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

Abstract

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.

Note: Funding: Direct Funding for the Sisonke Study was provided by the National Treasury of South Africa, the National Department of Health, Solidarity Response Fund NPC, The Michael & Susan Dell Foundation, The Elma Vaccines and Immunization Foundation - Grant number 21- V0001, and the Bill & Melinda Gates Foundation – grant number INV-030342.

Declaration of Interests: The authors in this article have no conflicts of interest. The investigational product was donated by JNJ, the study was funded by the South African Government, the BMGF, the Solidarity Response Fund, the Michael & Dell Foundation and the ELMA Vaccines and Immunization Foundation..

Ethics Approval Statement: The Protocol was reviewed and approved by the SAHPRA, and all health research ethics committees associated with Sisonke clinical research sites. Approvals and data sharing agreements enabled research team access to anonymized unvaccinated datasets post matching. A protocol safety team met each week to review all safety events, break-through infections and deaths. The Protocol Safety Committee provided independent oversight of the study.

Trial Registration: The trial was registered at South African National Clinical Trial Registry (DOH-27- 022021-6844); clin.gov number (NCT04838795) and the Pan African Clinical Trials Registry (PACTR202102855526180).