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.