SARS-CoV-2 delta variant: a persistent threat to the effectiveness of vaccines
Authors: Ramachandran Thiruvengadam, Akshay Binayke, Amit Awasthi
Journal: The Lancet Infectious Diseases (2021)

Vaccine effectiveness studies are important tools to assess the usefulness of vaccines during the post-approval period in the real-world context. Global experience in evaluating many previous vaccines has enabled formulation of best practices and guidelines for conducting such observational epidemiological studies in a short time frame,1WHOEvaluation of COVID-19 vaccine effectiveness. World Health Organization, Geneva2021Google Scholar to guide immunisation policies. These studies are of particular importance during the COVID-19 pandemic, where the roll-out of vaccines has been much faster than usual. In The Lancet Infectious Diseases, Devashish Desai and colleagues2Desai D Khan AR Soneja M et al.Effectiveness of an inactivated virus-based SARS-CoV-2 vaccine, BBV152, in India: a test-negative, case-control study.Lancet Infect Dis. 2021; (published online Nov 23.)https://doi.org/10.1016/S1473-3099(21)00674-5Summary Full Text Full Text PDF PubMed Scopus (52) Google Scholar report the findings from their test-negative, case-control, vaccine effectiveness study of a whole-virion inactivated SARS-CoV-2 vaccine, BBV152, during the peak of the second wave of the COVID-19 pandemic in New Delhi, India, which was presumably driven by the delta (B.1.617.2) variant. The adjusted vaccine effectiveness against symptomatic COVID-19 after two doses of BBV152, with the second dose administered at least 14 days before RT-PCR testing, was 50% (95% CI 33–62). This is, to our knowledge, a first independent report on the vaccine effectiveness of BBV152, which is being administered to millions of people in India and other low-income and middle-income countries.3Government of India Ministry of Health and Family WelfareCo-WIN dashboard: India COVID-19 vaccination status.https://dashboard.cowin.gov.in/Date: 2021Date accessed: September 29, 2021Google Scholar The key message of the study is the reduced effectiveness of BBV152, even with two doses of vaccine, against SARS-CoV-2 infections attributed to the delta variant compared with the effectiveness against the wild type (77·8% [95% CI 65·2–86·4]) that was reported in the phase 3 trial.4Ella R Reddy S Blackwelder W et al.Efficacy, safety, and lot-to-lot immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152): interim results of a randomised, double-blind, controlled, phase 3 trial.Lancet. 2021; (published online Nov 11.)https://doi.org/10.1016/S0140-6736(21)02000-6PubMed Google Scholar It is important to note that the vaccine effectiveness estimated was not against delta variant infections only, but against infections that occurred during the surge in SARS-CoV-2 cases dominated by the delta variant.5Dhar MS Marwal R Vs R et al.Genomic characterization and epidemiology of an emerging SARS-CoV-2 variant in Delhi, India.Science. 2021; 0eabj9932Google Scholar A strength of the study by Desai and colleagues is the test-negative, case-control design in an organised study population—employees of a tertiary-level health-care institution—who were offered unbiased vaccination and testing services. The study has some methodological limitations, such as absence of comorbidity data and no objective assessment of previous infection, as discussed by the authors. 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.5Dhar MS Marwal R Vs R et al.Genomic characterization and epidemiology of an emerging SARS-CoV-2 variant in Delhi, India.Science. 2021; 0eabj9932Google Scholar, 6Fisman DN Tuite AR Evaluation of the relative virulence of novel SARS-CoV-2 variants: a retrospective cohort study in Ontario, Canada.CMAJ. 2021; 193: E1619-E1625Crossref PubMed Scopus (160) Google Scholar 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.7Harder T Külper-Schiek W Reda S et al.Effectiveness of COVID-19 vaccines against SARS-CoV-2 infection with the delta (B.1.617.2) variant: second interim results of a living systematic review and meta-analysis, 1 January to 25 August 2021.Euro Surveill. 2021; 262100920Google Scholar, 8Reis BY Barda N Leshchinsky M et al.Effectiveness of BNT162b2 vaccine against delta variant in adolescents.N Engl J Med. 2021; (published online Oct 20.)https://doi.org/10.1056/NEJMc2114290Crossref Scopus (73) Google Scholar Furthermore, this study was conducted in a high-risk population with a high exposure to SARS-CoV-2 in a tertiary care hospital caring for patients with COVID-19, in the context of a massive surge in infections, with high test-positivity rates of up to 34%, which could have been the key factor for the observed reduction in vaccine effectiveness. Although BBV152 might not be as effective against symptomatic infection by the delta variant as it was against the wild type, a more useful outcome of vaccination is the protection against moderate and severe COVID-19. Moderate-to-severe disease warrants hospitalisation and intensive medical care, and therefore puts strain on health-care systems. Vaccination has been shown to protect against hospitalisation and death, even during the delta surge.7Harder T Külper-Schiek W Reda S et al.Effectiveness of COVID-19 vaccines against SARS-CoV-2 infection with the delta (B.1.617.2) variant: second interim results of a living systematic review and meta-analysis, 1 January to 25 August 2021.Euro Surveill. 2021; 262100920Google Scholar This study does not provide evidence in this regard. But, if one were to consider vaccine effectiveness studies for other inactivated vaccines which indicated a better protection against moderate-to-severe disease than infection, it could be presumed that BBV152 might also have a similar performance.9Wang F An Z Rodewald L et al.Guangdong's study of the effectiveness of China's inactivated vaccines against the SARS-CoV-2 B.1.617.2 (delta) variant.China CDC Wkly. 2021; 3: 728-730Crossref PubMed Scopus (6) Google Scholar, 10Li X-N Huang Y Wang W et al.Effectiveness of inactivated SARS-CoV-2 vaccines against the delta variant infection in Guangzhou: a test-negative case-control real-world study.Emerg Microbes Infect. 2021; 10: 1751-1759Crossref PubMed Scopus (179) Google Scholar Future studies should be designed with the emphasis to evaluate protection against moderate-to-severe COVID-19 and to analyse immune correlates of protection, such as neutralising antibodies and antigen-specific T-cell response, against the wild type and the delta variant in BBV152-vaccinated individuals. This emphasis might provide evidence on the need for a booster dose, especially in populations with comorbid conditions. 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. We declare no competing interests. Effectiveness of an inactivated virus-based SARS-CoV-2 vaccine, BBV152, in India: a test-negative, case-control studyThis study shows the effectiveness of two doses of BBV152 against symptomatic COVID-19 in the context of a huge surge in cases, presumably dominated by the potentially immune-evasive delta (B.1.617.2) variant of SARS-CoV-2. Our findings support the ongoing roll-out of this vaccine to help control the spread of SARS-CoV-2, while continuing the emphasis on adherence to non-pharmacological measures. 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