Effectiveness of the Ad26.Cov2.S Vaccine in Health Care Workers in South Africa

Background: The Sisonke phase 3B open-label implementation study vaccinated health care workers (HCWs) with the single dose Ad26.COV2.S vaccine during two phases of the South African COVID-19 epidemic, dominated first by the Beta followed by the Delta variant of concern.Methods: HCWs were vaccinated over 3 months (17 February -17 May 2021). Vaccine effectiveness (VE) against COVID-19 related hospitalisation, hospitalisation requiring critical or intensive care and death, ascertained 28 days or more post vaccination was assessed up until 17 July 2021. Nested sub-cohorts (A and B) from two national medical scheme administrators / managed care organisations comparing unvaccinated population counterparts matched for COVID-19 risk, were evaluated to assess VE using a matched retrospective cohort design. To validate VE we also compared HCWs with matched unvaccinated HCWs in a nested sub-cohort using a provincial health service data system. Findings: Over the three-month period, 477 234 HCWs were vaccinated in 122 vaccination sites across South Africa. VE derived from the A and B datasets comprising 215 813 HCWs was 83% (95% CI 75-89) to prevent COVID-19 deaths, 75% (95% CI 69-82) to prevent hospital admissions requiring critical or intensive care and 67% (95% CI 62-71) to prevent COVID-19 related hospitalisations. The VEs for all three outcomes were consistent across the three datasets. The VE was maintained in older HCWs and those with comorbidities including HIV infection. VE remained consistent throughout the Beta and Delta dominant phases of the study. Interpretation: The single-dose Ad26.COV2.S demonstrates effectiveness against severe COVID-19 disease and death post -vaccination, and against both Beta and Delta variants providing real world evidence for its use globally.