Editor’s Note: This letter was published on October 20, 2021, at NEJM.org.


BNT162b2 and ChAdOx1 nCoV-19 Vaccine Effectiveness against Death from the Delta Variant

To the Editor:

We recently reported vaccine effectiveness for the BNT162b2 vaccine (Pfizer–BioNTech) and the ChAdOx1 nCoV-19 vaccine (AstraZeneca) against infection and hospitalization caused by the B.1.617.2 (delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Scotland.1 At that time, the number of deaths was too small to allow estimation of vaccine effectiveness against death from infection with the delta variant.

We used a Scotland-wide surveillance platform (Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 [EAVE II]) that includes individual-level linked data on vaccination, testing, viral sequencing, primary care, hospital admissions, and mortality among 5.4 million people (approximately 99% of the Scottish population).2,3 We conducted a cohort study and used Cox regression to estimate vaccine effectiveness against death from delta variant infection from April 1 to August 16, 2021, among adults 18 years of age or older, who were followed up to September 27, 2021.3 Our methods and findings are summarized below, with additional details provided in the Supplementary Appendix, available with the full text of this letter at NEJM.org. The EAVE II protocol is also available at NEJM.org.

At the date of swab testing, persons were defined as being unvaccinated or vaccinated with either one or two vaccine doses.4 Cases of SARS-CoV-2 infection were defined by a positive result on reverse-transcriptase–polymerase-chain-reaction (RT-PCR) testing. Testing was performed with the TaqPath COVID-19 Combo Kit (Thermo Fisher Scientific). True S gene “dropout” (indicating the presence of an S gene mutation not found in the delta variant) was defined as a negative result for the S gene and cycle threshold (Ct) values of less than 30 for the OR and N genes. Positivity for the S gene was defined as Ct values of less than 30 for the S gene and valid Ct values for the OR and N genes.1 Death from coronavirus disease 2019 (Covid-19) was defined as a death for which Covid-19 was recorded on the death certificate or death that occurred within 28 days after a positive RT-PCR test.1,4

Hazard ratios were adjusted for age, sex, socioeconomic status, and number of relevant coexisting conditions.5 Vaccine effectiveness was estimated as 1 minus the hazard ratio.

A total of 1,563,818 adults underwent testing in the community. Our mortality analysis was based on 114,706 adults who tested positive for SARS-CoV-2. Sequencing data showed that 99.5% of S-positive infections were caused by the delta variant and that 98.8% of delta variant infections were S-positive (Fig. S1 and Table S1 in the Supplementary Appendix). Among adults who tested positive, those who were unvaccinated tended to be much younger, to have fewer coexisting conditions, and to have a lower socioeconomic status and were more likely to be men than those who were vaccinated; these differences tended to be especially pronounced in comparison with those who received the ChAdOx1 nCoV-19 vaccine (Table S2).

Vaccine Effectiveness in Preventing Death from Covid-19, Stratified According to Age Group, Vaccination Status, and Vaccine (All Community Cases from April 1 to August 16, 2021, with Follow-up Conducted until September 27, 2021).

Overall, 201 deaths from Covid-19 were caused by SARS-CoV-2 that had been tested and found to be S-positive or S-negative (Table 1). Among persons 18 to 39 years of age who had infections for which data on S gene status were available, no deaths occurred among those who were fully vaccinated, as compared with 17 deaths among those who were unvaccinated. Among those who were 40 to 59 years of age, vaccine effectiveness against death from Covid-19 was 88% (95% confidence interval [CI], 76 to 93) for ChAdOx1 nCoV-19 and 95% (95% CI, 79 to 99) for BNT162b2; vaccine effectiveness was 90% (95% CI, 84 to 94) and 87% (95% CI, 77 to 93), respectively, among those 60 years of age or older. Overall, vaccine effectiveness against death from the delta variant 14 or more days after the second vaccine dose was 90% (95% CI, 83 to 94) for BNT162b2 and 91% (95% CI, 86 to 94) for ChAdOx1 nCoV-19 (Table S3).

A limitation of this study is the fact that it was based on an analysis of community samples. In addition, 1.8% of samples did not yield S gene categorization because of missing data in the Ct fields.

In summary, we found that the BNT162b2 and ChAdOx1 nCoV-19 vaccines offered substantial protection against death from Covid-19 caused by the delta variant.

Aziz Sheikh, M.D.
University of Edinburgh, Edinburgh, United Kingdom

Chris Robertson, Ph.D.
University of Strathclyde, Glasgow, United Kingdom

Bob Taylor, Ph.D.
Public Health Scotland, Glasgow, United Kingdom

Supported by a grant (MR/R008345/1) from the Medical Research Council; a grant (MC_PC_19004) from BREATHE–The Health Data Research Hub for Respiratory Health, funded through the U.K. Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK; Public Health Scotland; and the Scottish Government Director General for Health and Social Care.

Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org.

This letter was published on October 20, 2021, and updated on October 25, 2021, at NEJM.org.

The data used to undertake this analysis are not publicly available because they are based on deidentified national clinical records. These data are available, subject to approval by the NHS Scotland Public Benefit and Privacy Panel, by application through the Scotland National Safe Haven. The R code used to perform this analysis is available from https://github.com/EAVE-II.

  1. 1. Sheikh A, McMenamin J, Taylor B, Robertson C. SARS-CoV-2 delta VOC in Scotland: demographics, risk of hospital admission, and vaccine effectiveness. Lancet 2021;397:2461-2462.

  2. 2. Simpson CR, Robertson C, Vasileiou E, et al. Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II): protocol for an observational study using linked Scottish national data. BMJ Open 2020;10(6):e039097-e039097.

  3. 3. Mulholland RH, Vasileiou E, Simpson CR, et al. Cohort profile: Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) database. Int J Epidemiol 2021;50:1064-1074.

  4. 4. Vasileiou E, Simpson CR, Shi T, et al. Interim findings from first-dose mass COVID-19 vaccination roll-out and COVID-19 hospital admissions in Scotland: a national prospective cohort study. Lancet 2021;397:1646-1657.

  5. 5. Clift AK, Coupland CAC, Keogh RH, et al. Living risk prediction algorithm (QCOVID) for risk of hospital admission and mortality from coronavirus 19 in adults: national derivation and validation cohort study. BMJ 2020;371:m3731-m3731.

Supplementary Material

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