Efficacy of two doses of COVID-19 vaccine against severe COVID-19 in those with risk conditions and residual risk to the clinically extremely vulnerable: the REACT-SCOT case-control study

Objectives To determine whether COVID-19 efficacy varies with clinical risk category and to investigate risk factors for severe COVID-19 in those who have received two doses of vaccine. Design Matched case-control study (REACT-SCOT). Setting Population of Scotland from 1 December 2020 to 8 September 2021. Main outcome measure Severe COVID-19, defined as cases with entry to critical care or fatal outcome. Results Efficacy against severe COVID-19 of two doses of vaccine was 94% (95 percent CI 93% to 96%) in those without designated risk conditions, 89% (95 percent CI 86% to 91%) in those with moderate risk conditions, but only 73% (95 percent CI 64% to 79%) in those designated as clinically extremely vulnerable (CEV) and eligible for shielding. Of the 641 cases of severe COVID-19 in double-vaccinated individuals, 47% had moderate risk conditions and 38% were CEV. In the double-vaccinated CEV group, the rate ratio for severe disease (with no risk condition as reference category) was highest in solid organ transplants at 101 (95% CI 47 to 214) but even in this subgroup the absolute risk of severe COVID-19 was low (35 cases in 23678 person-months of follow-up). Conclusions Two doses of vaccine protect against severe COVID-19 in CEV individuals but the residual risk in double-vaccinated individuals remains far higher in those who are CEV than in those who are not. These results lay a basis for determining eligibility for additional measures including passive immunization to protect those at highest risk.