Effectiveness of Covid-19 vaccines against variant B.1.617.2 (delta)

study design

We used two methods to estimate the effect of vaccination on the delta variable. First, we used a negative case-control design of the test to estimate the efficacy of the vaccine against episodic disease caused by the delta variant, compared to the alpha variant, during the period when the delta variant was prevalent. This approach has been described in detail elsewhere.10 In summary, we compared the vaccination status of people with symptoms of Covid-19 and the vaccination status of people who reported symptoms but tested negative. This approach helps control biases related to health-seeking behavior, test access, and status ascertainment.

For secondary analysis, the proportion of subjects with cases caused by the delta variant was estimated relative to the main circulating virus (alpha variant) according to vaccination status. The underlying assumption was that if a vaccine had some efficacy and was equally effective against each variant, a similar proportion of cases with either variant would be expected in the unvaccinated and in the vaccinated. Conversely, if the vaccine was less effective against the delta variant than against the alpha variant, the delta variant would be expected to account for a higher proportion of cases occurring more than 3 weeks after vaccination than in unvaccinated subjects. Details of this analysis are described in Section S1 in the Supplementary Appendix, which is available with the full text of this article at NEJM.org. The authors certify the accuracy, completeness of the data, and trial fidelity of the protocol.

data sources

vaccination status

Data on all people in England who have been vaccinated with Covid-19 vaccines are available in the National Immunization Registry (NIMS). Data on vaccinations that occurred up to May 30, 2021, including the date each dose of vaccine was received and type of vaccine, were extracted on June 1, 2021. Vaccination status was classified as receiving a single dose of vaccine among people who developed symptoms after 21 days or more. From receiving the first dose until the day before receiving the second dose, such as among people who developed symptoms 14 days or more after receiving the second dose, and when receiving the first or second dose among people who developed symptoms 21 days or more after receiving the first dose (including any period after receiving the second dose).

SARS-CoV-2 Test

PCR testing for SARS-CoV-2 is done in the UK by hospitals and public health laboratories, as well as by community testing using the test from the car or at home, and is available to anyone with symptoms consistent with Covid-19 ( high fever, new persistent cough, or loss or change in sense of smell or taste). Data were extracted for all positive PCR tests between October 26, 2020 and May 30, 2021. Data were also extracted for all negative community tests registered among people who reported symptoms for case-control analysis. Children under 16 years of age were excluded as of March 21, 2021. Data were limited to subjects who reported symptoms, and only those tested within 10 days after onset of symptoms were included, in order to account for the reduced sensitivity of the PCR test after this period .25

Define the variable

Whole genome sequencing was used to identify delta and alpha variants. The proportion of all positive samples that were sequenced increased from about 10% in February 2021 to nearly 60% in May 2021.4 The sequencing is performed in a network of laboratories, including the Wellcome Sanger Institute, where a high proportion of samples have been tested, and whole genome sequencing has been allocated to variant definitions based on mutations in Public Health England.26

Spike gene target status on PCR was used as a second approach to identify each variant. The labs used the TaqPath test (Thermo Fisher Scientific) to test three genetic targets: Spike (s), a nucleocapsid (n), and open reading frame 1ab (ORF1ab). In December 2020, an alpha variant was observed to be associated with a negative test on s goal, so s The target-negative condition was later used as a proxy for variable identification. The alpha variant accounts for between 98% and 100% of s Target – negative results in England. Among the serial samples tested positive for s Target, the delta variant was in 72.2% of samples in April 2021 and in 93.0% in May (as of May 12, 2021).4 For the test-negative case-control analysis, only samples tested in laboratories with the TaqPath assay were included.

data link

The three data sources described above were linked using an NHS number (a unique identifier for each person receiving medical care in the UK). These data sources were also correlated with data on the patient’s date of birth, surname, first name, zip code, sample identifiers and sample dates.


Multiple covariates that may be associated with the likelihood of a vaccine being offered or accepted and the risk of exposure to Covid-19 or specifically to any of the variables analyzed were also extracted from the National Immunization Management System and test data. These data included age (in the 10-year age groups), gender, multiple deprivation index (a national indicator of the level of deprivation based on small geographic areas of residence,27 Assessed in quintiles), race or ethnic group, nursing home status, date of travel abroad (ie outside the UK or Ireland), geographic region, period (calendar week), health and social care professional status, and status of the person in a vulnerable group Clinically very good.28 In addition, for the test-negative case-control analysis, a history of SARS-CoV-2 infection prior to initiation of the vaccination program was included. People were considered to have traveled if, when ordering the test, they reported that they had traveled outside the UK and Ireland in the previous 14 days or if they were tested in a quarantine hotel or while quarantined at home. Zip codes were used to identify the Multiple Deprivation Index, and unique property reference numbers were used to identify care homes.29

statistical analysis

For the test-negative case-control analysis, logistic regression was used to estimate the odds of a case with confirmed symptoms by PCR for Covid-19 among vaccinated subjects compared to unvaccinated subjects (control group). Cases are identified as having a delta variant by sequencing or if they are s Target-positive TaqPath PCR assay. Cases were identified as containing an alpha variant by sequencing or if they did s Objective-negative to the TaqPath PCR assay.

If a person tested positive on several occasions within a 90-day period (which may represent one episode of illness), only the first positive test was included. No more than three randomly selected negative test results were included for each person. Negative tests in which the sample was obtained within 3 weeks before the positive result or after the positive result could be a false negative; Therefore, this was excluded. Tests performed within 7 days after a previous negative result were also excluded. Persons who had previously tested positive before the analysis period were also excluded in order to estimate vaccine efficacy in fully susceptible subjects. All covariates were included in the model as was done with case analyzes and pre-test controls, with calendar week included as a factor and no interaction with region.

regarding s Target – Positive or – Negative mode, only subjects who tested positive on the other two PCR gene targets were included. Assignment of a delta variable based on s Target status restricted for the week of April 12, 2021 and beyond in order to achieve high specificity for s Objective-positive test for the delta variable.4

Vaccine efficacy for the first dose was estimated among people who developed symptoms 21 days or more after receiving the first dose of vaccine, and vaccine effects for the second dose were estimated among people who developed symptoms at the date that was 14 days or more after receiving the second dose. A comparison was made with unvaccinated subjects and subjects who developed symptoms at 4 to 13 days post-vaccination in order to help explain the differences in underlying infection risk. The period from the day of vaccine administration (Day 0) to Day 3 was excluded because interaction with the vaccine could cause an increase in tests leading to results biases, as previously described.10

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