Discovery Health contributes key control group to first at-scale, real-world study of J&J COVID-19 vaccine's effectiveness (published in Lancet journal).

In mid-March 2022, the prestigious Lancet journal published new research reporting on the effectiveness of the single-dose Ad26.COV2.S vaccine (Johnson & Johnson) against severe COVID-19, during two waves of the South African COVID-19 epidemic.

The study, titled " Effectiveness of the Ad26.COV2.S vaccine in health-care workers in South Africa (the Sisonke study): results from a single-arm, open-label, phase 3B, implementation study " was led by top South African scientists linked to the South African Medical Research Council, The Desmond Tutu Health Foundation, Centre for the Aids Programme of Research in South Africa (CAPRISA), and other leading local academic institutions.

"We are humbled and privileged to have had the opportunity to support such an important research study," explains Shirley Collie, Chief Healthcare Analytics Actuary, Discovery Health . "This study was conducted by a collaboration of some of South Africa's foremost scientists. Discovery Health's access to highly organised data relating to vaccination status and outcomes among administered medical scheme members allowed us to provide a fundamental control group data set to the researchers. We are proud to have played a role in seeing this research completed, and are very excited by the research findings."

- Read the study in full .

Effectiveness of Johnson & Johnson vaccine against Beta and Delta variants

During the course of the study, the Beta (B.1.351) and then the Delta (B.1.617.2) SARS-CoV-2 variants of concern were dominant, driving South Africa's second and third waves of infection respectively. The delta-driven third wave was South Africa's deadliest COVID-19 wave.

- Key dates: According to the Network for Genomic Surveillance in South Africa the Beta-driven second wave spanned 20 November 2020 to 16 May 2021 and the Delta-driven third wave spanned 17 May to 14 Nov 2021.

The primary objective of the study was to assess the Ad26.COV2.S vaccine's (Johnson & Johnson COVID-19 vaccine) effectiveness against serious illness caused by Beta or Delta SARS-CoV-2 variant infection, 28 days or longer post vaccination.

Findings summarised:

This analysis found the Ad26.COV2.S vaccine to be:

1. 83% (95% CI: 75%-89%) effective in preventing COVID-19 related deaths
2. 75% (95% CI: 69%-82%) effective in preventing COVID-19 related hospital admissions requiring critical or intensive care
3. 67% (95% CI: 62%-71%) effective in preventing COVID-19 related hospitalisations.

8 reasons why this study's findings are important now and into the future

Here are top insights gleaned from the study:

1. This study accessed a significant sample size at 215 813 matched individuals. To facilitate the cohort design, control group data from Discovery Health administered medical scheme data (Scheme A) and the Government Employees Medical Scheme (GEMS/Scheme B) was used. These large and comprehensive datasets enabled high rates of matching, optimising generalisability of findings.
   • Health-care workers in South Africa are predominantly female and middle-aged (i.e., aged 40-60 years) and so the matched population was also predominantly female and middle-aged, restricting the number of men and older people included in the study. However, subgroup analyses confirmed similar protection in men and older people.
   • Active and passive surveillance were used, with prospective follow-up for two years, emphasising the long-term nature of the research.

2. This research study supports existing real-world effectiveness data on the single-dose Ad26.COV2.S COVID-19 vaccine.
   • To date, there has been little real-world effectiveness data for the Ad26.COV2.S vaccine particularly where the Beta or Delta variants of concern have circulated. However, smaller real-world effectiveness studies investigating Ad26.COV2.S have been conducted in other regions of the world and largely support this study's findings.

3. This study was not only conducted during South Africa's third and deadliest COVID-19 Delta wave, but also during the transition in dominance from one variant of concern (Beta) to another (Delta). This means that a single-dose vaccine provided good protection within two to five months after vaccination and this effectiveness was maintained with the emergence of a second variant of concern, in a large cohort of highly exposed health-care workers, many of whom have HIV.

4. The study provides the first reassurance that the vaccine protects people with comorbidities, including HIV, from severe COVID-19 illness. This is information that is much needed in a global context where fewer than 2500 people with HIV have participated in published efficacy trials.
   1. Additionally, worldwide, health-care workers are critical essential workers, who face ongoing, high exposure to SARS-CoV-2, and having been highly affected by the pandemic, they an important group to study.
   2. South Africa is a country with a large burden of comorbidities and the majority of health-care workers who have died due to COVID-19 have had at least one comorbidity (many had multiple comorbidities).

5. Furthermore, vaccine effectiveness is upheld for clinically important endpoints - during surges when morbidity and mortality are severely affected by restricted health system capacity (in particular ICU services), and despite the emergence of a new variant of concern.

6. There is an urgent need to expand the Ad26.COV2.S vaccine evidence base in the face of the Delta variant, given the reports of reduced effectiveness of other COVID-19 vaccines in settings where variants such as Beta or Delta are still dominant.

7. This study has important policy ramifications, especially for the sub-Saharan region, which faced three variants of concern in quick succession over the course of 2020 and 2021, constrained access to effective vaccines against these variants, and logistical difficulties in rapidly scaling up delivery.

8. Single-dose regimens also offer an opportunity to move quickly and efficiently to protect susceptible populations. The Ad26.COV2.S vaccine remains an important vaccine in settings where alternative regimens impose cold-chain logistics or require people in remote areas or dependent on daily paid work to return for a second vaccination soon after their first dose.

Research findings

As of data cut-off (17 July 2021):

1. Among matched, vaccinated individuals:
   1. 302 COVID-19 related hospitalisations occurred (153 in scheme A and 149 in scheme B)
   2. 63 COVID-19 related hospital admissions requiring critical or intensive care occurred (19 in scheme A and 44 in scheme B)
   3. 28 COVID-19 related deaths occurred.
2. Among matched unvaccinated members of the general population :
   1. 897 COVID-19 related hospitalisations occurred (444 in scheme A and 453 in scheme B)
   2. 256 COVID-19 related hospital admissions requiring critical or intensive care occurred (110 in scheme A and 146 in scheme B)
   3. 163 COVID-19 related deaths occurred.

Vaccine effectiveness derived from the total matched cohort was, across all three outcomes:

1. 83% (95% CI: 75%-89%) effectiveness in preventing COVID-19 related death
2. 75% (95% CI: 69%-82%) effectiveness in preventing COVID-19 related hospitaladmissions requiring critical or intensive care
3. 67% (95% CI: 62%-71%) effectiveness in preventing COVID-19 related hospitalisations.

Vaccine effectiveness remained consistent across sample groups and across second and third waves.

Most breakthrough infections in the sample group - highly exposed health-care workers - were asymptomatic or mild, with less than 1% of health-care workers having a severe SARS-CoV-2 infection that resulted in hospitalisation or death.

• Vaccine effectiveness for all three outcomes (admission, admission to critical care or ICU and death) was consistent across scheme A and scheme B.
• Vaccine effectiveness was maintained in older health-care workers and those with comorbidities including HIV infection.
• Vaccine effectiveness remained consistent during the second and third wave, for both schemes A and B.

In conclusion

"This study, alongside other real-world effectiveness studies, confirms the effectiveness of the Ad26.COV2.S vaccine against severe COVID-19 across two distinct waves of infection," says Collie. "The fact that this protection was also evident in people living with comorbidities and HIV - who would usually be at high-risk of severe COVID-19 illness - is a critical finding and provides support for the continued use of this of this vaccine globally."

Study authors note that:

- "Real-world effectiveness studies have shown the loss of effectiveness of COVID-19 vaccines over time. This loss in effectiveness could be attributed to waning immunity or the emergence of a new variant of concern. The Sisonke study will add critical information to the durability of the single-dose regimen. The recent addition of a booster to the Sisonke study, per a protocol amendment on 25 October 2021, will provide critical information on effectiveness of booster doses administered from 6 to 9 months after initial vaccination. For the world's most unvaccinated region, this single-dose vaccine provides a robust, practical, and effective emergency solution to mitigate the worst effects of COVID-19."

Research funding

This research was funded 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, and the Bill & Melinda Gates Foundation. The funders of the study had no role in the study design, data collection, data analysis, data interpretation or writing of the report.

Interested in knowing more or reporting on these findings?

Please email MEDIA_RELATIONS_TEAM@discovery.co.za to request any updated data available since publication and to obtain any further context required.

Did you find this post interesting?

You may also be interested in reading our related post - our 14 December 2021 press release summarising our broader analysis of the Omicron variant. We cover the way in which the two-dose Pfizer-BioNTech vaccination provided 70% protection against severe complications of COVID-19 requiring hospitalisation, and 33% protection against COVID-19 infection, during the Omicron wave of infection from November 2021 into the first months of 2022

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