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S Afr Med J . Real-world effectiveness of Ad26.COV2.S or BNT162b2 booster vaccines against severe COVID-19 in adults who received a primary dose of

tetano

Editor, Senior Moderator
S Afr Med J


. 2025 Aug 1;115(7):e2532.
doi: 10.7196/SAMJ.2025.v115i7.2532. 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

L Fairall[SUP] 1 [/SUP], N Yende-Zuma[SUP] 2 [/SUP], Tarylee Reddy[SUP] 3 [/SUP], N Garrett[SUP] 4 [/SUP], A Goga[SUP] 5 [/SUP], S Bennet[SUP] 6 [/SUP], N Folb[SUP] 6 [/SUP], I Seocharan[SUP] 3 [/SUP], S Mametja[SUP] 7 [/SUP], M Semenya[SUP] 7 [/SUP], S R N Simelane[SUP] 8 [/SUP], L-G[SUP] 9 [/SUP], G E Gray[SUP] 10 [/SUP]



Affiliations
Abstract

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.


 
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