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

This research has not been peer-reviewed. It is a preliminary report that should not be regarded as conclusive, guide clinical practice or health-related behaviour, or be reported in news media as established information.


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.


Matched case-control study (REACT-SCOT).


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.


Efficacy against severe COVID-19 of two doses of vaccine was 93% (95 percent CI 90% to 95%) in those without designated risk conditions, 89% (95 percent CI 85% to 92%) in those with moderate risk conditions, but only 66% (95 percent CI 52% to 76%) in those designated as clinically extremely vulnerable (CEV) and eligible for shielding. Of the 330 cases of severe COVID-19 in double-vaccinated individuals, 47% had moderate risk conditions and 41% 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 98 (95% CI 29 to 332) but even in this subgroup the absolute risk of severe COVID-19 was low (14 cases in 16079 person-months of follow-up).


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 suggest that any policy of offering booster doses to doubly-vaccinated individuals should focus initially on the clinically vulnerable, and lay a basis for determining eligibility for passive immunization to protect those at highest risk.

Author list

Paul M McKeigue, David A McAllister, Chris Robertson, Sharon Hutchinson, Stuart McGurnaghan, Diane Stockton, Helen M Colhoun, for the PHS COVID-19 Epidemiology and Research Cell

Novel Coronavirus SARS-CoV-2