The delta COVID-19 variant has contributed to a surge in the number of COVID cases across the globe, including a notable increase in cases in the UK. A recent study aimed to estimate the effectiveness of COVID-19 vaccines against symptomatic disease caused by the delta variant using data from the real-world setting.
The delta COVID variant
The B.1.617.2 delta COVID-19 variant first emerged in India in December 2020 following a surge in cases, and has now been detected across the globe. As of 19th May 2021, the variant has been detected in 43 countries across 6 different continents in GISAID.
The delta variant is characterised by spike protein mutations, including T478K, D614G and P681R. The P681R mutation affects the S1/S2 cleavage site and studies have suggested that strains with mutations at that site may have increased replication, leading to higher viral loads and increased transmission. Immunogenicity data has not yet been reported for the delta variant. Furthermore, no data has been reported on the effectiveness of COVID-19 vaccines against clinical outcomes with this variant.
COVID-19 vaccines
The UK has achieved rapid rollout of COVID-19 vaccines, starting with deployment of the Pfizer-BioNTech BNT162b2 mRNA vaccine from December 2020. Subsequently, the Oxford-AstraZeneca ChAdOx1 adenovirus vector vaccine was approved for use from January 2021, and more recently the Moderna mRNA-1273 vaccine. Following advice from the Joint Committee of Vaccines and Immunisation, a decision was made to use an extended dosing interval of 12 weeks to maximise the number of individuals receiving the first dose of the vaccine.
Evidence from clinical trials has found that vaccines are highly effective at preventing symptomatic disease. This has since been backed by real-world evidence showing high levels of effectiveness against symptomatic disease, infection and severe disease. The early findings from clinical trials were primarily undertaken in settings where the original strain was the main circulating virus. Therefore, data on the effectiveness of the vaccines against different variants is limited.
In this present study, the researchers aimed to estimate the effectiveness of COVID-19 vaccines against symptomatic disease with the delta variant.
Study design to assess the effectiveness of COVID-19 vaccines against the delta variant
Two approaches were used to estimate the effectiveness of vaccination on the delta variant.
Firstly, a test negative case control (TNCC) design was used to estimate vaccine effectiveness against symptomatic disease with the delta variant compared with the alpha variant (B.1.1.7 variant) over the same period. In brief, this approach compares vaccination status on symptomatic cases to those who report symptoms but test negative. This helps to control biases related to health seeking behaviours, access to testing and case ascertainment.
Secondly, the proportion of cases with the delta variant relative to the alpha variation was estimated by vaccination status. The underlying assumption was that if the vaccine is equally effective against each variant, then a similar proportion of cases with either variant would be observed in unvaccinated compared to vaccinated individuals. Conversely if the vaccine is less effective against the delta variant, the researchers expected there to be a higher proportion of delta variant cases more than three weeks after vaccination, when compared with unvaccinated individuals.
Data sources
Data on all individuals in England vaccinated with COVID-19 vaccines is available in the national vaccination register. The extracted data included date of each dose and vaccination type. Whole genome sequencing data was used to identify the different variants. Additionally, a range of covariates was extracted from the National Immunisation Management System (NIMS) and PCR testing data. These covariates included those associated with the likelihood of being offered or accepting a vaccine, and the risk of exposure to COVID or specifically to either of the variants analysed.
Are COVID vaccines effective against the delta variant?
Using their approach, the researchers found that effectiveness was notably lower after 1 dose of the vaccine for the delta variant. Overall, the effectiveness of the vaccines against the delta variant was 33.5% compared to 51.1% with the alpha variant. With the Pfizer vaccine, two dose effectiveness was reduced from 93.4% with the alpha variant to 87.9% with the delta variant. Similarly, after two doses of the AstraZeneca vaccine effectiveness reduced from 66.1% with the alpha variant to 59.8% with the delta variant. Sequenced cases detected after one or two doses of vaccination had a higher chance of infection with the delta variant compared to unvaccinated cases.
Overall, after two doses of either the Pfizer or AstraZeneca there were only marginal differences in vaccine effectiveness with the delta variant. Absolute differences in vaccine effectiveness were most obvious with only one dose. This data supports maximising vaccine uptake with two doses among vulnerable groups.
Limitations of this study in evaluating the effectiveness of COVID vaccines
The findings of this study are observational, and should therefore be interpreted with caution. Low sensitivity or specificity of PCR testing could result in cases and controls being misclassified, which would attenuate vaccine effectiveness estimates. Moreover, difference in timing of rollout for the two vaccines may have reduced follow-up post two doses of AstraZeneca. This difference in follow-ups could have also attenuated the results of this study. Furthermore, the numbers of individuals in the UK who have received the Moderna vaccine were too small to be able to estimate vaccine effectiveness for this vaccine.
Summary
This study aimed to assess the effectiveness of COVID-19 vaccines against the delta variant using data from the real-world setting. It was found that the vaccine was as effective against the delta variant after two doses. However, it is important that these findings are triangulated with emerging in vitro data on immune response in vaccinated individuals to account for limitations in the data used to carry out this study.
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