Vaccine efficacy against severe COVID-19 in relation to delta variant (B.1.617.2) and time since second dose in patients in Scotland (REACT-SCOT): a case-control study

Reports have suggested that the efficacy of vaccines against COVID-19 might have fallen since the delta (B.1.617.2) SARS-CoV-2 variant replaced the alpha (B.1.1.7) variant as the predominant variant. We aimed to investigate, for the two main classes of vaccine, whether efficacy against severe COVID-19 has decreased since delta became the predominant variant and whether the efficacy of two doses of vaccine against severe COVID-19 wanes with time since second dose. In the REACT-SCOT case-control study, vaccine efficacy was estimated using a matched case-control design that includes all diagnosed cases of COVID-19 in Scotland up to Sept 8, 2021. For every incident case of COVID-19 in the Scottish population, ten controls matched for age rounded to the nearest year, sex, and primary care practice, and alive on the day of presentation of the case that they were matched to were selected using the Community Health Index database. To minimise ascertainment bias we prespecified the primary outcome measure to assess vaccine efficacy as severe COVID-19, defined as diagnosed patients with entry to critical care within 21 days of first positive test, death within 28 days of first positive test, or any death for which COVID-19 was coded as underlying cause. Although the data extracted for this study included cases presenting up to Sept 22, 2021, the analyses reported here are restricted to cases and controls presenting from Dec 1, 2020, to Sept 8, 2021, ensuring follow-up for at least 14 days after presentation date to allow classification of hospitalisation and (for most cases) severity based on entry to critical care or fatal outcome. During the study period, a total of 5645 severe cases of COVID-19 were recorded; these were matched to 50 096 controls. Of the severe cases, 4495 (80%) were not vaccinated, and of the controls, 36 879 (74%) were not vaccinated. Of the severe cases of COVID-19 who had been vaccinated, 389 had received an mRNA vaccine and 759 had received the ChAdOx1 vaccine. The efficacy of vaccination against severe COVID-19 decreased in May, 2021, coinciding with the replacement of the alpha SARS-CoV-2 variant by the delta variant in Scotland, but this decrease was reversed over the following month. In the most recent time window centred on July 29, 2021, the efficacy of two doses was 91% (95% CI 87–94) for the ChAdOx1 vaccine and 92% (88–95) for mRNA (Pfizer or Moderna) vaccines. The efficacy of the ChAdOx1 vaccine against severe COVID-19 declined with