Background: Relatively few COVID-19 cases and deaths have been reported through much of sub-Saharan Africa, including South Sudan, although the extent of SARS-CoV-2 spread remains unclear due to weak surveillance systems and few population-representative serosurveys. Methods: We conducted a representative household-based cross-sectional serosurvey in Juba, South Sudan. We quantified IgG antibody responses to SARS-CoV-2 spike protein receptor-binding domain and estimated seroprevalence using a Bayesian regression model accounting for test performance. Results: We recruited 2,214 participants from August 10 to September 11, 2020 and 22.3% had anti-SARS-CoV-2 IgG titers above levels in pre-pandemic samples. After accounting for waning antibody levels, age, and sex, we estimated that 38.5% (32.1 - 46.8) of the population had been infected with SARS-CoV-2. For each RT-PCR confirmed COVID-19 case, 104 (87-126) infections were unreported. Background antibody reactivity was higher in pre-pandemic samples from Juba compared to Boston, where the serological test was validated. The estimated proportion of the population infected ranged from 30.1% to 60.6% depending on assumptions about test performance and prevalence of clinically severe infections. Conclusions: SARS-CoV-2 has spread extensively within Juba. Validation of serological tests in sub-Saharan African populations is critical to improve our ability to use serosurveillance to understand and mitigate transmission.

G lobally, >100 million cases and >2.6 million deaths had been attributed to coronavirus disease (COVID-19) as of March 14, 2021 (1). Most cases have been reported in Europe and the Americas. In Africa, >2.9 million cases and ≈75,000 deaths have been reported (1). Reasons for the lower reported incidence and death associated with COVID-19 in Africa during the fi rst 6-8 months of the pandemic are unclear but may include differences in age distribution, immune history, climate, early mitigation measures, and epidemiologic connectivity between geographic regions (2,3). However, our understanding of the true spread of severe acute respiratory virus coronavirus 2 (SARS-CoV-2) has been obscured by limited testing capabilities, underreported deaths, and undetected mild or asymptomatic infections (4). Populationbased serological surveys, hundreds of which have been conducted worldwide, can help shed light on the extent of this underestimation of SARS-CoV-2 infections (5,6). As of March 18, 2021, only 16 studies published or available in preprint had been conducted in sub-Saharan Africa (7)(8)(9)(10)(11)(12)(13)(14)(15)(16) H. Majiya et al., unpub. data,

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