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Serum neutralizing antibodies (nAbs) induced by vaccination have been linked to protection against symptomatic and severe coronavirus disease 2019. However, much less is known about the efficacy of nAbs in preventing the acquisition of infection, especially in the context of natural immunity and against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune-escape variants. Here we conducted mediation analysis to assess serum nAbs induced by prior SARS-CoV-2 infections as potential correlates of protection against Delta and Omicron infections, in rural and urban household cohorts in South Africa. We find that, in the Delta wave, D614G nAbs mediate 37% (95% confidence interval: 34–40%) of the total protection against infection conferred by prior exposure to SARS-CoV-2, and that protection decreases with waning immunity. In contrast, Omicron BA.1 nAbs mediate 11% (95% confidence interval: 9–12%) of the total protection against Omicron BA.1 or BA.2 infections, due to Omicron’s neutralization escape. These findings underscore that correlates of protection mediated through nAbs are variant specific, and that boosting of nAbs against circulating variants might restore or confer immune protection lost due to nAb waning and/or immune escape. However, the majority of immune protection against SARS-CoV-2 conferred by natural infection cannot be fully explained by serum nAbs alone. Measuring these and other immune markers including T cell responses, both in the serum and in other compartments such as the nasal mucosa, may be required to comprehensively understand and predict immune protection against SARS-CoV-2.

Understanding the build-up of immunity with successive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the epidemiological conditions that favor rapidly expanding epidemics will help facilitate future pandemic control. We analyzed high-resolution infection and serology data from two longitudinal household cohorts in South Africa to reveal high cumulative infection rates and durable cross-protective immunity conferred by prior infection in the pre-Omicron era. Building on the history of past exposures to different SARS-CoV-2 variants and vaccination in the more representative urban cohort given South Africa’s high urbanization rate, we used mathematical models to explore the fitness advantage of the Omicron variant and its epidemic trajectory. Modelling suggests the Omicron wave likely infected a large fraction (44% - 81%) of the population, leaving a complex landscape of population immunity primed and boosted with antigenically distinct variants. We project that future SARS-CoV-2 resurgences are likely under a range of scenarios of viral characteristics, population contacts, and residual cross-protection.

BackgroundSeveral circumcision devices have been evaluated for a safe and simplified male circumcision among adults. The PrePex device was prequalified for voluntary male medical circumcision (VMMC) in May 2013 by the World Health Organization and is expected to simplify the procedure safely while reducing cost. South Africa is scaling up VMMC.ObjectiveTo evaluate the overall unit cost of VMMC at a mixed site vs. a hypothetical PrePex-only site in South Africa.DesignWe evaluated the overall unit cost of VMMC at a mixed site where PrePex VMMC procedure was added to routine forceps-guided scalpel-based VMMC in Soweto, South Africa. We abstracted costs and then modeled these costs for a hypothetical PrePex-only site, at which 9,600 PrePex circumcisions per year could be done. We examined cost drivers and modeled costs, varying the price of the PrePex device. The healthcare system perspective was used.ResultsIn both sites, the main contributors of cost were personnel and consumables. If 10% of all VMMC were by PrePex at the mixed site, the overall costs of the surgical method and PrePex were similar – US$59.62 and $59.53, respectively. At the hypothetical PrePex-only site, the unit cost was US$51.10 with PrePex circumcisions having markedly lower personnel and biohazardous waste management costs. In sensitivity analysis with the cost of PrePex kit reduced to US$10 and $2, the cost of VMMC was further reduced.ConclusionsAdding PrePex to an existing site did not necessarily reduce the overall costs of VMMC. However, starting a new PrePex-only site is feasible and may significantly reduce the overall cost by lowering both personnel and capital costs, thus being cost-effective in the long term. Achieving a lower cost for PrePex will be an important contributor to the scale-up of VMMC.