In regard to the COVID-19 vaccine, differences in effectiveness against the SARS-CoV-2 Delta variant were more pronounced after receipt of a single dose compared with 2 doses, according to results of a study published in The New England Journal of Medicine.

To estimate the effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca COVID-19 vaccines against the Delta and Alpha variants, researchers designed a test-negative case-control study. The researchers obtained data on all sequenced and symptomatic cases of COVID-19 in England during the period in which the Delta variant began circulating to estimate the proportion of patients infected with either variant according to vaccination status.

A total of 38,592 sequenced COVID-19 samples were linked to vaccination status. Of patients aged 16 years and older who were fully vaccinated against COVID-19, the total number of linked samples was 19,109, with 14,837 and 4272 samples infected with the Alpha and Delta variants, respectively.

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In a pooled analysis of patients who received only the first dose of either type of COVID-19 vaccine, the effectiveness was decreased among those with the Delta variant (30.7%; 95% CI, 25.2-35.7) compared with those with the Alpha variant (48.7%; 95% CI, 45.5-51.7). When considered separately, results of the effectiveness of a single dose of the COVID-19 vaccine were similar for both the Pfizer-BioNTech and Oxford-AstraZeneca vaccines. The absolute difference in the effectiveness of the COVID-19 vaccine against the Delta variant vs the Alpha variant was 11.9% and 18.7% with the Pfizer-BioNTech and Oxford-AstraZeneca vaccines, respectively.

Among patients who received 2 doses of either vaccine type,  the vaccine was 87.5% effective against the Alpha variant (95% CI, 85.1 to 89.5) and 79.6% effective against the Delta variant (95% CI, 76.7-82.1). Of patients who received 2 doses of the Pfizer-BioNTech vaccine, the vaccine was 93.7% effective against the Alpha variant (95% CI, 91.6-95.3) and 88.0% effective against the Delta variant (95% CI, 85.3-90.1). In regard to patients who received 2 doses of the Oxford-AstraZeneca vaccine, the vaccine was 74.5% effective against the Alpha variant (95% CI, 68.4-79.4) and 67.0% effective against the Delta variant (95% CI, 61.3-71.8).

According to the researchers, the results of this study were observational and should be interpreted with caution. Further study limitations included potential misclassification of cases and controls from low sensitivity or specificity results of polymerase chain reaction testing, differences in vaccine coverage among population groups with increased or decreased exposure to the Delta variant, and reliance on assumptions that residual confounding in the study design would equally affect the estimates of effectiveness for both vaccine types.

Researchers concluded, “Our finding of reduced effectiveness after the first dose would support efforts to maximize vaccine uptake with two doses among vulnerable groups in the context of circulation of the Delta variant.”


Bernal JL, Andrews N, Gower C, et al. Effectiveness of Covid-19 vaccines against the B.1.617.2 (Delta) variant. N Engl J Med. 2021;385(7):585-594. doi:10.1056/NEJMoa2108891