Real-world effectiveness of Ad26.COV2.S or BNT162b2 booster vaccines against severe COVID-19 in adults who received a primary dose of Ad26.COV2.S in South Africa during the Delta period: A retrospective cohort study using medical scheme data

Background. From March 2020 to June 2022, South Africa (SA) confronted successive waves of COVID‐19, each linked to emerging SARS‐CoV‐2 variants. Vaccines played a critical role in preventing severe disease and death, but as new SARS‐CoV‐2 variants emerged, with increasing breakthrough infections, questions arose about the real‐world effectiveness of first‐generation vaccines containing the ancestral strain against evolving variants including Delta and Omicron BA.1 and BA.4/5 SARS‐CoV‐2. Objectives. To assess the real‐world effectiveness of ancestral strain booster doses (either Ad26.COV2.S or BNT162b2) in preventing severe COVID‐19 outcomes, including hospitalisation, admission to critical care and death, among essential workers in SA who received a primary dose of Ad26.COV2.S against emerging SARS‐CoV‐2 variants. Methods. A retrospective cohort study was conducted using data from a large private health insurance scheme. Individuals who received a single dose of Ad26.COV2.S as their primary vaccination were included. Time‐varying Cox regression models were used to assess the effectiveness of boosting with either Ad26.COV2.S or BNT162b2 v. not boosting against severe COVID‐19 outcomes associated with emerging variants, adjusting for various demographic and clinical factors. Results. By August 2021, a total of 407 961 individuals received a first dose of Ad26.COV2.S, of whom 350 688 were eligible for and 332 286 included in the vaccine effectiveness (VE) analysis. Of these, 206 359 (62%) received no further doses, while 113 957 (34%) received a second dose of Ad26.COV2.S and 11 970 (4%) received a second dose of BNT162b2 by August 2022. During the follow‐up period (November 2021 ‐ August 2022), 1 125 COVID‐19‐related hospital admissions, 198 admissions to critical care and 41 COVID‐19‐related deaths were recorded. Adjusted relative VE against severe outcomes was 34% (95% confidence interval (CI) 19 ‐ 45) for hospital admission, 51% (95% CI 22 ‐ 70) for critical care admission, and 89% (95% CI 13 ‐ 98) for COVID‐19‐ related death. Conclusion. While most participants remained unboosted, administration of either ancestral strain Ad26.COV2.S or BNT162b2 vaccination provided protection against severe COVID‐19 outcomes among essential workers in SA during the dominance of the Omicron BA.1 and BA.4/5 variants, demonstrating cross‐strain protection.