Efficacy of vaccination against severe COVID-19 in relation to Delta variant and time since second dose: the REACT-SCOT case-control study

Objectives - To investigate: (1) whether vaccine efficacy against severe COVID-19 has decreased since Delta became the predominant variant; (2) whether efficacy wanes with time since second dose. Design - Matched case-control study. Setting - Population of Scotland from 1 December 2020 to 19 August 2021. Main outcome measure - Severe COVID-19, defined as cases with entry to critical care or fatal outcome. Results - Efficacy 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 against severe COVID-19 was 91% (95 percent CI 86% to 95%) for the AstraZeneca product and 92% (95 percent CI 85% to 95%) for mRNA (Pfizer or Moderna) products. Against the broader category of hospitalised or fatal COVID-19, efficacy in this time window was slightly lower: 88% (95 percent CI 85% to 90%) for the AstraZeneca product, 91% (95 percent CI 88% to 93%) for mRNA vaccines. Efficacy against COVID-19 declined rapidly in the first two months since second dose but more slowly thereafter. For hospitalised or fatal COVID-19 the model best supported by the data was one in which efficacy was the sum of a rapidly waning effect with half-life of 17 (95% CI 9 to 39) days and a time-invariant efficacy of 83%. Conclusions - These results are reassuring with respect to concerns that efficacy against severe COVID-19 might have fallen since the Delta variant became predominant. Although there is considerable uncertainty attached to any extrapolation into the future, these results suggest that the rapid early waning of efficacy against hospitalised COVID-19 after the second dose tapers off within a few months. This weakens the rationale for policies based on delivering booster doses to the entire population, rather than to vulnerable individuals for focused protection.