86.8% [95% CI: 84.53–88.77]. PCR test positivity of SARS-CoV-2 was 10%, with the Omicron and Delta variants accounting for 44.1% and 8.8% of infections, respectively. Vaccination (cOR = 10.5, 95% CI: 4.97–26.9, p < 0.001) and older age, particularly the 60+ age group (cOR = 6.05, 95% CI: 2.44–20.2, p < 0.001), were associated with an increase in odds of seropositivity among participants. High seropositivity of SARS-CoV-2 in Accra was an indication of high exposure and transmission rates and/or high vaccine-induced seroprevalence.