The study, published in The Lancet Infectious Diseases journal, assessed 2,714 hospital workers from the All India Institute of Medical Sciences (AIIMS) in Delhi, India, from Apr 15 – May 15, 2021, who were symptomatic and underwent RT-PCR testing for COVID-19.

The delta variant was the dominant strain in India during the study period, accounting for approximately 80 percent of all confirmed COVID-19 cases.

BBV152, developed by Bharat Biotech (India), is a Vero cell-derived, inactivated whole-virion vaccine formulated with a novel adjuvant and administered in a two-dose regimen, 28 days apart.

In January 2021, BBV152 was approved for emergency use in India for people aged 18. The World Health Organization (WHO) added BBV152 to its list of approved emergency use COVID-19 vaccines in November 2021.

This new study was conducted during India’s second COVID-19 surge in a high-exposure population (healthcare workers) who were primarily offered the BBV152 vaccine, thus presenting a unique opportunity to evaluate its real-world effectiveness.

“Our study offers a more complete picture of how BBV152 performs in the field and should be considered in the context of COVID-19 surge conditions in India, combined with the possible immune evasive potential of the delta variant. Our findings add to the growing body of evidence that rapid vaccine rollout programmes remain the most promising path to pandemic control while public health policies must continue to include additional protective measures, such as mask-wearing and social distancing,” says Dr Manish Soneja, Additional Professor of Medicine at AIIMS in New Delhi.

The study was carried out at AIIMS, a tertiary care hospital and COVID-19 treatment centre. The hospital’s COVID-19 vaccination centre exclusively offered BBV152 beginning on January 16, 2021, to all of its 23,000 employees.

Researchers conducted a test-negative control study between Apr 15 and May 15, 2021, to evaluate the effectiveness of BBV152 vaccine against symptomatic RT-PCR confirmed SARS-CoV-2 infection.

Of the 2,714 employees in the study population, 1,617 people tested positive for SARS-CoV-2 infection, and 1,097 tested negative.

Positive cases were matched to negative RT-PCR tests (controls) using a 1:1 ratio based on age and gender.

The odds of vaccination with BBV152 were compared between cases and controls and adjusted for occupational exposure to COVID-19, previous SARS-CoV-2 infection, and infection dates.

The adjusted vaccine effectiveness against symptomatic COVID-19 after two doses of BBV152 with the second dose administered 14 or more days before undergoing RT-PCR testing was 50 percent.

The effectiveness of two vaccine doses remained stable over the seven week follow-up period.

The majority of eligible participants were tested for SARS-CoV-2 infection during the first 20 days of the 30-day study when the test positivity rate for COVID-19 was at its peak in India. Requests for testing gradually declined toward the end of the study period (from May 6 to May 15).

The median interval between receipt of the last vaccine dose and the end of the study period (May 15, 2021) for those who had received one dose was 37 days (range 7 to 119) days and 50 days (range 5 to 103) days for those who had received two doses.

The adjusted vaccine effectiveness of the first dose, estimated after 7 and 21 days, was low, which is consistent with the performance of other vaccines against the delta variant and indicates the importance of a second dose to achieve vaccine effectiveness.

“Findings from the study confirm previous research indicating that two doses of BBV152 are required to achieve maximum protection and that all vaccine roll-out plans must follow the recommended dosing schedule. More research is needed to better understand how these findings translate to BBV152’s effectiveness against delta and other variants of concern, especially related to severe COVID-19 infection, hospitalisation, and deaths,” says Dr Parul Kodan, Assistant Professor of Medicine at AIIMS in New Delhi.

An essential component of any vaccine roll-out plan is an assessment of vaccine effectiveness post-licensure in a real-world setting because its real-world performance can often differ from controlled trial conditions.

Indeed, the authors acknowledge that the vaccine effectiveness estimated in this study is lower than the efficacy reported by a recently published phase 3 randomised control study of BBV152.

The authors note that several factors may be responsible for the lower vaccine effectiveness in this study. Firstly, this study population only included hospital employees who may have a higher risk of exposure to COVID-19 infection than the general population.

Secondly, the study was conducted during the peak of India’s second wave of COVID-19 with high test positivity rates for both hospital employees and residents of Delhi.

Thirdly, the prevalence of circulating variants of concern, especially delta, may have contributed to BBV152’s lower effectiveness.

The authors acknowledge several limitations in the study. Most importantly, this study does not estimate the vaccine effectiveness against hospitalisation, severe disease, and death, which require further assessment.

Additionally, the study was not designed to estimate vaccine effectiveness for different time intervals after vaccination or to determine if vaccine effectiveness changed over time. Another limitation was the absence of data on comorbidities and prior COVID-19 infection, which may affect health-seeking behaviour as well as vaccine effectiveness.

While the study took place during the surge of the delta variant, RT-PCR positive patients were not tested for SARS-CoV-2 variants.

Therefore, the authors could not definitively estimate the vaccine effectiveness against symptomatic COVID-19 due to a specific variant. Future studies should examine the delta variant’s vaccine escape potential.

“Our study took place when the COVID-19 test positivity rate in Delhi was around 35 percent – the highest since the beginning of the pandemic. It is an important factor to consider while interpreting the impact of any vaccine. Availability of a safe and effective vaccine, addressing vaccine hesitancy to achieve good pace and coverage are cornerstone to a successful universal vaccination programme,” said Professor Naveet Wig, Head of Medicine at AIIMS, New Delhi.

Writing in a linked comment, Dr Ramachandran Thiruvengadam, Dr Akshay Binayke, and Dr Amit Awasthi of the Translational Health Science and Technology Institute (India), who were not involved in the study, says, “The decline in vaccine effectiveness against SARS-CoV-2 infection during a delta-driven surge in cases is neither surprising nor exclusive to inactivated SARS-CoV-2 vaccines including BBV152."

"The delta variant has high transmissibility, infectivity, and virulence, which causes severe disease. These attributes might have contributed to a reduced vaccine effectiveness against symptomatic infections, which has been reported to be as low as 56% for other vaccines in multiple studies worldwide…Future studies should be designed with the emphasis to evaluate protection against moderate to-severe COVID-19…Nevertheless, faced with the challenge of protecting as much of the population as possible, the ongoing vaccination drive should be continued as a public health intervention against SARS-CoV-2, along with strict adherence to other non-pharmacological interventions, particularly in the context of variant-driven surges,”  Dr Ramachandran Thiruvengadam, Dr Akshay Binayke, and Dr Amit Awasthi said.