Efficacy of vaccination against severe COVID-19 in relation to Delta variant and time since second dose: the REACT-SCOT case-control study
Authors: McKeigue Paul M , McAllister David A , Hutchinson Sharon J , Robertson Chris , Stockton Diane , Colhoun Helen M ,   for the PHS COVID-19 Epidemiology and Research Cell
Published: September 2021

AbstractBackgroundThe objectives of this study were to investigate whether vaccine efficacy against severe COVID-19 has decreased since Delta became the predominant variant; (2) whether efficacy wanes with time since second dose.MethodsEfficacy was estimated in a matched case-control study that includes all diagnosed cases of COVID-19 in Scotland up to 19 August 2021. The main outcome measure was severe COVID-19, defined as cases with entry to critical care or fatal outcome.FindingsEfficacy of vaccination against severe COVID-19 decreased in May 2021 coinciding with the replacement of the B.1.1.7 (Alpha) by the B.1.617.2 (Delta) variant in Scotland, but this decrease was reversed over the next month. In the most recent time window, the efficacy of two doses was 91% (95 percent CI 87% to 94%) for the AstraZeneca product and 92% (95 percent CI 88% to 95%) for mRNA (Pfizer or Moderna) products. Efficacy of the AstraZeneca product against severe COVID-19 declined with time since second dose to 69% (95 percent CI 52% to 80%) at 20 weeks from second dose. Efficacy of mRNA vaccines declined in the first ten weeks from second dose but more slowly thereafter to 93% (95 percent CI 88% to 96%) at 20 weeks from second dose.InterpretationThese results are reassuring with respect to concerns that efficacy against severe COVID-19 might have fallen since the Delta variant became predominant, or that efficacy of mRNA vaccines wanes with increasing time since second dose. However it is now clear that efficacy of the AstraZeneca vaccine against severe COVID-19 wanes substantially by 20 weeks from second dose, suggesting that delivery of booster doses should initially focus on those who received this type of vaccine.FundingNo specific funding was received for this work. HC is supported by an endowed chair from the AXA Research Foundation.Research in contextEvidence before this studySeveral reports have suggested that efficacy of COVID-19 vaccines has fallen since the Delta variant became predominant, or that efficacy wanes with time since second dose. The starting point for this study was the evidence of waning efficacy cited by the CDC, the FDA and more recently the UK Joint Committee on Vaccination and Immunisation in support of their recent recommendations for delivery of booster doses for the general population.Added value of this studyThis study shows that efficacy of both AstraZeneca and mRNA vaccines against severe COVID-19 (fatal or requiring critical care) remains high (around 90%) in the most recent time window, but that efficacy of the AstraZeneca vaccine wanes to about 70% by 20 weeks from second dose. In contrast efficacy of the mRNA vaccines wanes rapidly at first but stabilises at about 90% by 20 weeks from second dose.Implications of all the available evidenceThese results suggest that booster doses of vaccine are not needed for those who have received two doses of mRNA vaccine, except for vulnerable individuals who may require a third primary dose.